ANALYSIS OF ALTERNATIVES non-confidential report
Legal name of applicant(s): ARKEMA
Submitted by: ARKEMA
Substance: BIS(2-ETHYLHEXYL) PHTHALATE (DEHP)
Use title: Formulation of DEHP in compounds, dry-blends and plastisol formulations
Industrial use in polymer processing by calendering, spread coating, extrusion, injection moulding to produce PVC articles [except erasers, sex toys, small household items (<10cm) that can be swallowed by children, clothing intended to be worn against the bare skin; also toys, cosmetics and food contact material (restricted under other EU regulation)]
Use number: Uses 1 and 2
ANALYSIS OF ALTERNATIVES
© Arkema 2013 The information in this document is the property of Arkema and may not be copied, communicated to a third party, or used for any purpose other than that for which it is supplied, without the express written consent of Arkema.
While the information is given in good faith based upon the latest information available to Arkema, no warranty or representation is given concerning such information, which must not be taken as establishing any contractual or other commitment binding upon Arkema or any of its subsidiary or associated companies.
ii Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
CONTENTS
1 SUMMARY ...... 1
1.1 Background to this Application for Authorisation ...... 1 1.1.1 Identity of the Applicant...... 1 1.1.2 Background to the applied-for uses ...... 1 1.1.3 Hazards leading to listing of the substance under Annex XIV of the REACH Regulation ...... 3 1.1.4 Organisation of this AoA...... 4
1.2 Identification and screening of potential alternatives ...... 5
1.3 Assessment of suitability and availability of potential alternatives substances ...... 6 1.3.1 Overview of approach ...... 6 1.3.2 Reduction of overall risks ...... 6 1.3.3 Technical and economic feasibility of potential alternative substances ...... 15
1.4 Summary of the findings on the suitability of potential alternative substances ...... 16
1.5 Conclusion ...... 16
1.6 Actions required for making the alternatives suitable and available ...... 16
2 ANALYSIS OF SUBSTANCE FUNCTION ...... 18
2.1 Introduction ...... 18
2.2 Introduction to plasticised polymers ...... 18 2.2.1 Roles and material flows in the polymers and plastics industries ...... 18 2.2.2 Role of plasticisers ...... 18 2.2.3 Role of DEHP in the applied-for uses ...... 21 2.2.3.1 Scope of this Analysis of Alternatives ...... 21 2.2.3.2 Identification of applied-for uses for DEHP...... 21
2.3 Technical feasibility considerations from the perspective of the applicant ...... 21 2.3.1 Technical characteristics of DEHP manufacture...... 21 2.3.2 Parameters of technical feasibility from the applicant’s perspective ...... 22 2.3.2.1 Production integration ...... 22 2.3.2.2 Availability of precursors...... 23 2.3.2.3 Production plant requirements and feasibility of process modification ...... 25
2.4 Technical considerations in selecting a plasticiser ...... 27 2.4.1 Overview of plasticiser types ...... 27 2.4.2 How to select a plasticiser ...... 27 2.4.3 General Purpose plasticisers and commercial success of DEHP...... 31 2.4.4 Technical feasibility and selection criteria for DEHP and alternatives ...... 32 2.4.4.1 Introduction ...... 32 2.4.4.2 Approach to information collection ...... 32 2.4.4.3 General technical comparison criteria...... 33 2.4.4.4 Core Criterion 1: PVC compatibility ...... 34 2.4.4.5 Core Criterion 2: Processability ...... 36 2.4.4.6 Core Criterion 3: Plasticiser efficiency ...... 37 2.4.4.7 Core Criterion 4: Permanence ...... 39 2.4.4.8 Secondary Criterion 1: Low temperature performance ...... 40 2.4.4.9 Secondary Criterion 2: Clarity / Colour ...... 41 2.4.4.10 Secondary Criterion 3: Elastic recovery...... 42 2.4.4.11 Secondary Criterion 4: Odour ...... 42
Use number: 1,2 Legal name of applicant: Arkema iii
ANALYSIS OF ALTERNATIVES
2.4.4.12 Secondary Criterion 5: Melting / Freezing point ...... 43 2.4.4.13 Secondary Criterion 6: Sterilisability ...... 43 2.4.4.14 Secondary Criterion 7: Printability and adhesion properties ...... 44 2.4.5 Summary of technical requirements for DEHP as a plasticiser in PVC ...... 44
3 IDENTIFICATION OF POSSIBLE ALTERNATIVES ...... 47
3.1 Introduction and scope of analysis ...... 47
3.2 Description of efforts made to identify possible alternatives...... 48 3.2.1 Research and development activities ...... 48 3.2.1.1 Activities of the applicant ...... 48 3.2.1.2 Activities of downstream users of DEHP...... 48 3.2.2 Data searches for the purposes of this Analysis of Alternatives ...... 49 3.2.3 Consultations ...... 50 3.2.3.1 Overview of key consultees ...... 50 3.2.3.2 Consultation with the applicant ...... 51 3.2.3.3 Consultation with downstream users ...... 52
3.3 Identification of potential alternative substances ...... 55 3.3.1 Master list of potential alternatives ...... 55 3.3.1.1 Knowledge of alternatives amongst downstream users...... 58 3.3.2 Screening of potential alternative substances for suitability as DEHP replacement...... 58 3.3.2.1 Approach to the screening process ...... 58 3.3.2.2 Screening of potential alternatives for overall suitability ...... 58 3.3.2.3 Screening of potential alternatives against initial comparison criteria ...... 58 3.3.3 Final list of potential alternative substances for detailed analysis ...... 59
4 SUITABILITY AND AVAILABILITY OF POSSIBLE ALTERNATIVES...... 62
4.1 General remarks...... 62
4.2 Alternative 1: Alternative substance – ALKYLSULPHONIC PHENYL ESTER (ASE) ...... 63 4.2.1 Substance ID and properties of ASE ...... 63 4.2.1.1 Name and other identifiers for the substance ...... 63 4.2.1.2 Composition of the substance...... 63 4.2.1.3 Physicochemical properties ...... 64 4.2.1.4 Classification and labelling ...... 64 4.2.1.5 REACH Registration Status of ASE ...... 65 4.2.2 Technical feasibility of ASE ...... 65 4.2.2.1 Technical feasibility from the perspective of the applicant ...... 65 4.2.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 65 4.2.3 Reduction of overall risk due to transition to ASE ...... 67 4.2.4 Availability of ASE ...... 67 4.2.5 Economic feasibility of ASE ...... 67 4.2.6 Conclusion on suitability and availability for ASE ...... 68
4.3 Alternative 2: Alternative substance – ACETYL TRIBUTYL CITRATE (ATBC) ...... 69 4.3.1 Substance ID and properties of ATBC ...... 69 4.3.1.1 Name and other identifiers for the substance ...... 69 4.3.1.2 Composition of the substance...... 69 4.3.1.3 Physicochemical properties ...... 70 4.3.1.4 Classification and labelling ...... 71 4.3.1.5 REACH Registration Status of ATBC ...... 71 4.3.2 Technical feasibility of ATBC ...... 72 4.3.2.1 Technical feasibility from the perspective of the applicant ...... 72 4.3.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 72
iv Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.3.3 Reduction of overall risk due to transition to ATBC ...... 74 4.3.4 Availability of ATBC ...... 74 4.3.5 Economic feasibility of ATBC ...... 74 4.3.6 Conclusion on suitability and availability for ATBC ...... 74
4.4 Alternative 3: Alternative substance – GLYCERIDES, CASTOR-OIL-MONO-, HYDROGENATED, ACETATES (COMGHA) ...... 75 4.4.1 Substance ID and properties of COMGHA ...... 75 4.4.1.1 Name and other identifiers for the substance ...... 75 4.4.1.2 Composition of the substance...... 76 4.4.1.3 Physicochemical properties ...... 76 4.4.1.4 Classification and labelling ...... 77 4.4.1.5 REACH Registration Status of COMGHA ...... 77 4.4.2 Technical feasibility of COMGHA ...... 77 4.4.2.1 Technical feasibility from the perspective of the applicant ...... 77 4.4.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 77 4.4.3 Reduction of overall risk due to transition to COMGHA ...... 79 4.4.4 Availability of COMGHA ...... 79 4.4.5 Economic feasibility of COMGHA...... 79 4.4.6 Conclusion on suitability and availability for COMGHA ...... 79
4.5 Alternative 4: Alternative substance – DI(2-ETHYLHEXYL)ADIPATE (DEHA) ...... 80 4.5.1 Substance ID and properties of DEHA...... 80 4.5.1.1 Name and other identifiers for the substance ...... 80 4.5.1.2 Composition of the substance...... 80 4.5.1.3 Physicochemical properties ...... 80 4.5.1.4 Classification and labelling ...... 81 4.5.1.5 REACH Registration Status of DEHA ...... 82 4.5.2 Technical feasibility of DEHA ...... 83 4.5.2.1 Technical feasibility from the perspective of the applicant ...... 83 4.5.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 83 4.5.3 Reduction of overall risk due to transition to DEHA ...... 84 4.5.4 Availability of DEHA ...... 84 4.5.5 Economic feasibility of DEHA ...... 84 4.5.6 Conclusion on suitability and availability for DEHA ...... 84
4.6 Alternative 5: Alternative substance – DIETHYLHEXYLSEBACATE (DEHS) ...... 85 4.6.1 Substance ID and properties of DEHS ...... 85 4.6.1.1 Name and other identifiers for the substance ...... 85 4.6.1.2 Composition of the substance...... 85 4.6.1.3 Physicochemical properties ...... 85 4.6.1.4 Classification and labelling ...... 86 4.6.1.5 REACH Registration Status of DEHS ...... 86 4.6.2 Technical feasibility of DEHS ...... 86 4.6.2.1 Technical feasibility from the perspective of the applicant ...... 87 4.6.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 87 4.6.3 Reduction of overall risk due to transition to DEHS ...... 87 4.6.4 Availability of DEHS ...... 87 4.6.5 Economic feasibility of DEHS...... 87 4.6.6 Conclusion on suitability and availability for DEHS ...... 88
4.7 Alternative 6: Alternative substance – DI(2-ETHYLHEXYL) TEREPHTALATE (DEHT) ...... 88 4.7.1 Substance ID and properties of DEHT (DOTP) ...... 88 4.7.1.1 Name and other identifiers for the substance ...... 88 4.7.1.2 Composition of the substance...... 89 4.7.1.3 Physicochemical properties ...... 89
Use number: 1,2 Legal name of applicant: Arkema v
ANALYSIS OF ALTERNATIVES
4.7.1.4 Classification and labelling ...... 89 4.7.1.5 REACH Registration Status of DEHT ...... 90 4.7.2 Technical feasibility of DEHT ...... 90 4.7.2.1 Technical feasibility from the perspective of the applicant ...... 90 4.7.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 90 4.7.3 Reduction of overall risk due to transition to DEHT ...... 92 4.7.4 Availability of DEHT ...... 92 4.7.5 Economic feasibility of DEHT ...... 92 4.7.6 Conclusion on suitability and availability for DEHT ...... 93
4.8 Alternative 7: Alternative substance – DPHP Bis(2-propylheptyl) Phthalate (DPHP) ...... 93 4.8.1 Substance ID and properties of DPHP ...... 93 4.8.1.1 Name and other identifiers for the substance ...... 93 4.8.1.2 Composition of the substance...... 94 4.8.1.3 Physicochemical properties ...... 94 4.8.1.4 Classification and labelling ...... 95 4.8.1.5 REACH Registration Status of DPHP ...... 95 4.8.2 Technical feasibility of DPHP ...... 95 4.8.2.1 Technical feasibility from the perspective of the applicant ...... 95 4.8.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 95 4.8.3 Reduction of overall risk due to transition to DPHP ...... 95 4.8.4 Availability of DPHP ...... 96 4.8.5 Economic feasibility of DPHP ...... 96 4.8.6 Conclusion on suitability and availability for DPHP ...... 96
4.9 Alternative 8: Alternative substance –DI-ISODECYLPHTHALATE (DIDP) ...... 97 4.9.1 Substance ID and properties of DIDP ...... 97 4.9.1.1 Name and other identifiers for the substance ...... 97 4.9.1.2 Composition of the substance...... 98 4.9.1.3 Physicochemical properties ...... 98 4.9.1.4 Classification and labelling ...... 99 4.9.1.5 REACH Registration Status of DIDP ...... 100 4.9.2 Technical feasibility of DIDP ...... 100 4.9.2.1 Technical feasibility from the perspective of the applicant ...... 100 4.9.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 100 4.9.3 Reduction of overall risk due to transition to DIDP ...... 101 4.9.4 Availability of DIDP ...... 101 4.9.5 Economic feasibility of DIDP...... 101 4.9.6 Conclusion on suitability and availability for DIDP ...... 101
4.10 Alternative 9: Alternative substance – 1,2-CYCLOHEXANEDICARBOXYLIC ACID, DIISONONYLESTER (DINCH) ...... 102 4.10.1 Substance ID and properties of DINCH ...... 102 4.10.1.1 Name and other identifiers for the substance ...... 102 4.10.1.2 Composition of the substance...... 102 4.10.1.3 Physicochemical properties ...... 103 4.10.1.4 Classification and labelling ...... 104 4.10.1.5 REACH Registration Status of DINCH ...... 104 4.10.2 Technical feasibility of DINCH ...... 104 4.10.2.1 Technical feasibility from the perspective of the applicant ...... 104 4.10.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 104 4.10.3 Reduction of overall risk due to transition to DINCH ...... 105 4.10.4 Availability of DINCH ...... 105 4.10.5 Economic feasibility of DINCH ...... 105 4.10.6 Conclusion on suitability and availability for DINCH ...... 105
vi Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.11 Alternative 10: Alternative substance – Di-isononylphthalate (DINP) ...... 106 4.11.1 Substance ID and properties of DINP ...... 106 4.11.1.1 Name and other identifiers for the substance ...... 106 4.11.1.2 Composition of the substance...... 106 4.11.1.3 Physicochemical properties ...... 107 4.11.1.4 Classification and labelling ...... 108 4.11.1.5 REACH Registration Status of DINP ...... 109 4.11.2 Technical feasibility of DINP ...... 109 4.11.2.1 Technical feasibility from the perspective of the applicant ...... 109 4.11.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 110 4.11.3 Reduction of overall risk due to transition to DINP ...... 110 4.11.4 Availability of DINP ...... 111 4.11.5 Economic feasibility of DINP...... 111 4.11.6 Conclusion on suitability and availability for DINP ...... 111
4.12 Alternative 11: Alternative substance – TRIOCTYLTRIMELLITATE (TOTM) ...... 112 4.12.1 Substance ID and properties of TOTM ...... 112 4.12.1.1 Name and other identifiers for the substance ...... 112 4.12.1.2 Composition of the substance...... 112 4.12.1.3 Physicochemical properties ...... 112 4.12.1.4 Classification and labelling ...... 113 4.12.1.5 REACH Registration Status of TOTM ...... 114 4.12.2 Technical feasibility of TOTM ...... 114 4.12.2.1 Technical feasibility from the perspective of the applicant ...... 114 4.12.2.2 Technical feasibility from the perspective of the downstream user (information from literature) ...... 114 4.12.3 Reduction of overall risk due to transition to TOTM ...... 115 4.12.4 Availability of TOTM ...... 115 4.12.5 Economic feasibility of TOTM ...... 115 4.12.6 Conclusion on suitability and availability for TOTM ...... 115
5 OVERALL CONCLUSIONS ON SUITABILITY AND AVAILABILITY OF POSSIBLE ALTERNATIVES FOR THE APPLIED-FOR USES ...... 116
5.1 Conclusion on suitability and availability of potential alternative substances ...... 116
5.2 Planned future Research and Development for the replacement of DEHP...... 118
Annex 1: List of data sources ...... 119
Annex 2: Justification for submitting a single Analysis of Alternatives for both applied-for uses ...... 123
Annex 3: List of supplementary data sources considered for the purposes of the AoA ...... 124
Annex 4: Reduction of overall risk due to transition to the potential alternative substances ...... 126
Use number: 1,2 Legal name of applicant: Arkema vii
ANALYSIS OF ALTERNATIVES
1 SUMMARY
1.1 Background to this Application for Authorisation
1.1.1 Identity of the Applicant This Analysis of Alternatives (AoA) constitutes part of the Application for Authorisation (AfA) submitted by Arkema. The substance of concern is Bis(2-ethylhexyl) phthalate (hereafter referred to as DEHP, but also known as DOP), EC Number 204-211-0, CAS Number 117-81-7. The manufacture of DEHP takes place at Chauny, France. For the purposes of this AfA, the applicant has acted as a member of a group of manufacturers of DEHP which has been known as the DEHP Authorisation Task Force (ATF). All members of the ATF are submitting separate AfAs. In relation to an AoA, Article 60(5) of the REACH Regulation states that: “When assessing whether suitable alternative substances or technologies are available, all relevant aspects shall be taken into account by the Commission, including: 1. Whether the transfer to alternatives would result in reduced overall risks to human health and the environment, taking into account the appropriateness and effectiveness of risk management measures; 2. The technical and economic feasibility of alternatives for the applicant”. Accordingly, the AoA has been performed primarily from the perspective of the applicant (the manufacturer of DEHP, Arkema) with relevant information also provided from the perspective of the downstream users who form the applicant’s customer base for DEHP. This information is relevant because the feasibility of potential alternatives for the applicant cannot be robustly assessed without also gauging the feasibility of potential alternatives down the supply chain.
1.1.2 Background to the applied-for uses DEHP is used as a general purpose plasticiser in PVC for indoor and outdoor uses including: flooring, roofing, wires, cables, hoses, profiles, coated fabrics (such as artificial leather for bags, and book covers), medical devices, as well as primary packaging of medicinal products and active pharmaceutical substances.
Role and importance of plasticisers A plasticiser is a substance which when added to a material, usually a polymer, produces a product which is flexible, resilient and easier to handle. Plasticisers are liquids of low or negligible volatility or low molecular weight solids and, in addition to the processability, end-product softness, flexibility and extensibility (Sen, 2008) of a polymer, they deliver a series of other concomitant effects. These include lowering of the glass transition temperature (Tg) and softening temperature, reduction of strength, and increased impact resistance. A plasticiser acts by lowering the intermolecular forces between the polymer chains and should be compatible with the polymer or exudation will occur. Plasticisers that are highly compatible with PVC are known as primary plasticisers, while plasticisers that have limited compatibility are known as secondary plasticisers (Sen, 2008). Plasticisers are developed to satisfy demanding technical and economic requirements and, due to their technical performance, versatility and cost-effectiveness, phthalate-based plasticisers are the most widely used type within the EU and globally.
Use number: 1,2 Legal name of applicant: Arkema 1
ANALYSIS OF ALTERNATIVES
The uses of DEHP for which Authorisation is sought are: 1. Formulation of DEHP in compounds, dry-blends and plastisol formulations; and
2. Industrial use in polymer processing by calendering, spread coating, extrusion, injection moulding to produce PVC articles [except erasers, sex toys, small household items (<10cm) that can be swallowed by children, clothing intended to be worn against the bare skin; also toys, cosmetics and food contact material (restricted under other EU regulation)]
Because these two applied-for uses form part of the same supply chains and may be undertaken by the same downstream actors, they are considered together for the purposes of this AoA1. A wide range of articles and preparations may be produced through the formulation and industrial processing of DEHP. Here, “formulation” (or compounding) means the production of semi-final products such as PVC compounds or plastisol, and “processing” means the conversion of PVC compounds into the plastic articles themselves. Apart from industrial applications of the plasticised PVC articles, certain end applications of DEHP involve some degree of professional use as well as consumer use. These include items such as: flooring, hoses and cables, car undercoating, use of coated fabrics or films, assembly and installation of profiles, gaskets, etc. In other cases, professional use essentially relates to clothing such as heavy duty waterproof rainwear and footwear, which is not intended to be worn directly against bare skin. DEHP is also used in the manufacture of medical devices2 due to:
Its flexibility in a variety of physical forms from tubes to membranes;
Its chemical stability and the ability to sterilise its PVC compounds easily;
Its low cost which makes it a material of choice for disposable items; and
The lack of current evidence of unacceptable adverse consequences in patients3. DEHP plasticised PVC is also used in the manufacture of blood bags and is particularly valuable in this application as the substance has a unique role in that it helps to prolong the life of the blood for up to 6-8 weeks after blood collection4. Importantly, this AfA specifically excludes a sub-set of those consumer articles for which an Authorisation of use of DEHP is not sought by the applicant. Excluded from the “applied-for uses” is the use of DEHP in the production of clothing intended to be worn against the bare skin, or articles which can be swallowed by children, or which may involve intensive contact with mucous
1 Further justification for this approach is provided in Annex 2 to this AoA. 2 Exempt from authorisation under Articles 60(2) and 62(6) of the REACH Regulation EC No 1907/2006. 3 More specific performance criteria that are necessary for plasticised polymers used in medical devices are (a) for medical sheet applications – tensile strength and cold flexibility (because solutions must be cold-storable) and clarity are important; and (b) for medical tubing applications – elastic recovery must be optimised to assure that tubing does not kink during use (http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_014.pdf).
4 See here: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_014.pdf.
2 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
membranes. More specifically, the following uses are not supported by the applicant and are therefore excluded from the scope of this AfA:
Erasers;
Adult toys (sex toys and other articles for adults with intensive contact with mucous membranes);
Small (<10 cm) PVC items available in the home environment (without attachment to larger objects), which can be swallowed by small children; and
Textiles/clothing intended to be worn against the bare skin. There are further exclusions from the scope of this AfA. These include:
Potential uses which are already restricted under existing EU legislation, namely the use of DEHP in:
Toys;
Cosmetics; and
Food contact materials
Use of DEHP in the formulation and processing of rubber articles;
Use of DEHP in the formulation of end product mixtures such as:
Sealants;
Adhesives; and
Paints.
1.1.3 Hazards leading to listing of the substance under Annex XIV of the REACH Regulation The hazard profile of DEHP, together with the potential risks that this substance may pose, has been the subject of extensive expert assessment, including a European risk assessment report (EU RAR) (European Chemicals Bureau, 2008). This assessment reached a number of conclusions which indicated that some concern was warranted with regard to human exposures (including workers, consumers and from exposure via the environment)5. DEHP was included in the Candidate List for Authorisation following ECHA’s decision, ED/67/2008 on 28 October 2008, based upon its classification as Toxic to Reproduction, Category 2 (i.e. Category 1B, under the Classification, Labelling and Packaging Regulation (CLP)); this was based largely on information from the EU RAR, supplemented by limited additional information (ECHA, 2008). DEHP was further reviewed in a background document prepared in support of its inclusion in Annex XIV (ECHA, 2009), again drawing on the EU RAR together with data collected by a consortium of consultants (COWI, IOM and Entec).
5 Environmental concerns were also identified.
Use number: 1,2 Legal name of applicant: Arkema 3
ANALYSIS OF ALTERNATIVES
Since DEHP meets the criteria in Article 57(c) of the REACH Regulation and it is possible to determine a toxicological threshold, it was noted that if the risks to human health from the use of the substance arising from its toxicity to reproduction are demonstrated to be adequately controlled in accordance with Section 6.4 of Annex I and that this is documented in the applicant’s chemical safety report (CSR), an authorisation would be granted in accordance with Article 60(2) (‘adequate control route’); if not, an authorisation shall be granted in accordance with Article 60(4) (‘socio- economic route’). Alongside the Authorisation process, in 2011, the Danish authorities submitted a proposal for a restriction (together with the justification and background information documented in an Annex XV dossier) on the placing on the market and use of articles containing four classified phthalates (DEHP, benzyl butyl phthalate (BBP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP)), specifically in articles that are intended for indoor use, or in articles that come into contact with skin or mucous membranes, on the grounds of the aforementioned Toxic to Reproduction, Category 1B CLP classification. The Annex XV restriction report was made publicly available by ECHA on 16/09/2011. The final opinions of the ECHA Committees (i.e. the Committee for Risk Assessment (RAC), and the Committee for Socio-Economic Analysis (SEAC)) were reached, by consensus, on 12/06/2012 and 05/12/2012, respectively. These are summarised below: “RAC considers that the proposed restriction is not justified because the available data do not indicate that currently (2012) there is a risk from combined exposure to the four phthalates. The regulatory requirements and consequent reduction in use are further reducing the risk, as will the authorisation requirements imposed on these phthalates in the next few years” (ECHA, 2012a). and “Taking into account RAC’s conclusions that the proposed restriction is not justified because the available data do not indicate that currently (2012) there is a risk from combined exposure to the four phthalates and that the regulatory requirements and consequent reduction in use are further reducing the risk, as will the authorisation requirements imposed on these phthalates in the next few years, SEAC has no basis to support the proposed restriction” (ECHA, 2012a). This AfA takes into consideration, and expands upon, the discussions held at the time on the scrutiny of the Danish restriction proposal. It must be noted, however, that the scope of this AfA is significantly different as it covers the industrial use of DEHP as well as the service life of specific PVC articles plasticised with DEHP, which may be used by professional users and consumers.
1.1.4 Organisation of this AoA This AoA comprises two distinct parts:
The non-confidential document: this is the present document that is intended for publication on ECHA’s website for the purposes of public consultation; and
The Confidential Annex: this is a separate document which provides more detail on the analysis of potential alternative plasticisers from the applicant’s perspective and which, due to its commercially sensitive contents, cannot be made available to the public. This document has been submitted to ECHA for the consideration of the RAC and SEAC.
4 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
1.2 Identification and screening of potential alternatives In research undertaken on the availability of potential alternatives to DEHP from the perspective of the applicant, the following conclusions have been reached:
The only realistic alternatives are alternative substances. Whilst a flexible PVC processor producing plastic articles could potentially consider a different plastic material to flexible PVC as a potential alternative, for the applicant, a chemical manufacturer, an alternative material (or technique) cannot be a technically or economically feasible alternative. Alternative materials, which could act as replacements to DEHP plasticised PVC are alien to the technical capabilities of the applicant and have not been considered; and
Whilst the applicant could theoretically consider and potentially implement the manufacture of an alternative substance, the production of a range of alternative substances would be profoundly unfeasible from a practical and economic perspective and thus it has not been considered in this AoA (further justification for this approach is provided in Section 3.1). Through research and consultation, a comprehensive list of 43 potential alternative plasticiser substances has been developed. After initial analysis, this list was refined to a short list of 11 substances intended for more detailed analysis (see Table 1.1 and Section 3.3). This initial analysis took into account the results of extensive consultations with supply chain stakeholders and considered the analyses and results of past evaluations and authority opinions on the availability and suitability of alternatives for DEHP. The refined group of alternatives contains representative substances from a broad range of chemical groups including: alkylsulphonic phenyl esters, esters of monoglycerides of hydrogenated castor oil, adipates, citrates, phthalates, hydroxyphthalates, sebacates, terephthalates and trimellitates. The range of alternatives covered by this selection comprehensively addresses the requirements of the supply chain covered by this AfA, and therefore adequately covers the potentially feasible alternatives from the perspective of the applicant. Table 1.1: Shortlist of Selected Potential Alternative Substances IUPAC Name Other common names/acronyms EC Number CAS Number Tributyl O-acetylcitrate 201-067-0 77-90-7 Acetyltri-n-butyl citrate (ATBC, Citroflex A-4) Sulfonic acids, C10-21- Alkylsulphonic phenyl ester (ASE, 293-728-5 91082-17-6 alkane, Ph esters Mesamoll) Bis(2-propylheptyl) phthalate DPHP 258-469-4 53306-54-0 Bis(2-ethylhexyl) adipate 203-090-1 103-23-1 Di-octyl adipate (DEHA)
Di-octyl adipate (DOA) Bis(2-ethylhexyl) DEHT 229-176-9 6422-86-2 terephthalate Dioctyl terephthalate (DOTP) Di-isodecyl phthalate DIDP 271-091-4 and 68515-49-1 and 247-977-1 26761-40-0 Di-isononyl' phthalate DINP 271-090-9 and 68515-48-0 and 249-079-5 28553-12-0 1,2-Cyclohexanedicarboxylic Di-iso-nonyl-1,2- *605-439-7 EU 166412-78-8, acid, 1,2-diisononyl ester cyclohexanedicarboxylate (DINCH, USA and Canada Hexamoll) 474919-59-0
Use number: 1,2 Legal name of applicant: Arkema 5
ANALYSIS OF ALTERNATIVES
IUPAC Name Other common names/acronyms EC Number CAS Number Bis(2-ethylhexyl) sebacate DEHS 204-558-8 122-62-3 Dioctyl sebacate Glycerides, castor-oil mono-, Glycerides, Castor-oil-mono-, *616-005-1 736150-63-3 hydrogenated, acetates hydrogenated, acetates (COMGHA) Component A Not available 330198-91-9 Component B Not available 33599-07-4 Tris(2-ethylhexyl) benzene- 222-020-0 3319-31-1 1,2,4-tricarboxylate Trioctyltrimellitate (TOTM)
Tri(2-ethylhexyl) trimellitate, (TEHTM)
Further information is presented in the Confidential Annex with regard to details of the downstream markets consulted with. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 1.2
1.3 Assessment of suitability and availability of potential alternatives substances
1.3.1 Overview of approach The assessment of the suitability and availability of alternatives has been undertaken primarily from the perspective of the applicant. However, the perspective of downstream users has also been considered; more specifically, the technical feasibility and market availability of the potential alternative substances for the downstream users is discussed here. This is because only alternatives that would (in principle) be technically suitable for downstream users could be successfully placed on the market by the applicant. On the other hand, the cost to stakeholders at the downstream user level is presented in the Socio- economic Analysis (SEA).
1.3.2 Reduction of overall risks The CSR accompanying this AfA demonstrates adequate control - based on very conservative assumptions, exposure to DEHP is below the effect threshold (it should be noted that the recent RAC derived no-effect level document for DEHP has been taken into consideration. This is addressed further in the CSR). Therefore, the risks associated with the endpoint of concern, reproductive toxicity, (as well as other human health endpoints and the environment) are adequately controlled. Consequently, the use of any alternative (whether commercially proven or not) would not result in a discernible benefit to human health or the environment. A more detailed analysis of the hazard and risk profiles of the 11selected potential alternative substances is available in Annex 4. Only a brief summary is provided here alongside a summary table, which gives an overview of the hazard classification for these substances as well as a brief overview of their regulatory and CLP status (Table 1.2). Key conclusions include the following:
There are some substances which have a lower hazard/risk profile than DEHP. These however, are generally substances that cannot act as a general purpose plasticiser like DEHP and,
6 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
therefore, would be able to replace only a modest percentage of the applicant’s current DEHP sales;
There are some substances for which there are uncertainties as to whether their use would result in an overall reduction of risks compared to the applied-for use scenario. Some may not be REACH registered (hence the body of evidence is limited), some may have raised concerns among the regulators already, therefore may be subject to Substance Evaluation following their listing on the Community Rolling Action Plan (CoRAP), while others may be accompanied by hazard classification notifications which may raise concern on their long-term effects; and
There are finally some alternative substances (typically alternative phthalate esters) that have been attracting attention from regulators and other stakeholders, and which have currently uncertain long-term prospects as suitable alternatives (in light of their human health and/or environmental effects).
Use number: 1,2 Legal name of applicant: Arkema 7
ANALYSIS OF ALTERNATIVES
Table 1.2: Hazard classification and labelling for the selected potential alternative substances Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
DEHP Repr. 1B H360FD n/a Currently on Annex XIV
ASE Not classified - 53 REACH Registered;
H413 (May There were 23 companies that notified the substance with Previously the subject of a temporary TDI by EFSA cause long a single hazard, i.e. Aquatic Chronic 4. No other Aquatic lasting harmful 23 notifications were recorded. Chronic 4 effects to aquatic life)
ATBC The lead registrant and a further 1,284 notifiers did not Not currently REACH Registered (original registration 1285 - - classify the substance. appears to have been withdrawn);
Differences between classifications notified by various - - 58 58 notifiers found the available data lacking. parties H220 12 companies notified the substance with a classification Flam. Gas 1 (Extremely of Muta. 1B (H340) and Carc. 1B (H350), accompanied flammable gas) by Note K. Note K states that the classification as a H340 (May carcinogen or mutagen need not apply if it can be shown Muta. 1B cause genetic that the substance contains less than 0.1% w/w 1,3- defects) butadiene (EINECS No 203-450-8). If the substance is not classified as a carcinogen or mutagen, at least the H350 (May Carc. 1B precautionary statements (P102-) P210-P403 or the S- cause cancer) 19 phrases (2-) 9-16 should apply. Therefore, it is H315 (Causes reasonable to assume that under certain circumstances Skin Irrit. 2 skin irritation) ATBC may be accompanied by impurities (1,3- butadiene), which could lead to a Carc. 1B and Muta. 1B H319 (Causes classification. Eye Irrit. 2 serious eye irritation) Other companies notified for skin and eye irritation (3 Aquatic H412 (Harmful and 6 respectively) and there was a single company who Chronic 3 to aquatic life
8 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
with long notified for chronic aquatic toxicity. lasting effects) In total, there were 19 companies who classified the substance in 4 distinct notifications.
COMGHA No notifications were available for COMGHA, Not REACH registered; Component A, or Component B. No CLP classification notified
DEHA 768 The lead registrant and a further 767 notifiers did not REACH registered; Not classified - classify the substance. TDI established by EFSA; 28 Data lacking. - - Differences between classifications notified by various H315 (Causes 49 A further 49 notifiers classified the substance in 9 distinct parties; Skin Irrit. 2 skin irritation) notifications. H319 (Causes Entered in CoRAP list update (2013-2015) because of Eye Irrit. 2 serious eye Most of the companies who notified a hazard for DEHA CMR concerns irritation) have mentioned irritating properties (skin irrit.2, eye H400 (Very irrit.2) and aquatic toxicity (mainly Acute 1 but also Aquatic toxic to aquatic Chronic 1). Acute 1 life)
Aquatic H410 (Very Chronic 1 toxic to aquatic There were single cases that mentioned Acute toxicity to life with long humans, Carcinogenicity 2 and Reproductive toxicity 2, lasting effects) but the reason for these classifications are not clear and may be connected to impurities that the specific H302 (Harmful Acute Tox. 4 companies had in their product. if swallowed) H332 (Harmful Acute Tox. 2 if inhaled) Carc.2 H351
Use number: 1,2 Legal name of applicant: Arkema 9
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
(Suspected of causing cancer) H361 (Suspected of Repr. 2 damaging fertility or the unborn child) H411 (Toxic to Aquatic aquatic life Chronic 2 with long lasting effects) The notifier didn’t fill the rest of the information. H319
DEHS No 262 The lead registrant and a further 261 notifiers did not Not REACH registered; - classify the substance. classification Only minor differences in CLP classifications notified by - - 1 Data lacking. various parties 3 There were 3 companies that notified the substance with H302 (Harmful Acute Tox 4 a single hazard, i.e. Aquatic Toxic 4 (oral). No other if swallowed) notifications were recorded.
DEHT No 165 The lead registrant and a further 164 notifiers did not Not REACH registered; - classify the substance. classification Some differences in CLP classifications notified by - - 34 Data lacking. various parties (particularly regarding reprotoxic classification) H413 (May There was only a single company which classified the Aquatic cause long substance, as Aquatic chronic 4 and Reproductive Chronic 4 lasting harmful 1 toxicant 2. effects to
10 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
aquatic life) H361 (Suspected of Repr. 2 damaging fertility or the unborn child) DPHP - The lead registrant and a further 121 notifiers did not REACH registered; - - classify the substance. Not classified under CLP
2 DIDP 1 No 381 The lead registrant and a further 380 notifiers did not REACH Registered; - classify the substance. classification TDI established by EFSA; H315 (Causes 25 A further 32 companies classified the substance in 2 Skin Irrit. 2 skin irritation) distinct notifications. 25 of them classified it as skin and Only minor differences in CLP classifications notified by H319 (Causes eye irritant 2 and 7 as just eye irritant 2. various parties Eye Irrit. 2 serious eye irritation) 7
H319 (Causes Eye Irrit. 2 serious eye irritation)
DIDP 23 No 98 - classification H411 (Toxic to 85 A further 85 companies classified the substance in 4 Aquatic aquatic life distinct notifications. Chronic 2 with long
Use number: 1,2 Legal name of applicant: Arkema 11
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
lasting effects)
H400 (Very 41 of them classified it as acute toxic and 66 as aquatic Aquatic toxic to aquatic chronic (43 as aquatic chronic cat. 2 and 23 as aquatic Acute 1 life) chronic cat. 1). There was a single notification where the Aquatic H410 (Very company classified it as skin irritant 2 and eye irritant 2. Chronic 1 toxic to aquatic life with long lasting effects)
H315 (Causes Skin Irrit. 2 skin irritation) H319 (Causes Eye Irrit. 2 serious eye irritation) DINCH 129 The lead registrant and a further 128 notifiers did not REACH Registered; classify the substance. No - TDI established by EFSA; classification Not classified under CLP
DINP 14 No 243 REACH Registered; - classification 70 The lead registrant and a further 69 notifiers found that TDI established by EFSA; - - data was lacking. Some differences in CLP classifications notified by H400 (Very 29 A further 29 companies classified the substance in 4 various parties (particularly regarding reprotoxic Aquatic toxic to aquatic distinct notifications. classification); Acute 1 life) Recent opinion by RAC on human health hazard H361 identifies concerns (Suspected of The vast majority of the companies (24) classified it as Repr. 2 damaging aquatic acute cat.1. There were also 3 companies who fertility or the classified it as reprotoxicant cat. 1 and a single case for unborn child)
12 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
H315 (Causes each of skin irritant 2 and eye irritant 2. Skin Irrit. 2 skin irritation) H319 (Causes Eye Irrit. 2 serious eye irritation) 5 DINP 2 No 794 The lead registrant and a further 793 notifiers did not - classification classify the substance
- - 59 Data lacking. H413 (May 53 A further 53 companies classified the substance in 4 cause long distinct notifications. Aquatic lasting harmful Chronic 4 effects to aquatic life) All companies classified it with one or another aquatic Aquatic hazard. 30 of the companies classified it as Acute Acute 1 Aquatic toxicant cat. 1, 28 as Chronic Aquatic cat. 4 and H410 (Very 23 as Chronic Aquatic cat.1. There was also a single Aquatic toxic to aquatic company who also classified it as Acute toxic 4 Chronic 1 life with long (inhalation). lasting effects) H400 Aquatic Tox H332 (Harmful 4 if inhaled) H400 (Very Aquatic toxic to aquatic Acute 1 life) TOTM No 353 The lead registrant and a further 353 notifiers did not REACH Registered; - classify the substance. classification Some differences in CLP classifications notified by H361 91 A further 91 companies classified the substance in 6 various parties (particularly regarding reprotoxic Repr. 2 (Suspected of distinct classifications. classification); damaging
Use number: 1,2 Legal name of applicant: Arkema 13
ANALYSIS OF ALTERNATIVES
Substance Hazard Hazard Number Additional classification and labelling comments Regulatory and CLP status Name Class and Statement of Category Code(s) notifiers Code(s)1 (labelling)
fertility or the Entered in CoRAP list (2012-2014) due to environmental unborn child) PBT concern Reproductive toxicity cat.2 was notified by 52 of the H312 (Harmful companies as the single hazard of the substance. Acute Tox. 4 in contact with skin) H319 (Causes Eye Irrit. 2 serious eye 23 companies classified it as acute toxic 4 (dermal) and irritation) eye irritant 2, while there were 10 who classified it as H315 (Causes skin, eye and respiratory irritant (STOT SE 3). Skin Irrit. 2 skin irritation) H335 (May cause There were also 6 companies that classified it as Aquatic STOT SE 3 respiratory Chronic 4. irritation) H413 (May cause long Aquatic lasting harmful Chronic 4 effects to aquatic life) Please note: Notifications from the classification and labelling inventory relate to the substance which is placed on the market, including all impurities. These impurities can also contribute to final hazard profile of marketed substance.
1 The various hazards that were notified are collectively presented for each hazard. For most of them, overlaps may exist among the different notifications, because some classifications were present in more than one of them.
2DIDP 1 (CAS number 68515-49-1, EC number 271-091-4) 3DIDP 2 (CAS number 26761-40-0, EC number 247-977-1) 4DINP 1 (CAS number 68515-48-0, EC number 271-090-9) 5DINP 2 (CAS number 28553-12-0, EC number 249-079-5)
14 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
1.3.3 Technical and economic feasibility of potential alternative substances There is a clear link between technical and economic feasibility for the applicant and for the applicant’s downstream users; even if an alternative plasticiser can be (or become) technically feasible for the applicant, if it is not technically feasible (useable) for the downstream users or if it is sold at an uncompetitive price, the alternative would not gain sufficient market share to make its production economically feasible. The key conclusion is that the technical and economic feasibility of each alternative is a combination of:
Its (potential) acceptability by downstream users in technical and economic terms;
Its (potential) future sales (i.e. ability to replace at least a significant part of the current DEHP sales); and
The accessibility of its manufacturing technology and of its precursors to the applicant. With regard to the acceptability of the selected potential alternative substances by downstream users, the following general conclusions can be reached:
The technical requirements for the use of an alternative plasticiser in an industrial setting must be combined with the performance requirements of PVC articles during the service life of those articles. This increases the complexity of the technical criteria each alternative must meet before it is considered a feasible alternative;
A significant proportion of the alternatives are not general purpose plasticisers but rather find limited or niche applications, particularly in applications for which DEHP has already been substituted as a result of past regulatory action (i.e. in toys, childcare products, etc.), or specific technical applications which benefits from isolated, key advantages of the selected alternative plasticiser (e.g. high or low-temperature applications); and
For many of the selected potential alternative substances, the cost of the plasticiser would significantly increase upon the replacement of DEHP. Production costs might become more than double in certain cases, taking into account the per tonne price of certain alternatives and the need for increased loading for some of them. In relation to the potential future sales of each of the selected potential alternative substances (based on information from consultation), two groups can be identified:
Sales for the majority of the selected substances would not be expected to amount to more than a modest share of the applicant’s current DEHP sales (it would be much lower than 50% and would vary by substance, on occasion being far lower than 10%); and
Sales for a few selected potential alternative substances might theoretically be able to replace a more substantial percentage of current DEHP sales but, importantly, they could not replace all DEHP applications and there are issues with their availability to the applicant or questions over the future regulatory situation and importantly, the technical feasibility of manufacture by the applicant can be highly uncertain. Finally, and most crucially, the applicant may face severe technical and market obstacles in their quest to manufacture several of the selected alternative substances. More specifically, uptake of their manufacture at the industrial scale may be severely hindered by:
Use number: 1,2 Legal name of applicant: Arkema 15
ANALYSIS OF ALTERNATIVES
The need for a complete or partial plant conversion;
The relevant manufacturing technology being protected by patents to which access is not available (or could perhaps become available at a considerable cost);
The precursors to specific alternatives not being readily available on the market in quantities sufficient to allow the production and sale of volumes of plasticisers that could justify the significant investment required in a new production line; and
The presence of established suppliers who have a market advantage and thus could become the preferred suppliers to the applicant’s current downstream users. Without having secured (a) market acceptability, (b) access to the necessary technology, and (c) long-term supply reliability of the precursors to any given alternative substance, the technical and economic feasibility and viability of a new substance within the applicant’s portfolio cannot be guaranteed. The Confidential Annex explains that none of the selected potential alternative substances can be considered to meet the minimum technical and feasibility criteria to act as a replacement for DEHP.
1.4 Summary of the findings on the suitability of potential alternative substances This is presented in Section 4.
1.5 Conclusion The conclusion of the AoA is that there are no alternatives to DEHP that are currently available to the applicant for the applied-for uses. Of particular note is the fact that, as described in detail in the Confidential Annex and in the SEA, the applicant would face significant difficulties in accessing the manufacturing technology and/or precursor chemicals required to move to some of the alternatives, including those which may be acceptable to a significant percentage of downstream users. With regard to this public document, conclusions regarding the suitability of potential alternatives can be found in Section 5. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 1.5
1.6 Actions required for making the alternatives suitable and available For several of the selected potential alternative substances, there are no realistic prospects for them becoming technically and economically feasible for the applicant: they are destined to act as specialist plasticisers and their market share is extremely unlikely to reach levels that would make their manufacture viable and profitable in the long-term. For a sub-group of those, the limitations on access to the manufacturing technology (presence of patents, etc.) certainly eliminate any thought of future manufacture. For other alternative substances, which may have more realistic prospects of capturing a significant percentage of the market (and some may have already done so), there are the two key prerequisites for the applicant to consider switching to them from DEHP:
16 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Changes in market conditions that would allow for long-term secure access to the supply of precursors, or to raw materials for those precursors, in an environment that would encourage competition amongst suppliers (i.e. long term supply at long term reasonable price); and
Certainty on the envisaged long-term regulatory pressures that each alternative substance may face. It is clear that the research on the effects of certain alternatives that are promoted as the main replacements for DEHP has not been concluded and it would not be prudent for the applicant to plan and execute a transition to an alternative substance which may sooner or later face similar regulatory pressures. The Confidential Annex and the SEA explain these prerequisites in more detail. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4
Use number: 1,2 Legal name of applicant: Arkema 17
ANALYSIS OF ALTERNATIVES
2 ANALYSIS OF SUBSTANCE FUNCTION
2.1 Introduction As noted in Section 1, the analysis of technical feasibility has to be carried out from two different perspectives: that of the applicant and that of the applicant’s supply chain. Thus, the analysis of substance function must also take into account both of these perspectives. The discussion on substance function has been organised as follows:
Material flows in the plastics industry and the role of polymer plasticisers are discussed in Section 2.2;
Technical feasibility considerations from the perspective of the applicant are discussed in Section 2.3; and
Technical feasibility criteria from the perspective of downstream users are discussed in Section 2.4.
2.2 Introduction to plasticised polymers
2.2.1 Roles and material flows in the polymers and plastics industries Polymers can be defined as the virgin products of the chemical/petrochemical industry that have undergone no significant post-reactor treatments. Plastic materials can, however, be defined as polymers which have been modified in some way, for example, through the addition of additives and processing under pressure and/or heat in order to satisfy a variety of performance criteria relating to their end-use application (OECD, 2004). Four distinct activities fall under the general heading of the plastics industry – polymer manufacture, compounding, conversion and “in-house” manufacture. The relationship between these activities is illustrated in Figure 2.1. Figure 2.2 highlights the basic processes used by the plastics industry. The figure describes (in general terms) the complexity of processes involved in the use of DEHP in the formulation of PVC compounds and the processing of these compounds in the manufacture of plasticised PVC articles. The CSR confirms that both formulation and processing (the two applied-for uses, see below) are described by a considerable number of process categories (PROC codes).
2.2.2 Role of plasticisers The polymer modification of interest to this AoA is the softening of a polymer. Two main methods exist for softening a polymer (ECPI, 2010b):
Internal plasticisation, through co-polymerisation by using chemicals that modify the polymer or monomer so that its flexibility is increased; or
External plasticisation, by the addition of a suitable plasticising agent, i.e. by preparing a blend consisting of a resin and a plasticiser.
18 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Figure 2.1: Manufacturing stages of the plastics industry Source: OECD (2004)
Use number: 1,2 Legal name of applicant: Arkema 19
ANALYSIS OF ALTERNATIVES
Figure 2.2: Plastics processing and use (overview) Source: OECD (2004)
As noted by Titow (1984), the formal definition for a ‘plasticiser’ was adopted by the International Union of Pure and Applied Chemistry (IUPAC) in September 1951, and is as follows: “A plasticiser or softener is a substance or material incorporated into a material (usually a plastic or an elastomer) to increase its flexibility, workability or distensibility. A plasticiser may reduce the melt viscosity, lower the temperature of the second-order transition or lower the elastic modulus of the melt”.
20 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Essentially, when combined with PVC, plasticisers convert the rigid, intractable resins into workable compounds which can exhibit a wide range of properties depending on the type and concentration of plasticisers used. The properties required for plasticisers, or the plasticised PVC products, generally include compatibility with the resins, non-volatility, non-flammability, good heat and light stability, good low temperature performance and non-toxicity (Titow, 1984). Titow (1984) notes that resins plasticised internally by co-polymerisation are generally inferior to externally plasticised systems in strength and low temperature properties. Furthermore, ECPI (2010b) notes that external plasticisation is the preferred and most common route because of the lower overall costs and the fact that the use of external plasticisers gives the manufacturer of the final article a certain degree of freedom in devising different formulations for a range of products. Notably, more than 98% of plasticisers used in plastics materials are used in PVC, with a small quantity of specialised materials being used in polyamides (nylon) (OECD, 2004).
2.2.3 Role of DEHP in the applied-for uses
2.2.3.1 Scope of this Analysis of Alternatives DEHP is an external plasticiser and this is the role of concern to this AfA. In this Application, Authorisation is sought exclusively in relation to the use of DEHP in the formulation and processing of flexible PVC (‘flexible PVC’ is also known as ‘soft’ or ‘plasticised’ PVC). DEHP is also used as a plasticiser in other polymer products and non-PVC formulations and products, for example, adhesives, rubber, etc. These are not relevant to this Application.
2.2.3.2 Identification of applied-for uses for DEHP The two applied-for uses of relevance to this Application are as follows. Applied-for use 1: PVC formulation Title: Formulation of DEHP in compounds, dry-blends and plastisol formulations. Applied-for use 2: Processing of polymers Title: Industrial use in polymer processing by calendering, spread coating, extrusion, injection moulding to produce PVC articles [except erasers, sex toys, small household items (<10cm) that can be swallowed by children, clothing intended to be worn against the bare skin; also toys, cosmetics and food contact material (restricted under other EU regulation)].
2.3 Technical feasibility considerations from the perspective of the applicant
2.3.1 Technical characteristics of DEHP manufacture The manufacture of DEHP (a diester) requires two key raw materials, an alcohol and an acid (or the respective anhydride). The alcohol is 2-ethylhexan-1-ol (hereafter referred to as 2-EH) and the acid is phthalic anhydride (hereafter referred to as PA). Esters derived from PA as the acid component are called phthalate esters, or simply phthalates. In other words, for the manufacture of other phthalates, different alcohols are needed but the anhydride will still be PA.
Use number: 1,2 Legal name of applicant: Arkema 21
ANALYSIS OF ALTERNATIVES
Of great importance for the availability of the precursor alcohols is the availability of their own precursors. Different alcohols come from different raw materials/precursors; for example:
DEHP: the precursor alcohol is 2-EH. This alcohol is derived from n-butyraldehyde;
Di-isononyl phthalate (DINP): the precursor alcohol is isononyl alcohol (isononanol). This alcohol is derived from C4 petrochemicals or octenes;
Di-isodecyl phthalate (DIDP): the precursor alcohol is isodecyl alcohol (isodecanol). This alcohol is derived from nonenes; and
Di-propylheptyl phthalate (DPHP): the precursor alcohol is 2-propylheptyl alcohol. This alcohol is derived from mixed butenes. Many of the other potential non-phthalate alternatives for DEHP are alternative esters, for example, terephthalates, adipates, trimellitates, etc. As a result, similar approaches need to be taken for their manufacture. For instance, for bis(2-ethylhexyl) terephtalate (DEHT, also referred to as dioctyl terephthalate, DOTP), the alcohol is the same as for DEHP but the acid component6 is derived from terephthalic acid rather than phthalic anhydride.
2.3.2 Parameters of technical feasibility from the applicant’s perspective With the view of assessing the technical feasibility of different alternative substances, from the applicant’s perspective, technical feasibility of a specific potential alternative will be a function of three technical criteria:
Production integration;
Availability of the raw material precursors; and
Production plant requirements.
2.3.2.1 Production integration Oxo-plants are industrial plants involved in the manufacture and/or use of oxo-alcohols. These are alcohols produced by the oxo-process (also known as hydroformylation) in which an alkene (olefin) reacts with syngas (CO and H2) in the presence of a catalyst; the products of this reaction are aldehyde isomers. Subsequently, the aldehyde is hydrogenated to obtain an alcohol (with a carbon number one higher than the reacting alkene). Production integration is very important in the phthalates industry and for the viability of oxo- plants. There are distinct advantages to having the 2-EH and PA precursors to DEHP being manufactured either on the same site where the DEHP plant is located, or at a separate plant that is owned by the company that manufactures DEHP. All three members of the DEHP ATF are integrated on either the alcohol or the anhydride side of the DEHP manufacturing process, or both. The discussion below is generic and additional information that is specific to the applicant is presented in the Confidential Annex.
6 The “acid component” refers to one half of the plasticiser diester moiety. The precursor here could be an acid, anhydride, acid chloride, or ester. However, most relevant for large volume production are the acids, anhydrides and other esters (e.g. dimethyl terephthalate).
22 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.1
Integration on the alcohol In addition to the possibility of purchasing the substance on the open market, EU-based DEHP manufacturers (e.g. members of the DEHP ATF) may manufacture 2-EH internally, either on the site that produces DEHP or a different site with the substance then transported to the DEHP manufacturing plant. With regard to 2-EH that is internally manufactured, only a certain percentage of this is actually used in the manufacture of DEHP. The remainder is either used internally in unrelated applications or is sold to EU and non-EU customers.
For any DEHP manufacturer integrated on the production of 2-EH, a refused Authorisation would have significant direct and indirect impacts, such as the loss of production integration, which would eliminate the economic benefits derived from such arrangement. It is important to note that it is integration with raw materials that delivers a contribution to economic viability. The reduction in internal demand for 2EH will result in the applicant having to compensate for this on other markets. Integration on the anhydride All members of the DEHP ATF manufacture PA internally. In all three cases, the entire amount is manufactured on the same site where the DEHP manufacturing plant is located. The tonnage of PA that is not used internally in the manufacture of DEHP is used internally (for other purposes), sold to affiliated companies or sold to other customers.
For all DEHP manufacturers integrated on the production of PA, a refused Authorisation would have significant direct and indirect impacts:
Loss of production integration, which would eliminate the economic benefits derived from such an arrangement;
Affiliated companies could witness an increase in the price or stoppage of supply of PA by the applicant. This could affect the economics of their production that is entirely separate to the manufacture of DEHP by the applicant. It is important to note that it is integration with raw materials that delivers a contribution to economic viability. The cessation of DEHP production at the Chauny site could also result in closure of the PA and fumaric acid production plants, as the site as a whole will become unviable.
2.3.2.2 Availability of precursors For a move to manufacture of an alternative plasticiser to be technically and economically feasible, the precursor raw materials to the chosen alternative substance should be available to the applicant in sufficient quantities, and at a sufficiently competitive price to replace the current production volumes of DEHP. For the purposes of this AoA, the following criteria are assumed to determine whether or not the precursors are available:
The alcohol and the anhydride must be readily available on the EU market at a price that does not disproportionately undermine the profitability of the production plant;
They must be available in sufficient quantities to enable production of economically feasible levels of the alternative plasticiser (i.e. the scale of plant required to earn a return on
Use number: 1,2 Legal name of applicant: Arkema 23
ANALYSIS OF ALTERNATIVES
investment), taking into account the costs of investing in any plant modifications or new plant required for technical reasons; and
There must be a high level of certainty that these precursors will remain available on the market over normal investment time horizons (i.e. for 15 years as a minimum) and that they can and will be available to the applicant at a suitable price. Clearly, where the alternative would require a different alcohol and/or acid it may not meet the above criteria for availability. Of course, where the alternative is based on the same alcohol (or acid) as DEHP (for example, 2-EH used in the manufacture of bis(2-ethylhexyl)adipate, also known as DEHA), then it is clear that the precursor would be available to the applicant, and related impacts may therefore be reduced. Of particular concern is the market availability of alternative alcohols. It is generally acknowledged that the availability of alcohols for the manufacture of alternative plasticisers currently with the greatest market share is limited and controlled by a relatively small number of large companies, as shown in the SEA, and Confidential Annex. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Annex 2
These suppliers manufacture some of the alternative plasticisers themselves. Thus, at present, they are competitors to the applicant. By supplying alcohols to the applicant, they would effectively allow the applicant to enter their existing markets for the alternative plasticisers as a direct competitor. Therefore, there is concern as to whether these few alcohol suppliers would be willing to supply their product to the applicant at a sufficiently competitive price to effectively allow the applicant’s product to compete directly with theirs. Such an uncertain and potentially unreliable supply of raw materials would leave the applicant exposed to the strategic market manoeuvring of the few large alcohol suppliers. This is an uncertain ground on which future manufacture of an alternative cannot be established with a long- term view. The situation with the availability of acid precursors is also complicated. As is explained in the Confidential Annex, the identities of precursors to some alternative substances are not clear and the applicant’s knowledge of the relevant markets is limited. For the manufacture of other potential alternative substances, new acids which are not currently manufactured by the applicant would be required, but could potentially be sourced from the open market. Still, production integration for the applicant would be lost. Finally, there are potential alternative substances for which PA would still be needed. PA availability is guaranteed in the short term (as the applicant, like all ATF members, is integrated on PA), but production of PA may not be viable in the longer term if capacity utilisation is low and downstream markets for the anhydride are insufficient. In other words, unless the applicant can secure a sufficient level of sales of the alternative(s) that requires PA, the future of PA production would not be guaranteed. It is also worth noting that phthalates are subject to ongoing regulatory scrutiny, further complicating the prospects for future use of PA as a precursor to an alternative phthalate ester.
24 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
2.3.2.3 Production plant requirements and feasibility of process modification The technical feasibility of modifying the applicant’s existing DEHP production plant, or construction of a new plant so as to manufacture any of the potential alternative substances will depend on:
Ability to produce the acid and/or the alcohol precursors in the existing production plant;
Differences in production techniques including the consideration of continuous versus batch production, plant set-up, manufacturing conditions and parameters (temperature, pressure, pH, duration) which may place variable requirements upon the production plant installation;
Ability to convert all or part of the existing DEHP manufacturing unit to the production of the alternative, taking into account the differences in the chemical properties of the precursor materials;
Differences in handling requirements for the precursors (e.g. in terms of transport and storage and any associated on-site requirements); and
Ability to develop the required knowledge for the manufacture of the selected alternative substance through R&D and investment. It must be noted that there may be alternative substances for which their manufacturing technology might be protected by patents which would restrict the availability of the technology to the applicant. Ability to produce the acid or the alcohol precursor in the existing production plant It is important to consider the potential for use of the existing production equipment when different precursors to the plasticiser need to be used. A practical example is given here with respect to the use of alternative acid precursors. All DEHP ATF members currently produce PA on or near their DEHP plant in a dedicated plant unit. One method of PA production is via oxidation of o-xylene at elevated temperatures (Technobell, 2013). The resulting PA is then isolated by use of switch condensers (GEA, 2013). The physical properties of PA are key to the success of this process; its melting point is 130-134°C and it sublimes at 295°C7. These attributes enable the switch condensers to condense the PA vapour to a solid and then isolate it as a liquid. If the same equipment and process were to be used to oxidise p-xylene to produce a fairly similar acid, such as terephthalic acid (the precursor acid to DEHT), the differences in their physical properties would result in the switch condenser clogging with solid terephthalic acid. This is because the sublimation point of terephthalic acid is 402°C and it does not melt to produce a liquid (at ambient pressure)8. Thus, any switch to a different acid precursor will render this plant unit obsolete and, because these plant units are continuous operation plants, they cannot be repurposed. Therefore, if the applicant were to begin production of a new acid precursor, detailed engineering studies and considerable expenditure (with the associated financing and capital costs) would be required to commission a new plant unit.
7 Physical properties of phthalic anhydride: http://www.chemspider.com/Chemical-Structure.6552.html 8 Physical properties of terephthalic acid: http://www.chemspider.com/Chemical-Structure.7208.html
Use number: 1,2 Legal name of applicant: Arkema 25
ANALYSIS OF ALTERNATIVES
Continuous versus batch production There are key differences between continuous and batch production processes for plasticiser manufacture. A continuous process is accompanied by certain key limitations:
Adapting the existing equipment would be more costly;
Production of an alternative plasticiser as a replacement for DEHP could potentially entail higher risks, as the continuous process would be optimised for the production of one single high-volume product in order to make the production costs economical and avoid the necessity to invest in new storage facilities. Such facilities would be costly to build. By contrast, in a batch process, the ability to ‘test/trial’ different alternatives is (in general) likely to involve less significant investment in ‘substance specific’ equipment but may also require e.g. the availability of storage; this can be a limiting factor to production of several different alternatives for batch producers;
The applicant would need assurance from market analysis that there would be sufficient demand for the alternative plasticiser to make such an investment worthwhile; and
The applicant would need to secure competitive access (in terms of price) to the corresponding raw materials at the required volume and guaranteed for the long term. Put simply, a continuous process favours the manufacture of an alternative plasticiser in bulk, if there is a market for the substance, while a batch process allows greater flexibility. Ability to convert all or part of the existing DEHP plasticiser unit As discussed above, batch plants are designed to be flexible although at an additional cost, making them more suitable for higher value products. Applicants operating batch units are likely to be able to produce a number of related alternative substances with only minimal changes in the technical process. Substances that differ more significantly from the original substance are likely to need more considerable modifications and potentially a new plant. For example, it is likely that a batch- process plant currently manufacturing DEHP would be able to manufacture other phthalates, terephthalates, trimellitates and alkyl esters, but would not be suitable for the production of phosphate or sulphonate esters (IPPEC, 2011). In the case of batch processes, the proportion of the plant-equipment that could be converted to the production of alternatives depends largely on the degree of difference between the chemical reactivities and properties of the precursors and products of the alternative materials and those of 2- EH, PA and DEHP. For ATF members operating continuous DEHP production plants, a significant portion of the plant equipment would become redundant when switching to the production of an alternative material. If reaction temperatures or other conditions (e.g. catalysts, residence times) are changed then large portions of the plant would need to be specified and tested to ensure plant operational safety margins. Because of the complexity and strict operating margins of continuous plants, it may be more economically sound to commission a new plant, rather than attempt to balance new and old equipment. Differences in handling requirements for the precursors If the applicant were to lose the integration of existing precursors to their plasticiser production, this could impact upon the flexibility and reliability of supply to their downstream supply chain. To be able to serve customers throughout demand fluctuations, a predictable supply of the alcohol and/or acid component would need to be established. If the applicant was no longer in control of the
26 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
manufacture of the precursors, the applicant would be obliged to create some inventory in order to be able to serve the needs of his customers without interruption. This would lead to a certain lock- up of capital which would impact the economics of the business. Access to the technology A switch to an alternative plasticiser requires the development of the necessary knowledge on how the precursors need to be handled, how they must be reacted, what conditions need to be achieved in the reactor, etc. in order for (a) the manufacture to be undertaken safely, (b) the quality of the final product to be acceptable to the customers, and (c) the yield of the reaction to be such that it can be run profitably in the long-term. Developing such knowledge is a process that takes time as it requires considerable R&D work: it may start in the laboratory, technical parameters may be tested in a pilot plant and thereon production may be trialled at the industrial scale before the actual production of the alternative substance starts. Moreover, a number of alternative substances, particularly newer entries into the plasticisers market, may have intellectual property rights attached to them or to the processes used in their manufacture. The holder of the relevant patents is likely to be another manufacturer/competitor, in which case they may be reluctant to grant the applicant access to the technology. A patent issue may also arise in relation to the manufacture of alcohols or other precursors, unless the applicant is able to source the precursors at a competitive price on the free market. Holders of patents on the technology for the production of precursors are also likely to be manufacturers of alternative plasticisers and it is therefore highly uncertain that they would consider granting the applicant access to their patented manufacturing technology.
2.4 Technical considerations in selecting a plasticiser
2.4.1 Overview of plasticiser types An overview of the different plasticiser families with a quick presentation of their main areas of application is given in Table 2.1.
2.4.2 How to select a plasticiser Plasticisers are not universally suitable for use in any polymer matrix. Some parameters or properties of a plasticiser that may be of value in a given polymer matrix for one type of application may be detrimental in another. For example, a high rate of diffusion will increase efficiency and the rate of gelation during processing but may also make for poorer performance in the end product. Plasticisers are as important as the choice of resin, as it is the combination that is responsible for the physical properties of the plasticised product, its processing performance, and its cost. In selecting a plasticiser, the downstream user must consider a number of technical parameters, such as compatibility, efficiency, permanence, and economy, which depend on specific technical criteria before the ultimate goals of the production and final product (article) can be achieved. This decision-making process can be described as shown in Figure 2.3.
Use number: 1,2 Legal name of applicant: Arkema 27
ANALYSIS OF ALTERNATIVES
Technical dependency Technical parameter Ultimate goal
- Polarity Adequate processing parameters for the - Structural configuration Compatibility plasticised compound - Size of molecule
- Volatility Performance, longevity and marketing Permanence - Susceptibility to extraction characteristics of the end product (article)
- Raw material costs Economics of production remain Economy - Conversion costs favourable
Figure 2.3: Decision-making process for selecting a plasticiser In practice, the choice of plasticiser is generally a compromise between the processing technique (that has) to be used, the end application of the plasticised material and economic factors. It is for this reason that DEHP, as a general purpose plasticiser, has been so successful: it can address the needs of a wide range of users and applications, at a cost-effective price, allowing the production of a variety of products/articles from a small number (if not single) of production lines. The role of general purpose plasticisers is described further below.
28 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 2.1: Overview of plasticiser families Plasticiser family Short description Key notes on applications Phthalates The most commonly used plasticisers in the world. In Europe, ca. 1 PVC applications: Electrical cables, Hoses, Flooring, Wall million tonnes of phthalates are produced each year, of which coverings, Coated textiles, Luggage, Sports equipment, Roofing, Pool approximately 93% are used to make flexible PVC. liners, Footwear, Medical devices such as tubing and blood bags.
Manufactured by reacting PA with alcohol(s) which range from methanol Non-PVC applications: Coatings, Rubber products, Adhesives, and ethanol (C1/C2) up to tridecyl alcohol (C13), either as a straight Sealants chain or with some branching. Low molecular weight Include DEHP, DBP, DIBP and BBP and represent about 11% of the (LMW) phthalates European market. High molecular weight Include DINP, DIDP, DPHP, DIUP, and DTDP and represent just around (HMW) phthalates 85% of all the phthalates currently being produced in Europe Aliphatic dibasic acid Based on aliphatic dibasic acids with carbon numbers ranging from C5 esters (glutaric) to C10 (sebacic). Adipates Alcohols of similar chain length to those used in phthalate manufacturing In PVC applications, adipates offer enhanced low temperature (typically in the C8 to C10) range can be esterified with adipic acid, properties compared to phthalates. In plastisol applications, adipates rather than PA, to produce a range of adipate plasticisers, e.g. di-2- impart low plastisol viscosities due to their lower neat viscosities ethylhexyl adipate (DEHA). Sebacates Di-2-ethylhexyl sebacate (DOS) and di-2-ethylhexyl azelate (DOZ) are These plasticisers impart low temperature performances superior to & Azelates the most common members of this group, but di-isodecyl sebacate adipates but also command a significant premium, and their use is (DIDS) is also used. generally limited to extremely demanding low temperature flexibility specifications (e.g. underground cable sheathing in arctic environments) Benzoate esters Di-benzoate plasticisers are obtained by direct esterification of benzoic Used primarily in non PVC applications such as PVAc based acid with glycols. adhesives, latex caulks and polysulphide sealants Citrates Citric acid is the starting material for a number of citrate ester Toys, Pacifiers, Medical devices, Packaging films. plasticisers, such as tributyl citrate, acetyl tributyl citrate, triethyl citrate, 58% are used in food and beverage applications, 24% in household acetyl triethyl citrate and tri-2-ethylhexyl citrate. detergents and cleaners, 9% in pharmaceuticals and 9% in industrial applications Epoxy esters Esters containing an epoxy group such as epoxidised soybean oil (ESBO) Used to improve heat stability in the production of PVC articles by and epoxidised linseed oil (ELO). They are formed by the oxidation of techniques such as extrusion, calendering, injection moulding, an olefinic double bond to an oxirane structure. rotational moulding and spread coating. They are also used in rubbers, epoxy resins, paints and coatings. These can act as lubricants but also act as secondary stabilisers for PVC due to their epoxy content which can remove HCl from the degrading polymer
Use number: 1,2 Legal name of applicant: Arkema 29
ANALYSIS OF ALTERNATIVES
Plasticiser family Short description Key notes on applications Phosphate Esters Triaryl phosphates and alkyl diaryl phosphates are the two important The principal advantage of phosphate esters is their improved fire categories of flame retardant phosphate plasticisers. Phosphate esters can retardancy compared to phthalates. The fire performance of PVC, help produce low smoke, low flammable flexible PVC. relative to other polymeric materials, is extremely good due to its high halogen content, but the addition of certain plasticisers may impair this property Terephthalates Terephthalates are the other commercial isomeric form of phthalates. Applications focused on low temperature properties, better resistance Terephthalates are esters of terephthalic acid and include the 1,4 to soapy water extraction and lower volatility. In plastisols, DEHT benzenedicarboxilic acid ester often referred to as DEHT (di- provides lower initial viscosity and better viscosity stability but (2ethylhexyl) terephthalate) or DOTP (di-octyl terephthalate). requires higher fusion and processing temperature Triglyceride Different types of glycerol esters have been proposed as alternatives to plasticisers low phthalates, their limited availability and higher costs currently limit their use. Trimellitates Trimellitates are produced by the esterification of C7-C10 alcohols with Due to their low volatility, these plasticisers are used in the trimellitic anhydride (TMA), which is similar in structure to PA with the automotive industry (dashboard PVC skin produced by slush exception of a third functionality on the aromatic ring. Consequently, moulding) and in the insulation or sheathing of electrical cables esters are produced in the ratio of three moles of alcohol to one mole of anhydride. Common esters in this family are Tris-2-ethyhexyl trimellitate (Tri-octyl trimellitate - TOTM), L79TM, an ester of mixed semi-linear C7 and C9 alcohols, and L810TM, an ester of mixed C8 and C10 linear alcohols.
Glycerol Acetylated This plasticiser is made from fully hardened castor oil and acetic acid. Expected main PVC applications for such esters are toys, bottle cap esters Castor oil is extracted from the seeds of the castor oil plant, which is an liners, screw cap liners for e.g. jam, teething rings, cling film, tubes annual plant grown in India, Brazil and China. The castor oil contains and conveyor belts in the food industry and medical equipment between 85% to 95% ricinoleic acid. The performance of castor oil is improved by modifying its structure (hardening) and replacing the longer chain acids with acetic acid. The resulting fully acetylated glycerol monoester has a lower molecular weight, improving the compatibility and processability of the plasticiser. Source: Reproduced from: ECPI (2010a)
30 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
2.4.3 General Purpose plasticisers and commercial success of DEHP As highlighted by Wilkes et al. (2005) plasticiser types can be allocated into three subgroups relating to their performance characteristics in PVC:
General Purpose Plasticisers (GP): these provide the desired flexibility to PVC along with an overall balance of optimum properties at the lowest cost. These are dialkyl phthalates (including DEHP), along with low cost oils called “extenders”;
Performance Plasticisers (PP): these contribute secondary performance properties desired in flexible PVC beyond the GP type, while imposing somewhat higher costs. Key performance criteria are “Strong solvents”, “Low temperature” and “Low volatility”. These include specific phthalates and other types of plasticisers. Strong solvents have higher polarity and/or aromatic properties. Conversely, low temperature plasticisers, such as aliphatic dibasic esters, are less solvating and have higher diffusivity. Low volatility requires high molecular weight plasticizers, such as trimellitates and polyesters (polymeric); and
Specialty Plasticisers (SP): these provide properties beyond those typically associated with flexible PVC, designed for general purpose or specialty characteristics. These exceptional characteristics are typically a function of specific chemical plasticiser families and may vary as a function of isomeric structure and/or homologues. Such properties are shown in Table 2.2 as “Low diffusivity”, “Stability”, and “Flame resistance”. Few phthalates meet these special requirements. Specialty plasticisers impose even higher costs than PP grade plasticisers. Table 2.2: Plasticiser Family / Performance Overview Performance plasticisers Specialty plasticisers General Family Strong Low Low Low Flame Purpose Stability Solvent Temperature Volatility Diffusivity Resistance Phthalates Trimellitates Aliphatic dibasic esters Polyesters Epoxides Phosphates Extenders Miscellaneous = Primary performance function =Secondary performance function Source: Wilkes et al. (2005)
DEHP is a prime example of a GP plasticiser: it offers good all-round performance and is therefore used to deliver cost-effective performance in general purpose products. DEHP possesses reasonable plasticising efficiency, fusion rate9 and viscosity10 (of great importance for plastisol
9 The ability to blend into the polymer melt. 10 The viscosity of a fluid is a measure of its resistance to gradual deformation by shear stress or tensile stress. For liquids, it corresponds to the informal notion of “thickness”.
Use number: 1,2 Legal name of applicant: Arkema 31
ANALYSIS OF ALTERNATIVES
applications). The ability of DEHP to address the needs of PVC formulation and processing and be used in the production of a multitude of PVC articles cannot be overemphasised.
2.4.4 Technical feasibility and selection criteria for DEHP and alternatives
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 2.4.4
2.4.4.1 Introduction The analysis of the technical feasibility of alternatives to DEHP has to consider how the roles and/or tasks of DEHP can be fulfilled by another substance or technology. Therefore, an analysis of how DEHP and alternative substances perform within the two applied-for uses is required, i.e. formulation of PVC compounds, and processing of PVC compounds into articles. In other words, the technical requirements and practical considerations of the downstream users (those using DEHP and those processing PVC compounds that contain DEHP) are of key importance to this analysis. Furthermore, the selection of plasticiser by a downstream user (e.g. a PVC converter) is not merely dictated by how DEHP facilitates the production process. Its performance in the end product may be even more important, i.e. whether a plasticiser in the final PVC article is able to perform in a particular way or display specific desirable qualities and characteristics. Thus, the technical requirements of the end-user (often an end-consumer) also need to be taken into consideration when establishing technical criteria for alternative plasticisers.
2.4.4.2 Approach to information collection Whilst the scientific and technical literature has been consulted on the role of plasticisers such as DEHP, another important source of information is the current users of DEHP, who have first-hand knowledge of the requirements their flexible PVC compounds and articles must meet. In order to collect such data, a series of questionnaires were disseminated to the customers of the three ATF companies applying for Authorisation11, as well as to industry associations whose members may be downstream users of DEHP plasticised PVC. The applicant believes that the survey undertaken for the purposes of this AfA is the widest and most comprehensive ever to be made in the EU and presents a very representative analysis of the EU PVC conversion market. Requests for information were sent out to over 200 customers of the DEHP ATF, with this including compounders/formulators, traders/distributors (some of whom disseminated questionnaires to their customers) and article producers who may or may not also use DEHP on-site to produce plasticised PVC for their own use. Individual companies on the list were contacted using a standardised email, with follow-ups carried out by telephone and email. There was a high level of cooperation with over 80 customers providing feedback. Note that there were several iterations to the survey work, with initial contact followed by requests for more detail and various follow-up questions to clarify uses and issues concerning technical and economic feasibility (and hence economic impacts).
11 At the time of this survey, Oltchim was also participating in the DEHP ATF and its customers were also surveyed. Details on the consultation efforts made during the preparation of this AoA are provided in Section 3.2.3 (also, further details regarding Oltchim’s participation within the ATF are provided in Section 3.2.3.3).
32 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
In addition to those companies providing detailed information on their use of DEHP, there were further responses from companies which have either moved away from DEHP or which are planning on moving away from DEHP. The survey indicated that the two most important criteria are the cost of the plasticiser followed by its compatibility with PVC. Clearly, if the substance has a poor compatibility with PVC, its ability to work as a PVC plasticiser is diminished. Nevertheless, various specific applications of PVC compounds/articles have different key requirements that the alternative plasticiser must meet. Consultees were asked to identify the relevant and additional comparison criteria by application category, which showed that compatibility, processability, heat stability and colour were consistently important across a range of applications. Other criteria were only of primary concern in a smaller number of applications. However, most applications rely on multiple criteria and it can be expected that those applications that have more stringent requirements (indicated by a wide range of relevant comparison criteria) also have a smaller range of alternative plasticisers able to deliver the necessary specifications. The identities and relative importance of the comparison criteria that are relevant across the range of applications of DEHP-containing PVC as established from the downstream user consultation are presented in the Confidential Annex to this AoA.
Following the receipt and analysis of information from the first consultation, a secondary search of scientific and technical literature was undertaken. The aim of this secondary search was to build upon information received from the initial stages, clarify the meaning of certain criteria (which can often be interpreted differently by different stakeholders) and provide a robust and reliable means of comparing the potential alternatives to DEHP. To this end, the final list of technical feasibility and selection criteria (which is applied to the prioritised list of potential alternatives, assessed in Section 4) was developed and is described below.
2.4.4.3 General technical comparison criteria As indicated above, the selection of a plasticiser for the formulation of a PVC compound requires the balancing of diverging qualities, properties and parameters of the plasticiser and of the polymer for the plastic material. It must also be remembered that PVC is used in a multitude of products. Therefore, being able to choose a plasticiser that strikes the right balance across a very wide range of products is extremely desirable for the commercial success of EU businesses. DEHP is generally considered to be the industry standard due to the fact that it is in the mid-range of plasticiser properties at an attractive price point. As specific properties are more important for some applications than others, certain plasticisers find more extensive use in particular application areas than others. As noted by Wadey (undated), the PVC technologist must ascertain the most important properties for an application and then make the correct choice of plasticiser. As a result, when identifying the critical properties of DEHP in its use in PVC, it is important that the following points are considered:
Overarching critical properties that allow the use of a plasticiser in PVC compounding;
Critical properties of the plasticiser, which make it suitable for use in the manufacturing process that leads to the formulation of the compounds, dry-blends and plastisol formulations;
Use number: 1,2 Legal name of applicant: Arkema 33
ANALYSIS OF ALTERNATIVES
Critical properties of the resulting formulations (which are associated with / depend on the presence of DEHP), which need to be achieved in order for the final product (PVC article) to function as required and prescribed by the customer and/or end-user; and
Critical properties of the end-products (which are associated with / depend on the presence of DEHP), which need to be achieved in order for these to be successfully sold on the market and deliver the functionality required by the end-user over a minimum time period. The list of technical criteria used in assessing the technical feasibility of alternative substances is provided in Table 2.3. The table also indicates which of these are ‘Core Criteria’ (of highest importance, as discussed further below). Table 2.3: Technical feasibility and selection criteria for the assessment of alternatives Specific technical feasibility and selection Secondary Criteria category Core Criterion criteria Criterion Overarching criteria PVC compatibility Criteria relating to the Processability substance properties and the Efficiency manufacturing process (of flexible PVC) Melting/freezing point Low temperature performance Clarity Criteria relating to the Elastic recovery performance of the PVC end- product Odour Sterilisability Printability and adhesion properties Criteria relating to the lifetime Permanence of the PVC Article Source: Literature search and consultation
2.4.4.4 Core Criterion 1: PVC compatibility12 Description and importance Information from literature: Compatibility is often cited in the literature as the first and foremost criterion for a plasticiser in terms of importance. Koleske (1995) notes that compatibility is the ability of two or more substances (e.g. a plasticiser and PVC) to mix together without objectionable separation, and, in the case of plasticisers, it is primarily a measure of the solvency or strength of the positive interactions between the plasticiser and the polymer which attract them together. Han (2005) notes that the compatibility of the plasticiser and intended polymer depends on the polarity, structural configuration and molecular weight of the plasticiser. Good compatibility results from the plasticiser and PVC polymer having a similar chemical structure. The preceding text implies that this criterion is closely linked with the processability of the plasticiser. Indeed, Zweifel et al. (2009) note that plasticisers with strong solvating characteristics for the resin enhance melt rheology and the ease of attaining the thermal conditions required for
12 Information has been obtained from http://www.academia.edu/1555847/PVC_Coating (accessed on 10 July 2013).
34 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
gelation and fusion of the polymer system. Less compatible plasticisers, on the other hand, usually impair processability. The notion of ‘compatibility’ does not simply relate to the PVC formulation lifecycle stage. For example, Daniels (2012) states that to a plastics compounder, ‘compatibility’ indicates that compound ingredients will remain associated with the polymer throughout the life of the product. Similarly, Wilson (1996) states that compatibility relates to whether plasticised formulations remain stable and free of separation of the components during service. Such terms imply that compatibility is often also interpreted in a long-term context, relating to the service life of the resultant flexible PVC article. Information from consultation: further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion There are several theoretical techniques and a number of practical technological tests by which plasticisers may be assessed for their compatibility with PVC. These are discussed briefly below (taken from Titow (1984)):
µ Value: this is a numerical index of the interaction (or mixing) between polymer and plasticiser, and can be determined from the swelling equilibrium of a lightly cross-linked polymer immersed in plasticiser;
Solubility parameter δ: the Hildebrand solubility parameter δ is directly related to a compound’s cohesive energy density and is a constant for any given compound. It can be shown that the miscibility of a solvent and solute (or PVC polymer and plasticiser) will in general be greater the smaller the difference between their solubility parameters. These values are therefore a guide to compatibility and miscibility;
Clear point temperature: this has been variously termed clear point, solid-gel transition, fusion point, solution temperature, and apparent melting temperature, but essentially it is the temperature at which a mixture of PVC and plasticiser becomes clear or undergoes an apparent phase change;
Flory-Huggins interaction Parameter χ: it has been shown that the Flory theory of melting in the presence of diluents could be applied to PVC-plasticiser interaction, and that the χ values correlate well with observed compatibilities;
Ap/Po ratio (polarity ratio): Van Veerson & Meulenberg (1967) devised a simplistic way of representing the polar – non-polar balance of a plasticiser by a single figure. It is calculated by dividing the number of C atoms in a plasticiser molecule by the number of ester groups present. Aromatic C atoms are not counted. The Ap/Po ratio of a wide range of plasticisers correlate well with a number of properties, including melting point, specific gravity, elastic modulus and water absorption;
Loop or roll compatibility tests: these are simple tests for assessing the compatibilities of plasticisers or plasticiser mixtures in a given PVC formulation. A number of test method variations exist, with differing degrees of severity, but the general principle is that a test strip is moulded from the compound and rolled into a fairly tight roll / bent into a loop of fixed dimensions, and stored under controlled conditions. Compatibility is judged (visually – and therefore subjectively) on the amount of plasticiser exuding out of the compound, when tension is released from the inner surfaces of the PVC sample; and
Use number: 1,2 Legal name of applicant: Arkema 35
ANALYSIS OF ALTERNATIVES
Maximum torque temperature: this is a method of assessing the interaction between plasticisers and PVC by means of relative fusion temperature in a Brabender Plastograph. The solubility parameter (δ), clear point temperature and Ap/Po ratio appear to be the three techniques most frequently cited in literature to determine compatibility. However, these might have limitations:
With regard to the solubility parameter methods, in a study of 12 plasticisers, Ramos-Devalle & Gilbert (1990) found that solubility parameters were capable of classifying plasticisers of a given family in terms of their compatibility with PVC, but were not useful for comparing plasticisers from different families. HallStar (undated) notes that plasticiser compatibility with an amorphous polymer (or the amorphous phase of a partially crystalline polymer), δ, normally requires values that do not differ by more than +1.5 (calories/cm3)1/2;
Relating to the Ap/Po ratio, low values (2-5) indicate high compatibility, whereas esters with Ap/Po ratios greater than ca. 14 are insufficiently compatible with PVC to be used as a plasticiser (Wilson, 1996). However, Patrick (2005) states that the polarity ratio alone is not able to compare plasticiser activities from different families; and
With regard to the clear point temperature, the lower the value the more compatible the plasticiser. Titow (1984) reports that this method has shown the relative ordering of plasticisers to be fairly consistent, despite a variation in published values and wide differences in experimental techniques. Despite the large variety of methods available to assess the compatibility of plasticisers, in the context of this AoA, it is not suitable to derive a performance scale or value range against which potential alternatives to DEHP can be assessed. This is because the importance and interpretation of this criterion appear to vary significantly in the perspectives of different stakeholders. Furthermore, as can be deduced from the above text, it is clear that PVC compatibility has a direct relationship with separately defined important criteria (i.e. processability and permanence). Consequently, for simplicity and clarity, the compatibility of potential alternative plasticisers is assessed in a qualitative/semi-quantitative manner. An additional note of importance is raised by Patrick (2005), who states that plasticiser compatibility limits can be influenced by the presence of other plasticisers and organic additives, particularly if they have a lower compatibility. Kutz (2011) adds that in most cases of exudation involving the more common plasticisers, the causative agent is not the plasticiser itself but other factors such as poor choice of stabiliser or partially decomposed stabilisers, or excessive use of lubricants. It is important to consider the influence of such external factors within the overall scope of the assessment.
2.4.4.5 Core Criterion 2: Processability Description and importance Information from literature: Processability is one of the core criteria against which any material serving as a plasticiser is judged. Wilkes et al. (2005) describe processability as the ease with which various processes combine the liquid plasticiser with the PVC polymer. Processability has also been noted to relate to how easily the PVC compound can be compounded and formed into the end product (Wilson, 1996) (this links to plasticiser efficiency, see Core Criterion 3). Processability is therefore a criterion that is relevant for both applied-for-uses (i.e. formulation and processing).
36 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
To achieve a usable plasticised PVC product, the polymer and plasticiser must be fully solvated or fused. The fusion or gelation temperatures are related to the solvating strength of the plasticiser and to the size of the plasticiser molecule. Plasticisers with solubility parameters close to that of PVC (i.e. highly compatible plasticisers) require less energy to solvate or fuse the PVC polymer while large plasticiser molecules require more thermal energy to plasticise the polymer (Craver & Carraher, 2000). Volatility is typically the limiting factor on use levels of strong solvating plasticisers. Higher molecular weight plasticisers typically offset volatility while imposing constraints on the ease of processing (Wilkes et al., 2005). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion No performance scale can be suitably defined. The processability of the plasticiser is somewhat dependent on the processing technique being used. Determining overall suitability is a fine balance which has to take into account other confounding factors (e.g. low volatility is typically associated with a lower level of plasticiser efficiency). The question of acceptability can therefore rest on comparative formulating costs and other critical properties (present at the specific conditions of use); consequently, each potential alternative will have to be assessed semi-quantitatively on an individual basis against this criterion.
2.4.4.6 Core Criterion 3: Plasticiser efficiency Description and importance Information from literature: The efficiency of a plasticiser refers to its ability to impart a desired property at low concentrations in the matrix (and/or in a cost-effective manner to the user). The higher the amount of plasticiser required to produce the desired property, the less efficient it is (Ramos-deValle, 1988). Typically, plasticiser efficiency is used to describe the ability of a plasticiser to make the product softer (as this is often the standard desired effect) and is reported as a ratio of the slope of the hardness versus plasticised concentration, the latter expressed in parts per hundred resin (phr) (Craver & Carraher, 2000). Importantly, it should be noted that similar efficiency comparisons can be made for other mechanical properties, but good hardness test reliability and the common practice of a designated room temperature hardness value supports its use in quantifying plasticising efficiency (Wilkes et al., 2005). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion A quantitative measure of relative plasticising efficiency is developed by determining the plasticiser concentration (in phr) required to meet a specific hardness versus some reference standard. For most applications, the reference standard chosen for PVC plasticisers is DEHP (Grossman, 2008). An example comparing DEHP and the potential alternative plasticiser DINP is described below (Figure 2.4). From the ratio of DINP phr that is required to achieve a defined hardness to the DEHP phr required for the same hardness, a quantitative substitution factor (SF) is developed for DINP
Use number: 1,2 Legal name of applicant: Arkema 37
ANALYSIS OF ALTERNATIVES
versus DEHP in providing equal hardness properties to flexible PVC at room conditions (Grossman, 2008). Durometer is one of several measures of the shore hardness of a material. To achieve a Durometer A of 80, 56.2 phr of DINP is required, versus 52.9 phr DEHP. Thus the SF calculated for DINP is SF = 56.2 / 52.9, or 1.06. This means that for the given hardness, 6% additional DINP is required to give the same hardness as that obtained with DEHP13. The SFs enable the formulator to readily approximate the needed formulation changes, as the effects of different plasticisers are considered (Grossman, 2008).
Figure 2.4: Shore A hardness versus plasticiser concentration (Source: Grossman (2008))
Consequently, using DEHP as the reference standard, the general rule for alternative substances would be to favour a SF lower than or similar to that of DEHP. However, as noted by Wilkes et al. (2005), the question of suitability rests on comparative formulating costs and other critical properties provided at the specified room temperature hardness. As a general rule, plasticisers associated with a high level of plasticising efficiency will have a higher level of volatility, which can cause processing issues, and lower the degree of permanence in the final article. Consequently, efficiency cannot be used as a ‘standalone’ technical criterion and must take these additional factors into consideration (as with the other criteria). This issue was also highlighted by consultees, who noted that it was important to take into account the ‘relative efficiency’ of DEHP and potential alternatives.
13 While this example targets 80 Durometer hardness, the calculation can be used at any specified hardness, or other property, required for the given end product of flexible PVC, although, as noted by Grossman (2008), it is this comparison that provides the most useful performance and economic basis.
38 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
2.4.4.7 Core Criterion 4: Permanence Description and importance Information from literature: Plasticisers are not permanently bound to the PVC polymer, but are free to self-associate and to associate with the polymer at differing sites. Thus, under certain conditions, plasticisers can leave the flexible PVC product (Craver & Carraher, 2000). Obviously, it is generally a desirable characteristic that, once a plasticiser is compounded with the PVC polymer, it should be permanently retained. The loss of the plasticiser would not only cause changes to the properties of the system, but may also have undesirable external side effects. For example, plasticised PVC floor tiles bedded with a bitumen adhesive may blister or lift as result of migration from the tile to the adhesive. Permanence is therefore a necessary property of a good plasticiser (Titow, 1984). As noted by Titow (1984), there are, in practice, three specific modes of loss of plasticiser from a plasticised composition, these are:
Volatilisation – in which plasticiser is lost at a surface into air;
Extraction – in which plasticiser is lost at a surface into a liquid, and
Migration – in which plasticiser is lost by transference between two surfaces in intimate contact. Plasticiser volatilisation is directly related to the vapour pressure of the plasticiser14, and volatile losses will occur during processing and use at elevated temperatures. Changes of as little as one carbon number of the alcohol group in a common series of esters can cause a significant reduction in losses (Craver & Carraher, 2000). The rate of extraction is related to the solvating strength of the solvent for the plasticiser. For example, water extracts plasticisers from PVC slowly, oils demonstrate a slightly higher level of extraction, and low molecular weight organic solvents demonstrate a much higher level of extraction. Plasticiser molecular size is the most important factor in providing resistance to plasticiser migration or extraction. As the molecular size of the plasticiser increases, tendency for plasticiser migration or extraction is reduced (Craver & Carraher, 2000). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion It is not possible to define a suitable performance scale which could be used for assessing the criterion ‘permanence’ in its entirety. As noted above, there are factors separate to the specific properties of a plasticiser which can influence rates of volatilisation, extraction and migration in flexible PVC articles. Despite this, a common (comparative) approach when considering permanence is to focus on the volatility of the plasticiser, by assessing its vapour pressure. The importance of the volatility of the plasticiser will depend on the conditions of use of the flexible PVC article in question. As noted by Patrick (2005) the large tonnage plasticisers used in
14 Wilkes et al. (2005) note that volatile losses of plasticisers are influenced by solvency strength for the polymer and oxidative degradation, as well as the ambient airflow rate. However, in the scientific and technical literature it appears that vapour pressure is often the most significant measurable and comparative factor.
Use number: 1,2 Legal name of applicant: Arkema 39
ANALYSIS OF ALTERNATIVES
most applications of flexible PVC have molecular weights in the range of 390-450 (DEHP is at the low end of this range). Whilst their vapour pressures at ambient temperature are too low to measure, with increasing temperature the rate of evaporation increases to a point where depletion of plasticisers can have a serious effect on the physical properties of the plastic. Consequently, in higher temperature applications, the importance of plasticiser volatility will increase. This would appear to be in agreement with the view of Wilson (1996), who states that volatility is one of the primary performance criteria for plasticisers and defines their suitability for service at elevated temperatures. Applications where the consideration of volatility is particularly important include electrical insulation (where loss of plasticisers due to volatilisation may lead to insulation failure through degradation of polymer jacketing) and use in enclosed spaces, such as car interior trim, where high volatility may lead to concerns with regard to a reduction of clarity caused by windscreen fogging. As one may expect, industry already takes such parameters into consideration. The cable industry, for example, uses a spectrum of plasticisers with different levels of volatility according to the temperature of operation of the end product. These range from DEHP, for applications rated up to 70°C, to linear C8-10 trimellitate, which is suitable for thin walled wiring used at temperatures in excess of 105°C (Wilson, 1996). Notably, Wilkes et al. (2005) identify a sub-category of plasticisers (under ‘performance plasticisers’) specifically based on the characteristic of ‘low volatility’, adding that two chemical families are recognised for their use as low volatility plasticisers – trimellitates and polyesters (also referred to as polymerics). Consequently, the importance of ‘volatility’ in the consideration of overall permanence, as part of the assessment of a potential alternative to DEHP, has to take into account the specific conditions of use of the article made from flexible PVC. For those articles of relevance to this AfA, (for simplicity) it is appropriate to state that it will perhaps be favourable that the volatility of a substitute plasticiser should be equal to or lower than DEHP. Of course, a plasticiser with a lower level of will also be generally associated with:
A higher ease of processing, but also
A lower level of plasticiser efficiency. The question of acceptability can therefore rest on comparative formulating costs, and other critical properties (relevant to the specific conditions of use). As a result, the assessment of this criterion, in the analysis of the suitability and availability of possible alternatives is undertaken in a qualitative/semi-quantitative fashion.
2.4.4.8 Secondary Criterion 1: Low temperature performance Description and importance Information from literature: The flexibility of plasticised PVC is strongly temperature dependent with increased stiffening and embrittlement at low temperatures (Patrick, 2005). The addition of plasticisers to a PVC product reduces the lower useful temperature limit of the finished product. As many flexible PVC products are used in conditions and climates where they may experience low (sub-zero) temperatures, it is necessary that their properties should not be affected by extreme conditions to the point where serviceability would be impaired. Securing this objective is essentially a matter of formulation, supplemented by proper compounding (to ensure good inter- blending of all formulation components) and care in processing (Titow, 1984).
40 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Low temperature properties (both low temperature modulus and brittleness) are significantly influenced by plasticiser level (phr) and type (Wilkes et al., 2005). Some plasticisers are more efficient in providing low-temperature flexibility than others. It is known that aliphatic diesters of adipic, azelaic and sebacic acids are the preferred plasticisers for very low temperature applications. Furthermore, the linear phthalates based on linear C9 alcohols, linear C11 alcohols and linear C9/C11 blends offer enhanced low-temperature performance over the corresponding branched esters (Kutz, 2011). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability / suitability of a performance scale for the criterion
Low temperature modulus values can be determined by ASTM D 1043 (Clash-Berg, Tf), while brittleness temperature can be determined by ASTM D 746 (TB) (Wilkes et al., 2005). Using these approaches, Wilkes et al. (2005) show that the low temperature flex and brittleness for PVC, using different plasticisers at equivalent plasticiser levels, can show significant variation. When assessing this criterion, however, it is often more practical to take into account plasticiser efficiency and the formulation of the plasticiser in PVC to an equivalent room temperature hardness. Due to the lower efficiency of some plasticisers, despite showing similar low temperature properties at similar phr levels, when present in a plasticised PVC compound at an equivalent level of hardness, they can display superior low temperature performance (because of their higher concentration). It is not suitable to define a performance scale for this criterion, as the need for specific low temperature qualities will differ between end-use applications. Alternatives can, however, be comparatively assessed on a qualitative/semi-quantitative basis.
2.4.4.9 Secondary Criterion 2: Clarity / Colour Description and importance Information from literature: The direct effect of clarity and colour on the resultant material is rarely related to the quality of the plasticiser. Plasticisers are usually transparent and colourless liquids with optical properties clearly indicated by their manufacturers. Clarity may be affected by incompatibility with the resin (incompatibility is sometimes encountered with polymeric plasticisers) or be linked to the effect of moisture absorption (some plasticised and unplasticised materials become cloudy and turn white on moisture absorption; this is a temporary state which can be reversed by drying). If the plasticiser contributes to cloudiness, the polarity of the plasticiser should be evaluated. Polar plasticisers are more likely to contribute to water absorption, which causes reversible cloudiness (Wypych, 2004). Refractive indices of plasticiser and polymer are linked to brilliance. The closer both indices are to each other, the better the brilliance of the compound. Usually this is achieved by selection of a plasticiser of high refractive index. It should be noted that refractive index is not the only determinant. An incompatibility or tendency for the plasticiser to crystallise offsets gains due to the refractive index match (Wypych, 2004). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users.
Use number: 1,2 Legal name of applicant: Arkema 41
ANALYSIS OF ALTERNATIVES
Availability / suitability of a performance scale for the criterion No performance scale can be established as importance varies by end-product.
2.4.4.10 Secondary Criterion 3: Elastic recovery Description and importance Information from literature: Elastic recovery is defined as the fraction of a given deformation that behaves elastically. A perfectly elastic material has an elastic recovery of one. A perfectly plastic material has an elastic recovery of zero. The dimensions are expressed as per cent recovery for a given per cent elongation (Rosato et al., 2000). The importance of elastic recovery varies across flexible PVC end-products. In medical uses, for example, elastic recovery must be optimised to assure that tubing does not kink during use (Plastemart, 2003). Rojek & Stabik (2007) note that window gaskets also should have good elastic recovery under a long time of compression. Information from consultation: further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion No performance scale can be established as it varies by end-product.
2.4.4.11 Secondary Criterion 4: Odour Description and importance Information from literature: This criterion relates to the odour a plasticiser may impart to the flexible PVC end-product during its service life and is of particular importance in food packaging applications, where it is necessary to control odours in order to avoid tainting of the packaged contents. It should be noted that there are certain restrictions on the use of DEHP in food contact materials which come into contact with fatty foods in the European Union (EU Directive 2007/19/EC). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion As noted by Iowa State University (2004), odourants15 can act as additive agents, counteractants, masking agents, or be synergistic in nature. The combination of two odourants can have an odour equal to that of either one of the components, have an odour less than that of one of the components, have an odour equal to the sum of the components, or even have an odour greater than the sum of the components. Notably, Titow (1984) states that odour control agents can be used in some formulations to impart a smell (e.g. a leather-like odour to PVC handbags or upholstery) or to mask odour of another formulation component. Consequently, the odour of the final PVC article is likely to be dependent on its entire formulation (and not just the plasticiser it contains). It is,
15 I.e. substances capable of eliciting an olfactory response.
42 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
however, clear that a favourable plasticiser property will be to not impart any unwanted odour (or taste) to the end product. There is no absolute value for the odour which can be used as a performance scale in our analysis, although this may be discussed in a qualitative manner where relevant.
2.4.4.12 Secondary Criterion 5: Melting / Freezing point16 Description and importance Information from literature: As noted by HallStar (1983), plasticiser freezing point is an important factor in relation to shipping and storage concerns, especially during winter months. Esters with high freezing points, e.g. above -34°C (-30°F), may solidify during shipment or storage and may need to be warmed up until they become pourable or pumpable (unless heated tanks are used for their transport). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion The suitability of a plasticiser in terms of its freezing point will depend on the individual circumstances of each company in the supply chain. Alternatives should have freezing points that do not cause logistical, storage or processing issues when compared with DEHP. As indicated above, freezing points higher than -34°C may be less favourable, although in reality the range is likely to be variable. This point will be considered briefly for each substance in the suitability and availability of potential alternative substances.
2.4.4.13 Secondary Criterion 6: Sterilisability Description and importance Information from literature: Sterilisability is a criterion of particular relevance to the use of PVC in medical devices. Single and multi-use medical devices which come into contact with humans must be pre-sterilised before use in order to minimise the risk of infection (Blass, 2001). Consequently, for materials to be suitable for use in medical devices they must be compatible with common sterilisation methods. Common sterilisation methods include steam autoclaving, ethylene oxide sterilisation, and ionizing radiation (either gamma or electron beam). Steam autoclaving places a severe burden on the prospective medical material with the use of high temperature (such as 121ºC) and pressure. Ethylene oxide is currently being phased out due to worker exposure and environmental concerns, while long-term shelf life stability is an issue for the material post radiation sterilisation (Shang & Woo, 2002). Although medical devices are exempt from authorisation (under Articles 60(2) and 62(6) of the REACH Regulation), this criterion is of importance as manufacturers using DEHP may produce articles used in both medical and non-medical applications.
16 It should be noted that freezing point has little value for predicting low temperature functionality of the final PVC compound (HallStar, 1983).
Use number: 1,2 Legal name of applicant: Arkema 43
ANALYSIS OF ALTERNATIVES
Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability/suitability of a performance scale for the criterion Rapra Technology (2006) notes that part of PVC’s beneficial qualities, amongst a number of other factors, is its ability to be steam sterilisable at 121ºC and resistant to ɣ radiation. Little information has been found in literature with regard to the necessity for plasticisers to have specific values which will ensure that a PVC medical device is more or less sterilisable (by the common methods). Therefore, it is not possible to define a quantified performance scale for this criterion.
2.4.4.14 Secondary Criterion 7: Printability and adhesion properties Description and importance Information from literature: This criterion relates to any constraints a plasticiser may impart to the printability and adhesion properties of a flexible PVC end-product during its service life. As noted by PVC Europe (undated), adhesion properties and the printability of plastic relate to the molecular structure of polymers. Generally, polar and amorphous structures offer better properties. In contrast, non-polar and crystalline structures inherently cause difficulty in adhesion and printing, unless the product surface is treated and the effectiveness of such surface treatment is comparatively low. The adhesion property and printability of various plastics is reported by PVC Europe (undated), and PVC itself is reported to have good printability. Diffusion of plasticiser can, however, affect printing ink adhesion, both initially and in the long term. For example, if a long period intervenes between film manufacture and decorating, a condition of high plasticiser surface concentration may develop that interferes with ink adhesion (usually, surface cleaning corrects that condition). In such instances, it appears that the problem would therefore be linked with permanence concerns. Long-term ink adhesion or performance depends on the compatibility of the ink binder with the plasticiser. Many ink resins are compatible, but service testing should be done (Chemical Fabrics & Film Association, undated). Information from consultation: Further information relevant to this criterion was received via consultation with downstream users. Availability / suitability of a performance scale for the criterion It is not suitable (and may not be possible) to define a performance scale for this criterion as printability and adhesion needs will differ between end-use applications. Alternatives can, however, be comparatively assessed on a semi-quantitative basis. It appears unlikely that any potential alternative plasticisers would impart significant printability or adhesion problems to PVC, in the short-term at least. As noted above, compatibility of the ink binder with the plasticiser is also of importance in the long term and can be deduced by service testing.
2.4.5 Summary of technical requirements for DEHP as a plasticiser in PVC The following table summarises the key parameters for the use of DEHP in the production of PVC articles and outlines the criteria against which the technical suitability of alternatives can be assessed.
44 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 2.4: Parameters for DEHP in the production of PVC articles
Plasticiser in PVC. DEHP makes it possible to achieve the required compound Task(s) performed by the processing characteristics, while also providing flexibility in a large variety of end- substance use products made of PVC Physical form of product Colourless oily liquid (at 20°C and 1013 hPa) Concentration of substance in Variable; typically 30% product From the perspective of the applicant, this includes criteria related to:
Possibilities for production integration Availability of precursors Compatibility with existing plant capabilities and limitations Availability of downstream market (customer demand) sufficient to ensure profitability in the medium to long-term From the perspective of downstream users, critical properties of DEHP which are critical to its function (from the perspective of downstream users) and need to be considered in the assessment of technical feasibility1 of alternatives include (see Section 2.4):
Critical properties and quality Core properties: criteria it must fulfil PVC Compatibility Processability Efficiency Permanence Secondary properties: Low temperature performance Clarity Elastic recovery Odour Melting/Freezing point Sterilisability Printability and adhesion properties Formulation of DEHP in compounds, dry-blends and plastisol formulations: Assumed consumption: applicant-specific tonnage cannot be disclosed Continuous and batch processes Typical concentration in final article: 30%
Industrial use in polymer processing by calendering, spread coating, extrusion, Function conditions injection moulding to produce PVC articles [except erasers, sex toys, small (frequency of use and quantity household items (<10cm) that can be swallowed by children, clothing intended used in the applied-for uses) to be worn against the bare skin; also toys, cosmetics and food contact material (restricted under other EU regulation)]:
Assumed consumption: applicant-specific tonnage cannot be disclosed Continuous and batch processes Typical concentration in final article: 30%
Use number: 1,2 Legal name of applicant: Arkema 45
ANALYSIS OF ALTERNATIVES
Formulation of DEHP in compounds, dry-blends and plastisol formulations: Some operations are carried out at elevated temperature in closed systems: 100- 120°; during activities involving operator’s action, the temperature is estimated to be maximum 40°C
Industrial use in polymer processing by calendering, spread coating, extrusion, Process and performance injection moulding to produce PVC articles [except erasers, sex toys, small constraints household items (<10cm) that can be swallowed by children, clothing intended to be worn against the bare skin; also toys, cosmetics and food contact material (restricted under other EU regulation)]: Some operations are carried out at elevated temperature in closed systems up to 180°C. Some activities involving operator’s action take place at temperatures higher than ambient: the maximum temperature in those cases is estimated to be at 40°C Conditions under which the Only in the event of developing a technically and economically feasible substitute use of the substance could be from the perspective of the applicant eliminated Customer requirements EU/non-EU (e.g. FDA) pharmacopeia approvals associated with the use of the Critical properties related to downstream users (as shown above) substance Industry sector and legal Cost-effectiveness of plasticiser requirements for technical Compatibility with PVC and processability in existing equipment/processes acceptability that must be met EU/non-EU pharmacopeia approvals and the function must deliver 1Note: This is in terms of knock on effect to economic feasibility for the applicant (as discussed in Section 3.1).
46 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
3 IDENTIFICATION OF POSSIBLE ALTERNATIVES
3.1 Introduction and scope of analysis Article 60(5) of the REACH regulation states: “When assessing whether suitable alternative substances or technologies are available, all relevant aspects shall be taken into account by the Commission, including: 1. Whether the transfer to alternatives would result in reduced overall risks to human health and the environment, taking into account the appropriateness and effectiveness of risk management measures; 2. The technical and economic feasibility of alternatives for the applicant”. Consequently, and in line with the REACH regulation, the alternatives in this AoA have been analysed primarily from the perspective of the applicant, the manufacturer of DEHP, Arkema. However, important elements are also examined from the perspective of the downstream user. These include:
Technical feasibility – without an alternative being technically feasible for the downstream users, there would be no economic incentive for the applicant to manufacture it, as the downstream users would not purchase it for use. It is obvious that an alternative must meet the requirements of the applicant’s customers;
Economic feasibility (in a broad manner only and in terms of the knock-on-effect of economic feasibility for the applicant – this is assessed in detail within the SEA); and
Market availability – it is assumed that wide market availability and presence of established manufacturers/suppliers of the alternatives would reduce the likelihood of the applicant becoming the preferred supplier of the alternatives (thus affecting the economic feasibility of the alternative from the perspective of the applicant). When considering the context of this AoA, the following pertinent factors should also be taken into consideration:
The scope of what a company in the manufacturer’s downstream supply chain may consider as a feasible alternative is potentially significantly broader than that which can be rationally considered as technically or economically feasible from the perspective of the applicant. For example, a flexible PVC processor producing plastic articles could consider a different plastic material to flexible PVC as a potential alternative. However, for the applicant, a chemicals manufacturer, an alternative material (or technique) would not logically be considered technically or economically feasible. For the applicant, only chemical substances can be considered as potentially feasible alternatives; and
Given the general purpose nature of DEHP as a plasticiser, and the substance’s use in a wide variety of end products, it should also be noted that (from the perspective of the applicant) replacing the substance with, for example, a broad range of alternative substances, suitable in specific applications, is also a not a feasible option. This is because:
Use number: 1,2 Legal name of applicant: Arkema 47
ANALYSIS OF ALTERNATIVES
The applicant would lose out on the benefits of integration and it is the integration with the precursors that generate current profit levels which make DEHP commercially viable;
Any economies of scale in terms of scale of production, length of production runs, distribution networks etc. would be lost, making alternatives more expensive per unit to produce. Having to procure different raw materials for a number of plasticisers as opposed to just one would mean the applicant would not benefit from any economies of scale when purchasing raw materials;
The applicant would need to simultaneously break into a number of new markets which are already supplied by competitors, requiring them to compete on price with already established and often larger companies;
Additional costs would be associated with cleaning and maintenance relating to multiple changes in plasticiser production; and
Multiple storage facilities would be required to cater for storage of the additional plasticisers / their precursors. As an output of initial literature review and consultation, for the purposes of this AoA, a comprehensive list of ca. 45 potential alternative substances was initially identified. This list was refined to a shorter list to identify the most relevant potential alternative substances; i.e. those that are the most likely to represent realistic alternatives (from the perspectives of both the applicant and the downstream markets) to be assessed in full as part of this AoA as potentially feasible replacements of a general purpose plasticiser such as DEHP. The description of efforts made to identify possible alternatives and the screening process applied to the short-listing of alternatives for the more detailed assessment is described below.
3.2 Description of efforts made to identify possible alternatives
3.2.1 Research and development activities
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 3.2.1
3.2.1.1 Activities of the applicant The applicant has undertaken work aimed at identifying technically feasible alternatives for them. This has included R&D aimed at identifying a replacement chemical substance, and research into the potential availability of the precursor materials. More details on the R&D activities of the applicant are described in the Confidential Annex.
3.2.1.2 Activities of downstream users of DEHP As downstream users formulate their products for a particular function and thus choose an appropriate plasticiser to achieve that effect, they are not tied to a particular substance unless it is the most suitable in terms of meeting customers’ requirements and/or providing qualities that other substances cannot.
48 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
There is, therefore, an incentive for flexible PVC compounders to trial alternative substances in order to achieve improvements in product properties or savings in processing or purchase price, resulting in profit margin increases and potentially increasing competitiveness and market share. Downstream users therefore are not necessarily allied to a particular substance (and therefore manufacturer) but have a vested interest to identify and use the plasticiser that best meets their needs for good quality products, affordable pricing and market differentiation. It is clear from the responses to the consultation carried out to support this application that most companies that carry out formulating and compounding activities have tried and tested a range of plasticisers. It is also clear that those companies that produce flexible PVC articles have also tested alternatives to DEHP. As a result, these downstream users have a good understanding of whether the alternatives that they have tested (and perhaps others that they have researched) are capable of delivering the properties that they or their customers require.
3.2.2 Data searches for the purposes of this Analysis of Alternatives A literature review was undertaken by the independent third party that has authored this AoA. The open literature has been searched for information on potential alternatives to DEHP for its role in the applied-for uses. The main approach has been to conduct a general search through a reputable online search engine and then further elaborate the search terms as new, detailed information was being obtained (see Table 3.1). Information was sought on:
The identities of potential alternative substances (including acronyms, synonyms, EC numbers and CAS numbers, where available);
The applicability of potential alternatives to different end-uses;
Technical feasibility, economic feasibility, and the human health and environmental impacts profile. Table 3.1: Key information sources used in the identification of potential alternatives Source Details Description Google http://www.google.com Search engine Google Scholar http://scholar.google.co.uk Scientific articles, patents Google Books http://books.google.co.uk/bkshp?hl=en&tab=wp Books Scirus http://www.scirus.com/ Scientific search engine
However, it is recognised that DEHP has been under scrutiny over many years and there is a significant body of work on alternative substances. Documents have been retrieved from a variety of sources including:
Scientific reports that have looked into DEHP and the availability and suitability of alternatives to DEHP; and
Reports commissioned or authored by public bodies that have in the past looked into the issue of DEHP. A good starting point has been the documentation that has been generated through two recent processes: the prioritisation of DEHP into Annex XIV of the REACH Regulation and the 2011 proposal made by the Danish authorities on a restriction for DEHP and three other phthalates.
Use number: 1,2 Legal name of applicant: Arkema 49
ANALYSIS OF ALTERNATIVES
3.2.3 Consultations
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 3.2.3
3.2.3.1 Overview of key consultees Extensive consultation was undertaken for the purposes of this AoA; for reasons of scientific robustness and due to concerns over confidentiality along the supply chain, this consultation was undertaken by the independent third party that authored this AoA. In this context, apart from the applicant, a considerable amount of information, expert advice and insight was provided by companies active in the ATF’s supply chain. More than 200 companies have been approached with requests for information (typically in the form of one or more written questionnaires) of which ca. 80 have made some contribution to this analysis (and/or the SEA). These companies are located across the EU including Western Europe, Central and Eastern Europe, Southern Europe and Scandinavia. A small number of companies are located in European countries in the periphery of the EU. Attempts were also made to communicate with a range of industry associations who might be representing companies that could potentially be affected by a refused Authorisation. Industry sectors covered by such communication have included:
Plasticisers and speciality chemicals (British Association of Chemical Specialities (UK));
Plastics manufacturers and converters (PlasticsEurope (EU), British Plastics Federation (UK), European Plastics Converters (EU));
Footwear (European Confederation of the Footwear Industry (EU));
Flooring (European PVC Floors Manufacturers (EU), European Resilient Flooring Manufacturers' Institute (EU), European Carpet and Rug Association (EU));
General engineering (incl. metal) and construction (Council of European Employers of the Metal, Engineering and Technology-Based Industries (EU), Council of European Producers of Materials for Construction (EU), Europacable (EU), European Coil Coating Association (EU), European PVC Window Profile and Related Building Products Association (EU), The European Plastic Pipes and Fittings Association (EU));
Textiles and clothing (European Apparel and Textile Organisation (EU));
Automotive manufacture (European Automobile Manufacturers’ Association (EU), European Association for Automotive Suppliers (EU), The Society of Motor Manufacturers and Traders (UK));
Aerospace (Aerospace & Defence Association of Europe (EU));
Electrical installations (The British Electrotechnical and Allied Manufacturers’ Association (BEAMA));
Sealants and adhesives (Association of European Adhesive Manufacturers (EU), British Adhesives & Sealants Association (UK)); and
Rubber (International Institute of Synthetic Rubber Producers (Global)).
50 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
The contributions directly received from the industry associations have generally been very limited. Of note, a response was received from the automotive sector, details of this are provided in the SEA.
3.2.3.2 Consultation with the applicant In order to gain the information required for this AoA, the applicant was asked to provide significant quantities of data to the independent third party who authored this AoA. A large amount of this information was requested in the form of responses to three written questionnaires.
Questionnaire 1: a questionnaire was originally used for the collection of information in March 2012. The questionnaire concerned the socio-economic impacts on DEHP manufacturers from a theoretically refused Authorisation. The majority of the information from this is used in the SEA for this application, although some parts are relevant to the AoA here (specifically in respect to the economic feasibility of alternatives). Information was gathered from this survey on:
The integration of the applicant’s DEHP manufacturing facility in relation to the two key raw materials for the manufacture of DEHP, the phthalic anhydride and the alcohol;
Details of plant operation, including potential effects on production from a theoretically refused Authorisation (integration losses);
Plant capabilities for a switch to the manufacture of alternative plasticisers;
Employment details and potential impacts on employment from the loss of DEHP; and
State of competition in the EU.
Questionnaires 2 and 3: following the outcome of the consultation with downstream users, the applicant more recently (March - April 2013) provided information on sets of more specific AoA and SEA related questions. This was in the form of two separate questionnaires. The SEA questionnaire (mentioned here for completeness) specifically addressed the impact of any potential non-use scenarios identified as possibly relevant to the applicant. The AoA questionnaire contained questions specific to the shortlist of potential alternative substances, as well as questions to establish the applicant’s baseline/business as usual scenario. Information was sought on:
Output units and anticipated future demand;
Turnover, investment and operational costs;
Costs associated with the non-use of DEHP;
Employment impacts;
Future liabilities and indirect effects;
Research and development activities; and
The availability of potential alternative substances. In addition to the questionnaires, information was gathered via:
Use number: 1,2 Legal name of applicant: Arkema 51
ANALYSIS OF ALTERNATIVES
Exchange of draft documents: The independent party who authored this AoA shared preliminary outputs with the applicant. These were accompanied by a series of questions aimed at filling gaps, addressing queries and exploring new issues that arose as information was being collected and processed;
Face-to-face meetings: several meetings were held with the applicant (but also with the ATF as a whole); and
Telephone conversations: regular conference calls were held with the ATF. When necessary, specific telephone interviews and discussions were held with the individual applicant.
3.2.3.3 Consultation with downstream users Description of the supply chain The supply chain involving the manufacture and use of DEHP is comprised of several different links, moving from raw materials suppliers to post-consumer waste recyclers. Figure 3.1 provides a simplification of the supply chain. As can be seen from the figure, the supply chain starts with the manufacture or supply of the precursor alcohol and phthalic anhydride, involves the manufacture of DEHP itself, and then proceeds to encompass a number of downstream links. The latter will include formulation and trade to users further downstream by distributors. Downstream use may then involve either further formulation/compounding or industrial processing, including several stages of transactions amongst distributors.
Figure 3.1: An overview of the DEHP supply chain Industrial compounders/processors may produce end-use articles themselves, as well as sell compounds to others; article producers may either sell end-use articles or may produce components for more complex articles which are then incorporated by other manufacturers into the end-use
52 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
article. The end-use articles may either be used or installed by professional users (e.g. waterproof clothing, window profiles, flooring) or be sold to consumers. At their end of life stage, the end articles may then be collected for recycling, with this being done via a supply chain involving waste collectors, processors (shredding and micronising or other more sophisticated processing methods), converters and article producers; in some cases processors may also be article producers. Challenges in the communication within the supply chain Communicating with the ATF supply chain has faced several challenges which have influenced the scope of consultation. These may be summarised as follows (and apply to each ATF applicant):
Distance of the applicant from downstream users: the applicant (as can be seen from Figure 3.1) has little if any contact with the final manufacturer of PVC articles and in very few cases the manufacturer has direct contact with the end-user. At the same time, the end-user and the final manufacturer of PVC articles may have limited knowledge on who the actual manufacturer of DEHP is;
Variable level of understanding of technical issues: many of the users towards the end of the supply chain are unlikely to have sufficient understanding of some of the technical properties delivered by the PVC compound supplied by their supplier. Thus, they have been unable to make detailed input to the analysis of alternatives. These users located towards the end of the supply chain may also have a limited understanding of Authorisation requirements;
Need for avoiding disruption along the supply chain: it has been important to ensure that communication with actors along the supply chain would not harm the commercial interests of the applicant and the applicant’s direct customers and would not cause undue disruption or concern; and
Confidential business information (CBI): effective communication within the supply chain was also hindered in some cases due to concerns relating to CBI. This has prevented some parts of the supply chain from giving full and precise information on specific uses and possibly on potential alternatives. However, the consultant co-ordinating the consultation exercise offered users the possibility of supplying information under a Non-Disclosure Agreement, and several consultees made use of this facility. Selection of downstream users to contact The following approach was taken in identifying relevant downstream users to contact:
Use of customer lists from ATF members: each of the four original ATF17 members were asked to provide a list of their customers to the independent third party who authored this AoA, under appropriate signed Non-Disclosure Agreements. A combined master list was created and was further elaborated with additional names as they became available. The use of a combined, single list of downstream users has been warranted for the following reasons:
It was originally intended that the AfA would be made jointly across all four members. Therefore, combination of the outputs from all downstream users was necessary;
17 Originally Oltchim of Romania was a member of the DEHP Authorisation Task Force. However, the company withdrew from the process when it went into receivership. We continued to use the information for all four companies because it provided a good market overview and, if Oltchim stops supplying the substance, the other ATF members would probably take over a large proportion of its customers’ demands.
Use number: 1,2 Legal name of applicant: Arkema 53
ANALYSIS OF ALTERNATIVES
Some downstream users may purchase DEHP from more than one DEHP manufacturer (ATF member). Therefore, trying to split the information collected by the applicant would not only be complicated, but it might also breach confidentiality (note that several downstream users did not wish to share their specific stand-alone information with the DEHP manufacturers);
With the overall AfA approach (and specifically the SEA) in mind, it would not be appropriate to only look at a single ATF member’s customers when trying to gauge market level effects, as all ATF members are applying for authorisation.
Retrieval of customer lists from downstream users: on a number of occasions, companies that were contacted confirmed that they may not use DEHP themselves but rather sell it downstream (distributors). Others confirmed the manufacture of PVC compounds with DEHP (processors), but were not able to advise on the onward use of the compound. In such cases, these companies were asked to provide the contact details of their relevant customers, or, alternatively, to forward a questionnaire to their customers. On many occasions, positive responses were received and this further enhanced penetration of the supply chain;
Direct communication between ATF members and downstream users: additional help was received from DEHP ATF members who contacted some of their customers (traders) directly to request their participation in the consultation exercise, often with good results. Survey responses were amalgamated and then analysed. It was important to protect the confidentiality of the data provided by downstream users and this was only possible by amalgamating responses. Using this approach, a list of over 200 customer companies potentially linked to the use of DEHP in the EU was developed. These companies were directly contacted and invited to provide information on alternatives. The following types of downstream users were contacted (often on more than one occasion, for example, when no response was forthcoming):
Distributors of DEHP and of DEHP-containing PVC compound;
Formulators of DEHP-containing PVC compound;
Processors of DEHP-containing PVC compound, i.e. article manufacturers;
Users of DEHP-containing PVC articles (only few cases). It is clear that the level of supply chain penetration beyond the first tier of customer critically depended on the degree to which first level consultees gathered data from their customers or passed the questionnaire on to their downstream users. Downstream User Questionnaires Three core questionnaires18 were disseminated to downstream users during the preparation of this AoA:
An introductory ‘alternative focussed’ questionnaire, in September 2011;
A second questionnaire in the form of an Excel matrix which focused on applications of DEHP- plasticised PVC, in November 2011; and
18 An additional questionnaire was issued in March 2012 with a focus on the use of DEHP in rubber.
54 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
A third questionnaire, focusing on SEA issues, in June 2012. The first downstream user questionnaire collected information mainly on two aspects:
Section 1 focused on the consultees use of DEHP; and
Section 2 focused on the comparison of DEHP to alternative substances. The second downstream user questionnaire focused on two elements:
The list of applications for DEHP-plasticised PVC which are of relevance to the supply chain of the ATF members; and
The transformation processes (during mixing, shaping and finishing) used in the manufacture of PVC compound and PVC articles by downstream users. Where practical, information from this questionnaire (on the tonnage of DEHP used in each relevant identified end-use application) was also combined with the outputs of the first downstream user questionnaire on the suitability of potential alternative substances. This analysis allowed the applicant to gain an overall perspective of the potential market for each alternative substance in the current ATF supply chain, from which some indication as to the economic feasibility of potential alternative substances (analysed in Section 4 of this AoA) could be identified and assessed. The third downstream user questionnaire was focused on compliance costs for downstream users from a theoretically refused Authorisation for DEHP. The independent third party who authored this AoA collated all of the information received from respondents to enable it to be used anonymously. Names and locations of companies and/or their association to a specific DEHP ATF member have not been given and will not be made available to anyone outside the authors and non-disclosure agreements have been signed to this effect. These confidentiality arrangements were essential to gaining the full participation of survey respondents, who would not have provided this information to the applicant companies. The author analysed the collected information to provide an overall picture of the EU market. The overall tonnage of DEHP consumed by all responding customers of the original four ATF applicant companies (provided in the Confidential Annex (along with further information on the approach to the consultation)) was a significant share of the DEHP placed on the market and confirms the assertion that the downstream user survey for the purposes of this AfA has been the most comprehensive market survey to have ever been made in relation to the use of DEHP in the EU.
3.3 Identification of potential alternative substances
3.3.1 Master list of potential alternatives
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 3.3.1
The detailed literature review and consultation exercise identified 43 substances which could potentially act as an alternative to DEHP in the uses associated with the applicant’s supply chain. These are presented in Table 3.2.
Use number: 1,2 Legal name of applicant: Arkema 55
ANALYSIS OF ALTERNATIVES
Table 3.2: Master List of Potential Alternative Plasticisers No Substance name Other common EC Number CAS Number names/acronyms 1 Tributyl O-acetylcitrate 201-067-0 77-90-7 Acetyltri-n-butyl citrate (ATBC, Citroflex A-4) 2 Trihexyl 2-acetyloxypropane-1,2,3- - 24817-92-3 tricarboxylate Acetyltri-n-hexyl citrate (ATHC, Citroflex A-6) 3 Sulfonic acids, C10-21-alkane, Ph esters Alkylsulphonic phenyl ester 293-728-5 91082-17-6 (ASE, Mesamoll) 4 Benzyl 2-ethylhexyl adipate Benzyl octyl adipate (BOA) 261-234-9 58394-64-2 5 Bis(2-propylheptyl) phthalate DPHP 258-469-4 53306-54-0 6 Butyl 2-ethylhexyl phthalate Butyl octylphthalate (BOP) 201-623-2 85-69-8 7 2-(2-butoxyethoxy)ethyl acetate Butyl diglycol acetate 204-685-9 124-17-4 8 Bis(2-ethylhexyl) adipate 203-090-1 103-23-1 Di-octyl adipate (DEHA)
Di-octyl adipate (DOA) 9 Bis(2-ethylhexyl) hydrogen phosphate DEHPA 206-056-4 298-07-7 10 Bis(2-ethylhexyl) terephthalate DEHT 229-176-9 6422-86-2 Dioctyl terephthalate (DOTP) 11 Dibutyl sebacate DBS 203-672-5 109-43-3 12 Oxydiethylene dibenzoate Diethylene glycol 204-407-6 120-55-8 dibenzoate (DEGD, DEGDB, Santicizer 9200) 13 Di-isodecyl phthalate DIDP 247-977-1 68515-49-1 and 26761-40- 0 14 1,2-Benzenedicarboxylic acid, di-C6-8- Di-isoheptyl phthalate 276-158-1 71888-89-6 branched alkyl esters, C7-rich (DIHP) 15 Diisohexyl phthalate DIHP 276-090-2 71850-09-4 16 Diisononyl adipate DINA 251-646-7 33703-08-1 17 Di-isononyl' phthalate DINP 249-079-5 68515-48-0 and 28553-12- 0 18 1,2-Cyclohexanedicarboxylic acid, 1,2- Di-iso-nonyl-1,2- *605-439-7 EU 166412-78- diisononyl ester cyclohexanedicarboxylate 8, USA and (DINCH, Hexamoll) Canada 474919-59-0 19 Bis(2-ethylhexyl) sebacate DEHS 204-558-8 122-62-3
Dioctyl sebacate 20 Diphenyl tolyl phosphate Diphenyl cresyl phosphate 247-693-8 26444-49-5 21 2-ethylhexyl diphenyl phosphate 214-987-2 1241-94-7 22 Oxydipropyl dibenzoate Dipropylene glycol 248-258-5 27138-31-4 dibenzoate (DGD)
56 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
No Substance name Other common EC Number CAS Number names/acronyms 23 Soybean oil, epoxidized Epoxidised soy bean oil 232-391-0 8013-07-8 (ESBO) 24 Glycerides, castor-oil mono-, Glycerides, Castor-oil- *616-005-1 736150-63-3 hydrogenated, acetates mono-, hydrogenated, acetates (COMGHA) Component A Not available 330198-91-9 Component B Not available 33599-07-4 25 Triacetin Glycerol triacetate (GTA, 203-051-9 102-76-1 1,2,3-Propantriyl triacetate, Triacetin)
26 Not available H-640 (polymeric Not available Not available plasticiser) 27 Not available Hexanedioic acid, bis (2-(2- Not available Not available butoxyethoxy)ethyl ester (bisoflex, edenol) 28 Phenol, isopropylated, phosphate (3:1) Isopropylated phenyl 273-066-3 68937-41-7; phosphates 26967-76-0 29 1,2-Benzenedicarboxylic acid, di-C9-11- Linear phthalate 271-085-1 68515-43-5 branched and linear alkyl esters 30 Not available N-butyryl-tri-n-hexyl citrate Not located on 82469-79-2 (BTHC, Citroflex B-6) dissemination portal, pre reg or C&L inv 31 Toluene-2-sulphonamide O-toluene Sulphonamide 201-808-8 88-19-7 (OTSA) 32 Polycaprolactone PCL Not located on 25248-42-4 dissemination (for PCL 700) portal, pre reg or C&L inv 33 Not available Polymeric adipate-type Not available Not available plasticisers (BP Amoco Chemicals) 34 Not available Polymeric plasticiser Not available 208945-13-5 Palamoll®652 35 Siloxanes and Silicones, di-Me Silicone oils (Dimethyl *613-156-5 63148-62-9 polysiloxane) 36 Not available Sorbitol esters Not available Not available 37 Tris(methylphenyl) phosphate Tricresyl phosphate (mixed) 215-548-8 1330-78-5 38 Ethylenebis(oxyethylene) dibenzoate Triethylene glycol 204-408-1 120-56-9 dibenzoate (TEGDB, Benzoflex T 150) 39 1-isopropyl-2,2-dimethyltrimethylene Trimethyl pentanyl 229-934-9 6846-50-0 diisobutyrate diisobutyrate (TXIB) 40 Tris(2-ethylhexyl) benzene-1,2,4- Trioctyltrimellitate (TOTM) 222-020-0 3319-31-1 tricarboxylate Tri(2-ethylhexyl) trimellitate, (TEHTM)
41 Tri-p-tolyl phosphate Tri-p-cresyl phosphate 201-105-6 78-32-0 (without ortho compounds) 42 Triphenyl phosphate Triphenyl phosphate 204-112-2 115-86-6 43 Tris(2-ethylhexyl) phosphate Tris(2-ethylhexyl) 201-116-6 78-42-2 phosphate (TOP)
Use number: 1,2 Legal name of applicant: Arkema 57
ANALYSIS OF ALTERNATIVES
No Substance name Other common EC Number CAS Number names/acronyms * Noted as a temporary list number in the ECHA database of pre-registered substances Source: Literature search and consultations
3.3.1.1 Knowledge of alternatives amongst downstream users Downstream users were asked in the first questionnaire to identify alternative substances that they were familiar with and they had trialled or evaluated. The results are provided in the Confidential Annex. Generally, downstream users were familiar with almost the entire master list of alternatives.
3.3.2 Screening of potential alternative substances for suitability as DEHP replacement
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 3.3.2
3.3.2.1 Approach to the screening process19 A two-fold approach was followed in order to screen the master list of alternatives into a manageable list of (in principle) realistic potential alternatives for the replacement of DEHP. Further discussion of the approach and the results (which are based on consultations with downstream users) are provided in the Confidential Annex. Some further (broad) details on the overall approach to the screening exercise, in addition to the identification of the final list of potential alternative substance for detailed analysis, are presented below.
3.3.2.2 Screening of potential alternatives for overall suitability Rankings by downstream users with respect to the overall suitability of the potential alternatives as replacements for DEHP are provided in the Confidential Annex. These are based on initial responses to the first downstream user questionnaire.
3.3.2.3 Screening of potential alternatives against initial comparison criteria Overview of comparison criteria Having identified the most important and realistic potential alternatives from within the master list of substances (from the perspective of the ATF downstream users), further information was then requested from downstream users on:
What criteria they would be consider in an effort to select a suitable DEHP replacement for their applications and which criteria should be considered to be the most important; and
How the shortlisted potential substances would fare against these criteria from the perspective of the downstream users.
19 It should be noted that the screening process was undertaken in late 2011, and the information from consultation used in this process was obtained from responses received up until the end of October 2011. Responses received after this date were utilised in the more in depth analysis of shortlisted alternative substances (in Section 4).
58 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
The results of the identification and ranking of technical comparison criteria have been shown in Section 2.4.4.2 (and the corresponding section of the Confidential Annex to this AoA). Technical comparison of alternatives to the selected comparison criteria The downstream users were subsequently asked to compare the potential alternative substances to DEHP against the technical criteria which had either been pre-identified or identified by the consultees. The results of the comparison and further details are provided in the Confidential Annex.
3.3.3 Final list of potential alternative substances for detailed analysis For the generation of the final list of potential alternative substances to be assessed in detail in this AoA (Section 4), we have taken into consideration:
The screening of the list of 43 alternative substances for overall technical feasibility from the perspective of downstream users (assessed in the Confidential Annex) which resulted in a shorter list of 13 substances;
The screening of the 13 shortlisted substances by comparison to DEHP against selected technical comparison criteria (assessed in the Confidential Annex); and
The knowledge and expertise of the applicant (and of the ATF members more generally) as well as the need to make the final list as inclusive and representative as possible, while ensuring a manageable and realistic workload for the preparation of the AoA. The final list of 11 selected potential alternative substances (from the shortlist of 13) assessed (in Section 4) is given in Table 3.3 overleaf. The refined group of 11 potential alternatives contains representative substances from a broad range of chemical groups including alkylsulphonic phenyl esters, esters of monoglycerides of hydrogenated castor oil, adipates, citrates, phthalates, hydroxyphthalates, sebacates, terephthalates and trimellitates. The range of alternatives covered by this selection comprehensively addresses the requirements of the supply chain covered by this AfA, and also covers the potentially feasible alternatives from the perspective of the applicant. In Section 4, as well as further considering aspects relevant to the downstream user (and, by proxy, the applicant), further and extensive considerations are also given to other more specific aspects of feasibility from the perspective of the applicant (as discussed in Section 2). Table 3.3: Final list of potential alternatives for detailed assessment of technical and economic feasibility and availability
IUPAC Name Other EC CAS Rationale for inclusion or exclusion from Conclusion common Num Number final list of potential alternative names/acr ber substances onyms 1 Tributyl O- Acetyltri- 201- 77-90-7 ATBC appears to perform reasonably well Included acetylcitrate n-butyl 067-0 against the initial technical comparison citrate criteria (ATBC, Citroflex A-4)
Use number: 1,2 Legal name of applicant: Arkema 59
ANALYSIS OF ALTERNATIVES
IUPAC Name Other EC CAS Rationale for inclusion or exclusion from Conclusion common Num Number final list of potential alternative names/acr ber substances onyms 2 Sulfonic Alkylsulph 293- 91082- ASE appears to perform well against the Include (to acids, C10-21- onic phenyl 728-5 17-6 initial technical comparison criteria but fails ensure alkane, Ph ester (ASE, some of them. Its inclusion would serve to completeness) esters Mesamoll) include a representative of the alkylsulphonic phenyl esters family in the final list to ensure that the list is as representative and inclusive as possible 3 Bis(2- Di-octyl 203- 103-23-1 DEHA appears to perform reasonably well Included ethylhexyl) adipate 090-1 against the initial technical comparison adipate (DEHA) criteria Di-octyl adipate (DOA)
4 Bis(2- DEHT 229- 6422-86- DEHT appears to perform well against the Included ethylhexyl) 176-9 2 initial technical comparison criteria terephthalate Dioctyl terephthala te (DOTP) 5 Bis(2- DPHP 258- 53306- The applicant considers DPHP to be an Included propylheptyl) 469-4 54-0 emerging plasticiser and a close analogue of phthalate DINP and DEHP. Therefore, it is prudent to include it in the final list 6 Di-isodecyl DIDP 247- 26761- DIDP appears to perform well against the Included phthalate 977-1 40-0 and initial technical comparison criteria and 68515- 271- 49-1 091-4 7 Di-isononyl DINP 249- 28553- DINP appears to perform well against the Included phthalate 079-5 12-0 and initial technical comparison criteria and 68515- 271- 48-0 090-9 8 1,2- Di-iso- *605- EU DINCH appears to perform reasonably well Included Cyclohexaned nonyl-1,2- 439-7 166412- against most but not all of the initial icarboxylic cyclohexan 78-8, technical comparison criteria acid, 1,2- edicarboxy USA diisononyl late and ester (DINCH, Canada Hexamoll) 474919- 59-0 9 Bis(2- DEHS 204- 122-62-3 A comparison against the initial technical Included (to ethylhexyl) 558-8 comparison criteria is not available, ensure sebacate suggesting low potential for successful use completeness) Dioctyl in a wide range of applications. Its sebacate inclusion would serve to include a representative of the sebacate family in the final list to ensure that the list is as representative and inclusive as possible
60 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
IUPAC Name Other EC CAS Rationale for inclusion or exclusion from Conclusion common Num Number final list of potential alternative names/acr ber substances onyms 10 Soybean oil, Epoxidised 232- 8013-07- In the vast majority of consultation Excluded epoxidized soy bean 391-0 8 responses, ESBO has been viewed as only oil (ESBO) suitable when used as a secondary plasticiser in conjunction with DEHP (or other primary plasticiser) and thus could not be viewed as a true alternative to a general purpose plasticiser such as DEHP 11 Glycerides, Glycerides, *616- 736150- Comparison against the initial technical Included (to castor-oil Castor-oil- 005-1 63-3 comparison criteria is not available, ensure mono-, mono-, suggesting low potential for successful use completeness) hydrogenated, hydrogenat in a wide range of applications. Its acetates ed, acetates inclusion would serve to include a (COMGH representative of the glycerides family in A) the final list to ensure that the list is as Component Not 330198- representative and inclusive as possible A availa 91-9 ble Component Not 33599- B availa 07-4 ble 12 Not available H-640 Not Not The applicant confirms that its role on the Excluded (polymeric availa available market as a potential alternative plasticiser plasticiser) ble is far from established as a realistic alternative to DEHP 13 Tris(2- Trioctyltri 222- 3319-31- TOTM appears to perform well against the Included (to ethylhexyl) mellitate 020-0 1 initial technical comparison criteria but fails ensure benzene- (TOTM) some of them. Its inclusion would serve to completeness) 1,2,4- include a representative of the trimellitate tricarboxylate Tri(2- family in the final list to ensure that the list ethylhexyl) is as representative and inclusive as trimellitate, possible (TEHTM)
Please note that a fuller version of this table is available in the Confidential Annex to this AoA. This includes additional rationale for inclusion or exclusion from the final list of potential alternative substances, based on outputs of the consultation exercise. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 3.3.3
Use number: 1,2 Legal name of applicant: Arkema 61
ANALYSIS OF ALTERNATIVES
4 SUITABILITY AND AVAILABILITY OF POSSIBLE ALTERNATIVES
4.1 General remarks
The authors note that information provided within this section is comprehensively supported by information provided within the Confidential Annex. Furthermore, a list of supplementary data sources consulted for the purposes of the AoA are presented in Annex 3 of this document. The reader should also be aware that, with regard to the reduction of overall risk due to transition to the potential alternative substances, only short summaries are presented within Section 4. A full assessment is, however, provided in Annex 4 of this document. The rationale for this approach has been to provide the reader uninterrupted analysis relating to the overall hazards and risks posed by the potential alternative substances.
62 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.2 Alternative 1: Alternative substance – ALKYLSULPHONIC PHENYL ESTER (ASE)
4.2.1 Substance ID and properties of ASE
4.2.1.1 Name and other identifiers for the substance Table 4.1 presents the identity of ASE. Table 4.1: Identity of ASE Parameter Value Source EC number 293-728-5 1 EC name Sulfonic acids, C10-21-alkane, Ph esters 1 CAS number 91082-17-6 1 IUPAC name Sulfonic acids, C10-21-alkane, Ph esters 1 ASE Mesamoll Other names 1 Mesamoll II Mesamoll TP LXS 51067 Mono-ester: C16H26O3S-C27H48O3S Molecular formula Di-ester: C22H34O9S3-C39H56O9S3 2 Tri-ester: C28H34O9S3-C39H56O9S3 SMILES notation No information identified - Molecular weight No defined MW -
Mono-ester
Molecular structure 2
Di-ester
Tri-ester Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: EFSA (2009)
4.2.1.2 Composition of the substance
The substance is a mixture in which the main components are alkyl (C10-C21)sulphonic acid, mono-, di- and tri-esters with phenol. The substance contains also alkyl (C10-C21)sulphonic acid, tetra-ester with phenol as a minor component (<1%). Phenol, alkanes and chloroalkanes are present as impurities. The substance is lipophilic and stable under manufacturing and intended use conditions (EFSA, 2009).
Use number: 1,2 Legal name of applicant: Arkema 63
ANALYSIS OF ALTERNATIVES
4.2.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of ASE. The information has been collected from the ECHA dissemination portal, and other sources. Table 4.2: Physicochemical properties of ASE Property Value Remarks Source Physical state at 20°C and The substance is odourless and characterised by a Liquid 1 101.3 kPa yellowish colour <-150°C No melting point was determined 1 Melting/freezing point approx. -32°C Pour point (ISO 3016) 4 There is evidence, provided by visual observations, 300 - 400°C at 101.3 Boiling point that the boiling is paralleled by the decomposition 1 kPa of the test item
Density 1.0568 g/cm³ at 20°C Mean value from three replicates 1
2.94 10-4 Pa at 20°C 1 Vapour pressure 4.89 10-4 Pa at 25°C 1 Surface tension - No information identified 2.2 mg/L at 20°C 1 Water solubility
From study undertaken to OECD Guideline 117 5.7-11.3 at 40°C (Partition Coefficient (n-octanol / water), HPLC 1 m Method) adopted 1989. Study includes including Partition coefficient n- mono, di and tri sulfonic phenyl esters octanol/water Depends on the degree of esterification and the - alkyl chain length (C10-C21). It ranges from 4 to 3 11for the mono-, di- and tri-alkylsulphonic esters. Flash point 210 - 240°C 2 Considering the flash point and boiling point, the Flammability - 5 substance is not flammable Explosive properties - Not explosive (due to chemical structure) 5 Self-ignition temperature - No information identified Oxidising properties - No oxidising properties (due to chemical structure) 5 Granulometry - Not relevant Sources: 1: European Chemicals Agency (2013): http://echa.europa.eu/ 2: ESIS Internet site: http://esis.jrc.ec.europa.eu/ 3 : EFSA (2009) 4: Lanxess (2005) 5: Personal communication with ATF members
4.2.1.4 Classification and labelling An online search using the substance’s CAS number was undertaken on the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013). No information on harmonised classification and labelling for ASE is available. However, according to the Inventory, two aggregated notifications have been made. These are presented in Table 4.3.
64 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.3: Notified classification and labelling of ASE according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s)
Not Classified 53 H413 (May cause long Aquatic Chronic 4 H413 lasting harmful effects to 23 aquatic life) Source: European Chemicals Agency: http://echa.europa.eu/
4.2.1.5 REACH Registration Status of ASE An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal on 7 June 201320. Information from the portal notes that ASE has been registered under REACH at a tonnage band of between 10,000 and 100,000 tonnes per annum.
4.2.2 Technical feasibility of ASE
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.2.2
4.2.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.2.2.2 Technical feasibility from the perspective of the downstream user (information from literature) Slightly different forms of ASE are available on the market, with these including Mesamoll itself, Mesamoll II and Mesamoll TP LXS 51067. The exact differences between these substances are not easily distinguishable from the available literature, and all of these products share the same CAS number. According to Lanxess (2005), the main difference between Mesamoll II and Mesamoll is the former’s reduced volatility. The new grade Mesamoll TP LXS 51067 is a fast-solvating plasticizer for PVC processing, particularly suitable for producing plastic floor coverings and wall coatings (Lanxess, 2010). The recently published Final Background Document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) provides a valuable assessment of the technical and economic feasibility of the substance as a replacement for DEHP in PVC21. For this substance, much of the information provided is of direct relevance to DEHP and the end-use
20 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances 21 Or, more specifically, as a replacement in PVC articles intended for use indoors and articles that may come into direct contact with the skin or mucous membranes containing DEHP in a concentration greater than 0.1% by weight of any plasticised material.
Use number: 1,2 Legal name of applicant: Arkema 65
ANALYSIS OF ALTERNATIVES
articles relevant to this AfA. Therefore, relevant information from this report is summarised below. It should be noted though that the information in the Final Background Document is largely sourced from the manufacturer of this substance. RAC and SEAC (2012) notes that ASE is available and already in use in several products. The substance has been reported by Danish manufacturers to be used in toys and, since 2002, ASE has been used in at least one brand of waterbeds. Another study concludes that it is possible to use ASE as a substitute for the normally used phthalate plasticisers in PVC coated textile fabrics such as tents, tarpaulins, rainwear and workwear. In RAC and SEAC (2012), Lanxess also provides information on application areas for ASE among ‘traditional DEHP applications’, as listed in Table 4.4. The table also indicates the level of market experience in each application area according to Lanxess (as interpreted from qualitative text by the RAC and SEAC (2012) report authors). Table 4.4: Applications of ASE as a DEHP substitute and level of relevant market experience Polymer Application Market experience * Calendering of film, sheet and coated products 2 Calendering of flooring, roofing, wall covering 4 Extrusion of hose and profile 2 Extrusion of wire and cable 2 Extrusion of miscellaneous products from compounds 2 Injection moulding of footwear and miscellaneous ? Spread coating of flooring 2 Spread coating of coated fabric, wall covering, coil coating, etc. 2 Car undercoating 2 * Market experience categories interpretation: 1) Main alternative on market; 2) Significant market experience; 3) Examples of full scale experience; 4) Pilot/lab scale experience Adapted from source: RAC and SEAC (2012)
A document on product profiles further cites relevant end-use applications for Mesamoll in PVC (Bayer, undated), as being:
Children’s toys;
Gloves;
Interior film / trim for automotive use;
Luggage and seat coverings (artificial leather);
Roofing membrane;
Shoe soles; and
Truck tarpaulins. Interestingly others, including competitors (ExxonMobil) in the plasticisers market, suggest that the range of applications is more limited, instead linking its use to mainly toy and food contact applications (e.g. ExxonMobil, 2010). However, it must be remembered that neither children’s toys nor food are relevant to the applied-for uses of DEHP in this AoA (as they are especially excluded from the AoA due to being restricted under other EU legislation).
66 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.5 provides comparisons between ASE and DEHP for selected parameters. Table 4.5: Comparison of ASE and DEHP for some selected parameters Plasticiser in PVC, Shore A hardness Volatility,% lost, 1 Extracted in Extracted in conc. 40% =67 phr day at 87 °C over water,% kerosene (jet fuel, in same PVC resin activated carbon etc.),% DEHP 69 4.5 0.01 4.4 ASE 72 5.3 0.03 4.8 Adapted from source: Sears and Darby (1982) in RAC and SEAC (2012)
As noted in RAC and SEAC (2012), the producer Lanxess presents ASE as having the following characteristics:
Outstanding gelling capacity with a large number of polymers including PVC, resulting in lower processing temperatures and shorter processing times;
High saponification resistance especially compared to DEHP, due to ASE's chemical structure; this is especially beneficial for articles which come into contact with water and alkalis;
Good compatibility with a large number of polymers, including polyvinyl chloride (PVC);
Outstanding resistance to weathering and light; and
Good dielectric properties which give plasticised PVC outstanding weldability at high frequencies leading to shorter cycle times than with other plasticisers.
4.2.3 Reduction of overall risk due to transition to ASE Based on the assessment of the hazard profile of ASE, it would appear to be a suitable alternative in terms of its potential lower toxicity to human health but is similar to DEHP in terms of its environmental hazard profile. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.2.3
4.2.4 Availability of ASE From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). In addition, the manufacture of this substance is based on technology which appears to be protected by patent. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.2.4
4.2.5 Economic feasibility of ASE From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain is low. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.2.5
Use number: 1,2 Legal name of applicant: Arkema 67
ANALYSIS OF ALTERNATIVES
4.2.6 Conclusion on suitability and availability for ASE In terms of the substance’s overall human health and environmental hazard profile, ASE would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.2.6
68 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.3 Alternative 2: Alternative substance – ACETYL TRIBUTYL CITRATE (ATBC)
4.3.1 Substance ID and properties of ATBC
4.3.1.1 Name and other identifiers for the substance The following table presents the identity of the substance. Table 4.6: Identity of ATBC Parameter Value Source EC number 201-067-0 1 EC name Tributyl O-acetylcitrate 1 CAS number 77-90-7 1 IUPAC name Tributyl 2-acetoxypropane-1,2,3-tricarboxylate 4 1,2,3-propanetricarboxylic acid, 2- (acetyloxy)-, tributyl ester Citric acid, tributyl ester, acetate (8CI) Other names Tributyl 2-acetylcitrate 2 Citroflex A-4 CITROFOL BII
Molecular formula C20H34O8 1 SMILES notation O=C(OCCCC)CC(OC(=O)C)(C(=O)OCCCC)CC(=O)OCCCC 2 Molecular weight 402.48 3
Molecular structure 1
Sources: 1: ESIS Internet site: http://esis.jrc.ec.europa.eu/ 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.6259.html 3: Chemical Book Internet site: http://www.chemicalbook.com/CASEN_77-90-7.htm 4: European Chemicals Agency: http://echa.europa.eu/
4.3.1.2 Composition of the substance No information was available on constituents or impurities of the commercially available substance from the ECHA dissemination portal22. ATBC is marketed by Vertellus (formerly Morflex), under the product name Citroflex A-4, and by Jungbunzlauer under the product name CITROFOL® BII. A quick search on the Internet can reveal several commercially available ATBC products with a purity of 98% and above. Some further details on substance purity of ‘CITROFOL® BII’ are provided in Table 4.7.
22 Following a more recent search on the ECHA dissemination portal, the substance no longer appears. The reason for this is not known.
Use number: 1,2 Legal name of applicant: Arkema 69
ANALYSIS OF ALTERNATIVES
Table 4.7: CITROFOL® BII substance specifications ATBC Assay (GC) min. 99.0% Acidity (as citric acid) max. 0.02% Colour (APHA) max. 30 Turbidity (NTU) max. 2 Specific Gravity [a]25 1.045 - 1.1055 Refractive Index [a]25° approx. 1.441 Water max. 0.25% 1. Adapted from source: Jungbunzlauer (undated)
4.3.1.3 Physicochemical properties The following table presents the key physicochemical properties of ATBC. The information has been collected from the ECHA dissemination portal and other sources, including consultation with stakeholders. Table 4.8: Physicochemical properties of ATBC Property Value Remarks Source Physical state at 20°C and Colourless, slightly viscous 1 101.3 kPa liquid -57°C at 101.3 kPa 1 Melting/freezing point -59°C 2 331°C at 97.64 kPa 1 Boiling point 327°C 2 Density 1.0528 g/cm³ at 20°C 1 6.93 x 10-3 kPa at 20°C 3 EPISUITE 4.00 (MPBPVP v1.43), 4.94 x 10-5 kPa at 25°C 1 Vapour pressure Modified Grain method 6.1 x 10-7 kPa at 25°C 4 0.11 kPa at 170°C 2 Surface tension 54.6 mN/m at 4 mg/L 1 4.49 mg/L at 20°C 1 Water solubility <100 mg/L 3 EPIWIN (v 3.10), WSKOWWIN 2.045 mg/L 3 Program (v 1.40) Partition coefficient n- 4.86at 40°C and pH 7.1 1 octanol/water 217.9°C at 101.7 hPa 1 Flash point 204°C 2 Data waiving – study scientifically Flammability No data 1 unjustified Data waiving – study scientifically Explosive properties No data 1 unjustified Self-ignition temperature No data Data waiving – study scientifically 1 Oxidising properties No data unjustified Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/
70 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Property Value Remarks Source 2: ATBC Technical Datasheet, Vertellus Internet site: http://www.vertellus.com/Documents%5CTechSheet%5CCITROFLEX%20A4%20English.pdf 3: US EPA Robust Summary and Test Plant: http://www.epa.gov/hpv/pubs/summaries/acetlcit/c15025rs.pdf 4: US Consumer Product Safety Commission: http://www.cpsc.gov/about/cpsia/phthalsub.pdf
4.3.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for ATBC is available. However, several notified classifications and labellings have been identified. These are presented in Table 4.9. In addition, the Inventory suggests that the lead registrant and a further 1,284 notifiers did not classify the substance; a further 58 notifiers also found the available data lacking. However, twelve companies notified the substance with a classification of Muta. 1B (H340) and Carc. 1B (H350), accompanied by Note K. Note K states that the classification as a carcinogen or mutagen need not apply if it can be shown that the substance contains less than 0.1% w/w 1,3- butadiene (EINECS No 203-450-8). If the substance is not classified as a carcinogen or mutagen, at least the precautionary statements (P102-)P210-P403 or the S-phrases (2-)9-16 should apply. Therefore, it is reasonable to assume that under certain circumstances ATBC may be accompanied by impurities (1,3-butadiene) which could lead to a Carc. 1B and Muta. 1B classification. Table 4.9: Notified classification and labelling of ATBC according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s) Flam. Gas 1 H220 H220 GHS02 GHS08 Muta. 1B H340 H340 12 GHS04 Carc. 1B H350 H350 Dgr Skin Irrit. 2 H315 H315 GHS07 3 Eye Irrit. 2 H319 H319 Wng GHS07 Eye Irrit. 2 H319 H319 3 Wng Aquatic Chronic 3 H412 H412 1 Source: European Chemicals Agency: http://echa.europa.eu/
4.3.1.5 REACH Registration Status of ATBC An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal23 on 7 June 2013. Information regarding the substance was not available. An earlier search of the portal search (on 4 June 2012) had suggested that the substance was registered under REACH and therefore is likely to be placed on the market at more than 1,000 tonnes per annum.
23 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
Use number: 1,2 Legal name of applicant: Arkema 71
ANALYSIS OF ALTERNATIVES
4.3.2 Technical feasibility of ATBC
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.3.2
4.3.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.3.2.2 Technical feasibility from the perspective of the downstream user (information from literature) The Final Background Document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) provides an assessment of the technical and economic feasibility of the substance as a replacement for DEHP in PVC24. For this substance, much of the information provided is of direct relevance to DEHP and the end-use articles relevant to this AfA. It should be noted though that the information in the Final Background Document is largely sourced from one of the manufacturers of this substance. As noted in RAC and SEAC (2012), Vertellus (formerly Morflex) has claimed the following:
ATBC is compatible with PVC resin, as well as with a range of other polymers. ATBC has mostly been used in products used for sensitive purposes such as medical products, food contact products and children’s toys, as a replacement for DEHP or DEHA. It is, however, too extractable to be useful in some of the applications in the medical area where contact with lipids is important; and
Beyond its uses in food contact polymers and vinyl toys, variants may find additional applications. ATBC Special has been developed under a patented manufacturing process. A special version for use in pharmaceutical coatings is sold as ATBC, PG. Similarly, another identified producer of the substance (Jungbunzlauer) confirms that as a primary plasticiser, ATBC is used in PVC for certain medical tubes and bags where it is claimed to demonstrate good compatibility and equivalent performance in PVC compared with standard plasticisers (Jungbunzlauer, undated) (Jungbunzlauer, undated b) (Jungbunzlauer, undated). Wilkes et al. (2005) similarly notes that citrates are promoted for plasticised PVC applications facing exceptional toxicological and/or environmental constraints, such as some blood bags and food wraps. Citrates are also used in toys produced by the plastisol process. The market experience with ATBC has been summarised by RAC and SEAC (2012) as follows.
24 Or, more specifically, as a replacement in PVC articles intended for use indoors and articles that may come into direct contact with the skin or mucous membranes containing DEHP in a concentration greater than 0.1% by weight of any plasticised material.
72 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.10: Applications of ATBC as a DEHP substitute and level of relevant market experience Application Market experience * Polymer applications: Calendering of film, sheet and coated products 3 Calendering of flooring, roofing, wall covering Extrusion of hose and profile 3 Extrusion of wire and cable Extrusion of miscellaneous products from compounds 2 Injection moulding of footwear and miscellaneous Spread coating of flooring Spread coating of coated fabric, wall covering, coil coating, etc. Car undercoating *Market experience categories interpretation: 1) Main alternative on market; 2) Significant market experience; 3) Examples of full scale experience; 4) Pilot/lab scale experience Adapted from source: RAC and SEAC (2012)
ECPI (2010a) provides a useful overview of the main drawback of the citrates group of substances noting that they lack the permanency offered by the high molecular weight phthalates, while having a much higher cost. They also exhibit higher volatility loss, higher fogging, higher level of extraction, limiting their use for the production of durable goods such as cables, flooring or roofing membranes. Table 4.11 provides further comparisons between ATBC and DEHP for selected parameters. Table 4.11: Comparison of ATBC with DEHP for various parameters in PVC at 50 phr DEHP ATBC Hardness, Durometer A, 10 s 79 78 Modulus at 100% elongation (psi) 1368 1348 Tensile strength (psi) 2748 2862 Ultimate elongation (%) 395 400 a Clash-Berg T4 (10,000 Psi) (ºC) -8.4 -7.6 a Clash-Berg Tf (100,000 Psi) (ºC) -38.8 -35.6 Brittle pointb (ºC) -24.5 -18.5 Volatile lossc (air) (%) 4.8 12.1 Volatile lossd (A/C) (%) 3.4 7.0 Water extractione (%) 0.7 1.2 Soapy water extractionf (%) 2.7 9.5 ASTM Oil #3 extractiong (%) 11.4 10.9 Silica gel migrationh (%) 12.2 17.0 Note: T4 and Tf are torsion flex indicators at specific conditions aASTM D 1043 bASTM D 746 c24 hours at 100ºC dASTM D 1203, 24 hours at 70ºC e10 days at 40ºC f24 hours at 60ºC in 1% soap solution g24 hours at 60ºC in ASTM No, 3 oil h24 hours at 70ºC in 100-mesh silica Note: All results of volatility and extraction losses are reported as a percentage of plasticiser loss and not weight loss of the PVC compound Source: Adapted from Grossman (2008)
Use number: 1,2 Legal name of applicant: Arkema 73
ANALYSIS OF ALTERNATIVES
4.3.3 Reduction of overall risk due to transition to ATBC The available evidence suggests that ATBC may pose a lower hazard than DEHP. Thus it could tentatively be suggested as a suitable alternative in terms of hazard potential but there is some uncertainty regarding this possibility since a number of CLP notifiers have proposed a classification of 1B for mutagenicity and carcinogenicity. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.3.3
4.3.4 Availability of ATBC From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). This is due to process technology constraints (the precursor materials should be available to the applicant). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.3.4
4.3.5 Economic feasibility of ATBC From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is low (it should be noted that ATBC is a speciality plasticiser and is not considered to be a viable alternative in the general purpose applications of DEHP – particularly those of relevance to this AoA). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.3.5
4.3.6 Conclusion on suitability and availability for ATBC In terms of the substance’s overall human health and environmental hazard profile, it can be tentatively stated that ATBC would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.3.6
74 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.4 Alternative 3: Alternative substance – GLYCERIDES, CASTOR-OIL-MONO-, HYDROGENATED, ACETATES (COMGHA)
4.4.1 Substance ID and properties of COMGHA
4.4.1.1 Name and other identifiers for the substance Table 4.12 presents the identity of COMGHA. Table 4.12: Identity of COMGHA Parameter Value Source EC number 616-005-1 (COMGHA - temporary list number) 1 EC name No information identified - 736150-63-3 (COMGHA) CAS number 330198-91-9 (component A) 2 33599-07-4 (component B) IUPAC name No information identified - Other names GRINDSTED® SOFT-N-SAFE 4 C H O (component A) Molecular formula 27 48 8 2 C25H46O6 (component B) O=C(OC(COC(=O)CCCCCCCCCCCCCCCCC)COC(=O)C)C SMILES notation 3 (component B only) 500.7 (component A) Molecular weight 2 442.6 (component B)
Molecular structure Component A 2
Component B Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: SCENIHR (2007) 3 : ChemSpider Internet site: http://www.chemspider.com/ 4 : RAC and SEAC (2012)
Use number: 1,2 Legal name of applicant: Arkema 75
ANALYSIS OF ALTERNATIVES
4.4.1.2 Composition of the substance COMGHA is a mixture of two components: A (Ca. 84%: 12-(Acetoxy)-stearic acid, 2,3- bis(acetoxy)propyl ester), and a minor component B (Ca. 10%: Octadecanoic acid, 2,3- (bis(acetoxy)propyl ester) (SCENIHR, 2007). As can be deduced, these components represent 94% of the substance. The remaining impurities are documented in the following table. Table 4.13: COMGHA impurities Impurity Value Octadecanoic acid, 12-acetoxy, 2-hydroxy, 3-acetoxypropyl ester 2% Octadecanoic acid, 12-oxy, 2,3-bis(acetoxy)propyl ester 1.5% Octadecanoic acid, 12-actyloxy, 2(acetoxy)-1,3-propanediyl ester 1.1% Octadecanoic acid, 3-(acetoxy)-2-hydroxypropyl ester 1.0% As max 3 ppm Pb max 5 ppm Hg max 1 ppm Cd max 1 ppm Source: SCENIHR (2007)
4.4.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of COMGHA. A significant proportion of the needed information proved impossible to find in publicly available sources. Table 4.14: Physicochemical properties of COMGHA Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Melting/freezing point -21.5°C Pour point 1 Boiling point >300°C 1 Density 1.1014 1 Vapour pressure - No information identified - Surface tension - No information identified -
Water solubility - No information identified -
Partition coefficient n- - No information identified - octanol/water Flash point 245°C 1 Flammability - No information identified - Explosive properties - No information identified - Self-ignition temperature - No information identified - Oxidising properties - No information identified - Granulometry - Not relevant - Source: 1: Danisco: http://www.danisco.com/softnsafe/doc/snsbrochure.pdf
76 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.4.1.4 Classification and labelling An online search was performed using the CAS numbers in the recently published ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013). No information on harmonised classification and labelling for COMGHA, component A or component B is available. In addition, no aggregated notifications have been identified.
4.4.1.5 REACH Registration Status of COMGHA An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal25 on 7 June 2013. Information from the portal notes that the substance has not yet been registered (component A and component B are not registered or pre-registered). It should be noted that COMGHA has been pre-registered with an envisaged registration deadline of May 2018.
4.4.2 Technical feasibility of COMGHA
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.4.2
4.4.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.4.2.2 Technical feasibility from the perspective of the downstream user (information from literature) The Final Background Document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) provides an assessment of the technical and economic feasibility of COMGHA as a replacement for DEHP in PVC26. For this substance, much of the information provided is of direct relevance to DEHP and the end-use articles relevant to this AfA. It should be noted that the information in the Final Background Document is largely sourced from the manufacturer of this substance. As noted in RAC and SEAC (2012), Danisco characterises COMGHA/ GRINDSTED® SOFT-N- SAFE as an efficient, one-to-one replacement for most conventional plasticisers, such as phthalates. Danisco claims that COMGHA meets the quality, durability and functional properties achieved by phthalate-based solutions. The company further argues that COMGHA can be directly applied, without any further alteration to the formulation or processing. With particular regard to COMGHA’s potential applicability to PVC, Danisco claims its product compares favourably to phthalates with a chain of C8-C11 (DEHP to DUP) showing equivalent or superior properties. The main applications for COMGHA in PVC are identified as:
25 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances 26 Or, more specifically, as a replacement in PVC articles intended for use indoors and articles that may come into direct contact with the skin or mucous membranes containing DEHP in a concentration greater than 0.1% by weight of any plasticised material.
Use number: 1,2 Legal name of applicant: Arkema 77
ANALYSIS OF ALTERNATIVES
Food contact applications;
Other potentially 'sensitive' applications e.g. some medical devices;
Flooring formulations;
Carpet backing;
Coated fabrics;
Wire & cable applications; and
Plastisol applications. Danisco goes on to claim that, compared with traditional plasticisers such as DEHP and DINP, COMGHA can perform consistently well in applications such as vinyl flooring, wallpaper, shrink wrap film, textile dyes, ink applications, adhesives and sealants. In application tests with toys for young children, COMGHA is suggested to provide the same level of efficiency as DEHP, when measured according to the Shore A scale. TGA analysis has shown that COMGHA is considerably less volatile than DEHP under all conditions. COMGHA has also been compared with DEHP in numerous flexible PVC applications that perform a sensitive medical role, including tubing and medical film. Danisco claims that the test results show that COMGHA meets all requirements in the extrusion, calendering and injection moulding applications where it has been evaluated. In medical applications where plasticiser migration is a particular concern, COMGHA is suggested to have demonstrated high extraction resistance in aqueous and oily media. In RAC and SEAC (2012), Danisco also provides information on application areas and market experience for COMGHA among ‘traditional DEHP applications’, as seen in Table 4.15. Table 4.15: Applications of COMGHA as a DEHP substitute and level of relevant market experience Application Market experience * Polymer applications: Calendering of film, sheet and coated products 2 Calendering of flooring, roofing, wall covering 1 Extrusion of hose and profile 3 Extrusion of wire and cable 3 Extrusion of miscellaneous products from compounds 3 Injection moulding of footwear and miscellaneous 3 Spread coating of flooring 1 Spread coating of coated fabric, wall covering, coil 2 coating, etc. Car undercoating N/A *1Market experience categories interpretation: 1) Main alternative on market;2) Significant market experience; 3) Examples of full scale experience Adapted from source: RAC and SEAC (2012)
Table 4.16 shows further comparisons between COMGHA and DEHP for selected parameters.
78 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.16: Comparison of COMGHA and DEHP for some selected parameters
Plasticiser (at 40 Shore A, after 15 Tensile strength, 100% modulus, Max. elongation,% phr) sec MPa MPa COMGHA 88 25 9.1 367 DEHP 90 22.2 8.5 320 Adapted from source: Danisco (2012) in RAC and SEAC (2012)
4.4.3 Reduction of overall risk due to transition to COMGHA Based on the assessment of the hazard profile of COMGHA, it would appear to be a suitable alternative in terms of its potential toxicity to human health and the environment. However, the incomplete nature of the database (in terms of its toxicokinetic behaviour) introduces a measure of uncertainty to the comparative analysis. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.4.3
4.4.4 Availability of COMGHA From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). In addition, the manufacture of this substance is based on technology which appears to be protected by patent. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.4.4
4.4.5 Economic feasibility of COMGHA From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is very low. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.4.5
4.4.6 Conclusion on suitability and availability for COMGHA In terms of the substance’s overall human health and environmental hazard profile, COMGHA would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.4.6
Use number: 1,2 Legal name of applicant: Arkema 79
ANALYSIS OF ALTERNATIVES
4.5 Alternative 4: Alternative substance – DI(2-ETHYLHEXYL)ADIPATE (DEHA)
4.5.1 Substance ID and properties of DEHA
4.5.1.1 Name and other identifiers for the substance Table 4.17 presents the identity of DEHA. Table 4.17: Identity of DEHA Parameter Value Source EC number 203-090-1 1 EC name Bis(2-ethylhexyl) adipate 1 CAS number 103-23-1 1 IUPAC name Bis(2-ethylhexyl) adipate 1 Di-octyl-adipate (DOA) Di(2-ethylhexyl) adipate (DEHA) Other names Hexanedioic acid, bis (2-ethylhexyl) ester 1,2 Adipic acid, bis (2-ethylhexyl) ester Di-2-ethylhexyl hexane-1,6-dioate Molecular formula C22H42O4 1 SMILES notation O=C(OCC(CC)CCCC)CCCCC(=O)OCC(CCCC)CC 2 Molecular weight 370.5665 2
Molecular structure 3
Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.7358.html 3: ESIS Internet site: http://esis.jrc.ec.europa.eu/
4.5.1.2 Composition of the substance Commercially available DEHA with purity of 100% appears to be available (Eastman, 2012a).
4.5.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DEHA. The information has been collected from literature sources and consultation.
80 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.18: Physicochemical properties of DEHA Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Measured; Lide DR (1998): CRC Handbook of Melting/freezing point -67.8°C Chemistry and Physics, 79thed. Boca Raton, FL: 1 CRC Press Inc. (cited in HSDB) Measured; SRC PhysProp (2008), Syracuse Boiling point 417°C at 1013.25 hPa 1 Research Corporation Database Density 0.92 g/cm³ at 20°C DIN 51757, pycnometer method 1 Estimated value through graphic extrapolation 3 x10-8 kPa at 20°C 1 analogous tothe vapour pressure of tetracosane Vapour pressure 1.13 x10-7 kPa at Felder J.D. et al. (1986): Environmental 1 20°C Toxicology and Chemistry, Vol. 5, pp. 777-784 Predicted data is generated using the ACD/Labs’ Surface tension 32.23 dyne/cm 2 ACD/PhysChem Suite 0.0032 mg/L at 22°C Felder, JD, Adams, WJ& Saeger, VW (1986): 1 Assessment of the Safety of Dioctyl Adipate in Water solubility 0.78 mg/L at 22°C Freshwater Environments, Environ. Toxicol. Chem. 1 Vol 5, pp. 777-784 Partition coefficient n- OECD Guideline 117 (Partition Coefficient (n- 8.94 at 25°C 1 octanol/water octanol / water), HPLC Method) Closed cup 196°C at 1013.25 hPa Database from Berufsgenossenschaftliches Institut 1 für Arbeitsschutz, dated 2007 Flash point Lewis, R.J. Sr. (1993): Hawley’s Condensed 196°C at 1013.25 hPa Chemical Dictionary, Twelfth Edition, p. 394, Van 1 Nostrand Reinhold Considering the flash point and the boiling point, Flammability Not relevant 3 the substance is not flammable Explosive properties Not relevant Not explosive (due to chemical structure) 3 Measured National Fire Protection Association (1997): Fire 377°C at 1013.25 hPa Protection Guide to Hazardous Materials 12ed., 1 Quincy, MA: National Fire Protection Association, Self-ignition temperature p. 325-44 (cited in HSDB) Measured 340°C at 1013.25 hPa GESTIS Database, Berufsgenossenschaftliches 1 Institut für Arbeitsschutz No oxidising Oxidising properties 1 properties Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.7358.html 3: Personal communication with ATF members
4.5.1.4 Classification and labelling An online search using the substance’s CAS number was undertaken on the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013). No information on harmonised classification and labelling for DEHA is available. However, according to the Inventory, 11 aggregated notifications have been made. Information is presented in Table 4.19. In addition, the
Use number: 1,2 Legal name of applicant: Arkema 81
ANALYSIS OF ALTERNATIVES
Inventory also suggests that the lead registrant and a further 767 notifiers did not classify the substance; a further 28 notifiers found the available data lacking. Table 4.19: Notified classification and labelling of DEHA according to CLP criteria Classification Labelling Hazard Number of Hazard Class and Pictograms Signal Statement Hazard Statement Code(s) Notifiers Category Code(s) Word Code(s) Code(s) Skin Irrit. 2 H315 H315 (Causes skin irritation) GHS07 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) GHS09 23 Wng Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) GHS09 H410 (Very toxic to aquatic life with 11 Aquatic Chronic 1 H410 Wng long lasting effects) GHS09 Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) 6 Wng Skin Irrit. 2 H315 H315 (Causes skin irritation) GHS07 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) GHS09 4 Wng Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) H312 (Harmful in contact with skin) Acute Tox. 4 H302 H302 (Harmful if swallowed) Skin Irrit. 2 H315 H315 (Causes skin irritation) GHS06 GHS09 1 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) Dgr Acute Tox. 2 H332 H332 (Harmful if inhaled) Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) GHS08 Carc. 2 H351 H351 (Suspected of causing cancer) 1 Wng H361 (Suspected of damaging fertility GHS08 Repr. 2 H361 1 or the unborn child) Wng Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) GHS08 H411 (Toxic to aquatic life with long 1 Aquatic Chronic 2 H411 Wng lasting effects) H319 1 Source: European Chemicals Agency: http://echa.europa.eu/
4.5.1.5 REACH Registration Status of DEHA An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal27 on 7 June 2013. Information from the portal notes that the substance has been registered under REACH with the indicated tonnage being between 10,000 and 100,000 tonnes per annum.
27 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
82 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.5.2 Technical feasibility of DEHA
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.5.2
4.5.2.1 Technical feasibility from the perspective of the applicant From the perspective of the applicant, this substance may be a technically feasible alternative for DEHP. However, due the lack of economic feasibility this has not been investigated.
4.5.2.2 Technical feasibility from the perspective of the downstream user (information from literature) DEHA is classed as an aliphatic dicarboxylic acid ester. This class of plasticiser is typically used to help extend the temperature range of plasticised PVC products. The substance can be used as either a primary or secondary plasticiser (Kutz, 2011). Some literature suggests that DEHA has replaced the phthalates in thin plasticised PVC films used for food packaging (Dalgaard, et al., 2003). Patrick (2005) cites the characteristics of the substance as improved low temperature performance, higher volatility, low viscosity plastisols, noting a ‘typical use’ of the substance as a blending plasticiser used in combination with polymeric plasticiser for food cling wrap. Table 4.20 shows comparisons between DEHA and DEHP for selected parameters. Table 4.20: Comparison of DEHA with DEHP for various parameters in PVC at 50 phr DEHP DEHA Hardness, Durometer A, 10 s 79 78 Modulus at 100% elongation (psi) 1368 1092 Tensile strength (psi) 2748 1797 Ultimate elongation (%) 395 414 a Clash-Berg T4 (10,000 Psi) (ºC) -8.4 -30.8 a Clash-Berg Tf (100,000 Psi) (ºC) -38.8 -66.5 Brittle pointb (ºC) -24.5 -56.5 Volatile lossc (air) (%) 4.8 7.1 Volatile lossd (A/C) (%) 3.4 7.6 Water extractione (%) 0.7 1.5 Soapy water extractionf (%) 2.7 11.0 ASTM Oil #3 extractiong (%) 11.4 34.7 Silica gel migrationh (%) 12.2 23.0 Note: T4 and Tf are torsion flex indicators at specific conditions aASTM D 1043 bASTM D 746 c24 hours at 100ºC dASTM D 1203, 24 hours at 70ºC e10 days at 40ºC f24 hours at 60ºC in 1% soap solution g24 hours at 60ºC in ASTM No, 3 oil h24 hours at 70ºC in 100-mesh silica Note: All results of volatility and extraction losses are reported as a percentage of plasticiser loss and not weight loss of the PVC compound Adapted from source: Grossman (2008)
Use number: 1,2 Legal name of applicant: Arkema 83
ANALYSIS OF ALTERNATIVES
Relative to phthalates, adipates are more volatile, exhibit poorer fusion and compatibility with PVC, have higher migration rates and are generally more costly. As a result, it is not uncommon to use adipates in blends with other plasticisers to attain the desired combination of properties (ECPI, 2010a).
4.5.3 Reduction of overall risk due to transition to DEHA In terms of the substance’s overall human health and environmental hazard profile, DEHA would appear to be a suitable replacement for DEHP. However, it should be noted that DEHA has recently been entered onto the CoRAP list update for the years 2013-2015 (ECHA, 2013) because of concerns regarding its CMR status. Hence, from a regulatory risk management perspective it is not reasonable to consider this a suitable alternative at this time, given the identified human health concern and the substance evaluation process currently in progress. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.5.3
4.5.4 Availability of DEHA From the perspective of the applicant, it is reasonable to assume that the substance would be available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.5.4
4.5.5 Economic feasibility of DEHA From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is low. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.5.5
4.5.6 Conclusion on suitability and availability for DEHA Based on our current understanding, in terms of the substance’s overall human health and environmental hazard profile, DEHA would appear to be a suitable replacement for DEHP. However, taking a wider view that includes the regulatory risk management perspective, it may not be reasonable to consider this substance a suitable alternative at this time given that the substance is currently the subject of an evaluation process. In addition, from the perspective of the applicant, the substance is also not an economically feasible alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.5.6
84 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.6 Alternative 5: Alternative substance – DIETHYLHEXYLSEBACATE (DEHS)
4.6.1 Substance ID and properties of DEHS
4.6.1.1 Name and other identifiers for the substance Table 4.21 presents the identity of DEHS. Table 4.21: Identity of DEHS Parameter Value Source EC number 204-558-8 1 EC name Bis(2-ethylhexyl) sebacate 1 CAS number 122-62-3 1 IUPAC name Bis(2-ethylhexyl) sebacate 2 bis(2-ethylhexyl) decanedioate 2-Ethylhexyl sebacate Other names 2 Dioctyl sebacate Plexol 201
Molecular formula C26H50O4 2 SMILES notation CCCCC(CC)COC(=O)CCCCCCCCC(=O)OCC(CC)CCCC 2 Molecular weight 426.6728 2
Molecular structure 2
Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: Chemspider: http://www.chemspider.com/Chemical-Structure.28959.html
4.6.1.2 Composition of the substance No information has been identified.
4.6.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DEHS. Table 4.22: Physicochemical properties of DEHS Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Melting/freezing point - No information identified - Boiling point 212°C at 1 mmHg 1 Density 0.914 g/mL at 25°C 1 Vapour pressure - No information identified -
Use number: 1,2 Legal name of applicant: Arkema 85
ANALYSIS OF ALTERNATIVES
Property Value Remarks Source Surface tension - No information identified - Water solubility - No information identified - Partition coefficient n- - No information identified - octanol/water Flash point >113°C 1 Flammability - No information identified - Explosive properties - No information identified - Self-ignition temperature - No information identified - Oxidising properties - No information identified - Granulometry - Not relevant - Source: 1: Sigma-Aldrich Internet site: http://www.sigmaaldrich.com/catalog/product/aldrich/84822
4.6.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DEHS is available. However, notified classifications and labelling have been identified. These are presented in Table 4.23. The Inventory also suggests that the lead registrant and a further 261 notifiers did not classify the substance; a further individual notifier found the available data lacking. Table 4.23: Notified classification and labelling of DEHS according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s)
H302 (Harmful if GHS07 Acute Tox. 4 H302 3 swallowed) Wng
Source: European Chemicals Agency: http://echa.europa.eu/
4.6.1.5 REACH Registration Status of DEHS An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal28 on 7 June 2013. Information from the portal notes that the substance has not yet been registered. However, it should be noted that DEHS has been pre-registered with an envisaged registration deadline of November 2010, suggesting that it is placed on the market in volumes of less than 1,000 tonnes per annum.
4.6.2 Technical feasibility of DEHS
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.6.2
28 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
86 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.6.2.1 Technical feasibility from the perspective of the applicant From the perspective of the applicant, this substance may be a technically feasible alternative for DEHP. However, due to the lack of economic feasibility this has not been investigated.
4.6.2.2 Technical feasibility from the perspective of the downstream user (information from literature) DEHS has been reported to have superior low temperature performance and good flexibility, but inferior extraction resistance when compared to DEHP (Patrick, 2005). The substance commands a significant price premium, and its use is generally limited to extremely demanding low temperature flexibility specifications (e.g. underground cable sheathing in arctic environments) (ECPI, 2010a).
4.6.3 Reduction of overall risk due to transition to DEHS In terms of the substance’s overall human health and environmental hazard profile, DEHS would appear to be a suitable replacement for DEHP. However, such conclusions cannot be established with great confidence at this time with respect to human health hazard because of the limited dataset available and the potential developmental concerns arising from read-across. The environmental hazard posed by DEHS appears unlikely to be substantially different from DEHP. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.6.3
4.6.4 Availability of DEHS From the perspective of the applicant, it is reasonable to assume that the substance would be available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.6.4
4.6.5 Economic feasibility of DEHS From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is very low (it should be noted that DEHS, a sebacate, is a speciality plasticiser and is not considered to be a viable alternative in the general purpose applications of DEHP – particularly those of relevance to this AoA). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.6.5
Use number: 1,2 Legal name of applicant: Arkema 87
ANALYSIS OF ALTERNATIVES
4.6.6 Conclusion on suitability and availability for DEHS In terms of the substance’s overall human health and environmental hazard profile, DEHS would appear to be a suitable replacement for DEHP. However, the conclusion on the human health hazard potential is subject to considerable uncertainty at this time because of the limited dataset and concerns regarding potential developmental toxicity based upon read-across. From the perspective of the applicant, the substance is also not an economically feasible alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.6.6
4.7 Alternative 6: Alternative substance – DI(2-ETHYLHEXYL) TEREPHTALATE (DEHT)
4.7.1 Substance ID and properties of DEHT (DOTP)
4.7.1.1 Name and other identifiers for the substance Table 4.24 presents the identity of DEHT. Table 4.24: Identity of DEHT Parameter Value Source EC number 229-176-9 1 EC name Bis(2-ethylhexyl) terephthalate 1 CAS number 6422-86-2 1 IUPAC name Bis(2-ethylhexyl) terephthalate 1 Eastman (TM) DOTP Plasticizer; Sasa Plus 88; Other names GL300; 1 DOTP; DEHT
Molecular formula C24H38O4 2 SMILES notation O=C(OCC(CC)CCCC)c1ccc(C(=O)OCC(CC)CCCC)cc1 2 Molecular weight 390.5561 2
Molecular structure 1
Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: ChemSpider Internet Site: http://www.chemspider.com/Chemical-Structure.21471.html
88 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.7.1.2 Composition of the substance DEHT is a clear liquid at room temperature and is manufactured at >98% purity. Minor impurities (present at <2%) include 2-ethylhexyl methyl terephthalate (OECD, 2003).
4.7.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DEHT. Table 4.25: Physicochemical properties of DEHT Property Value Remarks Source Physical state at 20°C and Liquid The substance is colourless and has a slight odour 1 101.3 kPa <-67.2°C 1 Melting/freezing point -48°C 2 417°C at 101.325 kPa 1 Boiling point 400 °C 2 0.98 g/cm³ at 20°C 1 Density 0.986 at 25°C 2 0.001 Pa at 25°C Estimated 1 Vapour pressure 1 mmHg at 217°C 2 32.7 ± 1 mN/m at Surface tension 1 22°C 0.4 µg/L at 22.5 ± 1.5 Water solubility Mean value from two tests 1 °C Result in sea water. Based on study with Klimisch score of 3 1.8x105 1 Partition coefficient n- octanol/water Result in well water. Based on study with Klimisch 5.2x105 at 25°C 1 score of 3 212°C ± 2°C at Flash point Determined on the basis of three results 1 101.325 kPa Considering the flash point and boiling point, the Flammability - 3 substance is not flammable Explosive properties - Not explosive due to chemical structure 3 Self-ignition temperature 387 ± 5°C at 98 kPa - Oxidising properties - No oxidizing properties (due to chemical structure) 3 Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: Sigma-Aldrich Internet Site: http://www.sigmaaldrich.com/catalog/product/aldrich/525189 3 : Personal communication with ATF members
4.7.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DEHT is available. However, a single notified classification and labelling entry has been identified. This is presented in Table 4.26. The
Use number: 1,2 Legal name of applicant: Arkema 89
ANALYSIS OF ALTERNATIVES
Inventory also suggests that the lead registrant and a further 164 notifiers did not classify the substance. In addition, a further 34 notifiers found the available data lacking. Table 4.26: Notified classification and labelling of DEHT according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s) H413 (May cause long H413 lasting harmful effects to aquatic life) GHS08 1 H361 (Suspected of Wng H361 damaging fertility or the unborn child) Source: European Chemicals Agency: http://echa.europa.eu/
4.7.1.5 REACH Registration Status of DEHT An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal29 on 7 June 2013. Information from the portal notes that the substance has been registered under REACH, with an indicated tonnage of between 10,000 and 100,000 tonnes per annum.
4.7.2 Technical feasibility of DEHT
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.7.2
4.7.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.7.2.2 Technical feasibility from the perspective of the downstream user (information from literature) The recently published Final Background Document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) provides a valuable assessment of the technical and economic feasibility of the substance as a replacement for DEHP in PVC30. For this substance, much of the information provided in RAC and SEAC (2012) is of direct relevance to DEHP and the end-use articles relevant to this AfA. Therefore, relevant information has been summarised from this report, below. It should be noted that the information in the Final Background Document is largely sourced from one of the manufacturers of this substance.
29 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances 30 Or, more specifically, as a replacement in PVC articles intended for use indoors and articles that may come into direct contact with the skin or mucous membranes containing DEHP in a concentration greater than 0.1% by weight of any plasticised material.
90 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
As noted in RAC and SEAC (2012), Eastman Chemicals claims that DEHT is a good general purpose plasticiser for PVC, with performance equal to or better than most orthophthalate plasticisers (such as DEHP). It offers good performance properties, good low temperature flexibility, resistance to extraction by soapy water and good non-migration properties. In plastisols, DEHT results in low initial viscosity and good keeping viscosity. Potentially relevant applications/uses include:
Coatings for cloth;
Electric connectors;
Flexible film;
Sheet vinyl flooring;
Toys;
Traffic cones;
Vinyl compounding;
Vinyl gloves;
Vinyl products;
Vinyl water stops; and
Walk-off mats. Information was also provided by Eastman Chemicals on application areas for DEHT among ‘traditional DEHP applications’ (RAC and SEAC, 2012), as reported in Table 4.27. The table also indicates the level of market experience in each application area according to Eastman (as interpreted from qualitative text by the RAC and SEAC (2012) report authors). Table 4.27: Applications of DEHT as a DEHP substitute and level of relevant market experience Polymer Application Market experience * Calendering of film, sheet and coated products 2 Calendering of flooring, roofing, wall covering 2 Extrusion of hose and profile 2 Extrusion of wire and cable 2 Extrusion of miscellaneous products from compounds 2 Injection moulding of footwear and miscellaneous 2 Spread coating of flooring 2 Spread coating of coated fabric, wall covering, coil 2 coating, etc. Car undercoating - *Market experience categories interpretation: 1) Main alternative on market; 2)Significant market experience; 3) Examples of full scale experience; 4) Pilot/lab scale experience Adapted from source: RAC and SEAC (2012)
It is also noted that Eastman have recently (April 2013) begun to market an enhanced grade of DEHT (Eastman 168 SG) targeted at applications such as medical devices, toys, childcare articles,
Use number: 1,2 Legal name of applicant: Arkema 91
ANALYSIS OF ALTERNATIVES
and food contact applications (Eastman, 2013). Table 4.28 shows comparisons between DEHT and DEHP for selected parameters. Table 4.28: Comparison of DEHT and DEHP for some selected parameters Plasticiser DEHP DEHT Loading necessary to reach 62 66 70 Shore A hardness (phr) Tensile strength, MPa (ASTM D412) 16.8 16.4 Elongation, % 311 308 (ASTM D412) Modulus, MPa 6.8 6.9 (ASTM D412) Tear resistance, kN/m (ASTM D624) 53.8 50.6 Brittleness temperature, °C (ASTM D746) -41 -47 Fusion torque, mg 1368 980 Base formulation in addition to plasticizer (phr): OxyVinyls 500F PVC (100), ESO (5), calcium stearate (0.15), zinc stearate (0.2), stearic acid (0.2) Adapted from source: Eastman (2012b)
4.7.3 Reduction of overall risk due to transition to DEHT The human health hazard posed by DEHT is slightly lower than DEHP and the environmental hazard posed by this substance appears similar. Hence, this may constitute a suitable alternative in terms of potential hazard. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.7.3
4.7.4 Availability of DEHT From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). This is due to process technology constraints (the precursor materials should be available to the applicant). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.7.4
4.7.5 Economic feasibility of DEHT From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is only modest. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.7.5
92 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.7.6 Conclusion on suitability and availability for DEHT In terms of the substance’s overall human health and environmental hazard profile, DEHT would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically or economically feasible alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.7.6
4.8 Alternative 7: Alternative substance – DPHP Bis(2-propylheptyl) Phthalate (DPHP)
4.8.1 Substance ID and properties of DPHP
4.8.1.1 Name and other identifiers for the substance Table 4.29 presents the identity of DPHP. Table 4.29: Identity of DPHP Parameter Value Source EC number 258-469-4 1 EC name bis(2-propylheptyl) phthalate 1 CAS number 53306-54-0 1 IUPAC name bis(2-propylheptyl) phthalate 1 1,2-benzenedicarboxylic acid, di-2-propylheptyl ester Other names DPHP 1,2,4 Palatinol 10-P
Molecular formula C28H46O4 1 SMILES notation O=C(OCC(CCC)CCCCC)c1ccccc1C(=O)OCC(CCC)CCCCC 2 Molecular weight 446.6624 2
Molecular structure 3
Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.83367.html 3: ESIS Internet site: http://esis.jrc.ec.europa.eu/ 4: BASF: http://www.basf.com/group/corporate/en/brand/PALATINOL_10_P
Use number: 1,2 Legal name of applicant: Arkema 93
ANALYSIS OF ALTERNATIVES
4.8.1.2 Composition of the substance No information is available on constituents or impurities of the commercially available substance, including in the ECHA dissemination portal31. A search of the Internet revealed one manufacturer of commercially available DPHP products32.
4.8.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DPHP. Table 4.30: Physicochemical properties of DPHP Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Melting/freezing point -48°C Pour point 1
Boiling point Ca. 252.5-253.4°C 1 at 7 hPa OECD Guideline 109 (Density of Liquids and Density 1 0.96 g/cm³ at 20°C Solids) 3.7 x10-8 kPa at Effusion method: by loss of weight or by 1 Vapour pressure 20°C trapping vaporisate 0.99 hPa at 211.2°C OECD Guideline 104 (Vapour Pressure Curve) 1 Predicted data is generated using the ACD/Labs’ Surface tension 35.18 dyne/cm 1 ACD/PhysChem Suite EU Method A.6 (Water Solubility) Cited as Water solubility <0.0001 mg/L at 1 25°C Directive 92/69/EEC, A.6 Partition coefficient n- EU Method A.8 (Partition Coefficient) Cited as 1 octanol/water >6 at 25°C, pH 5.77 Directive 92/69/EEC, A.8 ISO 2719:2002 (Determination of flash point - 220°C at 1013.25 1 hPa Pensky-Martens closed cup method) Flash point 236°C at 1013.25 ISO 2719:2002 (Determination of flash point - 1 hPa Pensky-Martens closed cup method) Considering flash point and boiling point, the Flammability - 2 substance is not flammable Explosive properties - Not explosive (due to chemical structure) 2
Self-ignition temperature 345°C at 1013.25 Other guideline: German DIN 51794 1 hPa No oxidising Oxidising properties 1 properties Granulometry - Not relevant 1 Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: Personal communication with ATF members
31 Date of last search: 7 June 2013. 32 http://www.plasticizers.basf.com/portal/streamer?fid=228825
94 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.8.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DPHP is available. With regard to aggregated notifications, the Inventory suggests that the lead registrant and a further 132 notifiers did not classify the substance.
4.8.1.5 REACH Registration Status of DPHP An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal33 on 7 June 2013. Information from the portal notes that the substance has been registered under REACH, with an indicated tonnage of between 100,000 and 1,000,000 tonnes per annum.
4.8.2 Technical feasibility of DPHP Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.8.2
4.8.2.1 Technical feasibility from the perspective of the applicant The substance has been registered by the applicant as part of a project to investigate the feasibility of its production. This is discussed further in the SEA and the Confidential Annex to this document.
4.8.2.2 Technical feasibility from the perspective of the downstream user (information from literature) According to the manufacturer, BASF, due to its relative low volatility, Palatinol 10-P (DPHP) is most suitable for higher temperature requirement applications, such as wire & cable and automotive interior trim. Because of its good weathering behaviour, Palatinol 10-P performs very well in outdoor applications, such as roofing membranes and tarpaulins (BASF, 2013). The performance of this branched C10 phthalate ester is similar to that of DIDP, although it exhibits higher volatile losses and requires slightly higher processing temperatures (Grossman, 2008). Compared to DEHP, Patrick (2005) notes that DPHP is slightly less efficient, but has a lower volatility. 4.8.3 Reduction of overall risk due to transition to DPHP Though appearing to be somewhat less toxic than DEHP based on available DNELs, there are concerns as to its toxicity potential for multiple endocrine organs (i.e., pituitary, thyroid and adrenal glands) that cannot be adequately resolved using the available evidence base. Based on available information, it appears that DPHP and DEHP may show a somewhat similar environmental hazard potential. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.8.3
33 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
Use number: 1,2 Legal name of applicant: Arkema 95
ANALYSIS OF ALTERNATIVES
4.8.4 Availability of DPHP From the perspective of the applicant, the availability of this substance is currently under consideration; early indications suggest a number of issues that could negatively impact potential availability. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.8.4
4.8.5 Economic feasibility of DPHP From the perspective of the applicant, the outcome of the ongoing project is not yet available. However, it should be noted that economic feasibility issues have been identified - for example: a loss of process integration which would incur significant associated costs for the applicant. In addition, it should be noted that market demand for this substance in the ATF supply chain was not indicated; the supply chain survey reported that its potential use in the end-use applications of relevance to this AfA is very low. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.8.5
4.8.6 Conclusion on suitability and availability for DPHP Though appearing to be somewhat less toxic than DEHP based on available DNELs, from a regulatory risk perspective there are concerns as to its toxicity potential for multiple endocrine organs. From the perspective of the applicant, the substance cannot be considered an economically feasible or available alternative until the current research project has been formally concluded. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.8.6
96 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.9 Alternative 8: Alternative substance –DI-ISODECYLPHTHALATE (DIDP)
4.9.1 Substance ID and properties of DIDP
4.9.1.1 Name and other identifiers for the substance Table 4.31 presents the identity of DIDP. Table 4.31: Identity of DIDP Parameter Value Source EC number 271-091-4 and 247-977-1 2 1,2-Benzenedicarboxylic acid, di-C9-11-branched alkyl esters, C10-rich EC name 1 (EC number 271-091-4 / CAS number 68515-49-1 only) CAS number 68515-49-1 and 26761-40-0 2 1,2-Benzenedicarboxylic acid, di-C9-11-branched alkyl esters, C10- rich and IUPAC name 2 di-“isodecyl”phthalate Synonyms: 2 1,2-Benzenedicarboxylic acid, diisodecyl ester Other names Trade names: Jayflex DIDP 1 (EC number 271-091-4 / CAS number 68515-49-1 only)
Molecular formula C28H46O4 (mean) 2 O=C(OCCCCCCCC(C)C)c1ccccc1C(=O)OCCC SMILES notation 3 (EC number 271-091-4 / CAS number 68515-49-1 only) Molecular weight 446.68 g.mol -1 (mean) 2
CAS number 68515-49-1, EC number 271-091-4 Molecular structure 2
CAS number 26761-40-0, EC number 247-977-1 Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: European Chemicals Bureau (2003b) 3 : ChemSpider Internet Site : http://www.chemspider.com/Chemical-Structure.30996.html?rid=7ed262e6-02a0-4f04- 8fa2-838ecbd5e8df
Use number: 1,2 Legal name of applicant: Arkema 97
ANALYSIS OF ALTERNATIVES
4.9.1.2 Composition of the substance As can be seen in Table 4.31, DIDP is not an individual substance. Indeed, in the 2003 DIDP EU Risk Assessment Report (EU RAR) (European Chemicals Bureau, 2003b), two di “isodecyl” phthalate products (i.e. those reported in Table 4.31) were analysed and referred to as ‘DIDP’ throughout the report. For consistency (and where practicable), the same approach is taken in this analysis. The EU RAR notes that these two products are essentially prepared from the same feed, through an identical olefin oligomerisation process and through comparable oxo-alcohol manufacturing and phthalate esterification processes. The report adds that the two phthalates are considered fully interchangeable within their whole range of the market end uses, subsequently, in this document the two substances are referred to as DIDP. With regard to purity, impurities and additives, the EU RAR notes that DIDP is a complex mixture containing mainly C10-branched isomers and that phthalates are produced with a high degree of purity (>99.5%) in terms of ester content. However, information on trace impurities identified by manufactures, as reported in the EU RAR, can be seen in the following table. Table 4.32: Impurities of DIDP (according to manufacturers) Diisodecyl ether and Isodecyl benzoate (0.02 - 0.1% w/w) Isodecyl alcohol (0.01 - 0.05% w/w) Traces of other phthalates Water (max. 0.1% w/w) Note: Bisphenol A may be included upon request by customer Source: European Chemicals Bureau (2003b)
4.9.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DIDP. Table 4.33: Physicochemical properties of DIDP Property Value Remarks Source Physical state at 20°C and Liquid Substance is clear and colourless, with a mild odour 1 101.3 kPa Rough values, based on difficult and poorly Melting/freezing point ca. -45°C 2 reproducible measurements Theoretical value based on using linear regressions Boiling point >400°C at 101.3 kPa 2 relating vapour pressure to temperature Density 0.966 g/cm3 at 20°C Representative value 2 Mean of four values obtained by extrapolation of 2.8 x 10-5 Pa at 20°C 2 linear regression Vapour pressure Mean of four values obtained by extrapolation of 5.1 x 10-5 Pa at 25°C 2 linear regression Surface tension No data Test not feasible due to low solubility of DIDP 2 The substance forms stable emulsions and apparent Water solubility Ca. 0.2 µg/l water solubilities up to a maximum of 1 mg/l can be 2 observed Partition coefficient n- logKow = 8.8 Value used in risk assessment 2 octanol/water
98 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Property Value Remarks Source Flash point measurement may strongly depend on Flash point >200°C the presence of lighter components, the proportion 2 of which may vary Flammability Very low 2 Explosive properties None 2 Self-ignition temperature 380°C Representative value 2 Oxidising properties Not oxidising 2 Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: European Chemicals Bureau (2003b)
4.9.1.4 Classification and labelling DIDP 1 (CAS number 68515-49-1, EC number 271-091-4) A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DIDP is available. However notified classification and labelling entries have been identified. These are presented in Table 4.34. The Inventory also suggests that the lead registrant and a further 380 notifiers did not classify the substance. Table 4.34: Notified classification and labelling of DIDP 1 according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s) H315 (Causes skin Skin Irrit. 2 H315 irritation) GHS07 25 H319 (Causes serious eye Wng Eye Irrit. 2 H319 irritation) H319 (Causes serious eye GHS07 Eye Irrit. 2 H319 7 irritation) Wng Source: European Chemicals Agency: http://echa.europa.eu/
DIDP 2 (CAS number 26761-40-0, EC number 247-977-1) A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DIDP is available. However, notified classification and labelling entries have been identified. These are presented in Table 4.35. The Inventory also suggests that 98 notifiers did not classify the substance.
Use number: 1,2 Legal name of applicant: Arkema 99
ANALYSIS OF ALTERNATIVES
Table 4.35: Notified classification and labelling of DIDP 2 according to CLP criteria Classification Labelling Number of Hazard Class and Hazard Statement Hazard Statement Pictograms Signal Notifiers Category Code(s) Code(s) Code(s) Word Code(s) Aquatic Chronic 2 H411 GHS09 43
Aquatic Acute 1 H400 GHS09 23 H410 (Very toxic to Wng Aquatic Chronic 1 H410 aquatic life with long lasting effects) H400 (Very toxic to GHS09 Aquatic Acute 1 H400 18 aquatic life) Wng H315 (Causes skin Skin Irrit. 2 H315 irritation) GHS07 GHS08 1 H319 (Causes serious eye Eye Irrit. 2 H319 Wng irritation) Source: European Chemicals Agency: http://echa.europa.eu/
4.9.1.5 REACH Registration Status of DIDP An online search using the substance’s CAS numbers was undertaken on the ECHA Dissemination Portal34 on 7 June 2013. Information from the portal notes that DIDP 1 has been registered under REACH with an indicative tonnage band of 100,000 to 1,000,000 tonnes per annum (EC number 271-091-4 / CAS number 68515-49-1 only). No information was available with regard to DIDP 2.
4.9.2 Technical feasibility of DIDP
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.9.2
4.9.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints and entwined availability issues, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.9.2.2 Technical feasibility from the perspective of the downstream user (information from literature) DIDP has properties of volatility resistance, heat stability and electric insulation and is typically used as a plasticiser for heat-resistant electrical cords, leather for car interiors, and PVC flooring (ECPI, undated). RAC and SEAC (2012) notes that DIDP is a widely used phthalate and is now used as an alternative to many applications where DEHP was used earlier, often together with DINP.
34 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
100 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.9.3 Reduction of overall risk due to transition to DIDP In terms of the substance’s overall human health and environmental hazard profile, DIDP would appear to be a suitable replacement for DEHP. However, from a regulatory risk management perspective there remains some uncertainty regarding the potential significance of certain human health endpoints. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.9.3
4.9.4 Availability of DIDP From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.9.4
4.9.5 Economic feasibility of DIDP From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.9.5
4.9.6 Conclusion on suitability and availability for DIDP In terms of the substance’s overall human health and environmental hazard profile, DIDP would appear to be a suitable replacement for DEHP. However, from a regulatory risk management perspective there remains some uncertainty. In addition, the substance is not a technically feasible, economically feasible or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.9.6
Use number: 1,2 Legal name of applicant: Arkema 101
ANALYSIS OF ALTERNATIVES
4.10 Alternative 9: Alternative substance – 1,2-CYCLOHEXANEDICARBOXYLIC ACID, DIISONONYLESTER (DINCH)
4.10.1 Substance ID and properties of DINCH
4.10.1.1 Name and other identifiers for the substance Table 4.36 presents the identity of DINCH. Table 4.36: Identity of DINCH Parameter Value Source EC number 431-890-2 1 EC name No information identified - CAS number 166412-78-8 (outside US) 3 IUPAC name No information identified -
HEXAMOLL 2,3 Other names* Diisononyl hexahydrophthalate HEXAMOLL DINCH
Molecular formula C26H48O4 3 SMILES notation No information identified - Molecular weight 424.7 3
Molecular structure 3
Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: ESIS Internet site: http://esis.jrc.ec.europa.eu/ 3 : BASF (2009) * Both Hexamoll and DINCH are registered trademarks of BASF(see: http://www.plasticizers.basf.com/portal/5/de/dt.jsp?setCursor=1_233146&seite=hexamoll_dinch)
4.10.1.2 Composition of the substance The recent background document to the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) noted that DINCH is the hydrogenated parallel to DINP (Alternative 10), with the difference that the ring structure is cyclohexane instead of a benzene ring. Information with regard to the composition of the substance can be seen in Table 4.37 below.
102 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.37: Product specifications of Hexamoll® DINCH Product specifications Value Test method Specific Gravity @ 25°/25°C 0.942 - 0.952 ASTM D-4052 Ester content, by weight (% minimum) 99.5 ASTM D-3465 Acid Number, mg KOH/gm (maximum) 0.07 ASTM D-1045 Water, by weight (% maximum) 0.1 ASTM E-1064 Colour, Pt-Co units (APHA, max) 40 ASTM D-5386 Suspended matter COLSFFM* Visual Phthalate content (% maximum) 0.010 UV-BASF As, Ba, Cr, Hg, Pb, Sb, Se, Sn (ppm max.) 1 each ICP-MS Cd (ppm max.) 0.6 ICP-MS *Clear Oily Liquid Substantially Free of Foreign Matter Source: BASF (2009)
4.10.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DINCH. Table 4.38: Physicochemical properties of DINCH Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Melting/freezing point -54°C 1 Boiling point 394°C at 101.3 kPa Decomposition temperature >278°C 1 Density 0.95g/cm³ at 20°C 1 0.00000022 hPa at 20°C 1 Vapour pressure 2.2 10-8 kPa at 25°C 2 0.012 Pa at 50°C 1 Surface tension - No information identified - Water solubility <0.02 mg/L at 25°C pH 6.3, 7.4 1 Partition coefficient n- 1 octanol/water log Pow 10 at 25°C Flash point 224°C at 101.3 kPa 1 Not flammable, taking into account the boiling Flammability - 3 and flash point Not explosive under influence of flame. Less Explosive properties Not available sensitive to shock and friction than m- 1 dinitrobenzene Self-ignition temperature 330°C at 998 hPa 1 No oxidising properties (due to its chemical Oxidising properties - 3 structure) Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2: Personal Communication with ATF members
Use number: 1,2 Legal name of applicant: Arkema 103
ANALYSIS OF ALTERNATIVES
4.10.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DINCH is available. With regard to aggregated notifications, the Inventory suggests that the lead registrant and a further 128 notifiers did not classify the substance.
4.10.1.5 REACH Registration Status of DINCH An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal35 on 7 June 2013. Information from the portal notes that the substance has been registered under REACH through a joint submission (led by BASF). The associated tonnage data has been withheld as being confidential.
4.10.2 Technical feasibility of DINCH
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.10.2
4.10.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints and entwined availability issues, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.10.2.2 Technical feasibility from the perspective of the downstream user (information from literature) With regard to DINCH, the recently published Final Background Document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates (RAC and SEAC, 2012) provides a valuable assessment of the technical and economic feasibility of the substance as a replacement for DEHP in flexible PVC36. As noted in RAC and SEAC (2012), BASF claims that a combination of a good toxicological profile and a very low migration rate makes DINCH a suitable plasticiser for medical devices made with soft PVC products such as tubes for internal feeding and haemodialysis bags, respiratory tubes, catheters, gloves and breathing masks. BASF also claims that, thanks to its low migration rate, lack of odour and technical suitability, DINCH is a suitable plasticiser for toys and children’s articles such as dolls, inflatables and balls, figurines, modelling clay, swimming aids, baby and childcare articles, wire and cable for toys. The manufacturer also notes that due to its toxicological profile, its low migration rate, and its low solubility in water and ethanol, DINCH can be used for food contact applications such as cling film, hoses, sealants and cap closures, crown corks, artificial wine corks, gaskets and gloves.
35 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances 36 Or, more specifically, as a replacement in PVC articles intended for use indoors and articles that may come into direct contact with the skin or mucous membranes containing DEHP in a concentration greater than 0.1% by weight of any plasticised material.
104 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 4.39 shows comparisons between DINCH and DEHP for selected parameters. Table 4.39: Comparison of DINCH and DEHP for some selected parameters Plasticizer DEHP DINCH Loading necessary to reach 70 Shore A hardness (phr) 62 65 Tensile strength, MPa (ASTM D412) 16.8 15.9 Elongation, % (ASTM D412) 311 309 Modulus, MPa (ASTM D412) 6.8 6.9 Tear resistance, kN/m (ASTM D624) 53.8 51.0 Brittleness temperature, °C (ASTM D746) -41 -48 Fusion torque, mg 1368 850 Base formulation in addition to plasticizer (phr): OxyVinyls 500F PVC (100), ESO (5), calcium stearate (0.15), zinc stearate (0.2), stearic acid (0.2) Adapted from source: Eastman (2012b)
4.10.3 Reduction of overall risk due to transition to DINCH Although a renal toxicant, DINCH appears to show a more favourable human health hazard profile than DEHP. The substance also does not raise environmental concerns. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.10.3
4.10.4 Availability of DINCH From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). In addition, the manufacture of this substance is based on technology which appears to be protected by patent. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.10.4
4.10.5 Economic feasibility of DINCH From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.10.5
4.10.6 Conclusion on suitability and availability for DINCH In terms of the substance’s overall human health and environmental hazard profile, DINCH would appear to be a suitable replacement for DEHP. However, the substance is not a technically feasible, economically feasible, or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.10.6
Use number: 1,2 Legal name of applicant: Arkema 105
ANALYSIS OF ALTERNATIVES
4.11 Alternative 10: Alternative substance – Di-isononylphthalate (DINP)
4.11.1 Substance ID and properties of DINP
4.11.1.1 Name and other identifiers for the substance Table 4.40 presents the identity of DINP. Table 4.40: Identity of DINP Parameter Value Source EC number 271-090-9 and 249-079-5 1 EC name No information identified - CAS number 68515-48-0 and 28553-12-0 1 1,2-Benzenedicarboxylic acid, di-C8-10 branched alkylesters, C9 rich CAS number 68515-48-0, EC number 271-090-9 IUPAC name 1 Di-'iso'nonyl phthalate CAS number 28553-12-0, EC number 249-079-5 Other names 1,2-Benzenedicarboxylic acid, diisononyl ester 2
Molecular formula C26H42O4 (mean) 1 O=C(OCCCCCCC(C)C)c1ccccc1C(=O)OCCCCCCC(C)C SMILES notation 2 (CAS number 68515-48-0, EC number 271-090-9 only) Molecular weight 420.6 (mean) 1
CAS number 68515-48-0, EC number 271-090-9 Molecular structure 1
CAS number 28553-12-0, EC number 249-079-5 Sources: 1: European Chemicals Bureau (2003a) 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.513622.html?rid=8ea828cf-89fc-4f83- 84aa-8b781afaa9cf
4.11.1.2 Composition of the substance As can be seen in Table 4.40, DINP is not an individual substance. The EU RAR for DINP (European Chemicals Bureau, 2003a) reports that there are two different DINPs currently on the market:
106 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
DINP 1 (Cas Number: 68515-48-0) is manufactured by the “Polygas” process; and
DINP 2 (Cas Number: 28553-12-0), which is n-butene based. ‘DINP 3’ (also CAS 28552-12-0) was n- and iso-butene based, but has reportedly been discontinued. Further information from the EU RAR concerning ‘best estimates’ of the chain structures of the different DINPs are available. These are reported in the following table. Table 4.41: Best estimate in content (%) of the different chain structures of the DINPs Impurity DINP 1 DINP 2 DINP 3 Methyl ethyl hexanols 5 - 10 5 - 10 65 - 70 Dimethyl heptanols 45 - 55 40 - 45 20 - 25 Methyl octanol 5 - 20 35 - 40 - n-Nonanol 0 - 1 0 - 10 - Isodecanol 15 - 25 - - Source: European Chemicals Bureau (2003a)
With regard to purity, impurities and additives associated with DINPs, the EU RAR notes that it is a complex mixture containing mainly C9-branched isomers and that phthalates are produced with a high degree of purity (>99.5%) in terms of ester content. However, information on trace impurities identified by manufactures, as reported in the EU RAR, can be seen in the following table. Table 4.42: Impurities of DINP (according to manufacturers) Impurity Value Isononanol ca. 0.04% Isononylbenzoate ca. 0.03% N-butylisononyl phthalate ca. 0.1% Water 0.02 - 0.03% Source: European Chemicals Bureau (2003a)
Additionally, ECHA (2012a) states that although the isomeric composition of DINPs 1 and 2 differ, they are considered to be commercially interchangeable. Following what appears to be the now widespread approach, throughout this report DINP is used as a common name for both EC/CAS numbers (as reported in Table 4.40) unless specified otherwise.
4.11.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of DINP. Table 4.43: Physicochemical properties of DINPs Property Value Remarks Source Physical state at 20°C and DINPs are oily, viscous liquids at normal Liquid 1 101.3 kPa temperature and pressure
Use number: 1,2 Legal name of applicant: Arkema 107
ANALYSIS OF ALTERNATIVES
Property Value Remarks Source Rough value. Measurements difficult and poorly Melting/freezing point ca. -50°C 1 reproducible Boiling point >400°C 1 Density ca. 0.975 at 20°C 1
Vapour pressure 6x10-5 Pa at 20°C 1
Same value in DINP 1 and DINP 2 registration Surface tension 30.7 mN/m 3 dossiers
Water solubility 1 0.6 µg/l at 20°C Partition coefficient n- 1 octanol/water logKow = 8.8 Flash point >200°C 1 Very low degree of Flammability Value for DINP 1 only 3 flammability Explosive properties - Not explosive (due to chemical structure) 2 Self-ignition temperature ca. 380°C 1 Oxidising properties - No oxidising properties (due to chemical structure) 2 Granulometry - Not relevant - Sources: 1: European Chemicals Bureau (2003a) 2: Personal communication with ATF members 3: European Chemicals Agency: http://echa.europa.eu/
4.11.1.4 Classification and labelling DINP 1 A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DINP 1 is available. However, notified classification and labelling entries have been identified. This information is presented in Table 4.44. In addition, the Inventory also suggests that 243 notifiers did not classify the substance; a further 70 notifiers (including the lead registrant) found the available data lacking. Table 4.44: Notified classification and labelling of DINP 1 according to CLP criteria Classification Labelling Hazard Number of Hazard Class and Pictograms Signal Statement Hazard Statement Code(s) Notifiers Category Code(s) Word Code(s) Code(s) GHS09 Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) 24 Wng H361 (Suspected of damaging fertility GSH08 Repr. 2 H361 3 or the unborn child) Wng Skin Irrit. 2 H315 H315 (Causes skin irritation) GSH07 1 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) Wng Source: European Chemicals Agency: http://echa.europa.eu/
108 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
DINP 2 A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for DINP 2 is available. However, notified classification and labelling entries have been identified. This information is presented in Table 4.45. In addition, the Inventory also suggests that the lead registrant and a further 793 notifiers did not classify the substance; a further 59 notifiers found the available data lacking. Table 4.45: Notified classification and labelling of DINP 2 according to CLP criteria Classification Labelling Hazard Number of Hazard Class and Pictograms Signal Statement Hazard Statement Code(s) Notifiers Category Code(s) Word Code(s) Code(s) H413 (May cause long lasting harmful Aquatic Chronic 4 H413 28 effects to aquatic life) Aquatic Acute 1 H400 H410 (Very toxic to aquatic life with GHS09 23 Aquatic Chronic 1 H410 long lasting effects) Wng H400 1 Aquatic Tox 4 H332 H332 (Harmful if inhaled) GHS07 GHS09 1 Aquatic Acute 1 H400 H400 (Very toxic to aquatic life) Wng Source: European Chemicals Agency: http://echa.europa.eu/
4.11.1.5 REACH Registration Status of DINP An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal37 on 7 June 2013. Information from the portal notes that both DINP 1 and DINP 2 have been registered under REACH, with both also being registered at between 100,000 and 1,000,000 tonnes per annum.
4.11.2 Technical feasibility of DINP
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.11.2
4.11.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints and entwined precursor availability issues, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
37 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
Use number: 1,2 Legal name of applicant: Arkema 109
ANALYSIS OF ALTERNATIVES
4.11.2.2 Technical feasibility from the perspective of the downstream user (information from literature) Compared to DEHP, Patrick (2005) notes that DINP is slightly less efficient but has a lower volatility. Typical uses cited are toys and general purpose. DINP is a widely used phthalate and is now used as an alternative to many applications where DEHP was previously used. DINP is restricted in toys and childcare articles that can be put in the mouth by young children, and can therefore still be used in certain kinds of toys and childcare articles. DINP has a wide range of indoor and outdoor applications, with an estimated 95% used as a plasticiser for flexible PVC for construction and industrial applications, as well as durable goods (wire and cable, film and sheet, flooring, industrial hoses and tubing, footwear, toys, food contact plastics). The other 5% is used in non-PVC applications (e.g. rubbers, adhesives, sealants, paints and lacquers, lubricants) (DINP-facts (2011) in RAC and SEAC (2012)). Additional information has been obtained from a product brochure on the substance (Degussa, 2006), and is summarised below (these data should be viewed in the light of marketing material):
Wires and cables: The low volatility of DINP permits application in the cable industry for producing YI 4 and YI 5 cables (DIN VDE 0207 German Standard for Cables). Because DINP has lower vapour pressure than DOP, more DINP remains in the compound to give compliance with requirements for mechanical characteristics and thermal characteristics after heat-ageing;
Film, foils and sheets: The cold performance of DINP is considerably better than that of DEHP, and its volatility is lower, ensuring applicability for DINP in film, foils and sheets. Its improved cold flexibility and its low volatility are particularly useful features for external applications. Practical experience has shown that weight loss is reduced by about 50% when DINP is used rather than DEHP;
Tubing and profiles: Increasing requirements for cold flexibility and low migration in finished products (e.g. reinforced tubing) are positive aspects of using DINP; and Flooring, coated fabrics and other paste products: DINP is claimed to have significant advantages over DEHP in all types of paste processing (spreading, spraying, dipping, rotational moulding). Its excellent performance is based on substantially lower evaporation losses and better rheological properties. Pastes produced using DINP have lower viscosity and better storage stability.
4.11.3 Reduction of overall risk due to transition to DINP In terms of the substance’s overall human health and environmental hazard profile, DINP would appear to be a suitable replacement for DEHP. However, available evidence has identified concerns with regard to human health hazards posed by the substance and, given the not dissimilar DNELs suggested for the substance, together with the classification as a Aquatic Acute toxin 1 identified by some notifiers, from a regulatory risk management perspective, it may not be appropriate to consider DINP as a suitable alternative to DEHP. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.11.3
110 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
4.11.4 Availability of DINP From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.11.4
4.11.5 Economic feasibility of DINP From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.11.5
4.11.6 Conclusion on suitability and availability for DINP In terms of the substance’s overall human health and environmental hazard profile, DINP would appear to be a suitable replacement for DEHP. However, there are concerns regarding a number of human health hazards. In addition, the substance is not a technically feasible, economically feasible or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.11.6
Use number: 1,2 Legal name of applicant: Arkema 111
ANALYSIS OF ALTERNATIVES
4.12 Alternative 11: Alternative substance – TRIOCTYLTRIMELLITATE (TOTM)
4.12.1 Substance ID and properties of TOTM
4.12.1.1 Name and other identifiers for the substance Table 4.46 presents the identity of TOTM. Table 4.46: Identity of TOTM Parameter Value Source EC number 222-020-0 1 EC name tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate 1 CAS number 3319-31-1 1 IUPAC name tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate 1 Tris(2-ethylhexyl)benzene-1,2,4-tricarboxylate, trioctyl trimellitate; tri(2- Other names ethylhexyl) trimellitate (TEHTM); trioctyl benzene-1,2,4-tricarboxylate; 1 1,2,4-bezenetricarboxylic acid, trioctyl ester
Molecular formula C33 H54O6 1 O=C(OCC(CC)CCCC)c1cc(ccc1C(=O)OCC(CC)CCCC)C(=O)OCC(CC)CC SMILES notation 2 CC Molecular weight 546.8 1
Molecular structure 1
Sources: 1: SCENIHR (2007) 2: ChemSpider Internet site: http://www.chemspider.com/Chemical-Structure.17681.html
4.12.1.2 Composition of the substance As noted by Wilson (1996), trimellitate plasticisers are based on alcohols with (average) carbon numbers in the range of 7-9. The higher molecular weight structure of trimellitates relative to general purposes phthalate plasticisers gives them lower volatility and generally greater resistance to migration. Their main application is in higher temperature PVC cables. They are normally supplied containing a hindered phenol antioxidant to prevent thermo-oxidatively induced degradation of the polymer at high service temperature.
4.12.1.3 Physicochemical properties The following table summarises the available information on the physicochemical properties of TOTM. Table 4.47: Physicochemical properties of TOTM Property Value Remarks Source Physical state at 20°C and Liquid at standard temperature and pressure with Liquid 1 101.3 kPa pale yellow colour and faint odour
112 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Property Value Remarks Source Melting/freezing point Determined as pour point using method ASTM D 1 -43 °C 97 -02 Determined in accordance with ASTM, EPA and Boiling point 355 at 101.3 kPa 1 OECD methods Determined using ASTM, EPA, OECD and EU Density 1 988.5 kg/m3 at 20°C methods Vapour pressure determined according to EU Vapour pressure 6.8E-10 hPa at 25°C 1 Regulation (EC) No. 440/2008 Surface tension - Study scientifically unjustified 1 Calculated after 8 day slow stirring equilibration Water solubility 3.06 µg/l at 25°C (pH 1 4.81) time by means of UPLC-MS/MS Partition coefficient n- OECD Guideline 123 (Partition Coefficient (1- 8 at 25°C 1 octanol/water Octanol / Water), Slow-Stirring Method)
Flash point 224 °C at 101.3 kPa In accordance with ISO, EPA and EU methods 1 Flammability Non flammable 1 Explosive properties - Not explosive (due to chemical structure) 2 Self-ignition temperature - - Oxidising properties - No oxidizing properties (due to chemical structure 2 Granulometry - Not relevant - Sources: 1: European Chemicals Agency: http://echa.europa.eu/ 2 : Personal communication with ATF members
4.12.1.4 Classification and labelling A search of the ECHA C&L Inventory (based on notifications submitted/updated by 7 June 2013) suggests that no harmonised classification and labelling for TOTM is available. However, notified classification and labelling entries have been identified. This information is presented in Table 4.48. In addition, the Inventory also suggests that the lead registrant and a further 352 notifiers did not classify the substance. Table 4.48: Notified classification and labelling of TOTM according to CLP criteria Classification Labelling Hazard Number of Hazard Class and Pictograms Signal Statement Hazard Statement Code(s) Notifiers Category Code(s) Word Code(s) Code(s) H361 (Suspected of damaging fertility GHS08 Repr. 2 H361 52 or the unborn child) Wng Acute Tox. 4 H312 H312 (Harmful in contact with skin) GHS07 23 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) Wng Skin Irrit. 2 H315 H315 (Causes skin irritation) GHS07 Eye Irrit. 2 H319 H319 (Causes serious eye irritation) 10 Wng STOT SE 3 H335 H335 (May cause respiratory irritation)
Use number: 1,2 Legal name of applicant: Arkema 113
ANALYSIS OF ALTERNATIVES
Classification Labelling Hazard Number of Hazard Class and Pictograms Signal Statement Hazard Statement Code(s) Notifiers Category Code(s) Word Code(s) Code(s) H413 (May cause long lasting harmful Aquatic Chronic 4 H413 4 effects to aquatic life) H413 (May cause long lasting harmful 1 effects to aquatic life) H413 (May cause long lasting harmful Aquatic Chronic 4 H413 1 effects to aquatic life) Source: European Chemicals Agency: http://echa.europa.eu/
4.12.1.5 REACH Registration Status of TOTM An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal38 on 7 June 2013. Information from the portal notes that the substance has been registered under REACH, with an indicated tonnage of between 10,000 and 100,000 tonnes per annum.
4.12.2 Technical feasibility of TOTM
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.12.2
4.12.2.1 Technical feasibility from the perspective of the applicant Due to process technology constraints, from the perspective of the applicant, this substance is not a technically feasible alternative for DEHP.
4.12.2.2 Technical feasibility from the perspective of the downstream user (information from literature) Compared to DEHP, TOTM has been reported as having better extraction and migration resistance, good high temperature performance, but poorer low temperature performance. Relevant applications include high-specification electrical cable and sheathing, and medical devices (Patrick, 2005). Table 4.49 presents a comparison of TOTM and DEHP for some selected parameters. Table 4.49: Comparison of TOTM and DEHP for some selected parameters Plasticiser DEHP TOTM Loading necessary to reach 70 Shore A hardness (phr) 62 69 Tensile strength, MPa (ASTM D412) 16.8 17.3 Elongation, % (ASTM D412) 311 316 Modulus, MPa (ASTM D412) 6.8 7.3 Tear resistance, kN/m (ASTM D624) 53.8 57.8 Brittleness temperature, °C (ASTM D746) -41 -40 Fusion torque, mg 1368 1130
38 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on-chemicals/registered- substances
114 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Base formulation in addition to plasticizer (phr): OxyVinyls 500F PVC (100), ESO (5), calcium stearate (0.15), zinc stearate (0.2), stearic acid (0.2) Adapted from source: Eastman (2012b)
4.12.3 Reduction of overall risk due to transition to TOTM In terms of the substance’s overall human health and environmental hazard profile, TOTM would appear to be a suitable replacement for DEHP. However, there are significant concerns with regard to its human health hazard profile (in terms of liver toxicity, reprotoxicity and potential endocrine activity). TOTM is also undergoing Substance Evaluation under the REACH program, having been placed on the CoRAP list because of concerns regarding potential PBT properties. Hence, from a regulatory risk management perspective it is not reasonable to consider this a suitable alternative at this time. See Annex 4 for further details. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.12.3
4.12.4 Availability of TOTM From the perspective of the applicant, this substance is not available (it should be noted that from the applicant’s perspective availability considerations link to the ability of the applicant to manufacture the substance as an alternative). This is due to process technology constraints (the precursor materials should be available to the applicant). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.12.4
4.12.5 Economic feasibility of TOTM From the perspective of the applicant, this substance is not an economically feasible alternative for DEHP. In addition to a loss of process integration which would occur if this substance were to be produced instead of DEHP, significant production related costs would also be incurred. In addition, demand for this substance as an alternative in the ATF supply chain, in the end-use applications of relevance to this AfA, is very low (it should be noted that TOTM, a trimellitate, is a speciality plasticiser and is not considered to be a viable alternative in the general purpose applications of DEHP – particularly those of relevance to this AoA). Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.12.5
4.12.6 Conclusion on suitability and availability for TOTM In terms of the substance’s overall human health and environmental hazard profile, TOTM would appear to be a suitable replacement for DEHP. From a regulatory risk management perspective there are concerns regarding some aspects of its hazard profile and it is also the subject of ongoing regulatory evaluation. In addition, the substance is not a technically feasible, economically feasible, or available alternative. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 4.12.6
Use number: 1,2 Legal name of applicant: Arkema 115
ANALYSIS OF ALTERNATIVES
5 OVERALL CONCLUSIONS ON SUITABILITY AND AVAILABILITY OF POSSIBLE ALTERNATIVES FOR THE APPLIED-FOR USES
5.1 Conclusion on suitability and availability of potential alternative substances In the research undertaken on the availability of potential alternatives to DEHP from the perspective of the applicant, the following initial conclusions were reached:
The only realistic alternatives are alternative substances. Whilst a flexible PVC processor producing plastic articles could potentially consider a different plastic material to flexible PVC, for the applicant, a chemical manufacturer, an alternative material (or technique) cannot be a technically or economically feasible alternative. Alternative materials, which could act as replacements to DEHP plasticised PVC are alien to the capabilities of the applicant and have not been considered; and
Whilst the applicant could theoretically consider and potentially implement the manufacture of an alternative substance, the production of a range of alternative substances would be profoundly unfeasible from a technical and economic perspective and thus it has not been considered in this AoA (see Section 3.1). Subsequently, through research and consultation, a comprehensive list of 43 potential alternative plasticiser substances was identified. After initial analysis, this list was refined to a short list of 11 substances for more detailed analysis (see Table 1.1 and Section 3.3). The more detailed assessment of the suitability and availability of the refined list of alternatives has been undertaken primarily from the perspective of the applicant. However, the perspective of downstream users has also been considered (more specifically, the technical feasibility and market demand for the potential alternative substances for the downstream users is taken into consideration because only alternatives that would (in principle) be technically suitable for downstream users could be successfully placed on the market by the applicant). In addition, please note that with regard to relative regulatory risk, it is acknowledged that - based on current data and hazard profiles of the substances under discussion - the alternatives may be considered to have a lower hazard profile than DEHP. However, for many of these alternatives, regulators have been or are raising questions about potential human health or environmental concerns. Before a company can decide to invest in the manufacture of a new chemical substance, they need to be completely certain that the new product will be free of regulatory scrutiny over normal investment time horizons (say for the next 15-20 years in the case of an alternative plasticiser). Current issues regarding regulatory scrutiny of the potential toxicity of the substances are therefore relevant, and this is the reason for their inclusion in the table below, and throughout the AoA. Overall conclusions with regard to the assessment of each potential alternative substance, from the perspective of the applicant, are provided in Table 5.1, below.
116 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Table 5.1: Overall conclusions on suitability and availability, from the perspective of the applicant Potential Overall conclusion on suitability and availability, from the perspective of alternative the applicant substance ASE In terms of the substance’s overall human health and environmental hazard profile, ASE would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. ATBC In terms of the substance’s overall human health and environmental hazard profile, it can be tentatively stated that ATBC would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. COMGHA In terms of the substance’s overall human health and environmental hazard profile, COMGHA would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically feasible, economically feasible, or available alternative. DEHA Based on our current understanding, in terms of the substance’s overall human health and environmental hazard profile, DEHA would appear to be a suitable replacement for DEHP. However, taking a wider view that includes the regulatory risk management perspective, it may not be reasonable to consider this substance a suitable alternative at this time given that the substance is currently the subject of an evaluation process. In addition, from the perspective of the applicant, the substance is also not an economically feasible alternative. DEHS In terms of the substance’s overall human health and environmental hazard profile, DEHS would appear to be a suitable replacement for DEHP. However, the conclusion on the human health hazard potential is subject to considerable uncertainty at this time because of the limited dataset and concerns regarding potential developmental toxicity based upon read-across. From the perspective of the applicant, the substance is also not an economically feasible alternative.
DEHT In terms of the substance’s overall human health and environmental hazard profile, DEHT would appear to be a suitable replacement for DEHP. However, from the perspective of the applicant, the substance is not a technically or economically feasible alternative. DPHP In terms of the substance’s overall human health and environmental hazard profile, available information would suggest that DPHP is a suitable replacement for DEHP. However, from a regulatory risk management perspective there are some concerns as to the significance of its toxicity potential for a number of endocrine organs. From the perspective of the applicant, the substance cannot be considered an economically feasible or available alternative until the current research project has been formally concluded. DIDP In terms of the substance’s overall human health and environmental hazard profile, DIDP would appear to be a suitable replacement for DEHP. However,
Use number: 1,2 Legal name of applicant: Arkema 117
ANALYSIS OF ALTERNATIVES
Potential Overall conclusion on suitability and availability, from the perspective of alternative the applicant substance from a regulatory risk management perspective there remains some uncertainty regarding the potential significance of certain human health endpoints. In addition, the substance is not a technically feasible, economically feasible or available alternative from the perspective of the applicant. DINCH In terms of the substance’s overall human health and environmental hazard profile, DINCH would appear to be a suitable replacement for DEHP. However, the substance is not a technically feasible, economically feasible, or available alternative from the perspective of the applicant. DINP In terms of the substance’s overall human health and environmental hazard profile, DINP would appear to be a suitable replacement for DEHP. However, from a regulatory risk management perspective, the regulators’ concerns regarding a number of human health hazards, including with respect to endocrine activity, are of note. In addition, the substance is not a technically feasible, economically feasible or available alternative from the perspective of the applicant. TOTM In terms of the substance’s overall human health and environmental hazard profile, TOTM would appear to be a suitable replacement for DEHP. However, from a regulatory risk management perspective there are concerns regarding some aspects of its hazard profile and it is the subject of regulatory evaluation. In addition, the substance is not a technically feasible, economically feasible, or available alternative from the perspective of the applicant.
As can be deduced from the above table, none of the selected potential alternative substances can be considered as a feasible replacement for DEHP, from the applicant’s perspective. As also noted above, in terms of hazard reduction potential, the available information would indicate that the selected potential alternative substances do not raise concerns regarding their reproductive toxicity potential. Yet, the majority of the potential alternatives are far less researched than DEHP and could still be accompanied by concerns of their own (as identified in Section 4), both in relation to human health and the environment. It is important to note that, as shown in the CSR, exposure to DEHP is kept below the effect threshold during the formulation and use of the substance in the applied-for uses and, as such, no discernible benefit to worker or consumer health would arise from the use of any of the selected potential alternative substances. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 5.1
5.2 Planned future Research and Development for the replacement of DEHP Information on Research and Development is presented in the Confidential Annex. Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Section 5.2
118 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
APPENDICES
Annex 1: List of data sources BASF. (2009). Hexamoll® DINCH - Technical Data Sheet. Retrieved January 23, 2013, from http://www2.basf.us/plasticizers/pdfs/products/TDS_DINCH.pdf BASF. (2013). Palatinol®10 P - Primary plasticizer for PVC and PVC copolymers. Retrieved July 14, 2013, from http://www.basf.com/group/corporate/en/brand/PALATINOL_10_P Bayer. (undated). Product Profile - Bayer Agency Business - Functional Chemicals. Retrieved April 17, 2013, from http://www.bayer.co.th/webphp/download/FunctionalChemicalsProductsprofile02.pdf Blass, C. (2001). Role of Poly(Vinyl Chloride) in Healthcare. Shrewsbury: Rapra Technology Limited. Chemical Fabrics & Film Association. (undated). PLASTICIZER MIGRATION. Retrieved March 23, 2013, from http://www.chemicalfabricsandfilm.com/pdfs_researchSection/techSupport/plasticizer.pdf Craver, C., & Carraher, C. (2000). Applied Polymer Science: 21st Century: 21st Century. Oxford, UK: ELSEVIER . Dalgaard, M., Hass, U., Vinggaard, A., Jarfelt, K., Lam, H., Sorensen, I., . . . Ladefoged, O. (2003). Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats. Reproductive Toxicology, 17, 163-170. Daniels, P. (2012). Assessing Plasticizer Compatibility by Dynamic Mechanical Analysis. ExxonMobil. Retrieved March 28, 2013, from http://www.plasticsindustry.org/files/events/Paul%20Daniels_Monday.pdf Degussa. (2006). Vestinol 9 - Your plasticiser of choice for PVC applications. Retrieved April 16, 2013, from http://oxeno.biz/Internet/upload/produktdaten_DE/VESTINOL-Broschure.pdf Eastman. (2012a). Eastman(TM) DOA Plasticizer - SAFETY DATA SHEET. Retrieved from http://ws.eastman.com/ProductCatalogApps/PageControllers/MSDS_PC.aspx?Product=71013654 Eastman. (2012b). Eastman 168 non-phthalate plasticizer - the science of safety and innovation in medical devices. Retrieved April 12, 2013, from http://www.eastman.com/Literature_Center/L/L247.pdf Eastman. (2013). Eastman 168™ SG non-phthalate plasticizer. Retrieved from http://www.eastman.com/Brands/Eastman_plasticizers/Pages/ProductHome.aspx?product=7109353 3 ECHA. (2008). VHC Support Document. Bis(2-ethylhexyl) phthalate. Member State Committee Support Document for Identification of Bis(2-ethylhexyl) phthalate DEHP) as a Substance of Very High Concern. Retrieved 2013 26, 2013, from http://echa.europa.eu/doc/candidate_list/svhc_supdoc_dehp_publication.pdf ECHA. (2009). Background document for bis(2-ethylhexyl) phthalate (DEHP). Retrieved February 26, 2013, from http://echa.europa.eu/doc/authorisation/annex_xiv_rec/subs_spec_background_docs/dehp.pdf
Use number: 1,2 Legal name of applicant: Arkema 119
ANALYSIS OF ALTERNATIVES
ECHA. (2011). Guidance on the preparation of an application for authorisation. Retrieved March 26, 2013, from http://echa.europa.eu/documents/10162/13637/authorisation_application_en.pdf ECHA. (2012a). Committee for Risk Assessment (RAC), Committee for Socio-economic Analysis (SEAC) - Opinion on an Annex XV dossier proposing restrictions on four phthalates. Retrieved February 27, 2013, from http://echa.europa.eu/documents/10162/58050be8-f7be-4b55-b106- 76dda4989dd6 ECPI. (2010a). Specialty Plasticisers. Retrieved July 10, 2013, from Plasticisers and Flexible PVC Information Centre: http://www.plasticisers.org/en_GB/plasticisers/specialty-plasticisers ECPI. (2010b). Technical Information on Plasticisers. Retrieved March 20, 2013, from Plasticisers and Flexible PVC Information Centre: http://www.plasticisers.org/en_GB/science/technical- information-on-plasticisers ECPI. (undated). An information resource on the plasticiser diisodecyl phthalate. Retrieved July 2013, 3, from DIDP Information Centre: http://www.didp-facts.com/ EFSA. (2009). Scientific opinion on the safety evaluation of the substance, alkyl(C10- C21)sulphonic acid, esters with phenol, CAS No. 91082-17-6, for use in food contact materials. Retrieved from http://www.efsa.europa.eu/de/scdocs/doc/1398.pdf European Chemicals Bureau. (2003a). European Union Risk Assessment Report - 1,2- benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich and di-“isononyl” phthalate (DINP). Retrieved January 25, 2013, from http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/5395/1/EUR%2020784%20EN. pdf European Chemicals Bureau. (2003b). European Union Risk Assessment Report - 1,2- benzenedicarboxylic acid, di-C9-11- branched alkyl esters, C10-rich and di-“isodecyl” phthalate (DIDP). Retrieved January 23, 2013, from http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/5459/1/EUR%2020785%20EN. pdf European Chemicals Bureau. (2008). European Union Risk Assessment Report - bis(2- ethylhexyl)phthalate (DEHP). Retrieved February 26, 2013, from http://echa.europa.eu/documents/10162/e614617d-58e7-42d9-b7fb-d7bab8f26feb Exxon Mobil. (2010). Uses of Phthalates and Other Plasticizers. Retrieved April 18, 2013, from http://www.cpsc.gov//PageFiles/126379/godwin.pdf GEA. (2013). GEA Heat Exchangers - Switch Condenser. Retrieved April 12, 2013, from http://www.gea- luftkuehler.de/opencms/opencms/glk/en/Produkte/PSA_Switch_Condenser/Switch_Condenser.html Grossman, R. F. (2008). Handbook of Vinyl Formulating - Second Edition. Hoboken, New Jersey: John Wiley & Sons. Retrieved March 21, 2013 HallStar. (1983). Ester Plasticizers for Polar Elastomers with Emphasis on Low-Temperature. Retrieved March 25, 2013, from http://www.hallstar.com/techdocs/LOWTEMP.pdf Hallstar. (undated). The function and selection of ester plasticisers. Retrieved July 27, 2013, from http://www.hallstar.com/techdocs/The_Function-Selection_Ester_Plasticizers.pdf
120 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Han, J. (2005). Innovations in Food Packaging. Oxford: Elservier Academic Press. Iowa State University. (2004). The Science of Smell Part 3: Odor detection and measurement. Retrieved March 25, 2013, from http://www.extension.iastate.edu/Publications/PM1963C.pdf IPPEC. (2011). Retrieved April 16, 2013, from http://www.plasticizerplants.com/index.html Jungbunzlauer. (undated). Specialities - Citrofol, the natural solution to polymers. Retrieved from http://www.jungbunzlauer.com/fileadmin/uploads/pdf/specialties/CITROFOL_2012- 014FO_EN.pdf Koleske, J. (1995). Paint and Coating Testing Manual - Fourteenth Edition . Ann Arbor: American Society for Testing and Materials. Kutz, M. (2011). Applied Plastics Engineering Handbook: Processing and Materials. Elsevier. Lanxess. (2005). Mesamoll® - Technical Information. Retrieved April 16, 2013, from http://techcenter.lanxess.com/fcc/emea/en/products/datasheet/Mesamoll_II_(en).pdf?docId=815899 2&gid=8158969&pid=1154 Lanxess. (2010). Expansion of Mesamoll production in Uerdingen. Retrieved from http://www.lanxess.com/en/media-download/2010-00083e_rtf_en/ OECD. (2003). SIDS Initial Assessment Report For SIAM 17 - DI(2- ETHYLHEXYL)TEREPHTHALATE (DEHT) . OECD. (2004). OECD SERIES ON EMISSION SCENARIO DOCUMENTS Number 3 - EMISSION SCENARIO DOCUMENT ON PLASTICS ADDITIVES. OECD. Retrieved March 29, 2013, from http://search.oecd.org/officialdocuments/displaydocumentpdf/?cote=ENV/JM/MONO%282004%2 98&docLanguage=En Patrick, S. (2005). Practical Guide to Polyvinyl Chloride. Shrewsbury: Rapra Technology Limited. Plastemart. (2003, April 03). A new study on use of PVC based on DEHP and alternate plasticizers is not decisive. Retrieved from Plastemart.com: http://www.plastemart.com/upload/Literature/Use- of%20PVC-based-on-DEHP-alternative-plasticizers-undecisive.asp PVC Europe. (undated). Adhesion properties and printability. Retrieved March 20, 2013, from http://www.pvc.org/en/p/adhesion-properties-and-printability RAC and SEAC. (2012). Committee for Risk Assessment (RAC), Committee for Socio-economic Analysis (SEAC) - Background document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates. Retrieved April 8, 2013, from http://www.echa.europa.eu/documents/10162/3bc5088a-a231-498e-86e6-8451884c6a4f Ramos-deValle, L. (1988). Plasticization of poly(vinyl chloride): PVC/plasticizer compatibility and its relationship with processing and properties of plasticized PVC. Luis Francisco Ramos-deValle. Retrieved 2013 29, March, from https://dspace.lboro.ac.uk/dspace-jspui/handle/2134/6727 Ramos-Devalle, L., & Gilbert, M. (1990). PVC/plasticizer compatibility: Evaluation and its relation to processing. Journal of Vinyl Technology, 12(4), 22-225. Rapra Technology. (2006). Medical Polymers 2006, 5th International Conference Focusing on Polymers used in the Medical Industry. Smithers Rapra Ltd.
Use number: 1,2 Legal name of applicant: Arkema 121
ANALYSIS OF ALTERNATIVES
Rojek, M., & Stabik, J. (2007). Butadiene-acrylonitrile elastomers as PVC modifiers. Archives of Materials Science and Engineering, 28(1), 41-48. Rosato, D. V., Rosato, M., & Rosato, D. V. (2000). Concise Encyclopedia of Plastics. Massachusetts: Kluwer Academic Publishers. SCENIHR. (2007). PRELIMINARY REPORT ON THE SAFETY OF MEDICAL DEVICES CONTAINING DEHP- PLASTICIZED PVC OR OTHER PLASTICIZERS ON NEONATES AND OTHER GROUPS POSSIBLY AT RISK. Retrieved January 23, 2013, from http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_008.pdf Sen, A. (2008). Coated Textiles: Principles and Applications, Second Edition. Boca Raton: CRC Press - Taylor & Francis. Shang, S., & Woo, L. (2002). CHAPTER 38 - SELECTING MATERIALS FOR MEDICAL PRODUCTS. John Wiley & Sons. Retrieved March 22, 2013, from http://85.185.231.196/mekanik/Handbook%20of%20Materials%20Selection%20- %20Kutz,Myer/selecing%20materials%20for%20medical%20products.pdf Technobell. (2013). Phthalic Anhydride - Process details. Retrieved from http://www.technobell.info/web/index.php?option=com_content&view=article&id=29&Itemid=142 Titow, W. (1984). PVC Technology - Fourth Edition. Barking, England: Elsevier Applied Science Publishers. Van Veerson, G. J., & Meulenberg, A. J. (1967). Relation between the chemical structure and the efficiency of plasticizers. Kunststoffe, 57, 561-566. Wadey, B. L. (undated). Encyclopedia of Polymer Science and Technology. John Wiley & Sons. Retrieved July 27, 2013 Wilkes, C. E., Daniels, C. A., & Summers, J. W. (2005). PVC Handbook. HANSER. Retrieved March 20, 2013, from http://bilder.buecher.de/zusatz/14/14199/14199862_lese_1.pdf Wilson, A. (1996). Plasticisers: Selection, Applications and Implications (Vol. 8). Rapra Technology Ltd. Wypych, G. (2004). Handbook of Plasticizers . William Andrew Publishing / Chemtec Publishing . Zweifel, H., Maier, R., & Schiller, M. (2009). Plastics Additives Handbook - 6th Edition. Munich: HANSER.
122 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
Annex 2: Justification for submitting a single Analysis of Alternatives for both applied-for uses It is recognised by the applicant that the ECHA ‘Guidance on the preparation of an application for authorisation’ (ECHA, 2011), Section 2.2.4.2. states the following: “In circumstances where one application covers several uses, it is important to clearly set out the alternatives for each use. This can be achieved by developing a separate analysis of alternatives report for each use or by developing distinctly defined sections for each use in one report.” In this AoA, however, the applicant’s approach has not been to develop separate analyses, or to create distinctly defined sections for each use, but to merge these analyses. In coming to this decision, the applicant has considered a number of pertinent factors. Perhaps of most significance is the fact that the applicant is a manufacturer of DEHP, and the two applied-for uses in this AfA (i.e. formulation and processing) are undertaken by actors downstream of the applicant, in the same supply chain39. Given that the AoA must be undertaken from the perspective of the applicant, in this instance, differentiation regarding the feasibility of alternatives at rigid levels relevant to the applied-for uses is essentially immaterial, as it is clear that for any alternative to be feasible to the applicant (e.g. to exhibit economic feasibility), it must meet the needs of actors at both downstream user levels within the supply chain. Rationale for merging analyses for the applied-for uses is further strengthened when one considers that similar considerations are relevant to the assessment of DEHP’s function. This is because some parameters or properties of a plasticiser that may be of value in a given polymer matrix for one type of application may be detrimental in another. For example, a high rate of diffusion will increase efficiency and the rate of gelation during processing but may also make for poorer performance in the end product. Such aspects are discussed further in Section 2, but essentially, a good general purpose plasticiser (such as DEHP) must meet the balance of adequately fulfilling criteria and functional requirements which span the needs of users at all levels within the supply chain (and, in the context of this AoA, subsequently encompass both applied-for uses). Consequently, the applicant believes that the combined analysis applied within this document is realistically the only sensible and reasonable approach that could have been taken. The approach has not only been the most appropriate way to facilitate the preparation of the application (by e.g. simplifying consultations, and avoiding significant repetition when reporting), but also allows the reader to gain a more integrated picture on the use of DEHP, and why (from the perspective of the applicant) no feasible alternatives are currently available.
39 Note: individual actors may operate at more than one supply chain level and undertake activities relevant to both applied-for uses (i.e. formulation and processing).
Use number: 1,2 Legal name of applicant: Arkema 123
ANALYSIS OF ALTERNATIVES
Annex 3: List of supplementary data sources considered for the purposes of the AoA As noted in Section 4.1, to inform the reader, additional supplementary data sources consulted for the purposes of the AoA are as follows: Bisig, MD (2009): Plasticizer Market Update, presentation given at 20th Annual Vinyl Compounding Conference on behalf of BASF, July 19-21, 2009; Emanuel, C (2011): Plasticizer Market Update, presentation given at 22th Annual Vinyl Compounding Conference on behalf of BASF, July 10-13, 2011. CEF Panel. (2009). Scientific Opinion on the safety evaluation of the substance, alkyl(C10- 21)sulphonic acid, esters with phenol, CAS No. 91082-17-6, for use in food contact materials. EFSA journal, 7(12), 1398. Danisco. (2011). SOFT-N-SAFE™ White Paper - Sustainable and substantiated. Retrieved April 08, 2013, from http://www.danisco- softnsafe.com/fileadmin/user_upload/softnsafe/documents/Papers/sns-white-paper.pdf Danisco. (undated). GRINDSTED® SOFT-N-SAFE - The safe and sustainable plasticiser for PVC. Danisco. (undated). GRINDSTED® SOFT-N-SAFE fact sheet. Retrieved April 08, 2013, from http://www.pvc.dk/billeder/word/Fact_sheet_GRINDSTED_SOFT-N-SAFE_UK.pdf DuPont. (Undated). Case study: Safe alternative to phthalates for medical applications. Retrieved from DuPont: http://plasticadditives.dupont.com/by_application/case_study_safe_alternative_to_phthalates_for_m edical_applications/ ECHA. (2012). Evaluation of new scientific evidence concerning DINP and DIDP in relation to entry 52 of Annex XVII to Regulation (EC) No 1907/2006 (REACH). Retrieved January 25, 2013, from http://echa.europa.eu/documents/10162/dbc0e16f-eb29-4382-98a1-c08a33149fdc ECHA. (2013). Community rolling action plan (CoRAP) update covering years 2013, 2014 and 2015 http://echa.europa.eu/documents/10162/13628/corap_2013_en.pdf ECPI. (2013). Technical Properties of DPHP. Retrieved August 4, 2013, from DPHP Information Centre: http://www.dphp-facts.com/properties Frost & Sullivan. (2006). Danisco Wins Frost & Sullivan's Excellence in Research Award in the Food Packaging Industry for its Unique Plasticizer - GRINDSTED® SOFT-N-SAFE . Retrieved from Frost & Sullivan: http://www.frost.com/prod/servlet/press-release.pag?docid=57230979 Jungbunzlauer. (undated). Specialities - CITROFOL® (Product brochure). Retrieved April 11, 2013, from http://www.univareurope.com/uploads/documents/uk/Citrofol.pdf Lanxess. (2007). LANXESS plasticizers for toy and food contact applications. Retrieved from Lanxess: http://lanxess.com/en/corporate/products-solutions/product-news/lanxess-plasticizers-for- toy-and-food-contact-applications/ Lanxess. (2008). Mesmoll - Material Safety Data Sheet. Retrieved April 17, 2013, from http://www.sfm.state.or.us/cr2k_subdb/MSDS/MESAMOLL.PDF MBPL. (2010). Plasticisers. Retrieved 2013 4, July, from Michael Ballance Plastics Limited: http://www.ballance-plastics.co.uk/plasticisers.html
124 Use number: 1, 2 Legal name of applicant: Arkema
ANALYSIS OF ALTERNATIVES
OECD. (2000). SIDS Initial Assessment Report for SIAM 10. Bis(2-ethylhexyl)adipate (DEHA). Paris, France. Retrieved March 04, 2013, from http://www.chem.unep.ch/irptc/sids/OECDSIDS/103231.pdf OXEA. (2012). OXSOFT® - Phthalate-free, non-VOC plasticizers. Retrieved from http://www.phthalate-free-plasticizers.com/fileadmin/downloads/OXSOFT-Brochure.pdf Patentdocs. (undated). PLASTICIZER PREPARATIONS WITH GOOD GELLING PROPERTIES. Retrieved 2013 3, July, from Internet FAQ Archives: http://www.faqs.org/patents/app/20120129991 RAC. (2013). Committee for Risk Assessment - Opinion on the ECHA’s draft review report on “Evaluation of new scientific evidence concerning DINP and DIDP in relation to entry 52 of Annex XVII to Regulation (EC) No 1907/2006 (REACH)”. ECHA. Retrieved from http://echa.europa.eu/documents/10162/31ec5ce2-ec0f-4dcc-b572-b81f4d6fa7f2 Rahman, M., & Brazel, C. (2004). The plasticizer market: an assessment of traditional plasticizers and research trends to meet new challenges. Prog. Polym. Sci., 29, 1223-1248. SCENIHR. (2008). Opinion on the safety of medical devices containing DEHP-plasticized PVC or other plasticizers on neonates and other groups possibly at risk. Adopted after public consultation by the SCENIHR during the 22nd Plenary of 6 February 2008. Retrieved March 01, 2013, from http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_014.pdf TURI. (2006). Five Chemicals Alternatives Assessment Study. University of Massachusetts Lowell. TURI. (2008). Alternatives for significant uses of DEHP in Massachusetts. Retrieved from The Encyclopedia of the Earth : http://www.eoearth.org/article/Alternatives_for_significant_uses_of_DEHP_in_Massachusetts Vertellus. (2007). CITROFLEX® A-4 - Technical Data Sheet . Retrieved April 11, 2013, from http://www.vertellus.com/Documents%5CTechSheet%5CCITROFLEX%20A4%20English.pdf
Use number: 1,2 Legal name of applicant: Arkema 125
ANALYSIS OF ALTERNATIVES
Annex 4: Reduction of overall risk due to transition to the potential alternative substances
Please note: This Annex contains a comprehensive analysis of the reduction of overall risk associated with transition to each of the shortlisted potential alternative substances assessed in this AoA. For transparency, it is noted that this analysis has been produced by a separate author to the independent third party who authored the remainder of the AoA. Both parties have operated fully in agreement with ATF members, and under the provisions of Non-Disclosure Agreements that have been bilaterally signed. It should also be noted that (particularly in terms of formatting and configuration) the information in this Annex is provided as a standalone document. Consequently, for example, page numbers relate specifically to the page of the Annex and not the overall document, separate contents pages are provided, and the list of data sources used is provided at the end of this Annex (and not in the main list of data sources presented in Annex 1 of this document). The rationale for this approach has been to provide the reader uninterrupted analysis relating to the overall hazards and risks posed by the potential alternative substances.
Additional confidential information is presented in: DEHP AoA Confidential Annex.pdf, Annex 6
126 Use number: 1, 2 Legal name of applicant: Arkema
Hazard and Risk Evaluation of DEHP Alternatives
prepared on behalf of
the DEHP Authorisation Task Force (ATF)
June 2013
2 Evaluation of DEHP alternatives
Content
1 Human Health Hazard profiles ...... 7 1.1 General Remarks ...... 7 1.2 Alkylsulphonic phenyl ester (ASE) ...... 8 1.2.1 DNELs from ECHA‐Dissemination Data Base ...... 8 1.2.2 Other regulatory values ...... 8 1.2.3 Classification ...... 9 1.2.4 Data overview and discussion ...... 9 1.3 Acetyltri‐n‐butyl citrate (ATBC) ...... 10 1.3.1 DNELs from ECHA‐Dissemination Data Base ...... 10 1.3.2 Other regulatory values ...... 11 1.3.3 Classification ...... 12 1.3.4 Data overview and discussion ...... 12 1.4 Glycerides, Castor‐oil‐mono‐, hydrogenated, acetates (COMGHA) ...... 14 1.4.1 DNELs from ECHA‐Dissemination Data Base ...... 14 1.4.2 Other regulatory values ...... 14 1.4.3 Classification ...... 14 1.4.4 Data overview and discussion ...... 15 1.5 Di(2‐ethylhexyl)adipate (DEHA) ...... 16 1.5.1 DNELs from ECHA‐Dissemination Data Base ...... 16 1.5.2 Other regulatory values ...... 17 1.5.3 Classification ...... 18 1.5.4 Data overview and discussion ...... 18 1.6 Diethylhexylsebacate (DEHS) ...... 20 1.6.1 DNELs from ECHA‐Dissemination Data Base ...... 20 1.6.2 Other regulatory values ...... 20 1.6.3 Classification ...... 20 1.6.4 Other notified classifications: Acute Tox. 4 – H302Data overview and discussion ...... 21
3 Evaluation of DEHP alternatives
1.7 Di(2‐ethylhexyl) terephtalate (DEHT) ...... 22 1.7.1 DNELs from ECHA‐Dissemination Data Base ...... 22 1.7.2 Other regulatory values ...... 23 1.7.3 Classification ...... 23 1.7.4 Data overview and discussion ...... 23 1.8 DI(2‐propylheptyl) phthalate (DPHP) ...... 25 1.8.1 DNELs from ECHA‐Dissemination Data Base ...... 26 1.8.2 Other regulatory values ...... 26 1.8.3 Classification ...... 27 1.8.4 Data overview and discussion ...... 27 1.9 Di‐isodecylphthalate (DIDP) ...... 29 1.9.1 DNELs from ECHA‐Dissemination Data Base ...... 29 1.9.2 Other regulatory values ...... 30 1.9.3 Classification ...... 31 1.9.4 Data overview and discussion ...... 31 1.10 Di‐isononyl‐1,2‐cyclohexanedicarboxylate (DINCH) ...... 33 1.10.1 DNELs from ECHA‐Dissemination Data Base ...... 33 1.10.2 Other regulatory values ...... 34 1.10.3 Classification ...... 35 1.10.4 Data overview and discussion ...... 35 1.11 Di‐isononylphthalate (DINP) ...... 37 1.11.1 DNELs from ECHA‐Dissemination Data Base ...... 37 1.11.2 Other regulatory values ...... 38 1.11.3 Classification ...... 39 1.11.4 Data overview and discussion ...... 39 1.12 Trioctyltrimellitate (TOTM) ...... 41 1.12.1 DNELs from ECHA‐Dissemination Data Base ...... 41 1.12.2 Other regulatory values ...... 42 1.12.3 Classification ...... 42 1.12.4 Data overview and discussion ...... 43
2 Ecotoxicity Hazard profiles ...... 45
4 Evaluation of DEHP alternatives
2.1 General Remarks ...... 45 2.2 Alkylsulphonic phenyl ester (ASE, Mesamoll) ...... 45 2.2.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 45 2.2.2 Other regulatory values ...... 46 2.2.3 environmental classification ...... 46 2.2.4 Data overview and discussion ...... 46 2.3 Acetyltri‐n‐butyl citrate (ATBC, Citroflex A‐4) ...... 47 2.3.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 47 2.3.2 Other regulatory values ...... 48 2.3.3 environmental classification ...... 48 2.3.4 Data overview and discussion ...... 48 2.4 Glycerides, Castor‐oil‐mono‐, hydrogenated, acetates (COMGHA) ...... 50 2.4.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 50 2.4.2 Other regulatory values ...... 50 2.4.3 environmental classification ...... 50 2.4.4 Data overview and discussion ...... 51 2.5 Di(2‐ethylhexyl)adipate (DEHA, dioctyladipate, DOA) ...... 52 2.5.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 52 2.5.2 Other regulatory values ...... 52 2.5.3 environmental classification ...... 53 2.5.4 Data overview and discussion ...... 53 2.6 Dioctylsebacate (Diethylhexylsebacate) (DEHS) ...... 56 2.6.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 56 2.6.2 Other regulatory values ...... 56 2.6.3 environmental classification ...... 56 2.6.4 Data overview and discussion ...... 56 2.7 Di(2‐ethylhexyl) terephtalate (DEHT, dioctylterephthalate, DOTP) ...... 58
5 Evaluation of DEHP alternatives
2.7.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 58 2.7.2 Other regulatory values ...... 59 2.7.3 environmental classification ...... 59 2.7.4 Data overview and discussion ...... 59 2.8 Di(2‐propylheptyl) phthalate (DPHP) ...... 61 2.8.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 61 2.8.2 Other regulatory values ...... 61 2.8.3 environmental classification ...... 61 2.8.4 Other notified classifications: None Data overview and discussion ...... 61 2.9 Di‐isodecylphthalate (DIDP) ...... 63 2.9.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 64 2.9.2 Other regulatory values ...... 64 2.9.3 environmental classification ...... 64 2.9.4 Data overview and discussion ...... 64 2.10 Di‐iso‐nonyl‐1,2‐cyclohexanedicarboxylate (DINCH, Hexamoll DINCH) ...... 66 2.10.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 67 2.10.2 Other regulatory values ...... 67 2.10.3 environmental classification ...... 67 2.10.4 Data overview and discussion ...... 68 2.11 Di‐isononylphthalate (DINP) ...... 70 2.11.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 70 2.11.2 Other regulatory values ...... 70 2.11.3 environmental classification ...... 71 2.11.4 Data overview and discussion ...... 71 2.12 Trioctyltrimellitate (TOTM, tri(2‐ethylhexyl) trimellitate, TEHTM) ...... 74 2.12.1 Predicted no effect concentrations (PNECS) from Echa Dissemination data base ...... 74 2.12.2 Other regulatory values ...... 75
6 Evaluation of DEHP alternatives
2.12.3 environmental classification ...... 75 2.12.4 Data overview and discussion ...... 75
3 Migration data for alternative substances for assessment of human exposure ...... 77 3.1 General remarks ...... 77 3.2 Alkylsulphonic phenyl ester (ASE, Mesamoll) ...... 77 3.3 Acetyltri‐n‐butyl citrate (ATBC) ...... 78 3.4 Glycerides, Castor‐oil‐mono‐, hydrogenated, acetates (COMGHA) ...... 79 3.5 Di(2‐ethylhexyl) adipate (DEHA) ...... 79 3.6 Di(2‐ethylhexyl) sebacate (DEHS) ...... 79 3.7 Di(2‐ethylhexyl) terephtalate (DEHT) ...... 80 3.8 Di(2‐Propylheptyl) Phthalate (DPHP) ...... 80 3.9 Di‐isodecyl phthalate (DIDP) ...... 80 3.10 Di‐isononyl‐1,2‐cyclohexanedicarboxylate (DINCH) ...... 81 3.11 Di‐isononyl phthalate (DINP) ...... 81 3.12 Trioctyl trimellitate (TOTM) ...... 82
4 Comparative environmental exposure assessment ...... 83 4.1 Introduction ...... 83 4.2 Critical data for alternative substances ...... 83 4.3 Values used for comparative environmental exposure assessment ...... 88 4.4 PEC Calculations ...... 90
5 Summary and conclusions ...... 93 5.1 Comparative human health hazard evaluation ...... 93 5.2 Comparative environmental hazard evaluation ...... 97 5.3 Human exposure considerations ...... 100 5.4 Environmental Exposure considerations ...... 101 5.5 Overall conclusions...... 102
6 References ...... 104
7 Evaluation of DEHP alternatives
1 Human Health Hazard profiles
1.1 GENERAL REMARKS
The aim of this report (Annex 4 to the Public Analysis of Alternatives), undertaken in 2012 prior to the Socio‐Economic Analysis, is to provide a comparative risk evaluation between DEHP and the selected alternatives, ahead of an assessment of the technical and socio‐ economic feasibility of these alternatives . For that purpose, a short compilation of toxicity data of these alternatives has been done in this chapter. It summarises the information from REACH registration dossiers1, regulatory values of national and international organizations, harmonized and notified classifications and gives a short overview of toxic properties of each substance. The registration dossiers do not evidence the background of the derivation of the DNELs, so the specific key studies as well as the extrapolation factors used for it are not explained. Therefore all key studies of each registration dossier for the endpoints repeated dose, carcinogenicity, and reproductive (including developmental) toxicity are reported in tabular form (with the LOAELs and NOAELs stated in the dossier), and discussed in the “overview and discussion” sections. The latter only comprises scant descriptions of the relevant studies and for this reason acute toxicity is not reported at all, data on irritation and sensitization only briefly. Based on the available data, tentative DNELS for the relevant exposure pathways of the general population, long‐term oral and dermal exposure, were derived. These tentative DNELS for oral and dermal exposure of the general population are discussed and derived in light of official regulatory values (if available). These tentative non‐reference DNELs were derived to create a consistent set of DNELs for the purpose of direct comparison of the alternatives, based on currently available data (Registration dossier plus recent publications). All tentative DNELs are higher than that of DEHP. These tentative DNELs cannot be considered reference DNELs in any form. Notified classifications (concerning human health) are discussed in the context of the available data. As no reliable long‐term dermal studies are available, the dermal DNELs in the following sections emanate from the derived oral DNELs after cursory consideration of information on dermal exposure. Information on dermal absorption from the registration dossier as well as from review documents, such as EU Risk Assessment Reports, as far as available, is used. In general, all substances are well absorbed via oral exposure, but show limited absorption when exposed dermally. The data base for individual substances is highly variable.
The primary data searches on alternatives substances were completed in October 2012, so as to enable completion of the Analysis of Alternatives prior to undertaking the Socio‐
1 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
8 Evaluation of DEHP alternatives
Economic Assessment. New information from the ECHA dissemination database of registered substances was added in June, based on the data available as of the 7th June 2013.
1.2 ALKYLSULPHONIC PHENYL ESTER (ASE)
CAS‐No.: 91082‐17‐6 EC‐No.: 293‐728‐5 Synonyms: MESAMOLL, Sulfonic acids, C10‐21‐alkane, Ph(enyl) esters, alkylsulfonic acid ester of phenol
1.2.1 DNELS FROM ECHA-DISSEMINATION DATA BASE2
Table 1: DNELs derived for ASE
DNEL workers Key studies available from IUCLID long‐term dermal 0.93 mg/kg b.w. per No key study, probably route‐to‐route extrapolation (systemic) day Overall assessment factor: not stated long‐term inhalation 6.5 mg/m³ No key study, probably route‐to‐route extrapolation (systemic) Overall assessment factor: not stated General population long‐term dermal 0.47 mg/kg b.w. per No key study, probably route‐to‐route extrapolation (systemic) day Overall assessment factor: not stated long‐term oral 0.47 mg/kg b.w. per NOAEL in Key studies: (systemic) day Subchronic rat study, 228‐282.6 mg/kg b.w. per day Reproductive toxicity, rat: about 68 mg/kg b.w. per * day for F0 and F1 Developmental toxicity, rat: 300 mg/kg b.w. per day (maternal) and 1000 mg/kg b.w. per day (offspring) Overall assessment factor: not stated
*): calculation according to EFSA (2009)
1.2.2 OTHER REGULATORY VALUES A temporary TDI of 0.1 mg/kg b.w. per day was allocated (no further details) by EC (1995).
2 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
9 Evaluation of DEHP alternatives
The EFSA Panel on food contact materials, enzymes, flavourings and processing aids (CEF Panel) classified ASE in the Scientific Committee on food (SCF) List 3 (“Substances for which an ADI or a TDI could not be established, but where the present use could be accepted”), with a restriction of 0.05 mg/kg food and not to be used in articles for contact with fatty foods (EFSA, 2009).
1.2.3 CLASSIFICATION
1.2.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.2.3.2 Classification and labeling inventory database3 Harmonized classification: None Classification proposed by joint submission: No entry Other notified classifications: Not classified
1.2.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): ASE was absorbed after oral exposure in the rat. The half‐life in fat tissues was calculated to be 8 and 15 days (single and repeated doses, respectively) and there was no indication for accumulation in the liver after repeated exposure. No information was found with respect to dermal absorption, but no systemic toxic effects have been observed in acute dermal studies, indicating low absorption (Maag et al., 2010). ASE was not irritating to skin or eyes and a guinea pig maximisation test according to OECD 406 did not show sensitising properties. The repeated dose key study is a 90‐days feeding study (acc. to OECD 408) with a dose range of 750, 3000 and 12000 ppm in diet (55.4‐68.7; 228.0‐282.6; 985.2‐1488.5 mg/kg b.w. per day for males‐females, respectively). Effects at the highest dose were delayed growth and a slightly increased thromboplastin‐time in male rats only. The absolute and relative liver weight was dose‐related and significantly increased at all dose levels (kidney weight only at the highest dose level). According to the authors of the study report, the highest dose was considered as LOAEL and the mid dose as NOAEL (3000 ppm in diet, 228‐282.6 mg/kg b.w. per day). An identical NOAEL for this study is reported in the IUCLID 4‐file of 2000, as available on the ECB‐ESIS website, by Maag et al. (2010) and also by BUA (1996). EFSA (2009) considered the low dose group as NOAEL (“based on increases in liver weights along with increased lactate dehydrogenase activities at higher doses”). However, the altered enzyme activity was not reported in the study record of the registration dossier. COWI (2009)
3 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
10 Evaluation of DEHP alternatives
evaluated the same study with a LOAEL of 55.4 mg/kg b.w. per day (with reference to an IUCLID file of 1999, i.e. older than that available via ECB‐ESIS). No background details are available for this decision. Based on the available data the increased liver weight (without histopathological effects at higher doses) can be considered as adaptive response. Based on the growth reduction in male rats of the highest dose a NOAEL of 228 mg/kg b.w. per day (for males) seems to be plausible. The key study for reproductive toxicity is an OECD 415 one‐generation feeding study in rats with levels of 600, 3000, 15000 ppm in the diet. The NOAEL is reported by the authors to be 600 ppm (68 mg/kg b.w. per day for F0 females according to EFSA, 2009), based on F0/F1 generation effects (reduced body weights associated with absolute and/or relative increases in liver and kidney weights and prolonged developmental milestones: balano‐preputial separation, vaginal opening). EFSA (2009) derived an identical NOAEL from this study. Developmental toxicity was assessed by an OECD 414 study in rats (dose range 100, 300, 1000 mg/kg b.w. per day) with a maternal NOAEL of 300 mg/kg b.w. per day (reduction of feed intake and decreased body weight gain at highest dose). No adverse effects were observed in the offspring (NOAEL 1000 mg/kg b.w. per day). The substance was not mutagenic (with and without metabolic activation) in an Ames test, in 2 vitro mammalian cytogenetic tests (one acc. to OECD 473) and in a HGPRT gene mutation assay. No carcinogenicity study or long term repeated dose could be identified.
1.3 ACETYLTRI-N-BUTYL CITRATE (ATBC)
CAS‐No.: 77‐90‐7 EC‐No.: 201‐067‐0 Synonyms: Acetyl tributyl citrate, tributyl O‐acetylcitrate, Citroflex A‐4, 1,2,3‐ Propanetricarboxylic acid, 2‐(acetyloxy)‐, tributyl ester; tributyl 2‐acetoxypropane‐1,2,3‐ tricarboxylate
1.3.1 DNELS FROM ECHA-DISSEMINATION DATA BASE4
Table 2: DNELs derived for ATBC This information is based on a dossier which was available in October 2012. Currently there is no dossier on the ECHA dissemination website. DNEL workers Key studies available from IUCLID
4 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances, data as of October 2012: Currently no registration dossier available.
11 Evaluation of DEHP alternatives
long‐term dermal 2 mg/kg b.w. per day No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term inhalation 7.04 mg/m³ No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated General population long‐term dermal 1 mg/kg b.w. per day No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term inhalation 1.74 mg/m3 No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term oral 1 mg/kg b.w. per day NOAEL in Key studies: (systemic) Chronic rat study, NOEL: 100/300 mg/kg b.w. per day (males/females, toxicity) and 1000 mg/kg b.w. per day (carcinogenicity) Reproductive toxicity: Data waiving, only supporting studies available Rat (2‐generation study 1): 300 mg/kg b.w. per day (reproduction, F0), 1000 mg/kg b.w. per day (developmental toxicity, offspring) Rat (2‐generation study 2): 100 mg/kg b.w. per day (reproduction, F0), 100 mg/kg b.w. per day (developmental toxicity, offspring) Developmental toxicity (rat): 50 (maternal) and 250 (offspring) mg/kg b.w. per day Developmental toxicity (mouse): 50 (maternal) and 250 (offspring) mg/kg b.w. per day Overall assessment factor: not stated
1.3.2 OTHER REGULATORY VALUES No safety concern at current levels of intake when used as a flavouring agent (WHO, 2000). The Cosmetic Ingredient Review Expert panel (CIREP) concluded that ATBC is safe as used in cosmetics (Johnson et al., 2002).
12 Evaluation of DEHP alternatives
1.3.3 CLASSIFICATION
1.3.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.3.3.2 Classification and labeling inventory database5 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Muta. 1B ‐ H340/Carc. 1B ‐ H350, Skin Irrit. 2 ‐ H315, Eye Irrit. 2 ‐ H319
1.3.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): ATBC is absorbed orally and rapidly metabolised and excreted in the rat. In a toxicokinetic study it was recovered after oral exposure to 59 ‐ 70% in urine and cage rinse, 25 ‐ 36% in faeces, and 1‐2% expired and remaining in tissues and carcass. It is predicted to present a very low potential for toxicity via the dermal route of exposure because it is unlikely to be absorbed efficiently through the skin (EPA, 2003b). However, this holds true only for acute exposure, repeated dermal exposure produced systemic toxicity, even though observed in a less reliable study (CPSC, 2010b; Johnson, 2002). The substance did not cause skin irritation in human volunteers and was slightly irritating to the skin of guinea pigs in one older study, but not irritating in several rabbit studies. ATBC produced moderate “erythema” in the eyes of rabbits in an older study (same decription in CPSC, 2010b; Johnson, 2002). No sensitisation was observed in less reliable (not‐guideline) studies in humans and guinea pigs (Maag et al., 2010). In a repeated dose study following a 2‐generation feeding study with rats (doses about 100, 300, 1000 mg/kg b.w. per day) the F1 male and female offspring were exposed in utero, followed by an exposure of 13 weeks and 4 weeks of recovery (EPA, 2003b). It is stated as “according to guidelines OECD 408, and EU B.26”, which obviously refers to the subsequent subchronic toxicity part of the F1 generation. NOAEL values for systemic toxicity were 100 mg/kg b.w. per day for males and 300 mg/kg b.w. per day for females, obviously based on peroxisome proliferation in liver. At the highest dose level a slight reduction in body weight gain was seen in both sexes, liver weights were increased and hepatic hypertrophy (common finding at high doses of xenobiotics acc. to Maag et al., 2010) was seen in males and females. Reproductive effects of this 2‐generation study are reported below.
5 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
13 Evaluation of DEHP alternatives
A combined chronic/carcinogenicity study was performed in rats (2 years feeding study acc. to guidelines, daily intake about 100, 300 and 1000 mg/kg b.w. per day acc. to guidelines 875/318/EEC; 83/571/EEC; 91/507/EEC). Chronic toxicity was examined after 52 weeks. Observations included slight reductions in body weight and food consumption, changes in clinical chemistry parameters (indicating adaptive changes of metabolic activation). A relative liver weight increase along with an increased incidence of hepatocellular hypertrophy at 1000 mg/kg b.w. per day in males was considered by the authors as adaptive changes. According to them, the NOEL for this study was 100 mg/kg b.w. per day (males) and 300 mg/kg b.w. per day (females), based on reductions of body weights at higher doses. Occurrence of single cell necrosis in hepatocytes of individual high‐dosed males or females “remained unclear”. No treatment‐related carcinogenic effects were observed. The already mentioned 2‐generation study (study 1) was reported by the authors with a NOAEL of 300 mg/kg b.w. per day for parental animals (reported effects in high‐dose females: increased incidence of yellow staining in the perigenital and sacral regions) and 1000 mg/kg b.w. per day for developmental toxicity (EPA, 2003). The 2‐generation rat study 2 (about 100, 300 and 1000 mg/kg b.w. per day via food) is reported with NOAELs of 100 mg/kg b.w. per day for parental animals and for offspring. The observed effects were reduced parental body weights at 300 mg/kg b.w. per day and above. Slightly lower body weight and slightly higher mortality was observed among pups in the mid and high dose groups, but these effects were not considered to be treatment‐related by others, but attributed to reduced water consumption of the dams (EPA, 2003; Maag et al., 2010). Both key studies on developmental toxicity emanate from a Russian publication, reported with a NOAEL of 50 mg/kg b.w. per day (maternal) and 250 mg/kg b.w. per day (offspring) for both species. In these studies the animals were exposed 9 months prior to cross‐mating. The only effects observed were increases in body weight, length of the progeny and placental weight in the 250 mg/kg dose group (U.S. EPA, 2003). However, the lack of methodological details limits interpretation of these data (CPSC, 2010b). The substance was not mutagenic in vitro in Ames‐tests in Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100, gene mutation assays in CHO and L5178Y cells, and chromosome aberration in rat lymphocytes. Two available in vivo tests (chromosome aberration in rat bone marrow, UDS in rat hepatocytes) came also to negative results. All studies were performed according to or equivalent/similar to guidelines. A two year oral feeding carcinogenicity study has been carried out in rats (with body doses up to approx. 1000 mg/kg b.w. per day), but was not performed according to current standards. No significant treatment‐related effects were observed in this study (CPSC, 2010b; SCENIHR, 2008). No treatment‐related carcinogenic effects were observed in the long‐term rat study already described above. Further information: ATBC showed some signs of neurotoxicity when applied in a 3% gum acacia to the sciatic nerve in rats and in a 5% suspension of ATBC in 3% gum acacia to the conjunctival sac of the eye of a rabbit. The substance was found to block neural transmission in rats when placed in
14 Evaluation of DEHP alternatives
contact with a nerve trunk and to have local anaesthetic action in the rabbits (Maag et al., 2010). SCENIHR (2008) concluded that a dose of 100 mg/kg b.w. per day was the NOAEL for repeated exposure based on the discussed studies (the Russian developmental toxicity studies were not considered by SCENIHR). This is not in contrast to the LOAEL and NOAEL documented in the two Russian studies: no other doses than 50 and 250 mg/kg b.w. per day were tested, and the LOAEL for minor unspecific effects is close to the LOAELs observed in more reliable studies. Therefore the NOAEL of 100 mg/kg b.w. per day is also considered as suitable for deriving a DNEL.
1.4 GLYCERIDES, CASTOR-OIL-MONO-, HYDROGENATED, ACETATES (COMGHA)
CAS‐Nos.: 736150‐63‐3 (COMGHA); 330198‐91‐9 (component A); 33599‐07‐4 (component B) EC‐No.: no
1.4.1 DNELS FROM ECHA-DISSEMINATION DATA BASE6 Not registered
1.4.2 OTHER REGULATORY VALUES COMGHA is introduced in the list of additives according to “Commission Directive 2008/39/EC of 6 March 2008 amending Directive 2002/72/EC relating to plastic materials and articles intended to come into contact with food”.
1.4.3 CLASSIFICATION
1.4.3.1 Classification from REACH registration dossier The substance is currently not registered under REACH
1.4.3.2 Classification and labeling inventory database7 Harmonized classification: None Notified classifications: None
6 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances 7 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
15 Evaluation of DEHP alternatives
1.4.4 DATA OVERVIEW AND DISCUSSION Compilation of data cited in Maag et al. (2010), Danish EPA (2012) and NICNAS (2009). Toxicokinetic studies on COMGHA show that there is no significant absorption of the unchanged substance across the gastrointestinal epithelium and it does not appear to accumulate in tissues. COMGHA appears to be rapidly hydrolyzed in the gastrointestinal tract to acetic acid and fatty acids that undergo normal fatty acid alpha‐ and beta‐oxidation. No information was found with respect to dermal absorption, but no systemic toxic effects have been observed in acute dermal studies, indicating low absorption. The substance was not irritating to the skin and eyes of rabbits (studies acc. to OECD 404, 405) and also not a skin sensitizer in a local lymph node assay in mice (acc. to OECD 429) (Maag et al., 2010). In a 90‐day oral toxicity study (acc. to OECD 408) with extreme high doses (3, 8.5, 20 mL/kg b.w. per day administered by gavage) toxic effects were evident at the lowest dose tested (no NOAEL). In another 90‐day oral toxicity study (acc. to OECD 408) with lower doses (0, 500, 1600 or 5000 mg/kg b.w. per day) the NOAEL was ≥ 5,000 mg/kg b.w. per day. The peroxisomal enzyme activities in liver samples were not affected in this study. In a chronic toxicity study (acc. to OECD 452) rats received doses of 1500, 6000 and 15000 ppm in the diet. The concentration of the high dose group was increased during the study to 25000 and 30000 ppm. The mean body doses for both genders were 98, 392 and 1333 mg/kg b.w. per day, respectively. Dietary concentrations of up to 30000 ppm for a period of up to 12 months did not result in adverse effects of treatment (NOAEL 1333 mg/kg b.w. per day. The reproductive toxicity was studied in a two‐generation rat study in combination with a developmental neurotoxicity study (acc. to OECD 416/426) using rats receiving dietary concentrations of 1500, 6000 and 15000 ppm. In each generation, the highest doses were raised up to 20000 ppm and then 25000 ppm from the maturation period (intended average achieved dose of >1000 mg/kg b.w. per day). No adverse effects on reproduction and pre‐ and postnatal development could be observed in this two‐generation reproduction/developmental neurotoxicity study, including no adverse endocrine disrupting effect (anogenital distance, nipple counts). There was also no developmental neurotoxicity in the offspring. The NOAEL of the study was ≥ 25000 ppm (highest tested dose level), corresponding to average body doses of 1159 mg/kg b.w. per day (lowest average exposure in F0 males). The developmental toxicity was examined in rats and in rabbits (studies acc. to OECD 414) at oral doses of 100, 300 and 1000 mg/kg b.w. per day. No maternal or developmental toxicity was observed at dose levels up to 1000 mg/kg b.w. per day (NOAEL ≥ 1000 mg/kg b.w. per day). COMGHA was not mutagenic in an in vitro Ames test (acc. to OECD 471) and was also inactive in an in vitro mammalian cell gene mutation test (acc. to OECD 476). No clastogenic activity could be observed in the in vitro chromosome aberration test (acc. to OECD 473). The substance did not induce micronuclei in vivo (test acc. to OECD 474). Based on the
16 Evaluation of DEHP alternatives
available in vivo and in vitro genotoxicity studies COMGHA does not have genotoxic properties. No evidence of pre‐neoplastic changes was evident in 90‐days and chronic dietary studies in rats (see above).
1.5 DI(2-ETHYLHEXYL)ADIPATE (DEHA)
CAS‐No.: 103‐23‐1 EC‐No.: 203‐090‐1 Synonyms: Dioctyladipate, DOA, Bis(2‐ethylhexyl) hexanedioate, Hexanedioic acid, bis(2‐ ethylhexyl) ester
1.5.1 DNELS FROM ECHA-DISSEMINATION DATA BASE8
Table 3: DNELs derived for DEHA
DNEL workers Key studies available from IUCLID long‐term dermal 25.5 mg/kg b.w. per No key study, probably route‐to‐route (systemic) day extrapolation Overall assessment factor: 6 long‐term inhalation 17.8 mg/m³ No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: 9
General population long‐term dermal 13 mg/kg b.w. per day No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: 13 long‐term inhalation 4.4 mg/m3 No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: 40 long‐term oral 1.3 mg/kg b.w. per day NOAEL in Key studies: (systemic) Subacute rat: 200 mg/kg b.w. per day Subchronic mouse: 200 mg/kg b.w. per day Subchronic rat study, 551‐630 mg/kg b.w. per day Chronic rat study: 600 mg/kg b.w. per day (for
8 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
17 Evaluation of DEHP alternatives
toxicity, for carcinogenicity 1250 mg/kg b.w. per day) Chronic mouse study: LOAEL 1715 mg/kg b.w. per day (lowest dose tested, liver carcinogenicity) Reproductive toxicity: 170 mg/kg b.w. per day Developmental toxicity: 28 mg/kg b.w. per day Overall assessment factor: 130
1.5.2 OTHER REGULATORY VALUES A TDI on 0.3 mg/kg b.w. per day (derived by the EU Scientific Committee for Food, SCF, basis NOAEL 30 mg/kg b.w. per day in a teratogenicity study, see below) has been confirmed in a re‐evaluation (SCF, 2000). IRIS (EPA, 2013) lists a reference dose for oral exposure (RfD) of 0.6 mg/kg b.w. per day (dated 1992) and classifies the substance as carcinogen class C (possible human carcinogen, as of 1994). The RfD was based on two industrial studies (fertility and teratogenicity rat studies) with a LOAEL of 1080 mg/kg b.w. per day and a NOAEL of 170 mg/kg b.w. per day for changes in body and liver weight, increased liver weight of parents, delayed ossification and slightly dilated ureters in fetuses; reduced offspring weight gain, total litter weight, and litter size. The carcinogenicity assessment was based on the increased incidence of liver tumours in a NTP study in female mice, not in males or rats of both sexes (further details see below). A Canadian ADI of 0.5 mg/kg b.w. per day is based on the 2‐years feeding study with rats (Environment Canada, 2011). IARC (2000) listed DEHA in group 3 of carcinogens (limited evidence in animals). In relation to the structural analogue DEHP, IARC has concluded that the mechanism by which DEHP increases the incidence of hepatocellular tumours in rats and mice is not relevant to humans. DEHP produces liver tumours in rats and mice by a non‐DNA‐reactive mechanism involving peroxisome proliferation, which has not been demonstrated in human hepatocyte cultures or exposed nonhuman primates. This view of the species‐specific mechanism of hepatocarcinogenicity by peroxisome proliferators was confirmed more recently by CPSC (2010b) and Environment Canada (2011) (2011). DEHA was entered in the Community Rolling Action Plan (CORAP) list update covering the years 2013‐2015 (ECHA, 2013)9.
9 ECHA, European Chemicals Agency, CoRAP list of substances http://echa.europa.eu/web/guest/information‐ on‐chemicals/evaluation/community‐rolling‐action‐plan/corap‐table?search_criteria=203‐090‐1
18 Evaluation of DEHP alternatives
1.5.3 CLASSIFICATION
1.5.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.5.3.2 Classification and labeling inventory database10 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Skin Irrit. 2 ‐ H315/Eye Irrit. 2‐ H319, Carc. 2 ‐ H351/ Repr. 2 ‐ H361, Acute Tox. 4 – H302/H332
1.5.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): DEHA is rapidly and almost completely absorbed from the gastrointestinal tract of animals. After oral administration, DEHA is hydrolysed in the gastrointestinal tract to 2‐ethylhexanol, ethylhexanoic acid, ethylhexanedioic acid, 5‐hydroxyethylhexanoic acid, mono(2‐ethylhexyl) adipate and adipic acid. All metabolites were partially glucuronidated. There are quantitative differences between species, e.g. humans excrete mainly mono(2‐ethylhexyl) adipate (Environment Canada, 2011). About 100% of an administered dose was excreted in the urine, expired air and faeces (7‐8% in faeces) after a single oral dose in mice, about 70‐80% in urine and expired air in rats. Preliminary results from an in vitro dermal absorption study indicated that less than 1% of the applied amount of DEHA was passed through the skin and detected in the receptor fluid from an application of a roll‐on deodorant, while a higher portion was found to be bound in skin (Environment Canada, 2011). The authors of this report considered a dermal absorption of 10% appropriate and adequately conservative for use in exposure assessment, supported by the predicted value estimated on substance specific physical and chemical properties. No or only weak skin irritation was observed in studies on humans and animals. Minimal irritation to the eyes of rabbits was reported (CPSC, 2010b). There is no evidence for skin sensitizing activity. Several repeated dose studies in rats and mice have been reported with NOAELs of 200‐1715 mg/kg b.w. per day (see also Environment Canada, 2011). These values are at least slightly higher than the NOAELs for reproductive and developmental toxicity: Systemic toxicity was examined in a one‐generation rat study (similar to OECD 415) with food concentrations of 300, 1800, 12000 ppm (28, 170, 1080 mg/kg b.w. per day). Mean pup weight gain and total litter weight for both male and female offspring receiving the highest
10 http://echa.europa.eu/web/guest/information‐on‐chemicals/cl‐inventory‐database
19 Evaluation of DEHP alternatives
dose were reduced, and mean litter size was also slightly reduced. According to the authors of the study report, the high dose was considered as LOAEL and the mid dose as NOAEL (1800 ppm in diet, 170 mg/kg b.w. per day). The same dose regimen was used in a teratogenicity study (similar to OECD 414). The food concentration of 1800 ppm resulted in minimal foetotoxicity (reduced ossification and increase in the incidence of visceral variants). According to the authors, 300 ppm in diet (28 mg/kg b.w. per day) was the NOAEL for embryonic development. Remark: This evaluation may be over‐conservative, as Environment Canada (2011), EPA (2012) and OECD (2000) (2000) derived a NOAEL of 170 mg/kg b.w. per day from the study results (Environment Canada, 2011, criticizes the use of the results of this study as key study, because it is unpublished and incompletely described as well as cited differently by several secondary sources). The testicular effects of DEHA exposure were examined in several studies and it was found that the substance did not cause toxicity in the testes (CPSC, 2010). After oral exposure of rats to 200, 400, or 800 mg/kg b.w. per day from gestational day 7 to postnatal day 17, DEHA induced developmental toxicity (increased postnatal death, permanent decrease in offspring body weight) at doses ≥ 400 mg/kg b.w. per day and a prolonged gestation period at 800 mg/kg b.w. per day (NOAEL 200 mg/kg b.w. per day for developmental effects, 400 mg/kg b.w. per day for maternal toxicity), but not antiandrogenic effects in pre‐ and postnatal exposed Wistar rats: levels of reproductive hormones in males, sperm quality, weight and histopathology of male reproductive organs were unaffected (Dalgaard et al., 2003). The NOAEL from this study was confirmed by SCENIHR (2008) and Environment Canada (2011) as critical NOAEL for developmental toxicity (further studies with higher NOAELs and LOAELs are referred in these secondary sources). DEHA did not cause gene mutations in bacteria and mammalian cells in vitro, sister chromatid exchanges, chromosomal aberration or micronuclei in several mammalian cell systems in vitro (except one study with increased chromosomal aberrations in CHO cells without metabolic activation, where cytotoxicity was not examined). It did not induce unscheduled DNA synthesis in primary rat hepatocytes. In vivo genotoxicity studies with a negative outcome include micronuclei induction in mouse bone marrow or sex‐linked recessive lethal mutations in Drosophila melanogaster. A dominant‐lethal assay in mice observed a slight positive effect (i.p. application, associated with fertility effects as indicator of possible cytotoxicity). DEHA was tested in a NTP carcinogenicity study with rats and mice in dietary concentrations of 12000 and 25000 ppm (approx. 600 and 1250 mg/kg b.w. per day for rats and 1715, 3570 mg/kg b.w. per day for mice, respectively. The test substance was not carcinogenic to rats. It was carcinogenic for female mice (significant increase in hepatocellular carcinomas) and probably carcinogenic for male mice (non‐significant increase in hepatocellular adenomas). Several compounds containing the 2‐ethylhexyl group showed some hepatocarcinogenic activity, indicating that this moiety is responsible for hepatocarcinogenesis in mice (SCENIHR, 2008). The carcinogenic response in mice can be attributed to a specific mechanism of
20 Evaluation of DEHP alternatives
tumour induction in rodents involving peroxisome proliferation, which has not been demonstrated in human hepatocyte cultures or exposed nonhuman primates (e.g. IARC, 2000). Further relevant information from other sources: Some studies reported the lack of an antiandrogenic effect or estrogenic activity. No estrogenic activity was observed in transgenic mice, expressing an estrogen receptor (ER)‐ mediated luciferase (luc) reporter gene system (Environment Canada, 2011; SCENIHR, 2008). DEHA affected thyroid hormone function in rats (TH‐dependent rat pituitary GH3 cell proliferation, T‐screen), but not the estrogen receptor function in human breast MVLN cells (Ghisari and Bonefeld‐Jørgensen, 2009).
1.6 DIETHYLHEXYLSEBACATE (DEHS)
CAS‐No.: 122‐62‐3 EC‐No.: 204‐558‐8 Synonyms: Bis(2‐ethylhexyl) sebacate, Dioctylsebacate, Decanedioic acid, 1,10‐bis(2‐ethyl‐ hexyl) ester
1.6.1 DNELS FROM ECHA-DISSEMINATION DATA BASE11 Not registered
1.6.2 OTHER REGULATORY VALUES Not identified
1.6.3 CLASSIFICATION
1.6.3.1 Classification from REACH registration dossier The substance is currently not registered under REACH
1.6.3.2 Classification and labeling inventory database12 Harmonized classification: None Classification proposed by joint submission: Not classified
11 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances 12 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
21 Evaluation of DEHP alternatives
1.6.4 OTHER NOTIFIED CLASSIFICATIONS: ACUTE TOX. 4 – H302DATA OVERVIEW AND DISCUSSION The following data for DEHS are a compilation of the material available within the frame of the EPA HPV program (EPA, 2003a; 2008; undated via ChemID). No data on toxicokinetics are available for DEHS. In analogy to the structurally related diethylhexyl adipate, an efficient absorption via the oral route can be assumed. DEHS is not readily absorbed through the skin of guinea pigs (CIREP, 2010). DEHS was administered to F344 rats in the diet at 2% (about 1000 mg/kg b.w. per day) for 3 weeks. The study focused on peroxisome proliferation. The treatment induced hepatic peroxisome proliferation, and the liver weight and hepatic peroxisomal enzymes were increased. Decreases in triglycerides were also seen. 1,000 mg/kg b.w. per day was therefore the effect dose, no NOAEL can be derived from this single dose study. The substance was not irritating to the skin of rabbits. A cream containing 1.2% DEHS was tested in the in vitro EpiOcular MTT viability test. The ET50 was 495 min, indicating no eye irritating potential (CIREP, 2010). A four‐generation study with rats was reported with a control and single dose group of 200 ppm in diet (approx. 10 mg/kg b.w. per day). Growth, reproduction and suckling were unaffected. No adverse effects or histological changes (including reproductive organs) were reported, and no tumours were observed (This study was considered to be not assignable by EPA). Developmental toxicity: EPA (2008) made a read across from a study with the ditridecyl ester of adipic acid, with a NOAEL of 800 mg/kg b.w. per day and a LOAEL of 2000 mg/kg b.w. per day. However, due to the relevant differences in the alcohol groups between DEHS and this chemical compound, DEHA seems to be more suitable candidate for a read across. Therefore the NOAEL of 200 mg/kg b.w. per day in the study of Dalgaard et al. (2003) for developmental effects caused by DEHA is used to derive a DNEL. DEHS was tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 and E.coli wp2 uvrA with and without metabolic activation (acc. to OECD 471). DEHS was not mutagenic in these assays. Further information: DEHS was negative in an in vitro assay with genetically modified CHO cells expressing the human androgen receptor (AR) and therefore possesses no AR antagonistic properties (Vinggaard et al., 2008). Diethylhexylsebacate did not show tumour promoting activity in a rat liver foci test with a single oral treatment with a known carcinogen, followed by oral exposure of 500 mg DEHS/kg b.w. per day, 3‐times per week for 11 weeks. A metabolite of DEHS, 2‐ethylhexanol, was negative in Ames tests, mouse lymphoma test, did not induce unscheduled DNA synthesis in vitro and was not mutagenic in the mouse micronucleus test in vivo. No evidence of carcinogenicity was reported in an incompletely documented study with an
22 Evaluation of DEHP alternatives
unspecified number of rats fed a diet providing about 10 mg/kg b.w. per day for up to 19 months (CIREP, 2010).
1.7 DI(2-ETHYLHEXYL) TEREPHTALATE (DEHT)
CAS‐No.: 6422‐86‐2 EC‐No.: 229‐176‐9 Synonyms: Dioctylterephthalate, DOTP, 1,4‐Benzenedicarboxylic acid, 1,4‐bis(2‐ethylhexyl) ester, bis(2‐ethylhexyl)‐1,4‐benzenedicarboxylate
1.7.1 DNELS FROM ECHA-DISSEMINATION DATA BASE13
Table 4: DNELs derived for DEHT
DNEL workers Key studies available from IUCLID long‐term dermal 6.58 mg/kg b.w. per No key study, probably route‐to‐route (systemic) day extrapolation Overall assessment factor: 12 long‐term inhalation 23.2 mg/m³ No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: 3 General population long‐term dermal 3.95 mg/kg b.w. per No key study, probably route‐to‐route (systemic) day extrapolation Overall assessment factor: 20 long‐term inhalation 6.86 mg/m3 No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: 5 long‐term oral 3.95 mg/kg b.w. per NOAEL in Key studies (range: males‐females): (systemic) day Subchronic rat study, 277‐309 mg/kg b.w. per day Chronic rat study, 79‐102 mg/kg b.w. per day (toxicity) and ≥ 666‐901 mg/kg b.w. per day (carcinogenicity) Reproductive toxicity, rats: 447‐1349 mg/kg b.w. per day (F0‐reproductive toxicity), 133‐478 mg/kg
13 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
23 Evaluation of DEHP alternatives
b.w. per day (F0‐general toxicity), 159‐516 mg/kg b.w. per day (F1‐neonatal toxicity) Developmental toxicity, rat : 458 mg/kg b.w. per day (maternal), 747 mg/kg b.w. per day (offspring) Developmental toxicity, mouse: 197 mg/kg b.w. per day (maternal), 1382 mg/kg b.w. per day (offspring) Overall assessment factor: 20
1.7.2 OTHER REGULATORY VALUES Ball et al. (2012) derived a reference dose (RfD) of 0.2 mg/kg b.w. per day, based on a benchmark dose (lower confidence limit, BMDL10) of 54 mg/kg b.w. per day (extrapolation factors: each 10 for inter‐ and intraspecies differences, 3 for data base deficiencies, total 300). This BMDL was modeled from the experimental data of a combined chronic toxicity/carcinogenicity rat study (retinal degeneration in females with a NOAEL of 102 mg/kg b.w. per day).
1.7.3 CLASSIFICATION
1.7.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.7.3.2 Classification and labeling inventory database14 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Repr. 2 ‐ H361
1.7.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): DEHT is rapidly, but incompletely absorbed from the gastrointestinal tract (36% found unchanged in faeces). No systemic toxicity has been observed in acute dermal studies, indicating low absorption. A study to assess the dermal absorption rate confirmed that DEHT has a low potential to penetrate the skin (0.103 μg/cm2/hr) (CPSC, 2010; Maag et al., 2010; SCENIHR, 2008). The main metabolites of DEHT are terephthalic acid and 2‐ethylhexanol. In
14 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
24 Evaluation of DEHP alternatives
contrast to DEHP with the main metabolite mono(2‐ethylhexyl) phthalate only traces of mono‐ester were detected after DEHT exposure. DEHT did not irritate the skin of human volunteers or rabbits and was slightly irritating to the skin of guinea pigs A more recent study on rabbits (acc. to OECD 404) observed no dermal irritation (Ball et al., 2012). The substance was slightly irritating to the eyes of rabbits (study similar to OECD 405), but the effects were reversible. No skin sensitization was observed in humans (HRIPT) or guinea pigs (no guideline). Maag et al. (2010) criticised limitations of these studies. Another study showed DEHT to be sensitizing in guinea pigs, producing a strong reaction in 2/10 guinea pigs tested and a weak reaction in 6/10 guinea pigs (CPSC, 2010b). However, this result was obtained with a test substance from a pilot run and impurities in the material that were considered to be responsible for the sensitization. Therefore, the study was repeated with a production run and yielded a negative outcome (OECD, 2003a). In a 90‐day rat study (similar to U.S. EPA guideline, 799.9310 TSCA) with DEHT in dietary concentrations of 0.1, 0.5 or 1% the only significant treatment related effect was an increased relative liver weight in the highest dose group. There was no indication of peroxisome induction in animals from the 1.0% dose group. The NOAEL was 0.5%, corresponding to approximately 277‐309 mg/kg b.w. per day. Rats were exposed to 1,500, 6,000 and 12,000 ppm (79‐102, 324‐418, 666‐901 mg/kg b.w. per day for males and females, respectively) in the diet in a combined chronic toxicity/carcinogenicity study (acc. to OPPTS 870.4200). The exposure was well tolerated at all dose levels. Treatment‐related effects were reduced weight gain and food conversion efficiency, minor haematological effects in males and females receiving 6,000 and 12,000 ppm and retina degeneration at the same dose levels in females. High‐dose females showed a high incidence of dark kidneys. According to the authors the NOAEL for chronic toxicity was 1,500 ppm (79‐102 mg/kg b.w. per day for males and females, respectively), which was confirmed by Ball et al. (2012). There were no increased incidences of tumours at all dose levels (NOEL for carcinogenicity ≥ 666‐901 mg/kg b.w. per day). In a further combined chronic toxicity/carcinogenicity study DEHT was administered in the diets of rats to achieve body doses of 20, 142, and 1,000 mg/kg b.w. per day. Clinical evaluations revealed no treatment‐related effects. Eye opacities (cataracts) occurred frequently in all groups including the controls. Body weights and female liver weights were reduced in the high‐dose group, but not accompanied by consistent reductions in food consumption. There were no treatment‐related effects at 6 and 12 months of exposure except hyperplasia and/or transitional cell adenomas of the urinary bladder and adenomas or adenocarcinomas of the uterus in high‐dose group females (Maag et al., 2010). The reproductive toxicity was studied in a 2‐generation rat study (acc. to OECD 416, OPPTS 870.3800) at dietary levels of 3000, 6000 or 10000 ppm (133‐182, 265‐367, 447‐614 mg/kg b.w. per day for F0‐males, 184‐478, 372‐940, 595‐1349 mg/kg b.w. per day for F0‐females; 159‐256, 320‐523, 552‐893 mg/kg b.w. per day for F1‐males, 206‐516, 423‐1036, 697 1549 mg/kg b.w. per day for F1‐females). Reduced body weight gains in parents and offspring were evident at the 6000 ppm level and above (NOAEL 3000 ppm, 133‐478 for mg/kg b.w.
25 Evaluation of DEHP alternatives
per day for males‐females, respectively, of the F0 generation and 159‐516 mg/kg b.w. per day for males‐females, respectively, of the F1‐generation). No reproductive toxicity was observed in all exposed groups and delayed acquisition of developmental landmarks (balanopreputial separation) was attributed to reduced pup weight gain (NOAEL for reproductive toxicity 10000 ppm, 447‐1349 mg/kg b.w. per day for males‐females, respectively). No developmental toxicity was observed in a rat study (acc. to OECD 414 and OPPTS 870.3700) at dose levels of 3000, 6000 or 10000 ppm in the diet (226, 458, and 747 mg/kg b.w. per day). Therefore the developmental NOAEL was 747 mg/kg b.w. per day. Maternal toxicity in form of increased liver weights and reduced body weight gain was observed at the highest dose (NOAEL 6000 ppm, 458 mg/kg b.w. per day). A developmental toxicity mouse study (acc. to OECD 414) with food concentrations of 1000, 3000, 7000 ppm (corresponding to 197, 592 and 1382 mg/kg b.w. per day) observed comparable results: no developmental toxicity up to the highest dose tested (NOAEL 1382 mg/kg b.w. per day) with increased maternal liver weights at 3000 ppm and above (NOAEL 197 mg/kg b.w. per day). No mutagenic responses were observed in vitro in several Ames tests, an in vitro mammalian chromosome aberration test in CHO cells and a HGPRT‐gene mutation assay in CHO cells (all similar to corresponding guidelines). No carcinogenic effects were observed in the long‐term rat study described above. Maag et al. (2010) also referred most of these studies with an identical interpretation of the results. Further information from REACH registration dossier: Pregnant rats were exposed to 500 mg/kg b.w. per day on gestation days 12‐19. The anogenital distance was not significantly altered in male foetuses exposed to the test substance, and none of the genes representing major gene pathways that allow for normal male reproductive tract development were altered by the treatment. Results of an uterotrophic assay with immature females at doses up to 2,000 mg/kg b.w. per day on PND 19‐21 indicate that DEHT does not possess estrogenic activity. Pregnant rats were administered 750 mg/kg b.w. per day DEHT on gestation day 14 until postnatal day 3. No changes indicative of a feminization effect were induced in male pups. (Maag et al., 2010).
1.8 DI(2-PROPYLHEPTYL) PHTHALATE (DPHP)
CAS‐No.: 53306‐54‐0 EC‐No.: 258‐469‐4 Synonyms: DPHP, Bis(2‐propylheptyl)phthalate, 1,2‐Benzenedicarboxylic acid, 1,2‐bis(2‐ propylheptyl) ester, PALATINOL 10‐P
26 Evaluation of DEHP alternatives
1.8.1 DNELS FROM ECHA-DISSEMINATION DATA BASE15
Table 5: DNELs derived for DPHP
DNEL workers Key studies available from IUCLID long‐term dermal 102.08 mg/kg b.w. No key study, route‐to‐route extrapolation from the (systemic) per day oral 90‐day study Overall assessment factor: 24 The dermal absorption is considered to be 4%, the oral absorption is considered to be 50% long‐term inhalation 28.8 mg/m³ No key study, route‐to‐route extrapolation from the (systemic) oral 90‐day study Overall assessment factor: 12
General population long‐term inhalation 8.52 mg/m³ No key study, route‐to‐route extrapolation from the (systemic) oral 90‐day study Overall assessment factor: 20 long‐term dermal 61.25 mg/kg b.w. per No key study, probably route‐to‐route extrapolation (systemic) day Overall assessment factor: 40 The dermal absorption is considered to be 4%, the oral absorption is considered to be 50% long‐term oral 4.9 mg/kg b.w. per Overall assessment factor: 40 (systemic) day NOAEL in key studies: 196 mg/kg b.w. per day (peroxisome proliferation disregarded); 39 mg/kg b.w. per day (for peroxisome proliferation) Reproductive toxicity, rat: 600 mg/kg b.w. per day Developmental toxicity, rat: 200 mg/kg b.w. per day (maternal) and 200 mg/kg b.w. per day (offspring)
1.8.2 OTHER REGULATORY VALUES A NOAEL of 40 mg/kg b.w. per day for systemic effects in the repeated dose key study and the developmental toxicity key study and an extrapolation factor of 100, was used by BfR (2011), resulting in a tolerable dose of 0.4 mg/kg b.w. per day, to estimate margins of safety
15 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
27 Evaluation of DEHP alternatives
for consumer exposure. NICNAS (2007) used the same NOAEL to derive margins of safety for workers and consumer exposure.
1.8.3 CLASSIFICATION
1.8.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.8.3.2 Classification and labeling inventory database16 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: None
1.8.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): A 63‐years old male volunteer received an unspecified single oral dose of DPHP. The substance was hydrolysed to the respective monoester, which was apparently further metabolised. 34 % of the applied dose was excreted in the urine within 61 h, only <1 % of the applied dose in the form of the monoester, most of it as oxidised monoesters (bearing a hydroxyl‐ or keto group (approx.. 15‐17% each), less amounts (<5%) oxidised to the carbonic acid) (Wittassek and Angerer, 2008). DPHP was slightly irritating in guideline studies to skin or eyes and did not show sensitising properties in guinea pigs (NICNAS, 2007; Versar Inc., 2011). The repeated dose key study is a 90‐days rat feeding study (acc. to guidelines EU B.26 and OECD 408) with a range of 500, 2500 and 15000 ppm in diet (body doses of 36‐42, 181‐211 and 1187‐1344 mg/kg b.w. per day for males‐females, respectively). Effects at the highest dose were slightly, but significantly delayed growth, reduced haemoglobin and haematocrit, increased platelet counts, several clinical chemistry alterations, increased absolute liver weights and decreased absolute adrenal weights. Liver cell hypertrophy was accompanied by peroxisome proliferation, basophilic (thyrotrophic) cells in the anterior part of the pituitary gland in male rats were increased, and there was hypertrophy of the follicular epithelium of the thyroid glands in both sexes. At 2500 ppm in diet the liver cyanide‐insensitive palmitoyl‐ Coenzyme A‐oxidation was still increased and the histological alterations in liver, thyroid and pituitary gland were still observable. In the registration dossier, according to the endpoint study record reported there, the mid dose of 181‐211 (averaged 196) mg/kg b.w. per day was considered to be the NOAEL (disregarding peroxisome proliferation).
16 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
28 Evaluation of DEHP alternatives
NICNAS (2007) and BfR (2011) considered the liver and thyroid effects as relevant treatment‐ related effects and derived a NOAEL of 500 ppm (averaged dose 39‐40 mg/kg b.w. per day). NICNAS (2007) stated that the test substance was Di(isodecyl) phthalate (DIDP), but obviously it was DPHP. Versar Inc. (2011) reports a further 90‐days rat feeding study with dietary concentrations of 0, 500, 5,000 or 12,000 ppm (40, 420 or 1000 mg/kg b.w. per day). Food consumption and body weight gain was reduced at the highest dose. Red blood cell counts, haemoglobin, and haematocrit, and increased platelet counts were reduced in males at ≥ 420 mg/kg b.w. per day, and the livers of these animals showed histopathological lesions consistent with peroxisome proliferation. A vacuolization of the zona glomerulosa of the adrenals was evident in all treated animals of both sexes. Reproductive parameters of males were unaffected, except a decrease in sperm velocity at the highest dose. According to Versar Inc. (2011), this study was poorly reported and no definite conclusions can be drawn. As there is no long‐term study with DPHP, a combined toxicity/carcinogenicity study by Cho et al. (2008; 2010) with the structurally related Di‐isodecyl phthalate (DIDP) has to be discussed for hazard characterisation. Spongiosis hepatis is a typical effect of DIDP (and also Di‐isononyl phthalate, DINP) and the LOAEL of 22 mg/kg b.w. per day was chosen as critical LOAEL for repeated dose toxicity for DIDP by ECHA (2012). However, despite the great similarities between DPHP, DIDP and DINP, the toxic action seems to be somewhat different, as spongiosis hepatis was only observed after exposure to DIDP and DINP. Therefore the LOAEL for chronic exposure cannot be used for risk assessment of DPHP. The key study for reproductive toxicity is an OECD 416 two‐generation feeding study in rats with dietary concentrations corresponding to body doses of 40, 200 or 600 mg/kg b.w. per day. The highest dose resulted in reduced body weight gain in the F0 and F1 generation and reduced foetal weights in the F2 generation. Reproductive or further developmental effects were not observed. Systemic toxicity was evident at doses of 200 mg/kg b.w. per day in liver, kidneys and thyroid, at 600 mg/kg b.w. per day the pituitary gland was also affected. Therefore the NOAEL of this study was 40 mg/kg b.w. per day for systemic toxicity, 200 mg/kg b.w. per day for developmental and 600 mg/kg b.w. per day for reproductive effects. In the subchronic rat study referred by Versar Inc. (2011), see above, reproductive parameters of males were unaffected, except a decrease in sperm velocity at the highest dose of 1000 mg/kg b.w. per day. The toxicological significance in absence of other effects on sperm is unclear. No significant effects on reproduction were reported after exposure of rats to doses up to 1500 mg/kg b.w. per day for 3 months, but study details are not provided (Fabjan et al., 2006). The key study for developmental effects (according to guideline OECD 414) covered a dose range of 40, 200 or 1000 mg/kg b.w. per day, given to pregnant rats on gestation days 6‐19. The LOAEL for maternal and developmental effects was 1000 mg/kg b.w. per day, based on reduced maternal weight gain and increased post‐implantation losses, skeletal and visceral variations. No teratogenicity was observed. The NOAEL of this study was 200 mg/kg b.w. per day.
29 Evaluation of DEHP alternatives
The substance was not mutagenic (with and without metabolic activation) in an Ames test, in a HPRT‐test in CHO cells and a chromosome aberration test in V79 cells (all guideline studies). No information is available from in vivo‐studies. No carcinogenicity study or long term repeated dose could be identified. Cho et al. (2008; 2010) did not observe clearly treatment‐related tumours in a 2‐year toxicity/carcinogenicity study with the structurally related DIDP, where rats were fed diets containing 0.04, 0.2 or 0.8% DIDP (21.9, 110.3 and 479.2 mg/kg b.w. per day for males and 22.9, 128.2 and 619.6 mg/kg b.w. per day for females, respectively). DIDP induced liver adenomas in a 26‐week study in susceptible rasH2 mice (Cho et al., 2011). The increased incidence of liver adenomas in mice was assumed to be related to peroxisome proliferation and therefore they were not considered to be relevant to humans.
1.9 DI-ISODECYLPHTHALATE (DIDP)
CAS‐Nos.: 26761‐40‐0 and 68515‐49‐1 (1,2‐Benzenedicarboxylic acid, di‐C9‐11‐branched alkyl esters, C10‐rich) EC‐Nos.: 247‐977‐1 and 271‐091‐4 Synonyms: 1,2‐Benzenedicarboxylic acid, diisodecyl ester
1.9.1 DNELS FROM ECHA-DISSEMINATION DATA BASE17 For CAS‐No. 68515‐49‐1 (no registration dossier for CAS‐No. 26761‐40‐0)
Table 6: DNELs derived for DIDP
DNEL workers Key studies available from IUCLID long‐term dermal 41.67 mg/kg b.w. per NOAEL in Key study: 2500 mg/kg b.w. per day (systemic) day (systemic), and 500 mg/kg b.w. perday (local): Read‐across, identity of test substance DIDP (CAS 68515‐49‐1), subacute rabbit study, 0.5, 2.5 mL/kg b.w., 5 d/w, 6 weeks) Overall assessment factor: 60 long‐term inhalation 5.29 mg/m³ NOAEL in Key study: 500 mg/m3 (systemic, local (systemic) LOAEL; subacute rat study (500 mg/m3, 6 h/d, 10 exposures within 22 days) Overall assessment factor: 25 General population
17 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
30 Evaluation of DEHP alternatives
long‐term dermal 20.83 mg/kg b.w. per NOAEL in Key study: 2500 mg/kg b.w. per day (systemic) day (systemic), and 500 mg/kg b.w. perday (local): Read‐across, identity of test substance DIDP (CAS 68515‐49‐1), subacute rabbit study, 0.5, 2.5 mL/kg b.w., 5 d/w, 6 weeks) Overall assessment factor: 120 long‐term inhalation 1.3 mg/m3 in Key study, NOAEL: 500 mg/m3 (systemic), LOAEL (systemic) : 500 mg/m3 (local); subacute rat study (500 mg/m3, 6 h/d, 10 exposures within 22 days)Overall assessment factor: 50 long‐term oral 0.75 mg/kg b.w. per NOAEL in Key studies (range: males‐females): (systemic) day Subacute rat study, 280 mg/kg b.w. per day Chronic (carcinogenicity) rat study: 479.2‐619.6 mg/kg b.w. per day (carcinogenicity) and LOAEL 21.9‐22.9 mg/kg b.w. per day (toxicity) Reproductive toxicity: F0: 0,8%, 427‐1424 mg/kg b.w. per day for reproductive effects, 0.2%, 114 – 225 mg/kg b.w. per day for systemic effects, F1: 0.06%, 33 mg/kg b.w. per day for developmental toxicity Developmental toxicity: 500 mg/kg b.w. per day (maternal and foetal) Overall assessment factor: 200
1.9.2 OTHER REGULATORY VALUES The LOAELs and NOAELs for relevant endpoints after oral exposure as listed in the European Union Risk Assessment Report (RAR) (ECB, 2003b) partially deviate from the data in the REACH registration dossier. A subchronic dog study (90 days, performed 1968) with a NOAEL of 15 mg/kg b.w. per day and the NOAEL of 60 mg/kg b.w. per day from a 13‐weeks rat study were chosen by ECB (2003b) as critical for repeated dose toxicity. The critical NOAELs of 33 and 500 mg/kg b.w. per day for the endpoints reproductive toxicity and developmental toxicity, respectively, are identical in both dossiers. The CSTEE (2001a) criticised this approach due to the low quality of the NOAEL of the dog study already mentioned (small number of animals used, and that it was not possible to derive a reliable NOAEL from this study) and used the LOAEL of 77 mg/kg b.w. per day of this study together with the NOAEL of 55‐60 mg/kg b.w. per day from the 13‐weeks rat study (see above) and additionally a NOAEL from a further repeated dose rat study of 57 mg/kg b.w. per day to yield an overall evaluation of a NOAEL for repeated dose studies to be most likely to be in the range of 25 mg/kg mg/kg b.w. per day.
31 Evaluation of DEHP alternatives
EFSA (2005a) derived a TDI of 0.15 mg/kg b.w. per day, based on a NOAEL of 15 mg/kg b.w. per day for liver effects in a subchronic dog study (see data base in ECB, 2003, above) and an uncertainty factor of 100. This TDI was confirmed by SCCP (2007) and and SCHER (2008). CPSC (2010a; c) derived an ADI of 0.13‐0.17 mg/kg b.w. per day, based on the NOAEL of 13‐ 17 mg/kg b.w. per day in a chronic toxicity/carcinogenicity rat study by Cho et al. (2008). Details of this study are described below. The evaluation by ECHA (2012) of the identical study yielded a NOAEL of 22 mg/kg b.w. per day (the discrepancy to the NOAEL given in CPSC (2010) emanates from differences in dose estimates: the actual doses were adjusted upwards by a corrigendum by Cho et al. (2010), which could not be considered by CPSC). The Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) recently re‐evaluated DIDP and isomeric mixtures and listed the substance(s) as carcinogen class 3B (substances suspected of having carcinogenic potential) (Hartwig, 2011).
1.9.3 CLASSIFICATION
1.9.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification (for 68515‐49‐1)
1.9.3.2 Classification and labeling inventory database18 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: CAS‐No. 26761‐40‐0: Skin Irrit. 2 ‐ H315/Eye Irrit. 2 ‐ H319 CAS‐No. 68515‐49‐1: Skin Irrit. 2 ‐ H315 , Eye Irrit. 2 ‐ H319
1.9.4 DATA OVERVIEW AND DISCUSSION There is a multitude of publications and study reports dealing with the toxicity of DIDP and even a fractional amount cannot be considered here in detail. Therefore only the relevant studies with respect to critical LOAELs and NOAELs from the most recent evaluation of DIDP by ECHA (2012) are presented here. Several former evaluations by other institutions have been briefly summarised in section 1.9.2. DIDP was rapidly absorbed following oral exposure of animals and quickly metabolized: at least 56% of the administered dose were detectable in urine and bile within 72 h (NTP, 2003)). DIDP is probably cleaved to isodecyl alcohol and mono‐isodecylphthalate. The latter
18 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
32 Evaluation of DEHP alternatives
was further oxidised at the aliphatic chain to alcohol, ketone or carbonic acid. These metabolites are excreted in urine. Low absorption is assumed via the dermal route. In the EU Risk assessment report for DIDP 4% absorption was assumed in analogy to DINP (2008; 2010). Skin irritation studies with DIDP revealed no or moderate effects, which were reversible with possible desquamation. Observed eye irritating effects are weak and limited to conjunctiva. DIDP is not sensitising. However due to their adjuvant properties the phthalates (including DIDP) have been suggested to be possible contributors to the increasing prevalence of atopic (IgE‐mediated) allergic diseases and asthma. Due to the uncertainty with respect to a critical NOAEL based on the former studies with shortcomings (see 1.9.2), ECHA (2012) used the non‐carcinogenic liver effects reported in the combined chronic toxicity/carcinogenicity study by Cho et al. (2008; 2010) as critical effect dose for repeated dose effects. Rats were fed diets containing 0.04, 0.2 or 0.8% DIDP (21.9, 110.3 and 479.2 mg/kg b.w. per day for males and 22.9, 128.2 and 619.6 mg/kg b.w. per day for females, respectively). Spongiosis hepatis was significantly increased in a dose‐ dependent manner in all male treatment groups (not observable in controls of female animals). This was the most sensitive effect in this study, significant changes in the kidney and further liver effects were observed at the highest dose. Spongiosis hepatis is a typical effect of DIDP and Di‐isononyl phthalate (DINP) and the LOAEL of 22 mg/kg b.w. per day was chosen as critical LOAEL for repeated dose toxicity. Cho et al. (2008) did not observe clearly treatment‐related tumours in the 2‐year carcinogenicity study with rats. DIDP induced liver adenomas in a 26‐week study in susceptible rasH2 mice (Cho et al., 2011). The increased incidence of liver adenomas in mice was assumed to be related to peroxisome proliferation and therefore they were not considered to be relevant to humans. With respect to reproductive and developmental toxicity the most critical effect was the decreased survival of F2 pups observed in two overlapping 2‐generation studies with rats (similar to guideline EU B.35 and EPA OPPTS 870.3800). One of it is the Exxon study already considered by ECB (2003b) and the REACH registration dossier (also published by Huska et al. (2001). Animals received 0.2%, 0.4%, and 0.8% DIDP in diet. The more recent 2‐generation study (Hushka et al., 2001) used lower dietary concentrations of 0.02, 0.06, 0.2 and 0.4% (11‐ 26, 33‐76, 114‐254 and 233‐516 mg/kg b.w. per day for males and 13‐40, 38‐114, 134‐377 and 254‐747 mg/kg b.w. per day for females). Additional endpoints (e.g. AGD and nipple retention) were also examined in this study. Both studies revealed a LOAEL for decreased survival of F2 pups of 0.2% (114 mg/kg b.w. per day), the NOAEL of 33 mg/kg b.w. per day was evident from the study with lower doses (Hushka et al. 2001). The decreased survival of offspring in a 2‐generation study was observed at low doses, however, ECB (2003b) considered the effects as “not severe enough to justify a classification”. A developmental toxicity study by Hellwig et al. (1997) exposed rats to 40, 200 and 1000 mg/kg b.w. per day on gestation days 6‐15. Maternal toxicity (increased liver weight, vaginal haemorrhage and urine smeared fur) was evident at the highest dose. Foetal effects were skeletal variations (rudimentary cervical and/or 14th ribs) at the highest dose
33 Evaluation of DEHP alternatives
and increased incidences of dilated renal pelvis and hydroureter at all dose levels (without dose‐response and significance when litter incidences are compared). A re‐evaluation of the data of Hellwig et al. (1997) led to a reduction of the NOAEL from 200 (e.g. ECB, 2003b) to 40 mg/kg b.w. per day (NTP, 2003), based on an increase in total foetal variations per litter. This view was confirmed by ECHA (2012). Waterman et al. (1999) exposed pregnant rats to 100, 500 and 1000 mg/kg b.w. per day on gestation days 6‐15 (acc. to guideline Official Journal of European Communities L 133). The NOAEL for maternal effects (transient reduced body weight gain) as well as foetal effects (significant increases in skeletal variations) was considered to be 100 mg/kg b.w. per day by ECHA (2012). This is in contrast to the evaluation of the identical study by ECB (2003b) and the REACH registration dossier, where it was reported with a NOAEL of 500 mg/kg b.w. per day. The lower NOAEL was justified by a statistical re‐evaluation showing that a NOAEL of 100 mg/kg b.w. per day was more appropriate based on the incidence of cervical and accessory 14th ribs than the NOAEL of 500 mg/kg b.w. per day. This view was also accepted by the sponsor of the study (NTP, 2003). However, in view of the effects in the 2‐generation studies even the lower NOAELs of the two developmental toxicity studies are not critical for deriving the DNEL, but only supporting. DIDP was not mutagenic in bacterial mutation assays (with and without metabolic activation) and in a mouse lymphoma assay in vitro. It was not clastogenic in a mouse micronucleus assay in vivo. Therefore DIDP was not considered to be a genotoxic agent. No evidence of carcinogenicity comes from the study by Cho et al. (2008) described already above. Further information: The available studies do not indicate a substantial antiandrogenic or estrogenic activity of DIDP (ECHA, 2012).
1.10 DI-ISONONYL-1,2-CYCLOHEXANEDICARBOXYLATE (DINCH)
CAS‐Nos.: EU 166412‐78‐8, USA and Canada 474919‐59‐0 EC‐No.: 431‐890‐2 Synonyms: HEXAMOLL, Diisononyl hexahydrophthalate,
1.10.1 DNELS FROM ECHA-DISSEMINATION DATA BASE19
Table 7: DNELs derived for DINCH
DNEL workers Key studies available from IUCLID
19 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
34 Evaluation of DEHP alternatives
long‐term dermal 41 mg/kg b.w. per day No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term inhalation 35 mg/m³ No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated
General population long‐term dermal 25 mg/kg b.w. per day No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term inhalation 21 mg/m3 No key study, probably route‐to‐route (systemic) extrapolation Overall assessment factor: not stated long‐term oral 2 mg/kg b.w. per day NOAEL in Key studies (range: males‐females): (systemic) Repeated dose study: 107.1‐389.4 mg/kg b.w. per day (subchronic rat study with dietary exposure, no further details) Reproductive toxicity: general toxicity: F0: 1000 mg/kg b.w. per day, F1 100 mg/kg b.w. per day, developmental toxicity (F1 and F2): 1000 mg/kg b.w. per day (2‐generation rat study with dietary exposure, no further details) Developmental toxicity: 1200 mg/kg b.w. per day (maternal and foetal) (rat gavage study, no further details); 1000 mg/kg b.w. per day (reproductive performance/systemic toxicity as well as pre‐ /postnatal developmental effects (rat gavage study, no further details) Developmental toxicity: 1000 mg/kg b.w. per day (maternal and foetal) (rabbit study with dietary exposure, no further details) Overall assessment factor: not stated
1.10.2 OTHER REGULATORY VALUES EFSA (2006): A TDI 1 mg/kg b.w. per day was derived based on a NOAEL of 100 mg/kg b.w. per day in a 2‐generation rat study for renal effects and a default uncertainty factor of 100.
35 Evaluation of DEHP alternatives
The substance was listed in the Scientific Committee on food (SCF) list 2 (“Substances for which this Committee has established a TDI or a t‐TDI.”) NICNAS (2008) derived a TDI of 0.4 mg/kg b.w. per day, based on kidney effects in males in a combined chronic toxicity/carcinogenicity study with a NOAEL of 40 mg/kg b.w. per day and an overall safety factor of 100.
1.10.3 CLASSIFICATION
1.10.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.10.3.2 Classification and labeling inventory database20 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: None
1.10.4 DATA OVERVIEW AND DISCUSSION The key studies in the registration dossier (available via the ECHA website, Information on chemicals) are presented with only few details. Supporting information comes from other references as indicated below. DINCH is rapidly absorbed after oral administration and readily eliminated. After 48 hours more than 90% is excreted via urine and mainly via faeces. Bile and urine contained up to 50% of the administered dose. No information was found with respect to dermal absorption, but no systemic toxicity has been observed in acute dermal studies, indicating low absorption. 10% dermal absorption was assumed (Maag et al., 2010). The main metabolites of DINCH in rats is the monoisononyl ester (as glucuronide conjugate), which is the most abundant metabolite in bile, and the (unconjugated) urinary metabolites cyclohexane‐1,2‐ dicarboxylic acid and monohydroxyisononyl ester (Maag et al., 2010; Silva et al., 2012). DINCH was slightly irritating to the skin of rabbits (study acc. to OECD 404), mean scores for erythema were 2.0 in one animal and 1.7 in two animals. DINCH was not irritating to the eyes of rabbits (study acc. to OECD 405). No skin sensitisation was observed in a guinea pig maximisation test (study acc. to OECD 406) (BASF, 2010; Maag et al., 2010; NICNAS, 2008). In a repeated dose toxicity rat study (acc. to OECD 408) the substance was administered for 90‐days at dietary concentrations of 1500, 4500 and 15000 ppm. The NOAEL was 107.1‐ 389.4 mg/kg b.w. per day (males‐females, respectively), based on kidney weight changes in both sexes and the appearance of degenerated epithelial cells in the urine of males (BASF, 2010; EFSA, 2006; Maag et al., 2010; NICNAS, 2008).
20 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
36 Evaluation of DEHP alternatives
In a combined chronic toxicity/carcinogenicity study (acc. to OECD 453) rats were fed DINCH in doses of 40, 200 or 1,000 mg/kg b.w. per day. After 24 months of treatment, dose‐related follicular cell hyperplasia and increased number of follicular adenomas were observed in the thyroid glands of male rats administered ≥ 200 mg/kg b.w. per day and females at 1,000 mg/kg b.w. per day. However, thyroid effects in rats are probably secondary effects of liver enzyme induction and therefore of limited relevance to humans. This is supported by further studies on enzyme induction and cell proliferation (see below). Based on liver weight changes (both sexes) and kidney weight changes (males), the NOAEL was 40 mg/kg b.w. per day for males and 200 mg/kg b.w. per day for females. A significant increase in the number of mammary fibroadenomas of high dose females was not considered to be treatment‐ related, as the incidence in the control group was very low and the incidence in the high‐ dose group was only marginally higher than the historical incidence (BASF, 2010; EFSA, 2006; Maag et al., 2010; NICNAS, 2008). Remark: Deposition of α2μ‐microglobulin was observed in the proximal tubules of the renal cortex in all treated males in the 90‐day study, but not in the 2‐year study. The α2μ‐ microglobulin deposition is a specific effect in male rats without relevance for humans. However, kidney weight increases were also observed in female animals (NICNAS, 2008). A one‐generation reproduction toxicity test combined with a developmental toxicity test (similar to OECD 414 and OECD 415) with rats reported no adverse effects, the NOAEL for maternal and development toxicity was 1,000 mg/kg b.w. per day, the highest dose tested. Rats were exposed to 100, 300 or 1,000 mg/kg b.w. per day in a two‐generation study (not reported in the registration dossier. The NOAEL for fertility and reproductive performance was reported to be 1,000 mg/kg b.w. per day for the F0 and F1 generations. This was also the NOAEL for general toxicity of the F0 generation, and 100 mg/kg b.w. per day was the NOAEL for the F1 rats (vacuolization of kidney tubular epithelia in males and flaky thyroid follicular colloid in females at higher doses). No developmental toxicity was observed in both F1 and F2 generations, the NOAEL was 1,000 mg/kg b.w. per day (BASF, 2010; EFSA, 2006; Maag et al., 2010; NICNAS, 2008). Remark: The treatment‐related vacuolisation of the tubular epithelia of male F1 animals in the two‐generation study is considered as a relevant effect of treatment (NICNAS, 2008). Rabbits were administered doses of 100‐1,000 mg/kg b.w. per day via the diet in a developmental toxicity study (acc. to OECD 414). No adverse effects were reported, the NOAEL was ≥ 1,000 mg/kg b.w. per day for both maternal and foetal effects. In a developmental toxicity rat study (acc. to OECD 414) there were also no adverse effect, the NOAEL was ≥ 1,200 mg/kg b.w. per day, the highest dose tested (BASF, 2010; EFSA, 2006; Maag et al., 2010; NICNAS, 2008). DINCH did not produce mutagenicity in Ames tests (OECD 471) or in in vitro mammalian CHO cells with and without metabolic activation. No clastogenic activity was seen in a chromosome aberration assay (OECD 473) with and without activation. DINCH was also not found to be mutagenic in an in vivo mouse micronucleus test (OECD 474) (BASF, 2010; EFSA, 2006; Maag et al., 2010; NICNAS, 2008).
37 Evaluation of DEHP alternatives
The increased incidence of fibroadenomas observed in female rats of the combined chronic toxicity/carcinogenicity study is considered not to be related to treatment (see discussion above). Further information: No peroxisome proliferative effects were observed in studies with DINCH, in contrast to phthalate esters like DINP: the cyanide‐insensitive palmitoyl CoA oxidase activity was unaffected in the 90‐day study, and no peroxisome accumulation was observed in the other repeated dose studies. An increase of iodide uptake into the thyroid and the absence of radiolabelled iodide discharged after co‐administration with perchlorate support the finding that DINCH indirectly promotes the thyroid toxicity in the rat by inducing hepatic metabolic enzyme activities and is therefore not relevant for humans (NICNAS, 2008).
1.11 DI-ISONONYLPHTHALATE (DINP)
CAS‐Nos.: 28553‐12‐0 and 68515‐48‐0 (1,2‐Benzenedicarboxylic acid, di‐C8‐10‐branched alkyl esters, C9‐rich) EC‐Nos.: 249‐079‐5 and 271‐090‐9 Synonyms: 1,2‐Benzenedicarboxylic acid, diisononyl ester
1.11.1 DNELS FROM ECHA-DISSEMINATION DATA BASE21
Table 8: DNELs derived for DINP
DNEL workers Key studies available from IUCLID long‐term dermal 366 mg/kg b.w. per NOAEL in Key study: subchronic dermal rabbit (systemic) day study (read across), systemic NOAEL 2500 mg/kg b.w. per day, local NOAEL 500 mg/kg b.w. per day Overall assessment factor: 12 long‐term inhalation 51.72 mg/m³ NOAEL in Key study: subacute inhalation rat study 3 (systemic) (read across), NOAEC 500 mg/m (signs of irritation) Overall assessment factor: 3 General population long‐term dermal 220 mg/kg b.w. per NOAEL in Key study: subchronic dermal rabbit (systemic) day study (read across), systemic NOAEL 2500 mg/kg b.w. per day, local NOAEL 500 mg/kg b.w. per day
21 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
38 Evaluation of DEHP alternatives
Overall assessment factor: 20 long‐term inhalation 15.3 mg/m3 NOAEL in Key study: subacute inhalation rat study (systemic) (read across), NOAEC 500 mg/m3 (signs of irritation) Overall assessment factor: 5 long‐term oral 4.4 mg/kg b.w. per day NOAEL in Key studies (range: males‐females): (systemic) Chronic rat study, NOAEL 88.3‐108.6 mg/kg b.w. per day (toxicity and carcinogenicity) Reproductive toxicity: rat F0: NOAEL 500 mg/kg b.w. per day F1: BMDL05 0.16‐0.21% :200‐260 mg/kg b.w. per day Developmental toxicity: rat NOAEL 200 mg/kg b.w. per day (maternal), 1000 mg/kg b.w. per day (foetal) Overall assessment factor: 20
The same key study was used to derive DNELs for DIDP, but very different DNELs resulted in this case (DNEL workers long‐term dermal systemic for DIDP: 41.67 mg/kg b.w. per day; DNEL workerslong‐term inhalation 5.29 mg/m³ for DIDP).
1.11.2 OTHER REGULATORY VALUES The LOAELs and NOAELs for relevant endpoints after oral exposure as listed in the European Union Risk Assessment Report (RAR) (2003a) partially deviate from the data in the REACH registration dossier. The data base and NOAEL for repeated dose toxicity is identical in both documents, the reproductive toxicity study was evaluated with a LOAEL of 0.2% (instead of BMDL05 of 0.16‐0.21%), and another developmental toxicity with a NOAEL of 500 mg/kg b.w. per day was used for risk assessment in the RAR (details of the studies are presented in section 1.11.4). The NOAEL of 88 mg/kg b.w. per day was also confirmed by ECPI (2009), but the authors stated that “the true NAEL (No Adverse Effect Level) would lie between 15 and 152 mg/kg b.w. per day (a NOAEL of 15 and LOAEL of 152 mg/kg b.w. per day in the Exxon (1986) study and a NOAEL of 88.3 and LOAEL of 359 mg/kg b.w. per day in the Aristech 1994 study).” Further details on these studies are reported below. The CSTEE (2001b) also considered the chronic study in rats by Exxon (1986) also published by Lington et al. (1997) . This reports a NOAEL of 15 mg/kg b.w. per day, CSTEE (2001b) criticised this approach and proposed the use of benchmark doses of 12‐15 mg/kg b.w. per day, calculated from these two studies (performed by CPSC, see below). The Lington et al. (1997) data were discussed by ECB (2003a), but not included in the risk assessment.
39 Evaluation of DEHP alternatives
EFSA (2005b) considered the NOAEL of 15 mg/kg b.w. per day as critical to establish a TDI of 0.15 mg/kg b.w. per day. This approach was confirmed by SCCP (2007) and SCHER (2008). SCENIHR (2008) did not re‐evaluate the toxicity of DINP, but reports the NOAEL of 12‐15 mg/kg b.w. per day derived by CSTEE (2001). CPSC (2010d) derived an ADI of 0.12 mg/kg b.w. per day, based on the benchmark dose for liver effects from the Lington et al. (1997) study. ECHA (2012) used the NOAEL of 15‐18 mg/kg b.w. per day from the same study. The authors criticised the use of the NOAEL of 88 mg/kg b.w. per day by ECB (2003a), because the study by Lington et al (1997) is discussed, but not included in the risk assessment.
1.11.3 CLASSIFICATION
1.11.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.11.3.2 Classification and labeling inventory database22 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: CAS‐No. 68515‐48‐0: Repr. 2 ‐ H361, Skin Irrit. 2 ‐ H315/Eye Irrit. 2 ‐ H319 CAS‐No. 28553‐12‐0: Acute Tox. 4 – H332
1.11.4 DATA OVERVIEW AND DISCUSSION There is a multitude of publications and study reports dealing with the toxicity of DIDP and even a fractional amount cannot be considered here in detail. Therefore only the relevant studies with respect to critical LOAELs and NOAELs from the most recent evaluation of DIDP by ECHA (2012) are presented here. Several former evaluations by other institutions have been summarised in section 1.11.2. In animals and human volunteers, DINP was quickly and extensively absorbed by the oral route. About 50% of the administered dose was excreted in the urine of rats, 33% to 44% in humans. As a significant part of the DINP metabolites is excreted in the faeces via the bile the total absorption is higher. Dermal absorption is expected to be low. In an experimental study, 4% absorption through rat skin was found (ECB, 2003a, ECHA, 2012). Skin and eye irritation studies revealed only very slight effects, which were reversible within short time. DINP is not sensitising. However due to their adjuvant properties the phthalates (including DINP) have been suggested to be possible contributors to the increasing
22 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
40 Evaluation of DEHP alternatives
prevalence of atopic (IgE‐mediated) allergic diseases and asthma. DINP possibly possesses a potential for aggravation of atopic inflammatory processes. The key study in the REACH registration dossier and EU‐RAR is a chronic toxicity / carcinogenicity rat study (acc. to OECD 452) by Aristech (1994) with dietary concentrations of 500, 1500, 6000 and 12000 ppm (29.2, 88.3, 358.7, and 733.2 mg/kg b.w. per day for males and ca. 36.4, 108.6, 442.2, and 885.4 mg/kg b.w. per day for females). A NOAEL of 88‐ 103 mg/kg b.w. per day for males and females, respectively, was derived based on increased kidney weights in both sexes, histopathological findings in kidneys of males and liver toxicity not related to peroxisome proliferation (spongiosis hepatis in males, increased levels of liver transaminases, liver weights) at higher doses. A well performed study by Exxon (1986, also: Lington et al., 1997) exposed rats to dietary levels of 0.03, 0.3 and 0.6% for up to 2 years, corresponding to body doses of 15, 152 and 307 mg/kg b.w. per day for males and 18, 184 and 375 mg/kg b.w. per day for females, respectively. Based on non‐peroxisomal proliferation‐related chronic hepatic and renal effects (spongiosis hepatis in males, increased levels of liver transaminases, increased spleen liver and kidney weights at 0.3% (152‐184 mg/kg b.w. per day) and above, a NOAEL of 0.03% (15‐18 mg/kg b.w. per day) can be derived from this study. In high doses DINP caused reduced tests weights, reduced offspring survival, and visceral and skeletal variations (partially accompanied by maternal toxicity). The evaluation of NOAELS and LOAELs for the majority of reproductive and developmental toxicity by the various institutions e.g. listed under section 1.11.2 revealed these endpoints not to be the critical ones: i.e. the NOAEL from chronic toxicity studies were lower and therefore crucial for risk assessment. However, a LOAEL of 159 mg/kg b.w. per day for developmental effects can be derived from a study by Waterman et al. (2000). This 2‐generation study with rats exposed the animals to dietary levels of 0.2, 0.4 and 0.8% (premating doses for F1 and F2‐generation: 118‐264, 235‐523 and 467‐1090 mg/kg b.w. per day, gestational doses: 133‐153, 271‐307 and 543‐577 mg/kg b.w. per day, post‐partum doses: 159‐395, 347‐758 and 673‐1541 mg/kg b.w. per day). The lowest dietary level caused a decreased body weight in offspring (LOAEL 159 mg/kg b.w. per day), which is almost identical to the LOAEL from the chronic toxicity studies. Parental toxicity was evident at this dose level in form of microscopic liver changes (enlargement of hepatocytes), which may not have influenced the offspring effects. Therefore the LOAEL is almost identical to the LOAEL of the long‐term study (152‐184 mg/kg b.w. per day) by Lington et al. (1997). Furthermore, several recent published studies concerning the antiandrogenic properties of DINP showed effects at doses only slightly higher than the effect doses in chronic studies: Clewell et al. (2011a) exposed pregnant rats on the gestation days (GD) 12‐19 to 50, 250 and 750 mg/kg b.w. per day and observed reduced testicular testosterone level in testis on GD 19 and an increase in multinucleated gonocytes on GD20. A similar effect was observed by Boberg et al. (2011) at the lowest tested dose of 300 mg/kg b.w. per day, administered from GD 7 to PND 21, thus confirming the LOAEL of the study by Clewell et al. The observed effects were transient, but might be relevant in a critical phase of sexual differentiation, and
41 Evaluation of DEHP alternatives
permanent antiandrogenic changes have been observed in other studies at higher doses (ECHA, 2012). Two studies by Lee et al. (2006a; 2006b) are discussed in ECHA (2012), which reported reduced female sexual behaviour and reduced AGD in males, but also weak androgenic activity increasing the AGD in females, at even lower dietary levels (40 ppm in diet, corresponding to approx. 2 mg/kg b.w. per day). However, these results are considered of limited reliability (flaws in data reporting, not confirmed by others) and therefore this very low NOAEL was considered as only supportive, but not critical for risk assessment. In summary, the in vivo findings suggest that DINP has anti‐androgenic (but not estrogenic) potential but may also exhibit its effects through other modes of action (ECHA, 2012). DINP was not mutagenic in vitro in bacterial mutation assays or mammalian gene mutation assay (with and without metabolic activation). It was not clastogenic in one cytogenetic assay in vitro on CHO cells and in one in vivo assay in rat bone marrow cells. Therefore DINP was not considered to be a genotoxic agent. DINP is carcinogenic to rodents. Oral DINP exposure in the diet induced liver tumours in rats and mice of both sexes, kidney tumours in male rats, and mononuclear cell leukemia (MNCL) in rats. However there is a wide consensus, that these tumours are not relevant for humans since they have modes of actions which are considered to be not likely in humans (peroxisome proliferation, alpha‐2u‐globulin accumulation, strain‐specific effect in older F344 rats) Some authors discuss a possible relevance of MNCL for humans, but MNCL is suggested to be caused via a threshold mode of action with a higher NOAEL than that for other effects after repeated exposure (e.g. ECB, 2003a, ECHA, 2012).
1.12 TRIOCTYLTRIMELLITATE (TOTM)
CAS‐No.: 3319‐31‐1 EC‐No.: 222‐020‐0 Synonyms: TEHTM, Tri(2‐ethylhexyl) trimellitate,
1.12.1 DNELS FROM ECHA-DISSEMINATION DATA BASE23
Table 9: DNELs derived for TOTM
DNEL workers Key studies available from IUCLID long‐term dermal 22.5 mg/kg b.w. per No key study, route‐to‐route extrapolation
23 REACH registration dossier from http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances
42 Evaluation of DEHP alternatives
(systemic) day Overall assessment factor: 100 long‐term inhalation 3.97 mg/m³ No key study, route‐to‐route extrapolation (systemic) Overall assessment factor: 100 General population long‐term dermal 11.25 mg/kg b.w. per No key study, route‐to‐route extrapolation (systemic) day Overall assessment factor: 200 long‐term inhalation 0.98 mg/m3 No key study, route‐to‐route extrapolation (systemic) Overall assessment factor: 200 long‐term oral 1.13 mg/kg b.w. per NOAEL in Key studies: (systemic) day Sub chronic rat study: 225 mg/kg b.w. per day Reproductive toxicity: Repeated/reproductive/developmental toxicity screening, rat: 100 mg/kg b.w. per day (males), 1000 mg/kg b.w. per day (females, offspring) Developmental toxicity: 500 mg/kg b.w. per day (postnatal development), 1050 mg/kg b.w. per day (maternal and developmental toxicity) Overall assessment factor: 200
1.12.2 OTHER REGULATORY VALUES TOTM was entered in the Community Rolling Action Plan (CORAP) list covering the years 2012‐2014 due to environmental concerns (ECHA, 2013)24 (see also chapter 2.12).
1.12.3 CLASSIFICATION
1.12.3.1 Classification from REACH registration dossier Data conclusive but not sufficient for classification
1.12.3.2 Classification and labeling inventory database25 Harmonized classification: None Classification proposed by joint submission: Not classified
24 ECHA, European Chemicals Agency, CoRAP list of substances http://echa.europa.eu/web/guest/information‐ on‐chemicals/evaluation/community‐rolling‐action‐plan/corap‐table?search_criteria=203‐090‐1 25 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
43 Evaluation of DEHP alternatives
Other notified classifications: Repr. 2 ‐ H361, Acute Tox. 4 ‐ H312/Eye Irrit. 2 – H319, Skin Irrit. 2 ‐ H315/Eye Irrit. 2 – H319/STOT SE3 – H335
1.12.4 DATA OVERVIEW AND DISCUSSION Results of the key studies in the registration dossier (as available via the ECHA website, Information on chemicals, further references are stated separately): TOTM is only incompletely absorbed after oral exposure: 75% of the administered dose was eliminated in the faeces over 6 days, mostly (85% of faecal amount) as parent compound. No information was found with respect to dermal absorption, but no systemic toxic effects have been observed in acute dermal studies, indicating low absorption. 2‐ethylhexanol and one of the mono esters are actually absorbed after hydrolysis in the gastrointestinal tract. A slow elimination suggests that TOTM has potential to accumulate in body tissues (CPSC, 2010b; SCENIHR, 2008). TOTM was slightly irritating to the skin of rabbits and guinea pigs and did not act as a sensitizer in guinea pig studies. TOTM was not irritating or sensitizing in a HRIPT with human volunteers (CPSC, 2010b; OECD, 2002a; SCENIHR, 2008). A 28 days gavage study in rats (similar to OECD 407; 100, 300 and 1000 mg/kg b.w. per day) did not observe any adverse effect (NOAEL 1000 mg/kg b.w. per day). Another 28‐days rat study showed liver effects indicative of peroxisome proliferation at the highest dose of 0.67% TOTM in diet (650 mg/kg b.w. per day), the NOAEL was 0.2% (184 mg/kg b.w. per day). The key study for repeated dose toxicity was a 90 days rat study (according to OECD 408; 50, 225 and 1000 mg/kg b.w. per day via diet). The NOAEL of this study was 225 mg/kg b.w. per day, based on minor changes in some blood chemistry parameters, liver weight increase and microscopic pathology in liver and spleen in the high‐dose group. Several other repeated dose studies support these findings and revealed that TOTM is a peroxisome proliferator (CPSC, 2010b; OECD, 2002a). It caused the same spectrum of morphological and biochemical changes in the livers of rats as did DEHP, but was clearly less potent (a dietary level of 2% TOTM produced less peroxisome proliferation and enzyme induction than 0.67% DEHP) (SCENIHR, 2008). A NOAEL of 170 mg/kg b.w. per day for effects in the F0 and F1 generations was derived from a 1‐generation rat study with a dietary exposure of 300, 1800 and 12000 ppm (approx. 28, 170 and 1080 mg/kg mg/kg b.w. per day). The highest dose caused parental increased liver weight, offspring was affected by a reduced total litter weight and mean pup weight gain. Remark: This information is not assignable, as it was only included in a former version of the registration dossier (October 2012), but is no longer present in the dossier version of June 2013.A combined repeated dose toxicity study with reproduction/developmental toxicity screening (acc. to OECD 421) in rats with doses of 100, 300 and 1000 mg/kg b.w. per day revealed decreased spermatocytes and spermatids counts at 300 mg/kg b.w. per day
44 Evaluation of DEHP alternatives
and above. No other toxic effects were evident (NOAEL 100 mg/kg b.w. per day for males, 1000 mg/kg b.w. per day for females (SCENIHR, 2008). Both pre‐ and postnatal effects were examined in a rat study with daily doses of 100, 500 and 1050 mg/kg b.w. per day on gestation days 6‐19 or gestation day 6 through lactation day 20. No maternal toxicity was observed. Increases in the numbers of foetuses exhibiting displaced testes, renal cavitation, and hydroureter were evident, but were within historical control ranges for these endpoints. A slight but significant increase in the number of male offspring from high‐dose dams with retained areolar regions at post‐natal day 13 was only transient and no longer present at day 18. It was not considered to be toxicologically significant by the authors. Therefore, the high‐dose of 1050 mg/kg b.w. per day was considered by the authors as NOAEL for both maternal and developmental effects. TOTM was not mutagenic in several Ames tests with Salmonell typhimurium strains TA100, TA1535,TA98, TA1537 and Escherichia coli WP2 uvrA. It did not induce gene mutations in CHO cells or unscheduled DNA synthesis in primary rat hepatocytes in vitro. The substance was not clastogenic in Chinese hamster lung cell cultures. TOTM was inactive in a dominant‐ lethal test in mice. The available data suggest that TOTM is not genotoxic (CPSC, 2010b; OECD, 2002a; SCENIHR, 2008). No reliable long‐term carcinogenicity studies are available for TOTM. A less reliable, older study with strain A mice (high sensitivity for the development of lung tumours) did not observe a carcinogenic response (CPSC, 2010b; OECD, 2002a). The REACH registration dossier uses a read‐across of studies with di(2‐ethylhexyl)adipate in rats and mice (similar to OECD 451) with dietary levels of 12000 and 25000 ppm (600 and 1250 mg/kg b.w. per day for rats and 1715, 3570 mg/kg b.w. per day for mice, respectively). The test substance was not carcinogenic to rats. It was carcinogenic for female mice (significant increase in hepatocellular carcinomas) and probably carcinogenic for male mice (non‐significant increase in hepatocellular adenomas). SCENIHR (2008) stated that several compounds containing the 2‐ethylhexyl group showed some hepatocarcinogenic activity, indicating that this moiety is responsible for hepatocarcinogenesis in mice. Therefore these findings might also be relevant for TOTM. As TOTM is a peroxisome proliferator, the underlying mode of action is considered to be not likely in humans (ECHA, 2012). Further information: The substance was tested in human osteoblasts cell lines, devoid of endogenous estrogen receptors, but transfected with estrogen receptor (ER) alpha and beta. It showed an estrogenic action in both cell lines, which was additive with the response of estradiol estradiol (ter Veld et al., 2006).
45 Evaluation of DEHP alternatives
2 Ecotoxicity Hazard profiles
2.1 GENERAL REMARKS
In the following sections, only aquatic data are reviewed as terrestrial or sediment data are only sporadically available and no comparison on the basis of those data is possible. The latter data are only mentioned with regard to PNEC‐values derived for sediment or soil within REACH registration dossier as contained on the ECHA dissemination website. Where reliability categories of studies are mentioned these are always cited from the respective secondary source.
2.2 ALKYLSULPHONIC PHENYL ESTER (ASE, MESAMOLL)
Hazard assessments are available from BUA (BUA, 1996) and the REACH registration dossier as contained on the ECHA dissemination website. Only within REACH registration PNECS were derived.
2.2.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE26 Reported PNEC‐values and a short summary on available data as well as used assessment factors for derivation of PNECs are summarized in Table 10.
Table 10: PNECs from ECHA’s registered substances database
PNEC Conc. Database Aqua (freshwater) 0.002 mg/L No toxicity to aquatic organisms observed (key studies on acute toxicity for 3 trophic levels, RL1) up to solubility limit of 2 mg/L. PNEC derived by AF 1000 obviously on water solubility limit concentration. Aqua (intermittent 0.02 mg/L Same database as above. PNEC derived by AF 100. releases)
STP 100 mg/L Activated sludge respiration inhibition EC50 (3h) >10,000 mg/L. PNEC derived by AF 100.
Sediment (freshwater) 10.03 mg/kg No data available. PNEC derived from PNECfreshwater by dw equilibrium partitioning method.
Soil 2 mg/kg dw No data available. PNEC derived from PNECfreshwater by
26 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
46 Evaluation of DEHP alternatives
equilibrium partitioning method.
Oral 33.33 mg/kg No data on birds available. PNEC obviously derived from food mammalian toxicity data; AF of 90 used.
2.2.2 OTHER REGULATORY VALUES No other values are available.
2.2.3 ENVIRONMENTAL CLASSIFICATION
2.2.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.2.3.2 Classification and labeling inventory database27 Harmonized classification: None Classification proposed by joint submission: no entry Other notified classifications:: Aquatic Chronic 4 ‐ H413
2.2.4 DATA OVERVIEW AND DISCUSSION Water solubility of ASE is very limited (2.2 mg/L at 20°C according to registration dossier); test concentrations above this value are often achieved by solubilizers. The substance was not readily biodegradable (61% within 47 days, Manometric Respirometry Test).
Acute toxicity tests on fish (96 hours, OECD 203 or EU-method C.1) Two reliable static tests in Danio rerio are available (registration dossier), a limit test using saturated solution (2 mg/L, GLP) and another test with concentrations up to 100 mg/L (nominal, no solubilizers). In both tests no lethality was observed (LC0 ≥ 2mg/L and ≥ 100 mg/L, respectively). Also in a third reliable test using Oryzias latipes (limit test, GLP, REACH data‐set) the LC50 was above 100 mg/L nominal concentration (solubilizer).
Acute toxicity tests on aquatic invertebrates (48 hours) Only one reliable test on Daphnia magna performed compliant to GLP (EU‐method C.2, registration dossier) is available. With nominal concentrations up to 100 mg/L (static, no solubilizer) no immobilization was observed (EC0 ≥ 100 mg/L). Further tests on Daphnia magna with technical material are reported (BUA, 1996). Using filtrate from a nominal concentration of 10 g/L, immobilization was observed with dilutions
27 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
47 Evaluation of DEHP alternatives
(EC50 (48h) 0.41 mg/L), however no immobilization was observed using filtrate from more dilute stock solutions (1000 and 100 mg/L). The authors conclude that toxicity was caused most probably by impurities.
Toxicity tests on algae (72 hours) Only one reliable test on Desmodesmus subspicatus performed compliant to GLP (EU‐ method C.3, registration dossier) is available. In a limit test using saturated solution (static, no solubilizer) no adverse effects were observed (EC0 (growth rate) ≥ 2 mg/L). A further test on Desmodesmus subspicatus (reported as Scenedesmus s.) is reported testing the saturated solution prepared at 10 g/L. No toxic effects were observed (BUA, 1996).
Toxicity tests on microorganisms One reliable activated sludge respiration inhibition test (similar to OECD 209) reports a 3h EC50 of > 10 g/L (highest tested concentration). At the highest concentration tested, no respiration inhibition was observed (registration dossier). Available further tests (BUA, 1996) largely corroborate this result (Activated sludge respiration inhibition, Pseudomonas putida, Photobacterium phosphoreum; purity of test item not stated) for stock solutions prepared for the single species tests at nominal concentrations up to 500 mg/L. Slightly inhibiting effects on Photobacterium phosphoreum were observed with saturated solutions prepared at 10 g/L. No further ecotoxicological test results are available.
2.3 ACETYLTRI-N-BUTYL CITRATE (ATBC, CITROFLEX A-4)
The only hazard assessment for ATBC is available from the REACH registration dossier as contained on the ECHA dissemination website.
2.3.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE28 Reported PNEC‐values and a short summary on available data as well as obviously used assessment factors for derivation of PNECs are summarized in Table 11.
28 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances, data as of October 2012: Currently no registration dossier available.
48 Evaluation of DEHP alternatives
Table 11: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) 22 µg/L Fish: LC50 (96h) 38‐60 mg/L; Daphnia: EC50 (48h) 7.82 mg/L – NOEC (21d) ≥ 1.11 mg/L (meas); Algae: NOEC (72h, gr) 4.65 mg/L (meas). PNEC derived by AF 50 on long‐term NOEC from D. magna. Aqua (intermittent 78.2 µg/L Same database as above. PNEC derived by AF 100 on lowest releases) acute L(E)C50 (D. magna, 48h). STP 100 mg/L OECD 209: EC10(3h) >1000 mg/L. PNEC derived by AF 10.
Sediment (freshwater) 41.5 mg/L No data available. PNEC obviously derived from PNECfreshwater by equilibrium partitioning method.
Soil 8.29 mg/kg No data available. PNEC obviously derived from PNECfreshwater dw by equilibrium partitioning method.
Oral 1050 mg/kg No data on birds available. PNEC obviously derived from food mammalian toxicity data.
2.3.2 OTHER REGULATORY VALUES No other values are available.
2.3.3 ENVIRONMENTAL CLASSIFICATION
2.3.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.3.3.2 Classification and labeling inventory database29 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Aquatic Chronic 3 ‐ H412
2.3.4 DATA OVERVIEW AND DISCUSSION Water solubility of ATBC is limited (4.49 mg/L at 20°C, pH 6.7‐6.8) according to registration dossier). The substance was not readily but inherently biodegradable (OECD 302C, 82% within 28d).
29 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
49 Evaluation of DEHP alternatives
Acute toxicity tests on fish Three studies are available and reported in the registration dossier as well as under the High Production Volume Information System (HPVIS) of US EPA30. However, the most relevant 7‐ day prolonged toxicity study on 18‐hour old larval Pimephales promelas performed under GLP and according to U.S. EPA Method 1000.0 is rated reliable without restrictions under HPVIS whereas in the REACH dossier the study was considered as not reliable and is disregarded for risk assessment due to the prolonged exposure time (7 days compared to 96 hours). Obviously no solubilizers were used and the maximum applied nominal concentration was 10 mg/L. Test medium was renewed daily and all determined effect concentrations are based on mean measured concentrations. LC50 after 48 hours and 7d with 95% confidence interval was 2.8 (2.5 ‐ 3.2) mg/L and 1.9 (1.8 ‐ 2.1) mg/L, respectively. The 7d EC50 (effect parameter: dry weight of fish) was 1.4 (0.72 ‐ 2.7) mg/L and the NOEC (7d, fish dry weight) 0.355 mg/L. Two further studies (RL2 according to reach dossier, RL2B according to US‐EPA) with 96 hours exposure time are available (no data on purity, analytical monitoring with unsatisfactory recovery, effect data based on nominal concentrations). In synthetic seawater the LC50 determined on Fundulus heteroclitus is reported as 59 mg/L (nominal, flow through), the LC50 determined on freshwater fish Lepomis macrochirus was between 38 and 60 mg/L (key study in registration dossier). Both studies report sublethal effects at low test item concentrations.
Acute toxicity tests on aquatic invertebrates (48 hours) The most relevant acute toxicity test was performed on Ceriodaphnia dubia compliant to GLP (U.S. EPA’s OPPTS 850.1010) with reliability category 1A (US‐EPA) and 2 (registration dossier). The study was performed without solubilizers and the following mean measured effect concentrations were determined after 48 hours exposure time: LC50 (48h) 7.82 mg/L, NOEC 4.82 mg/L. In the registration dossier a further study on Daphnia magna (Key, RL2) is available (limit test at nominal 1.0 mg/L, no analytical monitoring, only 24 hours exposure time). The 24h EC50 was determined as > 1.0 mg/L nominal test item concentration.
Chronic toxicity test on aquatic invertebrates (21 days) From the registration dossier, a Daphnia magna reproduction test (OECD 211) is available (non‐GLP, analytical monitoring, limit test at 1.5 mg/L nominal concentration). Statistically significant effects on reproduction were determined in the solvent control relative to the control but not between solvent control and treatment (no data on size of effects and no original data reported). The NOEC (21d, reproduction and survival) is reported as ≥1.11 mg/L (mean measured).
Toxicity tests on algae (72 hours)
30 http://www.epa.gov/chemrtk/hpvis/index.html
50 Evaluation of DEHP alternatives
Only one reliable test on Desmodesmus subspicatus performed compliant to GLP (static, no solubilizer; EU‐method C.3) is available (registration dossier). The NOEC (72h, growth rate and yield) was determined as 4.65 mg/L (mean measured), the EC50 (72h, growth rate) as 74.4 mg/L (mean measured).
Toxicity tests on microorganisms The available Activated Sludge Respiration Inhibition study (OECD 209, RL1, registration dossier) resulted in an EC10 (3h) of > 1000 mg/L (nominal concentration). No further ecotoxicological test results are available.
2.4 GLYCERIDES, CASTOR-OIL-MONO-, HYDROGENATED, ACETATES (COMGHA)
The only hazard assessment for COMGHA is available from the National Industrial Chemicals Notification and Assessment Scheme of Australia (NICNAS, 2009).
2.4.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE31 COMGHA is currently not registered under REACH.
2.4.2 OTHER REGULATORY VALUES No other values are available. No PNEC was derived as no median effect concentrations were determined in aquatic toxicity tests. According to NICNAS, COMGHA is considered to be nontoxic to aquatic life at concentrations up to the solubility limit.
2.4.3 ENVIRONMENTAL CLASSIFICATION
2.4.3.1 Classification from registration dossier COMGHA is currently not registered under REACH.
2.4.3.2 Classification and labeling inventory database32 Harmonized classification: No Notified classifications: None
31 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances 32 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
51 Evaluation of DEHP alternatives
2.4.4 DATA OVERVIEW AND DISCUSSION Water solubility of COMGHA is very limited (60‐90 µg/L at 20°C; NICNAS, 2009).. The substance is readily biodegradable (98% in 28 days) and not expected to persist in the environment (NICNAS, 2009).
Acute toxicity tests on fish One study on Danio rerio according to OECD 203 (96 hours, semistatic) is available (NICNAS, 2009). Measured concentrations were substantially lower than nominal concentrations due to hydrophobicity of COMGHA (log Kow = 6.42) and concentrations declined rapidly during the 24 hours till renewal. Due to poor solubility, emulsions prepared with Ultra Turrax were tested. Sublethal and lethal effects were observed in the highest dose range only and were supposed to be mainly attributable to physical effects of substance deposition, especially on the gills (however no specific observations for test item, rather general tendency of hydrophobic substances). After 96 hours, at 0.28 mg/L measured concentration 6 of 10 fish were dead and all of the 10 fish of the next higher concentration of 0.73 mg/L (measured). The study summary concludes from these results the LC50 to be between 0.28 and 0.73 mg/L. However, from the summary data presented (no raw data reported) the LC50 would be rather below 0.28 mg/L, as already 60% of fish were dead at this concentration after 96 hours.
Acute toxicity tests on aquatic invertebrates (48 hours) One study summary on an acute toxicity test with Daphnia magna (48 hours, OECD 202) is available (NICNAS, 2009). Dose levels are not reported (neither nominal nor measured) and although immobilized daphnids were observed at all test concentrations, the numbers of immobilized daphnids per concentration group are not mentioned. Due to low test item solubility in water the substance was tested as an emulsion prepared by Ultra Turrax, thereby achieving concentrations above the water solubility limit. The EC50 determined from probit analysis is reported as 0.92 mg/L (48h, measured).
Toxicity tests on algae (72 hours) One study summary on a growth inhibition test with Pseudokirchneriella subcapitata (72 hours, static, continuous illumination; OECD 201) is available (NICNAS, 2009). Nominal concentrations tested were 0, 2.5, 5, 10, 20, 40, 80, and 160 mg/L. Due to low test item solubility in water the substance was tested as an emulsion prepared by Ultra Turrax, thereby achieving concentrations above the water solubility limit. After 72 hours only 5‐30% of the initial concentrations were detected which was attributed to adsorption of the hydrophobic test item to test flasks. The EC50 (72h, growth rate) is reported as 26 mg/L (measured), the NOEC (72h, growth rate) as 0.28 mg/L (measured). Maag et al. (2010) probably refers to the same study report but relates to nominal test item concentrations while mentioning that 70% to 95% loss over test period was observed. According to this source, the 72h EC50 is 106 mg/L nominal concentration (no data whether this refers to growth rate or yield).
52 Evaluation of DEHP alternatives
Toxicity tests on microorganisms Maag et al. (2010) reports the result from an Activated Sludge Respiration Inhibition study (OECD 209). The EC20 (no data on exposure time) was > 143 mg/L (no further data reported). No further ecotoxicological test results are available.
2.5 DI(2-ETHYLHEXYL)ADIPATE (DEHA, DIOCTYLADIPATE, DOA)
Hazard assessments are available from BUA (1997), OECD (2000), Environment Canada (2011) and the REACH registration dossier as contained on the ECHA dissemination website. PNECS were derived within the latter three sources.
2.5.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE33 Reported PNEC‐values and a short summary on available data as well as used assessment factors for derivation of PNECs are summarized in Table 12.
Table 12: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) 3.2 µg/L Fish: LC0 (96h) ≥ 0.78 mg/L; Daphnia: EC0 (48h) 250 mg/L – NOEC (21d) ≥ 0.77 mg/L (meas); Algae: EC20 (72h, bm) 400 mg/L (nom). PNEC obviously set equal to water solubility limit as reported by Letinski et al. (2002). Aqua (intermittent 3.2 µg/L PNEC obviously set equal to water solubility limit as reported releases) by Letinski et al. (2000). STP 35 mg/L OECD 209: NOEC (3h) >350 mg/L; PNEC derived by AF 10
Sediment (freshwater) 15.6 mg/kg No data available. PNEC derived from PNECfreshwater by dw equilibrium partitioning method. Soil 0.865 mg/kg Eisenia fetida: LC50 (14d) 865 mg/kg dw (nom). PNEC dw derived by AF 1000.
Oral ‐‐ No data
2.5.2 OTHER REGULATORY VALUES
Table 13: Further available PNEC values
33 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
53 Evaluation of DEHP alternatives
PNEC Conc. Data base Aqua (freshwater), 3.5 µg/L Assessment factor of 10 on 21‐day MATC (survival, Environment Canada reproduction, growth) in Daphnia magna of 0.035 mg/L (2011) and OECD (Felder et al., 1986). (2000)
2.5.3 ENVIRONMENTAL CLASSIFICATION
2.5.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.5.3.2 Classification and labeling inventory database34 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Aquatic Acute 1 ‐ H400, Aquatic Acute 1 ‐ H400/Aquatic Chronic 1 ‐ H410, Aquatic Acute 1 ‐ H400/Aquatic Chronic 2 ‐ H411
2.5.4 DATA OVERVIEW AND DISCUSSION Water solubility of DEHA is very limited. Only three sources are available. Letinski et al. (2002) reports a solubility of 3.2 µg/L (0.04 µg/L SD) derived by a slow stirring method (16‐ day equilibration time, appr. 1 mg/L initial concentration) in carbon treated well water at 20°C. Using obviously the same or a similar method, Robillard et al. (2008) determined a solubility close to this value of 5.5 (± 0.22) µg/L. Felder et al. (1986) determined a water solubility of 0.78 mg/L (± 0.16 mg/L) at 22°C in deionized water applying slow stirring (equilibration 5 days, sampling after 1,2 or 4 days, initial concentration 100 mL/10L). As experimental details in Felder et al. (1986) are lacking, in spite of slowly stirring and centrifugation performed an artificially high water solubility due to formation of micelles cannot be excluded albeit the different water sources might also influence the result. Thus, solubility in water around 5 µg/L seems to be more probable. Other values for water solubility are artifacts: OECD (2000) mentions an environmental concentration of < 0.5 µg/L (Felder et al., 1986) erroneously as solubility in water besides the other two values. In the REACH registration dossier 3.2 µg/L are reported with reference to OECD (2000)/Felder et al., the origin is however the value of Parkerton et al cited in OECD (2000) and published later (Letinski et al., 2002). DEHA proved to be readily biodegradable in several tests, e.g. OECD 301F (90% within 28d; registration dossier). Other degradation results are summarized in BUA (1997).
34 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
54 Evaluation of DEHP alternatives
Acute toxicity tests on fish Several acute toxicity tests are available (BUA, 1997; CHRIP Japan, o.J.; Environment Canada, 2011; Felder et al., 1986). 96‐hour tests (static, unmeasured) performed by Felder et al. (1986) on Lepomis macrochirus, Pimephales promelas, and Oncorhynchus mykiss according to US‐EPA‐guidelines produced no mortality at concentrations in excess of 100 times the water solubility (i.e. >78 mg/L35) and the NOEC was reported as larger than the water solubility (0.78 mg/L35). In a further test on Oncorhynchus mykiss (Hrudey et al., 1976 in Environment Canada, 2011; 96h, static, measured) the LC50 was determined to be between 54 and 110 mg/L. These high concentrations were achieved due to the self‐emulsifying properties of the test item without solubilizers. The authors suggested a physical coating effect as causative for lethalities observed. Further acute tests without observed effects at concentrations well above the water solubility corroborate these results (Poecilia reticulata, BUA, 1997; Oryzias latipes, CHRIP Japan, 1999).
Chronic toxicity tests on fish In a publication from Japanese Ministry of Environment (2003) test methods were developed using Oryzias latipes (Medaka) as test organism for detection of endocrine disrupting chemicals. As prove of principle several substances were tested including a range of phthalates and DEHA. Low binding affinity or negative results were achieved with receptor binding and transactivation assays for Medaka estrogen receptors and a transactivation assay for Medaka androgen receptor. In a 21 day vitellogenin assay using male fish no statistically significant increase was observed. In the same publication (Japan, 2003) a 70‐day partial life cycle test based on OECD TG 210 supplemented with gonadal histology and vitellogenin (VTG) analyses (60 inidivd. per conc. level, flow through, histology for n=20, 0.71‐87.1 µg/L measured) is reported. Testicular eggs were found in the solvent control (1 of 14 male fish) and in 1 of 10 male fish at DEHA concentration of 7.88 µg/L but not at the two lower and higher concentration levels. At the same concentration of 7.88 µg/L body weight (all fish of concentration group) was significantly increased (p < 0.01) which was not the case for the other concentration groups and the controls. Other parameters including vitellogenin, gonadosomatic and hepatosomatic index were not affected.
Acute toxicity tests on aquatic invertebrates A 96‐hour test (static, unmeasured) was performed by Felder et al. (1986) on Daphnia magna according to US‐EPA‐guidelines using no solubilizer. A LC50 of 0.66 mg/L (95% CI 0.48‐ 0.85) and a NOEC of <0.32 mg/L nominal concentration was reported. From 48 hour tests conducted by Huls AG (1996, in Environment Canada, 2011), CHRIP (1999) and BASF (BUA, 1997) EC50‐values of >1.6 mg/L, >50 mg/L (probably with solubilizer)
35 Water solubility according to Felder et al, 1986
55 Evaluation of DEHP alternatives
and > 500 mg/L (using Tween as solubilizer) were determined, respectively. CHRIP (2005) reports an EC50 (48h) > 3.2 µg/L.
For further invertebrates, LC50‐concentrations larger than the respective highest tested concentrations reported (Environment Canada, 2011; Felder et al., 1986).
Chronic toxicity test on aquatic invertebrates (21 days) All 4 available 21‐day studies on Daphnia magna are summarized in Environment Canada (2011). For the study CHRIP Japan (2005) no further details are available (>0.0032 µg/L). The study by Huls AG equals the key study from registration dossier. The studies performed by Felder et al. (1986) and Robillard et al. (2008) are assessed for reliability by Environment Canada (2011): Robillard et al. (2008) found no effects at an average concentration of 4.4 µg/L, employing a semi‐static test regime. The study was rated as not reliable because of highly variable concentrations at renewal time and very low concentration levels prior to renewal of less than 0.09 µg/L. In the flow‐through study by Felder et al. (1986) performed according to American guidelines (ASTM) actual concentrations were determined by employing radio‐ labeled DEHA and mean measured concentrations were 92.1% of nominal. Results from this study were found to be acceptable by Environment Canada (2011). According to Felder et al. (1986) mean young per adult per reproduction day was significantly affected at measured concentrations of 87 µg/L and 180 µg/L, with a NOEC of 24 µg/L and a LOEC of 52 µg/L (survival, mean adult length, reproduction). For the key study from registration dossier vehicle (MARLOWET R 40) was applied in equal amounts (by weight). Geometric mean measured concentration levels were 0.19, 0.39, 0.77 mg/L in semi‐static test design. The NOEC for reproduction is reported as ≥0.77 mg/L.
Toxicity tests on algae (72 hours) Algae proved to be not pronouncedly sensitive against DEHA exposure. CHRIP Japan (1999, probably employing solubilizer), Felder et al. (1986), Huls AG (in Environment Canada, 2011) and BASF (in BUA, 1997) report EC50‐concentrations (72h, 96h for Felder et al.) of <50 mg/L, >78 mg/L (100x water solubility), >1.4 mg/L, and ≥500 mg/L, respectively.
Toxicity tests on microorganisms In the available Activated Sludge Respiration Inhibition study (key study in registration dossier, EU Method C.11, RL2) not toxicity to microorganisms was observed: NOEC (3h) ≥350 mg/L. This study probably equals the study by Huls AG (1996) reviewed in Environment Canada (2011). Further studies support this result (EC50 Microtox assay >1000 mg/L and EC50 Pseudomonas inhibition test >10 g/L(BUA, 1997; Environment Canada, 2011).
56 Evaluation of DEHP alternatives
2.6 DIOCTYLSEBACATE (DIETHYLHEXYLSEBACATE) (DEHS)
The only hazard assessment for DEHS is available from US‐EPA High Production Volume Challenge Program (screening level). Ecotoxicity data for DEHS are published via High Production Volume Information System (HPVIS)36 and a screening assessment of the Diesters Category (including DEHS) is published within the Supporting Documents for Initial Risk- Based Prioritization of High Production Volume Chemicals37
2.6.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE38 DEHS is currently not registered under REACH.
2.6.2 OTHER REGULATORY VALUES No regulatory values are available. No PNEC was derived as no median effect concentrations were determined in aquatic toxicity tests with DEHS. According to US‐EPA HPV program compounds from the diesters category at and above C20 (including DEHS with C26) pose low acute and chronic hazard to aquatic plants, aquatic invertebrates and fish mainly due to their low water solubility.
2.6.3 ENVIRONMENTAL CLASSIFICATION
2.6.3.1 Classification from registration dossier DEHS is currently not registered under REACH.
2.6.3.2 Classification and labeling inventory database39 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Not classified for environmental hazards
2.6.4 DATA OVERVIEW AND DISCUSSION Water solubility of DEHS is very poor concluding from estimated (calculated40) values ‐6 ‐5 (5.15*10 ‐ 1.05*10 mg/L) and from other members of the diesters category. Within this category, the C26 representative adipic acid, diisodecyl ester has an experimentally determined water solubility of 4.4*10‐5 mg/L. The substance is readily biodegradable
36 http://ofmpub.epa.gov/oppthpv/quicksearch.display?pChem=101124 37 http://www.epa.gov/chemrtk/hpvis/rbp/Cat_Diesters_Web_SuppDocs_Sept2008.pdf 38 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances 39 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database 40 Using US-EPA’s EPI Suite
57 Evaluation of DEHP alternatives
however failing the 10‐day window (65% within 28 days). According to the screening assessment for the diesters category these compounds have a low potential to persist in the environment (deduced from ready biodegradability tests for category members and supporting compounds).
Acute toxicity tests on fish A study summary on a 96 hour study with Leuciscus idus under semistatic test regime is available (OECD 203). The study was performed as a limit test with a water accommodated fraction (WAF) prepared at 1000 mg/L nominal concentration. Analytical monitoring was done by TOC‐analysis of fresh and old media, however the only information given in the study summary is that determined concentrations in WAF test solutions were very low. No mortality was observed at the limit concentration (WAF, i.e. saturated solution). No information on sublethal effects is given in the study summary. Reliability rating performed by US‐EPA is reliable with restrictions (RL 2). Thus, the determined effect concentration is: LC50 (96h) > 1000 mg/L (nominal, WAF).
Acute toxicity tests on aquatic invertebrates A study summary on a 48 hour study with Daphnia magna under static test regime is available (OECD 202). The study was performed as a limit test with a water accommodated fraction (WAF) prepared at 1000 mg/L nominal concentration. Analytical monitoring was done by TOC‐analysis at 0 and 48 hours, however the only information given in the study summary is that determined concentrations indicated presence of test material in WAF test solutions but concentrations were very low. No immobilization was observed at the limit concentration (WAF, i.e. saturated solution). Reliability rating performed by US‐EPA is reliable with restrictions (RL 2). Thus, the determined effect concentration is: EC50 (48h) > 1000 mg/L (nominal, WAF).
Toxicity tests on algae (72 hours) A study summary on a 72 hour study with Scenedesmus subspicatus under static test regime is available (OECD 201). The study was performed as a limit test with a water accommodated fraction (WAF) prepared originally at 2000 mg/L nominal concentration and subsequently diluted with algal suspension to the nominal test item limit concentration of 1000 mg/L (WAF). Analytical monitoring was done by TOC‐analysis at 0 and 72 hours, however the only information given in the study summary is that determined concentrations showed very low test item concentrations at 0 hours. No algal growth inhibition was observed at the limit concentration (WAF, i.e. saturated solution). Reliability rating performed by US‐EPA is reliable with restrictions (RL 2). Thus, the determined effect concentration is: EC50 (72h, growth rate) > 1000 mg/L (nominal, WAF).
Toxicity tests on microorganisms No test data on microorganism toxicity are available. However, a study summary on a ready biodegradability test similar to OECD 301B (CO2‐evolution) is published under the HPV
58 Evaluation of DEHP alternatives
program. Within this test a toxicity control (with test item and reference substance) showed no inhibitory effects on biodegradation of reference item at test item concentrations applied in the test (20 mg C/L). Thus, at 20 mg C/L corresponding to 27.4 mg/L test item concentration microorganism toxicity is not expected. Higher concentrations had not been tested.
2.7 DI(2-ETHYLHEXYL) TEREPHTALATE (DEHT, DIOCTYLTEREPHTHALATE, DOTP)
Hazard assessments are available from OECD (2003b) and the REACH registration dossier as contained on the ECHA dissemination website. PNECS were derived within the latter source only. Apart from the key study for ready biodegradability in the REACH registration dossier the relevant studies are identical, therefore no further referencing is provided below.
2.7.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE41 Reported PNEC‐values and a short summary on available data as well as used assessment factors for derivation of PNECs are summarized in Table 14
Table 14: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) 0.08 µg/L Fish: LC50/NOEC (7d) ≥ 0.25 mg/L (flow through, meas.) – fish embryo and sac‐fry stages: NOEC (11d,hatch) ≥0.28 mg/L (meas.), NOEC (60d; mort, length, weight) ≥0.28 mg/L; Daphnia: EC50/NOEC (48h) ≥1.4 µg/L (meas.) – NOEC (21d) ≥ 0.76 µg/L (meas.); Algae: NOEC (72h, gr/bm) ≥0.86 mg/L (meas.). PNEC derived using AF of 10 on the chronic NOEC for Daphnia.
Aqua (intermittent 0.014 µg/L Same database as above. PNEC derived by AF 100 on lowest releases) acute L(E)C50 (D. magna, 48h). STP 1 mg/L OECD 209: NOEC (3h) ≥10 mg/L. PNEC derived using AF 10. Sediment (freshwater) 8.28 mg/kg Chironomus (OECD218): NOEC (28d) 180 mg/kg sed dw. dw PNEC‐derived using AF 100 (derivation of PNEC not reproducible from information given)).
41 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
59 Evaluation of DEHP alternatives
PNEC Conc. Data base Soil 15 µg/kg dw Plants: Germination EC50 (14d; Raphanus sativus & Lolium perenne, growth) >1.4 mg/L (meas), EC50 (14d; Glycine max, growth) >1.5 mg/L (meas) – PNEC‐derivation using AF 1000, extrapolation method partition coefficient (derivation of PNEC not reproducible from information given)
Oral 52.7 mg/kg No data food
2.7.2 OTHER REGULATORY VALUES No other values are available.
2.7.3 ENVIRONMENTAL CLASSIFICATION
2.7.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.7.3.2 Classification and labeling inventory database42 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Aquatic Chronic 4 – H413
2.7.4 DATA OVERVIEW AND DISCUSSION Water solubility of DEHT is very limited. Using the slow stir method to prevent formation of micelles, a water solubility of 0.4 µg/L in distilled deionized water had been determined at 22.5 °C (reliable study). DEHT proved to be readily biodegradable in a reliable study (RL 1) performed according to OECD 301B (73% within 28d; registration dossier).
Acute toxicity tests on fish Acute tests were performed on Pimephales promelas (96 h, static) and Oncorhynchus mykiss (7 d, flow through, RL1). Up to the nominal concentration of 984.0 mg/L no mortality was observed (unmeasured). For the study on Oncorhynchus mykiss acetone was used to aid
42 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
60 Evaluation of DEHP alternatives
solubilization. No mortality or sub‐lethal effects were observed up to the highest measured concentration of 250 µg/L (NOEC).
Chronic toxicity tests on fish In a chronic fish test on Oncorhynchus mykiss (71 d, flow through, RL1) for embryo and sac‐ fry stages (sub)lethal effects were assessed. The study was performed according to a proposed recommended bioassay procedure for egg and fry stages of freshwater fish from 1972 by US‐EPA. Acetone was used to aid solubilization. No mortality or sub‐lethal effects (hatchability, growth) were observed up to the highest measured concentration of 280 µg/L (NOEC).
Acute toxicity tests on aquatic invertebrates Reliable tests on Daphnia magna (48 h, static), Planorbella trivolvis (aquatic snail; 96 h, static) and Crassostrea virginica (Eastern Oyster; 96 h, flow through) were performed and no effects observed up to the highest tested concentrations: NOEC Daphnia magna ≥ 1.4 µg/L (survival; measured ‐ solubility enhanced by DMF) NOEC Planorbella trivolvis ≥ 984.0 mg/L (survival; nominal ‐ oily film on surface observed) NOEC Crassostrea virginica ≥ 624 µg/L (survival and shell deposition; measured ‐ solubility enhanced by acetone)
Chronic toxicity test on aquatic invertebrates (21 days) In a 21‐day flow‐through test on Daphnia magna reproduction (according to OECD Guideline 211, RL 1) no adverse effects were observed up to the highest tested concentration of 0.76 µg/L (NOEC survival, reproduction, growth; measured, solubility enhanced by acetone). The following mean measured concentrations had been tested: 0.039, 0.084, 0.17, 0.35 and 0.76 μg/L.
Toxicity tests on algae (72 hours) In a 72 hours static test on Selenastrum capricornutum (new name: Pseudokirchneriella subcapitata) according to OECD 201 (RL 1) no effects up to the highest tested concentration were observed: NOEC (biomass and growth rate) ≥ 860 µg/L (measured – DMF was added to aid solubilization).
Toxicity tests on microorganisms In the available Activated Sludge Respiration Inhibition study (according to OECD 209, RL 1) not toxicity to microorganisms was observed up to the highest tested concentration: NOEC (3h) ≥ 10 mg/L (nominal concentration).
61 Evaluation of DEHP alternatives
2.8 DI(2-PROPYLHEPTYL) PHTHALATE (DPHP)
Hazard assessments for DPHP are available from NICNAS (2007) and the REACH registration dossier as contained on the ECHA dissemination website. No PNECS were derived in these sources. As studies reviewed by (2007) are largely identical to those from the REACH registration dossier, no further referencing to NICNAS is provided for these studies.
2.8.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE43 No PNEC‐values were derived in the registration dossier as no effects were observed in acute and chronic studies with DPHP.
2.8.2 OTHER REGULATORY VALUES No other values are available.
2.8.3 ENVIRONMENTAL CLASSIFICATION
2.8.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.8.3.2 Classification and labeling inventory database44 Harmonized classification: None Classification proposed by joint submission: Not classified
2.8.4 OTHER NOTIFIED CLASSIFICATIONS: NONE DATA OVERVIEW AND DISCUSSION Water solubility of DPHP is very poor with an experimentally determined water solubility of < 0.1 µg/L at 25°C. The substance is readily biodegradable (80‐90% within 28 days; OECD 301B). In a screening test on adsorption/desorption (HPLC‐method) a log Koc > 5.63 was determined.
Acute toxicity tests on fish A reliable 96‐hours acute test on Danio rerio (Zebra fish) is available. The test was performed as a static test with analytical monitoring of test item concentration with the following nominal concentrations: 50, 100, 5000, 10000 mg/L (no solubilizer). The test item was
43 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances 44 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
62 Evaluation of DEHP alternatives
distributed in the test water using a glass rod. Undissolved test substance was visible at all concentrations at the water surface increasing with test item concentration. The LC0 (96 h) was determined as 10,000 mg/L nominal concentration (measured: 278%), thus the LC50 is larger than 10,000 mg/L nominal concentration. Measured concentrations after 96 hours were highly variable with values between 7.5% (100 mg/L nominal) and 278% (10,000 mg/L nominal), being below LOQ at the lowest nominal concentration of 50 mg/L. No further data are available.
Acute toxicity tests on aquatic invertebrates A reliable 48 hour study with Daphnia magna under static test regime is available (EU‐ method C.2, no solubilizers, analytical monitoring). The study was performed with 7 nominal concentration levels (1.56 mg/L to 100 mg/L) prepared by dilution of a water accommodated fraction prepared at 100 mg/L nominal concentration (stirring for 20 hours at 20°C, removal of undissolved material by centrifugation). Actual concentrations were below LOQ (0.1 mg/L) with the exception of the highest tested nominal concentration of 100 mg/L (0.24 mg/L measured). No immobilization was observed up to 12.5 mg/L nominal test item concentration, at the highest concentration of 100 mg/L (WAF, i.e. saturated solution) 3 of 20 daphnids were immobilized (15%). Thus, the determined effect concentrations are: EC50 (48h) > 100 mg/L (nominal, WAF), EC0 (48h) = 50 mg/L (nominal, WAF). No further data are available.
Chronic toxicity test on aquatic invertebrates (21 days) Brown et al. (1998) performed 21‐day reproduction tests with daphnia magna at very high phthalate ester concentrations (1 mg/L nominal) including DPHP. The test design was based on OECD guideline 202, part 2 (1984; now separate OECD guideline 211). This publication is the basis for the robust study summary in the REACH registration dossier (RL2, reliable with restrictions). Marlowet R40 was used at 10 mg/L (below CMC) as dispersant to keep the test items in solution and to reduce surface tension in the test vessels. Test design was semistatic, with renewal three times per week. Analytical verification of test item concentration resulted in mean actual concentration of 99% of nominal. With this test setup, no toxicity was observed for DPHP (NOEC = 1.0 mg/L). No further data are available.
Toxicity tests on algae (72 hours) A reliable 72 hour study with Scenedesmus subspicatus under static test regime is available (OECD 201, analytical monitoring). The study was performed with water accommodated fractions (WAF) prepared originally at 125 mg/L nominal concentration (stirring for 20 h) and subsequently (after removal of undissolved material by filtration through a 0.2 µm membrane filter) diluted to the nominal test item concentrations (12.5, 25, 50, 100 mg/L WAF). In the analytical determinations the test item was below the detection limit (1 mg/L)
63 Evaluation of DEHP alternatives
for all concentration levels assessed (12.5 mg/L, 100 mg/L and stock solution of 125 mg/L). The following (no)effect concentrations were determined:
EC50 (72 h, growth rate and biomass) > 100 mg/L (nominal, WAF);
EC10 (72 h, growth rate and biomass) > 100 mg/L (nominal, WAF); NOEC (72 h, growth rate and biomass) = 25 mg/L (nominal, WAF). No further data are available.
Toxicity tests on microorganisms A reliable Activated Sludge Respiration Inhibition study (according to EU Method C.11) is available. Nominal test concentrations applied were 100, 500 and 1000 mg/L. No toxicity to microorganisms was observed up to the highest tested nominal concentration of 1000 mg/L (slightly stimulating effect on respiration rate). The following effect concentrations were determined:
EC20 (3 hours) > 1000 mg/L nominal concentration
EC50 (3 hours) > 1000 mg/L nominal concentration This is supported by a study summary on a Pseudomonas putida growth inhibition test (NICNAS, 2007) performed with WAFs prepared by dilution of a WAF stock solution of nominal 10 g/L (stirring for 17 hours at room temperature; separation from insoluble material by centrifugation). WAFs between 31.25‐8,000 mg/L were tested (incubation period 16 hours). No inhibiting effects were observed, rather slightly stimulating effects for the highest test item concentrations (WAF) between nominal 1000 and 8000 mg/L). No further data are available.
2.9 DI-ISODECYLPHTHALATE (DIDP)
Hazard assessments are available from ECB (2003b) and the REACH registration dossier (for CAS 68515‐49‐1) as contained on the ECHA dissemination website. PNECS were derived in neither of these sources. Studies contained in the REACH registration dossier are largely identical to studies of the relevant literature, therefore referencing is restricted in those cases to the latter sources. In ECB (2003b) some additional older studies are reviewed not covered by the published literature which however are mentioned here only if relevant additional information can be retrieved for assessment.
64 Evaluation of DEHP alternatives
2.9.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE45 No PNEC‐values were derived in the registration dossier as no effects were observed in acute and chronic studies with DIDP.
2.9.2 OTHER REGULATORY VALUES No other values are available.
2.9.3 ENVIRONMENTAL CLASSIFICATION
2.9.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.9.3.2 Classification and labeling inventory database46
CAS 26761-40-0 Harmonized classification: None Classification proposed by joint submission: No entry Other notified classifications: Aquatic Chronic 2 ‐ H411 Aquatic Acute 1 ‐ H400/Aquatic Chronic 1 ‐ H410 Aquatic Acute 1 ‐ H400
CAS 68515-49-1 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Not classified for environmental hazards
2.9.4 DATA OVERVIEW AND DISCUSSION Water solubility of DIDP is very limited. Using the slow stir method to prevent formation of micelles, a water solubility of 0.17 µg/L at 20 °C in carbon treated well water had been determined (Letinski et al., 2002).
45 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances 46 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
65 Evaluation of DEHP alternatives
DIDP proved to be readily biodegradable but failing 10‐day window (OECD 301F, reliability 2; 67% within 28 days; key study registration dossier). Several other supporting studies are available.
Acute toxicity tests on fish Several 96‐hours acute tests were performed on Pimephales promelas, Oncorhynchus mykiss, Cyprinodon variegatus (sheepshead minnow, salt water), and Lepomis macrochirus (bluegill fish) with no mortalities (no sub‐lethal effects assessed) observed for all these species at measured concentrations slightly above the reported water solubility (between mean measured 0.37 and 1.00 mg/L). Results from static tests were comparable with those with flow‐through regime (Adams et al., 1995). Thus, EC50 was always larger than 0.37 mg/L measured concentration.
Chronic toxicity tests on fish Only one chronic fish toxicity test is available (Patyna et al., 2006). On Medaka (Oryzias latipes) a multigenerational study with emphasis on reproductive and developmental effects of DIDP was performed where DIDP was administered via fish flake diets at a concentration of nominal 20 µg/g (1 µg/g/fish/day; concentration in food analytically confirmed). The study was performed similar to OECD Guideline 210 (Fish, Early‐Life Stage Toxicity Test, flow through, 284 d) with evaluation of two generations. Medaka was selected because of its sensitivity to estrogenic compounds. Several biochemical, individual, and population parameters were evaluated. No statistically significant differences could be observed in regard to survival, development, reproduction, male‐to‐female ratio, gonadal‐somatic index, histological lesions, and EROD activity. However, increased concentrations of testosterone metabolites as marker for induction of hepatic microsomal testosterone hydroxylase were observed for females by factors of about 1.4 to 1.7 compared to solvent control (acetone) which itself had slightly increased levels of metabolites compared to the control. For males levels were only slightly elevated. Obviously this had no impact on gonad weight, eggs per female or the other endpoints monitored.
Acute toxicity tests on aquatic invertebrates A reliable test on Daphnia magna (48 h, static) without the use of solubilizers produced no effects up to the measured concentration of 0.02 mg/L DIDP (Adams et al., 1995). Two further tests on Daphnia magna (48 h, static) using solubilizers report EC50 > 0.32 mg/L (no immobilization observed, with acetone, measured) and EC50 > 1 mg/L (no effects observed, with detergent, nominal). Further tests were performed with mysid shrimp (Mysidopsos bahia, static) and midge (Paratanytarsus parthenogenetica, static) and again no effects were observed (EC50 > 0.08 and 0.64 mg/L measured, respectively).
Chronic toxicity test on aquatic invertebrates (21 days)
66 Evaluation of DEHP alternatives
In reliable 21‐day semi‐static tests on Daphnia magna reproduction (according to OECD Guideline 211) no adverse effects were observed using either no solubilizer and the slow stir method to achieve dissolution (mean measured concentration = NOEC = 3.4 µg/L; registration dossier) or high concentration achieved with dispersant (mean measured concentration = NOEC = 1.0 mg/L; registration dossier). In a reliable flow through test (21 days, survival & reproduction, no solubilizer) however a NOEC and a LOEC of 0.03 and 0.06 mg/L (mean measured; survival), respectively, was determined (Rhodes et al., 1995). As the authors state, concentrations were obviously higher than real water solubility due to micelle/microdroplet formation. As reproduction was not affected from DIDP but only parental survival and often entrapment on the surface together with a visible surface film was observed testing several high molecular weight phthalate esters (Rhodes et al., 1995), physical toxicity might be causal for the observed toxicity also in case of DIDP. This is corroborated by Brown et al. (1998) who performed 21‐day reproduction tests with daphnia magna at very high phthalate ester concentrations (1 mg/L nominal) including DIDP with dispersants (Tween 20 or Marlowet R40) keeping test items in solution and reducing surface tension in the test vessels. With this test setup, no toxicity was observed for DIDP (NOEC = 1.0 mg/L).
Toxicity tests on algae (72 hours) In a reliable 96 hours static test on Selenastrum capricornutum (new name: Pseudokirchneriella subcapitata) no effects up to the measured concentration of 800 µg/L DIDP were observed: NOEC (biomass and growth rate) ≥ 800 µg/L(Adams et al., 1995). Additional results are provided by ECB (2003b): NOEC (Selenastrum capricornutum, 196 h, sonication, measured) ≥ 1.3 mg/L and EC20 (Scenedesmus subspicatus, 72 h, solubilizer, nominal) ≥ 500 mg/L.
Toxicity tests on microorganisms In the available Activated Sludge Respiration Inhibition study (similar to OECD 209, RL 2, registration dossier) not toxicity to microorganisms was observed up to the highest tested concentration, however exposure time was limited to only 30 minutes: NOEC (0.5 h) ≥ 83.3 mg/L (measured concentration).
2.10 DI-ISO-NONYL-1,2-CYCLOHEXANEDICARBOXYLATE (DINCH, HEXAMOLL DINCH)
Hazard assessments for DINCH are available from NICNAS (2008) and the REACH registration dossier as contained on the ECHA dissemination website. PNECS were derived within the latter source only. As studies reviewed by NICNAS (2008) are largely identical to those from the REACH registration dossier, no further referencing to the dossier is provided for these studies.
67 Evaluation of DEHP alternatives
2.10.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE47 Reported PNEC‐values and a short summary on corresponding data base as well as used assessment factors for derivation of PNECs are summarized in Table 15.
Table 15: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) ‐‐ Aqua (intermittent ‐‐ releases) STP ‐‐ Sediment (freshwater) ‐‐ Soil 10 mg/kg dw Eisenia fetida: LC50 (14d) > 1000 mg/kg dw (nom). Plants: NOEC (20d; Avena sativa, Brassica napus & Vicia sativa; emergence & growth) ≥ 1000 mg/kg (nominal); PNEC‐ derivation obviously (no data from dossier) by using AF 100 (chronic data: WOE, see R7.C, p114)
Oral ‐‐
2.10.2 OTHER REGULATORY VALUES No other values are available.
2.10.3 ENVIRONMENTAL CLASSIFICATION
2.10.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.10.3.2 Classification and labeling inventory database48 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: None
47 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances 48 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
68 Evaluation of DEHP alternatives
2.10.4 DATA OVERVIEW AND DISCUSSION Water solubility of DINCH is very poor with an experimentally determined water solubility of < 20 µg/L at 25°C (pH 6.3, pH 7.4; according to registration dossier). The substance is not readily biodegradable (41% within 28 days; OECD 301B). However, the substance is ultimately biodegradable (64% within 38 days and 93% within 60 days) NICNAS (2008).
Acute toxicity tests on fish Studies available from ECHA dissemination database are lacking detailed information. From NICNAS (2008) a study summary on a 96‐hour toxicity test (according to EC Directive 92/69/EEC C.1, no solubilizers) with Brachydanio rerio (Zebra fish) is available (identical to key study in registration dossier). The test was performed as static limit test with a nominal test item concentration of 100 mg/L (no analytical verification). The test item was dispersed in the test water using ultra‐turrax stirrer for approximately one day. Undissolved material was observed at the water surface in the form of droplets during the experiment. The NOEC (96 h; mortality, appearance and behavior) was determined as 100 mg/L, thus the LC50 is larger than 100 mg/L nominal concentration. A further study is available from the registration dossier only (non‐key). The test design was semi‐static and the test organism again Brachydanio rerio (Zebra fish). While up to a duration of 72 hours no mortality was observed (LC50 >100 mg/L), the reported 96 hours LC50 and NOEC is given as ≥ 35 µg/L. It seems like these entries refer to measured concentrations and that it should rather read > 35 µg/L if the value for the NOEC is correct. But no further information is given as to verify these assumptions. No further data are available.
Acute toxicity tests on aquatic invertebrates Studies available from ECHA dissemination database are lacking detailed information. A study summary on a 48 hour study with Daphnia magna under static test regime (NICNAS, 2008) is available (OECD 202, no solubilizers; identical to key study in registration dossier). The study was performed with 4 test item concentrations from 12.5 to 100 mg/L (nominal concentration, no analytical determination). These nominal concentrations were tested as water accommodated fractions (WAF): After stirring of the test item in water, insoluble material was removed by centrifugation and appropriate dilutions used for the treatments were prepared. No immobilization was observed up to 100 mg/L nominal test item concentration (WAF, i.e. saturated solution). Thus, the determined effect concentration is: EC50 (48h) > 100 mg/L (nominal, WAF), EC0 (48h) = 100 mg/L (nominal, WAF). A further study is available from the registration dossier only (non‐key). No data on test design or guideline are given, tested species is given as “other aquatic crustacea: DM”. The NOEC is reported as ≥ 0.034 mg/L, thus probably referring to measured concentrations, but no information is given. No further data are available.
Chronic toxicity test on aquatic invertebrates (21 days)
69 Evaluation of DEHP alternatives
A study summary on a 21‐day semi‐static limit‐test on Daphnia magna reproduction (according to OECD Guideline 211) is available (NICNAS, 2008). The stock solution was prepared at 30 mg/L test item pre‐suspended in 25 µg/L Tween 20 (stirring, sonification, subsequent dilution to 1 L = stock solution). No significant differences between control and treatment were observed at the tested nominal limit concentration of 30 µg/L (21 µg/L measured concentration). Thus the NOEC (21 d; survival, reproduction) is reported as ≥ 21 µg/L (limit water solubility). This study is identical to the one from the registration dossier (but study summary is lacking detailed information). No further data are available.
Toxicity tests on algae (72 hours) A study summary (NICNAS, 2008) on a 72 hour study with Scenedesmus subspicatus under static test regime is available (OECD 201, no analytical monitoring). The study was performed with water accommodated fractions (WAF) prepared originally at 125 mg/L nominal concentration and subsequently (after removal of undissolved material by centrifugation at 17700 g) diluted to the nominal test item concentrations (6.25, 12.5, 25, 50 and 100 mg/L WAF). To prevent adsorption to glass vessels, before start of the test these were incubated over 24 hours at 100 rpm with WAF and subsequently rinsed with water. No algal growth inhibition but stimulation of growth was observed up to the highest concentration (WAF, i.e. saturated solution). Thus, the determined effect concentrations are:
EC50 (72 h, growth rate and biomass) > 100 mg/L (nominal, WAF); NOEC (72 h, growth rate and biomass) ≥ 100 mg/L (nominal, WAF). This study is identical to the key study from the registration dossier (but study summary is lacking detailed information). A further non‐key study is reported in the dossier, with a reported NOEC (72 hours; Desmodesmus subspicatus; growth rate & yiels) > 24 mg/L. No experimental information is given. No further data are available.
Toxicity tests on microorganisms A study summary on an Activated Sludge Respiration Inhibition study (OECD 209) is available (NICNAS, 2008). No toxicity to microorganisms was observed at a nominal test item concentration of 1000 mg/L. Thus the 3‐hour EC50 for DINCH was determined as > 1000 mg/L (nominal concentration). This study is identical to the key study from the registration dossier (but study summary is lacking detailed information). A further non‐key study is reported in the dossier, with a reported NOEC (3 hours) > 2000 mg/L. Neither test guideline nor any other experimental information is given. No further data are available.
70 Evaluation of DEHP alternatives
2.11 DI-ISONONYLPHTHALATE (DINP)
Hazard assessments are available from ECB (ECB, 2003a) and the REACH registration dossiers as contained on the ECHA dissemination website. Studies contained in the REACH registration dossier are largely identical to studies of the relevant literature, therefore referencing is restricted in those cases to the latter sources. In ECB (2003a) some additional older studies are reviewed not covered by the published literature which however are mentioned only if relevant additional information can be retrieved for assessment.
2.11.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE49 Reported PNEC‐values and a short summary on corresponding data base as well as used assessment factors for derivation of PNECs are summarized in Table 16.
Table 16: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) ‐‐ Aqua (intermittent ‐‐ releases) STP ‐‐ Sediment (freshwater) ‐‐ Soil 30 mg/kg dw Eisenia fetida: LC50 (14d) > 7372 mg/kg dw (meas., initial); Eisenia fetida: NOEC (56d, reprod) ≥ 982.4 mg/kg dw (meas., initial); Plants: NOEC (28d; Lactuca sativa; germination & growth; meas., arithmetic mean) ≥ 1387 mg/kg soil dw; Soil microorganisms: NOEC (33d; meas., initial) 9616 mg/kg soil dw PNEC derived using AF of 50
Oral 150000 g/kg No data on birds available. PNEC obviously derived from food mammalian toxicity data; AF of 10 used.
2.11.2 OTHER REGULATORY VALUES No other values are available.
49 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
71 Evaluation of DEHP alternatives
2.11.3 ENVIRONMENTAL CLASSIFICATION
2.11.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.11.3.2 Classification and labeling inventory database50 CAS 68515‐48‐0: Harmonized classification: None Classification proposed by joint submission: Not classifiedOther notified classifications: Aquatic Acute 1 ‐ H400 CAS 28553‐12‐0: Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Aquatic Acute 1 ‐ H400/Aquatic Chronic 1 ‐ H410 Aquatic Acute 1 ‐ H400
2.11.3.3 Other classifications Not classified according to Directive 67/548/EC (ECB, 2003a).
2.11.4 DATA OVERVIEW AND DISCUSSION Water solubility of DINP is very poor with an experimentally determined water solubility of 0.6 µg/L at 21°C (pH 7; according to registration dossier). The substance is readily biodegradable (81% within 28 days; OECD 301B).
Acute toxicity tests on fish Several 96‐hours acute tests were performed on Pimephales promelas, Oncorhynchus mykiss, Cyprinodon variegatus (sheepshead minnow, salt water), and Lepomis macrochirus (bluegill fish) with no mortalities (no sub‐lethal effects assessed) observed for all these species at measured concentrations slightly above the reported water solubility (between mean measured 0.10 and 0.52 mg/L). Results from static tests were comparable with those with flow‐through regime (Adams et al., 1995). Thus, EC50 was always larger than 0.10 mg/L measured concentration. A further 96‐hours acute test was performed on Brachydanio rerio
50 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database
72 Evaluation of DEHP alternatives
at a considerably higher exposure concentration of 102 mg/L (measured, emulsifier), with no lethality observed (LC50 > 102 mg/L).
Chronic toxicity tests on fish Only one chronic fish toxicity test is available (Patyna et al., 2006). On Medaka (Oryzias latipes) a multigenerational study with emphasis on reproductive and developmental effects of DINP had been performed where DINP was administered via fish flake diets at a concentration of nominal 20 µg/g (1 µg/g/fish/day; concentration in food analytically confirmed). The study was performed similar to OECD Guideline 210 (Fish, Early‐Life Stage Toxicity Test, flow through, 284 d) with evaluation of two generations. Medaka was selected because of its sensitivity to estrogenic compounds. Several biochemical, individual, and population parameters were evaluated. No statistically significant differences could be observed in regard to survival, development, reproduction, male‐to‐female ratio, gonadal‐ somatic index, histological lesions, and EROD activity. While posthatch survival for F0 was statistically significantly reduced compared to the untreated control in one assay, this was not the case in both the parallel F0‐assay and both F1‐assays. A significant observation was a transient alteration of red blood cell pigmentation which however was also observed for the solvent control to a similar extent and which had no impact on survival and development. Furthermore increased concentrations of testosterone metabolites as marker for induction of hepatic microsomal testosterone hydroxylase were observed for males by factors of about 2 compared to the control (statistically significant), however not the solvent control (acetone) which itself had slightly increased levels of metabolites compared to the control. Obviously this had however no impact on gonad weight, eggs per female or the other endpoints monitored.
Acute toxicity tests on aquatic invertebrates
Using solubilizer MARLOWET R40 (100 mg/L final concentration) an EC50 (immobilization, 48h) of > 74 mg/L DINP (technical grade, Vestinol 9) was determined for Daphnia magna in a reliable study. Similarly, Brown et al. (1998) performed an acute 48h‐test with daphnia magna employing 1 mg/L (nominal, analytically confirmed) DINP with dispersant (Marlowet R40) keeping test item in solution. No immobilization or flotation of organisms was observed. A reliable test on Daphnia magna (48 h, static) without the use of solubilizers produced no effects up to the measured concentration of 0.06 mg/L DINP (Adams et al., 1995). Further tests were performed with mysid shrimp (Mysidopsos bahia, static) and midge (Paratanytarsus parthenogenetica, static) and again no effects were observed (EC50 > 0.39 and 0.08 mg/L measured, respectively).
Chronic toxicity test on aquatic invertebrates (21 days) In reliable 21‐day semi‐static tests on Daphnia magna reproduction (according to OECD Guideline 211) no adverse effects with statistical significance were observed using either no solubilizer and the slow stir method to achieve dissolution (mean measured concentration =
73 Evaluation of DEHP alternatives
NOEC = 3.6 µg/L; registration dossier) or high concentration achieved with dispersant (mean measured concentration = NOEC = 101 mg/L; registration dossier). In a reliable flow through test (21 days, survival & reproduction, no solubilizer) however a NOEC and a LOEC of 0.034 and 0.089 mg/L (mean measured; survival & reproduction) was determined (Rhodes et al., 1995). As the authors state, concentrations were obviously higher than real water solubility due to micelle/microdroplet formation. As equally survival and reproduction was affected from DIDP and often entrapment on the surface together with a visible surface film was observed testing several high molecular weight phthalate esters (Rhodes et al., 1995), physical toxicity might be causal for the observed toxicity also in case of DINP. This is corroborated from test with other high molecular weight phthalate esters performed in parallel: Either parental survival only or equally parental survival and reproduction was affected but in no case was reproduction more sensitive than parental survival (Rhodes et al., 1995). No further information is however given as to how reproduction may be affected by physical effects, i.e. if neonates were possibly entrapped at the surface at higher concentrations. That surface effects may be crucial for observed effects is corroborated by results from (Rhodes et al., 1995), who performed 21‐day reproduction tests with daphnia magna at very high phthalate ester concentrations (1 mg/L nominal) including DINP with dispersant (Marlowet R40) keeping test items in solution and reducing surface tension in the test vessels. With this test setup, no toxicity was observed for DINP (NOEC = 1.0 mg/L, analytically confirmed).
Toxicity tests on algae (72 hours) In a reliable 72 hours static test on Desmodesmus subspicatus (limit test, solubilizer MARLOWET R 40 1:1) no effects up to the measured concentration of 88 mg/L DINP were observed: NOEC (biomass and growth rate) ≥ 88 mg/L (registration dossier). In a reliable 96 hours static test (no solubilizers) on Selenastrum capricornutum (new name: Pseudokirchneriella subcapitata) no effects up to the measured concentration of 1.8 mg/L DINP were observed: NOEC (biomass and growth rate) ≥ 1.8 mg/L (ECB, 2003a). Additional results are provided by ECB (2003a) corroborating these results.
Toxicity tests on microorganisms In an Activated Sludge Respiration Inhibition study (according to OECD 209, RL 2, registration dossier) no toxicity to microorganisms was observed up to the highest tested concentration, however exposure time was limited to only 30 minutes: NOEC (0.5 h) ≥ 83.9 mg/L (measured concentration). Additionally, the test item was investigated using the Microtox‐assay involving Photobacterium phosphoreum. Tween 20 was used as dispersant. Within 15 minutes no effects in terms of photoluminescence were observed: NOEC (15 min, meas. initial) = 83.9 mg/L.
74 Evaluation of DEHP alternatives
2.12 TRIOCTYLTRIMELLITATE (TOTM, TRI(2-ETHYLHEXYL) TRIMELLITATE, TEHTM)
Hazard assessments are available from OECD (2002b) and the REACH registration dossiers as contained on the ECHA dissemination website. Furthermore, TOTM was assessed within US‐ EPA High Production Volume Challenge Program (screening level). Ecotoxicity data for TOTM are published via High Production Volume Information System (HPVIS)51 and a screening assessment of the Trimellitate Category (including TOTM, Sept. 2009) is published52.
2.12.1 PREDICTED NO EFFECT CONCENTRATIONS (PNECS) FROM ECHA DISSEMINATION DATA BASE53 Reported PNEC‐values and a short summary on corresponding data base as well as used assessment factors for derivation of PNECs are summarized in Table 17.
Table 17: PNECs from ECHA’s registered substances database
PNEC Conc. Data base Aqua (freshwater) 60 ng/L Fish acute (OECD 203) & prolonged (OECD 204): no effects; Daphnia acute (OECD 202, no effects) & reproduction (OECD 211; EC50 (21‐d, reproduction): 89.1 mg/L; NOEC 55.6 mg/L); Algae (OECD 201; no effects, NOEC 100 mg/L) PNEC‐derived using AF of 50 (derivation of PNEC not reproducible from information given)
Aqua (intermittent 30 ng/L PNEC‐derived using AF of 100 (derivation of PNEC not releases) reproducible from information given)
STP 300 ng/L NOEC (OECD 209, 3h) 1000 mg/L PNEC‐derived using AF of 10 (derivation of PNEC ) Sediment (freshwater) 7.4 mg/kg Chironomus riparius: NOEC (28 d, emergence rate) 740 dw mg/kg dw.(measured) PNEC‐derived using AF of 100 Soil 95 µg/kg dw Seedling emergence and growth test (OECD 208), three species: EC50 (17‐18 days) > 100 mg/kg dw. PNEC‐derived using AF of 1000 Oral 125 µg/kg No data on birds available. PNEC obviously derived from food mammalian toxicity data; AF of 90 used.
51 http://ofmpub.epa.gov/oppthpv/quicksearch.display?pChem=100417 52 http://iaspub.epa.gov/oppthpv/hpv_hc_characterization.get_report?doctype=2 53 http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances
75 Evaluation of DEHP alternatives
2.12.2 OTHER REGULATORY VALUES No other values are available.
2.12.3 ENVIRONMENTAL CLASSIFICATION
2.12.3.1 Classification from registration dossier Not classified for environmental hazards (“Data conclusive but not sufficient for classification”).
2.12.3.2 Classification and labeling inventory database54 Harmonized classification: None Classification proposed by joint submission: Not classified Other notified classifications: Aquatic Chronic 4, H413
2.12.4 DATA OVERVIEW AND DISCUSSION Water solubility of TOTM is very poor with an experimentally determined water solubility of 0.386 µg/L at 25°C (key study) to 0.13 mg/L at 25°C (supporting study; according to registration dossier). The substance is neither readily biodegradable (32.9% within 28d, 42.9% within 39d; OECD 301F, registration dossier55) nor inherently biodegradable (12.3% within 28 d based on CO2‐evolution; 4.2% within 28d based on O2‐consumption according OECD 302 C; registration dossier).
Acute toxicity tests on fish A reliable 96‐hours acute test was performed on Oryzias latipes (semi‐static, limit test, hydrogenated castor oil HCO‐40 as solubilizer) and resulted in a LC50 > 100 mg/L (nominal concentration, analytically confirmed). At the limit concentration, 1 from 10 fish died (registration dossier). An additional result is available from OECD (2002b) for Salmo gairdneri (new name: Oncorhynchus mykiss): At the nominal limit concentration of 1 mg/L (no analytical verification, static design) no effects were observed after 96 hours. Further, no effects were observed in a 14‐day prolonged toxicity test with Oryzias latipes (OECD 204, flow‐through, HCO‐40 as solubilizer) at the highest tested concentration (75 mg/L nominal, analytically confirmed to be within 80‐95% of nominal) as reported in the registration dossier.
Chronic toxicity tests on fish
54 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database 55 In the robust study summary of the registration dossier, one replicate excluded due to excessive oxygen consumption due to breach or electrical malfunction was nonetheless included to derive a mean degradation ratio of 46.8% within 28 days, which is considered not to be valid.
76 Evaluation of DEHP alternatives
No data were identified.
Acute toxicity tests on aquatic invertebrates In a reliable acute toxicity test on Daphnia magna (OECD 202, HCO‐40 as solubilizer, static test design, analytical verification of test item concentrations) a 48 h EC50 of > 180 mg/L (nominal concentration) and a 48 h NOEC of 180 mg/L (nominal concentration) was determined. The mean measured concentration at 180 mg/L was 177.5 mg/L (mean) after 48 hours (registration dossier).
From OECD (2002b) a further EC50/NOEC (48 h, no analytical monitoring) of > 1 mg/L is available.
Chronic toxicity test on aquatic invertebrates (21 days) In a reliable 21‐day semi‐static tests on Daphnia magna reproduction (according to OECD Guideline 211, using solubilizer HCO‐40 1:1, analytical confirmation) the following effect values were calculated (nominal concentrations): NOEC (21 ‐day, reproduction): 55.6 mg/L; EC50 (21 ‐day, reproduction): 89.1 mg/L, LC50 (21‐day, parental) > 100 mg/L (registration dossier). A further reliable 21‐day reproduction test on Daphnia magna (flow through) using acetone to aid solubilization (final concentration not given) is available from the registration dossier. The highest nominal concentration applied was 0.1 mg/L. No statistically significant effects were observed: NOEC (21‐d; mortality, reproduction, parental growth) ≥ 0.082 mg/L (measured, geometric mean), LOEC (21‐d; mortality, reproduction, parental growth) > 0.082 mg/L (measured, geometric mean).
Toxicity tests on algae (72 hours) In a reliable 72 hours static limit test (with solubilizer HCO‐40 at 100mg/L) on Selenastrum capricornutum (new name: Pseudokirchnerella subcapitata; OECD 201) no effects were observed at the nominal limit concentration of 100 mg/L (registration dossier). Measured concentrations were 80.6 mg/L (t=0) and 68.8 mg/L (t=72 h).
Toxicity tests on microorganisms In a reliable Activated Sludge Respiration Inhibition study (according to OECD 209, RL 1, registration dossier) no toxicity to microorganisms was observed up to the highest tested concentration: NOEC (3 h) = 1000 mg/L (nominal concentration).
77 Evaluation of DEHP alternatives
3 Migration data for alternative substances for assessment of human exposure
3.1 GENERAL REMARKS
In the context of consumer exposure estimation, a comparison of migration for DEHP and its potential alternatives into a) saliva (for oral exposure) and b) sweat (for dermal exposure) are of crucial importance. For most alternatives, such data are not available. Rather, DEHP and its potential alternatives have been extensively tested in relation to migration from food contact materials (FCM) and medical devices. However, such data differ in several respects from the migration data required for an assessment of consumer exposure from PVC consumer articles. For example, the simulants used for FCM and medical devices testing (such as oils, alkaline water and more acidic simulants (simulant B for FCM: pH 2.5)) differ from the stimulants for consumer articles (neutral saliva and slightly acidic sweat (pH 5.5)). In addition, several other parameters differ (e.g. static FCM testing vs. dynamic testing for migration into saliva during mouthing activities). These and other problems have been extensively discussed in relation to the use of FCM migration data for a migration of chemicals from toys (van Engelen et al., 2008). They equally apply to a comparison of migration from FCM and medical devices with a migration from consumer articles. As a consequence, the following discussion focuses on the (generally sparse) migration data obtained with consumer articles, PVC sheets and toys/childcare articles. The FCM‐related data – primarily those related to extraction with water – are reported for comparison.
3.2 ALKYLSULPHONIC PHENYL ESTER (ASE, MESAMOLL)
One experiment showed a slightly higher extraction of ASE from PVC resin (40% plasticizer) into water (0.03%) compared to DEHP (0.01%), although these values are considered similar by the authors (Maag et al., 2010). No further experimental details are provided.
Tests with FCM found an overall low migration into 10 % ethanol over 10 days at 40°C (EFSA, 2009) and – according to producer’s information – a higher saponification resistance compared to DEHP (Maag et al., 2010; RAC/SEAC, 2012), but these data are not considered relevant to consumer exposure from PVC articles.
Overall, the extraction rate of ASE from PVC resin into water was somewhat higher compared to DEHP in one study with undefined conditions.
78 Evaluation of DEHP alternatives
3.3 ACETYLTRI-N-BUTYL CITRATE (ATBC)
A human volunteer study (5 males and 5 females, 18 to 30 years old) examined the migration of ATBC from PVC disks cut from a custom molded ball and two commercially available articles (a yellow rubber duck toy and a blue shampoo bottle top). Volunteers mouthed the test items, sucked on them and lightly chewed the disks for four consecutive 15 minute sessions. The mean migration rates were 1.53, 1.75 and 2.19 μg/min for the ball, the duck toy and the bottle top, respectively. The two largest subjects showed considerably higher migration rates and the highest migration rate was 10.1 μg ATBC/min (CSTEE, 2004). Since the area of the samples is not given for this unpublished report, the area‐normalised migration cannot be calculated.
The migration of ATBC from a PVC toy with 8% ATBC by sucking and chewing was examined in a 1 h experiment with human volunteers (Wildhack et al., 2001). ATBC migration from the toy was 677 (sucking) and 2255 µg/dm2 (chewing). Additional in vivo experiments were performed with both ATBC and DEHA (see below) migration from PVC plates (17‐39% plasticizer concentration) and showed the migration to be dependent of the shore hardness. ATBC migration range from about 1500 µg/dm2 (sucking, shore hardness 90) to about 5500 µg/dm2 (chewing, shore hardness 60). It is somewhat unclear from the data presentation, whether these data were also obtained during one hour. Related in vitro experiments with dynamic migration using artificial saliva (shaking using two different regimens as well as ultrasonic treatment) yielded considerably higher migration rates and ultrasonic treatment in particular was regarded as not suitable to replace in vivo studies (Wildhack et al., 2001).
CSTEE (CSTEE, 1999) reported the extraction of ATBC in 40 mm PVC discs in comparison to di‐isononylphthalate (DINP, see below), using a saliva simulant at a temperature of 60°C for 24h under static conditions. The loss from the discs is given as 0.8% (at 40% ATBC in disc) and 2.1% (at 60% ATBC in disc). The authors noted the rather extreme conditions in this study, with 40 mm thick disks (about 50 mm diameter) and the high temperature, making it difficult to compare the outcome with results from other studies. The discs were also cleaned with an organic solvent prior to the test. The study may, however, provide a relative statement of a faster extraction of DINP compared to ATBC.
Another experiment showed a higher ATBC extraction from PVC resin (conc. 40%) into water (0.09%) compared to DEHP (0.01%) (Maag et al., 2010). No further experimental details are provided. RAC/SEAC (2012) also noted the higher extractability in water/aqueous solutions compared to DEHP. Overall, migration rates of ATBC into saliva of human volunteers have been established in two different studies and can be used for comparison with other plasticizers (see section 3.3).
79 Evaluation of DEHP alternatives
3.4 GLYCERIDES, CASTOR-OIL-MONO-, HYDROGENATED, ACETATES (COMGHA)
Referring to the results of migration experiments with FCM, NICNAS (2009) noted that the “migration out of consumer products that are not intended to come into contact with foodstuffs is expected to be lower because the temperatures and length of exposure are expected to be lower than the food contact scenarios.” No specific data are reported.
Similarly, COMGHA has been considered to show a lower extractability than DEHP in acidic water solutions and ethanol/water solutions as well as in sunflower oil (RAC/SEAC, 2012). However, no migration data for saliva or sweat simulants are available, preventing any conclusion in relation to migration from consumer articles.
3.5 DI(2-ETHYLHEXYL) ADIPATE (DEHA)
The volunteer study by Wildhack et al. (2001) already mentioned above showed an approximately 3‐fold lower DEHA migration from PVC plates (17‐39% plasticizer concentration) compared to ATBC. DEHA migration ranged from about 500 µg/dm2 (sucking, shore hardness 90) to about 2000 µg/dm2 (chewing, shore hardness 60). It is somewhat unclear from the data presentation, whether these data were also obtained during one hour. As for ATBC, related in vitro experiments with dynamic migration using artificial saliva (shaking using two different regimens as well as ultrasonic treatment) yielded considerably higher migration rates and ultrasonic treatment in particular was regarded as not suitable to replace in vivo studies (Wildhack et al., 2001).
In a water extractability experiment (24 h at 50 °C) with 1 mm PVC sheets with 40% plasticizer, DEHA showed a 10‐fold higher loss (0.1%) compared to DEHP (0.01%) (SCENIHR, 2008).
More generally, CPSC (2010) noted that the adipates “have similar PVC compatibility as phthalates, but suffer from higher volatilities and higher migration rates, and are generally higher priced.“ In summary, DEHA seems to migrate from PVC and the in vivo data will be compared with those for other plasticizers in section 5.3.
3.6 DI(2-ETHYLHEXYL) SEBACATE (DEHS)
No data on the migration of DEHS from consumer articles or surrogate data on its extraction into water/aqueous solutions are available.
80 Evaluation of DEHP alternatives
3.7 DI(2-ETHYLHEXYL) TEREPHTALATE (DEHT)
In a water extractability experiment (24 h at 50 °C) with 1 mm PVC sheets with 40% plasticizer, DEHT showed a loss of 0.09% compared to 0.01% for DEHP (SCENIHR, 2008).
An extraction experiment showed a higher transfer rate from PVC resin (conc. 40%) into water of 0.09% compared to 0.02% for DEHP (Maag et al., 2010). No further experimental details are provided.
SCENIHR (2008) expected minimal consumer exposure based on the limited use in consumer products and low leaching of the compound out of the polymer matrix in its major use as a plasticiser. The latter statement, however, appears to be in conflict with the data presented above.
Overall, the few experimental data and the conclusions appear to be conflicting, so that no definite conclusion can be drawn.
3.8 DI(2-PROPYLHEPTYL) PHTHALATE (DPHP)
The most relevant information comes from a recent investigation by the German Federal Institute for Risk Assessment (BfR, 2011) that analysed in vitro migration from 4 articles (intended for children under 3 years of age) into artificial saliva. The head‐over‐heels method employed was developed for DINP and covers dynamic agitation to simulate biting/chewing on an article. While migration from one article was not detectable, migration rates for the other 3 articles were 5.6, 6.1 and 25.4 μg/cm2/h (BfR, 2011). This corresponds to a range of 0.93‐4.2 μg/10cm2 x min.
3.9 DI-ISODECYL PHTHALATE (DIDP)
ECB (2003b) and more recently ECHA (2012) summarised DIDP migration rates from toys and other articles. The most recent evaluation discussed the data for DIDP together with those for DINP. The authors derived identical migration rates, both for migration into saliva and for migration into sweat, for these two phthalates (ECHA, 2012). The data are presented in the following table.
Table 18: Migration values for DIDP Typical case Reasonable worst case Migration into saliva (µg/cm2/h) 14 45
81 Evaluation of DEHP alternatives
Migration into sweat (μg/cm2/h) 0.6 6
Overall, DIDP is expected to migrate from PVC articles at a rate similar to DINP and these data are discussed together with the data for other plasticizers in section 5.3.
3.10 DI-ISONONYL-1,2-CYCLOHEXANEDICARBOXYLATE (DINCH)
No data on the migration of DEHS from consumer articles or surrogate data on its extraction into water/aqueous solutions are available.
Many authors describe a lower migration/leaching of DINCH compared to DEHP, but the data exclusively relate to medical devices and FCM (CPSC, 2010b; Maag et al., 2010; RAC/SEAC, 2012). Maag et al. (2010) concluded that DINCH shows an 8‐fold lower migration than DEHP, however, no data are reported to confirm this statement. The source given is an online article, in which a BASF representative, the company producing DINCH, is outlining his arguments. The article goes on to say: “To BASF the likely industry answer remains staying with PVC, and as a result the supplier has invested steadily in development and capacity of its alternative to DEHP, Hexamoll DINCH, a non‐phthalate plasticizer with migration levels eight times lower than that of DEHP.” No differentiation by the materials covered by this statement or, indeed, no critical appraisal of the source is made by Maag et al. (2010).
SCENIHR (2008) also noted an 8‐fold lower leaching from medical devices into the fluids compared to DEHP, but overall concluded: “The information of the leaching from alternative plasticizers is sparse but may be expected to be of same order of magnitude”.
3.11 DI-ISONONYL PHTHALATE (DINP)
Maag et al. (2010) concluded a lower migration than DEHP, however, no data are reported to confirm this statement. Other documents by the Danish EPA (Tønning et al., 2009) reported no migration of DINP into saliva in vitro, but in vivo data indicate an identical or even higher migration rate compared to DEHP. In fact, the data on DINP migration from toys formed an important basis for the restriction of some phthalates in toys and childcare articles (CSTEE, 1998).
Detailed data on in vivo migration experiments largely reflecting the data also discussed in ECB (2003a) and ECHA (2012). Analysing the available in vivo migration data, a 95th percentile value for the migration rate of DINP from PVC was derived and used in this comparative assessment. The derived migration rate is close to the migration rate used for DEHP in the assessment of exposure to DEHP from consumer (exposure modelling approach used).
82 Evaluation of DEHP alternatives
As already mentioned above for DIDP, ECHA (2012) assumed identical migration rates for DIDP and DINP, both for migration into saliva and the migration into sweat.
3.12 TRIOCTYL TRIMELLITATE (TOTM)
No data on the migration of TOTM from consumer articles are available.
Adams et al. (2001) reported experimental data on weight loss of PVC containing TOTM, DEHP and other plasticizers after 24 h extraction with water at 50°C. The TOTM‐containing PVC weight loss was 0.13%, that for DEHP‐containing PVC 0.2%.
Another water extractability experiment (24 h at 50 °C) with 1 mm PVC sheets with 40% plasticizer, showed no loss for TOTM and 0.01% loss for DEHP (SCENIHR, 2008).
Other sources refer to the lower migration/leaching of TOTM compared to DEHP (CPSC, 2010b; Maag et al., 2010), but provide little experimental and this is exclusively related to FCM/medicinal products.
The data indicate that the migration rate of TOTM could be possibly lower compared to DEHP. However, no definite conclusions can be drawn. SCENIHR (2008) concluded: The information of the leaching from alternative plasticizers is sparse but may be expected to be of same order of magnitude.
83 Evaluation of DEHP alternatives
4 Comparative environmental exposure assessment
4.1 INTRODUCTION
On the following pages parameters most relevant for environmental fate of the substances are compiled and subsequently used for a comparative environmental exposure assessment. This assessment used ECETOC TRA v.3, with ERC1 and ESVOC SPERC1 (for manufacture) and calculated PEC values for STP (sewage treatment plant), freshwater and sediment.
4.2 CRITICAL DATA FOR ALTERNATIVE SUBSTANCES
Table 19: Physico-chemical and environmental fate properties data of alternative substances
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure
ASE No defined MW 0.000294 Pa at 20 °C mono, di and tri not readily biodegradable, but is 2.2 mg/L at 20°C CAS: 91082‐17‐6 (Sulfonic acids, C10‐ 0.000489 Pa at 25 °C sulfonic phenyl degradable as the pass level of 60 % (OECD 105) 21‐alkane, phenyl (OECD104) esters): degradation (BOD) was achieved after (ECHA, 2013) esters), approx. 379 47 days (EU Method C.4‐D) (ECHA, 2013) 8.8‐11.3 (mono), 6.7‐ 9.4 (di) and 5.7‐7.5 (ECHA, 2013) (tri), each at 40°C Aerobic biodegradation 31% in 28 days. (OECD 117) not readily biodegradable (ECHA, 2013) (Maag et al., 2010)
84 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure
ATBC 402.5 0.0494 Pa 25 °C 4.3 at 25 °C inherent biodegradability (OECD302C) 4490 µg/L at CAS: 77‐90‐7 (calculated) (estimated) ready biodegradability (OECD301D) 20 °C (OECD105) (ECHA, 2013) (ECHA, 2013; SCENIHR, (ECHA, 2013) (ECHA, 2013) 2008) 0.052 mm Hg =6.9 Pa In the modified MITI test with activated (20°C) 4.3 (22°C) sludge inoculum, 80% of the theoretical (Maag et al., 2010; (CPSC, 2010b) BOD was reached in 4 weeks. In the SCENIHR, 2008) static biometer EPA test (EPA 4.6 x 10‐6 mmHg = 835.3300), ATBC was characterised as 0,000613283 Pa readily biodegradable based >60% (25°C) ThCO2 observed within a 10‐14 day window following the lag period. Also in (CPSC, 2010b) the ASTM D 5338 test, ATBC was found to readily biodegradable as well as ultimately biodegradable (Maag et al., 2010)
COMGHA 500.7 (A), 442.6 (B) 0.00000011 Pa at 25 6.4 readily biodegradable when tested by 7000 µg/L CAS: 736150‐63‐3 °C (SCENIHR, 2008) OECD (Maag et al., 2010; (Maag et al., 2010) method 301: 98% degradation occurred SCENIHR, 2008) in 28 days (Maag et al., 2010)
85 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure
DEHA 370.57 8.5 x 10‐7 mm Hg = 8.94 at 25 °C readily biodegradable (OECD301F) 3.2 µg/L 1.13 x 10‐4 Pa at (OECD117) CAS: 103‐23‐1 (ECHA, 2013) (ECHA, 2013; Letinski 20°C (ECHA, 2013) Aerobic biodegradation in activated et al., 2002)
(CPSC, 2010b; ECHA, sludge, 28 days degradation > 66% 2013; SCENIHR, 8.114 (calculated) Considered readily biodegradable 2008) (Lambert et al., 2010) (Lambert et al., 2010)
DEHS 426.67 1.3 x 10‐7 hPa at 25°C 10,08 (estimated) Activated sludge, 28 days 0,35 µg/l at 25°C CAS: 122‐62‐3 (Lambert et al., (Lambert et al., 2010) Biodegradation = 65% (Lambert et al., 2010) 2010) Did not meet the 10 days criterion of the test (Lambert et al., 2010)
DEHT 390.56 < 0.001 Pa at 25 °C 5.72 (well water), 5.26 readily biodegradable (OECD301B) ca. 0.4 µg/L at 22.5°C CAS: 6422‐86‐2 (EU A.4) (sea water) (OECD107, (ECHA, 2013) (ECHA, 2013) tendency to (ECHA, 2013) EPA aerobic biodegradation ‐5 underestimate) 2.14 x 10 mmHg = guideline: 56% in 28 days, inherently (ECHA, 2013; SCENIHR, 0,0029 Pa (25°C) biodegradable 2008) (CPSC, 2010b; Maag (Maag et al., 2010) et al., 2010) 7.81; 8.39; 9.54 at 25°C (all calculated) (ECHA, 2013; Maag et al., 2010)
86 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure
‐6 DPHP 446.68 3.7 x 10 Pa at 20°C > 6 at 25°C (ECHA, Readily biodegradable according to < 0.1 µg/L at 25°C (ECHA, 2013) 2013) OECD 301B (RL1) (ECHA, 2013) (ECHA, 2013) 10.36 at 25°C calculated (ECHA 2013) DIDP 446.68 5.1 x10‐5 Pa at 25°C 8.8 at 25°C Key study: biodegraded to a high 0.17 µg/L at 21°C CAS: 26761‐40‐0 (ECB, 2003b; ECHA, (ECHA, 2013) extent, 67% , but did not meet the 10‐ (ECHA, 2013) day window requirement to be and 68515‐49‐1 2013) 0.2 μg/L at 20°C considered readily biodegradable (ECHA, 2012) (OECD301F) (ECHA, 2013) Supp.: readily biodegradable (OECD301F); rapidly biodegradable under acclimated conditions (EPA.OPPTS835.3170) (ECHA, 2013)
DINCH 424.6 2.2 x 10‐7 hPa at 20°C 10 at 25°C(exp) 41% degradation in the CO2 evolution <20 µg/L at 25°C CAS: 166412‐78‐8 (ECHA, 2013; Maag (ECHA, 2013) test (OECD 301B), (ECHA, 2013; et al., 2010) Not readily biodegradable SCENIHR, 2008) 10.0 (calculated) (Maag et al., 2010; NICNAS, 2008) (SCENIHR, 2008) DINP 420.6 6 x 10‐5 Pa at 20°C 8.8 at 25°C (OECD123) Readily biodegradable (70.5% after 28 0.6 μg/L at 20‐21°C CAS: 28553‐12‐0 (ECHA, 2012; 2013; (ECHA, 2012; 2013; days, OECD301F) (ECHA, 2012; 2013)
87 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure and 68515‐48‐0 SCENIHR, 2008) SCENIHR, 2008) (ECHA, 2013) 5.4 x 10‐7 mmHg = A shake flask CO2 evolution test ‐5 7.1 x 10 Pa at 25°C (soil and sewage showed): (CPSC, 2010b) biodegradation T 1/2 =5.31 days with a 7.1 day lag time (Lambert et al., 2010)
TOTM 546.8 6.8 x 10‐10 hPa at 25° 5.94 at 25°C Key: Ready biodegradability (OECD301F) 0.386 µg/L at 25°C CAS: 3319‐31‐1 C (EU A.4) (OECD107) Supp: 2 x Inherently degradable (no (ECHA, 2013; (ECHA, 2013) (CPSC, 2010b; ECHA, guideline; Modified MITI) SCENIHR, 2008) 3.9 x 10‐11 mm Hg = 2013) (ECHA, 2013) 100 mg/L (25°C) ‐11 5,2 x 10 hPa at 8.88 at 55°C (CPSC, 2010b) 25°C (OECD117) (CPSC, 2010b) (ECHA, 2013) 5.6 Pa at 20°C (SCENIHR, 2008)
DEHP 390.6 3.4 x 10‐5 Pa at20°C 7.5 Key studies: 2x Ready biodegradability 3 µg/L at 20°C CAS: 117‐81‐7 (ECB, 2008; SCENIHR, (ECB, 2008; SCENIHR, (OECD311; C.4‐C); 1 x inherent (ECB, 2008; ECHA, 2008) 2008) biodegradability (no guideline) 2013; SCENIHR, 7.2 x 10‐8 mmHg= 9.6 7.6 (ECHA, 2013) 2008) ‐6 x 10 Pa at 25°C (CPSC, 2010b) DEHP is assumed 285 µg/L (24°C)
88 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight (g/Mol) pressure (CPSC, 2010b) to be readily biodegradable (CPSC, 2010b) (ECB, 2008)
4.3 VALUES USED FOR COMPARATIVE ENVIRONMENTAL EXPOSURE ASSESSMENT
Table 20: Input data for assessing the comparative environmental exposure of alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight pressure
ASE 379 0.000489 Pa at 25 °C 8.8‐11.3 (mono), inherent biodegradable 2200 µg/L CAS: 91082‐17‐6 6.7‐9.4 (di) and 5.7‐7.5 (tri sulfonic phenyl esters),
ATBC 402.5 4.6 x 10‐6 mmHg = 4.3 ready biodegradability 4490 µg/L CAS: 77‐90‐7 0,000613283 Pa (25°C) COMGHA 500.7 0.00000011 Pa at 25 °C 6.4 (SCENIHR, readily biodegradable 7000 µg/L CAS: 736150‐63‐3 2008)(SCENIHR, 2008)(SCENIHR, 2008)(SCENIHR, 2008)
89 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight pressure
DEHA 370.57 8.5 x 10‐7 mm Hg = 1.13 x 8.94 readily biodegradable 3.2 µg/L 10‐4 Pa at 20°C CAS: 103‐23‐1
DEHS 426.67 1.3 x 10‐7 hPa at 25°C 10,08 inherent biodegradable 0,35 µg/L CAS: 122‐62‐3 DEHT 390.56 2.14 x 10‐5 mmHg = 5.72 readily biodegradable 0.4 µg/L CAS: 6422‐86‐2 0,0029 Pa (25°C)
‐6 DPHP 446.68 3.7 x 10 Pa at 20°C > 6 readily biodegradable 0.1 µg/L CAS: 53306‐54‐0
DIDP 446.68 5.1 x 10‐5 Pa at 25°C 8.8 readily biodegradable 0.17 µg/L CAS: 26761‐40‐0 and 68515‐49‐1 DINCH 424.6 2.2 x 10‐7 hPa at 20°C 10 Not readily 20 µg/L CAS: 166412‐78‐8 biodegradable
DINP 420.6 6 x 10‐5 Pa at 20°C 8.8 Readily biodegradable 0.6 µg/L CAS: 28553‐12‐0 and 68515‐48‐0 TOTM 546.8 6.8 x 10‐10 hPa at 25° C 5.94 Readily biodegradable 0.386 µg/L
90 Evaluation of DEHP alternatives
Substance Molecular Vapour Log PO/W Biodegradability Water solubility weight pressure CAS: 3319‐31‐1 DEHP 390.6 3.4 x 10‐5 Pa at20°C 7.5 readily biodegradable 3 µg/L CAS: 117‐81‐7
4.4 PEC CALCULATIONS
Results of comparative environmental exposure assessment, using ECETOC TRA v.3, with ERC1 and ESVOC SPERC1 Input data as shown in table above.
Table 21: Calculated PECs for alternative substances based on standard scenarios – DEHP in comparison to alternative substances 1-5
Input DEHP ASE ATBC COMGH DEHA DEHS DEHT A
Molecular 390,6 379 402,5 500,7 370,57 426,67 390,56 weight (g/mol)
VP (Pa) 0,00003 0,00048 0,00061 1,10E‐ 1,13E‐ 0,00000 2,90E‐ 4 9 3283 07 04 013 03
WS (mg/L) 0,003 2,2 4,49 7 0,0032 0,00035 0,0004
91 Evaluation of DEHP alternatives
Kow 316227 100000 19953 2,51E+0 8,71E+0 120000 5,25E+0 77 000 6 8 00000 5
Biodegradability readily inherent readily readily readily inherent readily test result biodegr ly biodegr biodegr biodegr ly biodegr adable biodegr adable adable adable biodegr adable adable, adable, fulfilling fulfilling criteria criteria
Assessment ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- method based based based based based based based based based based based based based based
PEC STP (mg/L) 776,033 0,776 814,39 2,44 1000,46 3,00 695,40 2,09 798,19 0,80 800,39 0,80 356,93 0,36
PEC freshwater 23,908 0,027 12,14 0,04 99,49 0,32 53,97 0,17 2,35 0,00 0,29 0,00 33,02 0,04 (mg/L)
PEC freshwater 358036 3995,05 462099 14928,8 38479,4 122,47 103900 3316,99 516507 5702,46 531780 6477,42 178894, 207,31 sediment (mg/kg 2,228 4 6,26 1 7 4,15 4,42 0,99 45 dw)
Table 22: Calculated PECs for alternative substances based on standard scenarios – DEHP in comparison to alternative substances 6-11
Input DPHP DEHT DIDP DINCH DINP TOTM
92 Evaluation of DEHP alternatives
Molecular weight 446,68 390,56 446,68 424,6 420,6 546,8 (g/mol)
VP (Pa) 3,70E‐06 2,90E‐03 5,10E‐05 2,20E‐07 6,00E‐05 6,80E‐10
WS (mg/L) 0,0001 0,0004 0,00017 0,02 0,0006 0,000386
Kow >1,00E+6 5,25E+05 6,31E+08 1,00E+10 6,31E+08 8,71E+05
Biodegradability readily readily readily not readily readily test result biodegrad biodegrad biodegrad biodegrad biodegrad biodegrad able able able able able able
Assessment ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- ERC- spERC- method based based based based based based based based based based based based
PEC STP (mg/L) 655,15 0,66 356,93 0,36 796,97 0,80 800,51 0,80 797,36 0,80 664,76 0,66
PEC freshwater 57,63 0,065 33,02 0,04 3,02 0,003 0,34 0,00 3,02 0,003 59,24 0,07 (mg/L)
PEC freshwater se‐ 526264,5 589,23 178894,4 207,31 5112238, 5640,82 5316212, 7126,96 5114778, 5644,01 483687,9 592,26 diment (mg/kg dw) 4 5 83 68 62 5
93 Evaluation of DEHP alternatives 5 Summary and conclusions
5.1 COMPARATIVE HUMAN HEALTH HAZARD EVALUATION
Table 23: Comparison tentative DNELs for alternative substances and DNELs for DEHP
Substance CAS No. DNELs - General Population (mg/kg bw/d) Di(ethylhexyl)phthalate 117‐81‐7 long‐term 0.048 (DEHP) oral (systemic) long‐term 0.72 dermal (systemic)
Substance CAS No. DNELs - General Population Remarks
ECHA Dissemination Portal Tentative DNELs
DNELs Comparison with Comparison with (mg/kg/bw/d) DNELs for DEHP DNELs for DEHP Alkylsulphonic phenyl ester 91082‐17‐6 long‐term oral 0.47 Higher Higher (ASE, MESAMOLL) (systemic)
long‐term 0.47 Lower Higher dermal (systemic)
94 Evaluation of DEHP alternatives
Acetyltri‐n‐butyl citrate 77‐90‐7 long‐term oral 1 Higher Higher (ATBC) (systemic) long‐term 1 Higher Higher dermal (systemic)
Glycerides, castor‐oil‐mono‐ 736150‐63‐3 long‐term oral Not registered Not applicable Higher , hydrogenated, acetates (COMGHA); (systemic) (COMGHA) 330198‐91‐9 long‐term Not registered Not applicable Higher (comp. A); dermal 33599‐07‐4 (systemic) (comp. B)
Di(2‐ethylhexyl)adipate 103‐23‐1 long‐term oral 1.3 Higher Higher Indications for (DEHA, DOA) (systemic) developmental toxicity, DEHA on CORAP long‐term 13 Higher Higher dermal (systemic) Diethylhexylsebacate (DEHS) 122‐62‐3 long‐term oral Not registered Not applicable Higher Indications for (systemic) developmental toxicity for related substance DEHA long‐term Not registered Not applicable Higher dermal (systemic) Di(2‐ethylhexyl) 6422‐86‐2 long‐term oral 3.95 Higher Higher terephtalate (DEHT, DOTP) (systemic)
long‐term 3.95 Higher Higher
95 Evaluation of DEHP alternatives dermal (systemic) Di(2‐propylheptyl) phthalate 53306‐54‐0 long‐term oral 4.9 Higher Higher (DPHP) (systemic) long‐term 61.25 Higher Higher dermal (systemic)
Di‐isodecyl‐phthalate (DIDP) 26761‐40‐0; long‐term oral 0.75 (registration Higher Higher 68515‐49‐1 (systemic) dossier) 0.073 (ECHA 2012) 0.075 (RAC Opinion 2013) long‐term 20.83 Higher Higher dermal (registration (systemic) dossier) 0.92 (ECHA 2012) 1.88 (RAC opinion 2013)
Di‐isononyl‐1,2‐ EU 166412‐ long‐term oral 2 Higher Higher cyclohexanedicarboxylate 78‐8, USA (systemic) (DINCH, HEXAMOLL) and Canada long‐term 25 Higher Higher 474919‐59‐0 dermal (systemic)
96 Evaluation of DEHP alternatives
Di‐isononylphthalate (DINP) 68515‐48‐0 long‐term oral 4.4 (REG) Higher Higher Indications for and 28553‐ (systemic) 0.15 (ECHA 2012) antiandrogenic effects 12‐0 0.075 (ECHA‐RAC 2013)
long‐term 220 (REG) Higher Higher dermal 1.88 (ECHA 2012) (systemic) 1.88 (ECHA‐RAC 2013) Trioctyltrimellitate (TOTM, 3319‐31‐1 long‐term oral 1.13 Higher Higher Indications for TEHTM) (systemic) developmental toxicity, TOTM on CORAP long‐term 11.25 Higher Higher (environment/suspected dermal PBT (systemic)
97 Evaluation of DEHP alternatives 5.2 COMPARATIVE ENVIRONMENTAL HAZARD EVALUATION
Table 24: Comparison tentative PNECs for alternative substances and PNECs for DEHP
Substance CAS No. PNECs (µg/l) Di(ethylhexyl)phthalate 117‐81‐7 Freshwater 1.3 (DEHP)
Substance CAS No. PNECs Remarks
ECHA Dissemination Portal (ATF) Tentative PNECs
Substance PNECs Comparison with Comparison with (µg/l) PNEC for DEHP PNEC for DEHP Alkylsulphonic phenyl ester 91082‐17‐6 Freshwater 2 Higher Not derived Acute data for 3 trophic (ASE, MESAMOLL) levels, no effects at concentrations at or above saturation level Acetyltri‐n‐butyl citrate 77‐90‐7 Freshwater 22 Higher Higher Chronic studies on (ATBC) invertebrates and algae, most sensitive species fish (7‐d prolonged toxicity test)
Glycerides, castor‐oil‐mono‐, 736150‐63‐3 Freshwater Not registered Not applicable Not derived Acute data for 3 trophic hydrogenated, acetates (COMGHA); levels, effects with (COMGHA) 330198‐91‐9 emulsions at high (comp. A); concentrations ascribed to
98 Evaluation of DEHP alternatives 33599‐07‐4 physical effects (comp. B) Di(2‐ethylhexyl)adipate 103‐23‐1 Freshwater 3.2 Higher Higher Chronic data for 3 trophic (DEHA, DOA) levels, most sensitive endpoint Daphnia magna reproduction with effects in the range of water solubility Diethylhexylsebacate (DEHS) 122‐62‐3 Freshwater Not registered Not applicable Not derived Acute data for 3 trophic levels at concentrations far above water solubility – no effects
Di(2‐ethylhexyl) terephtalate 6422‐86‐2 Freshwater 0.08 Lower Not derived Acute and chronic data for 3 (DEHT, DOTP) trophic levels, no effects at concentrations at or above saturation level
Di(2‐propylheptyl) phthalate 53306‐54‐0 Freshwater Not derived Not applicable Not derived Acute data for 3 trophic (DPHP) (no effect levels and chronic data for observed) Daphnia magna, no effects at or above saturation level
Di‐isodecyl‐phthalate (DIDP) 26761‐40‐0; Freshwater Not derived Not applicable Not derived Acute and chronic data for 3 68515‐49‐1 (no effect trophic levels, no relevant observed) effects at concentrations at or above saturation level Di‐isononyl‐1,2‐ EU 166412‐78‐ Freshwater Not derived Not applicable Not derived Acute data for 3 trophic cyclohexanedicarboxylate 8, USA and levels and chronic data for
99 Evaluation of DEHP alternatives (DINCH, HEXAMOLL) Canada Daphnia magna, no effects 474919‐59‐0 at or above saturation level Di‐isononylphthalate (DINP) 68515‐48‐0 Freshwater Not derived Not applicable Not derived Acute and chronic data for 3 and 28553‐12‐ trophic levels, no relevant 0 effects at concentrations at or above saturation level
Trioctyltrimellitate (TOTM, 3319‐31‐1 Freshwater 0.006 Lower Not derived Acute data for 3 trophic TEHTM) levels and chronic data for Daphnia magna, no effects at reported water solubilities; CORAP‐listed (environmental concerns/suspected PBT)
100 Evaluation of DEHP alternatives
5.3 HUMAN EXPOSURE CONSIDERATIONS
The data briefly discussed above focussed on studies relevant for an assessment of migration from PVC consumer articles. Some authors, such as CPSC (2010) and Maag et al. (2010), generalise the migration behaviour observed for FCM and/or medical devices and translate it simply into an expected behaviour for consumer articles. We consider such a simplified approach to be unjustified, given the many problems associated with it, as discussed by others in relation to toys (van Engelen et al., 2008). The available in vivo data on migration into saliva can be summarised as shown in the following table. All data were converted to an identical unit (µg/10 cm2 x min). Migration rates for DEHP and DINP were derived based on an extensive data evaluation. Note that ECHA (2012) assumes identical values for DIDP and DINP.
Table 25: Estimated migration rates into saliva of some alternative substances, for which in vivo data are available Migration into saliva (µg/10 cm2 x min)
ATBC in vivo migration (1 h), sucking (Wildhack et al., 2001) 1.1
ATBC, in vivo migration (1 h), chewing (Wildhack et al., 2001) 3.8
DEHA, sucking/chewing with different shore hardness* 0.83‐3.3
DINP (95th percentile from 15 mean values) similar to other phthalates
DINP and DIDP, typical case assumed in ECHA (2012) 2.3
DINP and DIDP, reasonable worst case assumed in ECHA (2012) 7.5
DEHP (taken for risk characterisation in this dossier; based on similar to other phthalates combined DINP/DEHP data )
* Assuming that the respective experiments were also carried out for 1 h; values approximated from figures.
While a detailed discussion of the different values derived is beyond the scope of this chapter, the data above show that migration of various alternative substances into saliva, for which in vivo data are available, is similar. For DPHP, only in vitro data are available, showing a migration rate that ranges between 0.93 and 4.2 μg/10 cm2 x min (see section 3.8 for details). These values appear to be similar to the ones for DINP/DIDP, but any conclusions are limited by the small sample size for DPHP (3 articles only). Data on the migration into sweat (which is important for dermal exposure assessment) are much more limited, but suggest a lower DEHP migration compared to DINP/DIDP.
101 Evaluation of DEHP alternatives Table 26. Estimated migration rates into sweat of some alternative substances Migration into sweat (µg/cm2 x h)
DINP and DIDP, typical case assumed in ECHA (2012) 0.6
DINP and DIDP, reasonable worst case assumed in ECHA (2012) 6
DEHP (taken for risk characterisation in this dossier) somewhat lower compared to DINP and DIDP
It should be noted that the value for DIDP/DINP in ECHA (2012) was actually derived from a combined migration/absorption study (Deisinger et al., 1998), performed with DEHP, with several assumptions for extrapolating it to DIDP/DINP, while the DEHP value is based on a statistical evaluation of DEHP migration data for a variety of PVC articles into sweat simulant No qualified data are available for the other alternative candidates. The extractability in neutral or aqueous solutions (oil simulants or alkaline solutions are not considered to be good predictors of the migration into aqueous media) indicates a comparable extraction for ASE, COMGHA, DEHT and DINCH, and a lower value for TOTM, compared to DEHP. However, the test systems are different from migration studies relevant for consumer exposure via oral (mouthing) and dermal pathways. In the light of these data, we follow the same approach that SCENIHR (2008) took in relation to DEHP alternatives in medical devices. These authors considered data on leaching from alternative plasticizers to be sparse, but expected it to be of the same order of magnitude (compared to DEHP).
5.4 ENVIRONMENTAL EXPOSURE CONSIDERATIONS Overall, environmental behavior is similar for all substances including DEHP (see calculated PECs in Table 21 and Table 22). Due to their poor water solubilities they tend to be distributed to sediment (and possibly soil) rather than water. Estimated PECs (please note that these PECs are only meant for comparison, they are calculated based on standard scenarios and assumptions and should not be taken as realistic exposure estimates) may deviate over several orders of magnitude, due to their properties. But estimated DEHP concentrations in STP, freshwater and sediment are never lower than by a factor of three in any of the scenarios, compared to any of the alternative substances.
102 Evaluation of DEHP alternatives 5.5 OVERALL CONCLUSIONS
Human health hazard profiles and risk considerations In comparison with the DNELs (general population) for DEHP, tentative DNELs for the alternative substances are higher. The database is incomplete for some of the substances, especially in comparison with the well investigated DEHP. The following substances have not been registered until the first REACH deadline and were not on the dissemination portal at 7 June 2013: Glycerides, Castor‐oil‐mono‐, hydrogenated, acetates (COMGHA) Diethylhexylsebacate (DEHS) Furthermore, although no respective classification proposal exists, there are indications for reproductive and/or hormone‐like effects for some of the substances, which might in the future lead to a classification. With respect to exposure considerations it was concluded above that the data available are not sufficient to clearly assess the migration behavior of the alternative substances. Few data are available for their migration to sweat or saliva. Therefore, considering their similar physico‐chemical properties, similar migration behavior is assumed for consumer exposure from articles, which is considered to be the most relevant exposure situation. Taken together, based on higher DNELs and similar exposure intensity, none of the evaluated alternative substances is considered to be less advantageous compared to DEHP. In conclusion, all alternative substances should be further investigated with respect to technical and socio‐economic feasibility and availability. However, it has to be noted that DEHA and DEHS data raise some concern for reproductive toxicity and that DEHA has recently be listed on CORAP due to human health consideration. Substitution of DEHP by these substances cannot be recommended before substance evaluation of DEHA is finalized. The reliability of the analysis and conclusions are restricted by the differences in the databases. Also, possible risks from future classifications as reproductive toxicants for some of the alternative substances have to be considered.
Environmental hazard profiles Environmental effects profiles of alternative substances show similarities to DEHP (for DEHP no PNECfreshwater could be derived, but the environmental quality standard (EQS) of 1.3 µg/L is used as a PNEC surrogate). Most of the substances are very lipophilic with low water solubility. These substances, as well as DEHP, did not reveal effects on aquatic test organisms, when tested in standard tests without use of solubilizers at concentrations up to the water solubility limit. Only for two substances aquatic toxicity was shown in such tests, and, hence, meaningful PNECs could be derived (ATBC, DEHA). Again, substantial differences in the database were observed. In conclusion, with the exception of two substances, similar effect profiles were observed for DEHP and for most of the alternative substances, with no toxicity observed in concentrations
103 Evaluation of DEHP alternatives at or below the water solubility limit. For the two substances, for which aquatic toxicity was observed, tentative PNECsfreshwater in the lower µg/L range were derived. Comparison of PECs calculated based on standard exposure scenarios shows that PECs may deviate substantially, but that PECs for DEHP in various compartments are always within a range of one order of magnitude of the highest PEC calculated. Therefore, considering the similar environmental effects profiles, none of the alternative substances should be ruled out as a substitute for DEHP based on environmental risks. TOTM has been listed on CORAP for environmental concerns/suspicion of PBT properties. Conclusion All alternative substances (with reservations in regard to DEHA and DEHS, see above, and TOTM) should be further investigated with respect to technical and socio‐economic feasibility and availability. The reliability of the analysis and conclusions are restricted by the differences in the databases.
104 Evaluation of DEHP alternatives 6 References
Adams, W.J.; Biddinger, G.R.; Robillard, K.A.; Gorsuch, J.W. (1995) A summary of the acute toxicity of 14 phthalate esters to representative aquatic organisms Environmental Toxicology and Chemistry, 14, 1569‐1574
Aristech, Chemical Corporation (1994) 2‐Year Dietary Oral Toxicity Study in Rats with Diisononyl Phthalate. TSCA 8(e) Submission 8EHQ‐ 0794‐13083. CAS Number 68515‐48‐0 (as cited in EC 2003a)
Ball, G.L.; McLellan, C.J.; Bhat, V.S. (2012) Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: a category approach Critical Reviews in Toxicology, 42, 28‐67
BASF (2010) IUCLID 166412‐78‐8_1,2‐Cyclohexandicarbonsäurediisononylester BASF SE / Ludwigshafen am Rhein / Germany https://www.cpsc.gov/about/cpsia/docs/robustDINCH01062010.pdf
BfR, Bundesinstitut für Risikobewertung (2011) DPHP in Spielzeug nachgewiesen: BfR bewertet Risiko des Weichmachers Stellungnahme Nr. 004/2012 des BfR vom 28. Juni 2011 http://www.bfr.bund.de/cm/343/dphp‐in‐spielzeug‐nachgewiesen‐bfr‐bewertet‐risiko‐des‐ weichmachers.pdf
Boberg, J.; Christiansen, S.; Axelstad, M.; Kledal, T.S.; Vinggaard, A.M.; Dalgaard, M.; Nellemann, C.; Hass, U. (2011) Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats Reproductive Toxicology, 31, 200‐209
Brown, D.; Croudace, C.P.; Williams, N.J.; Shearing, J.M.; Johnson, P.A. (1998) The effect of phthalate ester plasticisers tested as surfactant stabilised dispersions on the reproduction of the Daphnia magna Chemosphere, 36, 1367‐1379
105 Evaluation of DEHP alternatives BUA, Beratergremium für umweltrelevante Altstoffe (1996) C10‐C21‐Alkansulfonsäurephenylester (Nr. 180), Chloralkansulfonsäuren, Natriumsalze (Nr. 181), 2‐ Phosphono‐1,2,4‐butantricarbonsäure (Nr. 182), Diacetonketogulonsäure (Nr. 183), BUA‐ Stoffberichte 180‐183 S. Hirzel Verlag Stuttgart
BUA, Beratergremium für umweltrelevante Altstoffe (1997) Di‐(2‐ethylhexyl)adipat, BUA‐Stoffbericht 196 S. Hirzel Verlag Stuttgart
Cho, W.‐S.; Han, B.S.; Ahn, B.; Nam, K.T.; Choi, M.; Oh, S.Y.; Kim, S.H.; Jeong, J.; Jang, D.D. (2008) Peroxisome proliferator di‐isodecyl phthalate has no carcinogenic potential in Fischer 344 rats Toxicology Letters, 178, 110‐116
Cho, W.‐S.; Han, B.S.; Ahn, B.; Nam, K.T.; Choi, M.; Oh, S.Y.; Kim, S.H.; Jeong, J.; Jang, D.D. (2010) Corrigendum to “Peroxisome proliferator di‐isodecyl phthalate has no carcinogenic potential in Fischer 344 rats” [Toxicol. Lett. 178 (2008) 110–116] Toxicology Letters, 197, 156
Cho, W.‐S.; Jeong, J.; Choi, M.; Park, S.N.; Han, B.S.; Son, W.‐C. (2011) 26‐Week carcinogenicity study of di‐isodecyl phthalate by dietary administration to CB6F1‐rasH2 transgenic mice Archives of Toxicology, 85, 59‐66
CHRIP Japan (o.J.) Chemical Risk Information Platform (CHRIP) http://www.safe.nite.go.jp/english/db.html
CIREP, Cosmetic Ingredient Review Expert Panel (2010) Draft Report Dicarboxylic Acids and Their Salts as Used in Cosmetics. Esters of Dicarboxylic Acids as Used in Cosmetics August 30, 2010 http://www.cir‐safety.org/meeting/116th‐cir‐expert‐panel‐meeting
COWI, Consultancy within Engineering, Environmental Science and Economics (2009) Data on manufacture, import, export, uses and releases of bis(2‐ethylhexyl)phthalate (DEHP) as well as information on potential alternatives to its use
106 Evaluation of DEHP alternatives Author: Carsten Lassen (COWI), Sonja Hagen Mikkelsen (COWI), Jesper Kjølholt (COWI), Jakob Maag (COWI), Louise Bolving Hübschmann (COWI), Erik Hansen (COWI), Alison Searl (IOM) and Caspar Corden (ENTEC) Source: European Chemicals Agency (ECHA) http://www.cowi.com/menu/NewsandMedia/publications/WaterandEnvironment/2009/Pages/defa ult.aspx
CPSC, Consumer Product Safety Commission (2010a) Overview of Dialkyl Ortho‐Phthalates http://www.cpsc.gov/about/cpsia/phthalover.pdf U.S. Consumer Product Safety Commission, Bethesda, MD
CPSC, Consumer Product Safety Commission (2010b) Review of Exposure and Toxicity Data for Phthalate Substitutes http://www.cpsc.gov/about/cpsia/phthalsub.pdf U.S. Consumer Product Safety Commission, Bethesda, MD
CPSC, Consumer Product Safety Commission (2010c) Toxicity Review of Di(isodecyl) Phthalate http://www.cpsc.gov/about/cpsia/toxicityDIDP.pdf U.S. Consumer Product Safety Commission, Bethesda, MD
CPSC, Consumer Product Safety Commission (2010d) Toxicity review of Diisononyl phthalate April 7, 2010 http://www.cpsc.gov/about/cpsia/toxicityDINP.pdf
CSTEE, Scientific Committee for Toxicity, Ecotoxicity and the Environment (1998) Phthalate migration from soft PVC toys and child‐care articles Brussels
CSTEE, Scientific Committee for Toxicity, Ecotoxicity and the Environment (1999) Opinion on the toxicological characteristics and risks of certain citrates and adipates used as a substitute for phthalates as plasticisers in certain soft PVC products. Opinion adopted at the 11th CSTEE plenary meeting on the 28th of September 1999 http://ec.europa.eu/health/archive/ph_risk/committees/sct/documents/out45_en.pdf
CSTEE, Scientific Committee for Toxicity, Ecotoxicity and the Environment (2001a)
107 Evaluation of DEHP alternatives Opinion on the results of the Risk Assessment of: 1,2‐Benzenedicarboxylic acid di‐C9‐11‐branched alkyl esters, C10‐rich and di‐“isodecyl” phthalate. Report version Human health effects: Final report, May 2001. Opinion expressed at the 24th CSTEE plenary meeting, Brussels, 12 June 2001 http://ec.europa.eu/health/scientific_committees/environmental_risks/opinions/sctee/sct_out103_ en.htm
CSTEE, Scientific Committee for Toxicity, Ecotoxicity and the Environment (2001b) Opinion on the results of the Risk Assessment of: 1,2‐Benzenedicarboxylic acid, di‐C8‐10‐branched alkyl esters, C9‐rich and di‐“isononyl” phthalate. Report version Human Health Effects: Final report, May 2001. Opinion expressed at the 27th CSTEE plenary meeting Brussels, 30 October 2001 http://ec.europa.eu/food/fs/sc/sct/out120_en.pdf
CSTEE, Scientific Committee for Toxicity, Ecotoxicity and the Environment (2004) Opinion on the Risk Assessment for Acetyl Tributyl Citrate (ATBC) Plasticizer used in Children's Toys. Adopted by the CSTEE during the 41st plenary meeting of 8 January 2004 European Commission Health & Consumer Protection Directorate‐General Brussels
Dalgaard, M.; Hass, U.; Vinggaard, A.M.; Jarfelt, K.; Lam, H.R.; Sorensen, I.K.; Sommer, H.M.; Ladefoged, O. (2003) Di(2‐ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre‐ and postnatally exposed Wistar rats Reproductive Toxicology, 17, 163‐170
Danish EPA, Environmental Protection Agency (2012) 4th Draft Background Document Proposal for a Restriction Substance Name: Bis(2‐ Ehtylhexyl)Phthlate (DEHP), Benzyl Butyl Phthalate (BBP), Dibutyl Phthalate (DBP), Diisobutyl Phthalate (DIBP). Version Number: (4) May 4, 2012 Danish Environmental Protection Agency, Copenhagen
Deisinger, P.J.; Perry, L.G.; Guest, D. (1998) In vivo percutaneous absorption of [14C]DEHP from [14C]DEHP‐plasticized polyvinyl chloride film in male Fischer 344 rats [Erratum 'Food and Chemical Toxicology, 36, 1998] Food and Chemical Toxicology, 36, 521‐527
EC, European Commission (1995) Report of the Scientific Committee for Food. 33rd series. First report of the Scientific Committee for Food on certain additives used in the manufacture of plastic materials intended to come into contact with foodstuffs. Opinion expressed until 3 May 1992 Directorate General for Industry
108 Evaluation of DEHP alternatives
ECB, European Chemicals Bureau (2003a) European Union Risk Assessment Report: 1,2‐Benzenedicarboxylic Acid, Di‐C8‐10‐Branched Alkyl Esters, C9‐Rich and Di‐“Isononyl” Phthalate (DINP). 2nd Priority List. Vol. 35 EUR 20784 EN. European Commission. Joint Research Centre
ECB, European Chemicals Bureau (2003b) European Union Risk Assessment Report: 1,2‐Benzenedicarboxylic Acid, Di‐C9‐11‐Branched Alkyl Esters, C10‐Rich and Di‐“Isodecyl” Phthalate (DIDP). 2nd Priority List. Vol. 36 EUR 20785 EN. European Commission. Joint Research Centre
ECB, European Chemicals Bureau (2008) European Union Risk Assessment Report: bis(2‐Ethylhexyl)phthalate (DEHP). 2nd Priority List, Vol. 80 EUR 23384 EN. European Commission. Joint Research Centre
ECHA, European Chemicals Agency (2012) Evaluation of new scientific evidence concerning DINP and DIDP in relation to entry 52 of Annex XVII to Regulation (EC) No. 1907/2006 (REACH). Draft Review Report. Version 3. 7 May 2012 http://echa.europa.eu/documents/10162/13641/information_note_dinp_didp_en.pdf
ECHA, European Chemicals Agency (2013) Information on Chemicals ‐ Registered Substances Online: http://echa.europa.eu/web/guest/information‐on‐chemicals/registered‐substances
ECPI, European Council for Plasticisers and Intermediates (2009) Review of Recent Scientific Data on Di‐isononyl Phthalate (DINP) and Risk Characterisation for its use in Toys and Childcare articles. Technical report 2009‐0601‐DINP, June 2009 http://www.cpsc.gov/about/cpsia/docs/DINPToysExxon062009.pdf
EFSA, European Food Safety Authority (2005a) Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) on a request from the Commission related to Di‐isodecylphthalate (DIDP) for use in food contact materials. Question N° EFSA‐Q‐2003‐195. Adopted on 30 July 2005 The EFSA Journal, 245, 1‐14 http://www.efsa.europa.eu/en/efsajournal/doc/245.pdf
EFSA, European Food Safety Authority (2005b)
109 Evaluation of DEHP alternatives Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Di‐isononylphthalate (DINP) for use in food contact materials The EFSA Journal, 244, 1‐18 http://www.efsa.europa.eu/en/efsajournal/pub/244.htm
EFSA, European Food Safety Authority (2006) Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request related to a 12th list of substances for food contact materials The EFSA Journal, 395‐401, 1‐21 http://www.efsa.europa.eu/en/scdocs/doc/395.pdf
EFSA, European Food Safety Authority (2009) Scientific Opinion on the safety evaluation of the substance, alkyl(C10‐C21)sulphonic acid, esters with phenol, CAS No. 91082‐17‐6, for use in food contact materials EFSA Panel on food contact materials, enzymes, flavourings and processing aids (CEF) The EFSA Journal, 7, 1398
Environment Canada (2011) Screening Assessment for the Challenge. Hexanedioic acid, bis(2‐ethylhexyl) ester (DEHA), Chemical Abstracts Service Registry Number 103‐23‐1 Environment Canada, Health Canada, September 2011 http://www.ec.gc.ca/ese‐ees/default.asp?lang=En&n=39958D25‐1
EPA, Environmental Protection Agency (2003a) High Production Volume (HPV) Chemical Challenge Program. Test plan for the diesters category of the aliphatic esters chemicals Prepared by: American Chemistry Council’s Aliphatic Esters Panel http://www.epa.gov/hpv/pubs/summaries/alipestr/c13466rt.pdf
EPA, Environmental Protection Agency (2003b) High Production Volume (HPV) Chemicals Challenge Program, Assessment of Data Availability and Test Plan – Acetyl Tributyl Citrate, December 16, 2003, Appendix: Index of robust summaries of reliable studies and QSAR model data acetyl tributyl citrate) http://www.epa.gov/hpv/pubs/summaries/acetlcit/c15025.pdf
EPA, Environmental Protection Agency (2008) Supporting Documents for Initial Risk‐Based Prioritization of High Production Volume Chemicals. QUALITATIVE SCREENING‐LEVEL RISK CHARACTERIZATION FOR Diesters Category
110 Evaluation of DEHP alternatives U.S. Environmental Protection Agency http://www.epa.gov/chemrtk/hpvis/rbp/Cat_Diesters_Web_SuppDocs_Sept2008.pdf
EPA, Environmental Protection Agency (2013) Integrated Risk Information System (IRIS) online: http://www.epa.gov/IRIS/
EPA, Environmental Protection Agency (undated via ChemID) High Production Volume Information System (HPVIS) http://ofmpub.epa.gov/oppthpv/quicksearch.display?pChem=101124
Exxon, Biomedical Sciences (1986) Chronic Toxicity/Oncogenicity Study in F‐344 Rats. Test Material: MRD‐83‐260. Project No 326075 performed at Exxon Biomedical Sciences, Inc. Unpublished Laboratory Report (as cited in EC 2003a)
Fabjan, E.; Hulzebos, E.; Mennes, W.; Piersma, A.H. (2006) A category approach for reproductive effects of phthalates Critical Reviews in Toxicology, 36, 695‐726
Felder, J.D.; Adams, W.J.; Saeger, V.W. (1986) Assessment of the safety of dioctyl adipate in freshwater environments Environmental Toxicology and Chemistry, 5, 777‐784
Ghisari, M.; Bonefeld‐Jørgensen, E.C. (2009) Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions Toxicology Letters, 189, 67‐77
Hartwig, A. (2011) Gesundheitsschädliche Arbeitsstoffe, Toxikologisch‐arbeitsmedizinische Begründungen von MAK‐ Werten, Loseblattsammlung, 50. Lfg DFG Deutsche Forschungsgemeinschaft, WILEY‐VCH Verlag Weinheim http://onlinelibrary.wiley.com/book/10.1002/3527600418/topics
Hellwig, J.; Freudenberger, H.; Jäckh, R. (1997) Differential prenatal toxicity of branched phthalate esters in rats
111 Evaluation of DEHP alternatives Food and Chemical Toxicology, 35, 501‐512
Hushka, L.J.; Waterman, S.J.; Keller, L.H.; Trimmer, G.W.; Freeman, J.J.; Ambroso, J.L.; Nicolich, M.; McKee, R.H. (2001) Two‐generation reproduction studies in rats fed di‐isodecyl phthalate Reproductive Toxicology, 15, 153‐169
IARC, International Agency for Research on Cancer (2000) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 77. Some Industrial Chemicals WHO, World Health Organization, Geneva
Johnson, W. (2002) Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate International Journal of Toxicology, 21, Suppl. 2, 1‐17
Lambert, N.; Rostock, C.; Hetland, S. (2010) Environmental risks associated to plasticizers and sweeteners in the nordic countries Published: oslo/december 2010. bergfald miljørådgivere, kongens gate 3 0153 oslo. Project carried out for: the nordic screening group
Lee, H.‐C.; Ko, Y.G.; Im, G.S.; Chung, H.J.; Seong, H.H.; Chang, W.K.; Yamanouchi, K.; Nishihara, M. (2006a) Effects of phthalate/adipate esters exposure during perinatal period on reproductive function after maturation in rats Journal of Animal Science and Technology, 48, 651‐662
Lee, H.‐C.; Yamanouchi, K.; Nishihara, M. (2006b) Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats Journal of Reproduction and Development, 52, 343‐352
Letinski, D.J.; Connelly, M.J.; Peterson, D.R.; Parkerton, T.F. (2002) Slow‐stir water solubility measurements of selected alcohols and diesters Chemosphere, 48, 257‐265
112 Evaluation of DEHP alternatives Lington, A.W.; Bird, M.G.; Plutnick, R.T.; Stubblefield, W.A.; Scala, R.A. (1997) Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats Fundamental and Applied Toxicology, 36, 79‐89
Maag, J.; Lassen, C.; Brandt, U.K.; Kjølholt, J.; Molander, L.; Hagen Mikkelsen, S. (2010) Identification and assessment of alternatives to selected phthalates. Environmental Project No. 1341 Danish Environmental Protection Agency
Ministry of the Environment, Japan (2003) MEDAKA ‐ Oryzias latipes. Development of Test Methods and Suitability of Medaka as Test Organism for Detection of Endocrine Disrupting Chemicals Chemicals Evaluation and Research Institute, Japan
NICNAS, National Industrial Chemicals Notification and Assessment Scheme (2007) FULL PUBLIC REPORT 1,2‐Benzenedicarboxylic acid, bis(2‐propylheptyl) ester (Palatinol 10‐P) File No: EX/93 (STD/1054) March 2007 Australian Government, Department of Health and Ageing http://www.nicnas.gov.au/publications/CAR/new/EX/exFULLR/ex0000FR/ex93FR.pdf
NICNAS, National Industrial Chemicals Notification and Assessment Scheme (2008) 1,2‐Cyclohexanedicarboxylic acid, 1,2‐diisononyl ester (‘Hexamoll DINCH’) August 2008. File No: STD/1259 Australian Government Department of Health and Ageing http://www.nicnas.gov.au/publications/car/new/std/stdfullr/std1000fr/std1259fr.pdf
NICNAS, National Industrial Chemicals Notification and Assessment Scheme (2009) Glycerides, castor‐oil mono‐, hydrogenated, acetates. File No: STD/1334 Australian Government Department of Health and Ageing
NTP, National Toxicology Program (2003) NTP‐CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di‐ Isodecyl Phthalate (DIDP)
OECD, Organisation for Economic Co‐Operation and Development (2000)
113 Evaluation of DEHP alternatives SIDS Initial Assessment Report for SIAM 10. Bis(2‐ethylhexyl)adipate (DEHA) Paris, France http://www.chem.unep.ch/irptc/sids/OECDSIDS/103231.pdf
OECD, Organisation for Economic Co‐Operation and Development (2002a) SIDS Initial Assessment Report for SIAM 14 Paris, France, 26‐28 March 2002 http://www.chem.unep.ch/irptc/sids/OECDSIDS/indexcasnumb.htm
OECD, Organisation for Economic Co‐Operation and Development (2002b) SIDS Initial Assessment Report for SIAM 14. Tris(2‐ethylhexyl)benzene‐1,2,4‐tricarboxylate Paris, France
OECD, Organisation for Economic Co‐Operation and Development (2003a) OECD HPV Chemical Programme, SIDS Dossier, approved at SIAM 17 (11‐14 November 2003) http://webnet.oecd.org/Hpv/UI/SIDS_Details.aspx?id=C1534369‐697F‐46E5‐83A6‐626F8BC31554
OECD, Organisation for Economic Co‐Operation and Development (2003b) SIDS Initial Assessment Report for SIAM 17: Di(2‐ethylhexyl)terephthalate (DEHT) Arona, Italy, 11‐14 November 2003 Paris, France
Patyna, P.J.; Brown, R.P.; Davi, R.A.; Letinski, D.J.; Thomas, P.E.; Cooper, K.R.; Parkerton, T.F. (2006) Hazard evaluation of diisononyl phthalate and diisodecyl phthalate in a Japanese medaka multigenerational assay Ecotoxicology and Environment Safety, 65, 36‐47
RAC/SEAC, Committee for Risk Assessment, Committee for Socio‐economic Analysis (2012) Background document to the Opinion on the Annex XV dossier proposing restrictions on four phthalates. ECHA/RAC/RES‐O‐0000001412‐86‐07/S1 ECHA, European Chemicals Agency
Rhodes, J.E.; Adams, W.J.; Biddinger, G.R.; Robillard, K.A.; Gorsuch, J.W. (1995) Chronic toxicity of 14 phthalate esters to Daphnia magna and rainbow trout (Oncorhynchus mykiss) Environmental Toxicology and Chemistry, 14, 1967‐1976
Robillard, K.A.; Dufresne, D.L.; Gorsuch, J.W.; Stubblefield, W.A.; Staples, C.A.; Parkerton, T.F. (2008)
114 Evaluation of DEHP alternatives Aqueous solubility and Daphnia magna chronic toxicity of di(2‐ethylhexyl) adipate Bulletin of Environmental Contamination and Toxicology, 80, 539‐543
SCCP, Scientific Committee on Consumer Products (2007) Opinion on Phthalates in cosmetic products. SCCP/1016/06, 21 March 2007 http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_106.pdf
SCENIHR, Scientific Committee on Emerging and Newly‐Identified Health Risks (2008) Opinion on the safety of medical devices containing DEHP‐plasticized PVC or other plasticizers on neonates and other groups possibly at risk. Adopted after public consultation by the SCENIHR during the 22nd Plenary of 6 February 2008 http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_014.pdf
SCF, Scientific Committee on Food (2000) Opinion of the Scientific Committee on Food on a survey on dietary intake of the food contact material di‐2‐(ethylhexyl) adipate (DEHA) (expressed on 19 October 2000) http://ec.europa.eu/food/fs/sc/scf/out77_en.pdf
SCHER, Scientific Committee on Health and Environmental Risks (2008) Opinion on Phthalates in School Supplies European Commission, Health & Consumer Protection DG, Directorate C: Public Health and Risk Assessment, Unit C7 ‐ Risk Assessment, Brussels, Belgium http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_106.pdf
Silva, M.J.; Furr, J.; Preau, J.L.; Samandar, E.; Gray, L.E.; Calafat, A.M. (2012) Identification of potential biomarkers of exposure to di(isononyl)cyclohexane‐1,2‐dicarboxylate (DINCH), an alternative for phthalate plasticizers Journal of Exposure Science and Environmental Epidemiology, 22, 204‐211 ter Veld, M.G.; Schouten, B.; Louisse, J.; van Es, D.S.; van der Saag, P.T.; Rietjens, I.M.; Murk, A.J. (2006) Estrogenic potency of food‐packaging‐associated plasticizers and antioxidants as detected in ERalpha and ERbeta reporter gene cell lines Journal of Agricultural and Food Chemistry, 54, 4407‐4416
Tønning, K.; Jacobsen, E.; Pedersen, E.; Strange, M.; Brunn Poulsen, P.; Moller, L.; Buchardt Boyd, H. (2009)
115 Evaluation of DEHP alternatives Survey and Health Assessment of the exposure of 2 year‐olds to chemical substances in Consumer Products. Survey of Chemical Substances in Consumer Products, No. 102 Danish Environmental Protection Agency van Engelen, J.G.M.; Park, M.V.D.Z.; Janssen, P.J.C.M.; Oomen, A.G.; Brandon, E.F.A.; Bouma, K.; Sips, A.J.A.M.; van Raaij, M.T.M. (2008) Chemicals in Toys. A General Methodology for Assessment of Chemical Safety of Toys with a Focus on Elements. RIVM Report 320003001/2008 RIVM, Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, Netherlands
Versar Inc. (2011) FINALTOXICITY REVIEW FOR DI(2‐PROPYLHEPTYL) PHTHALATE Prepared by: Versar Inc. 6850 Versar Center Springfield, VA 22151 SRC, Inc. 7502 Round Pond Road North Syracuse, NY 13212 Prepared for: Kent R. Carlson, Ph.D. U.S. Consumer Product Safety Commission 4330 East West Highway Bethesda, MD 20814 May 16, 2011 http://www.cpsc.gov//PageFiles/125788/dphp.pdf
Vinggaard, A.M.; Niemela, J.; Wedebye, E.B.; Jensen, G.E. (2008) Screening of 397 chemicals and development of a quantitative structure ‐ activity relationship model for androgen receptor antagonism Chemical Research in Toxicology, 21, 813‐823
Waterman, S.J.; Ambroso, J.L.; Keller, L.H.; Trimmer, G.W.; Nikiforov, A.I.; Harris, S.B. (1999) Developmental toxicity of di‐isodecyl and di‐isononyl phthalates in rats Reproductive Toxicology, 13, 131‐136
Waterman, S.J.; Keller, L.H.; Trimmer, G.W.; Freeman, J.J.; Nikiforov, A.I.; Harris, S.B.; Nicolich, M.J.; McKee, R.H. (2000) Two‐generation reproduction study in rats given di‐isononyl phthalate in the diet Reproductive Toxicology, 14, 21‐36
WHO, World Health Organization (2000) Safety evaluation of certain food additives and contaminants. Fifty‐third Meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). WHO Food Additives Series: 44 Online: http://www.inchem.org/documents/jecfa/jecmono/v44jec14.htm
Wildhack, A.; Fiala, F.; Steiner, I. (2001)
116 Evaluation of DEHP alternatives Migrationsverhalten von Weichmachern in Bedarfsgegenständen Lebensmittelchemie, 55, 156
Wittassek, M.; Angerer, J. (2008) Phthalates: metabolism and exposure International Journal of Andrology, 31, 131‐138