ANALYSIS of ALTERNATIVES Public Version

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ANALYSIS OF ALTERNATIVES Public Version

Legal name of applicant: LANXESS Deutschland GmbH

Submitted by: LANXESS Deutschland GmbH

Substance: 1,2-Dichloroethane (EDC) EC Number: 203-458-1 CAS Number: 107-06-2

Use title: Use 1: Industrial use as a swelling agent during the sulphonation reaction of polystyrene-divinylbenzene copolymer beads in the manufacturing of strong acid cation exchange resins Use 2: Industrial use as a swelling agent and reaction medium during the phthalimidomethylation reaction of polystyrene-divinylbenzene copolymer beads in the manufacturing of anion exchange and chelating resins

Use numbers: 1 and 2

Disclaimer

This report has been prepared by Risk & Policy Analysts Ltd, with reasonable skill, care and diligence under a contract to the client and in accordance with the terms and provisions of the contract. Risk & Policy Analysts Ltd will accept no responsibility towards the client and third parties in respect of any matters outside the scope of the contract. This report has been prepared for the client and we accept no liability for any loss or damage arising out of the provision of the report to third parties. Any such party relies on the report at their own risk.

Table of contents

1 Summary ...... 1 1.1 Background to this analysis of alternatives ...... 1 1.2 Identification of potential alternatives for EDC and overall feasibility ...... 2 1.3 Technical feasibility of potential alternatives for EDC ...... 3 1.4 Economic feasibility of potential alternatives for EDC ...... 3 1.5 Risk reduction capabilities of the alternatives ...... 6 1.6 Availability of potential alternatives for EDC ...... 6 1.7 Actions needed to improve the suitability and availability of potential alternatives ...... 7

2 Analysis of substance function ...... 9 2.1 Introduction ...... 9 2.2 Background information on IERs ...... 10 2.3 Production and classification of IERs ...... 13 2.4 Overview of the applicant’s IER production activities ...... 17 2.5 Technical feasibility criteria for alternative substances...... 29 2.6 Technical feasibility criteria for alternative techniques ...... 34 2.7 Conclusion on technical criteria for alternatives ...... 35

3 Annual tonnage ...... 37

4 Identification of possible alternatives...... 38 4.1 Introduction and list of possible alternatives ...... 38 4.2 Description of efforts made to identify possible alternative ...... 38 4.3 Conclusion ...... 56

5 Suitability and availability of possible alternatives ...... 58 5.1 Alternative 1: 1,3-DCP (Uses 1 and 2) ...... 58 5.2 Alternative 2: 1,4-DCB (Use 2 only) ...... 66 5.3 Alternative 3: Solventless sulphonation technique (Use 1 only) ...... 73 5.4 Alternative 4: '''''' '''''''#E'''''' ''''''''''''' '' technique (Use 2 only) ...... 80

6 Overall conclusions on suitability and availability of possible alternatives ...... 93 6.1 Alternative substances and technologies considered ...... 93 6.2 Conclusions on comparison of alternatives to EDC ...... 93 6.3 Overall conclusion and future research and development ...... 96

7 Annex 1: Risk evaluation of alternative substances ...... 97 7.1 Methodological approach ...... 97 7.2 Hazard profiles for EDC and alternative substances ...... 98 7.3 Comparative assessment ...... 110 7.4 References for Annex 1 ...... 112

8 Annex 2: LANXESS screening - list of substances ...... 117

9 Annex 3: LANXESS IER products ...... 120

10 Annex 4: Qualification example - FDA food contact approval ...... 130

11 Annex 5: Justifications for confidentiality claims ...... 131

References ...... 132

List of abbreviations

AER: Anion Exchange Resin AfA: Application for Authorisation AoA: Analysis of Alternatives CR: Chelating Resin CSR Chemical Safety Report 1,4-DCB: 1,4-Dichlorobutane 1,3-DCP: 1,3-Dichloropropane DMEL: Derived Minimal Effect Level DNEL: Derived No Effect Level DVB: Divinylbenzene EDC: 1,2-Dichloroethane FDA: Food and Drug Administration NOAEC: No Observed Adverse Effect Concentration IER: Ion Exchange Resin NSF: National Sanitation Foundation (NSF International) OECD: Organisation for Economic Co-Operation and Development OEL: Occupational Exposure limit OGTP: Off-Gas Treatment Plant PNEC: Predicted No Effect Concentration PS: Polystyrene R&D: Research and Development ResAP: Council of Europe, Committee of Ministers Resolution SAC ER: Strong Acid Cation Exchange Resin SEA: Socio-Economic Analysis SIDS: Screening Information Dataset STOT: Specific Target Organ Toxicity STP: Sewage Treatment Plant SVHC: Substance of Very High Concern TRIPS: World Trade Organisation agreement on Trade-Related Aspects of Intellectual Property Rights

1 Summary

1.1 Background to this analysis of alternatives

This Application for Authorisation (AfA) has been submitted by LANXESS Deutschland GmbH. The substance of concern is 1,2-dichloroethane (hereafter referred to as EDC), EC No. 203-458-1, CAS No. 107-06-2. The applicant is applying for two uses of EDC which are associated with a combined consumption of '''''#B '''' (Use 1 accounts for ''''' '#B ''' and Use 2 for ''''''#B'''') of the substance:

 Use 1: Industrial use as a swelling agent during the sulphonation reaction of polystyrene- divinylbenzene copolymer beads in the manufacturing of strong acid cation exchange resins

 Use 2: Industrial use as a swelling agent and reaction medium during the phthalimidomethylation reaction of polystyrene-divinylbenzene copolymer beads in the manufacturing of anion exchange and chelating resins.

Both processes take place within the applicant’s Leverkusen production facility in Germany (discussed further in Section 2.4) and, to a certain extent, they are mutually supporting, with EDC circulated in one closed loop. In addition, as can be deduced from the use wording, the function of EDC in the processes shares significant similarities. Given these similarities, to avoid extensive repetition and ensure process synergies are elucidated, both uses of EDC have been assessed within a single AoA document, although where important (e.g. in the identification of technical feasibility criteria and the detailed assessment of the shortlisted alternatives) discussion on the uses has been separated1.

With regard to the relevant products manufactured by the applicant, strong acid cation exchange resins (SAC ERs), anion exchange resins (AERs) and chelating resins (CRs) are all sub-categories of ion exchange resin (IER) that find use across a very diverse range of downstream sectors, from water softening applications to waste decontamination in the nuclear industry. SAC ERs are characterised by their ability to exchange cations or split neutral salts and are useful across the entire pH range (Dow, 2000), AERs work by the same principal but replace negatively charged ions, and CRs exhibit a high degree of selectivity for a specific metal ion, or an exactly definable group of different metal ions (LANXESS, 2006).

The authorisation has been applied for so that EDC will continue to be used at the applicant’s plant until feasible and suitable alternatives for the two uses become available. Based on these considerations and timeframes associated with progressing R&D projects, the applicant is seeking a 4 year review period for Use 1 and a 12 year review period for Use 2.

For both uses, the argumentation in this AfA is based on two pillars:

 The lack of a (current) technically and economically feasible alternative for EDC that results in a reduction of risk, and  The demonstration that the socio-economic benefits from the continued use of the substance significantly outweigh the risks to human health, as shown in the accompanying Socio-Economic Analysis (SEA) document.

1 Throughout the document, for simplicity, Use 1 is referred to as the ‘sulphonation’ process, and Use 2 as the ‘phthalimidomethylation’ or ‘phthalimide’ process.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 1 1.2 Identification of potential alternatives for EDC and overall feasibility

The applicant has followed a detailed, stepwise and logical approach to screen over 100 potential alternative substances for EDC. The initial list was identified via the utilisation of the applicant’s in house information system software, in combination with an in-depth review of the available scientific and technical literature. Substances were shortlisted (or were eliminated from further consideration) based on the results of several screening steps. For the identification of alternative techniques extensive literature searches were also undertaken. The overall process resulted in the selection of four potential alternatives (two substances, one technique and one substance/technique combination) across the two uses, which proceeded to a detailed analysis in Section 5 of this AoA. These potential alternatives have been identified in the table below.

Table 1-1: Shortlist of alternatives to be assessed in Section 5 of AoA Shortlisted alternative Substance (CAS No) / Use 1 - Use 2 - technique Sulphonation Phthalimidomethylation 1,3-Dichloropropane (1,3-DCP) Substance (142-28-9)   1,4-Dichlorobutane (1,4-DCB) Substance (110-56-5)   Solventless sulphonation Technique   ''''''''''' '''#E''''''''''' technique Technique incorporating an alternative substance   ''''''''##E ''''''''

The overall outcome of the applicant’s analysis with regard to these potential alternatives is shown in Table 1-2. Additional detail on feasibility aspects is provided in the following sub-sections.

Table 1-2: Overall conclusions on suitability and availability of shortlisted alternatives Potential alternative Solventless '''''''' ''#E '''''''''''''' Key consideration 1,3-DCP 1,4-DCB sulphonation technique (for uses 1 & 2) (for use 2 only) (for use 1 only) (for use 2 only) Not at present Not at present Not at present Not at present Is the potential (could become (could become (could become (could become alternative feasible by feasible by feasible by feasible by March technically feasible? November 2023 at November 2023 at November 2021 2029 at the the earliest) the earliest) at the earliest) earliest) Uncertain Not at present Not at present Uncertain (increased (increased Is the potential although although operating costs but operating costs but alternative potentially in the potentially in the whether this makes whether this makes economically future (depends future (depends substance infeasible substance feasible? on R&D project on R&D project not concluded) infeasible not outcome) outcome) concluded) Does the potential alternative result in a No No Yes Yes reduction of risk? Not at present Not at present Not at present Is the potential (substance itself is (substance itself is Not at present (substance itself is alternative (and available but available but (could become available but associated associated process associated process feasible by associated process technology / process not feasible until not feasible until November 2021 not feasible until to implement it) November 2023 at November 2023 at at the earliest) March 2029 at the available? the earliest) the earliest) earliest)

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 2 1.3 Technical feasibility of potential alternatives for EDC

The technical feasibility of the potential alternatives varies significantly, although a common element is that no alternative can be considered technically feasible to implement until significantly later than the EDC Sunset Date in November 2017.

1,3-DCP meets the necessary technical comparison criteria for both the sulphonation and phthalimide processes, but due to the required R&D activities, engineering work and process parameter modifications, the substance cannot be deemed a technically feasible alternative at this time. If LANXESS was to implement the alternative, theoretically, this could be achieved by November 2023 at the earliest. For 1,4-DCB, a similar conclusion and theoretical implementation timescale has been reached, although this substance’s high boiling point means it could only be implemented for the applicant’s phthalimidomethylation use.

The solventless sulphonation technique appears to offer no technical advantages over the EDC- based process with the exception that no solvent would need to be utilised and in its current form it does not allow for the production of sufficient quality SAC ER products to replace those currently manufactured at Leverkusen. However, since '''''' ''''''''''#D''''''' '''' ''''''''', the applicant has been implementing a detailed R&D plan with the aim of improving the technical feasibility of this technique and eventually replacing the synthesis of all ''' '#C '' EDC-based SAC ER products with new optimised recipes. The practical steps of the R&D plan demonstrate that to make the technique technically feasible, a minimum of 4 years from the November 2017 Sunset Date is required.

The '''''''''' '#E'''''''''''''''' technique is a novel combination of an alternative technology and substance put forward by the applicant and in its present form it can certainly be considered an infeasible alternative to the EDC-based phthalimidomethylation process. In parallel with the applicant’s sulphonation R&D activities, since '''''''#D''''''''' LANXESS has been implementing a detailed R&D plan with the aim of demonstrating (and vastly improving) its technical feasibility. The aim of the applicant’s activities is to eventually replace the synthesis of all '''#C'''' EDC-based AER/CR products with new, optimised recipes that forego the use of EDC in their production. The practical steps of the R&D plan demonstrate that many hurdles will have to be overcome to make the technology technically feasible, and a minimum of 12 years from the November 2017 Sunset Date will be required. 1.4 Economic feasibility of potential alternatives for EDC

A summary of key economic feasibility considerations for each potential alternative is provided in Table 1-3, overleaf.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 3 Table 1-3: Overall conclusions on the economic feasibility of shortlisted alternatives Potential alternative Cost category 1,3-DCP 1,4-DCB Solventless sulphonation ''''''''''''#E ''''''''''''''''' technique (for uses 1 & 2) (for use 2 only) (for use 1 only) (for use 2 only) Investment costs (and ability to acquire finance) Research and development Major cost: ''''''''' '''#D''''''' (€1- Major cost: ''''''''#D ''''''''' (€1-10 Major cost: '''''''' '#D '''''''' Major cost: ''''' '''''#D ''''' (€1-10 activities 10 million) million) (€1-10 million) million) Cost of changes to the process Major cost: '''''''#D ' ''''''''' (€1-10 Major cost: ''''''''' '#D ''''''''''''' Major cost: ''''''''''#D '''''''' Major cost: '''''''''' #D '''''''''' (€10- plant (acquisition of new million) (€1-10 million) (€1-10 million) 100 million) equipment and cost of installation) Recertification and requalification Major cost: '''''''#D '''''''''' (€1-10 Major cost: '''''''''#D ' ''''''''''''' Major cost: ''''''''''''#D'''''''''''''' Major cost: '''''''''#D ' ''''''''' (€1-10 million) (€1-10 million) (€<1 million) million) Employee training costs 1 month of retraining activities 1 month of retraining activities 1 month of retraining 6 months of retraining activities would be required. This would would be required. This would activities would be required. would be required. Anticipated be a minor cost in the context be a minor cost in the context This would be a minor cost costs have not been quantified of overall implementation of overall implementation in the context of overall but are expected to be significant implementation Applicant’s ability to acquire Not straightforward due to high finances to implement Difficult because substance Difficult because substance costs but innovative character of alternative? does not result in a reduction of does not result in a reduction of Given the novel technique and risk, but not impossible risk, but not impossible expected health benefits for workers give a good chance Operating costs (compared to EDC based process) Energy costs Increase (due to higher steam Increase (due to higher steam Increase (due to higher Increase (due to higher electricity consumption) consumption) electricity and steam costs) and steam costs) Materials and service costs Increase (due to higher cost of Increase (due to higher cost of Decrease (as no solvent is Increase (due to the higher solvent) solvent) required in the process) solvent costs and quantities, additional costs for other raw materials and increased environmental service costs) Labour costs No significant change expected No significant change expected No significant change Increase expected Maintenance and laboratory costs No significant change expected No significant change expected No significant change Increase expected

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 4 Table 1-3: Overall conclusions on the economic feasibility of shortlisted alternatives Potential alternative Cost category 1,3-DCP 1,4-DCB Solventless sulphonation ''''''''''''#E ''''''''''''''''' technique (for uses 1 & 2) (for use 2 only) (for use 1 only) (for use 2 only) Other costs No significant change expected No significant change expected No significant change Increase expected

Additional considerations Changes to product quality Quality of products would be Quality of products would be Highly uncertain at this time. Highly uncertain at this time. anticipated to be retained anticipated to be retained Issues being addressed in Issues being addressed in R&D R&D plan plan Changes in production volumes Not anticipated to be an issue Not anticipated to be an issue A lower yield of functionalised Uncertain at this time. from a process perspective from a process perspective resins is expected to be obtained Issues being addressed in via this technique. Issues being R&D plan addressed in R&D plan Overall summary Investment costs of at least Investment costs of at least Investment costs of at least '''''' ''''''''#D '''''''''''' ''''''' '#D ''''''' Investment costs of at least ''''''#D ''' (€10-100 million) (€1-10 million) '''''''''' #D ''''''''' (€10-100 million) (€1-10 million) Increase in operating costs of at Increase in operating costs of Increase in operating costs of least 25-30% at least 5% at least 5% Operating costs will increase but these have not Other key factors: Other key factors: Other key factors: been quantified at present - product quality diminished Total cost of switching - from a hazard perspective, the - from a hazard perspective, the compared to current technology (investment costs, operating costs substance is not a suitable substance is not a suitable Other key factors: -significantly lower yield achieved and other key factors) alternative and its future alternative and its future - product quality diminished - capital investment and technical regulatory status (and longer regulatory status (and longer compared to current / engineering / analytical term economic feasibility) is term economic feasibility) is technology resources required to implement therefore uncertain therefore uncertain this option are substantial Additional R&D required for Substance would also require Substance would also require successful implementation Additional R&D required for registration. Associated costs registration. Associated costs (this is being undertaken) successful implementation (this for applicant estimated at up to for applicant estimated at up to is being undertaken) €350,000 €350,000

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 5 1.5 Risk reduction capabilities of the alternatives

In a separate detailed report (available as Annex 1 (Section 7) of this AoA) a comparative risk assessment for environmental and human health effects is described for 1,3-DCP, 1,4-DCB and ''''''''''' '''''''#E''''''''''''. No detailed assessment was undertaken for solventless sulphonation, as the technique removes altogether the need for a solvent within the process, and is therefore assumed to fulfil the requirement of leading to a reduction in overall risks to human health and the environment compared to EDC.

Based on the results of the comparative exposure assessment and risk characterisation, all alternative substances seem to be advantageous compared to EDC with regard to human health effects. However, 1,3-DCP is accompanied by positive genotoxicity test results and 1,4-DCB has not been adequately investigated for genotoxicity and carcinogenicity. Together with the close structural relationship to other dichlorinated short-chain aliphatics with proven or suspected carcinogenic properties, 1,3-DCP and 1,4-DCB are suspected of having carcinogenic properties of their own and thus cannot be considered suitable alternatives.

With regard to '''''''''' #E''''' '''''''''''', the substance is corrosive and local effects determine its toxicological profile. Appropriate risk management measures have to be implemented to adequately control respective risks. If this is ensured, it can be considered a suitable candidate from a human health perspective.

With regard to the environment, due to a higher aquatic toxicity and lower volatility, 1,3-DCP and 1,4-DCB lead to similar or even more severe environmental concerns than EDC. This corroborates their questionable suitability as alternatives from a risk reduction perspective. ''''''''''''' ''#E''''''''''''''', due to ''''' ''''''''' ''''#E ''''' '''' '''''''''' ''''''''', has a favourable environmental profile.

In conclusion, ''''''''''' ''#E ''''''''''''''''''' is the only substance that can reasonably be expected to lead to reduced risks for human health and the environment, when compared to EDC. 1.6 Availability of potential alternatives for EDC

With regard to availability, for 1,3-DCP, 1,4-DCB and '''''''''' ''#E '''''''''''''''''' (as part of the ''''#E '''''''' ''''''#E '''''''' technique), the applicant considered the following three factors (for the solventless sulphonation technique, as no solvent is required, only the last point was considered):

 Availability of the alternatives in quantities sufficient for the applicant’s production processes  Availability of the alternatives in the quality required by the applicant’s production processes  Access to the technology that allows the implementation of the alternatives as a replacement for EDC.

Neither 1,3-DCP or 1,4-DCB have been registered under REACH (although pre-registrations are available). Consequently, the substances are not considered available from an EU source, meaning they would have to be imported. The applicant is confident that they would theoretically be able to obtain sufficient volumes of either substance (and at the required quality), and has identified two non-EU suppliers for both substances. However, none of the identified suppliers are willing to register the substances meaning that LANXESS would be required to undertake these activities and absorb the associated costs (anticipated to be ≥ €350,000 in each case).

For ''''''''''' #E ''''''''''''', it is not envisaged that there would be any difficulties with regard to sourcing the alternative substance at the required quantity (the applicant has identified 8 EU suppliers and

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 6 >10 non-EU suppliers). The applicant can also state with a high level of confidence that sourcing the required quality of ''''''''''' ''#E ''''''''''''''' would not be an issue. However, the applicant does not at present (and could not until significantly beyond the Sunset Date) have access to the technology to fully implement '''''''''' ''#E ''''''''''', within the overall technique, as an alternative for EDC. Therefore, the ‘'''''''''''' '#E '''''''''''' technique’ is not considered available to the applicant.

In the same vein, the solventless sulphonation technique is also considered unavailable at this time (given that it can only be considered a technically feasible replacement after November 2021 at the earliest). 1.7 Actions needed to improve the suitability and availability of potential alternatives

The practical steps of the R&D demonstrate that to make the solventless sulphonation and ''''''#E '' '''#E'''''''''' techniques technically feasible, respectively, for sulphonation and phthalimidomethylation, a minimum of 4 and 12 years from the November 2017 Sunset Date are required. The expected timeline for the applicants R&D projects from proof of principle to plant implementation is provided in the following table.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 7

Table 1-4: Overall minimum foreseeable timeframe for the implementation of alternatives for the sulphonation and phthalimidomethylation uses Timeline Step 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 Overall minimum foreseeable timeframe for the implementation of the solventless sulphonation technique (Use 1 alternative) Proof of principle

Development

Validation #D

Plant implementation Overall minimum foreseeable timeframe for the implementation of the ''''''''''' ''#E ''''''''''' technique (Use 2 alternative) Proof of principle

Development

Validation J V#D

Plant implementation

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 8 2 Analysis of substance function

2.1 Introduction

This Application for Authorisation (AfA) is being submitted by LANXESS Deutschland GmbH, a wholly owned subsidiary of LANXESS AG, the parent company of the LANXESS Group.

As highlighted above, EDC is used by the applicant in two separate, albeit similar, uses:

 Industrial use as a swelling agent during the sulphonation reaction of polystyrene/ divinylbenzene (PS-DVB) copolymer beads in the manufacturing of strong acid cation exchange resins (SAC ERs)  Industrial use as a swelling agent and reaction medium during the phthalimidomethylation reaction of PS-DVB copolymer beads in the manufacturing of anion exchange resins (AERs) and chelating resins (CRs)

SAC ERs, AERs and CRs are all categories of Ion Exchange Resin (IER) that find use across a broad range of downstream sectors. Before a more detailed description of the applicant’s activities is provided, it is necessary for the reader to become familiarised with the IER sector more generally. Consequently, this section begins with the provision of background information, which includes:

 An introduction to the ion exchange process  An overview of the broad range of conventional and prospective uses of IERs  Information on the production of IERs (and their subsequent classification).

Following the provision of this information, the applicant’s overall activities in IER production are described and a detailed overview of the sulphonation and phthalimidomethylation processes, and EDC’s critical use as a swelling agent and reaction medium, is given. This is followed by analysis of the applicant’s approach to information collection and an overview of technical feasibility parameters that must be taken into account when considering the functional criteria a potential alternative for EDC is required to fulfil in each use.

This section has been structured to help the reader understand why the applicant’s specific uses of EDC are critical and why there are no alternatives that can be considered technically and economically feasible, and suitable at this time. An understanding of the overall sector is also vital when considering the applicant’s non-use scenarios in the corresponding SEA document, as a refused authorisation would not only affect their production of EDC-based SAC ER, AER and CRs but would also have ramifications that extend across a broader range of their production activities and also beyond their Leverkusen site.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 9 Consideration of this AoA in the context of other EDC Authorisation Consortium AfAs

This AoA has been prepared by an independent third party working on behalf of LANXESS Deutschland GmbH and a further seven EU-based users of EDC who collectively formed a EDC Authorisation Consortium (EDCAC). Activities of the EDCAC can be summarised within three broad areas: IERs, Pharmaceuticals and Slack Waxes. Of note, separate to this AoA (and AfA), there is one additional company within the consortium whose activities fall under the remit of ‘IERs’.

Despite similarities with regard to background information provided in the LANXESS Deutschland GmbH and other relevant user’s AoA documents, it must be emphasised that the possibility to replace EDC is (to a significant extent) based on company-specific processing parameters and customer requirements as well as a multitude of individual economic feasibility considerations. Consequently, the feasibility and availability of a ‘one size fits all’ alternative for LANXESS Deutschland GmbH and the other applicant should not by any means be assumed 2.2 Background information on IERs

2.2.1 Introduction

Ion exchange is the reversible interchange of ions between a solid (ion exchange material) and a liquid in which there is no permanent change in the structure of the solid. Ion exchange is commonly used in water treatment and provides a method of separation for many processes involving other liquids. It has special utility in chemical synthesis, food processing, medical research, mining, agriculture, drinking water purification and a variety of other areas (discussed further below) (Dow, 2000).

The utility of ion exchange rests with the ability to use and reuse the ion exchange material. The process occurs in a variety of substances and it has been used on an industrial scale since the early 1900’s with the introduction of water softening using natural and later, synthetic zeolites. Sulphonated coal, developed for industrial water treatment, was the first ion exchange material that was stable at low pH. The introduction of synthetic organic ion exchange resins in 1935 resulted from the synthesis of phenolic condensation products containing either sulphonic or amine groups which could be used for the reversible exchange of cations or anions (Dow, undated).

Conventional IERs contain an insoluble matrix fabricated from an organic polymer substrate that has the form of beads (spherical form) with a diameter in the range 0.5 – 1 mm. The beads are typically porous, providing a high surface area. Conventional IERs have a heterodisperse particle size distribution from about 0.3 mm to 1.2 mm (50-16 mesh) or are uniform particle sized resins with all beads in a narrow particle size range (Dow, 2000). Figure 2-1 shows examples of ‘typical’ IERs.

Figure 2-1: Examples of typical IER beads Source: Camden International (2014)

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 10 2.2.2 End uses

As noted above, ion exchange has a special utility in wide variety of processes. Table 2-1 presents some conventional and prospective applications of the broader range of ion exchange materials available, as described by Zagorodni (2007), and with some additional input from the applicant. The text and figures following the table highlight the common cyclic nature of IER use in some core applications.

Table 2-1: List of conventional and prospective applications of ion exchange materials Category Application Water preparation for different Preparation of pure and ultrapure deionised water purposes Water softening Potable water preparation Condensate polishing in power plants Removal of specific constitutes Dealkalisation Fluoride removal Removal of organic matter particularly colorants Oxygen removal Iron and manganese removal Cd2+ removal from drinking water Nitrate removal Ammonia removal Removal of radionuclides from drinking water Removal of other harmful ions from drinking water Nuclear industry Separation of uranium isotopes Waste decontamination Final storage of radioactive wastes Condensate polishing Decontamination and recuperation of Recycling of industrial water waste streams Removing of heavy metal ions Recuperation of metals Ammonia removal Recovery of calcium aconitate Removal of radioactive substances Isotope separation Eu3+ isotopes Lithium isotopes Boron isotopes Nitrogen isotopes Isotope analysis Pulp and paper industry Removal of inorganic salts from liquors Detoxification of by-products transferred for bio-cultivation Purification of sugars and polyhydric Purification of cane, corn, and beet sugars alcohols Purification of fructose Separation of monosaccharides Purification of glycerine Treatment of sorbitol Recovery of xylitol Food industry Removing off tasters and odours Recovery of glutamic-acid Purification of steviosides De-acidification of fruit juice Dairy Extraction of lactoperoxidase Purification of casein Winery Absorption of wine proteins in the production of wines Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 11 Table 2-1: List of conventional and prospective applications of ion exchange materials Category Application Stabilisation of wine Amino acids Recovery and purification of biological Proteins and biochemical substances Enzymes DNA Antibodies Biotechnology Separation of lactic acid from fermentative broth Production of L-glutamine Production of citric acid Organic acids Recovery and purification in Uranium hydrometallurgy Thorium Rare earths Tungsten Transition metals Gold, silver, platinum, palladium Solvent purification - Reagent purification - Preparation of inorganic salts - Catalysis Petroleum refining with zeolites Ethylbenzene synthesis Olefins isomerisation Catalytic reduction of nitrogen oxides Bisphenol A (BPA) synthesis Pharmaceuticals and medicine Antibiotics Vitamins Active ingredients Taste masking Tablet disintegration Controlled and sustained drug release Immobilisation of drugs in a carrier function Soil science and technology Artificial soils Remediation of contaminated soils Evaluation of soil properties Buffering - Analysis Chromatography Sample preparation, separation, concentrating, purification Replacement of analyte Drying of different media Desiccation of solvents with zeolites Gas drying with polymeric exchangers and zeolites Source: Zagorodni (2007) and Applicant’s information

As highlighted by Ramaswamy et al. (2013), ion exchangers are usually employed in cyclic processes (except when used on a very small scale). These cyclic operations involve sorption and desorption steps. For example, when considering water treatment applications such as water softening, a typical ion-exchange cycle will contain four steps (see Figure 2-2):

1. Backwash: removal of accumulated solids obtained by upflow of water to expand and fluidise the exchanger system

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 12 2. Regeneration2: In order to restore the original ionic form of the ion exchanger, a reagent called regenerant is passed slowly through the exchanger 3. Rinse: Regenerant is removed by passing water through the exchanger 4. Loading: the contaminated solution is then passed through the exchanger until leakage is detected.

Figure 2-2: Typical ion-exchange cycle for wastewater treatment Source: Ramaswamy et al. (2013)

Many ion-exchange columns operate in down-flow mode and are regenerated in the same direction. However, in order to obtain a better regeneration and lower leakage during loading, the regenerant can be passed counter-current to the loading flow. The retained solute can be a useful component in the chemical industry. The cycle is then modified to include a displacement step (see Figure 2-3).

Figure 2-3: Modified ion-exchange cycle to recover interesting compound Source: Ramaswamy et al. (2013) 2.3 Production and classification of IERs

2.3.1 Introduction

There are many aspects involved in the production of IERs. However, as noted by SCI (undated), the preparation and manufacture of these materials commonly distinguishes two steps:

 Formation of the polymer bead  Converting the bead to an active ion exchanger by attaching a suitable functional group.

The formation of the polymer bead substantially determines the characteristics of an ion exchanger, but decisive for its chemical mode of action are the functional groups. A broad schematic representation of this process is shown in Figure 2-4 and these steps are discussed further in the following sections.

2 The service period of IERs is not infinite and the capacity of the resins is exhausted when the bulk of the functional groups are full of ‘captured’ ions/molecules. This means that the IERs have to be regenerated (cleaned). Essentially, the beads are returned to their original state and reactivated by displacing the ions/molecules adsorbed during operation by the same functional groups that had been applied to the surface before service. Regeneration can be performed as often as required, although the capacity of the IERs will decrease over time (LANXESS, 2006).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 13

Figure 2-4: Production of IERs Source: LANXESS (2010)

2.3.2 Formation of the polymer bead

A variety of polymeric substrates can be used in ion exchange synthesis, including polymers of esters, amides and alkyl halides (Fritz & Gjerde, 2009). However, resins based on PS-DVB copolymers appear to be the most widely used ion exchangers3 (a schematic representation of this copolymer is presented in Figure 2-5). Indeed, Dardel (2013) notes that approximately 90% of all IERs are based on this polystyrenic matrix and Dow (2002) states that this polymer system has stood the test of time as the most stable, physically and chemically, of any commercially available to date. With regard to this form of resin, polystyrene is the primary component, with a small amount of divinylbenzene added during polymerisation as a cross-linking agent. The cross-linking confers mechanical stability upon the polymer bead and dramatically decreases its solubility – subsequently, final resin properties can be varied significantly by changing the amount of divinylbenzene cross- linking agent (Dow, 2002).

Clearly, the polymeric substrates used in the production of IERs are highly important. However, it should be noted that from a physical structure point of view (as explained by Zaganiaris (2011)) resins can be categorised into two main types, based on the way they are produced. In the first, the IER beads are homogeneous and are called microporous (or gel type) IERs. In the second, designated as macroporous (or macroreticular) IERs, the resin beads are heterogeneous and consist of interconnected macropores surrounded by gel-type microbeads agglomerated together.

Historically, production of both types of polymer bead has been undertaken by suspension polymerisation in a stirred reactor. More specifically:

 Microporous resins are produced by a suspension polymerisation in which styrene and divinylbenzene are suspended in water as droplets. The substances are kept in suspension in the reaction vessel through rapid, uniform stirring, and the use of a surfactant. Addition of a catalyst (e.g. benzoyl peroxide) initiates the polymerisation. The size of the beads is dependent on the stirring rates (faster stirring = smaller beads) (Fritz & Gjerde, 2009)

 Macroporous resins are prepared by a special suspension polymerisation process, where the suspended monomer droplets also contain inert diluents; the diluent is a good solvent for the monomers (but not for the material that is already polymerised). Consequently, the resin beads formed contain pools of diluent distributed throughout the bead matrix. When polymerisation is complete, the diluent is washed out of the beads to form the macroporous

3 Polyacrylic IERs also appear to be widely commercially available in e.g. weak acid cation exchange resins (discussed further below). Here, for simplicity, in the discussion of production, focus will remain on the PS- DVB copolymer.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 14 structure, which results in rigid spherical beads with a high surface area (Fritz & Gjerde, 2009).

Figure 2-5: Schematic representation of styrene-divinylbenzene copolymer Source: Fritz & Gjerde (2009)

Individual beads of gel-type and macroreticular IER are illustrated, respectively, in Figure 2-6 and Figure 2-7.

Macroporous resins, with their large effective surface area, facilitate the ion exchange process, that can be used with almost any solvent, irrespective of whether it is a good solvent for the un-crosslinked polymer, and take up the solvent with little or no change in volume. They make more rigid beads, facilitating ease of removal from the reaction system. In the case of the microporous resins, since they have no discrete pores, solute ions diffuse through the particle to interact with exchange sites. Despite diffusional limitations on reaction rates, these resins offer certain advantages: they are less fragile, require less care in handling, react faster in functionalisation and applications reactions, and possess higher loading capacities (Sigma Aldrich, undated).

Figure 2-6: Schematic representation of a gel type IER bead Source: Zaganiaris (2011)

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 15

Figure 2-7: Schematic representation of a macroreticular IER bead Source: Zaganiaris (2011)

2.3.3 Addition of the functional group

Once produced, the polymer beads need to be chemically activated to make them perform as ion exchangers. In this stage, suitable functional groups are chemically introduced into the polymeric matrix4 in a variety of different processes. It is the addition of the functional groups that determines the chemical behaviour of the IER. When activated, there are four primary types of IER, classified depending on their main acid-base characteristics:

 Strongly acidic cation (SAC) exchange resins, containing sulfonic acid groups, e.g. sodium polystyrene sulphonate or poly(2-acrylamido-2-methyl-1-propanesulfonic acid)  Strongly basic anion (SBA) exchange resins, containing quaternary amino groups, for example, trimethylammonium groups, e.g. poly (acrylamido-N-propyltrimethylammonium chloride)  Weak acidic cation (WAC) exchange resins, containing carboxylic acids  Weak basic anion (WBA) exchange resins, containing primary, secondary and/or ternary amino groups, e.g. polyethylene amine.

SAC exchange resins can neutralise strong bases and convert neutral salts into their corresponding acids. SBA resins can neutralise strong acids and convert neutral salts into their corresponding bases. These resins are utilised in most softening and full demineralisation applications. WAC and WBA resins are able to neutralise strong bases and acids, respectively. These resins are used for dealkalisation, partial demineralisation, or (in combination with strong resins) full demineralisation (General Electric, 2012).

Additional types of IERs include blends of cation and anion exchange resins (‘mixed bed resins’) and ampholytic resins (which contains both an anion and a cation as bound ion) (Sigma Aldrich, undated). Some IERs are also prepared with chelating properties, which, depending on the particular chelating agent and the application conditions, surround and isolate a specific metal ion or an exactly definable group of different metal ions (LANXESS, 2006). Figure 2-8 shows both cation and chelating resins in action.

The process of functionalisation varies significantly among the different categories of IER, and this can also have a significant impact on the cost of the final products. For example, in anion activation, processes are generally more complicated and expensive than for cation activation, with the IERs typically, although not exclusively, produced by a two-step process (SCI, undated).

4 In some instances, monomers are functionalised first and then polymerised into beads.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 16

A) Cation exchange resin in action. The functional B) Chelating resin in action. The functional groups groups carry a negative charge with the undesirable act as ‘clawed tentacles’, catching metal ions from the cation being replaced by the desired one solution Figure 2-8: Cation exchange and chelating resins in action. Note: Anion exchange resins operate by the same principal as cation exchange resins but with an opposite charge Source: LANXESS (2006)

In terms of the end products produced, Dorfner (1991) states that the following factors are decisive for the physical and chemical properties of a synthetic IER, and therefore prerequisites to be met during synthesis. These factors remain valid to this day:

 The IER must be highly polymeric and sufficiently cross-linked in order to be insoluble in water and other liquids and have good mechanic and thermic properties  The IER, having either a gel or a porous structure, must be sufficiently hydrophilic to make it possible for ions to diffuse through the structure at a finite and acceptable rate  The IER must contain an adequate number of accessible ionic exchange sites in order to yield a high exchange capacity  The IER must be as chemically stable as possible, so as to neither undergo degradation during use nor release parts or degraded parts of its structure  The IER must have a particle size distribution suitable for the envisaged application  The IER in the swollen state should be denser than water. 2.4 Overview of the applicant’s IER production activities

2.4.1 Introduction

As highlighted in Section 2.1, the applicant is a wholly owned subsidiary of LANXESS AG, the parent company of the LANXESS group. The LANXESS Group is a globally operating chemicals enterprise with a portfolio ranging from basic, specialty and fine chemicals to polymers. The responsibilities for the operational business of LANXESS are borne by 10 business units, which are geared towards the needs of the market:

 Advanced Industrial Intermediates  Inorganic Pigments  Liquid Purification Technologies  High Performance Elastomers  High Performance Materials  Leather  Material Protection Products  Rhein Chemie Additives  Saltigo Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 17  Tyre & Speciality Rubbers.

Currently, the production of IERs within the LANXESS Group is carried out under the remit of the ‘Liquid Purification Technologies’ business unit. The unit is one of the world's foremost suppliers of products for treating water and other liquid media and holds a leading position in the development and production of IERs, produced under the ‘Lewatit®’ product range (see Annex 2). The Group also have a strong position in the development of reverse osmosis membrane elements (produced under the ‘Lewabrane®’ product range).

As can be seen in the following figure, LANXESS’ IER production sites are located in Leverkusen (the facility of relevance to this AoA) and Bitterfeld, Germany, and in Jhagadia, India. The applicant, LANXESS Deutschland GmbH, directly controls the Leverkusen site and operates the Bitterfeld and Jhagadia sites through the respective wholly owned subsidiaries, ‘IAB Ionenaustauscher GmbH’ and ‘LANXESS India Private Limited’.

Figure 2-9: Location of LANXESS IER production and technical facilities Note: Red dots represent production sites and black dots represent technical service centres Source: LANXESS (2010)

Given the somewhat interdependent nature of EDC’s use in the applicant’s SAC ER, AER and CR production activities, further description of the relevant processes has been divided into 3 sub- sections. The first two respectively provide an overview of the sulphonation and phthalimidomethylation processes, combining literature and applicant-specific information. The third focuses on the coalescent nature of EDC’s consumption at the Leverkusen site.

2.4.2 Use 1: The sulphonation process

As highlighted above, the applicant uses EDC as a swelling agent for PS-DVB copolymer beads, during their sulphonation. Sulphonation is the process in which the copolymer beads are functionalised into SAC ERs via the addition of sulphonic acid functional groups, which form the fixed ions of the ion exchanger. As noted by Jackson (1991), the sulphonic acid groups can be introduced onto the PS- DVB copolymers by reaction with sulphuric acid, sulphur trioxide, fuming sulphuric acid or

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 18 chlorosulphonic acid (see Figure 2-10). Sulphuric acid is the most commonly employed sulphonation reagent and is used at elevated temperatures, sometimes in the presence of a catalyst.

Figure 2-10: Reaction schemes for the introduction of sulphonic acid functional groups onto PS-DVB copolymers Source: Jackson (1991)

A broader schematic of the SAC exchange resin production process is provided in Figure 2-11.

Figure 2-11: Synthetic procedure to produce SAC exchange resins Source: Dow (2000)

As can be seen from the above figure, in addition to the use of a sulphonating acid, it is also common to introduce a swelling agent prior to and during the sulphonation phase of SAC ER production. This is because (as highlighted by Harland (1994)) some of the most severe stresses and strains within a resin are sterically induced during activation of the copolymer with the functional group and the subsequent aqueous conditioning and rinses which complete the transition from a hydrophobic to a hydrophilic structure. In addition, upon hydration, IERs swell differentially because of the unsymmetrical distribution of crosslinking, thereby creating further strain within the resin beads.

The introduction of a swelling agent (such as EDC) can relieve the strains imposed during activation, thereby easing greatly the steric resistance to activation of what would otherwise be a collapsed copolymer structure.

Essentially, the process of ‘pre-swelling’ opens up the resin so that reactants can penetrate beneath the surface. As noted by Sherrington (1998), the swelling process itself occurs largely “from outside to the interior” and this behaviour has been treated quantitatively using the so-called ‘shrinking

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 19 core’ model5. Figure 2-12 schematically demonstrates the swelling and contraction of IERs in ‘good’ and ‘bad’ solvents6.

(a) shrinking glassy core to form an expanded gel in a good solvent; (b) contraction of swollen gel on addition to a bad solvent with bursting of resin due to osmotic shock Figure 2-12: Solvent response of gel-type resins Source: Sherrington (1998)

As noted by Dorfner (1991), experts can detect differences between pre-swollen cation exchange resins and those swollen without solvent (by microscopic examination), based on the inferior quality of the latter. Another benefit of using a pre-swelling agent is that the reaction time can be reduced. Without solvent to soften the copolymer bead, the reaction between the polymer and the acid is slower and it can take several hours for sulphonation to complete. In a plant that is running near capacity in a batch or semi-batch mode, it is important to reduce the time for any one batch, particularly where different products are made in the same equipment (Dow, 2006).

The use of swelling agents is also particularly important for highly cross-linked copolymers. This is because resins with a higher degree of cross-linking show more resistance to oxidising conditions that tend to de-crosslink the polymer. Activation becomes difficult because access to the interior of the bead is hindered by the high density of the matrix. The rate of exchange increases in proportion to the mobility of the ions inside the exchanger bead. If the structure is too dense, ionic motion is slowed down, thus reducing the operating capacity of the resin. The greater the ionic mobility in the resin, the poorer is the differentiation between the adsorption of ionic species with the same charge. Consequently, the degree of cross-linking in the resin must be increased when greater differences in ionic affinity are required (Ramaswamy, Huang, & Ramarao, 2013).

It is apparent (from, e.g. Sherrington (1998)) that EDC is a highly compatible and ‘good’ swelling solvent for the PS-DVB copolymer, and it is commonly considered as the benchmark solvent in the SAC ER production process. In patent EP1685166, for example, Marvin et al (2012) reinforce the importance of this solvent, stating that EDC is the most common solvent used in gel cation exchange resin processes. Furthermore patent EP1685166 A2 (Tegen, Tesch, & Harris, 2006) notes that the use of solvents, especially chlorinated solvents in gel cation exchange resin processes, has been a preferred method, and results in mechanically and osmotically stable cation exchange resins, with

5 This is a major model that has been developed for non-catalytic fluid-solid reactions (Gbor & Jia, 2004). 6 It is noted that the swelling solvent does not appear to be as critical in ion-exchange synthesis of macroporous substrates. This is because their surface is already ‘exposed’ and ready to be converted into an ion exchanger (Fritz & Gjerde, 2009). Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 20 low bead breakage, adding that the most common solvent used in gel cation exchange resin processes is EDC.

The specific parameters of the applicant’s sulphonation process are described in Table 2-2.

Table 2-2: Parameters for EDC use the sulphonation process Parameter Description EDC is used to swell PS-DVB copolymer beads during their sulphonation and functionalisation into SAC ERs. This sulphonation process is undertaken at the applicant’s Leverkusen IER manufacturing facility, alongside the manufacture of AERs and CRs (see following table). Tasks performed by the substance Swelling of the copolymer enhances the accessibility of sulphuric acid into its structure and achieves the sulphonation of the aromatic rings. EDC’s effectiveness and properties are particularly beneficial as they allow the process to be achieved in an efficient timescale. The solvent is also highly recoverable in the process Physical form of the Liquid (minimum 99.2% purity) product Concentration of the Average of ''''#C ''''% ('''''#C'''''''''% for special types of SAC ERs used in food and substance in the pharmaceutical applications) product The following technical criteria have been identified (these are discussed further in Section 2.5 and a sub-set of the criteria also apply to the implementation of an alternative technique):

Critical properties and - Solubility in sulphuric acid quality criteria EDC - Boiling point must fulfil - Freezing point - Swelling efficiency - Solvent stability - Final SAC ER quality EDC is utilised in ''#A' batches a day ('''''#A''' litres per batch). The quantity of EDC Function conditions has to be sufficient to swell the PS-DVB copolymer beads significantly, but not higher (frequency of use and than their maximum uptake capacity (i.e. not more than '''''' #A''' of the total reactor quantity used) content) Typically 90-100% sulphuric acid is used as a suspension agent (reaction medium) for Process and the sulphonation reaction. The process is undertaken at temperatures ranging from performance 100 – 150 °C for several hours (depending on the product being produced). At the constraints end of the reaction, recycling takes place via distillation It is not possible to remove EDC within the current process when technical and economic feasibility constraints are considered. The use of EDC is required to achieve high quality resins and the appropriate (and approved) performance level for a wide variety of SAC ER markets and applications.

Based on previous successful R&D activities, the applicant has demonstrated that some SAC ER products can be produced without using any solvent in the Can the use of EDC be sulphonation step and the applicant’s production facility in Bitterfeld manufactures eliminated and the SAC ERs via this technique (it is important to note that the SAC ERs produced with process continue? EDC in Leverkusen could not be sulphonated without EDC in Bitterfeld).

As shown Section 5.3, at ''''''' '''''''''#D'''''''' the applicant began implementing an R&D plan to investigate the potential for solventless sulphonation to be further implemented, at Leverkusen. Essentially, for some products produced at this site, this is potentially achievable. For other types of resins, especially those used as catalysts in chemical processes or those based on highly crosslinked copolymers, the elimination of EDC is more challenging and would lead to a dramatic drop in product Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 21 Table 2-2: Parameters for EDC use the sulphonation process Parameter Description quality which would be unacceptable for customers.

In considering solventless sulphonation as an option, each and every SAC ER produced at Leverkusen has to be individually investigated (this is essentially a staggered process to assess ''' #C'''' products). Lab investigations have begun with some products already passing development and validation stages. However, based on a provisional timeline the work will not be completed until at least 4 years after the Sunset Date for EDC. Customers could accept resin made with or without EDC provided the product Customer specifications, quality and performance criteria are met. The applicant’s customers, requirements especially in the areas of catalysis, condensate cleaning in power plants and ultra- associated with the pure water for the electronic industry require a very high quality product. At this use of the substance time, these products cannot be produced to a sufficient standard without the use of EDC as a swelling agent in the sulphonation process Significant qualification and certification requirements must be fulfilled for many of the applicant’s IER products. These will differ substantially depending on product sector and end-use. Furthermore, as Leverkusen is a global IER supply point, these requirements will also extend to customers outside the EU.

As an example, IERs used for drinking water applications will need qualifications in accordance with NSF (see http://www.nsf.org/about-nsf/) whereas those used in the treatment of food may be obliged to conform to the Council of Europe Resolution Industry sector and RESAP(2004)3 regarding ion exchange resins that can be safely used in food legal requirements for processing, and attain FDA compliance (21 CFR 173.25) as well as kosher and/or halal technical acceptability certification (further details surrounding an FDA approval are provided as a more that must be met and developed example, in Annex 4). the function must deliver Some of the applicant’s customers may also require ISO certificates and production audits or separate approvals (e.g. for nuclear power plants) and IERs manufactured by LANXESS may also need to attain standards necessary to meet the national registers of some countries (such as South Korea, Australia and Japan).

Given the complex and global scope of these requirements, it is perhaps unsurprising that the use of an alternative to EDC would trigger an extensive time and cost intensive recertification and requalification process

2.4.3 Use 2: The phthalimide process

As highlighted above, in addition to the preparation of SAC ERs the applicant also uses EDC in the production of AERs and CRs. In a similar fashion to the preceding process, EDC is utilised as a swelling agent for the PS-DVB copolymer. However, the substance also has an additional function acting as a reaction medium and aiding the stirability of the batch. Furthermore, in contrast to the widely established sulphonation process, the applicant’s AER/CR production route is somewhat unique, and has been the result of an extensive R&D program. The process also offers certain advantages over the more common chloromethylation route:

 The chloromethylation process introduces additional crosslinks together with chloromethyl groups. The phthalimide process allows functionalisation without additional crosslinking. This results in more swellable resins which display better exchange kinetics due to a better permeability to water, aqueous solutions and other liquids  Due to the lack of additional crosslinking during functionalisation, the phthalimide process allows the introduction of more than one functional group per aromatic ring, achieving average substitution degrees of the aromatic ring of up to 1.4 versus 0.8 for the Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 22 chloromethylation route. This not only results in a much better volume yield of resin per tonne of PS-DVB copolymer beads, but also gives access to an unprecedented combination of high exchange capacity and high exchange kinetics especially for chelating resins. LANXESS considers that the chelating resins manufactured by the phthalimide process are ‘best in class’ and exceed the performance of similar resin types available from competitors significantly, giving LANXESS a distinctive market advantage in this area  By converting the primary amino groups introduced by the phthalimide chemistry into tertiary amino groups, it is possible to access truly weak basic ion exchange resins devoid of any quaternary ammonium groups. The conversion of the chloromethyl groups from the chloromethylation process into tertiary amino groups always introduces a small amount (typically ≤10%) of quaternary ammonium groups. The absence of quaternary ammonium groups on the weak basic ion exchange resins from the phthalimide process confers these resins decisive performance advantages in many applications, especially in the food industry.

As can be seen, the applicant’s justification for their preference to use the phthalimide process is clear.

Given its unique nature, it should be noted that there is little information publicly available on process steps beyond that provided in the applicant’s patent literature (also detailed in Section 4.2.1), which demonstrates the process variations used to create different product grades. For the benefit of the reader, a general overview of the phthalimide process to AER and CR production, as undertaken by the applicant, can be given in four steps7 . EDC is utilised in Step 2:

Step 1 - Reacting monomer droplets made from monovinylaromatic compounds and polyvinylaromatic compounds, and optional porogens and/or initiators

The first step essentially involves the formation of the polymer beads. In the production of both AERs and CRs, reacting monomer droplets are made from at least one monovinylaromatic compound (i.e. styrene) and at least one polyvinylaromatic compound (i.e. divinylbenzene), and, if desired a porogen and/or an initiator.

Step 2 - Amidomethylating the resultant crosslinked bead polymers with phthalimide derivatives

In this step, first the amidomethylating reagent is prepared. This is achieved by dissolving a phthalimide (or phthalimide derivative) in a solvent and mixing with formalin. A bis(phthalimido) ether is then formed from this material with elimination of water.

Solvents used in this process step must be inert and suitable for swelling the PS-DVB copolymer, and this is where the applicant utilises EDC. In this step, the bead polymer is condensed with phthalimide derivatives. The catalyst used here comprises oleum, sulphuric acid, or sulphur trioxide.

At the end of this step, after the substitution reaction has taken place in EDC the solvent is eliminated by azeotropic distillation and is replaced by water.

Step 3 - Converting the amidomethylated bead polymers to aminomethylated bead polymers

The third process step involves the elimination of the phthalic acid residue, and with this, the release of the aminomethyl group via treatment of the phthalimidomethylated PS-DVB copolymer with aqueous or alcoholic solutions of an alkali metal hydroxide, such as sodium hydroxide or potassium hydroxide. This process allows the preparation of PS-DVB copolymers

7 See patents US 7053129 B1 and US 20020185443 A1.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 23 containing aminoalkyl groups with substitution of the aromatic rings at a level greater than 1. The resultant aminomethylated PS-DVB copolymer is finally washed with deionised water until free of alkali.

Step 4 – Functionalising the aminomethylated bead polymer

The last step in the process is essentially the further derivatisation of the primary amino groups of the aminomethylated PS-DVB copolymer. This is achieved by reacting the PS-DVB copolymer containing aminomethyl groups for AERs with alkylating agents (e.g. alkyl halides) in suspension and for CRs with compounds that give the functionalised amine chelating properties (e.g. chloroacetic acid or its derivatives).

Additional details on the phthalimide route, and the applicant’s use of EDC in the process are provided in Table 2-3.

Table 2-3: Parameters for EDC use in the phthalimidomethylation process Parameter Description EDC is used as a reaction medium and solvent for the in-situ preparation of the reactant bis(phthalimidomethyl)ether. It also acts as a swelling agent of PS-DVB copolymer beads and reaction medium for the phthalimidomethylation of the Tasks performed by the aromatic rings of the copolymer (in the production of AERs and CRs). substance

The process is undertaken at the applicant’s Leverkusen IER manufacturing facility, alongside the manufacture of SAC ERs (see preceding table) Physical form of the Liquid (minimum 99.2% purity) product Concentration of the Average of '''''#C'''''% substance in the product The following technical criteria have been identified (these are discussed further in Section 2.5 and a sub-set of the criteria also apply to the implementation of an alternative technique):

Critical properties and - Freezing point quality criteria EDC must - Swelling efficiency fulfil - Solvent stability - Final AER/CR quality - Azeotrope formation with water - Azeotrope properties - Degree of functionalisation Function conditions EDC is used in '#A ' batches a day ('''#A'''''' litres per batch). The quantity of EDC (frequency of use and has to be sufficient to secure the ‘stirability’ of the reaction batch quantity used) The process is undertaken at temperatures ranging from 60 – 100 °C for several Process and performance hours. Dry, water-free conditions are required for the reaction (these are constraints obtained by azeotropic distillation of contaminant water). Recycling is achieved by distillation at the end of the reaction

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 24 Table 2-3: Parameters for EDC use in the phthalimidomethylation process Parameter Description It is not possible to remove EDC within the current process when technical and economic feasibility constraints are considered. The use of EDC is required to achieve high quality resins and the appropriate (and approved) performance level for a wide variety of AER and CR markets and applications. EDC also acts as a reaction medium in the process and allows the batch to be stirred. Without the Can the use of EDC be use of the substance, no reaction would occur. eliminated and the process continue? The applicant is investigating a combination '''' '' '''''''''''''''''''' '''''''''''''' '''''''''''''''''''' ''''''''''''''''''' '''''''' ''''''' ''''''''''''''''''''' '''' ''''''#E ''''''''''''''''''''' ''''''''''''''' '''' '''''' ''''' ''' '''''''''''''' '''''''''''''''' Investigation into this novel combination of an alternative technology and substance has begun, but requires a significant timeframe to be implemented (12 years from the Sunset Date), as described in Section 5.4 Customers could accept resin made with or without EDC provided the product Customer requirements specifications, quality and performance criteria are met. The EDC based associated with the use of phthalimide route to AERs and CRs allows the production of highly substituted the substance species with pure chemical functionality, including e.g. primary amine functions for binding CO2 from breathable air Significant qualification and certification requirements must be fulfilled for many of the applicant’s IER products. These will differ substantially depending on product sector and end-use. Furthermore, as Leverkusen is a global IER supply point, these requirements will also extend to customers outside the EU.

As an example, IERs used for drinking water applications will need qualifications in accordance with NSF (see http://www.nsf.org/about-nsf/) whereas those used in the treatment of food may be obliged to conform to the Council of Europe Resolution RESAP(2004)3 regarding ion exchange resins that can be safely used in Industry sector and legal food processing, and attain FDA compliance (21 CFR 173.25) as well as Kosher requirements for and/or HALAL certification (further details surrounding an FDA approval are technical acceptability provided as a more developed example, in Annex 4). that must be met and the function must deliver Some of the applicant’s customers may also require ISO certificates and production audits or separate approvals (e.g. for nuclear power plants) and IERs manufactured by LANXESS may also need to attain standards necessary to meet the national registers of some countries (such as South Korea, Australia and Japan).

Overview of the applicant’s combined IER production activities at Leverkusen

A schematic overview of the IER production processes undertaken at the applicant’s Leverkusen facility is provided below.

The applicant uses EDC in two processes: the production of SAC ERs (Use 1) and AERs/CRs (Use 2). The role of the solvent is different in each of these uses but the processes share solvent recycling facilities and benefit from this linkage in terms of efficiency. The pathways of EDC through these processes are illustrated in Figure 2-13.

The two processes employ a single (combined) closed-loop of EDC, where the losses are mainly due to off-gases, some residual solvent in waste water and products as well as solvent decomposition. Both the off gases and waste water streams are treated. The off-gas is incinerated (at the Off-Gas

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 25 Treatment Plant, OGTP) and the water is treated in an on-site Sewage Treatment Plant (STP). Any lost solvent is replenished from a pure EDC tank supplied by tanker truck and the processes operate using a mixture of ‘pure’ and recycled EDC.

For the manufacture of SAC ERs the mixture is blended from the tanks and passed initially to EDC receiver (holding) tanks. The sulphonation reactor is filled with the required amount of recycled sulphuric acid. Thereafter the polymer beads are added to the acid under agitation. The EDC is then fed from the holding tank to the sulphonation reactor and the reaction mixture is kept for some time at T < 80 °C in order for EDC to imbibe the beads. The sulphonation reaction is started by heating up the reactor content to T > 100 °C. During the first phase of the reaction the reactor is kept under pressure to keep the polymer beads swollen with EDC. In a second phase the pressure is released to the condenser and the condensed EDC together with some condensed water generated by the sulphonation reaction is returned to the EDC holding tank. From here, the water saturated with EDC is passed to a separate tank that feeds into the AER/CR manufacturing process. The sulphonated product suspended in acid containing residual EDC is passed into a dilution vessel (DV) where water is added (not illustrated). The spent reaction acid is recycled for the next batch (recycled acid, not illustrated). Most of the dilution acid is also recycled and stored for the next dilution cycle (storage vessels not illustrated). Any excess of spent acid from the reaction step or from the dilution step is sent to a spent acid tank. This spent acid is sent back to a separate sulphuric acid plant within the Leverkusen Chempark where it is distilled into concentrated sulphuric acid thereby destroying any EDC residuals by oxidation.

At the end of the dilution step the dilute acid is stripped of EDC by air blowing and circulated through the SAC ER product for several hours to remove most of the residual EDC present in the SAC ER as well as in the dilute acid. The product suspended in the dilute acid stripped of EDC is eventually sent to a washing step where the dilute acid and the wash waters are transferred to the STP. The SAC ER is then sent to packaging.

The AER/CR manufacture has five steps: ether synthesis (using formaldehyde and phthalimide, ER), phthalimidomethylation of the resin beads (SR), removal of EDC by distillation (DR) followed by filtration of the AER/CR intermediate product (NF) and finally by the alkaline saponification of the phthalimide residue (AR). Again, a mixture of ‘pure’ and recycled EDC (without water) is used for the first two steps.

The ether synthesis is a condensation reaction producing water and takes place in a first reactor (ER). EDC and water are removed from the reactor by distillation using a phase-separator, feeding the EDC back into the reactor and the water (saturated with EDC) is passed into the distillation step (DR) via an intermediate water holding tank.

After completion of the ether synthesis the ether suspended in EDC is transferred by gravity into the substitution reactor (SR). After addition of the polymer beads the phthalimidomethylation reaction is started by heating up to T > 60 °C. At the end of the substitution reaction the beads suspended in EDC are transferred by gravity into the distillation reactor (DR). Water from the water holding tank is added continuously as EDC and water are removed from the reactor by distillation. The condensed water/EDC mixture is sent to a phase separator where the EDC is passed back into the recycled EDC tank and the water is sent back to the distillation reactor. The distillation is conducted until no EDC distills off. ''''' ''''''' '''''''''' ''''' ''''''''''''''''' '''''''''''''''''''' ''''' '''''''''' '''''''' '''''' ''''''''''' '''''''''''''' '''''''#A' '''''''''' '''''''''' '''''''''''' ''''''''''''''''''' ''''''''''' ''''''''''' ''''''''''''''''''''' ''''' '''''''' ''''''' '''''''''''''''''''''' '''' ''''''''''' '''' ''''''''''''' '''''' '''''''''''''''' '''''''' '''''''''''''''' '''' ''''''' '''''''''' '''' ''''''''''' ''''''' '''''''''' '''''' '''''''''''''''''''' At the end of this step the beads are transferred to a nutsche filter (NF) where they are filtered out of the water. The water contains some low level of residual EDC and this is treated in the STP. Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 26 The functionalised beads containing some residual EDC are then suspended in a sodium hydroxide solution and transferred into the alkaline cleavage reactor (AR). In this step the combined use of high concentration of sodium hydroxide (> 10 wt.-%) and high temperature (> 150 °C) cleaves off the phthalimide residue thereby liberating the primary amino group which is required for further derivatisation into AER/CR functional groups. Under the severe reaction conditions of the alkaline cleavage most of the residual EDC in the beads is transformed into vinyl chloride which is vented to the off-gas incineration plant at the end of the reaction.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 27

Figure 2-13: Use of EDC in production of SAC ERs and AERs/CRs Source: Applicant’s information Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 28 2.5 Technical feasibility criteria for alternative substances

2.5.1 Introduction

The development of technical feasibility criteria for EDC and its potential alternatives has been based on a combination of consultation between the independent third party that has authored this AoA and the applicant, in addition to a review of available scientific literature.

Through the use of a detailed written questionnaire (disseminated in March 2014) the applicant was asked to provide details of the (ideally) measurable, quantifiable technical performance criteria which EDC meets and that any alternatives (substances and techniques) would also need to meet before they are actively considered as replacements. These could relate to issues of molecular structure, solubility, transformation products, product purity, energy consumption, etc. anything that is relevant and important to the processes in which EDC is used and the roles it plays.

In parallel, scientific literature delving into the parameters of the applicant’s production processes and the assessment of the technical suitability of specific alternative techniques was collected and analysed (with the applicant’s assistance) and has been incorporated into the analysis. The role of EDC as a swelling agent of PS-DVB copolymer beads in the production of SAC ERs has been described above in Section 2.4 as has the substance’s role in the phthalimide route to produce AERs and CRs.

The criteria that shall be used in the assessment of the technical feasibility of selected alternatives, for each use, are distinguished in the following table.

Table 2-4: Technically feasibility criteria alternative substances will be assessed against in Section 5 of AoA Criterion Use 1 – Sulphonation Use 2 - Phthalimidomethylation 1. Solubility in sulphuric acid1  2. Boiling point  3. Freezing point   4. Swelling efficiency   5. Solvent stability   6. Final IER quality   7. Azeotrope formation with water  8. Azeotrope properties  9. Degree of functionalisation2  1 For phthalimidomethylation this criterion is not relevant since sulphuric acid is not the reaction medium 2 Not included as a criterion for sulphonation as the degree of functionalisation will likely be acceptable regardless of the use of EDC or another solvent

The discussion below explains the relevance and importance of the criteria and presents in more detail the threshold values (or ranges) that will be used in Section 5 for the comparison of the shortlisted alternatives to EDC. It should also be noted that even where criteria are the same for each use, threshold values may differ. Consequently, each use is assessed separately. In many instances, technical comparison criteria are also strongly interrelated and it is not possible to discuss or consider a criterion independently of several others.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 29 2.5.2 Use 1: Sulphonation

Criterion 1: Solubility in sulphuric acid

Importance of the technical criterion

The (lack of) solubility of the solvent in sulphuric acid is a key parameter to support the recycling of both components in the process. Essentially, as a portion of the sulphuric acid is diluted and diverted to waste water treatment in the dilution step of the process, if the solvent were miscible with the sulphuric acid, it would introduce considerable additional wastewater treatment requirements. A solvent demonstrating miscibility with sulphuric acid could also result in unacceptable levels of residual solvent in the final SAC ER products, to the extent that they would no longer be accepted by customers.

Threshold value

The applicant has indicated that to be able to successfully separate sulphuric acid from the solvent under process conditions, the alternative solvent must be immiscible with sulphuric acid and have a solubility < 1 % wt.

Criterion 2: Boiling point

Importance of the technical criterion

Solvent boiling point will affect the process pressure at reaction temperature as well as the ability for the solvent to be easily recovered and recycled. The ability to efficiently recover solvent within the process is an important economical and sustainability factor. In addition, higher boiling point solvents could result in unacceptable levels of residual solvent in the final SAC ER products, to the extent that they would no longer be accepted by customers.

Threshold value

The applicant has indicated that to be operated within acceptable process conditions, an alternative substance will be required to have a boiling point in the range of 80 – 120 °C.

Criterion 3: Freezing point

Importance of the technical criterion

Alternative solvents need to be in liquid form in storage tanks and must have a freezing point in an acceptable temperature range.

Threshold value / considerations

Alternative solvents should have a freezing point lower than 0 ˚C.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 30 Criterion 4: Swelling efficiency

Importance of the technical criterion

EDC is an excellent swelling solvent for the PS-DVB copolymers utilised by the applicant. As highlighted above, the sulphonation process requires the PS-DVB copolymer to be swollen to enhance the accessibility of sulphuric acid into the polymer structure and achieve the sulphonation of the aromatic rings. The ability of the solvent to sufficiently swell the copolymer during sulphonation will affect the quality of the beads, in addition to the efficiency of the process. Consequently, good swelling of the PS-DVB with the solvent is required in order to achieve the best quality / performance / cost balance for the end products.

Threshold value

EDC is an excellent swelling solvent for the PS-DVB copolymer utilised by the applicant. To measure the swelling efficiency of potential alternative substances, the applicant utilises the Hildebrand solubility parameter - this is a numerical value that indicates the relative solvency behaviour of a specific solvent (Barton, 1991).

Hildebrand solubility parameters have been determined for a wide range of solvents which makes the use of the parameters well suited for screening a large number of potential alternatives to EDC. As the copolymer beads in the applicant’s process consist of crosslinked polymer networks they are by nature insoluble in any solvent. They can, however, be swollen by solvents which are good solvents for the uncrosslinked polymer analogue of the beads, i.e. polystyrene.

It is generally accepted that a polymer can be expected to be soluble in a given solvent if the difference between the Hildebrand solubility parameter of the solvent and the Hildebrand solubility parameter of the polymer does not exceed 2 MPa1/2. For polystyrene literature reports a Hildebrand solubility parameter of about 19 MPa1/2 (Grulke, 1989).

Consequently, to be an acceptable potential alternative to EDC, an alternative solvent should have a Hildebrand solubility parameter in the range of 17-21 MPa1/2 (EDC itself has a Hildebrand solubility parameter of 20.2 MPa1/2).

Criterion 5: Solvent stability

Importance of the technical criterion

The ability of a solvent to remain inert during the sulphonation process is very important. The use of an inert solvent means that the substance can be recovered. This significantly reduces costs and issues associated with excess process waste. The solvent stability is directly linked to the annual consumption of the solvent and of the substance it is reacting with (e.g. sulphuric acid). Therefore, the stability of the solvent during the process affects the consumption of both solvent and sulphuric acid. In addition, the decomposition products may remain in the product, affecting product performance and introducing potential health issues for users of the SAC ERs.

Threshold value

Potential alternative substances must be inert (both chemically, and thermally) under the sulphonation process conditions, i.e. under strongly acidic conditions (90-100% sulphuric acid) at elevated temperatures (up to 150 °C).

The applicant has indicated an acceptability threshold of < 0.1 % wt. of solvent reacting per batch. Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 31 Criterion 6: Final SAC ER Quality

Importance of the technical criterion

The final-quality of the SAC ERs is clearly of very high importance, as the products produced by the applicant must fulfil the needs of their customers. Reduction in quality (particularly with regard to applications where a product qualification or certification is necessary) would not be accepted by customers, resulting in losses of sales for the applicant. In addition to final product performance parameters such as ion exchange capacity and catalytic activity (which would affect the economic viability of customers’ processes), IER bead integrity and process stability would be diminished if the quality of the final products were to decrease. The result of this could cause problems for downstream users e.g. cause filters to block. Such a situation would clearly be unacceptable.

Threshold value

The excellent quality standards achieved with the use of EDC must be maintained. Bead integrity must be high with IER products containing > 95 % whole perfect beads as delivered. IER bead process stability also needs to be high with > 80 % whole perfect beads after osmotic stability tests. For some less demanding applications (such as water softening), bead process stability of > 65-70 % could be tolerated but this would result a more limited market for the product.

Other product performance parameters will depend on the particular SAC ER product, and cannot therefore be quantified in a simple manner. Essentially, at minimum, the final SAC ER properties must be aligned with the needs of customers and meet necessary specification and quality control parameters.

2.5.3 Use 2: Phthalimidomethylation

Criterion 3: Freezing point

Importance of the technical criterion

Alternative solvents need to be in liquid form in storage tanks and must have a freezing point in an acceptable temperature range.

Threshold value / considerations

Alternative solvents should have a freezing point lower than 0 ˚C.

Criterion 4: Swelling efficiency

Importance of the technical criterion

EDC is an excellent swelling solvent for the PS-DVB copolymers utilised by the applicant. As highlighted above, the phthalimide process requires the PS-DVB copolymer to be swollen to facilitate the phthalimidomethylation reaction. The ability of the solvent to sufficiently swell the copolymer will affect the quality of the beads, in addition to the efficiency of the process (less swelling will result in a reduced yield of AERs/CRs per batch, as well as an overall reduction in effective plant capacity). Consequently, good swelling of the PS-DVB with the solvent is required in order to achieve the best quality / performance / cost balance for the end products.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 32 Threshold value

As highlighted under the discussion of sulphonation, to be an acceptable alternative to EDC, the Hildebrand solubility parameter for the alternative solvent must be in the range of 17-21 MPa1/2.

Criterion 5: Solvent stability

Importance of the technical criterion

The ability of a solvent to remain inert during the phthalimidomethylation process is very important. The use of an inert solvent means that the substance can be recovered. This significantly reduces costs and issues associated with excess process waste. The solvent stability is directly linked to the annual consumption of the solvent and of the substance it is reacting with. Therefore the stability of the solvent during the process affects the consumption of solvent and reagents. In addition, the decomposition products may remain in the product, affecting product performance and introducing potential health issues for users of the resins.

Threshold value

Potential alternative substances must be inert (both chemically, and thermally) under the phthalimidomethylation process conditions i.e. under strongly acidic conditions and elevated temperatures (up to 100 °C).

The applicant has indicated an acceptability range of < 0.1 % wt. of solvent reacting per batch.

Criterion 6: Final AER/CR Quality

Importance of the technical criterion

The final-quality of the AERs and CRs is clearly of very high importance, as the products produced by the applicant must fulfill the needs of their customers. Reduction in quality (particularly with regard to applications where a product qualification is necessary) will not be accepted by customers, resulting in losses of sales by the applicant. In addition to final product performance parameters such as ion exchange capacity and selectivity (which will affect the economic viability of customer processes), IER bead integrity and process stability would be diminished if the quality of the final products were to decrease, potentially blocking the array of filters produced by the applicant’s customers.

Threshold value

Other product performance parameters will depend on the particular AER/CR product, and cannot therefore be quantified in a simple manner. Essentially, at minimum, the final AER/CR properties must be aligned with the needs of customers and meet necessary specification and quality control parameters.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 33 Criterion 7: Azeotrope formation with water

Importance of the technical criterion

Dry, water-free conditions are required for the phthalimidomethylation reaction and these conditions are obtained via the azeotropic distillation of contaminant water in the process. Recycling of the solvent is achieved by distillation at the end of the reaction.

Threshold value

The potential alternative substance must form an azeotrope with water.

Criterion 8: Azeotrope properties

Importance of the technical criterion

There are additional favourable properties the azeotropic mixture should possess. Firstly, the mixture should have a low boiling point to allow the process to be undertaken efficiently (i.e. with low energy consumption). The composition of water respective to solvent in the mixture should also allow for an acceptable distillation time.

Threshold value

The applicant notes that, to be a replacement for EDC, a potential alternative substance would be required to form an azeotropic mixture with a boiling point in the range of 80 – 100 °C. Preferably, the water content of the azeotrope should also be in the range of 10 – 90 % wt.

Criterion 9: Degree of functionalisation

Importance of the technical criterion

The degree of functionalisation8 achieved using EDC is very important, as it affects the final quality of the AERs and CRs, as well as the overall process yield.

Threshold value

The achieved AER/CR yield will depend on the particular AER/CR product being manufactured, and cannot therefore be quantified in a simple manner. Essentially, at minimum, an alternative substance should achieve > 95 % of the ion exchange yield as compared with the EDC based process. 2.6 Technical feasibility criteria for alternative techniques

This AoA also discusses the availability and suitability of alternative techniques for each use. For sulphonation, it will be explained that alternative techniques essentially involve a process which removes the need for a solvent in the production of SAC ERs. For the phthalimide process, a novel alternative, combining a technique with an alternative substance is proven to be of most relevance to the applicant.

Given that both alternative technologies remove the need for an alternative substance to achieve all (for sulphonation) or part (for the phthalimide process) of the function of EDC, the list of technical

8 i.e. the chemical introduction of suitable functional groups into the polymeric matrix (Fritz & Gjerde, 2009).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 34 criteria that must be fulfilled by these technologies will forgo criteria that are relevant purely to the implementation of an alternative substance (e.g. ‘boiling point’).

Information submitted by the applicant and a review of the available literature confirms that the technical criteria that need to be considered for the comparison of the EDC-based process to the use of ‘solventless sulphonation’ include the following (see above for information on the importance of each of these technical criteria, and their threshold values):

 Final SAC ER quality

Likewise, for the phthalimide process, only the following technical criteria are of relevance to an alternative technique:

 Functionalisation degree  Final AER/CR quality.

As will be made clear in the following sections, with regard to the sulphonation process, it is testament to the applicant’s R&D efforts that some success has been achieved in removing the need for solvent in the production of certain SAC ER products at their Bitterfeld facility. However, this technology is not currently technically feasible for the wide range of SAC ERs produced by the applicant at Leverkusen.

For the phthalimide process, the applicant’s current technique forgoes the need of chloromethylation chemistry (the more common production route for AERs and CRs), and allows for the production of very high quality end-products. The applicant is already implementing a lengthy R&D plan in order to eliminate the use of EDC and a refused authorisation would have severe consequences.

These aspects are explored further in the corresponding SEA document. 2.7 Conclusion on technical criteria for alternatives

A summary of the technical feasibility criteria (and relevant threshold values or ranges) for alternative substances and technologies is provided, respectively for the sulphonation and phthalimide processes, in Table 2-5 and Table 2-6.

Table 2-5: Summary of technical feasibility criteria for alternatives to the sulphonation process Criteria relevant to... Relevant threshold Technical criteria Notes Alternative Alternative value or ideal range substance technique Solubility in sulphuric  N/A < 1 % wt. solubility acid Boiling point  N/A 80 – 120 ˚C Freezing point  N/A < 0 °C Swelling efficiency -Hildebrand solubility  N/A 17 – 21 MPa1/2 parameter < 0.1 % wt. reacting Solvent stability  N/A per batch Final SAC ER quality

- Bead integrity   > 95 % whole perfect beads Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 35 Table 2-5: Summary of technical feasibility criteria for alternatives to the sulphonation process Technical criteria Criteria relevant to... Relevant threshold Notes >value 80 % or whole ideal perfect range 65-70 % could be - Bead process stability   beads after osmotic tolerated with some stability tests products Must be aligned - Performance parameters with specific   No specific threshold customer requirements

Table 2-6: Summary of technical feasibility criteria for alternatives to the phthalimide process Criteria relevant to... Relevant threshold Technical criteria Alternative Alternative value or ideal Notes substance technique range Freezing point  N/A < 0 °C Azeotrope formation No specific Must form an  N/A with water threshold azeotrope with water Azeotrope properties

-Azeotropic boiling point  N/A 80 – 100 °C -Water content  N/A 10 – 90 % wt. Swelling efficiency

-Hildebrand solubility  N/A 17 – 21 MPa1/2 parameter < 0.1 % wt. reacting Solvent stability  N/A per batch > 95 % ion Functionalisation degree   exchange yield, as achieved with EDC Final AER/CR quality > 95 % whole - Bead integrity   perfect beads

- Bead process stability > 80 % whole perfect beads after   osmotic stability - Performance parameters tests Must be aligned with No specific   specific customer threshold requirements

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 36 3 Annual tonnage

As highlighted above, the applicant uses EDC at one EU location in Leverkusen, Germany. Annual tonnage information is provided for this facility below. The precise usage is based on 2014 data, however, the applicant notes that there has been no overall change in consumption for the 6 years preceding 2014 and (on the assumption of continued use) it is also expected that consumption will remain reasonably stable, ranging from ''''' ''' '''#B''''' ''''''''

Future R&D activities may, however, lead to a reduced consumption of the substance (see Sections 5.3.2 and 5.4.3 for further details relating to the substitution of EDC).

Confidential average tonnage of EDC in SAC ER, AER and CR production: ''''#B '. Of this amount, approximately ''''''' '''#B '''''''''' is used for phthalimide and ''''''''' ''''#B ''''''' is used for sulphonation.

Annual tonnage band for EDC in SAC ER, AER and CR production: 1-100 tpa.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 37 4 Identification of possible alternatives

4.1 Introduction and list of possible alternatives

The focus of this AoA will be on the alternatives identified in Table 4-1.

Table 4-1: Shortlist of alternatives to be assessed in Section 5 of AoA Shortlisted alternative Substance (CAS No) / Use 1 Use 2 technique (sulphonation) (phthalimidomethylation) 1,3-Dichloropropane (1,3- Substance (142-28-9)   DCP) 1,4-dichlorobutane (1,4- Substance (110-56-5)   DCB) Solventless sulphonation Technique   ''''''''''' '''#E''''''''''' technique Technique incorporating an alternative substance   '''''''''''#E ''''''''''

In arriving at this shortlist, the applicant has considered over 100 commercially available potential alternative substances and applied a systematic and thorough process of literature review, experimental laboratory work and expert analysis. In the following section, these R&D activities are described in further detail.

As the use of EDC is not of relevance to the downstream users of SAC ERs, AERs and CRs (customers will accept products as long as they meet the required technical and cost parameters), consultation with customers of LANXESS on the issue of alternative substances and techniques has not been undertaken. 4.2 Description of efforts made to identify possible alternative

4.2.1 Research and development

Past research

LANXESS has more than 70 years’ experience and expertise as a one-stop supplier of premium products for water treatment. Over this period, the applicant has carried out extensive and progressive R&D activities with regard to the improvement of ion exchange technologies. Since 1989 and the entry into force of the German “Gefahrstoffverordnung” (Dangerous Substances Ordinance), much research has focused on the identification of a replacement for EDC, and the applicant estimates internal expenditure of '''''''' '#D ''''''''''''' on the associated R&D efforts. These efforts have predominantly focused on the sulphonation process and it is important to note that LANXESS have successfully managed to implement a solventless sulphonation technique (discussed further below) at their separate Bitterfeld production facility, to produce a limited selection of SAC ER products (Section 5.3 explains the difficulties associated with the implementation of the solventless technology across a wider range of the applicant’s production activities).

With regard to the phthalimide process utilised in the production of AERs and CRs, it should be noted that the applicant is already implementing a unique technique (LANXESS understands that they are the only company in Europe utilising this special technology) which forgoes the use of chloromethyl methyl ether (a category 1A carcinogen) in the more common chloromethylation

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 38 production process. Consequently, the applicant considers their AER / CR production to be ‘greener’ than the standard method utilised by competitors but has also begun implementing an R&D plan to eliminate the use of EDC from the process, as will be discussed in the following sections.

For the benefit of the reader, a number of relevant patents covering past R&D activities undertaken by LANXESS have been highlighted in Table 4-2. These demonstrate the efforts made by the applicant to substitute EDC as well as improve their processes, and also highlight the diverse nature of end-products manufactured by the applicant, in addition to the highly technical production activities associated with the attainment of product variations.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 39 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication) Process for the production of US 3238153 Bayer AG Process for obtaining cation exchangers by a novel sulphonation process of polymers of a strongly acid cation exchangers (1966) monovinyl aromatic compound and a cross-linking agent and to produce cation exchange resins having a high sulphonation degree and increased capacities Anion exchange resins US 3882053 Bayer AG Process comprising condensing a crosslinked copolymer which contains aromatic nuclei and is (1975) a copolymer of at least one monovinyl compound and at least one polyvinyl compound, with at least one bis-(dicarbonimidoalkyl)ether in the presence of a Friedel-Crafts catalyst, hydrolysing resulting condensation product and optionally alkylating the hydrolysed product and the resulting exchange resin Process for the production of US 3989650 Bayer AG Relates to a new process for the production of crosslinked, water-insoluble synthetic resins anion exchangers - (1976) with anion exchanger properties wherein the crosslinked, water-insoluble organic polymers amidoalkylation of crosslinked containing aromatic nuclei are reacted, in the presence of swelling agents for the polymer and water insoluble aromatic-group in the presence of acid catalysts, with esters of N-hydroxyalkylamides or N-hydroxyalkylimides, containing polymers using esters and the acylamido alkylated reaction product is subsequently hydrolysed in a known manner. of cyclic N-hydroxyalkylimides The invention furthermore concerns new crosslinked water-insoluble synthetic resins with anion exchanger properties containing at least two aminoalkyl groups per aromatic nucleus Process for preparing synthetic US 4952608 Bayer AG Relates to a process for preparing anion exchangers based on crosslinked, water-insoluble resins having anion exchanger A (1990) organic polymers containing aromatic nuclei, in which, in the first step, N- properties by amidomethylating a hydroxymethylphthalimide is produced by reaction of phthalimide with aqueous formaldehyde backbone polymer containing solution in swelling agents in the presence of bases; if desired, this N- aromatic nuclei with a specially hydroxymethylphthalimide is converted in a 2nd step to the bis)phthalimidomethyl)ether or an prepared N-hydroxymethyl ester of N-hydroxymethylphthalimide; said polymers are aminomethylated wtih N-hydroxy- phthalimide methylphthalimide, bis)phthalimidomethyl) ether or an ester of N-hydroxymethylphthalimide in the presence of Friedel-Craft catalysts and swelling agents and the amidomethylated polymers are finally saponified to form the aminomethylated polymers, wherein, in the first reaction step, the base used for producing N-hy-droxymethylphthalimide is sodium hydroxide solution and this sodium hydroxide solution is added in such an amount and at such a rate that the reaction of phthalimide with formaldehyde takes place in the pH range of 5 to 6 Process for the manufacturing of EP 0838263 Bayer AG Highly acidic cation exchanger with improved properties are produced if one undertakes the cation exchangers which are low in (1998) sulphonation of the unfunctionalised polymerisates under high temperature and/or in the leaching absence of oxygen

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 40 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication) Process for the preparation of EP 0868444 IAB The invention concerns a process for the manufacturing of mechanically and osmoticically strongly acidic cation exchanger (1998) Ionenaustauscher stable, high-capacity strong acidic cationic exchangers with a grain size of ≥ 0.1 mm through GmbH Bitterfeld the sulphonation of gel like or porous bead polymers with sulphuric acid without the usage of inert chlorine containing swelling agent and/or acrylonitrile comonomers. According to the invention such kind of strong acidic cationic exchanger is through the sulphonation of gel like and porous bead polymers, manufactured through co-polymerisation of styrene and divinylbenzene with a share/proportion of cross-linking agents with up to 65 weight. -% divinylbenzene with or without inert agent, with 80-96 % sulphuric acid at temperatures of 125-180 °C and a reaction time of up to 20 h. According to the new process, strongly acidic cationic exchanger without the usage of the inert chlorine containing swelling agent EDC with the same or similar quality criteria and material characteristics can be manufactured as the product which has been manufactured with the conventional process '''''''''''' '''''''''''''''' ''' '''''''''''' '''' ''''''''''''''''''' '''''''''''''''''''' ''''''''' '''''''' ''''''''''''''''''''''' '' ''''''' '''''''''''''''''''''' ''''''' ''' ''''''''' ''''''''' ''''''''''''' ''''''''''''''''''''''''' '''''''' '''' '''''''' ''''''''' ''''''''''''''''''''''' '''''''''''''''''''''''''' ''''''''''''''''' '''''''' ''''''''''''''''''' ''''''''''' ''''''''''''''' '''''''''''''' ''''''''''''''''''''''''' ''''''' ''''''' '''''''''''''''''' '''''''''' ''''''' ''''''''''''''''' '''''''''''''''''''' '''''''''''' ''''''''''' ''' ''''''''''''''''''' '''''''''#D'''''' '''' '''''''''''' '''''''''''''''''''''' '''''''''''''' ''''''''' ''' ''''' ''''''''''' '''''''''''''''''' '''''''' ''''''''''''''''' ''''''' ''''''''' ''''''''''''''' ''''''''''''''' '''''''''''' '''''''''''' '''' '''''' '''''''''''''' '''''''''' ''''''''''' ''''''' '''''''''''' ''''''''''''''''' '''' '''''' '''''''''''''''''''' ''''' ''''''' '''''''''''''''''''' ''''' ''''''''''''''' ''''''''''''''''' ''''''''''''''''''' '''' ''''''' '''''''''''' '''''''' '''' ''''''''''''' '''''''''''' Process for the manufacturing of EP 0980 711 Bayer AG “The invention on hand relates to a process for the manufacturing of selective exchangers with selective exchangers (2000) imino acetic acid units of the general formula

In which X is taken for hydrogen or an alkali ion, on the basis of cross-linked vinyl aromatic polymerisation through the transformation of a primary amino group carrying weakly alkaline anion exchanger with mono-chlorine-acetic acid and/or an alkali-salt of the mono-chlorine- acetic acid Process for preparing US Bayer AG Process for the preparation of novel, heterodisperse chelate resins with the chelating

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 41 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication) heterodisperse chelating resins 2002018544 functional groups and to their use for adsorption of metal compounds, in particular alkaline 3 A1 (2002) earth metals, heavy and precious metal compounds as well as for the extraction of alkaline earth metals in brines of the chlor-alkali electrolysis, as well as in hydrometallurgy Production of cation exchange DE Bayer AG The production of cation exchange resin in the form of a stable gel, involving suspension resin beads for use e.g. in water 10050680 polymerisation of a mixture of 90-95% wt. styrene and 5-10% wt. DVB at a bath ratio (o/w) of purification, involves suspension (2002) (1:1)-(1:2.5) in presence of 5-8% wt. acrylonitrile (based on styrene plus DVB) in the aqueous polymerisation of styrene and phase, followed by sulphonation with sulphuric acid in the absence of swelling agent. An divinylbenzene in presence of Independent claim is also included for cation exchange resins obtained by this method acrylonitrile followed by ''''''''''' ''''''' ''''''''''''' ''''''' ''''''''' '''''''''''''' '''' ''''''' '''''''''''''''''' '''' ''''''''''''''''' '''''''''' '''''''''' '''' ''''''''' ''''''' '''''' sulfonation in absence of swelling ''''''''' '''''''''' ''''''''''''''''''''' ''''''' '''''''''''''''' ''''''''''' '''''' ''''''''' ''''''''''''''''' ''''' '''''''''''''''''' ''''''''''' ''''''''''''' ''' agent '''''''''''''''''''' '''''''''''''' '''' '''''''''''''' '''''''''''''''''''' '''#D'''''' ''''''''''''''' '''''''' '''''''''''' ''''''''''''''''''' '''' ''''''' '''''''''' ''' ''''' ''''''''''' '''''''''''''''' '''''''' '''''''''''''''''' '''''' ''''''' '''''''''''' '''' ''''''' ''''''''''''''' ''''''''''' '''''''' ''''''' '''''''''''''' '''''''''''''''''' '''' ''''''' ''''''''''''''''''' ''''' ''''''' ''''''''''''''''''' ''''' ''''''''''''''' ''''''''''''''''' '''''''''''''''''''' '''' '''''''' '''''''''''' '''''''' '''' '''''''''''' '''''''''''' Method for producing EP1078690 Bayer AG Process for the preparation of new, monodisperse ion exchangers having chelating functional monodispersed ion exchangers (2003) groups and to their use for adsorption of metal compounds, especially of heavy and precious with chelating groups and the use metal compounds, and alkaline earth metals from brines for the extraction of the alkali metal thereof chloride electrolysis Sugar juice colour removal using EP1205560 Bayer AG Process for decolorising sugar juices using monodisperse ion exchangers, preferably anion monodispersed anion exchangers (2003) exchangers, and the use thereof for the sugar juice Monodispersed anion exchanger EP1323473 Bayer AG Relates to a process for the preparation of new, monodisperse weakly basic anion exchangers, (2004) strong base or if appropriate of the poly(meth)acrylamide type, the ion exchanger itself as well as the use thereof Method for producing EP 1000659 Bayer AG Monodisperse gelatinous cation exchanger production by suspension of a seed polymer in a monodispersed gel-like cation (2004) continuous aqueous phase. The seed polymer is a crosslinked polymer with a swelling index of exchangers 2.5-7.5 and contains less than 1% wt. non-volatile soluble fraction Process for preparing US7053129 Bayer AG Relates to a process for preparing novel, monodisperse anion exchangers by (a) reacting monodisperse anion exchangers B1 (2006) monomer droplets made from monovinylaromatic compounds and polyvinylaromatic compounds, and optional porogens and/or initiators; (b) amidomethylating the resultant monodisperse, crosslinked bead polymers with phthalimide derivatives; (c) converting the amidomethylated bead polymers to aminomethylated bead polymers; and, (d) alkylating the Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 42 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication) aminomethylated bead polymers Chelate exchanger EP1687087 LANXESS Relates to novel carboxyl groups, and (CH2) mNR1R2 group-containing ion exchangers having (2006) Deutschland GmbH improved exchange kinetics and selectivity, a process for their preparation and their use for the adsorption of metals, particularly arsenic when they are additionally loaded with iron oxide Methylenaminoethylsulfonic acids- EP2330137 LANXESS Relates to chelating resins containing methylenaminoethylsulfonic groups, a process for their chelate resins (2009) Deutschland GmbH preparation and to their use for the removal of heavy metals from liquids, preferably process water in or from the electronics industry, electroplating industry and the mining industry Method for producing EP2025387 LANXESS Process for preparing novel monodisperse chelate resins based on crosslinked bead polymers monodisperse chelate resin (2009) Deutschland GmbH having aminomethyl groups and / or aminomethyl nitrogen heterocyclic groups which have a high absorption capacity for heavy metals and rapid kinetics Process for producing cation EP2077158 LANXESS A strongly acidic cation exchanger is obtained by sulphonating bead polymer formed from exchangers (2009) Deutschland GmbH aromatic vinyl monomer, crosslinker and vinyl ether and/or vinyl ester (0.2-20 weight%). An independent claim is included for manufacture of strongly acidic cation exchangers, which involves preparing mono-dispersed or hetero-dispersed bead polymer from vinyl aromatic monomer, crosslinker and vinyl ether and/or vinyl ester by suspension polymerization and converting bead polymer by the action of sulphuric acid, sulphur trioxide and/or chlorosulphonic acid. Heat resistent anion exchanger EP1908521 LANXESS Relates to heat-stable anion exchangers based on at least one aromatic monomer and at least (2010) Deutschland GmbH one crosslinker containing the structural elements of the general formula (I)

wherein Ak, Ak 'Ak' each independently the same or different for a C 1 -C 18 alkyl radical stand, n represents a straight number between 5 and 18, x + y = 2 and X Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 43 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication)

Cl, Br, OH, HCO 3, HSO 4, ½ (SO 4), ½ CO 3, NO 3, F, H 2 PO 4, ½ HPO 4, ½ PO 4, obtainable by reacting non-functional polyvinylaromatic bead polymers with phthalimide using oleum, sulphuric acid or sulphur trioxide as a catalyst, cleavage of the phthalic acid, followed by alkylation of the resulting aminomethylated crosslinked bead polymers with the general formula (II)

wherein n stands for a whole number between 5 and 18, Y for Br, Cl, I, or (SO 4) 1/2 is, X - -, -, 2-) -, a suitable counterion such as Cl Br, I (SO 4 1/2, NO 3 ", HCO 3 and Ak, Ak 'Ak' are each independently, identically or differently a linear or branched alkyl group having 1 to 18 carbon atoms, with or without functional groups Use of amphoteric ion exchangers EP2055383 LANXESS Relates to novel amphoteric ion exchangers which possess not only phthalamide groups of the (2010) Deutschland GmbH formula (I)

but also —(CH2)mNR1R2 groups and/or if appropriate —(CH2)mNR1R2R3 groups, wherein m is an integer from 1 to 4 and R1, R2, R3 in each case independently of one another are hydrogen, —CH3, —CH2CH3, —CH2CH2CH3, benzyl, —OCH2CH3 or —CH2CH2OH and X is H or Na or K, to a process for production thereof and also use thereof Picolylamine resins EP2259874 LANXESS Relates to novel methyl nitrogen heterocyclic resins as the functional group-containing tertiary (2013) Deutschland GmbH nitrogen atoms in structures of the general formula (1) Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 44 Table 4-2: Relevant past R&D undertaken by LANXESS Title Patent Applicant* Abstract / information from patent description number (year of publication)

R 1 stands for an optionally substituted radical from the series picolyl, or methylpiperidine methylquinoline, R 2 is a radical -CH 2 P (O) (OR 3) 2 or -CH 2 -S-CH 2 COOR 3, or -CH 2 -S-C 1 -C 4 alkyl or-CH 2 -S-CH 2 CH (NH 2) COOR 3 or-CH 2 -S-CH 2 -CH (OH) -CH 2 (OH), or

or its derivatives or C = S (NH 2), R 3 represents a radical from the series H, Na or K, m is an integer from 1 to 4, n and p are each independently of one another are numbers from 0.1 to 1.9 and the sum of n and p is equal to 2, and M is the polymer matrix, a process for their preparation and uses thereof, especially the use in the hydro-metallurgy, and electroplating Picolylamine resins EP2259875 LANXESS Relates to novel monodisperse methyl nitrogen heterocyclic resins as the functional group- (2014) Deutschland GmbH containing tertiary nitrogen atoms in structures of the general formula (I)

R 1 stands for an optionally substituted radical from the series picolyl, R 2 is a radical (CH 2) q COOR 3, R 3 represents a radical from the series H, Na or K, m is an integer from 1 to 4, n and p are each independently of one another are numbers from 0.1 to 1.9 and the sum of n and p is 2, q is 1 and M is the polymer matrix, as crosslinkers multifunctional ethylenically unsaturated compounds are used and be designated with additional carboxylic acid groups as monodisperse such polymer beads or methyl nitrogen heterocyclic resins in which at least 90 volume or mass% of the particles have a diameter which lies in the interval with a width of ± 10% of the most common diameter to the common diameter around a process for their preparation and uses thereof, in particular the use in hydrometallurgy and electroplating Note: LANXESS was formed from the 2004 realignment of the Bayer group. Consequently, historical Bayer patents are of relevance to the applicant’s past R&D activities. IAB Ionenaustauscher GmbH is also wholly owned subsidiary of LANXESS Deutschland GmbH

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 45

Current research by LANXESS

Consideration of potential alternative substances

LANXESS continues its research into the identification of a suitable alternative solvent and the placing of EDC into Annex XIV of the REACH Regulation has certainly provided further incentive for the development of a technically and economically feasible alternative to EDC, with an acceptable risk profile. Indeed, as part of the Authorisation process, the applicant has made extensive efforts towards identifying potential alternatives (with associated R&D work starting in ''''''#D'''''''''). This has involved a thorough and systematic review of literature, in combination with laboratory work to screen potential alternative substances, identifying those that warrant further and detailed examination (in Section 5 of this AoA9).

This ‘screening exercise’ can be broken down into 3 steps:

 Screening step 1: Initial identification of long list of potential alternatives  Screening step 2: Refinement based on expert assessment  Screening step 3: Preliminary hazard assessment

Each of these steps (and the subsequent results) is discussed in detail below, and by following this approach, LANXESS has been able to concentrate efforts and resources on those alternatives that are potentially most feasible, whilst ensuring that the scope of the search for potential alternatives has been as all-encompassing as practicable.

Important note

As may be expected, given that the applicant is applying for two similar uses of the EDC, internal R&D activities have concentrated on both uses and have been aligned where possible. As a result of this, the discussion below has also been merged for both uses, with notable synergies / divergences highlighted for the benefit of the reader

Screening step 1: Initial identification of long list of potential alternatives

The purpose of this first step was to identify an initial list of commercially available potential alternative substances, which would be assessed in the subsequent screening steps by LANXESS R&D team experts.

The initial list began with LANXESS utilising their in-house information system software database – DETHERM. The DETHERM database provides thermophysical property data (e.g. phase equilibrium data, vapour pressures, critical data, thermodynamic properties, transport properties, surface tensions and electrolyte data) for approximately 44,200 pure compounds and 139,400 mixtures10. Three selection criteria (liquid at room temperature, boiling point between 80 and 120 °C and Hildebrand solubility parameter between 17 and 21) were used to initially identify potential alternatives substances that may warrant further research.

9 As will be shown in this latter section, the applicant has already begun a rigorous and well defined R&D plan to move away from EDC for both uses, implementing alternatives when they become both technically and economically viable options. 10 See http://www.dechema.de/en/detherm.html. Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 46

The use of the DETHERM database was also complimented by a thorough search of scientific literature, patents and grey literature, as well as a survey on the patent activities of competitors. Key information sources used in this search have been summarised in Table 4-3.

Table 4-3: Key information sources used in literature searches Source Details Kirk-Othmer Encyclopedia "Ion Exchange", C. Dickert, Ion Exchange. Kirk-Othmer Encyclopedia of Chemical of Chemical Technology, Technology, 2000 2000 Ullmann's Encyclopedia of "Ion Exchangers", F. de Dardel, T. V. Arden, Ullmann's Encyclopedia of Industrial Industrial Chemistry Chemistry, 2002 Kirk-Othmer Encyclopedia "Friedel-Crafts Reactions", G.A. Olah, V.P. Reddy, G.K.S. Prakash, Kirk-Othmer of Chemical Technology Encyclopedia of Chemical Technology, 4th Edition, Vol 12, pp 159-199 Ullmann's Encyclopedia of "Acylation and Alkylation", M. Röper, E. Gehrer, T. Narbeshuber, W. Siegel, Industrial Chemistry Ullmann's Encyclopedia of Industrial Chemistry, 2000, DOI 10.1002/14356007.a01_185 Comprehensive Polymer "Carbocationic Polymerization: Styrene and substituted Styrenes", K. Science Matyjaszewski, Comprehensive Polymer Science: the Synthesis, Characterization, Reactions & Applications of Polymers. 1989, 3, 639-671 Encyclopedia of Polymer "Carbocationic Polymerization"; J.E. Puskas, G. Kaszas, Encyclopedia of Polymer Science and Technology Science and Technology, 3rd Edition 2003, Vol 5, pp 382-418 CAS (STN) http://www.cas.org/products/stn/dbss Derwent World Patents http://ip.thomsonreuters.com/product/derwent-world-patents-index Index (DWPI) Google https://www.google.com

With regard to the technical search of scientific literature and patents, LANXESS’ in house Innovation- Information services unit (which serves as an innovation hub to centrally coordinate the group’s R&D activities), undertook three core searches in relation to: ‘sulphonation without swelling agents’ (#1), ‘swelling agents for PS-DVB copolymers’ (#2) and ‘ion exchange and phthalimide’ (#3). The number of technical documents obtained from each search has been highlighted in the following table.

Table 4-4: Patent and technical literature search results Search # Number of patents technical literature documents identified (search medium) 1 78 (THOMSON REUTERS ON STN: 21, ACS on STN: 57) 2 84 (CAS: 42, DWPI: 42) 3 230 (CAS: 126, DWPI: 104)

As a result of the above searches and subsequent analysis, 106 potential alternative solvents (for both uses) were identified. This initial list is presented in Annex 2 (Section 8) of this report.

Screening step 2: Refinement based on expert assessment

Following the initial search of literature and identification of potential alternative substances, additional refinement was undertaken by the LANXESS R&D team to exclude substances for which it was clear that technical feasibility could not be achieved.

The first phase of the applicant’s approach to this screening step considered the similar process conditions associated with the sulphonation and phthalimidomethylation uses (e.g. the fact that they both work under strongly acidic conditions upon generation of a cationic reaction intermediate in the Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 47 presence of a Lewis acid catalyst). With such process considerations and the associated analytical expertise of LANXESS R&D staff in support, the applicant has been able to screen out substances that belong to several groups of compounds, as noted in the following table.

Table 4-5: Chemical groups excluded from further consideration Chemical Key points on feasibility in relation to Key points on feasibility in relation to the group the sulphonation process phthalimidomethylation process Esters Substances within this group will Substances within this group will decompose decompose under the reaction under the reaction conditions conditions Ketones Substances within this group will Substances within this group will decompose decompose under the reaction and/or react under the reaction conditions conditions Alcohols Substances within this group will react Substances within this group will react themselves themselves and inhibit the sulphonation and inhibit the phthalimidomethylation reaction reaction Ethers Substances within this group will Substances within this group will decompose decompose under the reaction under the reaction conditions conditions Aromatic Substances within this group will be Substances within this group will be functionalised hydrocarbons sulphonated under the reaction under the reaction conditions and be non- conditions and be non-recyclable recyclable Aliphatic Substances within this group will not Substances within this group will not swell the PS- hydrocarbons swell the PS-DVB copolymer beads DVB copolymer beads and will not dissolve the ether reagent

Following on from the assessment of chemical groups, with further expert interpretation and discretion from the LANXESS R&D team, a list of 16 potential alternative substances to be assessed on a more individual basis was formulated. The substances were chosen due to e.g. promising information that had been identified in the screening step 1 technical literature search or due to their similar structure (and perceived technical properties) to EDC.

In Table 4-6, the substances have been assessed against both sulphonation and phthalimidomethylation uses, with analysis taking the form of desk-based research or laboratory testing. Where relevant, the table includes the key reasons for the exclusion of potential alternatives from further consideration, primarily based on technical feasibility considerations identified in Section 2.5. The three substances which progressed from this phase to the final screening step are also identified.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 48

Although the substance has not proceeded to the formal preliminary hazard assessment below, the applicant also wishes to highlight its unfavourable harmonised EU classification as a category 2 carcinogen and category 1b reproductive toxicant ,,-trifluorotoluene 98-08-8 Laboratory Insufficient swelling efficiency. Insufficient swelling ability for the Substance excluded from tests Not stable in process (degrades partially copolymer beads; degrades partially under further consideration for both under the reactions conditions, which the reactions conditions, which leads to uses would lead to corrosion problems of the corrosion problems of the equipment and equipment and compromises the compromises the recyclability Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 49

Table 4-6: Results of screening step 2 Alternative group/ CAS Analysis Key points on substance feasibility in Key points on substance feasibility in Overall conclusion substance Number undertaken relation to the sulphonation process relation to the phthalimidomethylation process recyclability Chlorobenzene 108-90- Desk-based Not stable in process (will be Not stable in process (will be Substance excluded from 7 sulphonated under the reaction functionalised under the reaction further consideration for both conditions and be non-recyclable) conditions and be non-recyclable) uses 1,2-dichlorobenzene 95-50-1 Laboratory Boiling point too high (180 °C); may also Achieves no more than 65% Substance excluded from tests be sulphonated under the reaction functionalisation as compared to the EDC further consideration for both conditions based process. The aromatic nature of the uses substance will also make its removal down to required ppm levels in the final products extremely difficult 1,4-dichlorobenzene 106-46- Desk-based Boiling point too high (174 °C). Freezing Freezing point too high (50 °C); Substance excluded from 7 point too high (50 °C) unfavourable azeotrope further consideration for both uses Dimethylsulfoxide 67-68-5 Desk-based Boiling point too high (189 °C); might Does not swell the copolymer beads; no Substance excluded from react explosively with sulphuric acid at azeotrope given further consideration for both elevated temperatures uses Dimethylformamide 68-12-2 Desk-based Not stable in process. Will degrade Not stable in process. Will degrade under Substance excluded from under the reaction conditions the reaction conditions further consideration for both uses Nitromethane 75-52-5 Desk-based Potentially explosive; will not swell the Potentially explosive; will not swell the Substance excluded from copolymer beads copolymer beads further consideration for both uses 1-nitropropane 108-03- Desk-based Boiling point too high (131 °C); may May decompose explosively under the Substance excluded from 2 decompose explosively under the reaction conditions (strong acid) further consideration for both reaction conditions (strong acid) uses 2-Nitropropane 79-46-9 Desk-based May decompose explosively under the May decompose explosively under the Substance excluded from reaction conditions (strong acid) reaction conditions (strong acid) further consideration for both uses 1,1,2,2-tetrachlorethane 79-34-5 Desk-based Boiling point too high (146 °C) Final AER/CR quality issues Substance excluded from further consideration for both Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 50

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 51

Screening step 3: Preliminary hazard screening of potential alternative substances11

Based on preliminary feasibility considerations, a list of three potential alternative solvents was identified. An additional substance, '''''''''' '#E'''' '''''''''''''''', that is related to use of an alternative technique (see further discussion below) is also included. The intrinsic hazard properties of these substances were screened to identify and deselect those substance that possess critical hazard properties (e.g. CMR properties), which make them unsuitable as substitutes for EDC.

The following information was retrieved

 Registration status (which is also a first indication of market availability)  EU hazard classification  Any other relevant information on SVHC properties (e.g. existing restrictions, evaluations of carcinogenicity by other organisations (e.g. IARC), evidence for endocrine disrupting activity).

To this end, ECHA’s website12 was consulted and the respective substance searched by CAS Number. Registration status as well as the classification of substances was retrieved from this site. Also, any information on other REACH-related activities (e.g. listing as SVHC, information on restrictions, authorisation, etc.) were followed and evaluated regarding its potential consequences for using the substance as an alternative for EDC.

Furthermore, eChemPortal13 was consulted to check any involvement in other regulatory programmes and existing evaluations (e.g. OECD SIDS reports, US HPVIS, EU Risk Assessment Reports).

Relevant findings are documented in Table 4-7 below.

Table 4-7: Result of the hazard screening of potential alternative substances Substance CAS No. Registration Classification * Comments Conclusion status 1,2- 78-87-5 Full Flam. Liq. 2 H225 IARC (Vol 110): (Suspected) dichloropro registration, Acute Tox. 4 H302 Group 1 carcinogen, not pane >1000 Acute Tox. 4 H332 (carcinogen to eligible tonnes/y humans) H C+H proposal by RAC: Carc. 1B 1,3- 142-28-9 Pre- Flam. Liq. 3 H226 NTP 13. Report on Potential dichloropro registered Skin Irrit. 2 H315 Carcinogens: carcinogenic pane only Eye Irrit. 2 H319 techn. grade: properties to be STOT SE 3 H335 “reasonably clarified, possibly anticipated to be few data on a human aquatic toxicity carcinogen” 1,4- 110-56-5 Pre- Flam. Liq. 3 H226 Listed in OECD Presumably few dichloro- registered Skin Irrit. 2 H315 HPV program, but data on human

11 It is recognised that some preliminary hazard considerations were given in screening step 2. However, the considerations in step 3 were undertaken to provide a more thorough indication with regard to the hazards associated with promising substances, and a definitive decision with regard to whether they should be assessed further, or excluded from additional considerations 12 http://echa.europa.eu/search-chemicals 13 http://www.echemportal.org/echemportal/ Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 52

Table 4-7: Result of the hazard screening of potential alternative substances Substance CAS No. Registration Classification * Comments Conclusion status butane only Eye Irrit. 2 H319 no report toxicity STOT SE 3 H335 available '''''''''''#E ''''''''#E Full ''''''''''' ''''''' ''' ''''''''''' Corrosive, acute Sufficient data ''''''''''''''' '''''''' registration, '''''''''''' ''''''' ''' '''''''''' hazards dominate available for (part of an >1000 ''''''''' '''''''#E ''' ''''' ''''''''' toxicity profile evaluation alternative tonnes/y '''''''''' ''''''''' ''' '''''''''' technical '''''''''''''''''''' '''''' process) '''''''''''' '''''''' ''' ''''''''''' * Code for classification column: Bold: Harmonised Class. according to Annex XI of Reg. 1272/2008, normal: Class proposed in registration dossier (joint entry); italics: notified classification only

As a result of the screening activities, one substance from the initial list of four (1,2-dichloropropane) was considered ineligible for further evaluation, due to critical hazard properties (carcinogenicity). For 1,3-dichloropropane, there are data also indicating potential carcinogenic properties, but this needs further clarification. 1,4-DCB is not well investigated. For '''''''''' '''#E'''''''''''''''', which is used in an alternative technique, a reliable database is available.

Consideration of alternative techniques

Introduction

The ECHA guidance on REACH Authorisation (ECHA, 2011) states that: “a technical alternative could be a physical means of achieving the same function of the Annex XIV substance or perhaps changes in production, process or product that removes the need for the Annex XIV substance function altogether”.

Taking this into consideration, alternative techniques in the context of the applicant’s use of EDC essentially include the development and/or implementation of an alternative synthetic route and/or process that would allow the production of the desired SAC ERs, AERs and CRs without reliance on EDC.

Alternative techniques for the sulphonation process

In this instance, the alternative technique ‘solventless sulphonation’ has been identified and is of clear significance. In reality, ‘solventless sulphonation’ refers to a range of possible implementations of a technique. This means that this alternative can be carried out in a variety of different ways by altering the process parameters and conditions. As highlighted in the discussion of past R&D, LANXESS has successfully managed to implement a solventless technique to produce a number of IER products at their Bitterfeld facility.

Relevant patents on the technique filed by the applicant have been identified in Table 4-2 (see EP 0868444, DE 10050680, EP 1000659 and EP 2077158), whereas Table 4-8 identifies additional patents available in the open literature. Much of the information in the patents presents solventless sulphonation as a promising potential alternative technique and '''' ''''''''''#D'''' '''''''''' the applicant also began undertaking a detailed R&D plan in an attempt to implement this technique at Leverkusen; it is for this reason that a detailed assessment of this potential alternative is provided in Section 5.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 53

One obvious point to highlight is given that LANXESS has focused some of its past R&D on this area, and has experience of the process in implementation, if solventless sulphonation was currently a technically and economically feasible alternative to EDC-based SAC ER production at Leverkusen, there would be little incentive for the applicant to apply for the continued use of EDC.

Based on the patent literature by the applicant and others, the main process differences in the use of EDC and the solventless techniques are related to reaction time and temperature:

 Reaction time: Longer reaction times are required for solventless techniques in order to achieve comparable beads (Bachmann, Feistel, Seidel, Siekiera, & Karl-Heinz, 2001). The reaction time is of course related to reaction temperature  Reaction temperature: Higher temperatures are claimed to be required for solventless techniques in comparison to processes employing EDC (Bachmann, Feistel, Seidel, Siekiera, & Karl-Heinz, 2001). The solventless techniques require temperatures above the glass transition

temperature (Tg) of the beads for sulphonation to occur (Dow, 2006). The Tg can be expected to be dependent on the degree of cross-linking within the polymer, with higher degrees of cross- linking requiring higher temperatures. This would result in longer heating and cooling ramps to reach the desired temperature. This would further slow the process cycle time.

The assessment of solventless sulphonation will demonstrate that attempts to implement this alternative further will not be complete until at least 4 years after the Sunset Date for EDC.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 54

Table 4-8: Patents on non-solvent sulphonation available in open literature Patent number (year of Title Applicant Abstract / Information from patent description publication) Process for the DE3230559A1 Mitsubishi Process for the manufacturing of cation exchange resins in the absence of a swelling agent, made manufacturing of cation of an organic solvent. Based on PS-DVB copolymers with acrylic acid, methacrylic acid and low exchange resins acrylic ester groups Ion exchange resins EP 0361685 (1990) Rohm and Haas Ion exchange resin particles bearing ion exchange groups only in the most accessible portions of the particles possess kinetic advantages over fully functionalised resins in continuous-flow treatment of fluids. Resin beads are functionalised in an outer region that is from 32 to 73% of the bead radius thick: non-spherical or macroporous particles are similarly functionalized in a layer that is adjacent to the outer surface of the particle or to the surface of the macropores. Such a functionalization is obtained using a reagent system in which the functionalization rate is faster than the rate of diffusion of the reagent into the particle, and stopping the reaction when from 68% to 98% of the most readily accessible, functionalisable sites are functionalized Method for preparation of EP 1270609 (2002) Rohm and Haas An improved process for preparing strong acid cation exchange resins by sulphonation of wet strong acid cation crosslinked copolymer in the absence of organic swelling solvents is disclosed. This process exchange resins involves dewatering a crosslinked poly(vinylaromatic) copolymer to selected residual moisture levels of 3 to 35%, followed by non-solvent sulphonation, to provide strong acid cation exchange resins having enhanced physical stability and that are free of chlorinated-solvent contaminants Improved solventless EP 1685166 (2006) Dow Global A process for the preparation of styrene-divinylbenzene gel cationic exchange resins by sulfonation of exchange Technologies sulphonation in sulphuric acid, without the addition of a swelling agent or acrylic co-monomers, resins Inc. with relatively fast hydration rate. The use of temperature and acid concentration to increase the rate of sulphonation while controlling the side reaction of sulfone bridging minimizes reaction time while maximising bead quality

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 55

Alternative techniques for the phthalimidomethylation process

The applicant is also considering the use of an alternative technique employing '''''''''' #E '''''''''''' during the phthalimidomethylation process. The technique was identified by LANXESS R&D experts considering potential novel approaches that could be adopted (separate to the core of the team’s R&D efforts on potential alternative substances). In particular, the applicant sought to identify whether any aspects of the ‘solventless sulphonation’ process could be implemented in a similar manner to replace EDC in the phthalimidomethylation process.

The technique involves the use of '''''''''''#E'''''''''''''''' as a reaction medium (solvent) and reagent for the phthalimidomethylation reaction. However, the substance does not replace EDCs function as a swelling agent14. Instead, the requirement for the copolymer beads to be ‘swollen’ is intended to be made obsolete by other changes to technical parameters of the production process, which will allow for functionalisation to occur.

Notably, the use of ''''''''''' '''#E ''''''''''' as a solvent for the reaction between formalin (formaldehyde) and phthalimide '''''''''''' '''''''''''' '''' '''''' ''''''''''''''#E '''''''' '''' ''''''''''''''''''''''''''''''''''''''' ''''''''''''''' '''' '''''''''' '''' ''''''' '''''''''''''''''''''''''''''''''''''''''''' '''''''''' '''''''''''''''' ''''''''''''''''''' '''''''''''' '''''' ''''''''''''' ''''''''''''''''

Additional changes to the current production process (Step 2, as described in Section 2.4.3) can also be identified. These include:

 Re-optimisation and changes due to change of solvent to '''''''''' ''''#E '''''''''''' – these would be similar to the requirements introduced by a simple change of solvent, as described for 1,3- DCP and 1,4-DCB  Changes in reaction conditions, times and rates, by-product profile and any washing or purification steps '''''''''''''''' '''''' ''''''' ''''''''''''''''''''#E ''''''''''''''''''''''''''''''''''''' ''''''''''''' ''''''''' '''' ''''''''' ''''' ''''''''''''''''''''''''''''''''''''''''''' '''''''''''

After the production of amidomethylated (phthalimide protected) bead polymers, this technique could be expected be identical to the current process; Step 3 (see Section 2.4.3) involves removal of the same phthalimide group from the resin to produce aminomethylated bead polymers. The precursors and product are the same in both the current process and this proposed alternative technique. 4.3 Conclusion

The applicant has followed a detailed, stepwise and logical approach to screen over 100 potential alternative substances for EDC. The initial list was identified with LANXESS utilising their in-house information system software (DETHERM) in combination with an in depth review of the available scientific and technical literature, as well as competitor patents. A separate detailed search was undertaken to identify alternative techniques.

In a subsequent screening phase, via a process of desk-based research coupled with laboratory testing, individual substances and entire chemical groups were excluded from further consideration

14 Because '''''''''' ''#E '''''''''''''''' itself is not replacing the entire ‘function’ of EDC, we are referring to the potential alternative as the ‘'''''''''' '''''''#E '''''''''' technique’.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 56 based on technical feasibility parameters (e.g. esters were excluded as they would be unstable and decompose under sulphonation or phthalimidomethylation reaction conditions).

As a result of the above steps, four substances (including '''''''''''' '''#E ''''''''''''', a substance within an alternative technique) proceeded to a preliminary hazard assessment, with information retrieved on registration status, EU classification and any other relevant information on SVHC properties (e.g. existing restrictions, evaluations of carcinogenicity by other organisations (e.g. IARC), evidence for endocrine disrupting activity). eChemPortal15 was also consulted to check any involvement in other regulatory programmes and existing evaluations (e.g. OECD SIDS reports, US HPVIS, EU Risk Assessment Reports).

As a result of this assessment 1,2-dichloropropane was considered ineligible for further evaluation, due to critical hazard properties (carcinogenicity). For 1,3-DCP data also indicated potential carcinogenic properties, but was concluded to require further clarification. 1,4-DCB is not well investigated although for '''''''''''' '#E '''''''''''''', a reliable dataset is available.

With regard to alternative techniques, given that LANXESS implements the process of solventless sulphonation and a variety of promising claims on the process are available in the scientific and technical literature, this potential alternative is also assessed in Section 5. In addition, with regard to the applicant’s phthalimidomethylation process, an alternative unique technique utilising '''''#E '''' ''' '#E ''''''''''''' will be assessed.

15 http://www.echemportal.org/echemportal/

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 57

5 Suitability and availability of possible alternatives

Important note

As highlighted in Table 4-1, Section 5 of this AoA considers 4 potential alternatives. It must be reiterated that 1,3-DCP is being assessed as a potential alternative for both sulphonation and phthalimidomethylation uses. Consequently (particularly where technical implementation costs are concerned), their analysis has been merged.

Evidently, 1,4-DCB and the ''''''''''' '#E '''''''''''''''' technique are considered only an alternative for phthalimidomethylation and the solventless sulphonation technique is considered an alternative only for sulphonation 5.1 Alternative 1: 1,3-DCP (Uses 1 and 2)

5.1.1 Substance ID and properties

Name and other identifiers of the substance

The following table presents the identity of the substance.

Table 5-1: Identity of 1,3-dichloropropane Parameter Value Source EC number 205-531-3 1 EC name 1,3-dichloropropane 1 CAS number 142-28-9 1 IUPAC name 1,3-dichloropropane 2 Trimethylene dichloride; 142-28-9; Propane, 1,3- Other names dichloro-; 1,3-Dichloro-propane; UNII- 2 AJ1HQ2GUCP; R 270fa; CCRIS 9220; HSDB 5482

Molecular formula C3H6Cl2 2 SMILES notation C(CCl)CCl 3 Molecular weight 112.98574 2

Molecular structure 3

Sources (searches undertaken on 22 July 2015): 1: ECHA (Pre-registered substances): http://echa.europa.eu/en/information-on-chemicals/pre-registered- substances 2: Pubchem: http://pubchem.ncbi.nlm.nih.gov/ 3: Chemspider: http://www.chemspider.com/

Physicochemical properties

The following table presents the key physicochemical properties of 1,3-DCP (search undertaken on 22 July 2015).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 58

Table 5-2: Physicochemical properties of 1,3-DCP Property Value Remarks Source Physical state at 20°C and liquid 1 101.3 kPa Melting/freezing point -99.5 / -100 °C 2 Boiling point 120 °C at 760 mmHg 2 Density 1.1 ± 0.1 g/cm3 Predicted data 2 Vapour pressure 18.3 ± 0.2 mm Hg at 25 °C Predicted data 2 Surface tension 26.3 ± 3.0 dyne/cm Predicted data 2 Water solubility Partition coefficient log Pow: 2.00 1 Flash point 32.2 ± 0.0 °C Predicted data 2 Flammability Explosive properties Self-ignition temperature Oxidising properties Granulometry Sources: 1: Sigma Aldrich: http://www.sigmaaldrich.com/catalog/AdvancedSearchPage.do 2: Chemspider: http://www.chemspider.com/

5.1.2 Technical feasibility

A number of steps are taken here for the assessment of the technical feasibility of 1,3-DCP. These include:

 Step 1: Comparison of 1,3-DCP against the technical feasibility criteria. A detailed explanation of the technical shortcomings/differences to the EDC based production processes is provided  Step 2: Description of practical steps required for the implementation of the alternative. An analysis is given of the R&D, engineering and process modifications required for the conversion of the applicant’s Leverkusen plant to 1,3-DCP and a timeframe for such implementation is provided.

Comparison of 1,3-DCP to the EDC based process against key technical performance criteria

The use of 1,3-DCP as a potential alternative for the EDC based process has been proposed based on the substance’s initially promising technical feasibility characteristics, as highlighted in the screening exercise in Section 4.2. Table 5-3 presents a more in depth comparison of the performance of 1,3- DCP against the full list of technical comparison criteria identified in Section 2.5 for the sulphonation process. Similarly, a technical comparison for the phthalimide process is provided in Table 5-4.

Table 5-3: Comparison of 1,3 DCP and use of EDC according to technical feasibility criteria - sulphonation Technical criteria Relevant threshold value or ideal Values for 1,3-DCP (comparison and range comments) Solubility in sulphuric acid Must be immiscible with sulphuric Solubility <1% wt. acid (solubility <1% wt.) Boiling point 80 – 120 ˚C 121 °C - borderline Freezing point < 0 °C -99.5 °C

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 59

Table 5-3: Comparison of 1,3 DCP and use of EDC according to technical feasibility criteria - sulphonation Technical criteria Relevant threshold value or ideal Values for 1,3-DCP (comparison and range comments) Swelling efficiency -Hildebrand solubility 1/2 parameter 17 – 21 MPa 19.8 MPa1/2

Solvent stability < 0.1 % wt. reacting per batch < 0.1 % wt. Final SAC ER quality - Bead integrity > 95 % whole perfect beads > 95 %

- Bead process stability >80 % whole perfect beads after > 80 % osmotic stability tests All investigated products ''''''''''''

- Performance parameters '''''''''''''''''''''#D''''''' '''''''' '''''''' have No specific threshold performance meeting specifications

Table 5-4: Comparison of 1,3 DCP and use of EDC according to technical feasibility criteria -phthalimide route Technical criteria Relevant threshold value or ideal Values for 1,3-DCP (comparison and range comments)

Freezing point < 0 °C -99.5 °C Azeotrope formation with Must form an azeotrope with water Formed azeotrope water Azeotrope properties -Azeotropic boiling point 80 – 100 °C 88 °C -Water content 10 – 90 % wt. 64 % wt. Swelling efficiency -Hildebrand solubility 17 – 21 MPa1/2 19.8 MPa1/2 parameter Solvent stability < 0.1 % wt. reacting per batch < 0.1 % wt. > 95 % ion exchange yield, as achieved 100 % Functionalisation degree with EDC Final AER/CR quality 99 % - Bead integrity > 95 % whole perfect beads > 80 % whole perfect beads after 98 % - Bead process stability osmotic stability tests All investigated products '''''''' '''''''' ''''''' - Performance parameters No specific threshold '''''''#D ''''' ''''''''' have performance meeting specifications

As can be seen, 1,3-DCP meets the technical feasibility criteria set out by the applicant with the exception of its borderline acceptable boiling point for the sulphonation process (this is an issue which the applicant, however, believes could be overcome). Despite this, as will be described below, the substance is by no means a drop in replacement for EDC – product recipes would be required to be optimised for the new solvent in order to achieve the required quality and properties of end products.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 60

Required steps to allow 1,3-DCP as a technically feasible alternative to EDC

The replacement of EDC by 1,3-DCP would have notable practical (e.g. engineering) implications for the applicant’s activities at Leverkusen. The required R&D and engineering work (combined for both the sulphonation and phthalimide processes) has been summarised in the following table, along with information on the necessary modifications to process parameters. Given that the applicant has no plans to pursue this alternative, the theoretical timeframe for its implementation is assumed to start at the Sunset Date for EDC (i.e. November 2017).

Table 5-5: Steps to allow 1,3-DCP as an alternative to EDC Step Duration of each Notes step (and total duration) 1. R&D work 72 months Would be required for the optimisation of new ‘recipes’ for each product type. Piloting of the products with the new recipes and validation of these by LANXESS’ customers would also have to be undertaken. 2. Engineering work 12 months Engineering activities can be split into five stages: - Technical design - Installation of new tanks and tank farm - Hazard and operability study - Extension of process control system and additional piping - Pilot trials 3. Modification of 60 months Technical implementation (predominantly involving the process parameters addition of the tank farm) 4. Full recertification 24 months This is the minimum timeframe required (see additional and requalification discussion in the following section) Theoretical total 72 months Assuming full customer acceptance. Based on timeframe to implementation at the Sunset Date, November 2023 is the implement* earliest date this alternative could be put into full operation. *Note: The total duration accounts for overlaps between phases of engineering work, process parameter modifications, recertification and requalification.

Conclusion on the technical feasibility of 1,3-DCP

Despite 1,3-DCP largely meeting the necessary technical comparison criteria for both the sulphonation and phthalimide processes, due to the required R&D activities, engineering work and process parameter modifications, the substance cannot be deemed a technically feasible alternative at this time. If LANXESS was to implement the alternative, theoretically, this could be achieved by November 2023 at the earliest. However, as will be demonstrated in the following sections, the substance does not have a favourable hazard profile and on this basis cannot be considered a suitable alternative for EDC.

5.1.3 Economic feasibility

The cost of converting from EDC to 1,3-DCP needs to consider both investment costs and changes to operating costs.

Investment costs for the implementation of the alternative

There are several key investment costs for switching from EDC to 1,3-DCP: Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 61

 Access to technology and R&D: The applicant estimates total R&D costs of ''''''' ''#D''''''''''' (€1-10 million), associated with the implementation of this alternative. This is based on annual R&D program costs of ''''''''''''''''' '''''''''' #D''' ''' ''''''''' '''''''''' ''''''''''''.

 Plant conversion costs: there are three key steps under this:

 Plant downtime: The applicant anticipates a 1-month period of downtime. This is expected to result in an 8% reduction in AER sales from the phthalimide process in the year of the theoretical downtime, and a 15% reduction during the parallel test phase due to the implementation of pilot projects associated with more manual operations. This also assumes that sales of products not requiring the use of solvent (such as macroporous cation exchange resins) would continue during this time.  Acquisition of replacement equipment: As a replacement for both sulphonation and phthalimide processes, new tanks would be needed for 1,3-DCP to ensure a parallel operation with EDC during the trial and validation phases of implementation. Costs associated with the tanks/tankfarm for 1,3-DCP are estimated at '''''''' ''''#D'''''''''' (€1-10 million). An update in the process control system and additional piping are estimated to cost ''''''''' ''''''''''''' '''''''''' '''''''''''' '''#D''''''''' '''' ''''''' ''''''' ''''''''''''''''''''' ''''''''''' (€1-10 million)  Cost of installing new equipment (engineering cost): The applicant estimates the planning and engineering costs associated with the implementation of the replacement equipment at ''''''''' #D ''''''''''''' (<1 million).

 Requalification: Requalifications will be necessary in respect to different national legislation concerning drinking water and food applications (TüV, NSF, ResAP)16. The applicant estimates requalification costs of ''''''''' ''#D ''''''''' (up to €300,000 per product and ''''''#D ''''' '' products affected). The applicant also estimates that it would take 24 months for requalifications to be completed.

 Retraining: The applicant anticipates retraining activities associated with the implementation of the alternative to take 1 month. This includes briefing operators on the content of new Standard Operating Protocols (SOPs) and safety measures associated with the different properties of the alternative solvent as well as the introduction of new analytical procedures for determining residual amount of solvent in the final product.

Operating costs

The following table presents the range of operating cost elements considered by the applicant and provides a comparison of the costs arising under the applicant’s current process utilising EDC, and 1,3-DCP.

Given that the applicant presently produces with EDC approximately ''' #C'''''' varieties of SAC ER, AER and CR, it is not practical to provide a comparison of operating costs for individual grades. Consequently, an average value is used to demonstrate how much each cost category contributes to the overall operating cost.

16 Note: The sequence of events surrounding a FDA food contact approval have been provided as a further example in Annex 4).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 62

Table 5-6: Comparison of operating costs for production of SAC ERs, AERs and CRs between the applicant’s current processes utilising EDC, and 1,3-DCP Operating costs category Contribution to current Effect on cost element overall operating cost (%) (decrease, stay the same (i.e. no significant change) or increase) if EDC were replaced by 1,3-DCP Energy costs Electricity '''#C ''' No significant change Steam ''#C'''' Increase (+10%) Materials and service costs Cost of process solvent (currently EDC) ''''#C'''''' Increase (€5 kg, EDC is €0.5 kg) Raw materials (excluding water and EDC but ''''#C'''' No significant change including their delivery costs) Water N/A No significant change Environmental service costs (e.g. waste ''''#C''' No significant change treatment and disposal services) Transportation of your product N/A No significant change Labour costs Salaries, for workers on the production line N/A No significant change (incl. supervisory roles) Costs of meeting worker health and safety N/A No significant change requirements (e.g. disposable gloves, masks, etc.) Maintenance and laboratory costs Costs associated with testing, equipment N/A No significant change downtime for cleaning or maintenance (incl. maintenance crew costs and lab worker costs) Other costs Marketing, license fees and other regulatory N/A No significant change compliance activities Other general overhead costs (e.g. insurance N/A No significant change premiums, administration, etc.) Overall change in operating costs (%) +5% (estimate)

Energy: It has been indicated that energy costs associated with steam would increase by 10%. This is due to the substance having a higher boiling point for the sulphonation process, and forming an azeotropic mixture with a higher boiling point in the phthalimidomethylation process.

Materials and services: Additional operating costs would arise here, based on the relative price of 1,3-DCP in comparison with EDC (1,3-DCP is ten times more expensive than EDC, at a price of €5000/t). Given the very strong competition in the market (as described in the corresponding SEA document), LANXESS would not be able to pass on the associated increases in operating costs and would be noticeably disadvantaged as such.

Labour costs: No significant costs changes are likely to arise.

Maintenance costs: No significant costs changes are likely to arise.

Other costs: No significant changes have been identified with regard to other operational costs.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 63

Conclusion on economic feasibility

Overall, the conversion from EDC to 1,3-DCP would require significant modifications to the Leverkusen plant. Investment costs associated with ongoing R&D activities are estimated at '''''#C '''' '''''#C'''''''' (€1-10 million) and the acquisition and cost of installing new equipment has been estimated at ''''''''' '#C'''''''' (€1-10 million). In addition, there would be reduced turnover and profit during implementation due to the plant downtime. Retraining and requalification costs would also arise, the latter being estimated at more than ''''' '#C''''''' (€1-10 million). The applicant anticipates a 5% increase with regard to ongoing operating costs.

5.1.4 Reduction of overall risk due to transition to the alternative

Classification and labelling

A search of the ECHA C&L Inventory (undertaken on 29 August 2014) shows that only notified classification and labelling information is available for the substance. This is presented in the Table 5-7.

Table 5-7: Notified classification and labelling of 1,3-dichloropropane according to CLP criteria Classification Labelling Hazard Hazard Class and Statement Hazard Statement Code(s) Pictogram Signal Word Code(s) Category Code(s) Code(s) Flam. Liq. 3 H226 H226 Skin Irrit. 2 H315 H315 Eye Irrit. 2 H319 H319 GHS07 H335 (Not H335 STOT SE 3 GHS02 provided) Wng Flam. Liq. 2 H225 H225 Acute Tox. 4 H332 H332 Source: European Chemicals Agency (C&L Inventory): http://echa.europa.eu/regulations/clp/cl-inventory

Comparative risk assessment

Annex 1 (Section 7) of this document presents a detailed analysis of the hazards and risks of the selected potential alternatives. The reader is referred to the Annex, while here only a short summary of findings is presented.

-5 For this comparative risk assessment a DMELlong-term inhalation workers for EDC associated with a 1 x 10 risk level was derived from the exposure-risk relationship published by the Risk Assessment Committee (ECHA, 2015).

For the environmental assessment a PNECfreshwater was used, which is the same as derived in the registration dossier and by other evaluating bodies.

1,3-DCP was evaluated as a potential alternative substance.

For this comparative assessment available repeated dose studies were discussed, but it was noted that positive test results from genotoxicity tests are available, which indicate, together with the structural relationship with the carcinogens EDC, 1,2-dichloropropane and 1,3-dichloropropene, carcinogenic properties of the substance.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 64

Few aquatic toxicity data are available, which indicate that the aquatic toxicity is similar to EDC or even higher. No PNEC is available in the literature or from a registration dossier.

The available toxicological data indicate potential genotoxic and carcinogenic properties. Furthermore the substance, based on limited data, seems to have similar or higher aquatic toxicity and is expected to distribute to a larger extent to the aquatic environment, leading to higher exposure concentrations in the aquatic compartments, compared to EDC.

In conclusion, 1,3-DCP is not considered a suitable alternative to EDC.

5.1.5 Availability

Three elements of availability can be considered:

 Availability of the alternative in quantities sufficient for the applicant’s production processes  Availability of the alternative in the quality required by the applicant’s production processes  Access to the technology that allows the implementation of the alternative as a replacement for EDC.

With regard to the quantity of 1,3-DCP required, it is noted that the replacement ratio in the SAC ER production process is anticipated to be similar (1:1) to EDC. Consequently, one can assume that a comparable annual usage of 1,3-DCP would be required (i.e. ''#B''' tpa).

An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal17 on 22 July 2015. Information from the portal shows that the substance has not been registered under REACH (although a pre-registration is available). The substance is not considered available from an EU source, meaning it would have to be imported. The applicant is reasonably confident that they would theoretically be able to obtain sufficient volumes of 1,3-DCP (and at the required quality), and has identified two non-EU suppliers of the substance. However, none of the identified suppliers are willing to register 1,3-DCP on their own, meaning that LANXESS would be required to submit a full registration for the substance and absorb the associated costs. The applicant estimates that the costs for such a registration (including toxicological studies requested by ECHA as well as all administrative costs associated with filing a registration dossier) would be up to €350,000.

5.1.6 Conclusion on suitability and availability for 1,3-DCP

The above discussion has explained that although 1,3-DCP exhibits promising characteristics in relation to technical feasibility criteria, the substance could not be implemented until at least 6 years after the Sunset Date. This is due to significant and time consuming R&D, engineering and process modification requirements.

When considering economic feasibility, investment costs relating to ongoing R&D and new equipment are estimated at ''''''''' ''''''''#D'''' '''''''''''', with this value not taking into account reduced turnover and profit during implementation (due to plant downtime) as well as retraining. Changes to operating costs are not insignificant (estimated at +5%) and are mainly associated with the increased

17 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 65 cost of the process solvent and energy requirements. Given current market conditions18 such costs could not be passed onto the applicant’s customers, which would cause the applicant to be at a noticeable disadvantage.

Furthermore, a key factor with regard to the implementation of this alternative is that 1,3-DCP is expected to be genotoxic and carcinogenic. Based on this factor alone, the applicant considers 1,3- DCP an unsuitable replacement for EDC, as their current R&D plan is focused on the implementation of longer-term more sustainable alternatives (as demonstrated in Sections 5.3 and 5.4). 5.2 Alternative 2: 1,4-DCB (Use 2 only)

5.2.1 Substance ID and properties

Name and other identifiers of the substance

The following table presents the identity of the substance.

Table 5-8: Identity of 1,4-DCB Parameter Value Source EC number 203-778-1 1 EC name 1,4-dichlorobutane 1 CAS number 110-56-5 1 IUPAC name 1,4-dichlorobutane 2 Butane, 1,4-dichloro-; NSC 6288; EINECS 203-778- Other names 1; Tetramethylene dichloride; NSC6288; Butane,4- 2 dichloro-

Molecular formula C4H8Cl2 2 SMILES notation C(CCCl)CCl 3 Molecular weight 127.01232 2

Molecular structure 3

Physicochemical properties

The following table presents the key physicochemical properties of 1,4-DCB (search undertaken on 22 July 2015).

18 Please refer to the SEA document for a more in depth discussion of IER market conditions in the context of the applicant’s activities.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 66

Table 5-9: Physicochemical properties of 1,4-DCB Property Value Remarks Source Physical state at 20°C and Liquid Colourless 1 101.3 kPa Melting/freezing point -37/-38 °C 1 Boiling point 155 - 163 °C 1 Density 1.1 ± 0.1 g/cm3 Predicted data 1 Vapour pressure 4.2 ± 0.2 mm Hg at 25 °C Predicted data 1 Surface tension 27.3 ± 3.0 dyne/cm Predicted data 1 Water solubility Partition coefficient Flash point 40 °C 1 Flammability Explosive properties Self-ignition temperature Oxidising properties Granulometry Sources: 1: Chemspider: http://www.chemspider.com/

5.2.2 Technical feasibility

A number of steps are taken here for the assessment of the technical feasibility of 1,4-DCB. These include:

 Step 1: Comparison of 1,4-DCB against the technical feasibility criteria. A detailed explanation of the technical shortcomings/differences to the EDC based production processes is provided  Step 2: Description of practical steps required for the implementation of the alternative. An analysis is given of the R&D, engineering and process modifications required for the conversion of the applicant’s Leverkusen plant to 1,4-DCB and a timeframe for such implementation is provided.

Comparison of 1,4-DCB to the EDC based process against key technical performance criteria

Table 5-10 presents an in depth comparison of the performance of 1,4-DCB against the full list of technical comparison criteria identified in Section 2.5 for the phthalimidomethylation process.

Table 5-10: Comparison of 1,4-DCB and EDC according to technical feasibility criteria - phthalimide route Technical criteria Relevant threshold value or ideal Values for 1,4-DCB (comparison and range comments)

Freezing point < 0 °C -38 °C Azeotrope formation with Must form an azeotrope with water Forms azeotrope water Azeotrope properties -Azeotropic boiling point 80 – 100 °C 95 °C -Water content 10 – 90 % wt. 84 % wt. Swelling efficiency -Hildebrand solubility 17 – 21 MPa1/2 19.6 MPa1/2 parameter Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 67

Solvent stability < 0.1 % wt. reacting per batch < 0.1 % wt. > 95 % ion exchange yield, as achieved 100 % Functionalisation degree with EDC Final AER/CR quality > 95 % whole perfect beads 99 % - Bead integrity > 80 % whole perfect beads after 98 % osmotic stability tests - Bead process stability No performance problems identified

No specific threshold although the substance has had limited - Performance parameters investigation at this time

As can be seen, 1,4-DCB meets the technical feasibility criteria set out by the applicant. Despite this, as will be described below, the substance is by no means a drop in replacement for EDC – product recipes would be required to be optimised for the new solvent in order to achieve the required quality and properties of end products.

Required steps to allow 1,4-DCB as a technically feasible alternative to EDC

The replacement of EDC by 1,4-DCB would have notable practical (e.g. engineering) implications for the applicant’s activities at Leverkusen. The required R&D and engineering work has been summarised in the following table, along with information on the necessary modifications to process parameters. The theoretical timeframe to implement this alternative is assumed to start at the Sunset Date for EDC (i.e. November 2017).

Table 5-11: Steps to allow 1,4-DCB as an alternative to EDC Step Duration of each Notes step (and total duration) 1. R&D work 72 months Will be required for the optimisation of new ‘recipes’ for each product type. Piloting and validation of the products with the new recipes will also have to be undertaken by LANXESS’ customers 2. Engineering work 12 months Engineering activities can be split into five stages: - Technical design - Installation of new tanks and tank farm - Hazard and operability study - Extension of process control system and additional piping - Pilot trials 3. Modification of 60 months Technical implementation (predominantly involving the process parameters addition of the tank farm) 4. Full recertification 24 months This is the minimum timeframe required (see additional and requalification discussion in the following section) Theoretical total 72 months Assuming full customer acceptance. Based on timeframe to implementation at the Sunset Date, November 2023 is the implement* earliest date this alternative could be put into full operation *Note: The total duration accounts for overlaps between phases of engineering work, process parameter modifications, recertification and requalification. Although the number of recipes to be adapted for 1,4-DCB Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 68 would be less than in the case of 1,3-DCP (as the substance is a potential alternative only for the phthalimide process) the R&D capacity available for this substitution would be decreased as LANXESS would need to work on another alternative for the sulphonation process. Thus, the overall theoretical substitution timeframes remain the same for 1,3-DCP and 1,4-DCB

Conclusion on the technical feasibility of 1,4-DCB

Due to the required R&D activities, engineering work and process parameter modifications, the substance cannot be deemed a technically feasible alternative at this time. If LANXESS was to implement the alternative, theoretically, this could be achieved by November 2023 at the earliest. However, as will be demonstrated in the following sections, the substance does not have a favourable hazard profile and on this basis cannot be considered a suitable alternative for EDC.

5.2.3 Economic feasibility

The cost of converting from EDC to 1,4-DCB needs to consider both investment costs and changes to operating costs.

Investment costs for the implementation of the alternative

There are several key investment costs for switching from EDC to 1,4-DCB:

 Access to technology and R&D: The applicant estimates total R&D costs of '''''''' '#D''''''''''''' (€1-10 million), associated with the implementation of this alternative. This is based on annual R&D program costs of '''''''''''''''''' '''''''''' ''#D '''''''' '''''''''' ''''''''''''

 Plant conversion costs: there are three key steps under this:

 Plant downtime: The applicant anticipates a 1-month period of downtime. This is expected to result in an 8% reduction in AER sales from the phthalimide process in the year of the theoretical downtime, and a 15% reduction during the parallel test phase due to the implementation of pilot projects associated with more manual operations  Acquisition of replacement equipment: As a replacement for phthalimide chemistry, new tanks would be needed for 1,4-DCB to ensure a parallel operation with EDC during the trial and validation phases of implementation. Costs associated with the tanks / tankfarm for 1,4-DCB are estimated at '''''''' '#D''''''''''''' (€1-10 million). An update in the process control system and additional piping are estimated '''' ''''''' ''''''''''#D ''' ''''''''''' '''''''''''' '''''' ''''''''' '''' ''''''#D '''''''''''' '''''''''''''''''''''' '''''''''''' (€1-10 million)  Cost of installing new equipment (engineering cost): The applicant estimates the planning and engineering costs associated with the implementation of the replacement equipment as '''''''' #D'''''''''''' (€<1 million)

 Requalification: Requalifications will be necessary in respect to different national legislation concerning drinking water and food applications (TüV, NSF, ResAP)19. The applicant estimates requalification costs of over '''''''''#D '''''''''''' (up to €300,000 per product and more than ''#D' products affected). The applicant also estimates that it would take 24 months for requalifications to be completed

19 Note: The sequence of events surrounding a FDA food contact approval have been provided as a further example in Annex 4).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 69

 Retraining: The applicant anticipates retraining activities associated with the implementation of the alternative to take 1 month. This includes briefing operators on the content of new SOPs and safety measures associated with the different properties of the alternative solvent and the introduction of new analytical procedures for determining residual amount of solvent in the final products.

Operating costs

Given that the applicant presently produces with EDC approximately ''' #C'''''' varieties of AER and CR, it is not practical to provide a comparison of operating costs for individual grades. Consequently, an average value is used to demonstrate how much each cost category contributes to the overall operating cost.

Table 5-12: Comparison of operating costs for production of AERs and CRS between the applicant’s current phthalimidomethylation process utilising EDC, and 1,4-DCB Operating costs category Contribution to current Effect on cost element overall operating cost (%) (decrease, stay the same (i.e. no significant change) or increase) if EDC is replaced by 1,4-DCB Energy costs Electricity ''''#C'' No significant change Steam '''#C'''' Increase (+20%) Materials and service costs Cost of process solvent (currently EDC) '''''#C''' Increase (€5-10 kg, EDC is €0.5 kg) Raw materials (excluding water and EDC but ''''#C '''' No significant change including their delivery costs) Water N/A No significant change Environmental service costs (e.g. waste ''#C''' No significant change treatment and disposal services) Transportation of your product N/A No significant change Labour costs Salaries, for workers on the production line N/A No significant change (incl. supervisory roles) Costs of meeting worker health and safety N/A No significant change requirements (e.g. disposable gloves, masks, etc.) Maintenance and laboratory costs Costs associated with testing, equipment N/A No significant change downtime for cleaning or maintenance (incl. maintenance crew costs and lab worker costs) Other costs Marketing, license fees and other regulatory N/A No significant change compliance activities Other general overhead costs (e.g. insurance N/A No significant change premiums, administration, etc.) Overall change in operating costs (%) +5% (estimate) Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 70

Energy: It has been indicated that energy costs associated with steam would increase by 20%. This is due to the substance forming an azeotropic mixture with a higher boiling point in the phthalimidomethylation process.

Materials and services: Additional operating costs would arise here, based on the relative price of 1,4-DCB in comparison with EDC (1,4-DCB is between 10-20 times more expensive than EDC, at a price of €5000 – 10000/t). Given the very strong competition on the market (as described in the corresponding SEA document), LANXESS would not be able to pass on the associated increases in operating costs at would be noticeably disadvantaged as such.

Labour costs: No significant costs changes are likely to arise.

Maintenance costs: No significant costs changes are likely to arise.

Other costs: No significant changes have been identified with regard to other operational costs.

Conclusion on economic feasibility

Overall, the conversion from EDC to 1,4-DCB would require significant modifications to the Leverkusen plant. Investment costs associated with ongoing R&D activities are estimated at '''#D''''' ''''#D'''''''' (€1-10 million) and the acquisition and cost of installing new equipment has been estimated at ''''''''' #D''''''''''' (€1-10 million). In addition, there would be reduced turnover and profit during implementation due to the plant downtime. Retraining and requalification costs would also arise, the latter being estimated at more than ''''''''#D'''''''''''' (€1-10 million). The applicant anticipates a 5% increase with regard to ongoing operating costs.

5.2.4 Reduction of overall risk due to transition to the alternative

Classification and labelling

A search of the ECHA C&L Inventory (undertaken on 29 August 2014) shows that only notified classification and labelling information is available for the substance. This is presented in the following table.

Table 5-13: Notified classification and labelling of 1,4-DCB according to CLP criteria Classification Labelling Hazard Hazard Class and Statement Hazard Statement Code(s) Pictogram Signal Word Code(s) Category Code(s) Code(s) Flam. Liq. 3 H226 H226 GHS07 Skin Irrit. 2 H315 H315 Eye Irrit. 2 H319 H319 GHS02 STOT SE 3 H335 H335 Wng Aquatic Chronic 3 H412 H412 Source: European Chemicals Agency (C&L Inventory): http://echa.europa.eu/regulations/clp/cl-inventory

Comparative risk assessment

Annex 1 (Section 7) of this document presents a detailed analysis of the hazards and risks of the selected potential alternatives. The reader is referred to the Annex, while here a short summary of findings is presented only.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 71

For the environmental assessment a PNECfreshwater was used, which is the same as derived in the registration dossier and by other evaluating bodies.

1,4-DCB was evaluated as a potential alternative substance.

When scrutinizing available toxicity data it was noted that the toxicological database is incomplete and does not allow firm conclusions on the toxicity of the substance. Furthermore, few genotoxicity tests are available. Taking into account the positive genotoxicity test results for 1,3-dichloropropane, together with the structural relationship with the carcinogens EDC, 1,2-dichloropropane and 1,3- dichloropropene, carcinogenic properties of the substance cannot be excluded. The QSAR toolbox indicates structural alerts for carcinogenicity.

The few available aquatic toxicity data give similar effect levels as obtained for 1,3-DCP. Again, the database is not sufficient to fully assess the environmental effects of the substance.

The limited toxicological database does not allow an assessment for 1,4-DCB. But taking into consideration structural alerts and the similarity to known carcinogens a suspicion for potential genotoxic and carcinogenic properties results.

Furthermore the substance, based on limited data, seems to have similar or higher aquatic toxicity and is expected to distribute to a larger extent to the aquatic environment, leading to higher exposure concentrations in the aquatic compartments, compared to EDC.

In conclusion, 1,4-DCB is not considered a suitable alternative to EDC.

5.2.5 Availability

Three elements of availability can be considered:

With regard to the quantity of 1,4-DCB required, it is noted that the replacement ratio in the phthalimide production process is anticipated to be similar (1:1) to EDC. Consequently, one can assume that a comparable annual usage of 1,4-DCB would be required (i.e. '''#B''' tpa).

An online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal20 on 29 August 2014. Information from the portal shows that the substance has not been registered under REACH (although a pre-registration is available). The substance is not considered available from an EU source, meaning it would have to be imported. The applicant is confident that they would theoretically be able to obtain sufficient volumes of 1,4-DCB (and at the required quality),

20 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 72 and has identified two non-EU suppliers of the substance. However, none of the identified suppliers are willing to register 1,4-DCB on their own, meaning that LANXESS would be required to submit a full registration for the substance and absorb the associated costs. The applicant estimates that the costs for such a registration (including toxicological studies requested by ECHA as well as all administrative costs associated with filing a registration dossier) would be up to €350,000.

5.2.6 Conclusion on suitability and availability for 1,4-DCB

The above discussion has explained that 1,4-DCB could not be implemented until at least 6 years after the Sunset Date for EDC. This is due to significant and time consuming R&D, engineering and process modification requirements.

When considering economic feasibility, investment costs relating to ongoing R&D and new equipment are estimated at '''''''''#D''''''''''''', with this value not taking into account reduced turnover and profit during implementation (due to plant downtime) as well as retraining. Changes to operating costs are not insignificant (at +5%) and are mainly associated with the increased cost of the process solvent and energy requirements. Given current market conditions, such costs could not be passed onto the applicant’s customers, which would cause the applicant to be at a noticeable disadvantage.

Furthermore, an imperative point with regard to the implementation of this alternative is that 1,4- DCB is expected to be genotoxic and carcinogenic. Based on this factor alone the applicant considers 1,4-DCB an unsuitable replacement for EDC, as their current R&D plan is focused on the implementation of longer-term more sustainable alternatives (as demonstrated in Sections 5.3 and 5.4). 5.3 Alternative 3: Solventless sulphonation technique (Use 1 only)

5.3.1 Identification of the alternative technique

Please refer to Section 4.2.1, where a description of this alternative technique is available. This technique is considered an alternative only for the sulphonation process.

5.3.2 Technical feasibility

A number of steps are taken here for the assessment of the technical feasibility of the alternative technique, solventless sulphonation. These include:

 Step 1: Comparison of solventless sulphonation against the technical feasibility criteria. A detailed explanation of the technical shortcomings/differences to the EDC-based SAC ER production process is provided  Step 2: Description of practical steps required for the implementation of the alternative. An analysis is given of the R&D, engineering and process modifications required for the conversion of the applicant’s Leverkusen plant to the solventless sulphonation process and a timeframe for such implementation is provided

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 73

Comparison of solventless sulphonation to the EDC based process against key technical performance criteria

The use of solventless sulphonation as a potential alternative for the EDC based process has been proposed based on the fact that this technique is already recognised and commercially utilised in SAC ER production, and is also in use by LANXESS at their Bitterfeld site. The technique is also highlighted in variety of the applicant’s patents, as described in Section 4.

Table 5-14 presents a comparison of the solventless sulphonation process performance against the full list of technical comparison criteria, identified in Section 2.5.

Table 5-14: Comparison of solventless sulphonation and the use of EDC according to technical feasibility criteria Relevant threshold value or Values for solventless sulphonation Technical criteria ideal range (comparison and comments) Final SAC ER quality - Bead integrity > 95 % whole perfect beads > 95 %

- Bead process stability > 80 % whole perfect beads after 35 – 95 % depending on the product osmotic stability tests - Performance parameters Under investigation; first test results do No specific threshold not meet specifications but are encouraging

Detailed presentation of the technical characteristics of the alternative

Final SAC ER quality: The solventless process produces inferior quality SAC ER products compared to the EDC based process. Although the required bead integrity is achieved, problems remain with regard to bead process stability and some additional performance parameters. For example, issues have been identified with regard to the amount of leachables released by ‘solventless’ SAC ERs during service life and there can also be problems with the kinetics of ion exchange for all applications. Some additional difficulties can also be highlighted for specific types of SAC ERs (e.g. catalytic performance of catalyst SAC ER types and chromatographic separation performance for chromatographic SAC ER types).

Essentially, in its current form, the shift in the quality of SAC ERs achieved by this process would be unacceptable for the vast majority of the applicant’s customers (especially those SAC ERs used as catalysts in chemical processes or those based on highly crosslinked copolymers). However, as discussed below, the applicant is funding an extensive R&D programme in an attempt to improve the feasibility of this option and implement this alternative technique at the Leverkusen site in the future.

Required steps to allow solventless sulphonation as a technically feasible alternative to EDC

In ''''''''''''#D'''' ''''''''', the applicant began the technical phase of an R&D campaign in an attempt to assess the possibility for implementation of the solventless sulphonation process at the Leverkusen facility, and overcome the technical and economic feasibility barriers hindering its implementation. The initial proof of principle phase of this programme ran until '''''''#D'''''''''' and verified that there was indeed potential behind the applicant’s concept and it warranted further consideration.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 74

Subsequent to this phase, the applicant began following a detailed plan for the development, validation and plant implementation steps associated with all ''' #C''''' grades of SAC ER currently produced via the EDC-based process. Essentially, for SAC ERs to be converted to the solventless process, product recipes must be individually optimised in a procedure comprising the internal validation of product quality by pilot trials, as well as experimentation by customers to ensure their requirements are fulfilled. Technical solutions may also be required for the suitable implementation of the lab recipes into the plant, in addition to the installation of new equipment.

Table 5-15 breaks down the standard ''''''' '#D''''''''' timeline associated with the conversion of a single SAC ER product recipe to the solventless technique and includes plant implementation steps. Essentially, the steps highlighted within the table will be undertaken for each product, but in a staggered manner to ensure a consistent and manageable project workflow. In this respect, it is anticipated that there will be an approximate ''#D'' month gap between the start of the development phase for each individual product. Taking this into account, the total timeframe for implementation of the solventless technique across all SAC ERs is presented in Table 5-16. As can be seen, the applicant expects the R&D and plant implementation to be complete by the end of Q3 (September) 2021. There is the potential for feasibility barriers to remain for individual products; however, by ''''''#D''''''''''''', the applicant expects to have a good idea as to whether full scale implementation can be achieved. Certainty over this factor should be achieved by ''''''' #D' '''' ''''''''''.

Based on the current and anticipated future implementation of the applicant’s R&D plan, and considering the November 2017 Sunset Date for EDC, a minimum 4 year review period for the sulphonation use applied for in this AfA is required.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 75

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 76

Table 5-16: Overall timeframe for the implementation of the solventless sulphonation technique (for ''' #C''' SAC ER products) Timeline Step 2014 2015 2016 2017 2018 2019 2020 2021 Proof of principle Development #D'''

Validation

Plant implementation

Conclusion on the technical feasibility of solventless sulphonation

Because solventless sulphonation does not result in sufficient quality SAC ER products it is, in its current form, an infeasible alternative for the EDC-based sulphonation process. Since ''''''' ''''''''#D''' '''' '#D ''''', however, the applicant has been implementing a detailed R&D plan with the aim of improving the technical feasibility of this technique. This aims to lead to the eventual replacement of all ''' #C'''' EDC-based SAC ER products with new optimised recipes forgoing the use of solvent. The practical steps of the R&D plan demonstrate that to make the technique technically feasible, a minimum of 4 years from the November 2017 Sunset Date is required. This also assumes that the R&D does not identify further hindrances to the implementation of the alternative technique.

5.3.3 Economic feasibility of solventless sulphonation

Investment costs for the implementation of the alternative

There are several key investment costs for switching from EDC to solventless sulphonation:

 Access to technology and R&D: The applicant estimates total R&D costs of ''''''''' #D''''''''''''' (€1-10 million), associated with the implementation of this alternative technique. This is based on annual core R&D programme costs of '''''#D '' over a '''#D' time period (for simplicity this figure does not include scoping phase resources allocated to the project, also, the applicant does not anticipate significant R&D costs during the final years of implementation as these costs are covered primarily by plant conversion considerations, below). These activities are being undertaken by the equivalent of ''#D ' full-time staff (FTE) '''''''' '''''''''' '''' ''''''' ''''''' '''''''' ''''''''''''''''' '''''''''''''''' ''''''' ''''''''''''''''''' ''#D ''''''''' ''''''''''''''''' '''''' ''''''''''''''''''''' '''''''' '''''''''' ''''''''''''''''' ''''''' '''''''''' '''''''''''''''''' ''''''' ''''''''' '''' ''' '''''''''''''''''''''' ''''''''''''''''''''') working to define process conditions and demonstrate that fully acceptable product quality can be achieved for each SAC ER. ''' ''''''''' ''''''' ''''' ''''''''''' '''''''' ''''''' ''''''''''' '''''''''' ''''''' ''''' ''''''''''''''' '''' '''''' '''''' '''''''''''' '''''' '''''' '''''''''''''''''''' '''''''''''''''' ''''''''' ''''''''''''' ''#D '''''''' ''''''''''''' ''''''''' ''''''''''''''''' ''''''' '''''' '''''''' '''''''' '''''''' '''''' '''''''''''''''''''''' ''''''''''''''''''''''''''''' '''''''''''' '''''''''''''''''' ''''''''''''''''''''''

 Plant conversion costs: there are three key steps under this:

 Plant downtime: The applicant does not anticipate a period of downtime, provided that the installation is timed with the annual maintenance cycle  Acquisition of replacement equipment: ''''''''' '''''''''''' ''''''''''''''''''''''' '''''' ''''''' ''''''''''''''' '''''''''''' '''''''''''' ''''' ''''''''''''''''' '''''' ''''''' ''''''''''''''''''''''''''''' '''' ''' '''''''''''' '''''''''''''''''''''''''' ''''''' ''''''''''''''''' '''''''''''#D '''''''' ''''''' ''''''' ''''' ''''''' '''''''''''''''''''' ''''' '''''' Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 77

'''''''''''''' '''''''''' '''''''''''''F'' '''''' #D '''''''''''''''' '''''''''''' An update in the process control system and additional piping will also be required. Costs associated with these elements are estimated at ''''''''' ''''''''''#D '''' '''''''''' '''''''''''''' '''''' ''''''''''#D ''''''''''''''''''' '''''''''' (€1-10 million)  Cost of installing new equipment (engineering cost): The installation cost is estimated at 10% of the material costs, '''' '''''''''#D '''''''''' (€<1 million)

 Requalification: Requalifications will be necessary in respect to different national legislation concerning drinking water and food applications (TüV, NSF, ResAP)21. The applicant estimates total requalification costs up to €''''''#D '''''''' for SAC ERs, (€1-10 million) as these are the only products that would be produced using this alternative. The applicant also estimates that it would take 24 months for requalifications to be completed.

 Retraining: The applicant anticipates retraining activities associated with the implementation of the alternative to take 1 month.

Operating costs

Given that the applicant produces approximately ''' #C''' varieties of SAC ER, it is not practical to provide a comparison of operating costs for each individual grade. Consequently, an average value is used to demonstrate how much each cost category contributes to the overall operating cost.

Raw materials (excluding water and EDC but '''#C '' No significant change including their delivery costs) Water N/A No significant change Environmental service costs (e.g. waste ''#C ' No significant change treatment and disposal services) Transportation of your product N/A No significant change

21 Note: The sequence of events surrounding a FDA food contact approval have been provided as a further example in Annex 4).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 78

Table 5-17: Comparison of operating costs for production of SAC ERs between applicant’s current process utilising EDC and solventless sulphonation Operating costs category Contribution to current Effect on cost element overall operating cost (%) (decrease, stay the same (i.e. no significant change) or increase) if EDC is replaced by solventless sulphonation Labour costs Salaries, for workers on the production line N/A No significant change (incl. supervisory roles) Costs of meeting worker health and safety N/A No significant change requirements (e.g. disposable gloves, masks, etc.) Maintenance and laboratory costs Costs associated with testing, equipment N/A No significant change downtime for cleaning or maintenance (incl. maintenance crew costs and lab worker costs) Other costs Marketing, license fees and other regulatory N/A No significant change compliance activities Other general overhead costs (e.g. insurance N/A No significant change premiums, administration, etc.) Overall change in operating costs (%) Increase of uncertain magnitude

Energy costs: The applicant believes that a higher sulphonation temperature would be required for the solventless process than for the current process. This would result in increased energy costs but these have not been quantified for this analysis.

Materials and service costs: A decrease in material costs will be seen as no solvent will need to be purchased by the applicant. However, the service costs would remain. The incineration plant used for treatment of off-gases would still be required for other parts of the process and this is responsible for the majority of service costs.

Labour costs: No significant costs changes are likely to arise.

Maintenance and laboratory costs: No significant costs changes are likely to arise.

Other costs: No significant costs changes are likely to arise.

Conclusion on the economic feasibility of solventless sulphonation

Overall, the conversion from EDC to the solventless technique requires significant modifications to the Leverkusen plant. However, such plans for the implementation of the technique are underway and the applicant has also committed funding to this. Investment costs associated with ongoing R&D activities are estimated at ''''''''' #D'''''''''''''' (€1-10 million) and the acquisition and installation of new equipment has been estimated at '''''''''' '#D''''''''''' (€1-10 million). Retraining and requalification costs would also arise, the latter being estimated at more than '''''''''''#D '''''''''''' (€<1 million). The applicant expects a slight increase with regard to ongoing operating costs, although this cannot currently be quantified.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 79

5.3.4 Reduction of overall risk due to transition to the alternative

As this alternative removes altogether the need for a solvent to swell the PS-DVB copolymer beads during their sulphonation, it can be considered to result in a reduction of hazards and risks when compared with the EDC based process. As a result, unlike for the other potential alternatives, a detailed analysis of these aspects for solventless sulphonation is not provided in Annex 1.

5.3.5 Availability of the technology

According to ECHA (2011) “alternative techniques can be regarded as available when they are developed enough to allow implementation in the relevant industrial sector and they are reasonably accessible without undue delay to the operator”.

Clearly, given that (from a technical perspective) solventless sulphonation can only be implemented as a replacement for the applicant’s current sulphonation process a minimum of 4 years after the Sunset Date, the alternative technology cannot be considered ‘available’ at this time.

5.3.6 Conclusion on suitability and availability of solventless sulphonation

The above discussion has explained that although the solventless sulphonation technique is utilised by the applicant at their Bitterfeld production site, the extended use of this technology at Leverkusen cannot be considered feasible until after the November 2017 Sunset Date. This is primarily due to the different variety of SAC ERs produced at Leverkusen, which typically have a different level of DVB cross-linking, and for which it is more difficult to obtain the required product performance without using EDC.

After a promising proof of principle study undertaken during ''''''' ''''''' '#D''''''' '''' '''''''''', the applicant has put in place a detailed R&D plan to overcome the issues associated with the implementation of this technique. The practical steps of the plan essentially involve the replacement of all ''' '#C''' EDC- based SAC ER grades with a new and optimised recipe which forgoes the need for solvent. The plan, staggered for each grade of SAC ER, is estimated to reach completion in September 2021, meaning a minimum of 4 years from the Sunset Date are required. This also assumes that the R&D does not identify further hindrances to the implementation of the alternative technique.

When considering economic feasibility, investment costs relating to ongoing R&D and new equipment are estimated at '''''''''''' #D'''''''''''''' (€1-10 million), with this also not taking into account retraining costs. However, the applicant has committed funds to this project and does consider it feasible, again, assuming no further issues are identified.

Finally, as it removes altogether the need for a swelling solvent, the technique can be considered to result in a reduction of hazards and risks when compared to the EDC-based process. 5.4 Alternative 4: '''''''''' ''''#E'''''''''''''' technique (Use 2 only)

5.4.1 Identification of the alternative technique

The ‘'''''''''''' ''#E'''''''''''''''' technique’ combines the use of an alternative technique and alternative substance in an attempt to achieve the current functionality of EDC in the phthalimidomethylation

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 80 process (i.e. currently acting as a swelling agent for the PS-DVB copolymer, and a reaction medium for phthalimidomethylation to take place).

The applicant is proposing to address the swelling function of EDC via the implementation of a solventless technique, similar to the ‘solventless sulphonation’ discussed above (i.e. the removal of the solvent with the adaptation of other process parameters to obtain sufficient quality PS-DVB based AER/CR) in the presence of an alternative substance '''''''''''' ''#E ''''''''''''''' used as a reaction medium and to aid the stirrability of the batch.

Consequently the following analysis provides substance specific information for '''''''''' ''''#E '''''''' where appropriate, but, in the main, focus is on the implementation of the technique as a whole.

5.4.2 ''''''''''' #E'''''''''''''''' ID and properties

Name and other identifiers of the substance

The following table presents the identity of the '''''''''''' ''''#E''''''''''''''''.

Table 5-18: Identity of ''''''''''' ''#E''''''''''''''''' Parameter Value Source EC number ''''''''#E'''''''''' 1 EC name ''''''''''''#E ''''''''''''''''' 1 CAS number ''''''''#E '''''''' 1 IUPAC name '''''''''''''#E '''''''''''''''''' 1 Other names ''''''''''' ''#E '''''' ''''''''''''''''' 2 Molecular formula '''''''#E '''''''' 1 SMILES notation ''''''''''''#E ''''''''''''''''''' 2 Molecular weight ''''''#E '''''' -

Molecular structure #E 1

Sources (searches undertaken on 22 July 2015): 1: European Chemicals Agency: http://echa.europa.eu/ 2: Chemspider: http://www.chemspider.com/

Physicochemical properties

The following table presents the key physicochemical properties of ''''''''''' ''#E '''''''''''''''''''. The information has been collected from the ECHA dissemination portal (search undertaken on 22 July 2015).

Table 5-19: Physicochemical properties of '''''''''' ''''#E '''''''''''''' Property Value Remarks Source Physical state at 20°C and Liquid 1 101.3 kPa Melting/freezing point '''''''#E ''''' At standard temperature and pressure 1 Boiling point '''''''''' ''''' #E '''' ''''''''''' Pressure assumed 1 Density ''''''''' '''''#E ''''' '''' ''''' '''' 1 ''''' ''''''' '#E '' '''''''' '''' Measured 1 Vapour pressure ''' ''''''' '#E ''' ''''' '''' Extrapolated beyond the region where 1

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 81

Table 5-19: Physicochemical properties of '''''''''' ''''#E '''''''''''''' Property Value Remarks Source measured data exists Extrapolated beyond the region where ''''''''''''''#E '''' ''''' '''' 1 measured data exists Surface tension '''''''''''' #E ''''''' ''''' '''''' ''''' 1 Water solubility '''''''' ''''''#E ''''' ''''' '''' ''''''''' ''''''''''''' #E '''' ''''''''''' ''''''''''' 1 Partition coefficient ''''''' ''''#E ''''' '''''''''' 1 Flash point '''''#E ''''' 1 Flammability '''''' ''#E '''''''''''' 1 Explosive properties ''''''' ''#E ''''''''''''''' 1 Self-ignition temperature ''''''' '#E '''' 1 Oxidising properties ''''''' '''#E '''''''''''''' 1 Granulometry '''''''' '''#E ''''''''''' 1 Sources: 1. European Chemicals Agency: http://echa.europa.eu/

5.4.3 Technical feasibility

A number of steps are taken here for the assessment of the technical feasibility of the ''''''''''' '''#E ''''#E '''''''' technique. These include:

 Step 1: Comparison of the ''''''''''' ''#E '''''''''''''''''' technique against the technical feasibility criteria. A detailed explanation of the technical shortcomings/differences to the EDC-based AER/CR production process is provided  Step 2: Description of practical steps required for the implementation of the alternative. An analysis is given of the R&D, engineering and process modifications required for the conversion of the applicant’s Leverkusen plant to the ''''''''''' #E '''''''''''''''''' technique and a timeframe for such implementation is provided

Comparison of the '''''''''''' ''#E '''''''''''''''' technique to the EDC based process against key technical performance criteria

The use of the '''''''''''' ''''#E ''''''''''''''''' technique as a potential alternative for the EDC based process has been proposed based on initial feasibility tests that certainly warrant further investigation. Table 5-20 presents a comparison of this technique’s performance against the full list of technical comparison criteria, identified in Section 2.6.

Table 5-20: Comparison of the '''''''''' ''#E '''''''''''' technique and EDC according to technical feasibility criteria Technical criteria Relevant threshold value or ideal Values for ''''''''''' '#E '''''''''''''''''' range (comparison and comments)

Freezing point < 0 °C '''#E ''' °C (< 0 °C) Solvent stability < 0.1 % wt. reacting per batch Presently around 30 % wt.

> 95 % ion exchange yield, as achieved Functionalisation degree 80 % with EDC

Final AER/CR quality - Bead integrity > 95 % whole perfect beads 99 %

- Bead process stability > 80 % whole perfect beads after 98 % osmotic stability tests Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 82

- Performance parameters No specific threshold Under investigation

Detailed presentation of the technical characteristics of the alternative

Functionalisation degree: The ''''''''''' ''#E '''''''''''''''''' technique presently results in a lower yield of AERs/CRs and plant capacity will be reduced when compared with the EDC based process. This is a considerable disadvantage for the applicant.

Final SAC ER quality: The quality of SAC ERs achieved using the '''''''''''' '''#E '''''''''''''''''' technique is still under investigation.

It is clear that there are significant knowledge gaps that preclude the full comparison of technical characteristics of this technique to the EDC-based process. As discussed below, considerable R&D is being undertaken to establish the extent to which the '''''''''''' #E '''''''''''''''''''' technique can be employed, and its feasibility parameters improved.

Required steps to allow the ''''''''''' #E '''''''''''''''''''' technique as a technically feasible alternative to EDC

In ''''''''''''''#D '''''' '''''''''', the applicant began an R&D campaign in an attempt to assess the possibility for implementation of the '''''''''''' ''#E'''''''''''''''' technique at the Leverkusen facility, and to overcome the technical and economic feasibility barriers associated with its implementation. The initial proof of principle phase of this program is ran until ''''''' ''''''' '''#D '''''''' ''''''''' and it was concluded that the concept warrants further consideration.

As a result of this, the applicant intends to follow a detailed plan for the development, validation and plant implementation steps associated with all ''' '#C'''' grades of AERs and CRs currently produced via the EDC-based process.

Expectations are that the planned R&D work on the new chemistry might lead to more efficient processes with less consumption of raw materials and leaner equipment than assumed in the first estimate provided in this document. However, this will require in-depth investigation, and for now cautious assumptions can only be made. First, basic R&D work will be undertaken to understand the chemistry of the new process as well as its influencing factors. This will be followed by the testing of different catalysts, as well as an additional proof of principle study for 3-4 leading IER products. Raw material optimisation will be researched as will analysis of the recycling of product streams, waste management and technical handling of chemicals within the process. The development of a technically viable process will also involve optimisation of new recipes for each product type, as well as piloting of the new recipes and validation of the products by customers.

Unlike for corresponding R&D activities on the sulphonation use, the applicant has no previous experience of the '''''''''''' '''#E ''''''''''''''' technique. Essentially, the phases of it implementation would be completely novel. Issues could arise from the scale up of the recipes from the pilot phase, as associated techniques will be completely unproven. It is also uncertain whether the specified Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 83 product quality and performance parameters can be achieved and further uncertainty can be associated with customer tests which would not be initiated for several years.

All of these factors, on top of the need for additional steps in the R&D plan mean there is a significant timeframe associated with the applicant’s planned activities. Table 5-21 breaks down the standard '''' ''#D'''''''' timeline associated with the conversion of a single AER/CR product recipe to the ''''''''''' ''#E ''''''''''''''' technique, and includes plant implementation.

Essentially, the steps highlighted within the table will be undertaken for each product, but in a staggered manner to ensure a consistent and manageable project work flow. In this respect, it is anticipated that there will be an approximate '#D' month gap between the start of the development phase for each individual product. Taking this into account, the total timeframe for implementation of the '''''''''''' #E '''''''''''''''''' technique across all AERs/CRs is presented in Table 5-22. As can be seen, the applicant expects the R&D and plant implementation to be complete by the end of Q1 (March) 2029. There is the potential for feasibility barriers to remain but the applicant expects to have a good idea as to whether full scale implementation can be achieved by ''''''' '''''#D '' ''''' ''''''''', and certainty of this by ''''''''#D'''''''''.

Based on the current and anticipated future implementation of this R&D plan, and considering the November 2017 Sunset Date for EDC, the applicant requires a minimum 12 year review period for the phthalimidomethylation use applied for in this AfA.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 84

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 85

Table 5-22: Overall minimum foreseeable timeframe for the implementation of the ''''''''''#E ''''''''''''''''' technique (for all ''''#C''''' AER/CR products) Timeline Step 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 Proof of principle Development #D

Validation

Plant implementation

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 86

Conclusion on the technical feasibility of the '''''''''''' #E'''''''''''''''' technique

The ''''''''''#E ''''''''''''''' technique, in its current form, can certainly be considered an infeasible alternative to the EDC-based phthalimidomethylation process. Since '''''''''''#D'' ''''''''', however, the applicant has been implementing a detailed R&D plan with the aim of demonstrating (and vastly improving) the technical feasibility of this novel technique. This aim of the applicant’s activities is to eventually replace all '''#C''' AER/CR products with new, optimised recipes that forego the use of EDC in their production.

The practical steps of the R&D plan demonstrate that many hurdles would have to be overcome to make the technology technically feasible, and a minimum of 12 years from the November 2017 Sunset Date would be required. This also assumes that the R&D does not identify further issues.

5.4.4 Economic feasibility

Investment costs for the implementation of the alternative

There are several key investment costs for switching from EDC to the ''''''''''' '#E''''''''''''' production route:

 Access to technology and R&D: The applicant estimates total R&D costs of ''''' '#D''''''''''''' (€1-10 million), associated with the implementation of this alternative. This is based on annual R&D programme costs of ''''''''#D'''''''''' over a 12 year time period (the applicant does not anticipate significant R&D costs during the final years of implementation as these costs are covered primarily by plant conversion considerations, below). These R&D activities will be undertaken by the equivalent of '#D'' full-time staff '''''''' ''''''''' '''' ''''''' '''''''' ''''''' ''''''''''''''' '''''''''''''''' ''''''' '''''''''''''''' '''''''''' ''''''''''''''''' ''''''' ''''''''''''''''''''''' '''''''' '''''''''' '''''''''''''''''' '''''''' ''''''''''' ''''''''''''''''''' '''''''' '''''''''' '''' '''''''''''''''''''' ''''''' '''''''''' '''''''''''''''''''''' '''''''''''''''''''''' ''' '''''''''' '''''''' ''''' '''''''''' ''''''''' '''''' ''''''''''' '''''''''' ''''''' ''''' ''''''''''''#E ''''''''''''''''''' ''''''''''''' '''''''' ''''''''''''' ''''''''''''' '''''''''' '''''''''''' '''''''' ''''''''''''''''''' ''''''' '''' ''''''''' '''''''' '''''''' ''''' ''''''''''''''''''' ''''''''''''''''''''''''''' ''''''' ''''''''' ''''' ''''''' '''''''''''' ''''''''''''''''''' ''''''''''''''''''''

 Plant conversion costs: there are three key steps under this:

 Plant downtime: The applicant will be required to implement this technique in parallel with the existing EDC route and anticipates a 3 month period of downtime for each phthalimide production train. For the year in which downtime takes place, this is expected to result in a 25% reduction in AER/CR sales from the phthalimide process. An additional 25% in decrease in production and sales will occur during the parallel test phase due to pilotations and the need for more manual operations (usually a pilot batch is conducted under increased operator supervision and the cycle time of the reaction is longer to allow for additional analyses of the different steps reached. Also, for initial tests of the technical feasibility, temporary equipment which is not yet fully automated is usually installed. The lack of automation of this equipment necessitates more manual work. Operators involved in manual work and supervision of the pilot batches are not available in other parts of the plant and the reduced output from the plant in this phase results in less sales).  Acquisition of replacement equipment: This has been summarised in the table below. The process contains new production steps which require additional equipment and buildings.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 87

 Cost of installing new equipment (engineering cost): The applicant estimates the planning and engineering costs associated with the implementation of the replacement equipment at ''''' ''#D''''''''''' (€1-10 million).

Table 5-23: Replacement equipment requirements for the '''''''''' '#E''''''''''''''''' technique '''''''''''''''''''''''' '#D''''''''''''''''''' '''''''''''''''' '''''''' ''''#D ''''''''''''''' ''''''''''''''''''''''' ''''''''#D ' ''''' '''''''''''''''''''''' '''#D ''' ''''''''''' '''''' '''''''''''''#D '''''''''''' ''''''''''''''''' '''''''''' '''#D '''' ''''''' '''''' '''''''#D ''''''''''''''' '''#D ''' '''''''''''''''''' ''''#D ''''''''''' ''''''''' ''''''''''''' '''''' '''''''''''''''''''''''' '''''' ''''''''#D ''''''' '''''''''' '''''''''''''' ''''''' #D '''''''''' '''''''''''' '''''' ''''''''''' '''''''''''''''''' '''''' ''''''' #D '''''' '''''''''' ''''''''' ''''''''''''''#D '''''''''''''' ''''''''''''' '''''''' ''''''''''''''''' '''''''''''' '''''' ''''''''#D ''''''' '''''''''' '''''''' '''''''''''''' #D ''''' ''''''''''''''''''' '''''''''''''''''' ''#D '''' ''''''''''' ''''''' '''''#D ''''''''''''' '''''' '''''''''' ''''''''''''''''''' ''''#D ''' ''''''''''''''''''''''' #D '''' ''''''''''''' '''''''''''''''''''''' '''''' ''''''''#D ''''''' '''''''''' '''''#D '''' '''#D '''''

 Requalification: Requalifications will be necessary in respect to different national legislation concerning drinking water and food applications (TüV, NSF, ResAP)22. The applicant estimates requalification costs of over ''''''''' #D '''''''''''''' (up to €300,000 per product and more than '#D' products affected). The applicant also estimates that it would take 24 months for requalifications to be completed

 Retraining: The applicant anticipates retraining activities associated with the implementation of the alternative to take 6 months. This includes: new SOPs for use, safety, cleaning and maintenance procedures for new equipment and covering about '' #C ''''' products, new safety measures ''''''''''''''''''''' '''''''''' '''''#D '''''''''' '''' '''''''''''''''''''' ''''''''''''''''' ''''''''''''''' '''''''''''''''''''''''''' ''''''''''''''''''''''''''''''''''' ''''''''''''''''' and the use of the updated Process Control System.

Operating costs:

Given that the applicant produces approximately '''#C '''''' varieties of AER/CR, it is not practical to provide a comparison of operating costs for individual grades. Consequently, an average value is used to demonstrate how much each cost category contributes to the overall operating cost.

22 Note: The sequence of events surrounding a FDA food contact approval have been provided as a further example in Annex 4).

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 88

Table 5-24: Comparison of operating costs for production of SAC ERs between applicant’s current process utilising EDC and '''''''''' ''#E ''''''''''''''' Operating costs category Contribution to current Effect on cost element overall operating cost (%) (decrease, stay the same (i.e. no significant change) or increase) if EDC is replaced by ''''''' '#E'''''''''''''' Energy costs Electricity '''#C ''' Increase (+28%) Steam '''#C ''' Increase (+31%) Materials and service costs Cost of process solvent (currently EDC) '''''#C ''''' Increase (€1 kg, EDC is €0.5 kg) Raw materials (excluding water and EDC but '''''#C '''' Increase (+25%) including their delivery costs) Water N/A No significant change Environmental service costs (e.g. waste ''''#C ''' Increase (+30%) treatment and disposal services) Transportation of your product No significant change Labour costs Salaries, for workers on the production line N/A Increase (incl. supervisory roles) Costs of meeting worker health and safety N/A No significant change requirements (e.g. disposable gloves, masks, etc.) Maintenance and laboratory costs Costs associated with testing, equipment N/A Increase (+25%) downtime for cleaning or maintenance (incl. maintenance crew costs and lab worker costs) Other costs Marketing, license fees and other regulatory N/A Increase compliance activities Other general overhead costs (e.g. insurance N/A No significant change premiums, administration, etc.) Overall change in operating costs (%) +25-30%

It is important to note that it is currently anticipated that the lower functionalisation yield associated with this process (as highlighted in Section 5.4.3) will lead to a '''''''''' ''#D''''''''''''''' in plant capacity for AERs and CRs. Products produced via the phthalimide process account for approximately ''''#D'''' of the total turnover of the applicant’s IER business. Consequently – this reduction in capacity could cause a ''#D''' decrease in overall turnover, not considering further losses resulting from a possibly lower product quality for the resins manufactured with the new technique. Given the highly competitive nature of the IER market (as discussed in the corresponding SEA document), the applicant would not be able to raise prices to counter-balance this turnover reduction, and this would mean LANXESS would suffer a loss of earnings.

Furthermore, a reduction in plant capacity essentially means that the per unit output costs of the process will increase for several aspects. This is the primary reason for the operating cost increases described in further detail below.

Energy costs: Costs associated with both electricity and steam will increase significantly. This is the result of higher consumption of energy in the process, and the lower yield of functionalised resins this technique is expected to attain.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 89

Materials and service costs: The recovery rate for ''''''''''' '#E'''''''''''''''' in the process has not yet been established. The applicant estimates that '''#D'''' more ''''''''''' ''#E''''''''''''''' may have to be consumed when compared with EDC. As the price of ''''''''''' #E''''''''''''''''''' is double that of EDC, at €1000/t, the overall cost of the alternative substance may be '''#D'''' higher than at present. In addition, environmental service costs will also increase due to a higher chemical oxygen demand in the STP.

Labour costs: Considering per unit production costs, worker salaries will increase by 25% due to the lower yield functionalised resins this technique is expected to obtain.

Maintenance and laboratory costs: Costs associated with maintenance and laboratory testing are expected to increase by 25% due to the lower yield of functionalised resins this technique is expected to obtain.

Other costs: No other general overhead costs cost changes are likely to arise.

Conclusion on economic feasibility

Overall, the conversion from EDC to ''''''''''' '#E'''''''''''''''''' would require significant modifications to the Leverkusen plant. The applicant estimates total R&D costs of '''''' #D'''''''''''''' (€1-10 million) and investment costs (associated with the acquisition and cost of installing new equipment) of '''''#D '''''' '''''#D'''''''' (€10-100 million). In addition there would be a significant reduction in turnover and profit during implementation due to the plant downtime. Retraining and requalification costs would also arise, the latter being estimated at more than ''''''''#D ''''''''''''' (€1-10 million).

With regard to ongoing operating costs, although parameters may improve in line with the applicant’s ongoing R&D plan, at this stage a 25-30% increase is expected. This is predominantly due to lower yield of functionalised resins and much increased raw material consumption this technique is expected to attain.

5.4.5 Reduction of overall risk due to transition to the alternative

Classification and labelling

A search of the ECHA C&L Inventory (undertaken on 29 January 2015) shows that harmonised classification and labelling information is available for the '''''''''' #E'''''''''''''''''''''. This is presented in Table 5-25.

Table 5-25: Harmonised classification and labelling of '''''''''''' '#E''''''''''''''''''' according to CLP criteria Classification Labelling Hazard Hazard Class and Statement Hazard Statement Code(s) Pictogram Signal Word Code(s) Category Code(s) Code(s) '''''''''''#E ''' '''''#E '''''' ''''#E ''''' ''''''''#E ''''' '''''''''' '''#E '''''' ''' '''''#E ''''' ''''''#E ''''' ''''''#E '''''' '''''''' '''''#E ''''' ''''' '''''#E '''''' '''#E '''''' '''''#E ''''''' ''''''''''''#E ''''''' ''' '''''#E '''' '''''#E '''''' '''#E ''''' Source: European Chemicals Agency (C&L Inventory): http://echa.europa.eu/regulations/clp/cl-inventory

Comparative risk assessment

For the environmental assessment a PNECfreshwater of 1100 µg/L was used, which is the same as derived in the registration dossier and by other evaluating bodies.

'''''''''''' #E''''''''''''''''''' was evaluated as a substance to which exposure might occur as a consequence of using an alternative technique.

In the registration dossier a DNELlong-term inhalation workers of ''''''''' ''#E'''''''''' was derived. '''''''''''' ''#E '''''''''' is a corrosive substance and these local effects dominate the toxicological profile of the substance.

In an aqueous environment ''''''''''' '''''''''''''''''''' '''' #E '''''' ''''''''''''''''''''' '''' ''''''''''' '''''''. A PNECfreshwater of ''''''''' #E ''''''''' was derived in the registration dossier.

Based on a comparison of the effect profiles, '''''''''' ''#E '''''''''''''''''' is considered to be advantageous with regard to human health effects. Furthermore the substance is of low aquatic toxicity, ''''#E ''''' '''''''''#E ''''''''''''''' and is not expected to cause chronic effects in the aquatic environment.

In conclusion, ''''''''''' '''#E '''''''''''''''''' is considered to fulfil the requirement of leading to overall reduced risks, when used as an alternative for EDC.

5.4.6 Availability

Three elements of availability can be considered:

With regard to the quantity of '''''''''#E ''''''''''''''''' required, an online search using the substance’s CAS number was undertaken on the ECHA Dissemination Portal23 on 29 January 2015. Information from the portal shows that the substance has been registered under REACH with ''''' ''''''''''''#E '''''''''''''''''''''' ''''''''''#E ''''''''''''' '''''''' a joint submission of 100,000 – 1,000,000 tonnes per annum. Given the relatively low volume of substance that would theoretically be required by the applicant to replace EDC ('''''#B & #E '''' '''''') calculated from the anticipated '''''''''' ''''#E ''''''''''''' replacement ratio and current EDC consumption tonnage in Section 3), it is not envisaged that there would be any difficulties on sourcing the alternative substance at the required quantity (the applicant has identified 8 EU suppliers and >10 non-EU suppliers). The applicant can also state with a high level of confidence that sourcing '''''''''''' #E ''''''''''''''''' of the required quality would not be an issue.

However, as discussed in Section 5.4.3, the applicant does not at present (and could not until significantly beyond the Sunset Date) have access to the technology required for implementing '''''''''#E ''' ''''''''''''''''''''', within the overall technique, as an alternative for EDC. Therefore, the ''''''#E '''''' ''''''#E ''''''''''''' technique is not considered available to the applicant.

23 ECHA Registered substances database: http://echa.europa.eu/web/guest/information-on- chemicals/registered-substances Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 91

5.4.7 Conclusion on suitability and availability for the '''''''''''' #E''''''''''''''''' technique

Since '''''' #D'''''''''', the applicant has been implementing a detailed R&D plan with the aim of demonstrating (and vastly improving) the technical feasibility of this novel technique. This aim of the applicant’s activities is to eventually replace all ''' #C''''' AER/CR products with new, optimised recipes that forego the use of EDC in their production. The practical steps of the R&D plan demonstrate that many hurdles would have to be overcome to and a minimum of 12 years from the November 2017 Sunset Date would be required to make the technology technically feasible (and ‘available’).

In terms of economic feasibility, the conversion from EDC to ''''''''''' #E'''''''''''''''''' would require significant modifications to the Leverkusen facility, with combined R&D, equipment, installation and retraining costs totalling '''''''''' ''#D'''''''''''' (€10-100 million). In addition, the applicant anticipates a significant reduction in turnover and profit during implementation due to the plant downtime, as well as a 25-30% increase in operating costs (predominantly due to lower yield of functionalised resins and much increased raw material consumption this technique is expected to attain).

''''''''''' '''#E ''''''''''''''''' is considered to fulfil the requirement of leading to overall reduced risks, when used as an alternative for EDC.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 92

6 Overall conclusions on suitability and availability of possible alternatives

6.1 Alternative substances and technologies considered

The overall process resulted in the selection of four potential alternatives (two substances, one technique and one substance/technique combination) across the two uses, which proceeded to a detailed analysis in Section 5 of this AoA. These potential alternatives are shown in the table below.

Table 6-1: Shortlist of alternatives to be assessed in Section 5 of AoA Shortlisted alternative Substance (CAS No) / Use 1 - Use 2 - technique Sulphonation Phthalimidomethylation 1,3-Dichloropropane (1,3-DCP) Substance (142-28-9)   1,4-Dichlorobutane(1,4-DCB) Substance (110-56-5)   Solventless sulphonation Technique   ''''''''''' ''#E ''''''''''''''''' technique Technique incorporating an alternative substance   '''''''''#E '''''''''' 6.2 Conclusions on comparison of alternatives to EDC

6.2.1 Conclusions on technical feasibility

The solventless sulphonation technique appears to offer no technical advantages over the EDC- based process with the exception that no solvent would need to be utilised and in its current form it does not allow for the production of sufficient quality SAC ER products to replace those currently manufactured at Leverkusen with EDC. However, since '''''' ''''''''''''#D''''' '''' '''''''''', the applicant has been implementing a detailed R&D plan with the aim of improving the technical feasibility of this technique and eventually replacing all ''#C '''' EDC-based SAC ER products with new optimised

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 93

recipes. The practical steps of the R&D plan demonstrate that to make the technique technically feasible, a minimum of 4 years from the November 2017 Sunset Date is required.

The ''''''' ''''#E''''''''''''' technique is a unique combination of an alternative technology and substance put forward by the applicant and in its present form it can certainly be considered an infeasible alternative to the EDC-based phthalimidomethylation process. In parallel with the applicant’s sulphonation R&D activities, since '''''' '#D''''''' LANXESS has been implementing a detailed R&D plan with the aim of demonstrating (and vastly improving) the technical feasibility of this technique. This aim of the applicant’s activities is to eventually replace all ''#C''' AER/CR products with new, optimised recipes that forego the use of EDC in their production. The practical steps of the R&D plan demonstrate that many hurdles would have to be overcome to make the technology technically feasible, and a minimum of 12 years from the November 2017 Sunset Date would be required.

6.2.2 Conclusions on economic feasibility

Economic feasibility considerations have taken into account investment costs and changes to operating costs associated with the implementation of the potential alternatives.

Overall, the conversion from EDC to 1,3-DCP would require significant modifications to the Leverkusen plant. Investment costs associated with ongoing R&D activities are estimated at ''''#D ''''' ''''#D ''''''''' (€1-10 million) and the acquisition and cost of installing new equipment has been estimated at ''''''''' #D'''''''''''' (€1-10 million). In addition, there would be reduced turnover and profit during implementation due to the plant downtime. Retraining and requalification costs would also arise, the latter being estimated at more than ''''' '#D''''''''''' (€1-10 million). The applicant anticipates a 5% increase in their ongoing operating costs.

For 1,4-DCB significant modifications to the Leverkusen plant would also be required. R&D activities are estimated at '''''''' '#D''''''''''' (€1-10 million). However, as this substance is only a potential alternative for phthalimidomethylation, the acquisition and cost of installing new equipment is estimated to be slightly lower (at '''''''' #D'''''''' (€1-10 million)). Requalification costs would be lower, although still more than '''''''' ''#D''''''''' (€1-10 million). Retraining costs would also arise (these have not been quantified) and the applicant anticipates a 5% increase in their ongoing operating costs.

The implementation of solventless sulphonation would also require significant modifications to the Leverkusen plant. However, such plans for the implementation of the technique are underway and the applicant has also committed funding to this. Investment costs associated with ongoing R&D activities are estimated at '''''''' #D''''''''''''' (€1-10 million) and the acquisition and installation of new equipment has been estimated at '''''''''''#D ''''''''''''' (€1-10 million). In addition, retraining and requalification costs would also arise, the latter being estimated at more than '''''''''#D'''''''''''' (€<1 million). The applicant expects a modest increase in ongoing operating costs, although this cannot currently be quantified.

For the ''''''''''''#E '''''''''''''''''''' technique, the applicant estimates total R&D costs of '''''' '''#D''''''''''' (€1-10 million) and investment costs (associated with the acquisition and cost of installing new equipment) of '''''''''' '#D''''''''''' (€10-100 million). In addition there would be a significant reduction in turnover and profit during implementation due to the plant downtime. Retraining and requalification costs would also arise, the latter being estimated at more than ''''''' '#D''''''''''''' (€1-10 million). The applicant anticipates a 25 to 30% increase in their ongoing operating costs.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 94

6.2.3 Conclusions on risk reduction capabilities of the alternatives

In a separate detailed report (available as Annex 1 (Section 7) of this AoA) a comparative risk assessment for environmental and human health effects is described for 1,3-DCP, 1,4-DCB and ''''#E ''' ''''''''#E ''''' . No detailed assessment was undertaken for solventless sulphonation, as the technique removes altogether the need for a solvent within the process, and is therefore assumed to fulfil the requirement of leading to a reduction in overall risks to human health and the environment compared to EDC.

Based on the toxicological profile and the results of the risk characterisations the chlorinated carbon compounds seem not to be advantageous compared to EDC with regard to human health effects. 1,3-DCP exhibits positive genotoxicity test results and 1,4-DCB is not adequately investigated for genotoxicity and carcinogenicity. Together with the close structural relationship to other dichlorinated short-chain aliphatics with proven or suspected carcinogenic properties 1,3-DCP and 1,4-DCB are suspected of having carcinogenic properties on their own and thus cannot be considered suitable alternatives.

With regard to ''''''' ''' #E ''''''''''' , the substance is corrosive and local effects determine its toxicological profile. Appropriate risk management measures have to be implemented to adequately control respective risks. If this is ensured, it can be considered a suitable candidate from a human health perspective.

With regard to the environment, due to a similar or higher aquatic toxicity and lower volatility, 1,3- DCP and 1,4-DCB lead to similar or even more severe environmental concerns than EDC. This supports the argument on their questionable suitability as alternatives from a risk reduction perspective. ''''''''''''' '''''''''''''''''''''' '''''''' ''#E ''' '''''''''' '''''''''''''''''''' '''' '''''''''''' '''''''', provides a favourable environmental profile.

In conclusion, '''''''''''#E '''''''''''''''''' is the only substance leading to reduced risks for human health and the environment, when compared to EDC.

6.2.4 Conclusions on availability of alternatives

With regard to availability, for 1,3-DCP, 1,4-DCB and '''''''''#E ''''''''''''''''' (as part of the '''''''''' ''''#E ''''''''''''#E '''' technique), the applicants considered the following three factors (for the solventless sulphonation technique, as no solvent is required, only the last point was considered):

For '''''''''''#E ' '''''''''''''''''''', it is not envisaged that there would be any difficulties with sourcing the alternative substance at the required quantity (the applicant has identified 8 EU suppliers and >10 Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 95

non-EU suppliers) or quality. However, the applicant does not at present (and could not until significantly beyond the Sunset Date) have access to the technology to fully implement '''''#E ''''' ''''''''#E ''''''''''', within the overall technique, as an alternative for EDC. Therefore, the ‘''''''#E '''' ''''''''''' technique’ is not considered available to the applicant.

In the same vein, the solventless sulphonation technique is also considered unavailable at this time (given that it can only be considered a technically feasible replacement by Nov 2021 at the earliest). 6.3 Overall conclusion and future research and development

6.3.1 Overall conclusion

The overall outcome of the applicant’s analysis with regard to these potential alternatives is shown in the following table.

Table 6-2: Overall conclusions on suitability and availability of shortlisted alternatives Potential alternative Solventless ''''''''''' '#E '''''''''''''' Key consideration 1,3-DCP 1,4-DCB sulphonation technique (for uses 1 & 2) (for uses 1 & 2) (for use 1 only) (for use 2 only) Not at present Not at present Not at present Not at present Is the potential (could become (could become (could become (could become alternative feasible by feasible by feasible by March feasible by November technically feasible? November 2023 at November 2021 2029 at the 2023 at the earliest) the earliest) at the earliest) earliest) Uncertain Not at present Not at present Uncertain (increased (increased Is the potential although although operating costs but operating costs but alternative potentially in the potentially in the whether this makes whether this makes economically future (depends future (depends substance infeasible substance feasible? on R&D project on R&D project not concluded) infeasible not outcome) outcome) concluded) Does the potential alternative result in a No No Yes Yes reduction of risk? Not at present Not at present Not at present Is the potential (substance itself is (substance itself is Not at present (substance itself is alternative (and available but available but (could become available but associated associated process associated process feasible by associated process technology / process not feasible until not feasible until November 2021 not feasible until to implement it) November 2023 at November 2023 at at the earliest) March 2029 at the available? the earliest) the earliest) earliest)

6.3.2 Future research and development activities

As noted above, for both applied-for uses the applicant is currently implementing R&D projects aimed at the full substitution of EDC. Considerable barriers must be overcome for the applicant to preserve the high quality of the ''''''#C'''' '' separate EDC-based IER product grades that are currently produced and placed on the market. The practical steps of the R&D demonstrate that to make the solventless sulphonation and ''''''''''#E''''''''''''''''''''' techniques technically feasible, respectively, for sulphonation and phthalimidomethylation, a minimum of 4 and 12 years from the November 2017 Sunset Date is required.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 96

7 Annex 1: Risk evaluation of alternative substances

7.1 Methodological approach

Article 60 (5) of REACH requires the applicant to investigate whether the use of the alternative substance “would result in reduced overall risks to human health and the environment” (as compared to the Annex XIV substance EDC).

A first hazard screening was carried out to deselect from an initial list of potential alternatives those substances which are not eligible due to process parameters and critical hazard profiles (CMR substances or substances with similar levels of concern) (see Section 4.2.1).

From the remaining substances those candidates were selected which provide the highest chances for substituting EDC from a technical and economical perspective. In conclusion, three substances were selected for in-depth analysis:

 1,3-DCP(CAS 142-28-9)  1,4-DCB (CAS 110-56-5)  ''''''''''' '''''''''''''''''' '#E ''''''''' ''''''''''''''''''''

In order to comply with the REACH requirement in this section the hazard profiles of these substances are presented and both ecotoxicological and as well toxicological properties are compared (Section 7.2).

Literature searches (up to September 2014) for the alternative substances selected for in-depth evaluation were performed in bibliographic and other databases as appropriate (after consultation of existing assessments) and assessments available from eChemPortal and other sources were screened.

In detail, the following sources and search steps were used to retrieve relevant information:

 ECHA CHEM database (http://echa.europa.eu/search-chemicals)  eChemPortal (http://www.echemportal.org/echemportal/), with all related sources  bibliographic database Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)  the US NLM portal TOXNET (http://toxnet.nlm.nih.gov/ including the bibliographic database Toxline and other databases  ECOTOX database (http://cfpub.epa.gov/ecotox/)  the aquatic toxicity database CHRIP of the Japanese Ministry of Environment (http://www.safe.nite.go.jp/english/db.html)

As not only a comparison of hazard profiles is required but a comparison of substance properties on a risk basis, substance-specific properties influencing exposure behaviour are considered as well when deriving overall conclusions on risks from using the alternative substances.

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7.2 Hazard profiles for EDC and alternative substances

7.2.1 EDC (CAS 107-06-2)

Classification

Classification information for EDC is provided in the following figure.

Figure 7-1: EDC classification information Source: http://echa.europa.eu/web/guest/home (accessed on 6 August 2014)

Human Health

A reference value for long-term, inhalation exposure of workers of 16.7 µg/m3 associated with a risk level of 1 x 10-5 is used for the comparative assessment with the alternative substances here. This value is based on the exposure-risk relationship presented by RAC (ECHA, 2015b).

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Ecotoxicity

Existing reference values

Table 7-1: PNECs for EDC – values from ECHA CHEM compared to other assessments Reference value ECHA CHEM24 OECD SIDS (2002) CEPA (Canadian Environmental Protection Act, 1994)

PNECfreshwater (assessment 1100 µg/L (10) 1100 µg/L (10) 130 µg/L (20) factor)

PNECmarine-water 110 µg/L (100) (assessment factor)

PNECintermittent-releases 1360 µg/L (100) (assessment factor) PNECSTP (assessment 27800 mg/L (100) factor) PNECsediment freshwater 11.1 mg/kg sed. dw. (EPM)

PNECsoil 1.8 mg/kg soil dw. (EPM)

Basis for PNECfreshwater derived in ECHA CHEM and OECD SIDS (2002):

Acute and long-term aquatic toxicity data for species from three trophic levels are available. The lowest NOAEC observed was 11 mg/L from daphnia magna life cycle toxicity study. An assessment factor of 10 was used to derive PNECfreshwater.

Basis for PNECfreshwater derived by CEPA (Canadian Environmental Protection Act, 1994):

A study reporting effects on larval survival of northwestern salamander (Ambystoma gracile) was used as key study, with a LC50 of 2.54 mg/L (Black et al., 1982, unpublished). An assessment factor of 20 was applied.

The study by Black et al. investigated also toxicity of EDC to fish in several species. LC50 values obtained were consistently and substantially lower than those from other fish toxicity studies with the substance. The Black et al. study was criticised in OECD SIDS and was considered not reliable enough to be used for PNEC derivation, due to the non-reproducibility in other studies.

Conclusions

The lowest NOAEC of 11mg/l was reported for a long-term study with daphnia magna. The PNECfreshwater as derived in the registration dossier (ECHA CHEM) and by OECD SIDS (1100 µg/L) can be used for the comparative assessment.

24 http://echa.europa.eu/web/guest/home, assessed on 6 August 2014.

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7.2.2 1,3-Dichloropropane (CAS 142-28-9)

Classification

Classification information for 1,3-DCP is provided in the following figure (no harmonised classification is available).

Figure 7-2: 1,3-DCP classification information Source: http://echa.europa.eu/web/guest/home (accessed on 22 January 2015)

Human Health

Existing reference values

As the substance is only pre-registered, but not registered, no DNELs are available from ECHA CHEM.

Occupational exposure limits (OEL) are established only in Austria and Spain with a TLV of 75 ppm (IFA, 2015). No background documents are available.

1,3-DCP shows low acute toxicity and causes dermatitis after dermal exposure. At high air concentrations it is an eye, skin and respiratory tract irritant (ILS, 2000; NLM, 2015; WHO, 2003).

Subacute (14 days) oral exposure of rats to doses of 200, 600 and to 1800 mg/kg bw/day produced 100 % mortality at the highest dose within the first study week. No treatment-related differences in body weight, food consumption, or haematology data were observed in the low and mid dose groups. Absolute and relative kidney and liver weights were increased in mid dose males, and the relative (not absolute) weight of the testes/epididymis was decreased. Mid dose females had increased absolute and relative liver weights. Females of the low and mid dose groups showed increases in total protein, albumin was increased only in mid dose females. Mid dose males showed increases in potassium and decreases in blood urea nitrogen (Terrill et al., 1991). A subsequent 90 days study was performed with doses of 50, 200 and 800 mg/kg bw/day. Males in the high dose group had decreased body weights, and females showed urine-stained fur. Animals of the high dose group showed increased values of alkaline phosphatase, alanine aminotransferase (males only), Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 100

albumin, and total protein. These findings were accompanied by increases in liver weight for all exposed animals (in low dose group females only) and increased kidney weights (mid and high dose). Microscopic evaluations revealed centrilobular hepatocellular hypertrophy for the animals of the high dose group and an exacerbation of chronic progressive nephropathy in mid dose males and male and female high-dose animals (Terrill et al., 1991). Long-term studies are not available.

The reproductive effects of 1,3-DCP-were examined in a 2-year study with oral exposure of mice. The lowest effective dose was reported as 1.15 mmol/kg (113 mg/kg). No further details were provided in the secondary source (ILS, 2000). Doses up to 400 mg/kg bw/day for 14 days did not induce effects on the male rat reproductive system (testis weights, morphology, or detailed macroscopic and microscopic evaluation of the kidneys, testes, epididymis, ductuli efferentes, or vas deferens) (ILS, 2000; NLM, 2015).

The substance was mutagenic in S. typhimurium strain TA1535 with, but not without metabolic activation. No mutagenicity was observed with or without metabolic activation in TA98, TA100, TA1537, and TA1538; E. coli strains WP2 and WP2uvrA or Saccharomyces cerevisiae strain JDL (Dean et al., 1985). In another study it was mutagenic in TA100 with and without metabolic activation (Stolzenberg and Hine, 1980). These conflicting results in TA 100 are not due to concentration differences, as the maximum (negative) concentration of 4000 µg/plate in the study by Dean et al (1985) is higher than the concentration of 10 µmol/plate (approx. 1130 µg/plate) producing a positive result (Stolzenberg and Hine, 1980). Another Ames test did not observe mutagenicity in strains TA98, TA 100, TA 104 and TA 1535 and two glutathion-S-transferase positive strains (Tornero- Velez et al., 2004). A spot test in the Salmonella strains TA1530 and TA1535 without metabolic activation produced negative results (Buijs et al., 1984). No SOS repair was observed after exposure of E. coli strain PQ37 (von der Hude et al., 1988). DNA damage was reported in Bacillus subtilis only in the presence, but not absence of metabolic activation (Matsui et al., 1989). The substance was not mutagenic in one mouse lymphoma assay (Henry et al., 1998), but positive in another study with metabolic activation (ILS, 2000). Sister chromatid exchanges were induced by 1,3-DCP in V79 Chinese hamster cells with and without metabolic activation (von der Hude et al., 1987) and CHO cells (no information provided about metabolic activation) (ILS, 2000). No chromosome aberrations were induced in cultures of rat liver (RL4) cells, but it was tested only in the absence of metabolic activation (Dean et al., 1985; NLM, 2015). DNA-damage (Comet assay) and the induction of micronuclei (not clearly dose-dependent) were observed after exposure of human lymphocytes in vitro with or without metabolic activation (Tafazoli and Kirsch-Volders, 1996). Micronuclei were also induced in two of three lymphoblastoid, metabolically competent human cell lines (Doherty et al., 1996).

In vivo there was no induction of micronuclei in mice after i.p. exposure in doses up to 560 mg/kg bw (Crebelli et al., 1999). The compound did not induce sex-linked recessive lethal mutations in Drosophila after inhalation exposure up to 2400 mg/m3 (Kramers et al., 1991).

Carcinogenicity studies are not available. The structure-related substance 1,2-dichloropropane is not classified in the EU with respect to carcinogenicity, but the Committee on Risk Assessment (RAC), when discussing a proposal for harmonized classification in the EU, adopted an opinion for classifying the substance in Cat Carc. 1B25. Also, there is a self-classification of a joint submission as Cat Carc. 1B26. The IARC carcinogenicity classification was recently altered from 3 (IARC, 1999) to 1, based on evidence for high risks of cholangiocarcinoma in offset printing workers (Benbrahim-Tallaa et al., 2014). In Germany it is classified as carcinogen class 3B (DFG, 2014).

25 http://echa.europa.eu/search-chemicals 26 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database, assessed on 22 January 2015 Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 101

The structure-related substance 1,3-dichloropropene is not classified with respect to carcinogenicity (harmonized), but in a self-classification it is classified as Cat Carc. 227. The IARC carcinogenicity classification is 2B (IARC, 1999), that of US-EPA is B2 (EPA, 2015). In Germany it is classified as carcinogen Class 2 (DFG, 2014).

Conclusions

A LOAEL of 50 mg/kg bw/day was identified in a subchronic toxicity study. No carcinogenicity study is available. However, based on results from genotoxicity studies and comparisons with structurally related substances, 1,3-DCP is suspected to be genotoxic and carcinogenic.

Ecotoxicity

Existing reference values

As the substance is only pre-registered, but not registered, no PNECs are available from ECHA CHEM. Also, no other evaluations of the substance’s ecotoxicity are known.

Reference values for the aquatic environment from Japan and the Netherlands are reported by Schudoma (2001): for Japan a value of 2 µg/L is reported with the remark “health effects”. For the Netherlands a value of 76 µg/L is mentioned. Further information to assess the relevance of these values is not available.

Extensive literature searches provided relevant studies sufficient to evaluate the aquatic toxicity of the substance. The following table provides an overview on the most relevant studies.

Aquatic toxicity data are available for fish, invertebrates and algae. Further acute aquatic toxicity results are reported in the database ECOTOX28, with effect concentrations either supporting or being higher than the data given in the table below.

Table 7-2: Aquatic toxicity data for 1,3-dichloropropane Species Test type Endpoint Value Reference Remarks Fish Goldfish Acute toxicity 24 h LC50 160 mg/L (Bridie et al., test, ASTM D 1973) 1345 Sheepshead Acute toxicity test 96 h LC50 87 mg/L (Heitmuller et minnow al., 1981) (Cyprinodon variegatus) Fathead minnow Acute toxicity test 96 h LC50 131 mg/L (Geiger et al., (Pimephales 1985) promelas) Fathead minnow Acute toxicity test 96 h LC50 94.2 mg/L (Brooke et al., (Pimephales 1984) promelas) Guppy (Poecilia Long-term log LC50 2.87 (741 (Könemann, reticulate) lethality test (14 µmol/ = 83.7 1981) days) mg/L) Fathead minnow 32 d fish early life NOAEC 8 mg/L (Benoit et al.,

27 http://echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database, assessed on 22 January 2015 28 http://cfpub.epa.gov/ecotox/quick_query.htm, assessed 18. December 2014 Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 102

Table 7-2: Aquatic toxicity data for 1,3-dichloropropane Species Test type Endpoint Value Reference Remarks (Pimephales stage test 1982) promelas) (endpoints: hatchability, survival of 28 day old fish, weight) Invertebrates Daphnia magna Similar to OECD 24 h EC50 39 mg/L (Freitag et al., 202 (version of 1994) 1981) Daphnia magna Acute toxicity to 24 h EC50 67 mg/L Shell (1986, Unpublished invertebrates unpublished) data, available as cited in from ECOTOX29 secondary source only Daphnia magna Acute toxicity to 48 h EC50 280 mg/L (LeBlanc, 1980) invertebrates Daphnia magna Acute toxicity to 48 h EC50 150 mg/L (Genoni, 1997) Averaged from invertebrates 3 individual values from other sources Algae Pseudokirchneriella Similar to OECD 72 h ECr50 103.06 mg/L (Aruoja et al., Occlusive subcapitata 201 2014) conditions Scenedesmus Similar to OECD 72 h ECr50 221 mg/L (Freitag et al., subspicata 201 1994) Pseudokirchneriella Similar to OECD 96 h EC50 40 mg/L US EPA (1978) Unpublished subcapitata 201 as cited in data, available (measurement of NOAEC < 5.6 mg/L ECOTOX30 from Chlor. A conc.) secondary source only Amphibians Clawed toad Acute toxicity test 48 h EC50 63 mg/L (de Zwart and (Xenopus laevis) Slooff, 1987)

Bridié et al. (1979) investigated biodegradation of the substance in a screening test according to US standard method APHA No. 219. Over a time period of 5 days a biological oxygen demand of 16% of the theoretical demand was observed. As the time period is too short to conclude on biodegradation over 28 days no conclusion can be drawn from this study. For the purpose of the comparative assessment it is assumed that the substance is not readily biodegradable.

Conclusions

Based on acute toxicity data fish do not seem to represent the most sensitive species, but daphnia, with the lowest LC 50 value of 39 mg/L reported by Freitag et al. (1994). Although this study was performed according to an older version of the OECD guideline 202 and only a 24 h EC50 was determined (instead of 48 h), the value is considered reliable enough, as other daphnia studies report higher EC50 values. Although effect concentrations in the species tested are in a similar range as those for EDC a higher assessment factor would apply for 1,3-DCB due to the limited

29 http://cfpub.epa.gov/ecotox/quick_query.htm, assessed 18. December 2014 30 http://cfpub.epa.gov/ecotox/quick_query.htm, assessed 18. December 2014 Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 103

database. With an assessment factor of 1000 starting from this LC50 of 39 mg/L a PNECfreshwaster would be in the range of 40 µg/L.

7.2.3 1,4-Dichlorobutane (CAS 110-56-5)

Classification

Classification information for 1,4-DCB is provided in the following figure (no harmonised classification is available).

Figure 7-3: 1,4-DCB classification information Source: http://echa.europa.eu/web/guest/home (accessed on 22 January 2015)

Human Health

Existing reference values

As the substance is only pre-registered, but not registered, no DNELs are available from ECHA CHEM.

The oral acute toxicity of 1,4-DCB is low (Yu et al., 2013).

A 4-week repeated dose rat study was performed with oral doses of 0, 100, 300 and 1000 mg/kg bw/day. Exposure to the highest dose produced clinical signs of toxicity (salivation, hypoactivity, loss of fur). Salivation was also observed at the lower doses following administration. Statistically significant observations in the high dose group were decreased body weight gain, increase in alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase total cholesterol, total bilirubin, albumin, phospholipids and blood urea nitrogen. The aspartate aminotransferase activity was increased at the lowest dose, but without dose-response relationship. No haematological alterations were evident. Liver, kidney, heart and seminal vehicle weights were increased at this dose. Histopathological examinations were not performed. With respect to the alterations in clinical chemistry parameters, indicating liver and kidney damage and increased organ weights, the LOAEL of this study is considered to be 1000 mg/kg bw/day, with a NOAEL of 300 mg/kg bw/day (Yu et al., 2013).

A spot test in the Salmonella strains TA1530 and TA1535 with 1,4-DCB without metabolic activation produced negative results (Buijs et al., 1984). Negative results in Salmonella typhimurium and Escherichia coli are reported by Rim et al. (2011) with reference to the National Toxicology Program

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Database Search. However, this database has been retired and all traffic is now directed to the NTP CEBS database (http://tools.niehs.nih.gov/cebs3/ui/), which does not contain these results.

An in vivo mouse micronucleus test with 1,4-DCB produced a negative result (Rim et al., 2011).

As only few toxicological data are available, 1,4-DCB (and 1,3-DCP) were assessed for structural alerts using the QSAR Toolbox (http://www.qsartoolbox.org/). As for EDC, structural alerts were found for direct DNA binding capacity by nucleophilic substitution (SN2). These findings, together with the structural relationship with known carcinogens (1,2-dichloroethane, 1,3-dichloropropene, 1,2- dichloropropane) aggravate the concern for genotoxic and carcinogenic properties of 1,3-DCP and 1,4-DCB.

Conclusions

Based on the results of the subacute toxicity study, a NOAEL of 300 mg/kg bw/day was identified.

However, the database for 1,4-DCB is considered insufficient as no (sub-)chronic toxicity data, no carcinogenicity study and few supporting data are available. Very few genotoxicity studies are available for 1,4-dichlorobutane. The available fragmentary in vitro and in vivo genotoxicity data do not indicate a positive response, but the mutagenicity and carcinogenicity data from structurally related substances (see Section 7.2.2.) as well as structure-activity considerations imply the possibility of genotoxic and carcinogenic properties of 1,4-DCB.

Ecotoxicity

Existing reference values

As the substance is only pre-registered, but not registered, no PNECs are available from ECHA CHEM. Also, no other evaluations of the substance’s ecotoxicity are known.

In extensive literature searches aquatic toxicity data were found for fish and algae only. Brooke et al. (1984) investigated acute toxicity to fish in Fathead minnows (Pimephales promelas) and reported an 96 h LC50 of 51.6 mg/L. In the ECOTOX database31 a NOAEC for toxicity to algae (Scenedesmus subspicatus) of ≥ 250 mg/L is reported, with reference to a publication of Nendza and Wenzel (2006). In Nendza and Wenzel (2006), however, only a LC50 for algal toxicity of 390 mg/L is reported, without further details on the study or source (“Data on in-vivo aquatic toxicity (LC50, EC50) towards fish, daphnids, algae and bacteria were collected from the literature…”).

In the Japan CHEmicals Collaborative Knowledge database (J-CHECK)32 a biodegradation screening study is reported, which indicates that 1,4-DCB is not readily biodegradable (7% degradation within 4 weeks).

Conclusion

Acute toxicity data covering two trophic levels only are available. No further data could be found in the literature. The few available data indicate that the aquatic toxicity is in the same range as for 1,3-dichloropropane. Therefore, for this comparative assessment an aquatic toxicity similar to 1,3- DCP is assumed for 1,4-DCB. It must be emphasised that this approach is associated with high uncertainty.

31 http://cfpub.epa.gov/ecotox/quick_query.htm, assessed 18. December 2014 32 http://www.safe.nite.go.jp/jcheck//direct.action?TYPE=DPAGE1&CAS=110-56-5&MITI=2-61, assessed 12 January 2015 Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 105

7.2.4 ''''''''''' ''''''#E '''''''''''' '''''''' '''''''''''''''''

Classification

Classification information for '''''''''''' '#E ''''''''''''''''' is provided in the following figure.

Figure 7-4: '''''''''''' #E ''''''''''''''''''' classification information Source: http://echa.europa.eu/web/guest/home (accessed on 23 January 2015)

Human Health

Existing reference values

Table 7-3: DNELs (or DMELs) for ''''''''''' '#E '''''''''''''''' from ECHA-CHEM33 ECHA-CHEM Reference value (joint submission)

DNELlong-term workers inhalation ''''''#E '''''''''''''' DNELlong-term workers dermal no DNEL derived DNELlong-term general population inhalation no DNEL derived DNELlong-term general population dermal no DNEL derived

In ECHA CHEM no information is available on how the DNEL for inhalation exposure of workers was derived. No reference value is derived in OECD ('''#E '''''). The authors stated that “''''''''''#E '''''''''''''''''''' '''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''#E '''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''”.

The Occupational exposure limit (OEL) is ''' ''''''''' #E ''''''' '''''''''''''''' in most European and North American countries, with the exception of ''''''' ''''''''#E '''''''''''' in UK and Ireland (''''''' #E '''').

''''''''''' #E '''''''''''''''''''' is highly irritating to skin, eyes and mucous membranes (OECD, '''#E ''''''').

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'''''' '''''''''''''' ''''' '''''''''''''''''''''' '''''''''''' '''''''''' ''''''''''''''''''' '''' ''''''' ''''''''''''''''''' ''''''''''' '''''''''''''''''' '''''''''''''' ''''''' ''''''''''''''''''''''''''' ''''''''''''''' ''''''' '''''''''''''''''' '''' ''' ''''''''''''''''''' '''''''''' '''''''''''' ''''''''''''' '''' '''''''''''''''''''''''''' ''''' ''''''' ''''''''''' '''' ''''''' '''''''''''''''''''' ''''''''''''' ''''''' '''''''' ''''''''''''''''' '''' ''''''' '''''''' ''''''''''' ''''''''''''''''''''''''' ''''''''''''' '''''''''''' ''''''''''''' ''' ''''''''' ''''''' ''' ''''''''''''''''''''' ''''''''''''''' ''''''' '''''''''''' ''''''''' ''''''''''''' '''''''''''''''' '''' '''''' ''''''' ''''''' ''''''' '''''''''' ''''''''''' ''''''''''''''''''''' '''''''''' ''''''' ''''''' ''''''''' ''''''''''''''' '''''''''''' '''''' ''' '''''''' 34''' ''''''' ''''''' '''''''''''''' ''' ''''''' '''''''''' ''''''''' ''''''''' '''''''' ''''''''''''' ''''''' '''' '''''''''''''''' '''''''''' ''''''''' '''''''''''''' ''''' ''''''''' '''''''' ''''''''''''''' '''' ''''''' ''''''''' '''''''''''''''''''''''''''' ''''''' '''''''''''''' '''''''''' '''''' '''''''''''''' ''''' ''''''' '''''''''''''''''''''''''''''' '''''''' ''''''' ''''' ''''''' '''''''''''''' ''''''''' ''''''''''''''''' '''' '''''''''' ''''''''''''' ''''''''' '''''''''''''' '''' ''''''' ''''''''' '''''''''' '''''''''' ''''''''''''' ''''''''' '''''''''''''''''''''' '''' ''''''''' ''''''''''''' '''''''''''''''''''' '''' '''''''''' '''' ''''''' ''''''''''''''''''' ''''''''''''' '''#E '''''''''' ''''''' ''''''''''' ''''''' '''''''''''''''' ''''''''''''''' '''' '''''''' '''''''''''' ''''''''''' '''''''''''''''''''' ''''''' '''''''''' '''' ''''''''''''''''''''''' ''''''' ''''''''' '''''''''''' '''' '''''' ''''''''''''''''''' '''''''''''''''''''''' ''''''''''''' '''''''''''' ''''' ''''''''''''' ''''' ''''''' ''''''''''' '''''''''''''''''''''''''' '''''''''' ''''''''''''''''''''' ''''''''''''' ''''''''''''''''''''' '''''''' '''''''''''''''' ''''''' ''''''''''''''''''''''' '''''''''''''''''' ''''''''' ''''''''''''''''' '''' '''''''' ''''''''' '''''''''''' ''''''' ''''''''''''''' '''' ''''''' '''''''''''''''''''' '''''''''' ''''''' ''''''' '''''''''''''''' '''' ''''''' '''''''''' '''''''''''''''' ''''''''''''''''' ''''' ''''''''''''''''''''''''''''' ''''' '''''''''''''''''''''''' '''''''''''' ''''''''' '''''''''' '''' ''''' '''''''''' ''''''''' ''''''''''''''''' '''''''''' '''' ''''''''''''''''''''' ''''''' ''''''''''''''' '''''' '''''''''''''''''''''''''''''''''''''''''''''''''' '''''''''''''''' '''''''''''' '''''''''''''''''' '''' ''''''''''''''' '''''''''''''''''''''' '''' '''''''''' ''''''''' '''''''''''' ''''''''' '''''' ''''''' '''''''''' ''''''''''''''''''''''''''''' '''''''''''''' '''' ''''''' ''''''''''''' '''''''' ''''''''''''' ''''''' '''' ''''''''' '''' ''''''''' ''''''''''' ''''' '''' '''''' '''''''' ''''''''''''''' '''' '''''' '''''''''''' '''''''' '''''''''''''''''''''''' ''''''''''' ''''''''' ''''''''' '''''''''''''' '''' ''''''''' ''''''''''' '''''''''' '''' '''''''''''''''''' ''''''''''''' '''''''''''''

Conclusions

''' '''''''''' ''''' '''''''''''''''''''' ''''''''''''''''''' ''''' ''''''''''#E ' '''' ''''''' '''''''''''' '''''''' ''''''''''''' '''' ''''''' ''''''''''''''''''''' '''''''''''''''' ''''''''''' ''' ''''''''''''''''' '''' ''''''' ''''''''''''''' '''' '''''' '''''''''''''''''''''' '''''' ''''''''''''''''' ''''''''''' '''''' ''''''''''''''' '''''''''''' ''''' ''' ''''''''' '''''''' '''''''''''''''' ''''''' ''''''''''' ''' ''''''''' '''''' '''''' '''''''''''''''''''''' ''''''''''''''''''''' ''''''''''

For systemic effects after dermal exposure no meaningful DNEL can be established. The substance is corrosive to the skin and direct dermal contact has to be eliminated by suitable measures to the maximum extent.

34 http://echa.europa.eu/web/guest/information-on-chemicals, accessed on 23 January 2015. Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 107

Ecotoxicity

Existing reference values

Table 7-4: PNECs for '''''''''' '#E '''''''''''''''''' – values from ECHA-CHEM compared to other assessments Reference value ECHA-CHEM35 OECD SIDS ''''''#E '''''

PNECfreshwater (assessment factor) '''''''''' '''#E ''''''' '''''''''' ''''' ''''''#E ''' ''''''''''' PNECmarine-water (assessment factor) '''''''''' '''''#E '''' '''''''''''' PNECintermittent-releases (assessment ''''''''''' ''#E '''''''' '''''''' factor) PNECSTP (assessment factor) '''''''' '''#E '''''''' ''''''' PNECsediment freshwater ''''''''''''#E '''''''''''' ''''''' '''''''' '''''''''' ''''''''''''''''''''''''''''

PNECsoil '''''''' '''''''''''' ''''''' ''''''' '''''''''' ''''''''''''''#E '''''''''''''

The following key information is reported in ECHA CHEM.

35 http://echa.europa.eu/web/guest/home, assessed on 17 December 2014

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''''''''''''''''''''''''''''' '''''''' '''''''''''''''' ''''#E '''''''''' ''''''''' ''''''' ''''''''''''''''''' '''''''''''''' '''''''' ''''''''' '''''' ''''''''''''''''''''' ''''''''''' '''' ''''''''' ''''''''''' ''''''''''''' ''''''' ''''''' '''''''''''''''''' '''''''''' '''''''''' '''''''''''''

'''' ''''''' '''''''''' ''''''''' ''''''''''''' '''''' '''''#E ''''' '''''''''''''''''''' '''''''''''' '''''''''' ''' ''''''''''' '''' '''' ''''''''' ''''''' ''''''''''''''' '''''''''' '''' '''''' ''''''''''''''''''' '''''''' ''''''''''''' ''''''''''''''' ''''''''''' ''''''''''''''''''''''''''''' '''''' ''''''''''''''' '''''''''''

 ''''''' ''''''''''''''''''''''''' '''''''''''''''' '''''''' '''' ''''''''''' '''''''' '''''''''''''''''''''''''''' '''''''''''''''''''''''' ''''''''''''''''''''''''''''''''' '''''''''' ''''' '''''''''' '''''''''''''''''''''' ''''''''''' #E   '''''''''''' '''''''''''''' ''''''' ''''''''' ''''''''''''' '''''''' '''''''''''''''''' '''''''''' ''''' ''' ''''''''''''''''' ''''''''' ''''''''''''''' '''''''

'''''''' '''''''''''''' ''''''''' ''''''''' '''''#E '' '''''''''' ''''''''' '''''''''''''''''''''''''' '''''''' '''''''''''''' ''''' ''' '''' ''''''''''' ''' ''''''''''''''' '''' ''' '''''''''''' ''''''''''' ''''''' '''''''''' ''''''''''''' ''''' '''' '''''''''''''''''''' '''''''''''' '''' '''''''' '''' ''''''''''''' ''''''' '''''''''' ''''' ''''' '''''''''''

Conclusions

7.3.1 Human health considerations

The following DNELs/DMELs and toxicological data are available for the comparative assessment of alternative substances (for details see Section 7.2).

Table 7-6: DNELs/DMELs and PNECs for 1,2-EDC and alternative substances

Substance D(M)NELlong-term inhalation workers EDC 16.7 µg/m3

1,3-DCP Not available (LOAEL 50 mg/kg bw/day) suspicion for genotoxicity and carcinogenicity

1,4-DCB Not available (NOAEL 300 mg/kg bw/day) suspicion for genotoxicity and carcinogenicity ''''''''''''' #E ''''''''''''''''''' '''''''''''#E '''''''''''

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 109

A limited database is available for the two chlorinated aliphatic compounds 1,3-DCP and 1,4-DCB. The effect levels identified in repeated dose studies would lead to higher DNELs compared to the DMEL for EDC. However, they do not consider a probable mutagenicity or carcinogenicity.

For 1,3-dichloropropane a wide variety of genotoxicity tests were conducted in in vitro assays. Tests in bacteria and in vitro gene mutation tests in mammalian cells were in the majority of the tests positive. The in vivo gene mutation tests were mainly positive, however a micronucleus tests was negative for 1,3-dichloropropane.

On the basis of the available data EDC and 1,3-dichloropropane revealed a similar genotoxicity profile with a clear indication of a genotoxic potential for both substances.

The results from the ECHA QSAR toolbox show for 1,3-dichloropropane an alert for mutagenic / carcinogenic properties based on DNA alkylation by nucleophilic substitution.

The database for 1,4-dichlorobutane with regard to mutagenicity and carcinogenicity is small. Only one negative micronucleus test in bone marrow cells of ICR mice was identified. For 1,4- dichlorobutane as well as for 1,3-dichloropropane the ECHA QSAR toolbox shows an alert for mutagenic and carcinogenic properties, comparable to the alerts for 1,2-dochloroethane and 1,3- dichloropropane, based on DNA alkylation by nucleophilic substitution.

Based on the currently available data and taking workers safety into account, EDC, 1,3- dichloropropane and 1,4-dichlorobutane lead to similar human health concerns. In conclusion, neither 1,3-dichloropropane nor 1,4-dichlorobutane are advantageous compared to EDC.

''''''''''''' ''#E ''''''''''''''''''' differs from these substances with regard to its toxicological profile. The substance is neither classified as CMR compound nor were any indications for mutagenicity observed in several tests. Systemic effects are not expected ''''''' '''' '''''''' '''''''''''''''''' '''''#E ''''''''' ''''''''''''''''''' ''' '''''''''' '''''''' '''' ''''''' #E ''''' The matter of concern for '''''''''''' #E '''''''''''''''''' is the highly irritating effect to skin, eyes and mucous membranes, which have to be controlled by adequate risk management measures. From a human health perspective it is obvious that this compound is the only potential alternative for the IER production process. In addition to its advantageous health effects profile its lower volatility compared to EDC (see below) is expected to lead to lower inhalation exposures.

In conclusion, 1,3-DCP and 1,4-DCB are suspicious of having carcinogenic properties on their own and cannot be considered suitable alternative. The toxicological database for 1,4-DCB is very limited. '''''''''''' ''#E ''''''''''''''' is an irritating substance and local effects determine its toxicological profile. Appropriate risk management measures have to be implemented to adequately control respective risks. If this is ensured, it can be considered a suitable candidate from a human health perspective.

7.3.2 Environmental toxicity considerations

For discussion of the potential for environmental toxicity and exposure the following physicochemical substance properties are taken into consideration.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 110

Table 7-7: Ecotoxicity and environmental fate properties data of alternative substances (if not stated otherwise; ECHA, 2015a) Substance Molecular Vapour Log Biodegradability Water

weight pressure (Pa) PO/W solubility PNECfreshwater (g/Mol) [mg/L] EDC 98.96 10 247 (25°C) 1.45 Not ready 8490-9000 (20 1100 µg/L biodegradable °C) 1,3-DCP* 112.99 2426.5 (25°C) 2.0 Not ready 2640 (25°C) Not available biodegradable** (mass fraction (expected 0.264%) **** range: 40 µg/L) 1,4-DCB* 127.01 550.5 (25°C) 2.81 Not ready 1283 (22°C) Not available biodegradable** (mass fraction (expected 0.1283%) **** range: 40 µg/L) '''#E '''''''' ''''''#E '''''' '''''''' #E '''''#E ''''''''''''' ''''''#E '''''''''' '''''''''#E ' '''''''' ''''''''''''''''''' '''''''''''' '''''' ''''''''''''''''''''''''''''' ''''''''''' ''''''''''' '''#E ''''''''' ''''' ''''''''''''''''' '''''''''''''''' '''''''''' '''''''''' * data from Toxnet (http://chem.sis.nlm.nih.gov/chemidplus/), assessed on 12 January 2015 ** only insufficient data from Bridié et al. (1979), see discussion in Section 7.2.2, in absence of valid data and in analogy to 1,4-DCB *** J-CHECK (via eChemPortal): http://www.safe.nite.go.jp/jcheck/, assessed on 12 January 2015 **** IUPAC-NIST Solubility Database: http://srdata.nist.gov/solubility/index.aspx

Only limited data are available to assess the aquatic toxicity of 1,3-DCP and 1,4-DCB. Observed effect concentrations are in the same range as for EDC. But due to the small database a higher assessment factor would apply and a lower PNEC would result. It can be concluded that the two substances are of similar or even higher aquatic toxicity compared to EDC.

Similar aquatic toxicity profiles are not surprising taking the related chemical structures into account. The similarity is supported by the fact that all 3 chlorinated substances are not readily biodegradable.

Water solubility is decreasing from EDC to 1,4-DCB, but vapour pressure is decreasing more profoundly with increasing chain length. Therefore, due to their lower volatility 1,3-DCP and 1,4-DCB are expected to lead to higher concentrations in the freshwater compartment compared to EDC. Taking into account a similar or higher aquatic toxicity this corroborates their questionable suitability as alternatives with regard to environmental toxicity.

A PNEC of ''''''''#E '' ''''''''' for '''''''''' ''#E ''''' was derived in the registration dossier. This value is slightly higher than that of EDC. Furthermore the substance is readily biodegradable and is not expected to cause chronic effects '''' ''' ''' ''''''''''''''''''' '''' ''''''''''' ''''''#E '''''''''''''''''''''''' ''''''''''''' ''''''''''.

Due to the lower aquatic toxicity, the readily biodegradability ''''''' ''''''' '''''''#E '''''''''''' '''' ''''''''''''''''' ''''''''''''''''#E ''''''''''''''' ''''''''''''''''''' is considered to not possess a critical environmental toxicity.

In conclusion, from the substances investigated, ''''''''''' ''#E ''''''''''''''''' is the only substance leading to reduced risks for human health and the environment, when compared to EDC.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 111

7.4 References for Annex 1

Aruoja, V.; Moosus, M.; Kahru, A.; Sihtmäe, M.; Maran, U. (2014) Measurement of baseline toxicity and QSAR analysis of 50 non-polar and 58 polar narcotic chemicals for the alga Pseudokirchneriella subcapitata Chemosphere, 96, 23-32

Benbrahim-Tallaa, L.; Lauby-Secretan, B.; Loomis, D.; Guyton, K.Z.; Grosse, Y.; El Ghissassi, F.; Bouvard, V.; Guha, N.; Mattock, H.; Straif, K. (2014) Carcinogenicity of perfluorooctanoic acid, tetrafluoroethylene, dichloromethane, 1,2- dichloropropane, and 1,3-propane sultone The Lancet Oncology, 15, 924-925

Benoit, D.A.; Puglisi, F.A.; Olson, D.L. (1982) A fathead minnow Pimephales promelas early life stage toxicity test method evaluation and exposure to four organic chemicals Environmental Pollution. Series A, Ecological and Biological, 28, 189-197

Bridie, A.L.; Winter, M.; Wolff, C.J.M. (1973) Determination of Acute Toxicity to Fish of Shell Chemicals. I. AMGR. 0095.73 Shell Research B.V., The Hague

Bridie´, A.L.; Wolff, C.J.M.; Winter, M. (1979) BOD and COD of some petrochemicals Water Research, 13, 627-630

''''''''''''''''''''''' '''' '''''''''''''' ''''''''''''''''''''''''' ''''''' ''''''''''''#E '''''''''' '''''''''''''''''''''''' ''''''''''''''''''''''''''''''''''''''''' ''''''''''' ''''''' ''''''' '''''''''''''''''' '''''' '''''''''''''''''''''''''''''''' ''''''' ''''''''''''''' '''''''''''''''''''' Gesundheits-Ingenieur, '''''' '''''''''''''''

'''''''''''''''''''''' '''''' ''''''''''' '''' ''''''''''''' '''''''''''''''''''' ''''''' ''''''''''''''''#E ''''''''''' '''''''''''''''''''''''''''''''''''' ''''''''''' ''''''''''''' ''''''''''''''' '''''''''''''' '''' ''''''''''' '''''''''''''''''''''''''''''''''' '''''''''''''''''''''''''''''' '''''''''''''''''''''' ' Zeitschrift für Wasser- und Abwasser-Forschung, ''''' ''''''

Brooke, L.T.; Call, D.J.; Geiger, D.L.; Northcott, C.E. (1984) Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales promelas). Vol. 1 Superior Wis. U.S.A. : Distributed by Center for Lake Superior Environmental Studies University of Wisconsin-Superior

Buijs, W.; van der Gen, A.; Mohn, G.R.; Breimer, D.D. (1984) The direct mutagenic activity of , omega-dihalogenoalkanes in Salmonella typhimurium. Strong correlation between chemical properties and mutagenic activity Mutation Research - Letters, 141, 11-14

Canadian Environmental Protection Act (1994) Priority Substances List Assessment Report. 1,2-Dichloroethane Minister of Supply and Services Canada

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 112

Crebelli, R.; Carere, A.; Leopardi, P.; Conti, L.; Fassio, F.; Raiteri, F.; Barone, D.; Ciliutti, P.; Cinelli, S.; Vericat, J.A. (1999) Evaluation of 10 aliphatic halogenated hydrocarbons in the mouse bone marrow micronucelus test Mutagenesis, 14, 207-215 de Zwart, D.; Slooff, W. (1987) Toxicity of mixtures of heavy metals and petrochemicals to Xenopus laevis Bulletin of Environmental Contamination and Toxicology, 38, 345-351

Dean, B.J.; Brooks, T.M.; Hodson-Walker, G.; Hutson, D.H. (1985) Genetic toxicology testing of 41 industrial chemicals Mutation Research - Reviews in Genetic Toxicology, 153, 57-77

DFG, Deutsche Forschungsgemeinschaft (2014) MAK- und BAT-Werte-Liste 2014. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe. Mitteilung 50 WILEY-VCH Verlag GmbH, Weinheim

Doherty, A.T.; Ellard, S.; Parry, E.M.; Parry, J.M. (1996) An investigation into the activation and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human cells Mutagenesis, 11, 247-274

ECHA, European Chemicals Agency (2008) Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterisation of dose [concentration]-response for environment http://guidance.echa.europa.eu/

ECHA, European Chemicals Agency (2012a) Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version: 2.1 online: http://echa.europa.eu/documents/10162/17224/information_requirements_r8_en.pdf

ECHA, European Chemicals Agency (2012b) Guidance on information requirements and chemical safety assessment. Chapter R.14: Occupational exposure estimation. Version: 2.1 Helsinki, Finland

ECHA, European Chemicals Agency (2015a) Information on Chemicals - Registered Substances Online: http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances

ECHA, European Chemicals Agency (2015b) Application for Authorisation: Establishing a Reference Dose Response Relationship for Carcinogenicity of 1,2-Dichloroethane. RAC/33/2015/09 Rev1 Final Helsinki, Finland

EPA, Environmental Protection Agency (2015) Integrated Risk Information System (IRIS) online: http://www.epa.gov/IRIS/

Freitag, D.; Ballhorn, L.; Behechti, A.; Fischer, K.; Thumm, W. (1994) Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 113

Structural configuration and toxicity of chlorinated alkanes Chemosphere, 28, 253-259

Geiger, D.L.; Northcott, C.E.; Brooke, L.T.; Call, D.J. (1985) Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas) Center for Lake Superior Environmental Studies, University of Wisconsin

Genoni, G.P. (1997) Influence of the energy relationships of organic compounds on toxicity to the cladoceran Daphnia magna and the fish Pimephales promelas Ecotoxicology and Environmental Safety, 36, 27-37

Heitmuller, P.T.; Hollister, T.A.; Parrish, P.R. (1981) Acute toxicity of 54 industrial chemicals to sheepshead minnows (Cyprinodon variegatus) Bulletin of Environmental Contamination and Toxicology, 27, 596-604

Henry, B.; Grant, S.G.; Klopman, G.; Rosenkranz, H.S. (1998) Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 397, 313-335

IARC, International Agency for Research on Cancer (1999) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 71. Re-Evaluation of some Organic Chemicals, Hydrazine and Hydrogen Peroxide (Part 1-3) WHO, World Health Organization, Geneva

IFA, Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung (2015) GESTIS-Stoffdatenbank. Gefahrstoffinformationssystem der Deutschen Gesetzlichen Unfallversicherung http://www.dguv.de/ifa/de/gestis/stoffdb/index.jsp

ILS, Integrated Laboratory Systems, Inc. (2000) 1,1-Dichloropropene [563-58-6]. 1,3-Dichloropropane [142-28-9]. 2,2-Dichloropropane [594-20-7]. Final Review of Toxicological Literature October 2000 http://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/dichloropropanesils_508.pdf

'''''''''''''''''''''''''''''' ''''''''''' ''' '''''''''''''''''''' ''''''' ''''''''''''''''#E ''''''''''' '''''''''''''''''''''''''''''''''''' '''''''''''''''''''' ''''''' '''''''''''''''' ''''''''''' '''''''''''''''''''''''''''''''''''' ''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''' Zeitschrift für Wasser- und Abwasserforschung, ''''''''''''''''''''''''''''''

Könemann, H. (1981) Quantitative structure-activity relationships in fish toxicity studies. Part 1: relationship for 50 industrial pollutants Toxicology, 19, 209-221

Kramers, P.G.N.; Mout, H.C.A.; Bissumbhar, B.; Mulder, C.R. (1991) Inhalation exposure in drosophila mutagenesis assays: experiments with aliphatic halogenated hydrocarbons, with emphasis on the genetic activity profile of 1,2-dichloroethane Mutation Research, 252, 17-33

LeBlanc, G.A. (1980) Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 114

Acute toxicity of priority pollutants to water flea (Daphnia magna) Bulletin of Environmental Contamination and Toxicology, 24, 684-691

Matsui, S.; Yamamoto, R.; Yamada, H. (1989) The Bacillus subtilis/microsome rec-assay for the detection of DNA damaging substances which may occur in chlorinated and ozonated waters Water Science & Technology, 21, 875-887

'''''''''''''''''''''' '''''''' ''''''''''' '''''''' '''''''''''''''''''' '''''''' ''''''''''' '''''''''''' '''' '''''''' '''''''' '''''''''''''''''''' #E '''' '''''' ''''''''''''' ''''''''''''' ''''''''''' ''' '''''''' '''''''''''''''''''''' ''''' '''''' ''''''''''' ''''''' ''''''' ''''''''''''''' ''''''''''''''''' Cancer Research, ''''' ''''''''''''''''

Nendza, M.; Wenzel, A. (2006) Discriminating toxicant classes by mode of action - 1. (Eco)toxicity profiles Environmental Science and Pollution Research, 13, 192-203

NLM, U.S. National Library of Medicine (2015) Hazardous Substances Data Bank (HSDB) online: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

OECD, Organisation for Economic Co-Operation and Development ''''''''''' '''''''' ''''''''''' ''''''''''''''''''''' ''''''''''''' '''''' ''''''''''' ''' '''''#E ''''''' '''''''''''''' ''''''''' '''''''' '''''''''''' '''''''''''' '''''''''''''''''' '''''''''' ''''''' ''''''''''''''''''' http://www.chem.unep.ch/irptc/sids/OECDSIDS/indexcasnumb.htm

OECD, Organisation for Economic Co-Operation and Development (2002) SIDS Initial Assessment Report for SIAM 14 (Paris, France, 26-28 March 2002). 1,2-Dichloroethane http://www.chem.unep.ch/irptc/sids/OECDSIDS/indexcasnumb.htm

Rim, K.-T.; Kim, S.-J.; Kim, J.-K.; Chung, Y.-H.; Park, S.-Y.; Yang, J.-S. (2011) In vivo micronucleus test of methylcyclopentane and 1,4-dichlorobutane Journal of the Korean Society for Environmental Analysis, 14, 89-93

Schudoma, D. (2001) Environmental Quality Objectives for Hazardous Substances in the Aquatic Environment. UBA-Texte 83/01 Herausgegeben vom Umweltbundesamt, Berlin. http://www.umweltbundesamt.de/publikationen/environmental-quality-objectives-for-hazardous

Stolzenberg, S.J.; Hine, C.H. (1980) Mutagenicity of 2- and 3-carbon halogenated compounds in the Salmonella/mammalian-microsome test Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 115

Environmental Mutagenesis, 2, 59-66

Tafazoli, M.; Kirsch-Volders, M. (1996) In vitro mutagenicity and genotoxicity study of 1,2-dichloroethylene, 1,1,2-trichloroethane, 1,3- dichloropropane, 1,2,3,-trichloropropane and 1,1,3-trichloropropane, using the micronucleus test and the alkaline single cell gel electrophoresis technique (comet assay) in human lymphocytes Mutation Research, 371, 185-202

Terrill, J.B.; Robinson, M.; Wolfe, G.W.; Billups, L.H. (1991) The subacute and subchronic oral toxicity of 1,3-dichloropropane in the rat International Journal of Toxicology, 10, 421-430

Tornero-Velez, R.; Ross, M.K.; Granville, C.; Laskey, J.; Jones, J.P.; DeMarini, D.M.; Evans, M.V. (2004) Metabolism and mutagenicity of source water contaminants 1,3-dichloropropane and 2,2- dichloropropane Drug Metabolism and Disposition, 32, 123-131 von der Hude, W.; Behm, C.; Gürtler, R.; Basler, A. (1988) Evaluation of the SOS chromotest Mutation Research - Environmental Mutagenesis and Related Subjects, 203, 81-94 von der Hude, W.; Scheutwinkel, M.; Gramlich, U.; Fißler, B.; Basler, A. (1987) Genotoxicity of three-carbon compounds evaluated in the SCE test in vitro Environmental Mutagenesis, 9, 401-410

WHO, W.H.O. (2003) 1,3-Dichloropropane in Drinking-water Background document for development of WHO Guidelines for Drinking-water Quality WHO/SDE/WSH/03.04/35 http://www.who.int/water_sanitation_health/dwq/chemicals/13dichloropropane.pdf?ua=1

Yu, W.-J.; Lee, I.-C.; Lee, J.; Lee, S.-M.; Kim, S.-H.; Baek, H.-S.; Moon, C.; Chung, Y.-H.; Kim, J.-C. (2013) 4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats Laboratory Animal Research, 29, 48-54

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 116

8 Annex 2: LANXESS screening - list of substances

The table below highlights the 106 substances considered by LANXESS in the screening phase. As highlighted in Section 4.2, substances within certain groups were excluded due to known unfavourable characteristics (e.g. decomposition) they would exhibit in the sulphonation and phthalimidomethylation processes. Some substances were also tested in the applicant’s laboratory. The substances highlighted in green represent those assessed on an individual basis in Table 4-6.

Table 8-1: LANXESS list of substances from screening Substance name CAS number EC number 1,1,2-trichloroethane 79-00-5 201-166-9 1,1,2,2-tetrachloroethane 79-34-5 201-197-8 1,1-dibromoethane 557-91-5 209-184-9 1,1-dichloropropane 78-99-9 78-99-9 1,2-dichlorobenzene 95-50-1 202-425-9 1,2-dichloropropane 78-87-5 201-152-2 1,2-dimethoxyethane 110-71-4 203-794-9 1,3-dichloropropane 142-28-9 205-531-3 1,3-dichloropropene 542-75-6 208-826-5 1,3-dioxane 505-22-6 208-005-1 1,4-dichlorobenzene 106-46-7 203-400-5 1,4-dichlorobutane 110-56-5 203-778-1 1,4-dioxane 123-91-1 204-661-8 1-bromobutane 109-65-9 203-691-9 1-chloropentane 543-59-9 208-846-4 1-iodopropane 107-08-4 203-460-2 1-methylpyrrole 96-54-8 202-513-7 1-nitropropane 108-03-2 203-544-9 2,2-dimethylpropanol 75-84-3 200-907-3 2,3-dichlorobutane 7581-97-7 231-486-4 2,3-dichloropropene 78-88-6 201-153-8 2-bromobutane 78-76-2 201-140-7 2-butenal 4170-30-3 224-030-0 2-iodopropane 75-30-9 200-859-3 2-methyl-1,3-dioxolane 497-26-7 207-841-4 2-methyl-2-propene nitrile 126-98-7 204-817-5 2-methylbutan-2-ol 75-85-4 200-908-9 2-methylpentan-3-one 565-69-5 209-288-4 2-methylpropane-1-thiol 513-44-0 208-162-6 2-methylthiophene 554-14-3 209-063-0 2-nitropropane 79-46-9 201-209-1 3,4-dichlorobut-1-ene 760-23-6 212-079-0 3-methylbut-3-en-2-one 814-78-8 212-405-1 3-methylthiophene 616-44-4 210-482-6 4-methylpentan-2-one 108-10-1 203-550-1 4-methylphenanthrene 832-64-4 - Acetic acid 64-19-7 200-580-7 Allyl acetate 591-87-7 209-734-8 Benzene 71-43-2 200-753-7 Benzotrifluoride 98-08-8 202-635-0 Bis(chloromethyl) ether 542-88-1 208-832-8 Boron tribromide 10294-33-4 233-657-9

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 117

Table 8-1: LANXESS list of substances from screening Substance name CAS number EC number Bromotrichloromethane 75-62-7 200-886-0 Butane-1-thiol 109-79-5 203-705-3 Butane-2-thiol 513-53-1 208-165-2 Butyl formate 592-84-7 209-772-5 Butyl isocyanate 111-36-4 203-862-8 Butyryl chloride 141-75-3 205-498-5 Chlorobenzene 108-90-7 203-628-5 Cycloheptane 291-64-5 206-030-2 Cycloheptene 628-92-2 211-060-4 Cyclohexa-1,3-diene 592-57-4 209-764-1 Cyclohexane 110-82-7 203-806-2 Cyclohexene 110-83-8 203-807-8 Cyclopentylamine 1003-03-8 213-697-3 Diallylamine 124-02-7 204-671-2 Dichloroacetyl chloride 79-36-7 201-199-9 Dichloromethane 75-09-2 200-838-9 Diethyl ketone 96-22-0 202-490-3 Diethyl sulphide 352-93-2 206-526-9 Dimethyl carbonate 616-38-6 210-478-4 Dimethyl disulphide 624-92-0 210-871-0 Dimethylformamide 68-12-2 200-679-5 Dimethyl sulfoxide 67-68-5 200-664-3 Ethyl acrylate 140-88-5 205-438-8 Ethyl methacrylate 97-63-2 202-597-5 Ethyl propionate 105-37-3 203-291-4 Ethyl propyl sulphide 4110-50-3 223-890-4 Fluorobenzene 462-06-6 207-321-7 Isobutyl acetate 110-19-0 203-745-1 Isobutyl formate 542-55-2 208-818-1 Isobutyronitrile 78-82-0 201-147-5 Isopropenyl acetate 108-22-5 203-562-7 Isopropyl acetate 108-21-4 203-561-1 Isopropyl methyl sulfide 1551-21-9 - Isovaleraldehyde 590-86-3 209-691-5 Methyl acrylate 96-33-3 202-500-6 Methyl butyrate 623-42-7 210-792-1 Methyl isobutyrate 547-63-7 208-929-5 Methyl isopropyl ketone 563-80-4 209-264-3 Methyl methacrylate 80-62-6 201-297-1 Methyl propyl sulphide 3877-15-4 223-403-5 N-butyronitrile 109-74-0 203-700-6 Nitrobenzene 98-95-3 202-716-0 Nitromethane 75-52-5 200-876-6 Pentan-2-one 107-87-9 203-528-1 Pentylamine 110-58-7 203-780-2 Phosphoryl trichloride 10025-87-3 233-046-7 Piperidine 110-89-4 203-813-0 Propyl acetate 109-60-4 203-686-1 Propyl acrylate 925-60-0 213-120-5 Propyl formate 110-74-7 203-798-0 Pyrrolidine 123-75-1 204-648-7 Sec butylformate 589-40-2 -

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 118

Table 8-1: LANXESS list of substances from screening Substance name CAS number EC number S-ethyl ethanethioate 625-60-5 210-904-9 Tetrachloro-1,2-difluoroethane 76-12-0 200-935-6 Tetrachloroethylene 127-18-4 204-825-9 Tetrahydropyran 142-68-7 205-552-8 Thiophene 110-02-1 203-729-4 Tin tetrachloride 7646-78-8 231-588-9 Toluene 108-88-3 203-625-9 Trichloroacetaldehyde 75-87-6 200-911-5 Trichloroacetyl chloride 76-02-8 200-926-7 Trichloroethylene 79-01-6 201-167-4 Valeraldehyde 110-62-3 203-784-4 Vinyl propionate 105-38-4 203-293-5

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 119

9 Annex 3: LANXESS IER products

The following table identifies the wide range of IERs marketed by LANXESS (169 variations can be seen), as well as their potential applications. As discussed in Section 5, the procedure for manufacturing an individual grade of IER is intricate, collaborative and will differ depending on the requirements of the customer. Considering the applicant’s ongoing R&D strategy for the replacement of EDC, all of the ''' #C' '''''' AER and CR products produced via the phthalimidomethylation process will require a new recipe, which must be optimised as well as validated in pilot trials. A similar process of optimisation and validation is required for all '''#C ' ''''' SAC ER products currently produced via sulphonation.

When it is considered that the affected products amount to approximately half of the entire LANXESS IER range, it is perhaps unsurprising that major impacts would arise from a refused authorisation. The bulk of these impacts would be concentrated on the applicant, but if customers were no longer able to source required IER grades from LANXESS (as could particularly be the case for AERs and CRs), there would also be potential for significant disruption downstream. Such disruption would also be severe if products with complex requalification procedures are considered. These issues are further explored in the corresponding SEA document.

Table 9-1: LANXESS IER products Category Trade name Applications of IER Demineralisation, desalination, food industry, food LEWATIT® A 365 WBA processing, ion exclusion of fruit juice, water treatment LEWATIT® A 8071 SBA Chemical industry, demineralisation, desalination, LEWATIT® A 8072 WBA exchange, industrial water, raw water, water LEWATIT® A 8073 MBA treatment Condensate polishing, demineralisation, desalination, LEWATIT® A 8075 KR WBA energy, exchange, industrial water, power generation, waste water treatment, water treatment Metal industry, petrochemicals, removal, waste water LEWATIT® AF 5 Adsorber treatment, water treatment LEWATIT® ASB 1 SBA Chemical industry, demineralisation, desalination, LEWATIT® ASB 1 OH SBA exchange, industrial water, raw water, water LEWATIT® ASB 1 P SBA treatment LEWATIT® ASB 2 SBA Chemical industry, demineralisation, desalination LEWATIT® C 249 SAC Energy, exchange, industrial water, power generation, Process water, raw water, softening, water treatment #C Chemical industry, desalination, exchange, industrial LEWATIT® C 267 SAC water, potable water treatment, raw water, water treatment Chemical industry, decarbonisation, desalination, LEWATIT® CNP 80 WAC energy, exchange, industrial water, power generation, LEWATIT® CNP 80 WS WAC Process water, raw water, softening, water treatment LEWATIT® CNP C WAC Decarbonisation, desalination, household, sanitary, LEWATIT® CNP P WAC garden, potable water treatment, softening, softening LEWATIT® CNP-LF WAC of potable water, water treatment Decarbonisation, desalination, food industry, LEWATIT® CNP-LF NA WAC household, sanitary, garden, municipal water, potable water treatment, softening, water treatment

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 120

Table 9-1: LANXESS IER products Category Trade name Applications of IER Industrial water, metal industry, potable water LEWATIT® DW 630 SBA treatment, raw water, removal, softening of potable water, water treatment WBA/Adso Metal industry, potable water treatment, removal, LEWATIT® FO 36 rber softening of potable water, water treatment Agriculture, catalysis, chemical industry, fuels, LEWATIT® GF 101 SAC petrochemicals LEWATIT® GF 202 Cationic Agriculture, fuels, petrochemicals, purification Exchange, household, sanitary, garden, industrial LEWATIT® HD 50 Mixed bed water, raw water, water treatment LEWATIT® K 1000 U Extraction, metal industry, mining, pharmaceutical SBA SO4 industry / biotechnology, recovery, recycling LEWATIT® K 1131 S SAC LEWATIT® K 1137 SAC Catalysis, chemical industry, food industry, removal of LEWATIT® K 1221 SAC organic constituents, sugar industry LEWATIT® K 1461 SAC black LEWATIT® K 2420 SAC Catalysis, chemical industry LEWATIT® K 2431 SAC LEWATIT® K 2620 SAC LEWATIT® K 2621 SAC Catalysis, chemical industry, food industry, removal of LEWATIT® K 2624 SAC organic constituents, sugar industry LEWATIT® K 2629 SAC #C LEWATIT® K 2640 SAC LEWATIT® K 2649 SAC

Catalysis, chemical industry, energy, industrial water,

LEWATIT® K 3433 WBA power generation, process water, ultrapure water,

water treatment

Catalysis, chemical industry, extraction, industrial

water, metal industry, mining, pharmaceutical LEWATIT® K 6362 SBA industry / biotechnology, process water, removal,

water treatment

Food industry, industrial water, metal industry,

LEWATIT® K 6367 SBA mining, process water, purification, separation, water

treatment

Extraction, food industry, industrial water, metal industry, mining, pharmaceutical industry / LEWATIT® K 6462 SBA biotechnology, process water, recovery, recycling, removal, separation, water treatment Catalysis, chemical industry, energy, industrial water, LEWATIT® K 7333 SBA power generation, process water, ultrapure water, water treatment LEWATIT® MDS 1268 SAC Ca / 290 LEWATIT® MDS 1268 K SAC Food industry, separation, starches, sugar industry / 290

LEWATIT® MDS 1268 K SAC / 310

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 121

Table 9-1: LANXESS IER products Category Trade name Applications of IER LEWATIT® MDS 1368 SAC Ca / 290 LEWATIT® MDS 1368 SAC Ca / 320 LEWATIT® MDS 1368 K SAC / 320 LEWATIT® MDS 1368 SAC Na / 320 LEWATIT® MDS 1368 SAC Ca / 350 LEWATIT® MDS 1368 K SAC / 350 LEWATIT® MDS 1368 SAC Na / 350

LEWATIT® MDS 1368 SAC Na / 320 Chemical industry, condensate polishing, demineralisation, desalination, industrial water, LEWATIT® MDS 200 H SAC mining raw water, water treatment LEWATIT® MDS 2368 SAC

Food industry, separation, starches, sugar industry LEWATIT® MDS 4368 MBA #C

Chemical industry, industrial water, metal industry, mining, potable water treatment, process water, LEWATIT® MDS TP 207 Chelating purification, removal, rinse water, softening, waste water treatment, water treatment Chemical industry, flue gas, industrial water, metal industry, potable water treatment, purification, LEWATIT® MDS TP 208 Chelating recycling, removal, softening, softening of potable water, waste water treatment, water treatment Extraction, industrial water, metal industry, mining, pharmaceutical industry / biotechnology, purification, LEWATIT® MDS TP 220 Chelating recovery, recycling, removal, rinse water, separation, waste water treatment, water treatment Chemical industry, flue gas, industrial water, metal LEWATIT® MDS TP 260 Chelating industry, purification, recycling, removal, softening,waste water treatment, water treatment Chemical industry, demineralisation, desalination, LEWATIT® MonoPlus SBA energy, exchange, industrial water, power M 500 generation,raw water, water treatment Chemical industry, condensate polishing, LEWATIT® MonoPlus SBA demineralisation, desalination, energy, exchange, M 500 KR industrial water, power generation, water treatment Chemical industry, demineralisation, LEWATIT® MonoPlus SBA desalination,energy, exchange, industrial water, M 500 MB power generation,raw water, water treatment Chemical industry, condensate polishing, LEWATIT® MonoPlus SBA demineralisation, desalination, energy, exchange, M 500 OH industrial water, power generation, water treatment Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 122

Table 9-1: LANXESS IER products Category Trade name Applications of IER Chemical industry, condensate polishing, LEWATIT® MonoPlus demineralisation, desalination, energy, exchange, SBA M 600 industrial water, power generation, process water, raw water, water treatment LEWATIT® MonoPlus SBA M 800 Chemical industry, condensate polishing, LEWATIT® MonoPlus SBA demineralisation, desalination, energy, exchange, M 800 KR industrial water, power generation, water treatment LEWATIT® MonoPlus SBA M 800 OH LEWATIT® MonoPlus Chemical industry, condensate polishing, desalination, SBA M 880 KR exchange, industrial water, water treatment LEWATIT® MonoPlus Industrial water, metal industry, process water, WBA MK 51 removal, water treatment Adsorbing agents, chemical industry, condensate LEWATIT® MonoPlus polishing, demineralisation, desalination, energy, SBA MP 500 exchange, industrial water, power generation, process water, raw water, water treatment #C LEWATIT® MonoPlus SBA Chemical industry, condensate polishing, MP 500 KR demineralisation, desalination, energy, exchange, LEWATIT® MonoPlus SBA industrial water, power generation, water treatment MP 500 OH LEWATIT® MonoPlus SBA MP 600 Adsorbing agents, chemical industry, demineralisation,

LEWATIT® MonoPlus desalination, energy, exchange, industrial water, WBA MP 64 power generation, process water, raw water, water treatment LEWATIT® MonoPlus WBA MP 68 Chemical industry, condensate polishing, LEWATIT® MonoPlus SBA demineralisation, desalination, energy, exchange, MP 800 industrial water, power generation, water treatment LEWATIT® MonoPlus SBA MP 800 KR LEWATIT® MonoPlus Chemical industry, demineralisation, desalination, SBA MP 800 OH energy, exchange, power generation, water treatment LEWATIT® MONOPLUS SAC S 107 NS LEWATIT® MonoPlus S SAC Chemical industry, demineralisation, desalination, 108 energy, exchange, industrial water, power generation, LEWATIT® MonoPlus S SAC process water, raw water, softening, water treatment 108 H LEWATIT® MonoPlus S SAC Chemical industry, condensate polishing, desalination, 108 KR energy, exchange, industrial water, power generation, LEWATIT® MonoPlus S SAC water treatment 200 KR LEWATIT® MonoPlus S SAC 215 KR Chemical industry, condensate polishing, desalination,

LEWATIT® MonoPlus S exchange, industrial water, water treatment SAC 300 KR

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 123

Table 9-1: LANXESS IER products Category Trade name Applications of IER Chemical industry, condensate polishing, desalination, LEWATIT® MonoPlus energy, exchange, fine purification / polishing, Mixed bed SM 1000 KR industrial water, power generation, ultrapure water, water treatment Chemical industry, condensate polishing, desalination, LEWATIT® MonoPlus Mixed bed energy, exchange, industrial water, power generation, SM 1000 KR-7Li water treatment LEWATIT® MonoPlus Chemical industry, condensate polishing, industrial Mixed bed SM 900 KR water, process water, purification, water treatment Chemical industry, demineralisation, desalination, LEWATIT® MonoPlus SAC energy, exchange, power generation, softening, water SP 112 treatment Adsorbing agents, chemical industry, condensate polishing, demineralisation of ultrapure water, LEWATIT® MonoPlus SAC desalination, energy, exchange, industrial water, #C SP 112 H power generation, process water, raw water, softening, ultrapure water, water treatment Chemical industry, condensate polishing, desalination, LEWATIT® MonoPlus SAC energy, exchange, industrial water, power generation, SP 112 KR water treatment LEWATIT® MonoPlus Metal industry, potable water treatment, removal, SBA SR 7 softening of potable water, water treatment LEWATIT® MonoPlus Chemical industry, industrial water, metal industry, Chelating TP 207 mining, potable water treatment, process water, LEWATIT® MonoPlus purification, removal, rinse water, softening, waste Chelating TP 208 water treatment, water treatment Extraction, metal industry, mining, pharmaceutical LEWATIT® MonoPlus industry / biotechnology, purification, recovery, Chelating TP 207 XL recycling, removal, separation, waste water treatment, water treatment Extraction, metal industry, mining, pharmaceutical LEWATIT® MonoPlus industry / biotechnology, purification, recovery, Chelating TP 209 XL recycling, removal, separation, waste water treatment, water treatment Extraction, metal industry, pharmaceutical industry / LEWATIT® MonoPlus Chelating biotechnology, recycling, removal, waste water TP 214 treatment, water treatment Chemical industry, industrial water, metal industry, LEWATIT® MonoPlus metal recovery, mining, purification, recovery, Chelating TP 220 recycling, removal, rinse water, separation, waste water treatment, water treatment

Chemical industry, industrial water, metal industry, LEWATIT® MonoPlus metal recovery, mining, purification, recovery, Chelating TP 227 recycling, removal, rinse water, separation, waste water treatment, water treatment Chemical industry, industrial water, metal industry, LEWATIT® MonoPlus mining, potable water treatment, process water, Chelating TP 260 purification, removal, rinse water, softening, waste water treatment, water treatment

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 124

Table 9-1: LANXESS IER products Category Trade name Applications of IER Adsorbing agents, chemical industry, demineralisation, desalination, energy, exchange, industrial water, LEWATIT® MP 62 WBA power generation, process water, raw water, water treatment Chemical industry, industrial water, metal industry, organics / toc, potable water treatment, process LEWATIT® MP 62 PH WBA water, removal, waste water treatment, water treatment Chemical industry, industrial water, metal industry, organics / toc, potable water treatment, process LEWATIT® MP 62 WS WBA water, removal, waste water treatment, water treatment LEWATIT® MP 62 WS Catalysis, chemical industry, organics / toc, potable - DRIED water treatment, water treatment Adsorbing agents, chemical industry, demineralisation, desalination, energy, exchange, industrial water, LEWATIT® MP 64 MBA power generation, process water, raw water, water treatment Chemical industry, desalination, exchange, industrial LEWATIT® NM 60 Mixed bed water, raw water, water treatment Chemical industry, desalination, exchange, industrial LEWATIT® NM 60 SG Mixed bed water, raw water, ultrapure water, water treatment Chemical industry, demineralisation, desalination, LEWATIT® NM 91 Mixed bed energy, industrial water, power generation, process water, raw water, water treatment Chemical industry, condensate polishing, energy, #C LEWATIT® S 100 SAC exchange, industrial water, metal industry, power generation, removal, water treatment Chemical industry, condensate polishing, energy, LEWATIT® S 100 G1 SAC exchange, industrial water, metal industry, power generation, removal, water treatment Chemical industry, condensate polishing, desalination, LEWATIT® S 100 KR/H SAC energy, exchange, industrial water, power generation, CL-FREI water treatment Chemical industry, condensate polishing, energy, exchange, fine purification/polishing, food industry, LEWATIT® S 150 CP SAC industrial water, power generation, purification in the foodstuff-industry, water treatment Automotive industry, chemical industry, demineralisation, desalination, energy, exchange, food industry, household, sanitary, garden, machine and LEWATIT® S 1567 SAC equipment construction, metal industry, paper industry, potable water treatment, power generation, removal, softening, softening of potable water, water treatment Dairy products, demineralisation, desalination, food industry, food processing, gelatines, ion exclusion of LEWATIT® S 1568 SAC fruit juice, potable water treatment, softening, softening of whey, starches, sugar industry, water treatment

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 125

Table 9-1: LANXESS IER products Category Trade name Applications of IER Dairy products, demineralisation, desalination, food industry, food processing, gelatines, ion exclusion of LEWATIT® S 1668 SAC fruit juice, softening, softening of whey, starches Sugar industry, water treatment Catalysis, chemical industry, food industry, inversion LEWATIT® S 2328 SAC of sucrose, sugar industry Dairy products, demineralisation, desalination, food industry, food processing, gelatines, ion exclusion of LEWATIT® S 2528 SAC fruit juice, softening, softening of whey, starches, sugar industry, water treatment Dairy products, demineralisation, desalination, food industry, food processing, ion exclusion of fruit juice, LEWATIT® S 2568 SAC softening, softening of whey, starches, sugar industry, water treatment Demineralisation, desalination, fine purification/ LEWATIT® S 2568 H SAC polishing, food industry, purification in the foodstuff- industry, starches, sugar industry, water treatment Adsorbtion, dairy products, decolourization, #C demineralisation, desalination, food industry, food LEWATIT® S 4228 MBA processing, gelatines, ion exclusion of fruit juice, softening of whey, starches, sugar industry, water treatment Dairy products, decolourization, demineralisation, desalination, food industry, food processing, ion LEWATIT® S 4268 MBA exclusion of fruit juice, softening of whey, starches, sugar industry, water treatment Decolourization, demineralisation, desalination, food LEWATIT® S 4328 MBA industry, starches, sugar industry, water treatment Decolourization, demineralisation, desalination LEWATIT® S 4428 MBA Food industry, starches, sugar industry, water treatment Decolourization, demineralisation, desalination, food LEWATIT® S 4468 MBA industry, starches, sugar industry, water treatment

Adsorbtion, dairy products, decolourization, demineralisation, desalination, food industry, food LEWATIT® S 4528 WBA processing, gelatines, ion exclusion of fruit juice, potable water treatment, softening of whey, starches, sugar industry, water treatment

Decolourization, demineralisation, desalination, LEWATIT® S 5128 SBA Food industry, sugar industry, water treatment Dairy products, demineralisation, desalination, food LEWATIT® S 5228 WBA industry, food processing, gelatines, ion exclusion of fruit juice, softening of whey, water treatment Demineralisation, desalination, food industry, sugar LEWATIT® S 5328 MBA industry, water treatment Decolourization, food industry, food processing, LEWATIT® S 5428 SBA ion exclusion of fruit juice, sugar industry

LEWATIT® S 5528 SBA Decolourization, food industry, sugar industry

Decolourization, demineralisation, desalination, food LEWATIT® S 6268 SBA industry, gelatines, sugar industry, water treatment Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 126

Table 9-1: LANXESS IER products Category Trade name Applications of IER LEWATIT® S 6368 SBA Decolourization, demineralisation, desalination, Food industry, food processing, gelatines, ion LEWATIT® S 6368 A SBA exclusion of fruit juice, starches, sugar industry, Water treatment Decolourization, demineralisation of fruit juice/must LEWATIT® S 6368 A OH SBA demineralisation, desalination, food industry, food processing, starches, sugar industry, water treatment Decolourization, demineralisation, desalination, food LEWATIT® S 6368 A Anionic industry, food processing, ion exclusion of fruit juice, SULFATE starches, sugar industry, water treatment LEWATIT® S 6368 SBA Decolourization, food industry, sugar industry Sulfate Decolourization, demineralisation, desalination, fine LEWATIT® S 7468 SBA purification / polishing, food industry, starches, sugar industry, ultrapure water, water treatment Adsorbtion, dairy products, debittering, Adsorber decolourization, food industry, food processing, LEWATIT® S 7968 resin ion exclusion of fruit juice, softening of whey, sugar industry LEWATIT® S 8107 WAC Decarbonisation, desalination, household, sanitary, garden, potable water treatment, softening, softening LEWATIT® S 8227 WAC #C of potable water, water treatment Exchange, household, sanitary, garden, potable water LEWATIT® S 8227 Ca WAC treatment, softening of potable water, water treatment Exchange, household, sanitary, garden, water LEWATIT® S 8227 Mg WAC treatment

LEWATIT® S 8229 WAC Decarbonisation, desalination, household, sanitary, garden, potable water treatment, softening of potable water, water treatment LEWATIT® S 8229 DRY WAC

Decarbonisation, desalination, exchange, household, LEWATIT® S 8229 Plus WAC sanitary, garden, potable water treatment, softening / Ag softening of potable water, water treatment Decarbonisation, desalination, household, sanitary, LEWATIT® S 8229 PLUS WAC garden, potable water treatment, softening, X softening of potable water, water treatment Dairy products, decarbonisation, demineralisation, desalination, food industry, food processing, LEWATIT® S 8528 WAC ion exclusion of fruit juice, potable water treatment, softening, softening of whey, starches, sugar industry water treatment

Demineralisation, desalination, food industry, LEWATIT® S 9167 Mixed bed household, sanitary, garden, potable water treatment, softening of potable water, water treatment

Chemical industry, condensate polishing, desalination LEWATIT® SM 600 KR energy, exchange, fine purification / polishing, Mixed bed Cl-free industrial water, power generation, ultrapure water, water treatment LEWATIT® TP 207 Chelating Chemical industry, industrial water, metal industry Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 127

Table 9-1: LANXESS IER products Category Trade name Applications of IER LEWATIT® TP 208 mining, potable water treatment, process water LEWATIT® TP 214 purification, removal, rinse water, softening, LEWATIT® TP 260 waste water treatment, water treatment Extraction, metal industry, mining, pharmaceutical industry / biotechnology, purification, recycling LEWATIT® TP 272 Chelating removal, separation, waste water treatment, water reclamation, water treatment Demineralisation, desalination, electronics industry, LEWATIT® UltraPure SAC industrial water, pharmaceutical industry / 1211 MD biotechnology, raw water, water treatment Electronics industry, fine purification / polishing, LEWATIT® UltraPure SAC pharmaceutical industry / biotechnology, ultrapure 1213 MD water, water treatment Demineralisation of ultrapure water, electronics LEWATIT® UltraPure industry, industrial water, pharmaceutical industry / SAC 1221 MD biotechnology, raw water, ultrapure water, water treatment Demineralisation, desalination, electronics industry, LEWATIT® UltraPure MBA industrial water, pharmaceutical industry / #C 1231 MD biotechnology, raw water, water treatment Demineralisation, desalination, electronics industry, LEWATIT® UltraPure SBA industrial water, pharmaceutical industry / 1241 MD biotechnology, raw water, water treatment

Electronics industry, fine purification / polishing, LEWATIT® UltraPure SBA pharmaceutical industry / biotechnology, ultrapure 1243 MD water, water treatment,

Demineralisation, desalination, electronics industry LEWATIT® UltraPure SBA industrial water, pharmaceutical industry / 1261 MD biotechnology, raw water, water treatment LEWATIT® UltraPure 1292 MD LEWATIT® UltraPure

1294 MD Electronics industry, fine purification / polishing, LEWATIT® UltraPure Mixed bed pharmaceutical industry / biotechnology, ultrapure 1296 MD water, water treatment

LEWATIT® UltraPure

1299 MD

Extraction, industrial water, metal industry, mining pharmaceutical industry / biotechnology, process LEWATIT® VP OC 1026 Chelating water, purification, recovery, recycling, removal rinse water, separation, water treatment Adsorbing agents, chemical industry, electronics industry, extraction, industrial water, metal industry LEWATIT® VP OC 1064 Adsorber pharmaceutical industry / biotechnology, process MD PH resin water, purification, rinse water, ultrapure water, Waste water treatment, water treatment

Adsorbing agents, chemical industry, decolourization,

energy, flue gas, food industry, industrial water, LEWATIT® VP OC 1065 WBA metal industry, power generation, removal, sugar

industry, water treatment

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 128

Table 9-1: LANXESS IER products Category Trade name Applications of IER

LEWATIT® VP OC 1074 SBA Decolourization, food industry, sugar industry

Adsorbing agents, chemical industry, organics / toc, Adsorber LEWATIT® VP OC 1600 pharmaceutical industry / biotechnology, potable #C resin water treatment, water treatment Catalysis, chemical industry, organics / toc, potable LEWATIT® Regler ZL - water treatment, water treatment Source: Applicant’s information Legend: SAC: Strong Acid Cation exchange resin; WAC: Weak Acid Cation exchange resin; SBA: Strong Base Anion exchange resin; WBA: Weak Base Anion exchange resin; MBA: Mixed Base Anion exchange resin

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 129

10 Annex 4: Qualification example - FDA food contact approval

The steps that the applicant must follow when attempting to obtain a U.S. Food and Drug Administration (FDA) Food Contact Notification (FCN)36 are discussed below. This information has been provided to demonstrate the types of timescales and resources than can be associated with obtaining a qualification for an IER product.

First, it is important to note that each FCN is very specific and limited to the intended use. For example, if the applicant applies for the use of a resin in a filter for drinking water then the ‘food’ is water and the FCN will cover only bringing the resin into contact with drinking water in a filter. It is the responsibility of the manufacturer of a food contact substance to ensure compliance with specifications and limitations in all applicable approvals.

A notification for a food contact substance must contain sufficient information to demonstrate that the substance is safe for the intended use. This means that comprehensive data on chemistry, toxicology and environmental information must be submitted; including the exact composition of the substance and the nature and amount of any substances migrating from the resin into the food it is in contact with (under well defined test conditions). Any modification to the food contact substance (as would be associated with the implementation of a potential alternative substance to EDC) has to be communicated to FDA and may require the submission of a new notification.

The sequence of events will include first filing an application for a FCN together with the required information on the resin’s properties. Migration testing will then be required, and must be undertaken by an external certified analytical laboratory, transmitting the test results to FDA. The applicant will then answer comments and/or questions from FDA and in certain cases repeat some tests or carry out additional tests. Eventually a notification will be received (after paying the due fee). Approximately, an FCN process may take 2 years and cost €200,000.

36 This is essentially a Food Contact approval.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 130

11 Annex 5: Justifications for confidentiality claims

This document contains confidential business information and so cannot be made public as a whole. In particular, the publication of the submitted document must not cover items which were not made public by the applicant, i.e. financial plans and financial forecasts, sales plans, and other relevant information that may have an impact on the share price of the applicant.

The World Trade Organisation agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires signatory members (including EU-members) to maintain protection of undisclosed information, including company know-how that has been subject to reasonable steps to keep it secret (under Article 39.2). Much of the information claimed confidential below falls under the protection of TRIPS or Competition Law and therefore its public disclosure must be prevented.

Particular care has been taken to minimise the presence of confidential information in the AoA document and thus the confidentiality claims made by the applicant. However, it is necessary to include some confidential information to provide the rapporteurs and Committees the necessary information to fully evaluate this AfA in more quantitative terms.

The justifications of confidentiality are given in the table below. These can be grouped in two categories:

1. Trade Secrets – Detailed information relating to manufacturing processes, e.g. quantity of EDC used per batch, etc.

2. Business Secrets – Financial Information e.g. project cost estimates, cost of EDC etc.

Note: In this public version of the AoA the table of justifications has been removed as they are also considered to be confidential.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 131

References

Please note: References for the risk assessment of alternative substances have been provided separately (at the end of Annex 1).

Bachmann, R., Feistel, L., Seidel, R., Siekiera, & Karl-Heinz. (2001). Patent No. US6228896 B1. Retrieved June 26, 2014, from http://www.google.co.uk/patents/US6228896

Barton, A. (1991). Handbook of Solubility Parameters and Other Cohesion Parameters, 2nd edition. CRC Press.

Camden International. (2014). ION Exchange Resin. Retrieved June 26, 2014, from http://www.camdeninternational.com.ph/portfolio-items/ion-exchange-resin/#

Dardel, F. (2013). Ion Exchange. Retrieved from Ion exchange resin structure: http://dardel.info/IX/resin_structure.html

Dorfner, K. (1991). Ion Exchangers. Berlin: Walter de Gruyter & Co.

Dow. (2000). DOWEX Ion Exchange Resins. Fundaments of Ion Exchange. Dow Liquid Separations. Retrieved from http://www.dow.com/liquidseps

Dow. (2002). DOWEX Ion Exchange Resins Powerful Chemical Processing Tools. Retrieved from http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_0041/0901b80380041d4e.pdf?filepa th=liquidseps/pdfs/noreg/177-01395.pdf&fromPage=GetDoc

Dow. (2006). Patent No. EP 1685166 A2. Retrieved October 31, 2014, from http://www.google.com/patents/EP1685166A2?cl=en

Dow. (undated). DOWEX™ Ion Exchange Resins: Water Conditioning Manual. Retrieved from http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_0885/0901b80380885879.pdf?filepa th=liquidseps/pdfs/noreg/177-01766.pdf&fromPage=GetDoc

ECHA. (2011). Guidance on the preparation of an application for authorisation. Retrieved December 19, 2014, from http://echa.europa.eu/documents/10162/13637/authorisation_application_en.pdf

ECHA. (2015). APPLICATION FOR AUTHORISATION: ESTABLISHING A REFERENCE DOSE RESPONSE RELATIONSHIP FOR CARCINOGENICITY OF 1,2-DICHLOROETHANE. Retrieved August 8, 2015, from http://echa.europa.eu/documents/10162/13641/rac_33_dose_response+_1_2dichloroethane_en.pd f

Fritz, J. S., & Gjerde, D. T. (2009). Ion Chromatography, 4th, Completely Revised and Enlarged Edition.

Gbor, P. K., & Jia, C. Q. (2004). Critical evaluation of coupling particle size distribution with the shrinking core model. Chemical Engineering Science, 1979 – 1987.

General Electric. (2012). Chapter 08 - Ion Exchange. Retrieved June 26, 2014, from http://www.gewater.com/handbook/ext_treatment/ch_8_ionexchange.jsp

Grulke, E. (1989). Solubility Parameter Values in Polymer Handbook, 3rd Edition. (J. Brandrup, & E. Immergut, Eds.) Wiley.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 132

Harland, C. E. (1994). Ion Exchange Theory and Practice. Royal Society of Chemistry.

Jackson, P. E. (1991). Ion Chromatography. Elsevier.

LANXESS. (2006). Ion exchange resins: From beads to bright solutions. Retrieved January 20, 2015, from http://lanxess.com/en/media-download/lewatit-image-brochure_en/

Lanxess. (2010). Ion Exchange Resins – Purified water for the world.

Marvin, H., Randy, S., & William, I. (2012). Patent No. EP1685166. European Patent. Retrieved from https://register.epo.org/application?number=EP04822187&tab=main

Ramaswamy, S., Huang, H.-J., & Ramarao, B. V. (2013). Separation and Purification Technologies in Biorefineries. West Sussex, UK: John Wiley & Sons.

SCI. (undated). Resin Types and Production. Retrieved June 26, 2014, from http://www.soci.org/~/media/Files/Conference%20Downloads/2012/IEX%20Intro%20Water%20Sep t%202012/Brian_Windsor_resin.ashx

Sherrington, D. C. (1998). Preparation, structure and morphology of polymer supports. Chem. Comm., 2275-2286.

Sigma Aldrich. (undated). Ion Exchange Resins: Classification and Properties. Retrieved from https://www.sigmaaldrich.com/content/dam/sigmaaldrich/docs/Aldrich/Instructions/ion_exchange_resins.pdf

Tegen, M. H., Tesch, R. S., & Harris, W. I. (2006). Patent No. EP1685166 A2. Retrieved June 26, 2014, from http://www.google.com/patents/EP1685166A2?cl=zh

Zaganiaris, E. J. (2011). Ion Exchange Resins and Synthetic Adsorbents in Food Processing. Paris: Book on Demand GmbH. Retrieved from https://books.google.com/books?isbn=2810622515

Zagorodni, A. A. (2007). Ion Exchange Materials: Properties and Applications. Amsterdam: Elsevier.

Use numbers: 1 & 2 Legal name of the applicant: LANXESS Deutschland GmbH 133