Response to the BPA Global Industry Group S

Response to APERC’s Proposal Regarding Environment Canada’s Preliminary Categorization of Nonylphenol, Octylphenol and their Ethoxylates

Introduction

Environment Canada (EC) appreciates the input of the Alkylphenols & Ethoxylates Research Council (APERC) on the Canada’s Domestic Substances List (DSL). In the proposal that was provided, the APERC responded to Environment Canada’s request for input on the preliminary decisions for the ecological categorization of substances on the Domestic Substances List (DSL). APERC was interested in particular with the categorization of seven alkylphenols and eight alkylphenols ethoxylates on the DSL. Therefore their submission was focused on the preliminary categorization decisions for the substances listed in Table 1 below. The following paragraphs summarize the position of APERC and EC’s response to the submission.

Table 1. List of Alkylphenols and Alkylphenols Ethoxylates of interest for APERC and their Preliminary Categorization Decisions

EC Preliminary Categorization Decisions (October 20, 2005) Meets EC CAS RN Criteria? Persistent Bioaccumulative Inherently Toxic Nonylphenol 104-40-5 No Not P - QSAR Not B - Exp. iT - Exp. 11066-49-2 Yes Not P - QSAR B - QSAR iT - QSAR 25154-52-3 Yes P - Exp. Not B - Exp. iT - Exp. 84852-15-3 Yes Not P - QSAR B - QSAR iT - QSAR Nonylphenol Ethoxylates P (Exp.- Not iT (Exp.- 9016-45-9 No preliminary)* Not B preliminary* 26027-38-3 No P (Group) Not B Not iT (Group) 37205-87-1 No P (Group) Not B Not iT (Group) 68412-54-4 No P (Group) Not B Not iT (Group) Not iT (Exp.- 127087-87-0 No P (Group) Not B preliminary* Octylphenol 140-66-9 Yes Not P - QSAR B - QSAR iT - Exp. 1806-26-4 No P - Exp. Not B - Exp. Not iT - Exp. 27193-28-8 Yes Not P - QSAR B - QSAR iT - QSAR Octylphenol Ethoxylates Not P (Exp.- 9002-93-1 No preliminary* Not B iT - Exp. Not P (Exp.- 9036-19-5 No preliminary* Not B iT - Exp. 68987-90-6 No Not P (Group) Not B iT (Group) Response to APERC’s Proposal Regarding Environment Canada’s 2 Preliminary Categorization of Nonylphenol, Octylphenol and their Ethoxylates

Environment Canada Initial Proposal

Environment Canada’s preliminary categorization decision identified that five of the fifteen substances in APERC report of September 16th, 2005 were proposed to meet the ecological categorization criteria as PiT (1 substance) or BiT (4 substances).

APERC’s position

APERC presented information regarding the persistence and bioaccumulation potential of nonylphenol (NP), octylphenol (OP), nonylphenol ethoxylates (NPEs), and octylphenol ethoxylates (OPEs) on the DSL. The document, entitled “Assessment of the Persistence and Bioaccumulation potential for nonylphenol, octylphenol, and their ethoxylates for categorization and screening of the Canadian Domestic Substance List (DSL)”, presented experimental data and alternative interpretations of existing data regarding these substances.

APERC provides a weight of evidence summary of the available data, which concludes none of the various NP, NPE, OP, or OPE compounds meet Environment Canada’s criteria for categorization as persistent (P) or bioaccumulative (B). Although it is acknowledged that certain members of the family meet the criteria for inherent toxicity (iT) to environmental organisms, the fact that criteria for P and B are not met indicates that none of the NP, NPE, OP, or OPE compounds should be categorized as PiT or BiT.

Description and Grouping of Substances

A group, for the purposes of categorization of substances on the DSL, is a group of substances possessing structural and/or constitutional similarities which may create a predictable pattern in environmental effects.

EC accepts the grouping proposed by APERC because their approach is in line with EC’s grouping approaches for categorization (Environment Canada, 2005a; and 2005b).

Nonylphenol

Based on structural similarity and current understanding of the various CAS RNs used to describe nonylphenol, there are in principle two forms of the material, i.e., linear NP as described by CAS RN 104-40-5 and branched NP, as best described by CAS RN 84852-15-3 (Environment Canada and Health Canada, 2001). However, CAS RNs 84852-15-3; 25154-52-3 and 11066-49-2 are considered as equivalent synonyms for branched NP for the categorization purposes. Further, to be consistent with previous regulatory evaluations of NP, during the conduct of the categorization assessment Environment Canada considers all data from any of the isomers as representative for NP (US EPA 2004; ECB 2003; EU 2001).

2 Response to APERC’s Proposal Regarding Environment Canada’s 3 Preliminary Categorization of Nonylphenol, Octylphenol and their Ethoxylates

Nonylphenol Ethoxylates (NPEs)

The DSL contains five Nonylphenol Ethoxylates which have essentially the same structure and isomeric mix because they differ only with respect to their level of description regarding branching and position of the nonyl group on the phenol ring. Moreover, manufacturers use essentially the same starting materials to produce NPEs by the based-catalyzed reaction of para-nonylphenol (p-NP) with ethylene oxide (EO). Thus, CAS RNs 9016-45-9; 26027-38-3; 37205-87-1; 68412-54-4; and 127087-87-0 are considered as equivalent synonyms for NPE for the purpose of categorization.

Octylphenol (OP)

As previously described for nonylphenol, there are in principle two forms of octylphenol, i.e., linear OP as described by CAS RN 1806-26-4 and branched OP, as best described by CAS RN 140-66-9. However, based on structural similarity and current understanding of the various CAS RNs used to describe OP, and to be consistent with previous regulatory assessments (UKEA, 2005), EC considers CAS RNs 140-66-9; 1806-26-4; and 27193-28-8 as equivalent synonyms for OP for the purpose of categorization.

Octylphenol Ethoxylates (OPEs)

As previously explained for NPEs on the DSL, the three OPEs on the DSL (CAS RNs 9002-93-1; 9036-19-5; and 68987-90-6) are considered as equivalent synonyms for OPE for the purpose of categorization. The main difference with NPEs is the use of para-octylphenol (p-OP) instead of para-nonylphenol (p-NP) as starting material.

Bioaccumulation

Preliminary categorization decisions from EC had two of the four nonylphenol, and two of the three octylphenol as bioaccumulative, based on QSAR predictions (Table 1). While APERC provides experimental reliable studies (Gobas and Arnot, 2003; Environment Canada and Health Canada, 2001) for these substances, EC used them to replace the QSAR predicted pivotal values (Table 2). These experimental BCF values indicate that none of the various NP, OP or their ethoxylates meets EC’s criteria for categorization as B. Moreover, APERC provides a weight of evidence summary of available recent laboratory and field studies which supports this conclusion for NP (Liber et al. 1999; Tsuda et al. 2001; and Hu et al. 2005) and OP (Tsuda et al. 2001; Ferreira- Leach and Hill 2000 and 2001; and Pederson and Hill 2002).

Table 2. Revised Categorization Decisions on Bioaccumulation for NP and OP

CAS RN Decision log BCF (L/kg) Evidence/Basis for Decision Nonylphenol 104-40-5 Not B* 2.428135 Exp-Group; Analogy with 25154-52-3 and 84852-15-3

11066-49-2 Not B 2.428135 Exp-Group; Analogy with 84852-15-3

25154-52-3 Not B* 0.46 Exp. (CITI, 1992)* 84852-15-3 Not B 2.428135 Exp. (Giesy et al., 2000; Wart and Boeri, 1991; Brooke, 1993) Octylphenol 140-66-9 Not B 0.46 Exp. (CITI, 1992) 1806-26-4 Not B* 0.46 Exp-Group; Analogy with 140-66-9 27193-28-8 Not B 0.46 Exp-Group; Analogy with 140-66-9 Notes: *Did not change

Persistence

Environment Canada has categorized five members of the family of NP, OP, and ethoxylates as persistent based on experimental data, four members as persistent based on grouping, one member as not persistent based on grouping, and five members as not persistent based on QSAR models (Table 1).

Previous Persistence Based on Experimental Data

EC had originally proposed that one of the NP (CAS RN 25154-52-3) and one of the OP (1806-26-4) were persistent based on experimental data. These conclusions were based on the results from OECD 301C Modified MITI I test (CITI 1992). These studies represent conditions under ready biodegradability testing. However, the results were not conclusive because both CAS RNs failed the ready biodegradation test (the test result was 0% ThOD for both CAS RNs). A substance which fails a ready aerobic biodegradation test (test result <60% or <70% within 28 days, different tests have different pass cut-offs) is not necessarily persistent because of the stringent test conditions in which there is limited opportunity for the substance to degrade, but is said to have slower biodegradation. In fact, a substance having <20% ready biodegradation may not be persistent, but further testing is required (Aronson, 1999).

EC used these inconclusive ready biodegradation test results for these two CAS RNs not only because they were in line with QSAR predictions, but also because they were the most conservative value. EC did the same thing with CAS RNs 9016-45-9; 9002-93- 1 and 9036-19-5 for which we had MSDS with inconclusive ready biodegradation values (<70% biodegradation within 28 days).

Although there are some conflicting reports in the literature, in general NP, OP, OPEs and NPEs are not readily biodegradable in water using standard test methods.

Substantial biodegradation will occur after a period of acclimation. OPEs and NPEs are, therefore, inherently biodegradable, and the mechanism involves stepwise loss of ethoxy groups to lower NPE congeners, followed by the production of NPEC and NP, depending upon experimental conditions (Rudling and Solyom, 1974; Maki et al. 1994).

APERC provided EC with numerous studies and a weight of evidence summary of available relevant studies on the environmental persistence of these five CAS RNs using a variety of test systems, ranging from screening tests (ready and inherent biodegradability) to simulation tests (river die-away, soil degradation). These studies showed extensive biodegradation under various OECD test protocols.

Based on the results of these studies, the weight of evidence and after evaluation of the reliability of some of these studies (Appendix 1), EC is now proposing that CAS RNs 25154-52-3; 1806-26-4; 9016-45-9; 9002-93-1 and 9036-19-5 are not persistent based on experimental data for categorization. The rationale for the proposed categorizations for these CAS RNs is summarized in table 3.

Table 3. Revised Categorization Decisions on Persistence for NP/NPE and OP/OPE

CAS RN Decision Half-Life (days) Evidence/Basis for Decision Nonylphenol 104-40-5 Not P 5.8 Exp. (Ying and Kookana, 2003) 11066-49-2 Not P 10 Exp-Group; Analogy with 84852-15-3 25154-52-3 Not P 10 Exp-Group; Analogy with 84852-15-3 84852-15-3 Not P 10 Exp. (Staples et al., 1999, 2001 and others) Nonylphenol Ethoxylates 9016-45-9 Not P 30 Exp. (Staples et al., 1999, 2001 and others) 26027-38-3 Not P 30 Exp-Group; Synonym/Analogy with 9016-45-9 37205-87-1 Not P 30 Exp-Group; Synonym/Analogy with 9016-45-9 68412-54-4 Not P 30 Exp-Group; Synonym/Analogy with 9016-45-9 127087-87-0 Not P 30 Exp-Group; Synonym/Analogy with 9016-45-9 Octylphenol 140-66-9 Not P 5 Exp. (Staples et al., 1999, 2001 and others) 1806-26-4 Not P 5 Exp-Group; Analogy with 140-66-9 27193-28-8 Not P 5 Exp-Group; Analogy with 140-66-9 Octylphenol Ethoxylates 9002-93-1 Not P 5 Exp-Group; Synonym/Analogy with 9036-19-3 9036-19-5 Not P 5 Exp (Staples et al., 1999, 2001) 68987-90-6 Not P 5 Exp-Group; Synonym/Analogy with 9036-19-3 Note: To be conservative, we used the highest half-life obtained from reliable studies.

Previous Persistence Based on Grouping or QSAR Models

The new experimental data and groups are used to replace previous persistence decisions based on grouping or QSAR because experimental data are preferred over QSAR predictions (Table 3).

Conclusion

The information provided by APERC did contribute to the categorization decisions for the alkylphenols and alkylphenols ethoxylates on the DSL.

APERC contested Environment Canada’s proposal on bioaccumulation for some of the alkylphenols. APERC provided experimental data which could be used as a pivotal value to counter the QSAR predicted pivotal values offered by EC. Experimental BCF values for fish were also sufficient to support evaluation of these substances on the DSL; BCF values range from 12 to 741 L/kg wet weight for reliable studies, which are below the criteria that Environment Canada has defined for categorization of substances on the DSL (BCF > 5,000). EC is now concluding that these fifteen alkylphenols and alkylphenols ethoxylates are not bioaccumulative in aquatic environments, and therefore these substances do not meet the categorization criteria for bioaccumulation.

APERC also contested Environment Canada’s proposal on persistence. To be conservative, EC decisions for persistence was based on inconclusive ready biodegradation test results for some of these alkylphenols and alkylphenols ethoxylates. Based on the availability of ready biodegradability data provided by APERC to support evaluation of some of these substances on the DSL, estimated environmental half-lives for water and soil are in the range of 5 to 30 days, which are below the criteria that Environment Canada has defined for categorization of substances on the DSL (Water, Soil t½ < 182 days). This conclusion is supported by additional results of numerous simulation tests conducted with representative members of the family of NP, OP, and the ethoxylates. As a consequence, the additional studies provided by APERC were reviewed and their results considered more conclusive than the original data used for categorization. Environment Canada is now proposing that these substances do not meet the categorization criteria for persistence.

Although it is acknowledged that certain members of the family meet the criteria for inherent toxicity (iT) to environmental organisms, the fact that criteria for P and B are not met indicates that none of the members of the family should be categorized as PiT or BiT. These categorizations are also consistent with persistence and bioaccumulation conclusions in other governmental assessments of these compounds (EC-HC, 2001; US EPA, 2004; EU, 2001; ECB, 2003; UKEA, 2005).

Upon further review, Environment Canada concludes that these fifteen alkylphenols and alkylphenols ethoxylates on the DSL do not meet the ecological criteria for categorization.

REFERENCES

Ahel, M., McEvoy, J., and Giger, W. (1993). Bioaccumulation of the lipophilic metabolites of nonionic surfactants in freshwater organisms. Environ. Pollut., 79, 243- 248.

Aronson, D. and P.H. Howard. (1999). Evaluating Potential POP/PBT Compounds for Persistence. Syracuse Research Corporation, North Syracuse, New York. November.

Brooke, L.T. (1993). Acute and chronic toxicity of nonyphenol to ten species of aquatic organisms. EPA report 68 C-0034. U.S. Environmental Protection Agency, Duluth, MN.

Chemical Inspection and Testing Institute (CITI). (1992). Biodegradation and bioaccumulation data of existing chemicals based on the CSCL Japan. Chemical Inspection and Testing Institute, Tokyo, Japan. http://www.safe.nite.go.jp/english/kizon/KIZON_start_hazkizon.html.

Environment Canada. (2005a). Categorization Approach for Grouping DSL Polymers to Determine Persistence and Inherent Toxicity to Non-human Organisms. Existing Substance Branch, Ottawa.

Environment Canada. (2005b). The Use of a Category Approach for Ecological Categorization of the Organic UVCBs on the DSL Existing Substance Branch, Ottawa.

Environment Canada and Health Canada (EC-HC). (2001). Priority Substances List Assessment Report: Nonylphenol and Its Ethoxylates. www.ec.gc.ca/ccebl/eng/final/index_e.html.

European Chemicals Bureau (ECB). (2003). PBT Working Group Substance Information Sheets for Nonylphenol (CAS 25154-52-3) and Phenol, 4-Nonyl, branched (CAS 84852-15-3).

European Union. (2001). European Union Risk Assessment Report: 4-Nonylphenol (branched) and Nonylphenol: Final Report. http://ecb.jrc.it/DOCUMENTS/Existing- Chemicals/RISK_ASSESSMENT/REPORT/.

Ferreira-Leach, A.M.R., and Hill, E.M. (2000). Bioconcentration and metabolism of 4- tert-octylphenol in roach (Rutilus rutilus) fry. Analusis, 28(9), 789-792.

Ferreira-Leach, A.M.R., and Hill, E.M. (2001). Bioconcentration and distribution of 4- tert-octylphenol residues in tissues of the rainbow trout (Oncorhynchus mykiss). Marine Environ. Res., 51, 75-89.

Giesy, J.P., Pierens, S.L., Snyder, E.M., Miles-Richardson, S., Kramer, V.J., Snyder, S.A., Nichols, K.M., and Villeneuve, D.A. (2000). Effects of 4-nonylphenol on fecundity

7 Response to APERC’s Proposal Regarding Environment Canada’s 8 Preliminary Categorization of Nonylphenol, Octylphenol and their Ethoxylates and biomarkers of estrogenicity in fathead minnows (Pimephales promelas). Environ. Toxicol. Chem., 19(5), 1368-1377.

Gobas, F., and Arnot, J. (2003). Identification of bioconcentration and bioaccumulation factors for 8000 DSL substances. Report to Existing Substances Branch, Environment Canada, March 21, 2003.

Hu, J., Jin, F., Wan, Y., Yang, M., An, L. An, W., and Tao, S. (2005). Trophodynamic behavior of 4-nonylphenol and nonylphenol polyethoxylate in marine aquatic food web from Bohai Bay, North China: comparison to DDTs. Environ. Sci. Technol., 39, 4801- 4807.

Liber, K., Gangl, J.A., Corry, T.D., Heinis, L.J., and Stay, F.S. (1999). Lethality and bioaccumulation of 4-nonylphenol in bluegill sunfish in littoral enclosures. Environ. Toxicol. Chem., 18(3), 394-400.

Maki, H., N. Masuda, M. Y. Fujiwara, M. Ike and M. Fujita. (1994). Degradation of alkylphenol ethoxylates by Pseudomonas sp. strain TR01. Appl. Environ. Microbiol. 60: 2265–2271.

Pedersen, R.T., and Hill, E.M. (2002). Tissue distribution and depuration of 4-tert- octylphenol residues in the cyprinid fish, Scardinius erythrophthalmus. Environ. Sci. Technol., 36, 3275-3283.

Rudling, L. and P. Solyom. (1974). The investigation of biodegradability of branched nonyl phenol ethoxylates. Water Res. 8: 115–119.

Staples, C.A., Weeks, J., Hall, J.F., and Naylor, C.G. (1998). Evaluation of aquatic toxicity and bioaccumulaion of C8- and C9-alkylphenol ethoxylates. Environ. Toxicol. Chem., 17(12), 2470-2480.

Staples, C.A., Williams, J.B., Blessing, R.L., et al. (1999). Measuring the biodegradability of nonylphenol ether carboxylates, octylphenol ether carboxylates, and nonylphenol. Chemosphere, 38, 2029-2039.

Staples, C.A., Naylor, C.G., Williams, J.B., et al. (2001). Ultimate biodegradation of alkylphenol ethoxylate surfactants and their biodegradation intermediates. Environ. Toxicol. Chem., 20, 2450-2455.

Tsuda, T., Takino, A., Muraki, K., Harada, H., and Kojima, M. (2001). Evaluation of 4- nonylphenols and 4-tert-octylpheno contamination of fish in rivers by laboratory accumulation and excretion experiments. Wat. Res., 35(7), 1786-1792.

United Kingdom Environment Agency (UK EA). (2005). Environmental risk assessment report: 4-tert-octylphenol (CAS No: 140-66-9).

US Environmental Protection Agency Substance Registry System. (2004) http://www.epa.gov/srs/.

Ward, T.J., and Boeri, R.L. (1991). Bioconcentration test with nonylphenol and the fathead minnow Pimephales promelas. Chemical Manufacturers Association, Washington, DC.

Ying, G.G., and Kookana, R.S. (2003). Degradation of five selected endocrine- disrupting chemicals in seawater and marine sediment. Environ. Sci. Technol., 37, 1256-1260.

APPENDIX 1: ROBUST STUDY SUMMARY Persistence for CAS RNs 84852-15-3; 9016-45-9; 140-66-9 and 9036-19-5. Item Yes No Reference: Staples, C.A., C.G. Naylor, J.B. Williams, W.E. Gledhill (2001) Ultimate Biodegradation of Alkylphenol Ethoxylate Surfactants and their Biodegradation Intermediates. Environmental Toxicology and Chemistry. 20(11): 2450-2455.

Test Substance CAS # and name ( specify, but do not assess this item): 84852-15-3; 9016-45-9; 140-66-9 and 9036-19-5 Substance purity reported? (Y/N and specify) commercial grade X Method References (Y/N) X OECD, EU, national, or other standard method? (Y/N) OECD X If not a standard method, justification of the method/protocol provided? (Y/N) n/a Test design / conditions Study type (e.g., hydrolysis, biodegradation, etc. – specify, but do not assess): biodegradation Conditions type (aerobic or anaerobic - specify, but do not assess): aerobic Test medium (air, water, soil, or sediment - specify, but do not assess): water Information on stability of the substance in the media of concern available? ( do not assess this item) The study refers to another study where the half life in soil was 10.4 days Information on controls (Y/N and specify, positive or negative) positive & X negative Number of replicates (Y/N and specify) duplicate X Temperature (Y/N and specify) 22 +/- 2 degree C X Test duration (Y/N and specify) 35d X Analytical method / technique used (Y/N) X For photodegradation only Reactants of gas-phase reactions ( specify, but do not assess this item) Light source (Y/N and specify) Light spectrum and/or relative intensity based on sunlight intensity (Y/N) For hydrolysis only Measured concentrations reported? (Y/N) pH values reported? (Y/N and specify) For biodegradation only Ready or inherent biodegradation? ( specify, but do not assess this item) Ready Substance concentration (Y/N) 12-15mg/L X Inoculum source (Y/N) X Inoculum concentration or number of microorganisms (Y/N) X Results Endpoints / values / units ( do not assess this item): t ½= 8.2 days Information on breakdown products available? ( do not assess this item) Yes Overall score: 11/11=100% EC Reliability code: 1 Reliability category (high, satisfactory, low): High Comments: The half life was calculated using a calculated pseudo-first order rate constant. The calculation of the half-life was optimized by using different values for lag times and asymptote (iteratively) to find the best fit of the carbon dioxide formation data (using Larson’s equation). The values

10 Response to APERC’s Proposal Regarding Environment Canada’s 11 Preliminary Categorization of Nonylphenol, Octylphenol and their Ethoxylates chosen were those giving the narrowest standard deviation of calculated half-lives.