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Human health risk assessment of endocrine disruptors in pesticides – Follow-up of the Berlin Workshop from April 2016
Abstracts / Toxicology Letters 258S (2016) S62–S324
P22-030 Strategy of evaluation of the endocrine disruptor potential: Application to the analysis of new resins M. Gomez Berrada 1,∗ , M. Chiter 1 , M. Galonnier 1 , P. Pierré 1 , M. Chagnon 2 , L. Dahbi 2 , G. Lemkine 3 , P. Ferret 1 1
Safety Assessment Department, Pierre Fabre Dermo Cosmetique, Toulouse, France 2 Derttech « Packtox » LNC UMRU866, Nutox Team, Agrosupdijon, Université Bourgogne-Franche-Comté, Dijon, France 3 WatchFrog S.A., Evry, France Purpose: Epoxy-phenolic resins are widely used as inner coatings of aluminium tubes. These resins are mainly made from bisphenol A. Nevertheless, as BPA is a well-known endocrine disruptor developping alternative compounds is becoming a priority. Still it is necessary to make sure that these substitutes do not possess an endocrine disrupting activity as well. The objective of this study is to suggest a strategy of evaluation of the endocrine potential of a substance. Methods: Four commercial references of varnish coating 50 ml aluminium cans without BPA were tested. An aqueous solution was conditioned in these 50 ml cans and were stored at room temperature, and for 3 months at 40 ◦ C. The oestrogenic and androgenic potentials were assessed by: - Stably transfected transactivation in vitro assay on the cellular lineage hER␣-Hela-9903 to detect oestrogen receptor agonist; - Stably transfected transactivation in vitro assays on the cellular lineage MDA-kb2 to detect androgen receptor agonist and antagonist; - Evaluation of the potential for oestrogen disruption in vivo on Oryzias latipes. Results: The results obtained after three months at 40 ◦ C are as follows: -
Varnish A: positive-negative-negative Varnish B: positive-negative-punctual hormonal potential Varnish C: negative-negative-negative Varnish D: positive-negative-punctual hormonal potential
S315
products within the EU are regulated according to specific measures in the approval process. The development of harmonised scientific principles regarding endocrine disrupting properties are therefore an important precondition for creating uniform criteria at EU level as a basis for future human health assessments. According to provisions in the EU legislation for pesticides (biocidal and plant protection products), the European Commission was obliged to develop scientific criteria for the identification of EDs by 2013. At an expert meeting on the hazard identification of EDs in the regulatory context organised by the German Federal Institute for Risk Assessment (BfR) a consensus statement on EDs agreed among all participating scientists was reached on the identification of endocrine disruptors. However, the assessment of the corresponding risks on human health further requires consideration of dose-response relationships, including potency, exposure assessment, and risk characterisation, including susceptible subpopulations, severity and reversibility of effects. This emphasises the importance of the “One Substance – One Toxicological Assessment” philosophy, and has implications for data generation of both regulated and unregulated chemicals. The results of the meeting are intended to support the European Commission to develop scientific criteria for the regulation of EDs in pesticides and the development of regulatory guidance for the risk characterisation of pesticides which needs to be applicable for the approval process of active substances. Based on the roadmap of the European Commission which includes four options, the BfR suggests a further option2 which integrates the identification with a characterisation of substances regarding endocrine disrupting properties in a decision matrix. This option could inform the decision-making if a substance is eligible for approval because it might meet the criteria for negligible exposure/negligible risk from exposure http://dx.doi.org/10.1016/j.toxlet.2016.06.2075 P22-032 Identifying obstacles to the application of the one concentration approach for fish bioconcentration testing N. Burden 1,∗ , S.K. Maynard 2 , L. Weltje 3 , J.R. Wheeler 4 1
NC3Rs, United Kingdom Syngenta, Switzerland 3 BASF SE, Germany 4 Dow AgroSciences, United States 2
Conclusion: In view of these results, only the varnish C has been selected. This study highlights the complexity and the interest of an integrated approach in the evaluation of the endocrine disrupting activity. This strategy based on three standardized tests at different levels (in vitro/in vivo) allows the identification of the oestrogenlike potential of certain chemical substances. http://dx.doi.org/10.1016/j.toxlet.2016.06.2074 P22-031 Human health risk assessment of endocrine disruptors in pesticides – Follow-up of the Berlin Workshop from April 2016 V. Ritz ∗ , P. Marx Stoelting, R. Solecki German Federal Institute for Risk Assessment (BfR), Germany Due to the globally increasing concern with regard to possible adverse effects of endocrine disruptors (EDs), active substances with endocrine disrupting properties used in biocide and pesticide
Fish bioconcentration studies assist in determining the potential for substances to bioaccumulate. The resulting bioconcentration factor (BCF) value is used in Persistence, Bioaccumulation and Toxicity (PBT) and secondary poisoning assessments. Bioconcentration tests are resource intensive and use a minimum of 108 animals per study. Methods that replace, reduce or refine the use of fish for BCF testing could improve efficiency, reduce costs and support animal welfare considerations. The 2012 revision of the OECD Test Guideline for BCF testing (TG 305) provides the option to use one exposure concentration, when justification is provided, although two exposure concentrations may be required for some regulatory purposes. Recently this justification has been demonstrated for general chemicals and plant protection products. Where applied, the one concentration approach would reduce the number of fish used for this purpose by one third. We conducted a survey to determine how often the one concentration approach is applied in practice and identify the barriers to its widespread uptake. Thirty-one respondents were scientists
P22-030 Strategy of evaluation of the endocrine disruptor potential: Application to the analysis of new resins M. Gomez Berrada 1,∗ , M. Chiter 1 , M. Galonnier 1 , P. Pierré 1 , M. Chagnon 2 , L. Dahbi 2 , G. Lemkine 3 , P. Ferret 1 1
Safety Assessment Department, Pierre Fabre Dermo Cosmetique, Toulouse, France 2 Derttech « Packtox » LNC UMRU866, Nutox Team, Agrosupdijon, Université Bourgogne-Franche-Comté, Dijon, France 3 WatchFrog S.A., Evry, France Purpose: Epoxy-phenolic resins are widely used as inner coatings of aluminium tubes. These resins are mainly made from bisphenol A. Nevertheless, as BPA is a well-known endocrine disruptor developping alternative compounds is becoming a priority. Still it is necessary to make sure that these substitutes do not possess an endocrine disrupting activity as well. The objective of this study is to suggest a strategy of evaluation of the endocrine potential of a substance. Methods: Four commercial references of varnish coating 50 ml aluminium cans without BPA were tested. An aqueous solution was conditioned in these 50 ml cans and were stored at room temperature, and for 3 months at 40 ◦ C. The oestrogenic and androgenic potentials were assessed by: - Stably transfected transactivation in vitro assay on the cellular lineage hER␣-Hela-9903 to detect oestrogen receptor agonist; - Stably transfected transactivation in vitro assays on the cellular lineage MDA-kb2 to detect androgen receptor agonist and antagonist; - Evaluation of the potential for oestrogen disruption in vivo on Oryzias latipes. Results: The results obtained after three months at 40 ◦ C are as follows: -
Varnish A: positive-negative-negative Varnish B: positive-negative-punctual hormonal potential Varnish C: negative-negative-negative Varnish D: positive-negative-punctual hormonal potential
S315
products within the EU are regulated according to specific measures in the approval process. The development of harmonised scientific principles regarding endocrine disrupting properties are therefore an important precondition for creating uniform criteria at EU level as a basis for future human health assessments. According to provisions in the EU legislation for pesticides (biocidal and plant protection products), the European Commission was obliged to develop scientific criteria for the identification of EDs by 2013. At an expert meeting on the hazard identification of EDs in the regulatory context organised by the German Federal Institute for Risk Assessment (BfR) a consensus statement on EDs agreed among all participating scientists was reached on the identification of endocrine disruptors. However, the assessment of the corresponding risks on human health further requires consideration of dose-response relationships, including potency, exposure assessment, and risk characterisation, including susceptible subpopulations, severity and reversibility of effects. This emphasises the importance of the “One Substance – One Toxicological Assessment” philosophy, and has implications for data generation of both regulated and unregulated chemicals. The results of the meeting are intended to support the European Commission to develop scientific criteria for the regulation of EDs in pesticides and the development of regulatory guidance for the risk characterisation of pesticides which needs to be applicable for the approval process of active substances. Based on the roadmap of the European Commission which includes four options, the BfR suggests a further option2 which integrates the identification with a characterisation of substances regarding endocrine disrupting properties in a decision matrix. This option could inform the decision-making if a substance is eligible for approval because it might meet the criteria for negligible exposure/negligible risk from exposure http://dx.doi.org/10.1016/j.toxlet.2016.06.2075 P22-032 Identifying obstacles to the application of the one concentration approach for fish bioconcentration testing N. Burden 1,∗ , S.K. Maynard 2 , L. Weltje 3 , J.R. Wheeler 4 1
NC3Rs, United Kingdom Syngenta, Switzerland 3 BASF SE, Germany 4 Dow AgroSciences, United States 2
Conclusion: In view of these results, only the varnish C has been selected. This study highlights the complexity and the interest of an integrated approach in the evaluation of the endocrine disrupting activity. This strategy based on three standardized tests at different levels (in vitro/in vivo) allows the identification of the oestrogenlike potential of certain chemical substances. http://dx.doi.org/10.1016/j.toxlet.2016.06.2074 P22-031 Human health risk assessment of endocrine disruptors in pesticides – Follow-up of the Berlin Workshop from April 2016 V. Ritz ∗ , P. Marx Stoelting, R. Solecki German Federal Institute for Risk Assessment (BfR), Germany Due to the globally increasing concern with regard to possible adverse effects of endocrine disruptors (EDs), active substances with endocrine disrupting properties used in biocide and pesticide
Fish bioconcentration studies assist in determining the potential for substances to bioaccumulate. The resulting bioconcentration factor (BCF) value is used in Persistence, Bioaccumulation and Toxicity (PBT) and secondary poisoning assessments. Bioconcentration tests are resource intensive and use a minimum of 108 animals per study. Methods that replace, reduce or refine the use of fish for BCF testing could improve efficiency, reduce costs and support animal welfare considerations. The 2012 revision of the OECD Test Guideline for BCF testing (TG 305) provides the option to use one exposure concentration, when justification is provided, although two exposure concentrations may be required for some regulatory purposes. Recently this justification has been demonstrated for general chemicals and plant protection products. Where applied, the one concentration approach would reduce the number of fish used for this purpose by one third. We conducted a survey to determine how often the one concentration approach is applied in practice and identify the barriers to its widespread uptake. Thirty-one respondents were scientists