Evaluation of the endocrine activity of 2,4,6-tribromophenol, benzanthrone and benzophenone-2 based on Appendix 7.8-5 of REACH guidance document

Karen Duis, Henrik Holbech, Yohana M. Velasco-Santamaría

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Abstract

Within a project funded by the German Federal Environment Agency, the practicability of Appendix 7.8-5 of REACH guidance document R.7b was evaluated using three case study substances. Shortcomings in the guidance were identified. An assessment of potential endocrine activity in aquatic vertebrates was performed for benzanthrone, 2,4,6-tribromophenol and benzophenone-2, which differ in the amount of available data. Main focus was on effects on the estrogen/androgen axis. Potential endocrine activity was evaluated based on literature data and additional in vitro and in vivo testing. In the following, the main findings and the conclusions with regard to Appendix 7.8-5 are highlighted. (1) For benzanthrone, no binding to the estrogen receptor (ER) is predicted using QSAR methods, but potential metabolites with strong affinity to the ER were identified. At present, the endocrine activity of such metabolites is not considered in Appendix 7.8-5. Since many in vitro assays have limited metabolic capacity, this is a shortcoming for substances, for which no in vivo data are available. (2) Reporter gene assays indicate weak ER agonism of benzanthrone; in vitro results on androgen receptor mediated effects are conflicting. In such cases, additional guidance would be required to clarify in which cases further in vitro or in vivo tests should be performed. Currently, Appendix 7.8-5 provides little guidance on how to evaluate potential concern in cases where only QSAR and/or in vitro data are available. (3) 2,4,6-Tribromophenol has highest activity in tests, which are not part of most in vitro testing batteries (e.g. a sulfotransferase and a transthyretin binding assay). Hence, such effects might be overlooked. Generally, there appears to be a considerable risk that endocrine activity is not identified for data-poor substances, given that the initial assessment of endocrine activity according to Appendix 7.8-5 is only based on an evaluation of available information.
Original languageEnglish
Publication date24. Oct 2012
Number of pages1
Publication statusPublished - 24. Oct 2012
Event6th SETAC Europe Special Science Symposium: Environmental Endocrine Disrupter testing and evaluation - Hotel Marviaux, Brussel, Belgium
Duration: 24. Oct 201225. Oct 2012

Workshop

Workshop6th SETAC Europe Special Science Symposium
LocationHotel Marviaux
Country/TerritoryBelgium
CityBrussel
Period24/10/201225/10/2012

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