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Abstract
Endocrine disruption is considered a highly relevant hazard for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening tests with a focus on interference with estrogen, androgen, and thyroid hormone pathways in fish and amphibians have been developed. However, they use a large number of animals and short-term alternatives to animal tests would be advantageous. Therefore, the status of alternative assays for endocrine disruption in fish and frogs was assessed by a detailed literature analysis. The aim was to (i) determine the strengths and limitations of alternative assays and (ii) present conclusions regarding chemical specificity, sensitivity, and correlation with in vivo data. Data from 1995 to present were collected related to the detection/testing of estrogen-, androgen-, and thyroid-active chemicals in the following test systems: cell lines, primary cells, fish/frog embryos, yeast and cell-free systems. The review shows that the majority of alternative assays measure effects directly mediated by receptor binding or resulting from interference with hormone synthesis. Other mechanisms were rarely analysed. A database was established and used for a quantitative and comparative analysis. For example, a high correlation was observed between cell-free ligand binding and cell-based reporter cell assays, between fish and frog estrogenic data and between fish embryo tests and in vivo reproductive effects. It was concluded that there is a need for a more systematic study of the predictive capacity of alternative tests and ways to reduce inter- and intra-assay variability.
Acknowledgements
L. Ortega (Bayer Crop Science, USA) and UFZ colleagues R. Altenburger, T. Luckenbach, E. Küster, M. Schmitt-Jansen are thanked for critical discussion and suggestions for data analysis. We also would like to thank K. Schirmer and M. Knöbel (Eawag, Switzerland) for suggestions on regression analysis.
Declaration of interest
B. Demeneix is a co-founder of WatchFrog. Watchfrog develops and applies amphibian and fish embryo models for environmental and chemical testing. Authors S. Scholz and P. Renner are employed by the Helmholtz Centre for Environmental Research - UFZ, a public funded research institute of the Helmholtz Association exclusively dedicated to environmental research. These authors were compensated by ILSI-HESI and L’Oreal for the preparation of this review. All other authors contributed to the review as part of their normal employment. S. E. Belanger is employed by The Procter & Gamble Company in the Corporate Product Safety and Regulatory Affairs organization and is Co-chair of the ILSI-HESI Project Committee on Animal Alternative Needs in Environmental Risk Assessment. J. Denny and D. Villeneuve are employed by the US EPA, Office of Research and Development (ORD), National Health and Environmental Effects Research Laboratory (NHEERL). M. R. Embry is employed by a nonprofit institution, ILSI-HESI. M. McMaster is employed by Environment Canada, Water Science and Technology Division, National Water Research Institute (NWRI). The views expressed in this article are purely those of the authors and may not be regarded as stating an official position of the employing organisation. F. Busquet received a travel grant to present the review data at the Annual meeting of the Society of Toxicology in 2011, Washington, DC. This manuscript has been subjected to review by the US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. It also received internal review by Environment Canada, National Water Research Institute and was approved for publication. Government and academic authors were reimbursed for travel expenses to attend committee meetings and did not receive any other compensation. M. Léonard is employed by L’Oréal in the Research & Innovation organization and is also a Co-chair of the ILSI-HESI Project Committee on Animal Alternative Needs in Environmental Risk Assessment. The author’s affiliation is as shown on the cover page. The authors have sole responsibility for the writing and content of the paper.