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Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones
Citation:
Scholz, S., P. Renner, L. Ortego, S. Belanger, F. Busquet, R. Davi, B. Demeneix, J. Denny, M. Leonard, M. McMaster, Dan Villeneuve, AND M. Embry. Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, 43(1):45-72, (2013).
Impact/Purpose:
This is a literature review of in vitro tests for endocrine disruption including estrogen, androgen , and thyroid pathways for all vertebrates. It is an examination of the variability between different in-vitro assays, and their suitability to begin replacing traditional tests. As a review, the paper does not present new data or make any policy recommendations, but summarizes the state of the science. It will be of interest to scientists in government, academia, and industry working on in-vitro endocrine disruption assays.
Description:
Endocrine disruption is considered a highly relevant endpoint for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening for endocrine disruption – with focus on vertebrates (fish and amphibians) and estrogen, androgen and thyroid pathways - is included in screening programs such as the US EPA Endocrine Disruptor Screening Program. These screening assays, however, use a large number of animals and short-term alternatives to animal tests would be advantageous. In order to promote the development and/or implementation of alternative test methods that may replace, reduce or refine (3Rs) the use of animals, the present status of alternative assays for endocrine disruption in fish and frogs was assessed by a detailed literature review. The aim was to (1) determine the strengths and limitations of alternative assays and (2) 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 majority of alternative assays were measuring 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 ligand binding and reporter cell assays, between fish and frog estrogenic data and between fish embryo tests and in vivo reproductive effects. It was concluded that future developments should more systematically explore the predictive capacity of alternative tests and target at reducing their inter- and intra-assay variability.
