Science Inventory

Harmonized Cross-Species Assessment of Endocrine and Metabolic Disruptors by Ecotox FACTORIAL Assay

Citation:

Medvedev, A., L. Medvedeva, E. Martsen, M. Moeser, K. Gorman, B. Lin, B. Blackwell, Dan Villeneuve, K. Houck, K. Crofton, AND S. Makarov. Harmonized Cross-Species Assessment of Endocrine and Metabolic Disruptors by Ecotox FACTORIAL Assay. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 54(19):12142-12153, (2020). https://doi.org/10.1021/acs.est.0c03375

Impact/Purpose:

Endocrine disrupting chemicals (EDCs) often target nuclear receptors (NRs) that control endocrine and metabolic responses through transcriptional regulation, and thus are of high concern for human and environmental health. Owing in part to structural differences of NRs, adverse effects of EDCs can vary significantly among species. Here, we describe a single-well reporter assay (the Ecotox FACTORIAL™) enabling parallel assessment of compound effects on estrogen, androgen, thyroid, and PPARg receptors of multiple species, including representatives from mammals, birds, reptiles, amphibians, and fish. Using the assay allowed ranking of the hazard potential of environmental pollutants (e.g., bisphenols, polycyclic aromatic hydrocarbons, synthetic progestins) across species. Furthermore, the assay facilitated determining taxa-specific effects of surface water samples. Therefore, the Ecotox FACTORIAL enables harmonized assessment of the endocrine and metabolic disrupting activity of chemicals and surface water in human and wildlife species.

Description:

Environmental pollution is a threat to humans and wildlife species. Of particular concern are endocrine disrupting chemicals (EDCs). An important target of EDCs is nuclear receptors (NRs) that control endocrine and metabolic responses through transcriptional regulation. Owing in part to structural differences of NRs, adverse effects of EDCs vary significantly among species. Here, we describe a multiplexed reporter assay (the Ecotox FACTORIAL) enabling parallel assessment of compounds' effects on estrogen, androgen, thyroid, and PPARγ receptors of representative mammals, birds, reptiles, amphibians, and fish. The Ecotox FACTORIAL is a single-well assay comprising a set of species-specific, one-hybrid GAL4-NR reporter constructs transiently transfected into test cells. To harmonize cross-species assessments, we used a combination of two approaches. First, we used the same type of test cells for all reporters; second, we implemented a parallel detection of reporter RNAs. The assay demonstrated excellent quality, reproducibility, and insignificant intra-assay variability. Importantly, the EC50 values for NR ligands were consistent with those reported for conventional assays. Using the assay allowed ranking the hazard potential of environmental pollutants (e.g., bisphenols, polycyclic aromatic hydrocarbons, and synthetic progestins) across species. Furthermore, the assay permitted detecting taxa-specific effects of surface water samples. Therefore, the Ecotox FACTORIAL enables harmonized assessment of the endocrine and metabolic disrupting activity of chemicals and surface water in humans as well as in wildlife species.

Record Details:

Record Type:DOCUMENT( JOURNAL/ PEER REVIEWED JOURNAL)
Product Published Date:10/06/2020
Record Last Revised:02/22/2023
OMB Category:Other
Record ID: 357121