Case Study in 21st Century Ecotoxicology: Using In Vitro Aromatase Inhibition Data to Predict Short-Term In Vivo Responses in Adult Female Fish.

Autor: Villeneuve DL; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Blackwell BR; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Cavallin JE; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Cheng WY; US Environmental Protection Agency, Integrated Systems Toxicology Division, Research Triangle Park, North Carolina., Feifarek DJ; Student Services Contractor, US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Jensen KM; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Kahl MW; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Milsk RY; ORISE Participant, US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Poole ST; Student Services Contractor, US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Randolph EC; ORISE Participant, US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Saari TW; Student Services Contractor, US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota., Ankley GT; US Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, Minnesota.
Jazyk: angličtina
Zdroj: Environmental toxicology and chemistry [Environ Toxicol Chem] 2021 Apr; Vol. 40 (4), pp. 1155-1170. Date of Electronic Publication: 2021 Mar 10.
DOI: 10.1002/etc.4968
Abstrakt: The present study evaluated whether in vitro measures of aromatase inhibition as inputs into a quantitative adverse outcome pathway (qAOP) construct could effectively predict in vivo effects on 17β-estradiol (E2) and vitellogenin (VTG) concentrations in female fathead minnows. Five chemicals identified as aromatase inhibitors in mammalian-based ToxCast assays were screened for their ability to inhibit fathead minnow aromatase in vitro. Female fathead minnows were then exposed to 3 of those chemicals: letrozole, epoxiconazole, and imazalil in concentration-response (5 concentrations plus control) for 24 h. Consistent with AOP-based expectations, all 3 chemicals caused significant reductions in plasma E2 and hepatic VTG transcription. Characteristic compensatory upregulation of aromatase and follicle-stimulating hormone receptor (fshr) transcripts in the ovary were observed for letrozole but not for the other 2 compounds. Considering the overall patterns of concentration-response and temporal concordance among endpoints, data from the in vivo experiments strengthen confidence in the qualitative relationships outlined by the AOP. Quantitatively, the qAOP model provided predictions that fell within the standard error of measured data for letrozole but not for imazalil and epoxiconazole. However, the inclusion of measured plasma concentrations of the test chemicals as inputs improved model predictions, with all predictions falling within the range of measured values. Results highlight both the utility and limitations of the qAOP and its potential use in 21st century ecotoxicology. Environ Toxicol Chem 2021;40:1155-1170. © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
(© 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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