Interpreting estrogen screening assays in the context of potency and human exposure relative to natural exposures to phytoestrogens

Becker, Richard A., Hays, Sean M., Kirman, Christopher R., Aylward, Lesa L. and Wise, Kimberly (2014) Interpreting estrogen screening assays in the context of potency and human exposure relative to natural exposures to phytoestrogens. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 101 1: 114-124. doi:10.1002/bdrb.21085


Author Becker, Richard A.
Hays, Sean M.
Kirman, Christopher R.
Aylward, Lesa L.
Wise, Kimberly
Title Interpreting estrogen screening assays in the context of potency and human exposure relative to natural exposures to phytoestrogens
Journal name Birth Defects Research Part B: Developmental and Reproductive Toxicology   Check publisher's open access policy
ISSN 1542-9733
1542-9741
Publication date 2014-02
Year available 2014
Sub-type Article (original research)
DOI 10.1002/bdrb.21085
Open Access Status DOI
Volume 101
Issue 1
Start page 114
End page 124
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
While the Environmental Protection Agency and the Organization for Economic Cooperation and Development have developed validated in vitro and in vivo screening assays to measure interaction of substances with estrogen, androgen and thyroid pathway components, to date, methods to contextualize such results in terms of potencies and actual human exposures are lacking. To place endocrine screening results in the context of potency and human exposure, we propose a method that entails (1) calculating a benchmark dose for a response measured in an endocrine screen; (2) estimating the human urinary concentration (biomonitoring equivalent, BE) expected to correspond to this dose (BEBMD); (3) deriving the exposure:activity ratio (EAR) by comparing actual urinary values from human biomonitoring studies (e.g., National Health and Nutrition Examination Survey (NHANES)) to the BEBMD. Using OECD uterotrophic assay validation studies and NHANES results, we calculated EARs for genistein (EARGEN = 6.6 × 10-4) and bisphenol A (EARBPA = 8.8 × 10-7). The EARGEN is more than 700-fold greater than the EARBPA. Not only can these methods be applied to additional endocrine assays and compounds, they can contribute to weight of evidence decisions regarding the need for additional endocrine screening and testing-substances with low EARs may not warrant additional testing.
Keyword Biomonitoring
Endocrine disruption
Risk assessment
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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