Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data. (22nd September 2018)

• Record Type: Journal Article
• Authors: Dent, Matthew P; Li, Hequn; Carmichael, Paul L; Martin, Francis L
• Is Part Of: Toxicological sciences. Volume 167:Number 2(2019)
• Page Start: 375
• Page End: 384
• Publication Date: 2018-09-22
• Subjects: androgen receptor -- risk assessment -- in vitro approaches -- dietary comparison; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfy245
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX ® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure: activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances. Both diindolylmethane (DIM) and resveratrol are specifically acting dietary anti-androgens. The EARs for several anti-androgens were therefore expressed relative to the EAR of DIM, and how this 'dietary comparator ratio' (DCR) approach may be used to make safety decisions was assessed using an exposure-led case study for an anti-androgenic botanical ingredient. This highlights a pragmatic approach which allows novel chemical exposures to be put into context against dietary exposures to natural anti-androgenic substances. The DCR approach may have utility for other modes of action where appropriate comparators can be identified.