Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens.

Orton, F., Rosivatz, E., Scholze, M. and Kortenkamp, A. (2011) Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens. Environmental Health Perspectives, 119 (6). pp. 794-800. 10.1289/ehp.1002895.

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DOI: 10.1289/ehp.1002895

Abstract

Background: Evidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries.Objective: We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides.Methods: We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure-activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists ("active"), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists ("inactive"), and 13 had unknown activity, which were "out of domain" and therefore could not be classified with the QSAR ("unknown").Results: All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic.Conclusions: Due to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.

Item Type:Article
Uncontrolled Keywords:antiandrogen, AR-Lux, biomonitoring, endocrine disruption, fungicide.
Departments, units and centres:Department of Pharmacology > Centre for Toxicology
ID Code:2239
Journal or Publication Title:Environmental Health Perspectives
Deposited By:Library Staff
Deposited On:23 Jun 2011 10:58
Last Modified:23 Jun 2011 10:58

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