http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.1002895Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Anti-Androgens
Frances Orton, Erika Rosivatz, Martin Scholze, Andreas Kortenkamp
Abstract
Background: Evidence suggests that there is widespread decline in male reproductive health and anti-androgenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and endocrine disrupting data, with the majority of the published literature focused on pesticides that are no longer registered for use in developed countries.
Objective: The aim of this study was to utilise estimated human exposure data to select pesticides to test for anti-androgenic 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 anti-androgenic 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 with 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 anti-androgenic in our assay and 9 previously untested pesticides were identified as anti-androgenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, 7 compounds were classified as androgenic.
Conclusions: Due to estimated anti-androgenic 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 anti-androgenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.
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