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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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.
|Uncontrolled Keywords:||antiandrogen, AR-Lux, biomonitoring, endocrine disruption, fungicide.|
|Departments, units and centres:||Department of Pharmacology > Centre for Toxicology|
|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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