期刊
ENVIRONMENTAL HEALTH PERSPECTIVES
卷 119, 期 6, 页码 794-800出版社
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.1002895
关键词
antiandrogen; AR-Lux; biomonitoring; endocrine disruption; fungicide
资金
- European Commission [212502]
BACKGROUND: Evidence suggests that there is widespread decline in male reproductive health and that anti androgenic 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 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 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 anti-androgenic in our assay, and 9 previously untested pesticides were identified as anti androgenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, lambda-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds 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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