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Environ Health Perspect. 2011 Jun;119(6):794-800. doi: 10.1289/ehp.1002895. Epub 2011 Feb 10.

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

Author information

1
Centre for Toxicology, School of Pharmacy, University of London, London, United Kingdom. francesorton@gmail.com

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.

PMID:
21310686
PMCID:
PMC3114813
DOI:
10.1289/ehp.1002895
[Indexed for MEDLINE]
Free PMC Article

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