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

Frances Orton, Erika Rosivatz, Martin Scholze, Andreas Kortenkamp

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)794-800
Number of pages7
JournalEnvironmental Health Perspectives
Volume119
Issue number6
DOIs
Publication statusPublished - 1 Jun 2011

Keywords

  • Androgen Antagonists/classification
  • Androgens/classification
  • Cell Line, Tumor
  • Environmental Monitoring
  • Europe
  • Humans
  • Male
  • Pesticides/classification
  • Quantitative Structure-Activity Relationship
  • Tumor Stem Cell Assay
  • Yeasts

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