title: Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens.
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.
authors.affiliation: Centre for Toxicology, School of Pharmacy, University of London, London, United Kingdom. francesorton@gmail.com
authors.forename: Frances
authors.initials: F
authors.lastname: Orton
authors.forename: Erika
authors.initials: E
authors.lastname: Rosivatz
authors.forename: Martin
authors.initials: M
authors.lastname: Scholze
authors.forename: Andreas
authors.initials: A
authors.lastname: Kortenkamp
mesh_terms: D000726:Androgen Antagonists / Q000145:classification / Q000494:pharmacology*; D000728:Androgens / Q000145:classification / Q000494:pharmacology; D045744:Cell Line, Tumor; D004784:Environmental Monitoring; D005060:Europe; D006801:Humans; D008297:Male; D010575:Pesticides / Q000145:classification / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014410:Tumor Stem Cell Assay; D015003:Yeasts
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D010575:Pesticides