Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Anti-Androgen

Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Anti-Androgens

Frances Orton, Erika Rosivatz, Martin Scholze, Andreas Kortenkamp

Abstract

Background: Evidence suggests that there is widespread decline in male reproductive health and anti-androgenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and endocrine disrupting data, with the majority of the published literature focused on pesticides that are no longer registered for use in developed countries.

Objective: The aim of this study was to utilise 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 with 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, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, 7 compounds were classified 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.

…

EHP Journal Information

Environmental Health Perspectives (EHP) is a monthly journal of peer-reviewed research and news published by the U.S. National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. EHP's mission is to serve as a forum for the discussion of the interrelationships between the environment and human health by publishing in a balanced and objective manner the best peer-reviewed research and most current and credible news of the field. With an impact factor of 6.19, EHP is the top monthly journal in public, environmental, and occupational health and the second-ranked monthly journal in environmental sciences.

The environmental health sciences include many fields of study and increasingly comprise a multidisciplinary research area. EHP publishes articles from a wide range of scientific disciplines encompassing basic research; epidemiologic studies; risk assessment; relevant ethical, legal, social, environmental justice, and policy topics; longitudinal human studies; in vitro and in vivo animal research with a clear relationship to human health; and environmental medicine case reports. Because children are uniquely sensitive to their environments, EHP devotes a research section specifically to issues surrounding children's environmental health.

…