Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor.

Abstract

Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.

• Authors: Svjetlana Medjakovic, Alfred Zoechling, Petra Gerster, Margarita M Ivanova, Yun Teng, Carolyn M Klinge, Barbara Schildberger, Michael Gartner, Alois Jungbauer
• Journal: Environmental toxicology (Environ Toxicol) Vol. 29 Issue 10 Pg. 1201-16 (Oct 2014) ISSN: 1522-7278 [Electronic] United States
• PMID: 23436777 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Chemical References

• AR protein, human
• ESR1 protein, human
• Endocrine Disruptors
• Estrogen Receptor alpha
• Pesticides
• Receptors, Androgen
• Receptors, Aryl Hydrocarbon

Topics

• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Endocrine Disruptors (toxicity)
• Estrogen Receptor alpha (metabolism)
• Female
• Humans
• Male
• Pesticides (toxicity)
• Prostatic Neoplasms (metabolism)
• Receptors, Androgen (metabolism)
• Receptors, Aryl Hydrocarbon (metabolism)