Mechanistic Evaluation of the Combined Actions of Environmentally-Relevant Chemical Mixtures on Endocrine Signaling in Crustaceans
Year: 2008
Type: report
Abstract: Pharmaceuticals, personal care products, and other chemicals have been shown to accumulate in surface waters of North Carolina and many of these contaminants have the potential to disrupt endocrine signaling processes.The hypothesis was tested that mixtures of pharmaceuticals and other surface water contaminants, at levels individually considered to be safe, can adversely impact population biology of some crustaceans by modulating the endocrine signaling pathway responsible for sex determination.The hormone methyl farnesoate regulates sex determination, hemoglobin production, and other functions in many crustacean species.In the present study, several pharmaceuticals and other major surface water contaminants were evaluated for endocrine-disrupting activity (either as a methyl farnesoate mimic, antagonist, or potentiator).Chemicals were evaluated for their ability to alter sex-determination in offspring of the freshwater crustacean Daphnia magna.Combined effects of chemical mixtures of these chemicals were then mathematically modeled to identify mixtures scenarios that might pose risk to crustaceans and perhaps other species.Of the eleven compounds evaluated, 6 mimicked the action of methyl farnesoate and stimulated excess male offspring production.Most potent were the insect growth regulating insecticides pyriproxyfen and fenoxycarb.The insecticide methoprene was moderately active; while, the cyclodiene (dieldrin, chlordane) and cyclohexane (lindane) insecticides were weak methyl farnesoate agonists.Bisphenol A appeared to function as a methyl farnesoate potentiator.Other compounds, including the pharmaceuticals were not active.Mixtures modeling revealed that only the insect growth regulating insecticides were sufficiently potent to contribute to the excess production of male offspring at mixture formulations in which constituents were present at environmentally-relevant concentrations.Mixtures modeling in which constituents were present at equi-potent levels revealed mixture scenarios that elicited significant effects on sex ratios of offspring when constituents were present at levels that, individually, would not elicit effects.This study advanced our understanding of mixtures toxicity, provided significant insight into approaches for assessing the toxicity of chemical mixtures, and contributed to the development of free, interactive website for the evaluation of chemical mixtures toxicity (available at http://wang.tox.ncsu.edu/model5/).
Author: Gerald A. LeBlanc
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2109797522