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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies.

Authors: Leung, Maxwell C K; Meyer, Joel N

Published In Reprod Toxicol, (2019 Oct)

Abstract: Mitochondrial toxicity has been proposed as a potential cause of developmental defects in humans. We evaluated 51 organophosphate and carbamate pesticides using the U.S. EPA ToxCast and Tox21 databases. Only a small number of them bind directly to cholinesterases in the parent form. The hydrophobicity of organophosphate pesticides is correlated significantly to TSPO binding affinity, mitochondrial membrane potential reduction in HepG2 cells, and developmental toxicity in Caenorhabditis elegans and Danio rerio (p < 0.05). Structural analysis suggests that in some cases the Krebs cycle is a potential target of organophosphate and carbamate exposure at early life stages. The results support the hypothesis that mitochondrial effects of some organophosphate pesticides-particularly those that require enzymatic activation to the oxon form-may augment the documented effects of disruption of acetylcholine signaling. This study provides a proof of concept for applying new approach methodologies to interrogate mechanisms of action for cumulative risk assessment.

PubMed ID: 31315019 Exiting the NIEHS site

MeSH Terms: Animals; Caenorhabditis elegans/drug effects*; Caenorhabditis elegans/genetics; Caenorhabditis elegans/growth & development; Carbamates/chemistry; Carbamates/therapeutic use*; Citric Acid Cycle/drug effects; Cytochrome P-450 Enzyme System/metabolism; DNA Damage; Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Membrane Potential, Mitochondrial/drug effects; Mitochondria/drug effects*; Mitochondria/metabolism; Organophosphates/chemistry; Organophosphates/toxicity*; Pesticides/chemistry; Pesticides/toxicity*; Protein Binding; Quantitative Structure-Activity Relationship; Risk Assessment; Zebrafish/genetics; Zebrafish/growth & development*

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