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

Publication ,  Journal Article
Leung, MCK; Meyer, JN
Published in: Reproductive toxicology (Elmsford, N.Y.)
October 2019

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.

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Published In

Reproductive toxicology (Elmsford, N.Y.)

DOI

EISSN

1873-1708

ISSN

0890-6238

Publication Date

October 2019

Volume

89

Start / End Page

83 / 92

Related Subject Headings

  • Zebrafish
  • Toxicology
  • Risk Assessment
  • Quantitative Structure-Activity Relationship
  • Protein Binding
  • Pesticides
  • Organophosphates
  • Mitochondria
  • Membrane Potential, Mitochondrial
  • Humans
 

Citation

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Leung, M. C. K., & Meyer, J. N. (2019). Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies. Reproductive Toxicology (Elmsford, N.Y.), 89, 83–92. https://doi.org/10.1016/j.reprotox.2019.07.007
Leung, Maxwell C. K., and Joel N. Meyer. “Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies.Reproductive Toxicology (Elmsford, N.Y.) 89 (October 2019): 83–92. https://doi.org/10.1016/j.reprotox.2019.07.007.
Leung, Maxwell C. K., and Joel N. Meyer. “Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies.Reproductive Toxicology (Elmsford, N.Y.), vol. 89, Oct. 2019, pp. 83–92. Epmc, doi:10.1016/j.reprotox.2019.07.007.
Journal cover image

Published In

Reproductive toxicology (Elmsford, N.Y.)

DOI

EISSN

1873-1708

ISSN

0890-6238

Publication Date

October 2019

Volume

89

Start / End Page

83 / 92

Related Subject Headings

  • Zebrafish
  • Toxicology
  • Risk Assessment
  • Quantitative Structure-Activity Relationship
  • Protein Binding
  • Pesticides
  • Organophosphates
  • Mitochondria
  • Membrane Potential, Mitochondrial
  • Humans