Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice

Reprod Toxicol. 2012 Dec;34(4):489-97. doi: 10.1016/j.reprotox.2012.07.007. Epub 2012 Aug 3.

Abstract

The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 μmol/kg/day) or cis-permethrin (90 μmol/kg/day) alone or in combination (100 μmol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Carboxylesterase / metabolism
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / toxicity*
  • Cholinesterases / metabolism
  • Diazinon / administration & dosage
  • Diazinon / pharmacokinetics
  • Diazinon / toxicity*
  • Drug Interactions
  • Epididymis / drug effects
  • Epididymis / pathology
  • Insecticides / administration & dosage
  • Insecticides / pharmacokinetics
  • Insecticides / toxicity*
  • Liver / enzymology
  • Male
  • Mice
  • Permethrin / administration & dosage
  • Permethrin / pharmacokinetics
  • Permethrin / toxicity*
  • Sperm Count
  • Sperm Motility / drug effects
  • Testis / drug effects
  • Testis / metabolism
  • Testis / pathology
  • Testosterone / metabolism

Substances

  • Cholinesterase Inhibitors
  • Insecticides
  • Testosterone
  • Permethrin
  • Carboxylesterase
  • Acetylcholinesterase
  • Cholinesterases
  • Diazinon