title: Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice.
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.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Ai
authors.initials: A
authors.lastname: Okamura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yanagiba
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Jia
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.forename: Jun
authors.initials: J
authors.lastname: Ueyama
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D043182:Carboxylesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism; D003976:Diazinon / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004347:Drug Interactions; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D026023:Permethrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D013739:Testosterone; D026023:Permethrin; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D002802:Cholinesterases; D003976:Diazinon