title: Inhibition of trans-permethrin hydrolysis in human liver fractions by chloropyrifos oxon and carbaryl.
abstract: Permethrin, a pyrethroid insecticide, is one of several deployment-related chemicals that have been suggested as causative agents for Gulf War related illnesses. Hydrolysis of trans-permethrin (tPMT) is a major route of detoxication and a potential locus for interactions with chemicals with similar use patterns. This study examined the potential inhibitory effects of chlorpyrifos, carbaryl, pyridostigmine bromide and the insect repellent N,N-diethyl-m-toluamide (DEET) on tPMT hydrolysis in human liver fractions. Although chlorpyrifos was not inhibitory, its toxic metabolite, chlorpyrifos oxon, strongly and irreversibly inhibited tPMT hydrolysis at low concentrations (cytosolic and microsomal Ki values of 3 and 16 nM, respectively). Carbaryl, a known anticholinesterase agent, showed non-competitive inhibition kinetics, with Ki values two orders of magnitude higher than those for chlorpyrifos oxon. Although DEET was much less effective than either chlorpyrifos oxon or carbaryl, equimolar concentrations inhibited up to 45% of tPMT hydrolysis. Pyridostigmine bromide showed no inhibitory effects. This study suggests that interaction potential between organophosphorus and pyrethroid insecticides should be considered in safety assessments when both insecticides are deployed simultaneously.
authors.affiliation: Korea Institute of Toxicology, Yuseong, Taejeon, South Korea.
authors.forename: Jonghoon
authors.initials: J
authors.lastname: Choi
authors.forename: Ernest
authors.initials: E
authors.lastname: Hodgson
authors.forename: Randy L
authors.initials: RL
authors.lastname: Rose
mesh_terms: D012721:Carbaryl / Q000494:pharmacology*; D004390:Chlorpyrifos / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003671:DEET / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D008658:Inactivation, Metabolic; D007306:Insecticides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D026023:Permethrin / Q000493:pharmacokinetics*
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D003671:DEET; D026023:Permethrin; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D004390:Chlorpyrifos; D012721:Carbaryl