title: Cholinesterase inhibition and toxicokinetics in immature and adult rats after acute or repeated exposures to chlorpyrifos or chlorpyrifos-oxon.
abstract: The effect of age or dose regimen on cholinesterase inhibition (ChEI) from chlorpyrifos (CPF) or CPF-oxon (CPFO) was studied in Crl:CD(SD) rats. Rats were exposed to CPF by gavage in corn oil, rat milk (pups), or in the diet (adults) or to CPFO by gavage in corn oil. Blood CPF/CPFO levels were measured. With acute exposure, ChEI NOELs were 2 mg/kg CPF for brain and 0.5 mg/kg CPF for red blood cells (RBCs) in both age groups. In pups, ChEI and blood CPF levels were similar using either milk or corn oil vehicles. Compared to gavage, adults given dietary CPF (12 h exposure) had greater RBC ChEI, but lower brain ChEI at corresponding CPF doses, indicating an effect of dose rate. With repeated CPF exposures, ChEI NOELs were the same across ages (0.5 and 0.1 mg/kg/day for brain and RBCs, respectively). With CPFO dosing, the ChEI NOELs were 0.1 mg/kg (acute) and 0.01 mg/kg/day (repeated doses) for RBCs with no ChEI in brain at CPFO doses up to 0.5 (pup) or 10 mg/kg (adult) for acute dosing or 0.5 mg/kg/day for both ages with repeat dosing. Thus, there were no age-dependent differences in CPF ChEI via acute or repeated exposures. Pups had less ChEI than adults at comparable blood CPF levels. Oral CPFO resulted in substantial RBC ChEI, but no brain ChEI, indicating no CPFO systemic bioavailability to peripheral tissues.
authors.affiliation: Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA. mmarty@dow.com
authors.forename: M S
authors.initials: MS
authors.lastname: Marty
authors.forename: A K
authors.initials: AK
authors.lastname: Andrus
authors.forename: M P
authors.initials: MP
authors.lastname: Bell
authors.forename: J K
authors.initials: JK
authors.lastname: Passage
authors.forename: A W
authors.initials: AW
authors.lastname: Perala
authors.forename: K A
authors.initials: KA
authors.lastname: Brzak
authors.forename: M J
authors.initials: MJ
authors.lastname: Bartels
authors.forename: M J
authors.initials: MJ
authors.lastname: Beck
authors.forename: D R
authors.initials: DR
authors.lastname: Juberg
mesh_terms: D000375:Aging / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D002802:Cholinesterases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014886:Weaning
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D002802:Cholinesterases; D004390:Chlorpyrifos