title: Differential sensitivity of blood, peripheral, and central cholinesterases in beagle dogs following dietary exposure to chlorpyrifos.
abstract: Two studies were performed to find out whether exposure limits that protect brain acetylcholinesterase (AChE) will protect peripheral tissue AChE after exposure to chlorpyrifos (CPF), an organophosphate insecticide. In a methods-development study, male dogs (3/dose) were exposed to 0.0, 0.3, 0.6, or 1.2mg/kg/day CPF in their diets for 4 weeks. Mixed cholinesterase (mChE), AChE, and butyrylcholinesterase (BuChE) activities were measured in plasma, RBC, brain, left atrium and ventricle, diaphragm, quadriceps, and nodose ganglia. Plasma, brain and peripheral tissue BuChE was inhibited at all dose levels. While RBC AChE was inhibited at all doses, brain and peripheral AChE activities were unaffected. In the main study, dogs (4/sex/dose) were exposed to 0.0, 0.5, 1.0, or 2.0mg/kg/day CPF in their diets for six weeks and RBC AChE was significantly inhibited at all doses in both sexes. Diaphragm, quadriceps, and nodose ganglia AChE was unaffected by treatment. Brain AChE was decreased by approximately 6% compared to controls in high-dose groups, and this was considered a threshold effect. Left atrium AChE in high-dose dogs was 25.5% less (males) and 32.1% greater (females) than controls; these differences were attributed to chance. While peripheral tissue and brain AChE were not affected following exposure to 1.0mg/kg/day, RBC AChE was inhibited at all doses. These results show that RBC AChE is more sensitive than brain or peripheral tissue AChE to inhibition by CPF, and that protection of brain AChE would protect peripheral tissue AChE.
authors.affiliation: The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Marable
authors.forename: Jacques P J
authors.initials: JP
authors.lastname: Maurissen
authors.forename: Joel L
authors.initials: JL
authors.lastname: Mattsson
authors.forename: Richard
authors.initials: R
authors.lastname: Billington
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism*; D003964:Diaphragm / Q000201:enzymology; D004032:Diet; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005725:Ganglia, Autonomic / Q000201:enzymology; D006325:Heart Atria / Q000201:enzymology; D006352:Heart Ventricles / Q000201:enzymology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D010949:Plasma / Q000201:enzymology; D052097:Quadriceps Muscle / Q000201:enzymology
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos