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ToxSci Advance Access published online on August 14, 2008

Toxicological Sciences, doi:10.1093/toxsci/kfn164
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats

Russell L. Carr and Carole A. Nail

Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762

Send correspondence to: Russell Carr, Center for Environmental Health Sciences, College of Veterinary Medicine, Box 6100, Mississippi State University, Mississippi State, MS 39762-6100 USA, Phone: 662-325-1039, Fax: 662-325-1031, rlcarr{at}cvm.msstate.edu

Received June 12, 2008; revision received July 30, 2008; accepted August 4, 2008


   Abstract

Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in DMSO at a rate of 1.0 ml/kg. For comparison between these methods, rat pups were exposed daily from days 10-16 to CPS (5 mg/kg) either orally dissolved in corn oil or subcutaneously dissolved in DMSO, both at rates of either 0.5 or 1.0 ml/kg. A representative vehicle/route group was present for each treatment. Body weight gain was reduced in all treatment groups but was greater in the DMSO controls compared to the corn oil controls. At 4 hours following the final administration, serum carboxylesterase was inhibited >90% with all treatments. For cholinesterase (ChE) activity in the cerebellum, medulla-pons, forebrain, and hindbrain, and serum, inhibition in the CPS-oil groups was similar and inhibition in the CPS-DMSO groups was similar. However, significantly greater inhibition was present in the high volume CPS-DMSO group as compared to the CPS-oil groups. Inhibition in the low volume CPS-DMSO group was generally between that in the CPS-oil groups and the high volume CPS-DMSO group. These data suggest that using DMSO as a vehicle for CPS may alter the level of brain ChE inhibition.


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