ToxSci Advance Access published online on May 15, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm114
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Published by Oxford University Press 2007.
Comparison of Acute Neurobehavioral and Cholinesterase Inhibitory Effects of N-methyl Carbamates in Rat
* Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA
Analytical Chemistry Branch, Office of Pesticide Programs, US Environmental Protection Agency, Fort Meade, MD, USA
Corresponding author: V.C. Moser, Neurotoxicology Division (MD B105-04), 109 TW Alexander Dr., US EPA, RTP, NC 27711. 919-541-5075, FAX 919-541-4849. Moser.ginger{at}epa.gov
Received January 10, 2007; revision received May 1, 2007; accepted May 1, 2007
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Abstract |
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While the cholinesterase-inhibiting N-methyl carbamate pesticides have been widely used, there are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (RBCs), as well as motor activity (both horizontally and vertically directed) and clinical signs of overt toxicity. The chemicals tested were: carbaryl, carbofuran, formetanate, methiocarb, methomyl, oxamyl, and propoxur. All were administered orally and rats were tested in 20-minute activity sessions beginning 15 minutes after dosing; tissues were collected immediately after activity sessions. In general, motor activity was a sensitive measure of ChE inhibition for all these carbamate pesticides, and vertical activity showed the greatest magnitude of effect at the highest doses compared to either horizontal activity or ChE inhibition. Brain and RBC ChE activities were generally affected similarly. Pearson correlation coefficients of within-subject data showed good correlation between the behavioral and biochemical endpoints, with brain ChE inhibition and horizontal activity showing the highest correlation values. Determination of benchmark dose levels for 10% change in each endpoint also revealed that these two measures produced the lowest estimates. Thus, motor activity decreases are highly predictive of ChE inhibition for N-methyl carbamates, and vice versa.
Key Words: N-methyl carbamates; neurotoxicity; motor activity; cholinesterase; rats.
The information in this document has been funded wholly by the U.S. Environmental Protection Agency. It has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents necessarily reflect the views of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.