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TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.
Citation:
Padilla, S J., R S. Marshall, D L. Hunter, P. M. Phillips, K. L. McDaniel, V C. Moser, AND A. Lowit. TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oil); methomyl (MM; 3mg/kg in water); methiocarb (MC; 25 mg/kg in corn oil); oxamyl (OM; 1 mg/kg in water) or propoxur (PP; 20 mg/kg in corn oil). Brain and blood were taken at 0.5, 1.0, 2.0, 4.0 and 24 hrs after dosing for analysis of ChE activity using a radiometric method which limits the amount of reactivation of the ChE activity. This level of dosing produced at least 40% brain ChE inhibition with all compounds. The time-course study revealed that the time of peak effect (brain and RBC ChE inhibition) was very similar for all 5 carbamates: 0.5-1.0 hr after dosing. Two compounds, methomyl and oxamyl, however, showed significant recovery by 1.0 hr after dosing. By 24 hours after dosing, brain and RBC activity in all animals had returned to normal levels. For the dose-response study, each compound was administered at 5 different levels (plus vehicle control) and the tissues (brain and RBC) taken at 40 minutes after dosing for assessment using the radiometric assay. The lowest dose that significantly inhibited ChE activity in RBC was 15 mg/kg (CB); 1.25 mg/kg (MM); 25 mg/kg (MC); 0.5 mg/kg (OM) and 10 mg/kg (PP), and for brain was 7.5 mg/kg (CB); 0.6 mg/kg (MM); 2 mg/kg (MC); 0.5 mg/kg (OM) and 3 mg/kg (PP). Although linear regressions comparing ChE inhibition in brain and RBCs showed generally close correspondence, brain ChE was usually the more sensitive measure, especially at the lower dosages. The exception was OM where RBC ChE inhibition appeared to be more sensitive than brain ChE inhibition. This is an abstract of a proposed presentation and does not reflect Agency policy