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COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.
Citation:
Moser, V C., P. M. Phillips, K. L. McDaniel, R S. Marshall, S J. Padilla, AND A. Lowit. COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES. Presented at Society of Toxicology, New, LA, March 06 - 10, 2005.
Description:
The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans rats (n=10/dose) were dosed by oral gavage with either CB (3-50 mg/kg), PP (0.3-20 mg/kg), OM (0.07-1.5 mg/kg), MM (0.1-2.5 mg/kg) or MC (0.5-25 mg/kg). Ten minutes after dosing, rats were scored for obvious signs of cholinergic toxicity ("tox score"). Horizontal (HA) and vertical (VA) activity were tabulated during subsequent 20 minute sessions in a figure-eight chamber. Brain and blood tissues were taken immediately thereafter to determine ChE activity. Exposure to each of the carbamates resulted in decreased motor activity. Based on no-effect levels (NOELs), activity was equally (PP, MC) or less (CB, OM, MM) sensitive than ChE inhibition. Within-subject regressions indicated a better correlation between motor activity and brain ChE inhibition than with blood ChE. Activity measures decreased faster than did the brain ChE activity (i.e., slope<1), with the exception of CB (slope=1). The VA dose-response curves were significantly different from HA, with greater decreases in VA at the higher doses. Nonetheless, the correlation between HA and VA was good, indicating a high concordance of effect on both measures. The ranking of toxicity as measured by the tox score ranged from no effect (CB, MC, OM) to a dose-related increase in the incidence and severity (PP, MM). Thus, some carbamates showed pronounced effects on motor activity at doses that produced little or no obvious toxicity as evaluated by this crude score. This illustrates that observable signs of cholinergic toxicity are not predictive of the magnitude of behavioral neurotoxicity. Furthermore, activity, especially VA, is a very sensitive outcome of ChE inhibition produced by carbamates. This is an abstract of a proposed presentation and does not reflect Agency policy.