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TIME-COURSE OF ACUTE NEUROTOXICITY PRODUCED BY N-METHYL CARBAMATES IN PREWEANLING RATS.
Citation:
MCDANIEL, K., P. PHILLIPS, AND V. C. MOSER. TIME-COURSE OF ACUTE NEUROTOXICITY PRODUCED BY N-METHYL CARBAMATES IN PREWEANLING RATS. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Description:
N-methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread and long-term use, we could find no studies of a systematic comparison of neurotoxicity in young animals across this group of chemicals. To learn more about potential age-differential responses, we conducted time-course studies of seven carbamates in 17-day old Long-Evans male rats. Rats receive a single oral dose of either carbaryl (30 mg/kg), carbofuran (1 mg/kg), formetanate (3 mg/kg), methiocarb (12 mg/kg), methomyl (2.5 mg/kg), oxamyl (0.5 mg/kg), or propoxur (10 mg/kg). These doses were chosen based on data from range-finding studies. Treated rats were euthanized and blood and brain were collected 15, 45, 90, 180 min, or 24 hr after dosing; control tissues from rats dosed with the appropriate vehicle were collected at 45, 180 min, or 24 hr. A radiometric assay was used to obtain ChE levels for brain and erythrocytes (RBC). Almost all carbamates showed maximal ChE inhibition encompassing the 45-min time point. Methomyl was the only carbamate tested to show maximal inhibition only at 15 min, and by 45 min the enzyme activity was recovering. At 24 hr, all effects had recovered except for carbaryl-inhibited RBC (87% of control) and methomyl-inhibited brain (94% of control). The RBC inhibition was generally 10-30% greater (the least for formetanate, the greatest for carbaryl) than the brain inhibition with all carbamates except for propoxur, which showed the equal inhibition. The time-course of recovery of enzyme inhibition was similar for RBC and brain for all carbamates. These data determined the time of maximal effect to be used in follow-up dose-response studies for each chemical. Compared to previous work with these carbamates in adult LE male rats, the PND17 rats are somewhat more sensitive and slower to fully recover.
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