Volume :
5
Issue :
1
Abstract :
Respiratory failure is the primary cause of death in poisonings involving
carbamate insecticides. However, the mechanisms of respiratory toxicity
induced by carbamates remain unclear. The aims of this study were i) to
describe the respiratory effects of methomyl, ii) to assess the peripheral or
central origin of those effects, and iii) to study the dose-effect relationship of
atropine.
A dose of methomyl corresponding to 50% of the median lethal dose was
given intraperitoneally to rats. Ventilation at rest was assessed using whole
body plethysmography and core body temperature using infra-red telemetry.
The central or peripheral origin was assessed comparing the effect of
equipotent doses of atropine and methylatropine. The effects of dose of
atropine ranging from 1 to 10 mg/kg were assessed. Total cholinesterase
activities were determined using a radiometric method.
From 5 to 150 minutes post-injection, methomyl induced significant clinical
symptoms, including significant decreases in respiratory frequency, which
resulted from a significant increase in expiratory time. Methomyl induced a
significant inhibition of brain total cholinesterase activities; meanwhile,
atropine, but not methylatropine, completely reversed methomyl-induced
respiratory toxicity. The dose-effect study showed that the efficient dose of
atropine resulting in lowest adverse effects was 3 mg/kg while greater doses
were efficient but induced significant adverse effects.
Decrease in brain cholinesterase activities accompanied by a positive effect of
atropine, but not methylatropine, suggests a central origin of methomylinduced
respiratory toxicity. The 3 mg/kg single atropine dose yielded the best
compromise between antidotal activity and intrinsic effects.