Effects of topical fenthion on blood cholinesterase and vagal tone in dogs.

A 20% fenthion (0,0-dimethyl-0-(3-methyl-4-(methylthio)-phenyl) phosphorothionate) formulation was applied topically to dogs at 8 mg/kg, 2 treatments at 14-day intervals, and 33 mg/kg, 4 treatments at 7-day intervals. Control dogs received 4 treatments at 7-day intervals of the proprietary vehicle. Following the last dose, the dogs were observed for a 14-day period. Plasma cholinesterase (ChE) exhibited a significant dose-related response with maximum inhibition to 52% and 24% of pre-dose activity occurring 4 days after the final fenthion treatment of 8 and 33 mg/kg, respectively. Erythrocyte ChE activity showed a downward trend to 32% of normal activity measured 9 days following the last treatment of fenthion at 33 mg/kg. No cholinomimetic effects were observed. All dogs were challenged with atropine sulfate (0.02 mg/kg, sc) on the last day of the observation period. A 5 min electrocardiogram was analyzed to estimate V as that portion of the variance in the R-R intervals corresponding with the normal respiratory frequency band for dogs. The mean heart period, mean heart period variance, and mean of V had significant change when measured across time in the atropine challenge (0, 25, 70, and 100 min) with a pronounced decrease at 25 min. An attenuation of the V measure in the fenthion-treated groups indicated an altered muscarinic response to atropine from prior subacute fenthion exposure.