Induction of anticholinesterase tolerance in rats with doses of disulfoton that produce no cholinergic signs.

The induction of anticholinesterase tolerance has, in the past, been achieved by using multiple doses of organophosphorus ester insecticides that initially caused cholinergic signs. The purpose of this study was to ascertain whether anticholinesterase tolerance could be induced with doses of an anticholinesterase that produced no overt cholinergic signs. Rats were fed diets containing 0, 7.5, or 20 ppm disulfoton. Animals fed at the 7.5 ppm level were without cholinergic signs throughout the period of feeding. Rats from this group were significantly more resistant to the lethal effect of carbachol than rats given the control diet after 58 and 62 d on the diet. Animals fed 20 ppm disulfoton in the diet initially showed signs that gradually disappeared with time on the diet. Rats fed at this level were more resistant to the lethal effect of carbachol than controls on all challenge dates (30, 45, 58, and 62 d on the diets) and more resistant than animals fed 7.5 ppm only on d 38 and 45. Thus the organophosphorus ester insecticide disulfoton, fed to rats in a dietary concentration that depressed acetylcholinesterase but was insufficient to cause cholinergic signs, induced tolerance to the lethal effects of carbachol. The length of time on an experimental diet before resistance to carbachol could be demonstrated was greater for the experimental group given 7.5 ppm disulfoton than the group given 20 ppm disulfoton in the diet.