THE USE OF DOGS AS 2ND SPECIES IN REGULATORY TESTING OF PESTICIDES I - INTERSPECIES COMPARISON

The relevance of studies in dogs on regulatory testing of pesticides w as examined retrospectively using data of 216 pesticides (acaricides, fungicides, growth regulators and hormones, herbicides, insecticides, molluscicides, nematicides, rodenticides, synergists for insecticides) submitted for regulatory purposes during the past 40 years to the Fed eral Institute of Health Protection of Consumers and Veterinary Medici ne (BgVV), the competent national authority in Germany. At first the r elevance of the no-observed-effect levels (NOEL) for safety assessment was evaluated for each chemical in 4-week (subacute), 13-week (subchr onic) and 52/104-week (chronic) toxicity studies carried out on dogs, rats and mice. After subchronic and chronic application of fungicides the sensitivity of rats and dogs to the toxic chemicals was quite simi lar. However, the dog was generally a more sensitive species to toxic effects of insecticides than rat and mouse. On the other hand the NOEL was lower in the rat than the dog in chronic studies on herbicides. W hen the lowest-observed-effect level (LOEL) was evaluated in animal sp ecies, the dog was the most sensitive in similar to 15% of the studies . Mice were found to be the most sensitive species only in similar to 1% of the studies on 216 pesticides. Comparison of organ specific toxi city at the LOEL in subacute studies on fungicides and herbicides reve aled a poor correlation of target-specific organ toxicity across speci es. However, in the subchronic and chronic studies (13 and 52/104 week s) no significant differences in species-specific organ toxicity were observed in the three species rat, mouse and dog. The only exception w ere haematoxic effects in chronic studies on herbicides, which were mo re frequent in dogs (40%) than in rats and mice (20%). The results sup port the established concept that studies on dogs and rats are importa nt for the safety assessment of pesticides, while studies on mice do n ot provide further information, except for detection of an oncogenic p otential which is a further controversial issue. Further analysis of s ubacute, subchronic and chronic studies in dogs should reveal if all o f the studies are essential for safety assessment of pesticides.