The use of dogs as second species in regulatory testing of pesticides I. interspecies comparison

Abstract

The relevance of studies in dogs on regulatory testing of pesticides was 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 Federal Institute of Health Protection of Consumers and Veterinary Medicine (BgVV), the competent national authority in Germany. At first the relevance of the no-observed-effect levels (NOEL) for safety assessment was evaluated for each chemical in 4-week (subacute), 13-week (subchronic) 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 similar. 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. When the lowest-observed-effect level (LOEL) was evaluated in animal species, the dog was the most sensitive in ~15% of the studies. Mice were found to be the most sensitive species only in ~1% of the studies on 216 pesticides. Comparison of organ specific toxicity at the LOEL in subacute studies on fungicides and herbicides revealed a poor correlation of target- specific organ toxicity across species. However, in the subchronic and chronic studies (13 and 52/104 weeks) no significant differences in species- specific organ toxicity were observed in the three species rat, mouse and dog. The only exception were haematoxic effects in chronic studies on herbicides, which were more frequent in dogs (40%) than in rats and mice (20%). The results support the established concept that studies on dogs and rats are important for the safety assessment of pesticides, while studies on mice do not provide further information, except for detection of an oncogenic potential which is a further controversial issue. Further analysis of subacute, subchronic and chronic studies in dogs should reveal if all of the studies are essential for safety assessment of pesticides.