Evaluation of Necessity of 1-year Toxicity Study in Dogs - development of the New Tiered Approach for Toxicity Studies of Pesticide Considering Species Difference in "toxicity profile" and "toxicity dose-response".

Recently, a long-term (1-year) dog toxicity study has not been a mandatory toxicity study for application of agricultural chemical in the United States (US) and the European Union (EU). This study was conducted to propose a guide for making science-based judgement on the necessity of long-term dog toxicity study, which is one of required toxicity studies at toxicological evaluation in Japanese pesticide regulation system. In order to carry out the proposal we analyzed the results of toxicity studies including subacute (3-month) toxicity study in dogs or toxicity studies in other species in the pesticide evaluation reports published by the Food Safety Commission of Japan (FSCJ), the responsible regulatory body for toxicological evaluation of pesticides in food. In the analysis of evaluation reports of 286 pesticides ADI (acceptable daily intake) of 93 pesticides (32.5%) were established based on dog studies. The ADIs of 74 pesticides among them, however were not considered to have a big influence if the long-term dog toxicity study was omitted. With regard to the other four agents the possibility that the long-term dog study becomes unnecessary was considered by adding detailed examination. With respect to the remaining 15 agents, we could not judge that long-term dog study were unnecessary. The analysis indicated that the dog long term test could be omitted in most cases. On the other hand, it should be considered carefully necessity of the long-term dog study when the toxicological profiles observed in dogs and rats were different, when the toxicity susceptibility in dogs was considered high, when no no-observed-adverse-effect level (NOAEL) is specified in subacute toxicity study in dogs or when bioaccumulation in dogs is concerned. We also noted that the studies already conducted for pesticide registered previously should be used for their hazard evaluation.