Refinement of decision tree to assess the consequences of increased serum ALP in dogs: Additional analysis on toxicity studies of pesticides evaluated recently in Japan

Recently we provided a new interpretation that increased serum ALP in dogs is not adverse if no hepatotoxic finding coexists in the analysis of toxicity studies of over 200 pesticides evaluated in Japan (Yokoyama et al., 2019). We also proposed a decision tree to evaluate the adversity of the increased ALP. The present analysis was conducted to validate the reliability of this interpretation with 129 pesticides more recently evaluated. Before applying, the decision tree was revised to be consistent in all steps. The pesticides showed similar characterization of increased ALP to the previous analysis in that the increase was more frequent than in rats and that liver hypertrophy and hepatotoxicity commonly coexisted with an increase in ALP in dogs. When short- and long-term studies of 58 pesticides inducing ALP activity in dogs were applied to the revised tree, the increased ALP in 8 pesticides was judged not adverse in either study. The revision of the tree did not affect the NOAEL judgment of these pesticides; however, the revised routes contributed to the judgment more robustly. This study showed the reliability of our interpretation and applicability of the decision tree to evaluate the adversity of increased ALP in dogs.