Toxicological significance of increased serum alkaline phosphatase activity in dog studies of pesticides: Analysis of toxicological data evaluated in Japan

Increased serum alkaline phosphatase (ALP) activity is an indicator of hepatobiliary damage in humans and experimental animals. Practically, increased ALP accompanied by no other hepatotoxic changes is often encountered in toxicity studies of pesticides in dogs. Here, we analyzed the toxicological significance of increased ALP in response to 206 pesticides evaluated by the Food Safety Commission of Japan as toxicological evaluation reports in their risk assessment process. Our analysis indicated that increased ALP was more frequent in dogs (108/206) than in rats (36/206). In 87 of 108 pesticides, increased ALP was observed with hepatotoxicity in dogs. However, increased ALP had no specific relationship with certain types of hepatotoxicity and was not a sensitive marker of hepatotoxicity. Approximately 50% of 87 pesticides showing hepatotoxicity also induced liver hypertrophy. No hepatotoxic changes were seen with the remaining 21 pesticides, other than increases in liver weight and/or liver hypertrophy. Most of these 21 pesticides were phenobarbital-like liver metabolism enzyme inducers in rodents. These results suggested that increased ALP was not an indicator of hepatotoxicity in dogs if hepatotoxic findings were absent. This analysis provided a new interpretation of the toxicological significance of ALP in dogs and could contribute to toxicological evaluation of pesticides.