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.

中文翻译：

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狗农药研究中血清碱性磷酸酶活性增加的毒理学意义：在日本评估的毒理学数据分析。

血清碱性磷酸酶（ALP）活性增加是人和实验动物肝胆损伤的指标。实际上，在犬用农药的毒性研究中经常会遇到ALP增加而没有其他肝毒性变化的情况。在这里，我们分析了由日本食品安全委员会评估为206种农药的ALP升高的毒理学意义，作为其风险评估过程中的毒理学评估报告。我们的分析表明，狗（108/206）比大鼠（36/206）的ALP升高更为频繁。在108种农药中的87种中，观察到狗的肝毒性增加了ALP。但是，增加的ALP与某些类型的肝毒性没有特异性关系，并且不是肝毒性的敏感标志物。在显示出肝毒性的87种农药中，约有50％也会引起肝脏肥大。除肝脏重量增加和/或肝脏肥大以外，其余21种农药均未见肝毒性变化。这21种农药中的大多数是啮齿类动物的苯巴比妥样肝代谢酶诱导剂。这些结果表明，如果没有肝毒性的发现，增加的ALP含量并不是犬肝毒性的指标。该分析为狗中ALP的毒理学意义提供了新的解释，并可能有助于农药的毒理学评估。这些结果表明，如果没有肝毒性的发现，增加的ALP并不是犬肝毒性的指标。该分析为狗中ALP的毒理学意义提供了新的解释，并可能有助于农药的毒理学评估。这些结果表明，如果没有肝毒性的发现，增加的ALP并不是犬肝毒性的指标。该分析为狗中ALP的毒理学意义提供了新的解释，并可能有助于农药的毒理学评估。