Influence Factors to Be Considered on Establishment of the Reference Data of ALT, AST and ALP in Rats

Abstract

The present study investigated the possibility of providing data interchangeability among laboratories and to establish common reference values for each clinical chemistry parameter in rats. We analyzed the historical control data of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in untreated animals and those used as negative controls in non-clinical toxicity studies. The data were provided by 9 laboratories, which covered a study population of approximately 5,000 rats. The major factors contributing to the effects on ALT and AST were age and mode of measurement. The influence of age on ALT and AST values can be reduced by collecting data from a large number of male and female rats. It is also considered that common reference values can be established by classifying data by each mode of measurement or by standardization of measurement methods. On the basis of the significant differences between serum AST and plasma AST, it is considered necessary to use heparinized blood, which is not affected by the period from blood collection to plasma separation or by the methods of storage. The observed influences on ALP activity were age, sex, fasting/feeding behavior, and measurement mode, with these factors showing the greatest variation in the reference data. Accordingly, it is necessary to classify the data by each of these factors. As for measurement methods, N-methyl-D-glucamine (MEG) is expected to be used as the buffer of ALP measurement methods in rats.