As discussed in Chapter 6 (Hepatotoxicity), because the renal clearance of bilirubin is
very high in the rat the test is rarely sensitive enough to detect minor liver functional
Study design and regulatory requirements 13
change in rodents. Similarly, while gamma glutamyl transferase is a useful marker of
liver toxicity in the dog, an increase is rarely detected in rodents when exposed to a
hepatotoxic compound. Other tests suggested by regulatory authorities and professional
associations have also proved to be controversial.