MAXIMUM DOSAGE LEVEL IN TESTING LOW-TOXICITY CHEMICALS FOR CARCINOGENICITY IN RODENTS

Owing to the lack of sufficient theoretical and empirical information, the initial guidelines regarding animal carcinogenicity testing of ch emicals adopted the most conservative approach possible. One of the re commendations was that non-toxic chemicals be tested at a level as hig h as 5% of the diet. Since then, a wealth of information has been accu mulated, which indicates that such highly exaggerated dosage levels ar e not only unnecessary but produce scientifically misleading and regul atorily detrimental results that impede the development and evaluation of useful chemicals, including human drugs. This paper presents the r ationale supporting the necessity of revision of the outdated maximum level of dietary exposure from 5% to 1% or 1000 mg kg-1 day-1 when the test chemical is administered in drinking water or by gavage.