Preclinical toxicologic evaluation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA) in mice, dogs, and monkeys.

Male mice (CDF1) in a single-treatment schedule, male and female dogs in a single-treatment and in three multiple-treatment schedules, and male and female monkeys in one multiple-treatment schedule were used to evaluate the toxicity of 4'-(9-acridinylamino)methanesulfon-m-anisidide. Vehicle controls receiving anhydrous N,N-dimethylacetamide plus lactic acid were included in the dog and monkey studies. The liver was the major target organ of toxicity in mice. Lymphoid depletion and generalized bone marrow suppression were the most sensitive indicators of toxicity in dogs and monkeys. At high toxic doses, CNS and intestinal toxic effects were present. Hepatotoxic effects were most prominent in dogs after single iv injections. Multiple-dose regimens were more toxic than single-dose regimens in dogs, but inclusion of rest periods between multiple-treatment periods or reduction of the dose attenuated the toxic effects. The monkey was more resistant to drug toxicity than the dog. Local tissue reaction studies in guinea pigs and rabbits suggested that local irritation responses observed may have been due to the acidity of the drug and vehicle solutions.