Toxicology studies in mice, beagle dogs and rhesus monkeys given chlorozotocin (NSC 178, 248)

Chlorozotocin was studied for toxic effects in beagle dogs and rhesus monkeys. The results are the subject of this report. The compound was administered i.v. as single and 5 daily doses in dogs and monkeys; and, in dogs, as 10 consecutive daily doses, once weekly for 6 weeks and for 5 daily doses followed by 9 days rest repeated 3 times. The most prominent toxicities in both species were dose-related renal tubular lesions. These appeared as a necrosis at the most toxic levels and a nephrosis at lower doses. The latter change was also seen in animals surviving higher doses but only after a 6-week posttreatment period. Bone marrow hypoplasia and lymphoid atrophy were other common findings at the highest doses in both species. The same general pattern of toxicity appeared in extended treatment studies in dogs, but also included aspermatogenesis. Signs of hepatotoxicity were seen in dogs at the highest dose levels, while monkeys receiving lethal doses also evidenced a toxic gastroenteritis. A single monkey had a diabetic response following 1 treatment with a high non-lethal dose. Renal lesions found in mice following acute, single dose administration were similar to those described for the larger laboratory animals.