Abstract
The effects of prolonged chemical treatment with cyclophosphamide and 6-mercaptopurine were investigated in the dominant lethal test system. Groups of 15 male Holtzman rats were given 5 daily i.p. injections of the compounds per week for 10 weeks; dose levels were 0 (water), 5.0, 10.0 and 20.0 mg/kg in the cyclophosphamide study and 0 (dimethylsulfoxide), 12.5, 25.0 and 50.0 mg/kg in the 6-mercaptopurine study. Each study also contained a group given i.p. injections of triethylenemelamine (0.025 mg/kg), the positive control compound, which was diluted in water. After the final injection, each male rat was housed with 2 virgin females per week for 2 weeks. Females were killed 14 days from the midweek of cohousing and uterine contents were examined to evaluate the numbers of total implants, dead implants, dead implants per total implants and females with 1 or more, or 2 or more, dead implants. Results from the cyclophosphamide study indicated a positive dominant lethal effect in both weeks of mating. Negative results were obtained for all levels of 6-mercaptopurine treatment for both weeks, with the exception of 1 aberrant value at the 25.0-mg/kg level for week 1.
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