Abstract for TR-19

Bioassay of Procarbazine for Possible Carcinogenicity

CASRN: 366-70-1
Chemical Formula: C12H19N3O·ClH; C12H9N3O.ClH
Molecular Weight: 257.763
Synonyms/Common Names: N-iso-propyl-a-(2-methylhydrazino)-p-toluamide hydrochloride
Report Date: 1979

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Procarbazine is a methylhydrazine derivative which has been shown to have effective antineoplastic activity in advanced Hodgkin's disease and in oat-cell carcinoma of the lung. It has also been shown to have carcinogenic activity in rats and mice.

A bioassay of procarbazine for possible carcinogenicity was conducted by administering the test chemical by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice.

Groups of 34 or 35 males and 35 or 36 females of both species were administered procarbazine at one of two doses, either 15 or 30 mg/kg for rats, and either 6 or 12 mg/kg for mice. Injections were made three times per week for 26 weeks for the rats and 52 weeks for the mice. Following the periods of injection, the dosed animals were observed for a maximum period of 60 weeks for rats and 33 weeks for mice, depending on survival. Vehicle controls, used for statistical evaluation, consisted of 10 rats and 15 mice of each sex, administered saline solution on the same schedule as the test solution; the same numbers of rats and mice served as untreated controls. Pooled controls consisted of the vehicle controls from this bioassay together with the vehicle controls from two other bioassays similarly performed at the same laboratory. The pooled-control groups consisted of 40 rats of each sex and 45 mice of each sex. Surviving rats were killed at 86 weeks and surviving mice were killed at 85 weeks.

Mean body weights of low- and high-dose rats and of high-dose female mice were lower than those of the vehicle controls. Survival rates of both rats and mice showed significant dose-related trends.

In rats, malignant lymphomas, adenocarcinomas of the mammary gland, and the combination of olfactory neuroblastomas, adenocarcinomas, or carcinomas of the brain, olfactory bulb, or cerebrum were induced in statistically significant numbers.

In mice, malignant lymphomas or leukemias, olfactory neuroblastomas or undifferentiated carcinomas, alveolar/bronchiolar adenomas, and adenocarcinomas of the uterus were induced in statistically significant numbers.

It is concluded that under the conditions of this bioassay, procarbazine was carcinogenic for both Sprague-Dawley rats and B6C3F1 mice, producing several types of tumors in both of these two species.