Comparison of the clastogenic and carcinogenic effects of intravenous beta-propiolactone and benzo(a)pyrene in rats.

Scored at 24 hours, the LD-50 of a solution of beta-propiolactone administered intravenously to young rats was 225 +/- 55 mg/kg. Twenty-four hours after a single intravenous injection (100 mg/kg = 1.4 m mole/kg) of beta-propiolactone into male and female rats of both the Long-Evans and Sprague-Dawley strains, the incidence of breaks found in the chromosomes of metaphase marrow cells was low (8.8 percent vs. 5.0 percent in controls). The s5 chromosomes were preferentially damaged. A 200 mg/kg dose increased the incidence modestly to 11.3 percent. In comparison, a single intravenous dose of benzo(a)pyrene (40 mg/kg = 0.16 m mole/kg) produced a break incidence of 19 percent. In long-term experiments multiple (five) intravenous injections (100 mg/kg each) of beta-propiolactone given in a 6 week period elicited only two neoplasms (a chloro-leukemia and a mammary fibroadenoma) among 37 animals during the following 12-13 months. In contrast, four injections of benzo(a)pyrene (40 mg/kg) produced a 14-times greater mammary tumor incidence in the Sprague-Dawley female rat than did beta-propiolactone. Marrow cell chromosome examination indicated no significant chromosomal changes due to the earlier beta-propiolactone treatment except for one animal with a consistent 43-chromosome karyotype resulting from S1 trisomy; no neoplasm was evident in that animal. Earlier treatment with benzo(a)pyrene produced a persistent and significant elevation in break incidence. Both the carcinogenic and clastogenic effects of intravenous beta-propiolactone are low in rats and are not comparable in magnitude to those produced by benzo(a)pyrene.