Rees E D, Shuck A E, Lowry J Q, Smith T M, Lipscomb H
J Environ Pathol Toxicol. 1979 Jul-Aug;2(6):1475-85.
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.
在24小时时进行评分，静脉注射给幼鼠的β-丙内酯溶液的半数致死量为225±55毫克/千克。在对长-伊文斯和斯普拉格-道利两种品系的雄性和雌性大鼠单次静脉注射（100毫克/千克 = 1.4毫摩尔/千克）β-丙内酯24小时后，中期骨髓细胞染色体中发现的断裂发生率较低（8.8%，而对照组为5.0%）。s5染色体优先受损。200毫克/千克的剂量使发生率适度增加至11.3%。相比之下，单次静脉注射苯并(a)芘（40毫克/千克 = 0.16毫摩尔/千克）产生的断裂发生率为19%。在长期实验中，在6周内多次（五次）静脉注射（每次100毫克/千克）β-丙内酯，在接下来的12 - 13个月中，37只动物中仅引发了两个肿瘤（一个氯白血病和一个乳腺纤维腺瘤）。相比之下，四次注射苯并(a)芘（40毫克/千克）在斯普拉格-道利雌性大鼠中产生的乳腺肿瘤发生率比β-丙内酯高14倍。骨髓细胞染色体检查表明，除了一只动物因S1三体导致一致的43条染色体核型外，早期β-丙内酯处理未导致明显的染色体变化；该动物未出现肿瘤。早期用苯并(a)芘处理导致断裂发生率持续且显著升高。静脉注射β-丙内酯在大鼠中的致癌和致断裂作用均较低，其程度与苯并(a)芘产生的作用不可比。
