Melnick R L, Sills R C, Portier C J, Roycroft J H, Chou B J, Grumbein S L, Miller R A
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Carcinogenesis. 1999 May;20(5):867-78. doi: 10.1093/carcin/20.5.867.
Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to 1,3-butadiene, a trans-species carcinogen, inhalation studies were performed with chloroprene to evaluate its carcinogenic potential in rats and mice. Groups of 50 male and female F344/N rats and 50 male and female B6C3F1 mice were exposed to 0, 12.8, 32 or 80 p.p.m. chloroprene (6 h/day, 5 days/week) for 2 years. Under these conditions, chloroprene was carcinogenic to the oral cavity, thyroid gland, lung, kidney and mammary gland of rats, and to the lung, circulatory system (hemangiomas and hemangiosarcomas), Harderian gland, kidney, forestomach, liver, mammary gland, skin, mesentery and Zymbal's gland of mice. Survival adjusted tumor rates in mice were fit to a Weibull model for estimation of the shape of the dose-response curves, estimation of ED10 values (the estimated exposure concentration associated with an increased cancer risk of 10%) and comparison of these parameters with those for 1,3-butadiene. Butadiene has been identified as a potent carcinogen in mice and has been associated with increased risk of lymphatic and hematopoietic cancer in exposed workers. Shape parameter values for most of the neoplastic effects of chloroprene and 1,3-butadiene were consistent with linear or supralinear responses in the area near the lowest tested exposures. The most potent carcinogenic effect of 1,3-butadiene was the induction of lung neoplasms in female mice, which had an ED10 value of 0.3 p.p.m. Since the ED10 value for that same response in chloroprene exposed mice was also 0.3 p.p.m., we conclude that the carcinogenic potency of chloroprene in mice is similar to that of 1,3-butadiene. Cancer potency of chloroprene is greater in the mouse lung than in the rat lung, but greater in the rat kidney than in the mouse kidney and nearly equivalent in the mammary gland of each species.
氯丁二烯（2-氯-1,3-丁二烯）是一种高产量化学品，几乎专门用于生产聚氯丁二烯（氯丁橡胶）弹性体。由于其结构与跨物种致癌物1,3-丁二烯相似，因此对氯丁二烯进行了吸入研究，以评估其在大鼠和小鼠中的致癌潜力。将50只雄性和雌性F344/N大鼠以及50只雄性和雌性B6C3F1小鼠分成几组，使其暴露于0、12.8、32或80 ppm的氯丁二烯中（每天6小时，每周5天），持续2年。在这些条件下，氯丁二烯对大鼠的口腔、甲状腺、肺、肾和乳腺具有致癌性，对小鼠的肺、循环系统（血管瘤和血管肉瘤）、哈德氏腺、肾、前胃、肝、乳腺、皮肤、肠系膜和耳下腺具有致癌性。对小鼠的生存调整肿瘤发生率拟合威布尔模型，以估计剂量反应曲线的形状、估计ED10值（与癌症风险增加10%相关的估计暴露浓度），并将这些参数与1,3-丁二烯的参数进行比较。丁二烯已被确定为小鼠中的一种强效致癌物，并且与接触工人患淋巴和造血系统癌症的风险增加有关。氯丁二烯和1,3-丁二烯的大多数肿瘤效应的形状参数值在最低测试暴露附近的区域与线性或超线性反应一致。1,3-丁二烯最显著的致癌作用是在雌性小鼠中诱发肺肿瘤，其ED10值为0.3 ppm。由于氯丁二烯暴露小鼠中相同反应的ED10值也是0.3 ppm，我们得出结论，氯丁二烯在小鼠中的致癌效力与1,3-丁二烯相似。氯丁二烯在小鼠肺中的致癌效力大于大鼠肺，但在大鼠肾中的致癌效力大于小鼠肾，并且在每个物种的乳腺中几乎相当。
