Melnick R L, Sills R C
National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA.
Chem Biol Interact. 2001 Jun 1;135-136:27-42. doi: 10.1016/s0009-2797(01)00213-7.
1,3-Butadiene, isoprene (2-methyl-1,3-butadiene), and chloroprene (2-chloro-1,3-butadiene) are high-production-volume chemicals used mainly in the manufacture of synthetic rubber. Inhalation studies have demonstrated multiple organ tumorigenic effects with each of these chemicals in mice and rats. Sites of tumor induction by these epoxide-forming chemicals were compared to each other and to ethylene oxide, a chemical classified by the National Toxicology Program (NTP) and by the International Agency for Research on Cancer (IARC) as carcinogenic to humans. For this group of chemicals, there are substantial species differences in sites of neoplasia; neoplasia of the mammary gland is the only common tumorigenic effect in rats and mice. Within each species, there are several common sites of tumor induction; these include the hematopoietic system, circulatory system, lung, liver, forestomach, Harderian gland, and mammary gland in mice, and the mammary gland and possibly the brain, thyroid, testis, and kidney in rats. For studies in which individual animal data were available, mortality-adjusted tumor rates were calculated, and estimates were made of the shape of the exposure-response curves and ED10 values (i.e. exposure concentrations associated with an excess risk of 10% at each tumor site). Most tumorigenic effects reported here were consistent with linear or supralinear models. For chloroprene and butadiene, the most potent response was for the induction of lung neoplasms in female mice, with ED10 values of 0.3 ppm. Based on animal cancer data, isoprene and chloroprene are listed in the NTP's Report on Carcinogens (RoC) as reasonably anticipated to be a human carcinogen. Butadiene is listed in the RoC as known to be a human carcinogen 'based on sufficient evidence of carcinogenicity from studies in humans, including epidemiological and mechanistic information', with support from experimental studies in laboratory animals. Epidemiology data for isoprene and chloroprene are not considered adequate to evaluate the potential carcinogenicity of these agents in humans.
1,3 - 丁二烯、异戊二烯（2 - 甲基 - 1,3 - 丁二烯）和氯丁二烯（2 - 氯 - 1,3 - 丁二烯）是高产量化学品，主要用于合成橡胶的制造。吸入研究已证明，这些化学品中的每一种在小鼠和大鼠中都具有多种器官致癌作用。将这些形成环氧化物的化学品的肿瘤诱导部位相互比较，并与环氧乙烷进行比较，环氧乙烷被美国国家毒理学计划（NTP）和国际癌症研究机构（IARC）归类为对人类致癌的化学品。对于这组化学品，肿瘤形成部位存在显著的物种差异；乳腺肿瘤是大鼠和小鼠中唯一常见的致癌作用。在每个物种中，有几个常见的肿瘤诱导部位；这些部位包括小鼠的造血系统、循环系统、肺、肝、前胃、哈德氏腺和乳腺，以及大鼠的乳腺，可能还有脑、甲状腺、睾丸和肾脏。对于有个体动物数据的研究，计算了死亡率调整后的肿瘤发生率，并对暴露 - 反应曲线的形状和ED10值（即每个肿瘤部位与10%额外风险相关的暴露浓度）进行了估计。此处报告的大多数致癌作用与线性或超线性模型一致。对于氯丁二烯和丁二烯，最显著的反应是在雌性小鼠中诱导肺肿瘤，ED10值为0.3 ppm。根据动物癌症数据，异戊二烯和氯丁二烯被列入NTP的致癌物报告（RoC），被合理预期为人类致癌物。丁二烯被列入RoC，被列为“基于来自人类研究的充分致癌证据，包括流行病学和机制信息”的已知人类致癌物，并得到实验动物研究的支持。异戊二烯和氯丁二烯的流行病学数据不足以评估这些物质对人类的潜在致癌性。
