Melnick R L, Huff J, Chou B J, Miller R A
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Cancer Res. 1990 Oct 15;50(20):6592-9.
The carcinogenicity of inhaled 1,3-butadiene was evaluated in C57BL/6 x C3H F1 mice exposed to concentrations of this gas ranging from 6.25 to 625 ppm. Butadiene is a high production volume chemical, used mainly in the manufacture of synthetic rubber. In these 2-yr inhalation studies, a potent multisite carcinogenic response was observed, including neoplasms of the lung at concentrations as low as 6.25 ppm. Early occurrence and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm of butadiene reduced the number of animals at risk for the expression of later developing neoplasms at other sites; at lower exposure concentrations, dose responses were demonstrated for hemangiosarcomas of the heart and neoplasms of the lung, forestomach, Harderian gland, preputial gland, liver, mammary gland, and ovary. So far, no long-term studies on butadiene have been conducted at exposure concentrations that have not shown a carcinogenic response. In separate experiments with reduced exposure durations, butadiene induced neoplastic responses at multiple organ sites even after only 13 wk of exposure. Because of the correspondence between these animal data and recent epidemiology findings, there is a worldwide public health need to reevaluate current workplace exposure standards for 1,3-butadiene.
在暴露于浓度范围为6.25至625 ppm的1,3 - 丁二烯的C57BL/6 x C3H F1小鼠中评估了吸入1,3 - 丁二烯的致癌性。丁二烯是一种大量生产的化学品,主要用于合成橡胶的制造。在这些为期两年的吸入研究中,观察到了强烈的多部位致癌反应,包括在低至6.25 ppm的浓度下出现肺部肿瘤。暴露于625 ppm丁二烯的小鼠中致死性淋巴细胞淋巴瘤的早期发生和广泛发展减少了有机会在其他部位发生后期肿瘤的动物数量;在较低暴露浓度下,显示出心脏血管肉瘤以及肺部、前胃、哈德氏腺、包皮腺、肝脏、乳腺和卵巢肿瘤的剂量反应。到目前为止,尚未在未显示致癌反应的暴露浓度下对丁二烯进行长期研究。在暴露持续时间缩短的单独实验中,即使仅暴露13周后丁二烯也会在多个器官部位诱发肿瘤反应。由于这些动物数据与最近的流行病学研究结果相符,因此全球公共卫生领域有必要重新评估当前针对1,3 - 丁二烯的工作场所暴露标准。