Preston R J, Abernethy D J
Chemical Industry Institute of Toxicology, Research Triangle Park, NC.
IARC Sci Publ. 1993(127):225-33.
A large number of studies have been reported on the genotoxicity of styrene in vitro and in vivo and the potential effects on humans of occupational exposure. Because of a variety of technical problems and difficulties in data interpretation, it has not been clearly established whether styrene can induce chromosomal aberrations and/or sister chromatid exchange (SCE) in vivo in animals or humans. The importance of clarifying this situation led to the development of the study described in this paper. Male Fischer 344 rats were exposed to styrene at concentrations of 150, 500 or 1000 ppm for 6 h/day on 5 days/week for 4 weeks. A negative control (air) was included. An additional control (ethylene oxide, 150 ppm) group was included in an attempt to establish the usefulness of rat lymphocytes for cytogenetic analysis in this protocol of long-term exposure by inhalation. The choice of agent and of exposure was based on the expectation that they would produce a positive response for SCE and/or chromosomal aberrations under the assay conditions used. Peripheral blood samples were drawn at 1, 2, 3 and 4 weeks of exposure and at 4 weeks after the end of exposure. Cultures were established, and SCE (second mitosis) and chromosomal aberrations (first mitosis) were analysed. The frequency of chromosomal aberrations was not increased over that in the air controls in the animals exposed to styrene or ethylene oxide at any of the sampling times. Styrene did not induce SCE at any of the concentrations or sampling times; however, the frequency of SCE was increased following exposure to ethylene oxide at all sampling times, with a positive exposure-response relationship with time of exposure as the variable. The data are compared with other, similar sets reported in the literature, and their significance for predicting responses in people occupationally exposed to styrene is discussed.
关于苯乙烯的体外和体内遗传毒性以及职业暴露对人体的潜在影响，已有大量研究报告。由于存在各种技术问题和数据解读困难，目前尚未明确苯乙烯是否能在动物或人体体内诱发染色体畸变和/或姐妹染色单体交换（SCE）。明确这一情况的重要性促使开展了本文所述的研究。将雄性Fischer 344大鼠暴露于浓度为150、500或1000 ppm的苯乙烯中，每天暴露6小时，每周暴露5天，持续4周。设置了阴性对照组（空气）。还设置了一个额外的对照组（环氧乙烷，150 ppm），试图确定在这种长期吸入暴露方案中大鼠淋巴细胞用于细胞遗传学分析的有效性。试剂和暴露方式的选择基于这样的预期，即在所用的检测条件下它们会对SCE和/或染色体畸变产生阳性反应。在暴露的第1、2、3和4周以及暴露结束后4周采集外周血样本。建立培养物，并分析SCE（第二次有丝分裂）和染色体畸变（第一次有丝分裂）。在任何采样时间，暴露于苯乙烯或环氧乙烷的动物中，染色体畸变频率均未高于空气对照组。在任何浓度和采样时间，苯乙烯均未诱发SCE；然而，在所有采样时间，暴露于环氧乙烷后SCE频率均增加，以暴露时间为变量存在阳性暴露-反应关系。将这些数据与文献中报道的其他类似数据集进行了比较，并讨论了它们对于预测职业性接触苯乙烯人群反应的意义。
