Valberg P A, Watson A Y
Gradient Corporation, Cambridge, Massachusetts, USA.
Regul Toxicol Pharmacol. 1996 Aug;24(1 Pt 1):30-44. doi: 10.1006/rtph.1996.0062.
Chronic inhalation of diesel exhaust (DE) causes lung tumors in rats; epidemiologic studies suggest that DE may be a potential human carcinogen. We compared the DE unit risks for human lung cancer as derived by Smith and Stayner (1991), Hattis and Silver (1992), Pepelko and Chen (1993), California Environmental Protection Agency, Office of Environmental Health Hazard Assessment (1994), and the U.S. Environmental Protection Agency (USEPA) (1994). All five sets of authors used identical rat bioassay data (Mauderly et al., 1987). Although different in detail, the dose-response models were uniformly linear and nonthreshold. However, each set of authors chose a different approach in relating the rat data to DE unit risk in humans. The predicted unit risks for continuous lifetime exposure to 1 microgram/m3 DE differed by an 80-fold factor between the highest [8 x 10(-4), Hattis and Silver] and the lowest [0.1 x 10(-4), Pepelko and Chen]. The choice of dose-input parameters and how each group treated particle overload were the major factors affecting the different risk estimates. Several unanswered questions undermine the current use of the rat bioassay for DE risk assessment: (1) Differences in emission products and exposure scenarios between laboratory studies and human exposure, (2) occurrence of an apparent threshold in the rat-lung-tumor response, (3) uncertainty as to the appropriate lung-dose metric and its low-dose extrapolation, (4) the role of lung overload, and (5) the cause of species-specific biological susceptibility.
长期吸入柴油机废气（DE）可导致大鼠肺部肿瘤；流行病学研究表明，DE可能是一种潜在的人类致癌物。我们比较了史密斯和斯泰纳（1991年）、哈蒂斯和西尔弗（1992年）、佩佩尔科和陈（1993年）、加利福尼亚环境保护局环境卫生危害评估办公室（1994年）以及美国环境保护局（USEPA）（1994年）得出的人类肺癌DE单位风险。所有五组作者都使用了相同的大鼠生物测定数据（莫德雷等人，1987年）。尽管细节不同，但剂量反应模型均为线性且无阈值。然而，每组作者在将大鼠数据与人类DE单位风险联系起来时选择了不同的方法。预测的连续终生暴露于1微克/立方米DE的单位风险在最高值[8×10⁻⁴，哈蒂斯和西尔弗]和最低值[0.1×10⁻⁴，佩佩尔科和陈]之间相差80倍。剂量输入参数的选择以及每组对颗粒过载的处理方式是影响不同风险估计的主要因素。几个未解决的问题削弱了目前大鼠生物测定在DE风险评估中的应用：（1）实验室研究与人类暴露之间排放产物和暴露场景的差异，（2）大鼠肺部肿瘤反应中明显阈值的出现，（3）合适的肺部剂量指标及其低剂量外推的不确定性，（4）肺部过载的作用，以及（5）物种特异性生物易感性的原因。
