Kaneko T, Wang P Y, Sato A
Department of Environmental Health, Medical University of Yamanashi, Tamaho, Japan.
Int J Occup Med Environ Health. 1998;11(1):81-98.
The development of occupational exposure limits (OELs) in Japan is discussed by describing the OELs of two chemical compounds, benzene and trichloroethylene, as typical examples. As for benzene, sufficient epidemiological evidence has accumulated indicating that benzene is a human carcinogen. To establish the OEL for benzene, the OEL committee of the Japan Society for Occupational Health (JSOH) selected 9 cases of acute myeloic or monocytic leukemia out of the 14 cases of leukemia in the Pliofilm cohort, adopted the exposure estimate of Paustenbach et al. (52), and calculated the risk of benzene-induced leukemia by means of an average relative risk model. The lifetime risk of leukemia by exposure to benzene at 1 ppm for 40 years was calculated as 0.762 x 10(-3) with a 95% confidence interval between 0.621 x 10(-3) and 0.98.10(-3). The benzene level that causes one lifetime excess death from leukemia among 1,000 workers exposed to benzene for 40 years was 1.31 ppm, with a 95% confidence interval between 1.01 and 1.61 ppm. The OEL committee decided that benzene exposure should be controlled by a reference value corresponding to a lifetime risk (10(-3) or 10(-4)) of leukemia rather than by a time-weighted average (TWA) concentration. The committee has proposed that the benzene exposure level corresponding to the lifetime risk of 10(-3) is 1 ppm and that corresponding to the risk of 10(-4) is 0.1 ppm. In 1995, the International Agency for Research on Cancer (IARC) changed the carcinogenicity classification of trichloroethylene from Group 3 (not classifiable as to carcinogenicity to humans) to Group 2A (probably carcinogenic to humans). The OEL committee of the JSOH, however, reached the conclusion that since it has not been confirmed that trichloroethylene is a human carcinogen, and since carcinogenicity, if any, may be based on an epigenetic rather than genotoxic mechanism, it is not appropriate to establish the OEL of trichloroethylene presupposing that trichloroethylene is a carcinogen. The judgment of the OEL committee is that the OEL for trichloroethylene should be established on other than carcinogenicity findings, particularly on the basis of its neurological effects. In the light of accumulated evidence that a long-term exposure to trichloroethylene at 50 ppm will cause neurotoxic effects to industrial workers, the OEL committee has proposed 25 ppm (135 mg/m3) as a reference value for work environments. Finally, we propose that the general environmental air standards of benzene and trichloroethylene should be about 1/1,000 of the respective reference values for work environment.
通过将苯和三氯乙烯这两种化合物的职业接触限值作为典型例子进行描述，来探讨日本职业接触限值（OELs）的制定情况。对于苯，已有充分的流行病学证据表明其为人类致癌物。为确定苯的职业接触限值，日本职业卫生学会（JSOH）的职业接触限值委员会从普立菲尔姆队列研究中的14例白血病病例中选取了9例急性髓性或单核细胞白血病病例，采用了保斯滕巴克等人（52）的暴露估计值，并通过平均相对风险模型计算苯致白血病的风险。对于40年中暴露于1 ppm苯的情况，计算出白血病的终生风险为0.762×10⁻³，95%置信区间为0.621×10⁻³至0.98×10⁻³。在40年中接触苯的1000名工人中，导致1例白血病超额终生死亡的苯水平为1.31 ppm，95%置信区间为1.01至1.61 ppm。职业接触限值委员会决定，苯的接触应通过与白血病终生风险（10⁻³或10⁻⁴）相对应的参考值来控制，而非通过时间加权平均（TWA）浓度。该委员会提议，终生风险为10⁻³时对应的苯接触水平为1 ppm，风险为10⁻⁴时对应的苯接触水平为0.1 ppm。1995年，国际癌症研究机构（IARC）将三氯乙烯的致癌性分类从3类（无法分类为对人类致癌）改为2A类（可能对人类致癌）。然而，JSOH的职业接触限值委员会得出结论，由于尚未证实三氯乙烯是人类致癌物，且其致癌性（如果有的话）可能基于表观遗传而非基因毒性机制，因此在假定三氯乙烯为致癌物的前提下制定其职业接触限值是不合适的。职业接触限值委员会的判断是，三氯乙烯的职业接触限值应基于致癌性以外的数据来制定，特别是基于其神经学效应。鉴于有证据表明长期暴露于50 ppm的三氯乙烯会对产业工人造成神经毒性影响，职业接触限值委员会提议将25 ppm（135 mg/m³）作为工作环境的参考值。最后，我们提议苯和三氯乙烯的一般环境空气标准应分别约为工作环境参考值的1/1000。
