Repace J L, Lowrey A H
U.S. Environmental Protection Agency, Washington, D.C. 20460.
Risk Anal. 1993 Aug;13(4):463-75. doi: 10.1111/j.1539-6924.1993.tb00747.x.
Environmental tobacco smoke (ETS) has recently been determined by U.S. environmental and occupational health authorities to be a human carcinogen. We develop a model which permits using atmospheric nicotine measurements to estimate nonsmokers' ETS lung cancer risks in individual workplaces for the first time. We estimate that during the 1980s, the U.S. nonsmoking adult population's median nicotine lung exposure (homes and workplaces combined) was 143 micrograms (micrograms) of nicotine daily, and that most-exposed adult nonsmokers inhaled 1430 micrograms/day. These exposure estimates are validated by pharmacokinetic modeling which yields the corresponding steady-state dose of the nicotine metabolite, cotinine. For U.S. adult nonsmokers of working age, we estimate median cotinine values of about 1.0 nanogram per milliliter (ng/ml) in plasma, and 6.2 ng/ml in urine; for most-exposed nonsmokers, we estimate cotinine concentrations of about 10 ng/ml in plasma and 62 ng/ml in urine. These values are consistent to within 15% of the cotinine values observed in contemporaneous clinical epidemiological studies. Corresponding median risk from ETS exposure in U.S. nonsmokers during the 1980s is estimated at about two lung cancer deaths (LCDs) per 1000 at risk, and for most-exposed nonsmokers, about two LCDs per 100. Risks abroad appear similar. Modeling of the lung cancer mortality risk from passive smoking suggests that de minimis [i.e., "acceptable" (10(-6))], risk occurs at an 8-hr time-weighted-average exposure concentration of 7.5 nanograms of ETS nicotine per cubic meter of workplace air for a working lifetime of 40 years. This model is based upon a linear exposure-response relationship validated by physical, clinical, and epidemiological data. From available data, it appears that workplaces without effective smoking policies considerably exceed this de minimis risk standard. For a substantial fraction of the 59 million nonsmoking workers in the U.S., current workplace exposure to ETS also appears to pose risks exceeding the de manifestis risk level above which carcinogens are strictly regulated by the federal government.
美国环境与职业健康部门最近认定，环境烟草烟雾（ETS）是一种人类致癌物。我们开发了一个模型，首次允许利用大气尼古丁测量值来估算个体工作场所中不吸烟者接触ETS患肺癌的风险。我们估计，在20世纪80年代，美国不吸烟成年人群体（家庭和工作场所合计）尼古丁肺部暴露的中位数为每天143微克，而暴露最多的成年不吸烟者吸入量为每天1430微克。这些暴露估计值通过药代动力学模型得到验证，该模型得出了尼古丁代谢物可替宁的相应稳态剂量。对于美国处于工作年龄的成年不吸烟者，我们估计其血浆中可替宁的中位数约为每毫升1.0纳克，尿液中为6.2纳克；对于暴露最多的不吸烟者，我们估计其血浆中可替宁浓度约为10纳克/毫升，尿液中为62纳克/毫升。这些值与同期临床流行病学研究中观察到的可替宁值相差不超过15%。据估计，20世纪80年代美国不吸烟者因接触ETS而导致的相应中位数风险约为每1000名有风险者中有两例肺癌死亡（LCD），而对于暴露最多的不吸烟者，约为每100人中有两例LCD。国外的风险似乎类似。对被动吸烟导致肺癌死亡风险的建模表明，对于40年的工作寿命而言，在工作场所空气中8小时时间加权平均暴露浓度为每立方米7.5纳克ETS尼古丁时，会出现极小风险（即“可接受”风险，10^(-6)）。该模型基于由物理、临床和流行病学数据验证的线性暴露-反应关系。从现有数据来看，没有有效吸烟政策的工作场所大大超过了这一极小风险标准。对于美国5900万不吸烟工人中的很大一部分来说，目前工作场所接触ETS似乎也带来了超过明显风险水平的风险，超过这一水平的致癌物受到联邦政府的严格监管。
