Gaylor D W, Culp S J, Goldstein L S, Beland F A
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Risk Anal. 2000 Feb;20(1):81-5. doi: 10.1111/0272-4332.00008.
Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per microgram per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.
使用B6C3F1雌性小鼠进行了为期两年的慢性生物测定，这些小鼠被喂食了来自人造煤气废物场地的两种不同煤焦油混合物或苯并(a)芘（BaP）的几种浓度。该研究的目的是通过使用传统的监管方法来获得煤焦油混合物的癌症效力估计值，以用于人造煤气废物场地的修复。第二个目的是研究使用单一强效致癌物（在这种情况下为苯并(a)芘）的浓度来估计煤焦油混合物相对风险的有效性。研究表明，当煤焦油混合物中BaP的浓度大于6300 ppm时，BaP主导癌症风险。在这种情况下，最敏感的组织部位是前胃。使用低剂量线性外推法，基于前胃肿瘤，估计人类终生癌症风险为：风险<1.03×10⁻⁴（总饮食中煤焦油的ppm）+240×10⁻⁴（总饮食中BaP的ppm）。如果煤焦油混合物中BaP的浓度低于6300 ppm（更常见的情况），那么肺癌提供了最大的估计风险上限，风险<2.55×10⁻⁴（总饮食中煤焦油的ppm），且BaP对肺癌没有影响。根据这项良好实验室规范（GLP）研究，终生经口接触苯并(a)芘的癌症效力（斜率因子）上限为每千克体重每天每微克1.2×10⁻³，而美国环境保护局综合风险信息系统中列出的当前值为每千克体重每天每微克7.3×10⁻³。
