Application of benzo(a)pyrene and coal tar tumor dose-response data to a modified benchmark dose method of guideline development.
Application of benzo(a)pyrene and coal tar tumor dose-response data to a modified benchmark dose method of guideline development.
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DOI：
10.1289/ehp.6427
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发表时间：
2004-10
影响因子：
10.4
通讯作者：
Pester BA
中科院分区：
文献类型：
--
作者：
Fitzgerald DJ;Robinson NI;Pester BA
传统上，多环芳烃（PAHs）暴露的癌症风险评估是通过对动物肿瘤数据应用保守线性化多阶段（LMS）模型来进行的，苯并(a)芘（BaP）被认为是多环芳烃混合物中最有效的致癌物。由于有人认为，LMS对剂量使用95%的低置信限是不必要的保守，剂量反应的低剂量线性至零的假设意味着明确的机制理解，以及“可接受的”癌症风险取决于政策决定，因此已经开发了一种替代的癌症风险评估方法。部分基于新兴的基准剂量（BMD）方法，我们使用的改进的BMD方法涉及将一套传统的数学模型应用于肿瘤剂量-反应数据。这样就可以推导出对应于5%额外肿瘤发生率（BMD0.05）的平均剂量，并应用若干修正因子以达到指导剂量，即被认为对人类终生暴露安全的日剂量。将改进的BMD方法应用于最近来自BaP摄入研究的小鼠前胃肿瘤数据表明，指导剂量为0.08 μg/kg/天。基于这一点以及对膳食中BaP的理解，并考虑到BaP是土壤中常见的污染物，因此通过土壤摄入对人类健康构成风险，我们建议BaP土壤指导值为5ppm（毫克/千克）。摄入含有多环芳烃和BaP的煤焦油混合物的小鼠肿瘤数据表明，肺肿瘤而不是前胃肿瘤最普遍，BaP含量不能解释肺肿瘤。这就对基于BaP的毒性等效因子用于评估复杂多环芳烃混合物风险的普遍使用提出了质疑。新出现的数据表明，另一种多环芳烃化合物- 7h -苯并(c)芴-可能是肺肿瘤的致癌物。
Assessment of cancer risk from exposure to polycyclic aromatic hydrocarbons (PAHs) has been traditionally conducted by applying the conservative linearized multistage (LMS) model to animal tumor data for benzo(a)pyrene (BaP), considered the most potent carcinogen in PAH mixtures. Because it has been argued that LMS use of 95% lower confidence limits on dose is unnecessarily conservative, that assumptions of low-dose linearity to zero in the dose response imply clear mechanistic understanding, and that “acceptable” cancer risk rests on a policy decision, an alternative cancer risk assessment approach has been developed. Based in part on the emerging benchmark dose (BMD) method, the modified BMD method we used involves applying a suite of conventional mathematical models to tumor dose–response data. This permits derivation of the average dose corresponding to 5% extra tumor incidence (BMD0.05) to which a number of modifying factors are applied to achieve a guideline dose, that is, a daily dose considered safe for human lifetime exposure. Application of the modified BMD method to recent forestomach tumor data from BaP ingestion studies in mice suggests a guideline dose of 0.08 μg/kg/day. Based on this and an understanding of dietary BaP, and considering that BaP is a common contaminant in soil and therefore poses human health risk via soil ingestion, we propose a BaP soil guideline value of 5 ppm (milligrams per kilogram). Mouse tumor data from ingestion of coal tar mixtures containing PAHs and BaP show that lung and not forestomach tumors are most prevalent and that BaP content cannot explain the lung tumors. This calls into question the common use of toxicity equivalence factors based on BaP for assessing risk from complex PAH mixtures. Emerging data point to another PAH compound—7H-benzo(c)fluorene—as the possible lung tumorigen.
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影响因子：
3.4
作者：
Boyd, HB;Pedersen, F;Samsoe-Petersen, L
通讯作者：
Samsoe-Petersen, L
影响因子：
10.4
作者：
Goldstein, LS;Weyand, EH;Rodriguez, LV
通讯作者：
Rodriguez, LV
影响因子：
3.8
作者：
CRUMP, KS
通讯作者：
CRUMP, KS
影响因子：
3.4
作者：
Dourson, ML;Felter, SP;Robinson, D
通讯作者：
Robinson, D
影响因子：
3.6
作者：
BRUNE, H;DEUTSCHWENZEL, RP;SCHMAHL, D
通讯作者：
SCHMAHL, D