Benchmark dose method is one of the most famous quantitative approaches available for toxicological risks prediction. However, it is not fully clear how occupational health professionals can use it for specific workplace scenarios requiring carcinogen risk assessment. The paper explores the hypothesis that benchmark dose method allows to effectively approximate dose–response data on carcinogenic response, providing reasonable estimations of risks in the situations when a choice between more complex models is not warranted for practical purposes. Three case studies were analyzed for the agents with different levels of scientific confidence in human carcinogenicity: carbon nanotubes, amosite asbestos, and glyphosate. For each agent, a critical study was determined, and a dose–response slope factor was quantified, based on the weighted average lower bound benchmark dose. The linear slope factors of 0.111 lifetime excess cases of lung carcinoma per mg/m³ of MWCNT‐7 (in rats exposure equivalent), 0.009 cases of mesothelioma per f/cc‐years of cumulative exposure to amosite asbestos, and 0.000094 cases of malignant lymphoma per mg/kg/day of glyphosate (in mice equivalent) were determined. The correlations between the proposed linear predictive models and observed data points were R = 0.96 (R² = 0.92) for carbon nanotubes, R = 0.97 (R² = 0.95) for amosite asbestos, and R = 0.89 (R² = 0.79) for glyphosate. In all three cases, the linear extrapolation yielded comparable level of risk estimations with the “best fit” nonlinear model; for nanoparticles and amosite asbestos, linear estimations were more conservative. By performing a simulation study, it was demonstrated that a weighted average benchmark dose expressed the highest correlation with multistage and quantal‐linear models.

中文翻译：

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使用基准剂量模型进行定量风险评估：碳纳米管、石棉、草甘膦

基准剂量法是可用于毒理学风险预测的最著名的定量方法之一。然而，目前尚不完全清楚职业卫生专业人员如何将其用于需要致癌物风险评估的特定工作场所场景。该论文探讨了基准剂量法允许有效地近似致癌反应的剂量反应数据的假设，在实际目的无法保证在更复杂的模型之间进行选择的情况下，提供对风险的合理估计。对三个案例研究分析了对人类致癌性具有不同科学可信度的物质：碳纳米管、铁石棉和草甘膦。对于每种药物，确定了一项关键研究，并量化了剂量反应斜率因子，基于加权平均下限基准剂量。每mg/m 0.111肺癌终生超额病例的线性斜率因子³ MWCNT-7（大鼠暴露当量），每 f/cc 年累积暴露于铁石棉中 0.009 例间皮瘤，每 mg/kg/天草甘膦（小鼠等效）0.000094 例恶性淋巴瘤. 所提出的线性预测模型与观察到的数据点之间的相关性对于碳纳米管是R = 0.96 ( R ² = 0.92)，对于铁石棉R = 0.97 ( R ² = 0.95) 和R = 0.89 ( R ²= 0.79) 草甘膦。在所有三种情况下，线性外推产生了与“最佳拟合”非线性模型相当的风险估计水平；对于纳米颗粒和铁石棉，线性估计更为保守。通过进行模拟研究，证明加权平均基准剂量与多级和量子线性模型的相关性最高。