Using life expectancy as a risk assessment metric: The case of respirable crystalline silica

IF 3.1 Q2 TOXICOLOGY Computational Toxicology Pub Date : 2023-08-01 DOI:10.1016/j.comtox.2023.100285
Andrey A. Korchevskiy , Arseniy Korchevskiy
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Abstract

The change in age-related mortality patterns is an important characteristic of the population that can be used as a metric of risk by comparing exposed and non-exposed populations.

In this paper, the mortality parameters were predicted for populations exposed to crystalline silica, a proven lung carcinogen.

Seven hazard functions were tested for a dose–response relationship between lung cancer and characteristics of exposure. Life tables were calculated, along with parameters of the Gompertz-Makeham model for the force of mortality.

It was demonstrated, in particular, that exposure to crystalline silica in the range from 0.03 to 0.3 mg/m3 for 40 years starting at age 20 causes a predicted drop in average life expectancy in the range of from 0.15 to 1.38 years.

It was demonstrated that the lost life expectancy linearly correlates with relative risk (R = 0.995, R2 = 0.989, p< 0.00001). The probability of the life expectancy increasing while relative risk decreases was as low as 0.01.

It was found that exponential parameter α of the Gompertz-Makeham equation increases with crystalline silica exposure, while the two linear parameters A and R (which are negatively correlated between each other) increase or decrease with exposure depending on the duration and onset age. Modal age of death in the cohort decreases with cumulative exposure with R = -0.977, R2 = 0.954, p < 0.0001.

Based on several different approaches, it was suggested that the threshold of cumulative crystalline silica exposure concentration causing statistically significant change in the cohort life tables can be found in the range from 1.81 to 2.50 mg/m3-years. The change of average age of death in exposed male population does not exceed 1% below cumulative exposure of 3.5 mg/m3-years, and does not exceed 5% at cumulative exposure less than 9.8 mg/m3-years. It shows that no significant acceleration of death rate with age is happening even at the high levels of exposure to crystalline silica.

The study demonstrated the value and advantages of the use of life expectancy and other lifetable characteristics as a tool for quantitative risk assessment.

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使用预期寿命作为风险评估指标:可吸入结晶二氧化硅的案例
与年龄有关的死亡率模式的变化是人口的一个重要特征,可以通过比较受辐射人群和未受辐射人群来作为风险度量标准。在本文中,死亡率参数预测人群暴露于结晶二氧化硅,一个已证实的肺癌物质。对肺癌与暴露特征之间的剂量-反应关系进行了七种危害函数测试。计算了生命表,以及Gompertz-Makeham死亡率模型的参数。研究特别证明,从20岁开始连续40年暴露于0.03至0.3 mg/m3范围内的结晶二氧化硅可导致预期平均寿命下降0.15至1.38年。结果表明,预期寿命损失与相对危险度呈线性相关(R = 0.995, R2 = 0.989, p<0.00001)。预期寿命增加而相对风险降低的概率低至0.01。结果表明,Gompertz-Makeham方程的指数参数α随暴露时间的增加而增加,而两个线性参数A和R则随暴露时间的延长和年龄的增加而增加或减少。队列中死亡模态年龄随累积暴露而降低,R = -0.977, R2 = 0.954, p <0.0001.基于几种不同的方法,建议在1.81至2.50 mg/m3-年范围内发现累积结晶二氧化硅暴露浓度导致队列生命表发生统计学显著变化的阈值。在累计暴露3.5 mg/m3年以下,暴露男性人群平均死亡年龄变化不超过1%;在累计暴露低于9.8 mg/m3年时,暴露男性人群平均死亡年龄变化不超过5%。它表明,即使在高水平接触结晶二氧化硅的情况下,死亡率也没有随着年龄的增长而显著加速。该研究证明了使用预期寿命和其他生命周期特征作为定量风险评估工具的价值和优势。
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来源期刊
Computational Toxicology
Computational Toxicology Computer Science-Computer Science Applications
CiteScore
5.50
自引率
0.00%
发文量
53
审稿时长
56 days
期刊介绍: Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs
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