Goodman Julie E, Korchevskiy Andrey, Wylie Ann G
Gradient, Boston, MA, United States.
Chemistry & Industrial Hygiene, Inc., Lakewood, CO, United States.
Front Public Health. 2025 May 13;13:1569343. doi: 10.3389/fpubh.2025.1569343. eCollection 2025.
There is evidence to support several modes of action (MoAs), and particularly non-genotoxic MoAs, for mesothelioma induced by asbestiform elongate mineral particles (EMPs). In turn, these MoAs provide biological support for dose-response relationships that are non-linear and that include a threshold. However, statistical models of human data have not adequately addressed threshold dose-response relationships for asbestiform EMPs and mesothelioma. In addition, unlike other carcinogens, asbestiform EMPs are not uniform materials and display a range of properties.
Our objective was to review various approaches for applying threshold dose-response models to asbestiform EMPs and mesothelioma.
We collected data from several sources, including the Surveillance, Epidemiology, and End Results (SEER) Program and published case-control studies, cohort studies, and a meta-analysis that evaluated various mineral types of asbestos and mesothelioma risk. Several threshold-based models were fit to the available data. We also evaluated thresholds for certain fiber characteristics.
Certain characteristics of asbestiform EMPs, such as width, length, and surface area, likely have thresholds for mesothelioma. Theoretical models and models based on epidemiology data supported thresholds. A Monte Carlo evaluation of the threshold hypothesis for mesothelioma in a meta-analysis of occupational exposures to various mineral fiber types, using a cumulative exposure metric, demonstrated the likelihood of a threshold to be 72% for non-textile chrysotile, 80.9% for textile chrysotile, 84% for amosite, and 60% for crocidolite. A multi-stage clonal expansion (MSCE) model applied to the SEER mesothelioma registry data demonstrated a good fit with the inclusion of a threshold by a surrogate predictor of cumulative exposure to amphiboles. Finally, lung burden studies also support a threshold. Our preliminary estimate of a central-tendency cumulative exposure threshold level for non-textile chrysotile is ~90 f/cc-years. Based on our proposed approach, we suggest thresholds of 1.04 f/cc-years for amosite, 0.25 f/cc-years for crocidolite, and 4.3-10.9 f/cc-years for tremolite. Future studies should be conducted to support these estimates.
While uncertainties remain, many angles of scientific evidence support the existence of mineral-specific thresholds for mesothelioma.
有证据支持由石棉状细长矿物颗粒（EMPs）诱发间皮瘤的几种作用模式（MoAs），尤其是非遗传毒性作用模式。反过来，这些作用模式为非线性且包含阈值的剂量反应关系提供了生物学支持。然而，人类数据的统计模型尚未充分考虑石棉状EMPs与间皮瘤的阈值剂量反应关系。此外，与其他致癌物不同，石棉状EMPs并非均质材料，具有一系列特性。
我们的目的是综述将阈值剂量反应模型应用于石棉状EMPs和间皮瘤的各种方法。
我们从多个来源收集数据，包括监测、流行病学和最终结果（SEER）计划以及已发表的病例对照研究、队列研究，还有一项评估各种矿物类型石棉与间皮瘤风险的荟萃分析。将几种基于阈值的模型应用于现有数据。我们还评估了某些纤维特性的阈值。
石棉状EMPs的某些特性，如宽度、长度和表面积，可能对间皮瘤有阈值。理论模型和基于流行病学数据的模型支持阈值。在一项对各种矿物纤维类型职业暴露的荟萃分析中，使用累积暴露指标对间皮瘤阈值假说进行蒙特卡罗评估，结果表明，非纺织型温石棉的阈值可能性为72%，纺织型温石棉为80.9%，铁石棉为84%，青石棉为60%。应用于SEER间皮瘤登记数据的多阶段克隆扩增（MSCE）模型，在纳入闪石累积暴露的替代预测指标阈值后显示拟合良好。最后，肺部负荷研究也支持阈值。我们对非纺织型温石棉中心趋势累积暴露阈值水平的初步估计约为90纤维/立方厘米·年。基于我们提出的方法，我们建议铁石棉的阈值为1.04纤维/立方厘米·年，青石棉为0.25纤维/立方厘米·年，透闪石为4.3 - 10.9纤维/立方厘米·年。未来应开展研究以支持这些估计。
尽管仍存在不确定性，但多个角度的科学证据支持间皮瘤存在特定矿物阈值。
