Health Sciences Practice, Exponent, Inc. , Bellevue, WA , USA.
Crit Rev Toxicol. 2014 Jul;44(6):499-522. doi: 10.3109/10408444.2014.902423. Epub 2014 May 7.
U.S. Environmental Protection Agency (EPA) recently conducted a risk assessment for exposure to Libby amphibole asbestos that is precedent-setting for two reasons. First, the Agency has not previously conducted a risk assessment for a specific type of asbestos fiber. Second, the risk assessment includes not only an inhalation unit risk (IUR) for the cancer endpoints, but also a reference concentration (RfC) for nonmalignant disease. In this paper, we review the procedures used by the Agency for both cancer and nonmalignant disease and discuss the strengths and limitations of these procedures. The estimate of the RfC uses the benchmark dose method applied to pleural plaques in a small subcohort of vermiculite workers in Marysville, Ohio. We show that these data are too sparse to inform the exposure-response relationship in the low-exposure region critical for estimation of an RfC, and that different models with very different exposure-response shapes fit the data equally well. Furthermore, pleural plaques do not represent a disease condition and do not appear to meet the EPA's definition of an adverse condition. The estimation of the IUR for cancer is based on a subcohort of Libby miners, discarding the vast majority of lung cancers and mesotheliomas in the entire cohort and ignoring important time-related factors in exposure and risk, including effect modification by age. We propose that an IUR based on an endpoint that combines lung cancer, mesothelioma, and nonmalignant respiratory disease (NMRD) in this cohort would protect against both malignant and nonmalignant disease. However, the IUR should be based on the entire cohort of Libby miners, and the analysis should properly account for temporal factors. We illustrate our discussion with our own independent analyses of the data used by the Agency.
美国环保署（EPA）最近对接触利比角闪石石棉的风险进行了评估，这有两个原因。首先，该机构以前没有对特定类型的石棉纤维进行过风险评估。其次，风险评估不仅包括癌症终点的吸入单位风险（IUR），还包括非恶性疾病的参考浓度（RfC）。在本文中，我们回顾了该机构用于癌症和非恶性疾病的程序，并讨论了这些程序的优缺点。RfC 的估计值使用了基准剂量方法，该方法适用于俄亥俄州马里恩维尔的蛭石工人小亚群中的胸膜斑。我们表明，这些数据过于稀疏，无法为低暴露区域的暴露-反应关系提供信息，对于 RfC 的估计，这对于估计 RfC 至关重要，而且具有非常不同暴露-反应形状的不同模型同样适用于数据。此外，胸膜斑不代表疾病状况，似乎不符合 EPA 对不利状况的定义。癌症 IUR 的估计是基于利比矿工的一个亚群，丢弃了整个队列中绝大多数的肺癌和间皮瘤，并忽略了暴露和风险中的重要时间相关因素，包括年龄的影响修饰。我们建议，基于该队列中肺癌、间皮瘤和非恶性呼吸道疾病（NMRD）组合的终点的 IUR 将预防恶性和非恶性疾病。然而，IUR 应该基于利比矿工的整个队列，并且分析应该正确考虑时间因素。我们使用机构使用的数据进行了自己的独立分析，说明了我们的讨论。
