ToxStrategies, Asheville, NC, USA.
ToxStrategies, Cary, NC, USA.
Regul Toxicol Pharmacol. 2020 Jun;113:104651. doi: 10.1016/j.yrtph.2020.104651. Epub 2020 Mar 27.
Thousands of chemicals have limited, or no hazard data readily available to characterize human risk. The threshold of toxicological concern (TTC) constitutes a science-based tool for screening level risk-based prioritization of chemicals with low exposure. Herein we compare TTC values to more rigorously derived reference dose (RfD) values for 288 chemicals in the U.S. Environmental Protection Agency's (US EPA) Integrated Risk Information System (IRIS) database. Using the Cramer decision tree and the Kroes tiered decision tree approaches to determine TTC values, the TCC for the majority of these chemicals were determined to be lower than their corresponding RfD values. The ratio of log10(RfD/TCC) was used to measure the differences between these values and the mean ratio for the substances evaluated was ~0.74 and ~0.79 for the Cramer and Kroes approach, respectively, when considering the Cramer Classes only. These data indicate that the RfD values for Cramer Class III compounds were, on average, ~6-fold higher than their TTC value. These analyses indicate that provisional oral toxicity values might be estimated from TTCs in data-poor or emergency situations; moreover, RfD values that are well below TTC values (e.g., 2 standard deviations below the log10(Ratio)) might be overly conservative and targets for re-evaluation.
数以千计的化学物质的人体危害数据有限或根本无法获得，因此无法对其进行评估。毒理学关注阈值（TTC）是一种基于科学的工具，用于对暴露量低的化学物质进行基于风险的筛选分级。在此，我们将 TTC 值与美国环保署（US EPA）综合风险信息系统（IRIS）数据库中 288 种化学物质的更严格推导的参考剂量（RfD）值进行了比较。使用 Cramer 决策树和 Kroes 分层决策树方法来确定 TTC 值，发现这些化学物质的大多数 TCC 值均低于其相应的 RfD 值。使用 log10（RfD/TCC）的比值来衡量这些值之间的差异，对于评估的物质，这两个比值的平均值分别约为 0.74 和 0.79，仅考虑 Cramer 类时，分别对应于 Cramer 类和 Kroes 方法。这些数据表明，Cramer 类 III 化合物的 RfD 值平均比 TTC 值高约 6 倍。这些分析表明，在数据匮乏或紧急情况下，可能可以根据 TTC 值来估算暂定口服毒性值；此外，远低于 TTC 值的 RfD 值（例如，比 log10（Ratio）低 2 个标准差）可能过于保守，需要重新评估。
