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.

中文翻译：

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毒理学关注阈值（TTC）值与口服参考剂量（RfD）值的比较。

成千上万种化学药品的数量有限，甚至没有危险数据可用来描述人的风险。毒理学关注阈值（TTC）构成了一种基于科学的工具，用于筛选低暴露水平的基于风险的化学品优先级。在这里，我们将TTC值与美国环境保护局（US EPA）综合风险信息系统（IRIS）数据库中288种化学药品的更严格得出的参考剂量（RfD）值进行比较。使用Cramer决策树和Kroes分层决策树方法确定TTC值，可以确定大多数这些化学品的TCC低于其相应的RfD值。使用log10（RfD / TCC）的比值测量这些值之间的差异，所评估物质的平均比值为〜0.74和〜0。仅考虑Cramer类时，Cramer和Kroes方法分别为79。这些数据表明，Cramer III类化合物的RfD值平均比其TTC值高约6倍。这些分析表明，在数据贫乏或紧急情况下，可根据TTC估算临时的口服毒性值；此外，远低于TTC值的RfD值（例如，低于log10（Ratio）的2个标准偏差）可能过于保守，可能会成为重新评估的目标。