Evaluation of inhalation TTC values with the database RepDose
Evaluation of inhalation TTC values with the database RepDose
复制标题
DOI：
10.1016/j.yrtph.2010.06.009
复制
发表时间：
2010-11-01
影响因子：
3.4
通讯作者：
Mangelsdorf, I.
中科院分区：
文献类型：
--
作者：
Escher, S. E.;Tluczkiewicz, I.;Mangelsdorf, I.
毒理学关注阈值（TTC）定义了未知毒性物质的限值，低于该限值，膳食摄入被认为对人类健康没有影响。TTC概念已用于食品污染物或调味物质等的风险评估，并正在讨论将其应用于其他类别的化合物，如化妆品成分、家用产品、饮用水中的非相关代谢物和药品中的杂质。本出版物的目的是评估目前的TTC概念是否也可用于确定吸入接触的限值，使用数据库RepDose中的203种工业化学品的数据集，结果表明，第1类、第2类和第3类的无观测效应浓度值分布在六个数量级上，导致三类分布曲线之间有相当大的重叠。Cramer 1类（可能具有低毒性的化合物）、2类（可能具有中等毒性的化合物）和3类（疑似具有高毒性的化合物）的吸入阈值分析接近Munro描述的口服TTC方法。Cramer 1-3级的第5次无观测效应浓度导致Cramer 1级的阈值为1.5 x 10（-3）ppm，Cramer 3级的阈值为2.2 x 10（-5）ppm。由于可用化合物数量较少，无法推导出第2类的阈值。如果按身体剂量计算，第1类和第3类的吸入阈值（分别为71和4 μ g/人/d）大大低于Munro得出的口服阈值（1800和90 μ g/人/d）。研究表明，造成这种差异的原因之一是呼吸道对局部效应的高度敏感性。如果排除有机磷或具有遗传毒性警示结构的化合物，Cramer 1类中的TTC增加，而Cramer 3类中的TTC保持不变。基于这些分析，拟定了非遗传毒性化合物的两种吸入TTC：Cramer 1类为3.6 x 10（-3）ppm（180 μ g/人/d），Cramer 3类为2.4 x 10（-5）ppm（4 μ g/人/d）。(C)2010年爱思唯尔公司All rights reserved.
The thresholds of toxicological concern (TTCs) define limit values for substances of unknown toxicity below which dietary intake is considered to be of no concern to human health. The TTC concept has already been used for risk assessment of e.g. food contaminants or flavoring substances and is in discussion to be applied to other classes of compounds such as cosmetic ingredients, household products, non-relevant metabolites in drinking water, and impurities in pharmaceuticals. The present publication aimed to evaluate whether the current TTC concept can also be applied to define limit values for inhalation exposure, using a data set of 203 industrial chemicals from the database RepDose.It has been shown, that the NOEC values in classes 1, 2, and 3 are distributed over six orders of magnitude resulting in a considerable overlap between the distribution curves for the three classes. Inhalation thresholds for Cramer classes 1 (compounds likely to be of low-toxicity), 2 (compounds likely to be of moderate toxicity), and 3 (compounds suspect for high toxicity) were analyzed close to the approach described by Munro for oral TTCs. The 5th percentiles NOEC of Cramer classes 1-3 result in thresholds of 1.5 x 10(-3) ppm for Cramer class 1 and 2.2 x 10(-5) ppm for Cramer class 3. A threshold could not be derived for class 2 because of the small number of compounds available. If calculated as body doses, the inhalation thresholds for classes 1 and 3 (71 and 4 mu g/person/d, respectively) are considerably lower than the oral thresholds derived by Munro (1800 and 90 mu g/person/d). It has been shown that one reason for this difference is the high sensitivity of the respiratory tract to local effects.In a next step, the values obtained were further refined. If organophosphates or compounds with structural alerts for genotoxicity are excluded, the TTC in Cramer class 1 increases, whereas the TTC in Cramer class 3 remains the same. Based on these analyses two inhalation TTCs for non-genotoxic compounds are proposed: 3.6 x 10(-3) ppm (180 mu g/person/d) for Cramer class 1 and 2.4 x 10(-5) ppm (4 mu g/person/d) for Cramer class 3. (C) 2010 Elsevier Inc. All rights reserved.