Evonik Operations GmbH, Goldschmidtstr. 100, D-45127 Essen, Germany.
The Dow Chemical Company, 1803 Building, Midland, MI, 48674, USA.
Regul Toxicol Pharmacol. 2021 Dec;127:105074. doi: 10.1016/j.yrtph.2021.105074. Epub 2021 Oct 30.
The Threshold of Toxicological Concern (TTC) for non-genotoxic substances, a risk assessment tool to establish safe exposure levels for chemicals with insufficient toxicological data, is based on the 5th percentile of cumulated distributions of Point of Departures in a high amount of repeat-dose, developmental and reproductive toxicity studies, grouped by Cramer Classes. The lack of organosilicon compounds in this dataset has resulted in regulatory concerns over the applicability of the TTC concept for this chemistry. We collected publicly available, scientifically robust oral repeat-dose and DART studies for 71 organosilicon substances for inclusion in the existing TTC dataset, using criteria for evaluation of studies and derivation of points of departure analogous to the Munro and COSMOS TTC publications. The resulting 5th percentile of this dataset was 13-fold higher than the 5th percentile for Cramer Class III compounds reported by Munro (which is the default for silicon-containing substances). Both the existing TTC for Cramer Class III compounds from Munro (1.5 μg/kg bw/day) and the COSMOS TTC (2.3 μg/kg bw/day), recommended by the SCCS for cosmetics-related substances, provide a conservative and sufficiently protective approach for this class of chemistry.
毒理学关注阈值（TTC）是一种用于非遗传毒性物质的风险评估工具，用于确定具有有限毒理学数据的化学品的安全暴露水平。它基于大量重复剂量、发育和生殖毒性研究中起始点的累积分布的第 5 个百分位数，这些研究按 Cramer 分类进行分组。由于该数据集缺乏有机硅化合物，因此监管机构对 TTC 概念在该化学物质中的适用性表示关注。我们收集了公开的、科学上可靠的 71 种有机硅物质的口服重复剂量和 DART 研究，以便将其纳入现有的 TTC 数据集，使用类似于 Munro 和 COSMOS TTC 出版物的研究评估和起始点推导标准。该数据集的第 5 个百分位数比 Munro 报告的 Cramer 类 III 化合物的第 5 个百分位数（默认值为含硅物质）高 13 倍。Munro 为 Cramer 类 III 化合物推荐的现有 TTC（1.5μg/kg bw/day）和 SCCS 为化妆品相关物质推荐的 COSMOS TTC（2.3μg/kg bw/day）都为该类化学物质提供了保守和足够的保护方法。
