BASF SE, Experimental Toxicology and Ecology, Z 470, D-67056 Ludwigshafen, Germany.
Regul Toxicol Pharmacol. 2011 Feb;59(1):81-90. doi: 10.1016/j.yrtph.2010.09.009. Epub 2010 Sep 27.
The Threshold Toxicological Concern (TTC) is based on the concept that reasonable assurance of safety can be given if exposure is sufficiently low. Originally based on the evaluation of carcinogenicity studies more recently TTC evaluations for other toxicological end points have been published. Here we report on the evaluation of our data base for oral developmental toxicity studies (OECD 414) in rats with 92 and 93 NOAEL values for maternal and developmental toxicity, respectively. The 5th percentile of the NOAEL distributions were calculated to be 4 mg/kg bw/d for maternal and 5mg/kg bw/d for developmental toxicity. Adding the data for developmental toxicity provided by Kroes et al. (2004), a joint evaluation of 111 individual NOAEL values resulted in a 5th percentile value of 4 mg/kg bw/d. Using a safety factor of 500 (to account for a possible underrepresentation of chemical classes) on the 5th percentile a TTC value for developmental toxicity of 8 μg/kg bw/d based on the combined data and for maternal toxicity of 8 μg/kg bw/d based on our data base was calculated. Within the REACH context this value may serve as guidance whether to perform an animal experiment or to rely on a TTC value if estimated exposure is sufficiently low.
阈毒理学关注值（TTC）基于这样一种概念，即如果暴露水平足够低，则可以合理保证安全性。最初是基于致癌性研究的评估，最近已经发布了其他毒理学终点的 TTC 评估。在这里，我们报告了对我们的大鼠口服发育毒性研究（OECD 414）数据库的评估，其中母体和发育毒性的分别有 92 个和 93 个无观察到不良作用水平（NOAEL）值。NOAEL 分布的第 5 个百分位数计算为母体毒性为 4mg/kg bw/d，发育毒性为 5mg/kg bw/d。加入 Kroes 等人（2004 年）提供的发育毒性数据，对 111 个个体 NOAEL 值进行联合评估，得出第 5 个百分位数值为 4mg/kg bw/d。基于联合数据，对于发育毒性，在第 5 个百分位数上使用 500 的安全系数（以说明可能对化学类别代表性不足），计算出基于我们数据库的母体毒性的 TTC 值为 8μg/kg bw/d。在 REACH 背景下，如果估计暴露水平足够低，该值可以作为是否进行动物实验或依赖 TTC 值的指导。
