Abstract：
Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that \"all short carbon chain acids … are likely reproductive and developmental toxicants\". This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.
摘要：
阅读（RAx）和将化学品分类是毒理学中众所周知的概念。最近,ECHA提出了一种用于危险识别的支链羧酸（BCA）的分组方法，其中包括60多种支链饱和羧酸。分组仅基于结构考虑。由于两个成员的发展影响，ECHA假定“所有短碳链酸。..很可能是生殖和发育毒物。“这项工作分析了BCA的可用数据。通过消除BCA的金属和有机盐，可以显着减少该组中化合物的数量，未知或可变组成的化合物，和复杂的反应产物或生物材料（UVCB化合物）。对于所产生的减少数量的化合物，类似的物理化学数据和预期的类似生物转化支持分组。然而,对该组化合物的不良反应分析和机理信息表明，BCA，作为一个班级,不会对大鼠造成发育影响。相反，发育毒性仅限于具有共同作用模式（组蛋白脱乙酰酶抑制）的特定结构的选定BCA。因此，提议的分组范围不合理，更详细的分析表明，仅结构相似性不足以将支链羧酸分组以产生发育毒性。
