到目前为止,大约130个消毒副产物(DBPs)和几个DBPs组已经对一些内分泌终点进行了潜在的内分泌干扰作用测试。然而,目前尚不清楚哪些具体的DBPs,对于任何给定的内分泌终点,DBP组/亚组可能是毒性最强的物质或组/亚组。在这项研究中,我们试图解决这个问题。首先,更新了相关DBP的列表,和属于4个主要群体的1187个DBPs(脂肪族,芳香,脂环族,杂环)和84个亚组被描述。然后,高度优先的内分泌终点,DBP组/子组,并从18个端点确定特定的DBPs,4个主要群体,84个小组,和1187个特定的DBPs通过虚拟筛选方法。结果表明,大多数DBP不会干扰所讨论的内分泌终点,因为与内分泌终点相关的活性化合物的比例范围为0(人类甲状腺受体β)至32%(人类转甲状腺素蛋白(hTTR))。活性化合物比例大于10%的所有终点都属于甲状腺系统,强调DBPs对甲状腺系统的潜在破坏作用应给予更多关注。通过考虑活性速率和破坏作用的可能性,芳香族和脂环族DBPs可以比脂族和杂环DBPs具有更高的优先级。有2个(卤酚和雌激素DBPs),12和24个属于高的子组,中度,和低优先级的类,分别。对于单个DBP,有23人(2%),193(16%),和971(82%)DBPs属于高位,中度,和低优先级群体,分别。最后,通过体外测定确定4个DBPs的hTTR结合亲和力,所有测试的DBPs都表现出与hTTR的剂量依赖性结合效力,与预测结果一致。因此,应该做更多的努力来揭示那些高度研究优先的主要群体的潜在内分泌干扰,子组,和个人DBPs。
So far, about 130 disinfection by-products (DBPs) and several DBPs-groups have had their potential endocrine-disrupting effects tested on some endocrine endpoints. However, it is still not clear which specific DBPs, DBPs-groups/subgroups may be the most toxic substances or groups/subgroups for any given endocrine endpoint. In this
study, we attempt to address this issue. First, a list of relevant DBPs was updated, and 1187 DBPs belonging to 4 main-groups (aliphatic, aromatic, alicyclic, heterocyclic) and 84 subgroups were described. Then, the high-priority endocrine endpoints, DBPs-groups/subgroups, and specific DBPs were determined from 18 endpoints, 4 main-groups, 84 subgroups, and 1187 specific DBPs by a virtual-screening method. The results demonstrate that most of DBPs could not disturb the endocrine endpoints in question because the proportion of active compounds associated with the endocrine endpoints ranged from 0 (human thyroid receptor beta) to 32% (human transthyretin (hTTR)). All the endpoints with a proportion of active compounds greater than 10% belonged to the thyroid system, highlighting that the potential disrupting effects of DBPs on the thyroid system should be given more attention. The aromatic and alicyclic DBPs may have higher priority than that of aliphatic and heterocyclic DBPs by considering the activity rate and potential for disrupting effects. There were 2 (halophenols and estrogen DBPs), 12, and 24 subgroups that belonged to high, moderate, and low priority classes, respectively. For individual DBPs, there were 23 (2%), 193 (16%), and 971 (82%) DBPs belonging to the high, moderate, and low priority groups, respectively. Lastly, the hTTR binding affinity of 4 DBPs was determined by an in vitro assay and all the tested DBPs exhibited dose-dependent binding potency with hTTR, which was consistent with the predicted result. Thus, more efforts should be performed to reveal the potential endocrine disruption of those high research-priority main-groups, subgroups, and individual DBPs.