The environmental neuroactive chemicals list of prioritized substances for human biomonitoring and neurotoxicity testing: A database and high-throughput toxicokinetics approach

There is a diversity of chemicals to which humans are potentially exposed. Few of these chemicals have linked human biomonitoring data, and most have very limited neurotoxicity testing. Of particular concern are environmental exposures impacting children, who constitute a population of heightened susceptibility due to rapid neural growth and plasticity, yet lack biomonitoring data compared to other age/population subgroups. This study set out to develop a prioritized list of neuroactive substances, titled theEnvironmentalNeuRoactIveCHemicals (ENRICH) list, to be used as a defined screening library in the evaluation of human biological samples, with emphasis on early childhood-relevant environmental exposures. database mining approaches were used to prioritize chemicals based upon likelihood of neuroactivity, human exposure, and feasible detection in biological samples. Evidence of neuroactivity was compiled across high-throughput screening, animal testing, and/or human epidemiological findings. Chemicals were considered for their likelihood of human exposure and detection presence in biological samples (including metabolites), with additional evidence indicating presence within child-relevant products. The resulting list of 1827 chemicals were ranked using a Chemical Prioritization Index. Manual inclusion/exclusion criteria were employed for the top-ranking chemical candidates to ensure that chemicals were within the study's scope (i.e., environmentally relevant) and, for the purposes of biomonitoring, had properties amenable to mass spectrometry methods. These elements were combined to produce the ENRICH list of 250 top-ranking chemicals, spanning pesticides and those used in home maintenance, personal care, cleaning products, vehicles, arts and crafts, and consumer electronics, among other sources. Chemicals were additionally evaluated for high-throughput toxicokinetics to predict how much of a chemical and/or its metabolite(s) may reach urine, as an example biological matrix for practical use in biomonitoring efforts. This novel study couples databases and -based predictions to prioritize chemicals in the environment with potential neurological impacts for future study.

人类可能接触到各种各样的化学物质。这些化学物质中很少有与人类生物监测数据相关联的，而且大多数的神经毒性测试非常有限。尤其令人担忧的是环境暴露对儿童的影响，由于儿童神经快速生长和具有可塑性，他们属于易受影响的人群，但与其他年龄/人群亚组相比，缺乏生物监测数据。本研究着手制定一份神经活性物质的优先列表，名为环境神经活性化学物质（ENRICH）列表，用作评估人类生物样本的特定筛选库，重点是与幼儿期相关的环境暴露。利用数据库挖掘方法，根据神经活性的可能性、人类暴露情况以及在生物样本中可行的检测，对化学物质进行优先级排序。神经活性的证据是通过高通量筛选、动物试验和/或人类流行病学研究结果汇总而来的。考虑化学物质在人类中暴露的可能性以及在生物样本（包括代谢物）中可检测到的情况，还有其他证据表明其存在于与儿童相关的产品中。通过化学物质优先级指数对所得的1827种化学物质进行排名。对排名靠前的化学物质候选物采用人工纳入/排除标准，以确保化学物质在研究范围内（即与环境相关），并且就生物监测而言，具有适合质谱方法的特性。将这些要素结合起来，生成了包含250种排名靠前的化学物质的ENRICH列表，涵盖农药以及用于家庭维护、个人护理、清洁产品、车辆、工艺品和消费电子产品等来源的化学物质。此外，还对化学物质进行高通量毒代动力学评估，以预测一种化学物质和/或其代谢物有多少可能进入尿液，尿液作为生物监测工作中实际使用的一个生物基质示例。这项新颖的研究将数据库和基于数据库的预测相结合，对环境中具有潜在神经影响的化学物质进行优先级排序，以供未来研究。