Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable, as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds’ impacts on human health.

接触环境化学物质会损害神经发育，少突胶质细胞可能特别脆弱，因为它们的发育从妊娠期一直延伸到成年期。然而，很少有环境化学物质对少突胶质细胞的潜在风险进行了评估。在这里，我们在培养细胞中使用高通量发育筛选，确定了两类环境化学物质，它们通过不同的机制破坏少突胶质细胞的发育。四元化合物普遍存在于消毒剂和个人护理产品中，对发育中的少突胶质细胞具有强效和选择性的细胞毒性，而常见于家具和电子产品等家居用品中的有机磷酸酯阻燃剂会过早阻止少突胶质细胞的成熟。每一类化学物质都会损害小鼠产后少突胶质细胞和产前皮质发育的人类 3D 类器官模型中的少突胶质细胞发育。流行病学数据分析表明，不良的神经发育结果与儿童时期接触我们筛选出的顶级有机磷酸酯阻燃剂有关。这项工作确定了少突胶质细胞发育的毒理学弱点，并强调需要更深入地审查这些化合物对人类健康的影响。