Environmental chemicals impair oligodendrocyte development. A study identifies two classes of chemicals—quaternary compounds and organophosphate flame retardants—that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, found in disinfectants and personal care products, are selectively toxic to developing oligodendrocytes, while organophosphate flame retardants, common in household items, prematurely arrest oligodendrocyte maturation. These chemicals impair oligodendrocyte development in mice and human 3D organoids. Epidemiological data show that childhood exposure to the top organophosphate flame retardant is associated with adverse neurodevelopmental outcomes. The study highlights the need for further investigation into the impacts of these chemicals on human health. Quaternary compounds induce the integrated stress response, leading to apoptosis in oligodendrocytes. Organophosphate flame retardants inhibit oligodendrocyte development in both mice and humans. Exposure to these chemicals during early postnatal periods is linked to abnormal neurodevelopment, with increased risks of cognitive and motor impairments. The study underscores the toxicological vulnerabilities of oligodendrocyte development to common household chemicals and raises concerns about their impact on neurodevelopment. Continued research is needed to assess the full effects of these chemicals on human health.Environmental chemicals impair oligodendrocyte development. A study identifies two classes of chemicals—quaternary compounds and organophosphate flame retardants—that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, found in disinfectants and personal care products, are selectively toxic to developing oligodendrocytes, while organophosphate flame retardants, common in household items, prematurely arrest oligodendrocyte maturation. These chemicals impair oligodendrocyte development in mice and human 3D organoids. Epidemiological data show that childhood exposure to the top organophosphate flame retardant is associated with adverse neurodevelopmental outcomes. The study highlights the need for further investigation into the impacts of these chemicals on human health. Quaternary compounds induce the integrated stress response, leading to apoptosis in oligodendrocytes. Organophosphate flame retardants inhibit oligodendrocyte development in both mice and humans. Exposure to these chemicals during early postnatal periods is linked to abnormal neurodevelopment, with increased risks of cognitive and motor impairments. The study underscores the toxicological vulnerabilities of oligodendrocyte development to common household chemicals and raises concerns about their impact on neurodevelopment. Continued research is needed to assess the full effects of these chemicals on human health.