The 2018 Environmental Performance Index (EPI) named air pollution as the number one environmental threat to public health. Traffic-related air pollution (TRAP) is a sizable contributor to global air pollution, and diesel exhaust (DE) is a major source of TRAP (Yale Center for Environmental Law & Policy, 2018). Though the connection between air pollution and respiratory or cardiovascular diseases is widely known, more recent studies have begun to establish a connection between air pollution and diseases of the central nervous system (CNS). Epidemiological and animal studies have revealed both biochemical and behavioral variations in children or young animals exposed to elevated levels of air pollution, including increased risk of the development of autism spectrum disorder (ASD) (Flores-Pajot et al., 2016). These studies also suggest, much like with cardiovascular impacts, that oxidative stress and neuroinflammation play a large role in the CNS effects. Children diagnosed with ASD show morphological differences in the brain, high oxidative stress, and neuroinflammation as well as systemic inflammation. Growing evidence supports the notion that ASD is a result of interactions between genetic and environmental factors (Costa et al., 2022, chapter 42). This project measured the gene-environment interaction between the gene encoding glutamate-cysteine ligase modifier subunit (Gclm), the modulatory subunit of the rate limiting enzyme in glutathione (GSH) synthesis, and neurodevelopmental effects of TRAP exposure. GSH has a key function in combatting oxidative stress and children diagnosed with ASD have shown a 37% increase in GCLM protein and a 38% decrease in glutamate-cysteine ligase (GCL) activity. To study this gene-environment interaction for effects on the neurodevelopmental toxicity of DE, we used a Gclm heterozygous (Gclm+/-) mouse model, which exhibits decreased GSH-synthesizing activity when challenged with oxidative stress, due to the presence of only one functional Gclm allele, hypothesizing that Gclm+/- mice would see exacerbated effects from exposure to diesel exhaust (DE). C57Bl/6 wild-type (WT) dams bred with Gclm+/- sires were exposed to DE or filtered air (FA) throughout gestation, and litters containing the Gclm+/- and Gclm+/+ offspring continued to be exposed from post-natal day (PND) 0 to 21. Behavioral endpoints, measured in the offspring at 12 and 24 weeks old, showed deficits in repetitive behaviors and social novelty with DE exposure, but surprisingly these effects were not increased in the Gclm+/- mice. Biochemical endpoints were measured in the brain at 29 weeks old. Lipid peroxidation was higher in the brains of DE-exposed mice, and this effect was exacerbated in Gclm+/- males, but not Gclm+/- females. Finally, a clear effect of DE exposure was seen on neuroinflammation and microglial activation. These effects were not significantly exacerbated in the Gclm+/- mouse model, contrary to what was expected. Thus, the Gclm genotype of the offspring, and presumably their altered ability to induce GSH, was not sufficient to modulate the neurodevelopmental effects of DE exposure.