Neurobehavioral effects of low dose exposure to chemical mixtures: a review

Neurological disorders have become the leading cause of disease and disability worldwide, with 80% of these conditions being recorded in low- and middle-income countries. Scientific evidence has increasingly associated these disorders with exposure to xenobiotics, such as pesticides, heavy metals and endocrine-disrupting chemicals (EDCs). Recent studies have focused on the consequences of exposure to chemical mixtures and their potential neurotoxic effects. As reported, such exposures can adversely affect cognitive and motor skills, particularly when they occur prenatally or during the early stages of development. Long-term exposure to mixtures of these substances has been strongly related to oxidative stress, inflammation and neurodegeneration. This review aims to explore the neurobehavioral effects of low-dose xenobiotic combinations, stressing the potential long-term neurological damage from such exposure. The in vivo and epidemiological studies reviewed indicate that early-life exposure to chemical mixtures is linked to motor and cognitive disorders, increased anxiety prevalence and behavioral dysregulation. Mechanistic evidence suggests that these exposures may exacerbate oxidative stress, immune activation, and neuronal dysfunction, ultimately leading to neuroinflammation. Chemical interactions greatly affect neurotoxicity, often deviating from simple dose addition. Synergistic effects can arise at both low and high doses, while some studies also report antagonistic outcomes. The specific impacts depend on the chemicals involved, their ratios, and the biological endpoints assessed. Since pollutants like heavy metals can persist in the environment due to their resistance to natural degradation processes, innovative strategies are necessary to mitigate the detrimental effects of exposure to chemical mixtures on human health and the environment.