Mechanisms of Flame Retardant Toxicity and Their Impacts on Anxiety and Cognition in the Brain.

Flame retardants have been used extensively to reduce flammability in household and industrial materials raising significant concerns due to their toxicological effects, particularly on neurodevelopment and cognition. These chemicals, including legacy compounds such as polybrominated diphenyl ethers and newer organophosphate flame retardant, exhibit endocrine-disrupting properties that interfere with hormonal pathways, neurotransmission, and synaptic plasticity. Epidemiological studies have linked flame retardant exposure to adverse developmental outcomes, including anxiety and cognitive deficits. Mechanistic research reveals that flame retardants disrupt neurogenesis, synaptogenesis, and neurotransmitter pathways, often mediated through oxidative stress, mitochondrial dysfunction, and nuclear receptor modulation. Animal studies corroborate these findings, showing impaired spatial memory, altered anxiety-like behaviors, and disrupted neurochemical homeostasis following perinatal and postnatal exposure to flame retardants. Emerging organophosphate flame retardants, such as bis(2-ethylhexyl) phenyl phosphate, demonstrate comparable or increased toxicity, further emphasizing the need for regulatory scrutiny and safer alternatives. This review synthesizes current knowledge on the neurotoxic mechanisms of flame retardants, highlighting their impact on anxiety and cognition across developmental stages. Understanding these pathways is essential to mitigating the long-term environmental and human health effects of flame retardant exposure.