Transgenerational neurotoxicity of plasticizers diisooctyl phthalate (DIOP) in Caenorhabditis elegans

Diisooctyl phthalate (DIOP), a widely used plasticizer, induces significant neurotoxicity with transgenerational effects in C. elegans. Parental exposure to DIOP impaired locomotion and cognition while reducing neurotransmitters (dopamine, GABA) and suppressing nervous system gene expression, accompanied by dopaminergic neuron damage. Critically, these neurotoxic effects persisted in unexposed F1-F2 offspring, characterized by sustained neurotransmitter depletion, gene dysregulation, and neuronal deterioration. Recovery initiated in F3 generation with normalization observed in F4. Notably, elevated GST-4 expression across all generations indicates an oxidative stress response to DIOP toxicity. These findings demonstrate DIOP's inherent neurotoxic potential and its capacity for heritable transmission across generations, highlighting the need for re-evaluation of its safety thresholds as a plasticizer alternative.