Significant shifts in preclinical and clinical neurotoxicology: a review and commentary.

The ever-expanding prevalence of adverse neurotoxic reactions of the brain in response to therapeutic and recreational drugs, dietary supplements, environmental hazards, cosmetic ingredients, a spectrum of herbals, health status, and environmental stressors continues to prompt the development of novel cell-based assays to better determine neurotoxic hazard. Neurotoxicants may cause direct and epigenetic damage to the nervous tissue and alter the chemistry, structure, or normal activity of the nervous system. In severe neurotoxicity due to exposure to physical or psychosocial toxicants, neurons are disrupted or killed, and a consistent pattern of clinical neural dysfunction appears. exposure to neurotoxicants can lead to altered development of the nervous system [developmental neurotoxicity (DNT)]. Patients with certain disorders and certain genomic makeup may be particularly susceptible to neurotoxicants. Traditional cytotoxicity measurements, like cell death, are easy to measure, but insufficient at identifying current routine biomarkers of toxicity including functional impairment in cell communication, which often occurs before or even in the absence of cell death. The present paper examines some of the limitations of existing neurotoxicology in light of the increasing need to develop tools to meet the challenges of achieving greater sensitivity in detection and developing and standardizing methods for exploring the toxicologic risk of such neurotoxic entities as engineered nanomaterials and even variables associated with poverty.