Neurotoxicology of warfare arsenical, diphenylarsinic acid in humans and experimental models

Unused warfare chemical agents, developed in World Wars I/II dumped in the ocean or buried at various sites across the world, pose significant environmental and human health risks. This review provides description of the neurotoxicity of arsenic-based warfare chemicals known as arsenicals. We specifically described the neuropathogenesis of diphenylarsinic acid (DPAA), a chemical warfare-related organoarsenicals and a degradation product of diphenylchloroarsine (DA), diphenylcyanoarsine (DC), also known as Clark I and Clark II respectively. These arsenicals are potent emetics, which were buried at a former naval base in the town of Kamisu, Japan. Several decades after burial, their environmental decay led to contamination of underground water table. Consumption of the contaminated water by the residents manifested a neurological syndrome, which was associated with damage to the cerebellum and brainstem as well as behavioral deficits. We summarized the chronology of this damage as recorded by monitoring the exposed population over time (∼15 years). Several simulating animal studies in primates and murine models demonstrate that DPAA caused this syndrome.