Organic solvent neurotoxicity. Facts and research needs.

While many organic solvents are, in large doses, capable of inducing an acute, reversible narcotic state, few unequivocally induce chronic, long-lasting, or irreversible changes in nervous system structure and/or function. For organic solvents with proved neurotoxic properties, the type of neurological damage is closely related to the structure of the chemical agent, while the degree of impairment and the extent of reversibility are related to the potency, dose, and duration of exposure. Examples include solvents containing n-hexane or methyl n-butyl ketone, which have caused many cases of occupational neuropathy. Chronic inhalation abuse of pure toluene produces irreversible cerebellar, brainstem, and pyramidal-tract dysfunction, but comparable changes have not been found in solvent workers occupationally exposed to toluene. Ototoxicity is found in experimental animals exposed to toluene, xylene, or styrene. Impure trichloroethylene has a predilection for damaging the trigeminal nerve; dichloroacetylene, a breakdown product of trichloroethylene, is probably responsible for this neurotoxic property. Prolonged occupational exposure to mixed solvents, notably white spirit, has been reported to induce a mild, nonprogressive dementing illness with or without peripheral nerve dysfunction, but supporting data from neuropathological and experimental animal studies are lacking. Many other solvents have been reported to induce adverse effects in workers. The pivotal biological role of the nervous system and its vulnerability to selected organic solvents widely used in industry underline the urgent need for further clinical and experimental research on this problem.