Chemical-induced autoimmune reactions and Spanish toxic oil syndrome. Focus on hydantoins and related compounds.

Autoimmune diseases comprise a wide spectrum of overlapping, systemic and organ-specific disorders. Although, etiology and pathogenesis of such disorders are largely unknown, endogenous host factors and exogenous agents, such as viruses, bacteria, and small molecular weight chemicals, drugs and food components, are believed to be involved. The toxicological significance of low molecular weight compounds on induction of autoimmune disorders is illustrated by the toxic oil syndrome (TOS), a chemically induced epidemic, observed in Spain since 1981. The causative chemical(s) of TOS is still elusive, but an association between ingestion of refined aniline-adulterated rapeseed oil and the syndrome is well-documented. Epidemiological, clinical and immunopathological symptoms of TOS are briefly reviewed. The striking resemblance with immunological disorders, observed in man upon medication with hydantoins and related compounds, is demonstrated. The likeliness of formation of a hydantoin-related compound in the aniline-adulterated oil is evidenced and its role as possible toxic agent in TOS is proposed. Further, the presence of hydantoins and related compounds in food is briefly reviewed and it is suggested that these chemicals may account for a portion of idiopathic autoimmune diseases observed in man. The need for development of animal models to assess this kind of immunotoxicological effects is stressed.