Autoimmunity and toxicity testing.

Abstract

Major difficulties when addressing autoimmunity today within the context of regulatory toxicology are the following: (i) the incidence of auto-immunity related to chemical exposure is not known; (ii) the mechanisms involved are not understood in most instances; and (iii) no fully validated models are available. Although no relationship has been firmly established between the serum levels of autoantibodies and the development and/or the severity of autoimmune diseases, these are considered the hallmarks of autoimmunity. It has proved impossible so far to detect reproducibly autoantibodies indicative of organ-specific autoimmune reactions induced by chemicals in conventional toxicity testing. The detection of autoantibodies suggestive of a systemic autoimmune reaction has been successful with very few compounds only, and most often using non-conventional strains of animals. Genetically-deficient animal strains were sometimes helpful, but these models should be standardised and validated. This also applies to experimental autoimmune disease models. The popliteal lymph node (PLN) assay is potentially helpful, but more research and validation efforts are warranted. From a regulatory toxicology perspective, the search for serum autoantibodies, as it is performed today, does not seem to be a reliable tool, and progress is more likely to be expected from the design, standardisation and validation of dedicated models.