THE HOW, WHY AND WHEN OF IMMUNOLOGICAL TESTING

Immunotoxic effects include direct immunotoxicity, hypersensitivity and autoimmunity. Each effect requires a specific strategy to identify and assess the risks involved. At the moment, 2- or 3-tier protocols are considered the best modalities to detect an unexpectedly immunosuppressive compound and presumably an immunoenhancing compound as well. Such protocols are best conducted as 21-90 day rat studies. Contact sensitisation and anaphylaxis models in guinea pigs or mice are. also useful tools to predict hypersensitivity. Finally, only a few systemic autoimmune reactions may be predicted in mice or rats using the popliteal lymph node assay. Thanks to improved standardisation and interlaboratory validation, an increased risk for infections and lymphomas (immunosuppression), contact dermatitis, anaphylaxis (macromolecular compounds only) and systemic autoimmune reactions (e.g. lupus) can reasonably be predicted. As few guidelines are available concerning the immunotoxicity assessment of novel chemicals, it is proposed that tier-1 and contact sensitisation should be performed routinely whatever the compound whereas additional testing may be required on a case-by-case approach, taking into account the modalities of exposure (e.g. dose and duration), the exposed population and the nature of the compound (e.g. pharmaceuticals).