EARLY DETECTION OF IMMUNOTOXICITY - FROM ANIMAL STUDIES TO HUMAN BIOMONITORING

This paper introduces approaches to tests for potential immunotoxicity in rodents and man and the application for evaluation of risk. Chemic als can affect the immune system. Direct effects of chemicals can resu lt in malfunctioning of the system that can lead to decreased resistan ce to infections or tumors. Auto-immunity, a situation in which immune reactions to self components occur, can also be due to chemicals. Fin ally, chemicals can induce immune responses causing more harm to the t issue in which they take place than the chemical itself would have don e. This situation is called allergy or hypersensitivity. Assessment of potential immunotoxicity can be performed in experimental animals. An array of in vivo assays of the immune system, in addition to ex vivo/ in vitro assays are available to study the functional consequences of such immunotoxic effects. In particular host resistance models are val uable in this respect, since they offer endpoints that are relevant fo r estimation of risk to man. There is a number of examples of immunoto xic compounds. Data on direct immunotoxicity of chemicals are mainly d erived from animal research, whereas detailed information in man is av ailable only to a limited extent. The majority of such data comes from immunotherapeutic drugs, intentionally designed to influence the immu ne system. Environmental pollutants that are reported to have immunoto xic effects include among others dioxin and polychlorinated biphenyls oxidant gases. It is difficult at present to conclude from immunotoxic effects as they have been observed in man what their consequences are in terms of resistance to infections. Assessment of immunotoxic proce sses in man is difficult, as often detailed information is lacking and the immune system can only be studied to a limited extent. Although t ests are available to study immune responses in man, it is often not e asy to link the outcome of such assays to exposure to immunotoxicants. Few biomarkers for the immune system exist that provide specific info rmation on the toxic activity in man and extent of exposure, or (susce ptibility for) disease associated with chemical exposure.