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. Chemicals can affect the immune system. Direct effects of chemicals can result in malfunctioning of the system that can lead to decreased resistance to infections or tumors. Auto-immunity, a situation in which immune reactions to self components occur, can also be due to chemicals. Finally, chemicals can induce immune responses causing more harm to the tissue in which they take place than the chemical itself would have done. 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 valuable in this respect, since they offer endpoints that are relevant for estimation of risk to man. There is a number of examples of immunotoxic compounds. Data on direct immunotoxicity of chemicals are mainly derived from animal research, whereas detailed information in man is available only to a limited extent. The majority of such data comes from immunotherapeutic drugs, intentionally designed to influence the immune system. Environmental pollutants that are reported to have immunotoxic 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 processes in man is difficult, as often detailed information is lacking and the immune system can only be studied to a limited extent. Although tests are available to study immune responses in man, it is often not easy to link the outcome of such assays to exposure to immunotoxicants. Few biomarkers for the immune system exist that provide specific information on the toxic activity in man and extent of exposure, or (susceptibility for) disease associated with chemical exposure.