Epidemiology studies in immunotoxicity evaluations.

Studies in humans designed to detect immunomodulation from exposure to xenobiotics present challenging problems to epidemiologists and immunotoxicologists. Exposed and control groups must be carefully selected, exposure to the xenobiotic must be sufficiently high and well-documented, and the referent group should be as similar as possible to the exposed. Immune markers/functional tests in an individual may be influenced by sunlight exposure, medication, illness and use of recreational drugs; all of these potential confounding factors must be addressed. Sample acquisition is usually performed at sites geographically distant from the controlled environment of an investigator's laboratory, yielding an assortment of new problems that would not occur in clinical or hospital situations. Regulations and guidelines concerning the transport of biological samples and potential hazards of HIV and HBV exposures to personnel must be adapted to field conditions. Since the application of immunotoxicological techniques to populations exposed to xenobiotics is relatively new, and the ability to measure an increasing number of immune biomarkers of activation, suppression, autoimmunity or hypersensitivity is rapidly expanding, there are difficulties in the interpretation of statistically positive results (sometimes within the normal range) and their potential health significance. Finally, both biological and methodological factors complicate the assessment of dose-response/concentration effect relationships in human immunotoxicity studies, and traditional dose-response relationships may not always be present.