Studies in humans designed to detect immunomodulation from exposure to
xenobiotics present challenging problems to epidemiologists and immun
otoxicologists. Exposed and control groups must be carefully selected,
exposure to the xenobiotic must be sufficiently high and well-documen
ted, and the referent group should be as similar as possible to the ex
posed. Immune markers/functional tests in an individual may be influen
ced by sunlight exposure, medication, illness and use of recreational
drugs; all of these potential confounding factors must be addressed. S
ample acquisition is usually performed at sites geographically distant
from the controlled environment of an investigator's laboratory, yiel
ding an assortment of new problems that would not occur in clinical or
hospital situations. Regulations and guidelines concerning the transp
ort of biological samples and potential hazards of HIV and HBV exposur
es to personnel must be adapted to field conditions. Since the applica
tion of immunotoxicological techniques to populations exposed to xenob
iotics is relatively new, and the ability to measure an increasing num
ber of immune biomarkers of activation, suppression, autoimmunity or h
ypersensitivity is rapidly expanding, there are difficulties in the in
terpretation of statistically positive results (sometimes within the n
ormal range) and their potential health significance. Finally, both bi
ological and methodological factors complicate the assessment of dose-
response/concentration-effect relationships in human immunotoxicity st
udies, and traditional dose-response relationships may not always be p
resent. Published by Elsevier Science Ireland Ltd.