CHEMICAL-AGENTS AND THE IMMUNE-RESPONSE

Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased under standing of the immune system and an appreciation of its complex regul atory network. This has spawned a broad interest in the area of immnun otoxicology within the scientific community as well as certain concern s in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to ch emicals has increased, in part, due to the fact that chemical companie s are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease, of which 2-5% are from occupational exposure. Although there is not yet a clear und erstanding of dose-response relationships or disease predisposition, t here are many well-defined examples (isocyanates, anhydrides) of chemi cal sensitizers in humans and experimental animals. Evidence that chem icals suppress immune responses in humans is considerably less well es tablished, although there is a public perception that chemicals genera lly cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academ ic and industrial communities. As a consequence of these public and sc ientific concerns, many of the regulatory agencies are developing immu notoxicity testing guidelines. At the present, however, there are limi tations on adequate human methodology and data that allow the extrapol ation of animal data to assess human risk. The potential for human imm unosuppression remains of concern, however, because of a large databas e generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., h alogenated aromatic hydrocarbons) or occupationally (asbestos, benzene ) exposed to xenobiotics. This concern is exacerbated by current knowl edge regarding the long-term consequences of immunosuppression that ma y be associated with pathologic conditions (e.g., cancer, increased in fections). Likewise, exposure to immunotoxic xenobiotics may represent additional risk to individuals with already fragile immune systems (e .g., malnutrition, infancy, old age). In another light, there has been considerable public concern regarding ''chemical hypersensitivity syn drome'' (also referred to as ''multiple chemical sensitivities syndrom e'') and its relationship to hypersensitivity as well as immunosuppres sion. Although there exists- a substantial population who claim to hav e this disorder, the syndrome is not well understood. Several mediator s- have been proposed including disorders of immune regulation as well as conditioned responses to odors involving pharmacologic and/or psyc hologic mechanisms. At present, them is no definitive evidence that th ese syndromes are immunologically mediated.