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 understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immnunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies 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 understanding of dose-response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academic and industrial communities. As a consequence of these public and scientific concerns, many of the regulatory agencies are developing immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess human risk. The potential for human immunosuppression remains of concern, however, because of a large database generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., halogenated aromatic hydrocarbons) or occupationally (asbestos, benzene) exposed to xenobiotics. This concern is exacerbated by current knowledge regarding the long-term consequences of immunosuppression that may be associated with pathologic conditions (e.g., cancer, increased infections). 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 syndrome'' (also referred to as ''multiple chemical sensitivities syndrome'') and its relationship to hypersensitivity as well as immunosuppression. Although there exists- a substantial population who claim to have this disorder, the syndrome is not well understood. Several mediators- have been proposed including disorders of immune regulation as well as conditioned responses to odors involving pharmacologic and/or psychologic mechanisms. At present, them is no definitive evidence that these syndromes are immunologically mediated.