aldicarb exhibited an altered number of T cells, including decreased CD4:CD8 ratios (Fiore et al., 1986). Immunologic effects also have been reported in individuals exposed to methyl isocyanate, an intermediate in the production of carbamate pesticides, after an industrial accident in 1984 in Bhopal, India (Deo et al., 1987). The effects of immune response included an increase in the number of CD4 and total T cells, but decreases in lymphocyte mitogenesis. Several persistent immune alterations, also primarily cell-mediated, have been reported in Michigan residents who ingested dairy products contaminated with polybrominated biphenyls (Bekesi et al., 1978), although Silva et al. (1979) were unable to detect any immune abnormalities in a similarly exposed cohort. Individuals occupationally exposed to 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD), which is one of the subregistries established by the ATSDR (Jennings et al., 1988), also demonstrated immune changes. Jennings showed that antinuclear antibodies and immune complexes were detected significantly more frequently in the blood of dioxin-exposed workers. In addition, the number of leukocytes in peripheral blood cells was elevated in dioxin-exposed workers. Some of these changes were not confirmed in a later study (Evans et al., 1988), perhaps because of a technical error; other observations were confirmed. Benzene-induced pancytopenia, a classic symptom of chronic benzene exposure, is an immunodeficiency disease by virtue of the reduced number of immunocompetent cells that result from altered marrow function (Snyder, 1984). In fact, lymphopenia is common after exposure to organic solvents (Browning, 1965; Capurro, 1980). Alterations in the number of some cell types (decreases in CD3 and CD4) were reported to occur in solvent-exposed workers (Denkhaus et al., 1986); the effects might have some specificity.

In addition to environmental chemicals, a large number of therapeutic substances, as well as abused recreational drugs, can alter immune function in humans. Among these are diphenylhydantoin, ethanol, cocaine, and isobutyl nitrites (Newell et al., 1984; Specter et al., 1986).

Although most of the xenobiotics that alter the human immune system also can affect experimental animals, clinical studies often have been criticized for incomplete or inconsistent diagnosis of immunodeficiency, lack of clinical changes, small group size, inability to establish exposure levels, or lack of reproducibility. As might be expected, there are several studies in which immune functions were not shown to be affected after the subjects were exposed to presumably high levels of chemicals, even though the agents, such as heavy metals and TCDD, are known to be immunotoxic in animals (Reggiani, 1980; Kimber et al., 1986). Furthermore, there is no evidence that xenobiotics can influence immune systems in the general population (except through occupational or inadvertent exposure).

The question of population-wide immune system effects would be difficult to answer, because the immunologic effects one might expect in the general population would likely be subtle. The tests routinely used for clinical assessment of immunosuppressed function in humans are not very sensitive. The difficulty in identifying a recently exposed, well-defined cohort is substantial. There is considerable immunologic variability in the general population. A consensus exists that further clinical studies with better-defined cohorts and more sensitive tests will be required to assess the true potential of xenobiotics to affect human health.

A growing body of research in immunotoxicology has shown that many xenobiotic substances cause immunosuppression in laboratory animals (Table 5-3). Immunologic effects often are accompanied by increased susceptibility to challenge with infectious

Front Matter (R1-R18)

Summary (1-8)

1 Introduction (9-22)

2 The Structure and Function of the Immune System and Mechanisms of Immunotoxicology (23-32)

3 Biologic Markers for Immune-Mediated Disease (33-52)

4 Autoimmune Diseases (53-62)

5 The Capacity of Toxic Agents to Compromise the Immune System (Biologic Markers of Immunosuppression) (63-82)

6 Animal Models for Use in Detecting Immunotoxic Potential and Determining Mechanisms of Action (83-98)

7 Human Immune-System Biologic Markers of Immunotoxicity (99-112)

8 Application of Biologic Markers of Immunotoxicity in Epidemiology (113-126)

9 Use of Biologic Markers in Controversial Areas of Environmental Health (127-140)

10 Summary and Recommendations (141-148)

References (149-182)

Glossary (183-192)

Biographies (193-198)

Index (199-206)