PRINCIPLES OF TOXICOLOGY

The mainstay of treatment of multiple-chemical sensitivity involves avoidance of what are regarded
as the inciting chemicals. In some cases, this can be taken to extremes, involving near isolation in
specially controlled environments. Vitamins and mineral supplements are often recommended, as well
as intravenous gammaglobulin, ostensibly to fortify the immune system. “Neutralization” doses of
extracts identified positively in provocation–neutralization tests are sometimes recommended to relieve
or prevent symptoms. Reports of efficacy of these treatments are either anecdotal or from poorly
controlled studies. Objective evidence that any of these treatments leads to improvement in the patient’s
condition is generally considered to be absent.
10.8 SUMMARY
A fully functioning immune system is vital for defense against pathogenic microorganisms and to
prevent the emergence of cancerous cells. It is a complex system, requiring the cooperation of many
types of cells. The immune system is capable of both specific and nonspecific responses to insults.
Specific responses are elicited by macromolecules recognized by the body as being foreign, termed
antigens. The presence of an antigen can trigger a humoral response (i.e., the production of antibodies
that bind rather specifically to that molecule) or a cell-mediated response in which cells carrying the
antigen on their surface are attacked by specialized immune cells (e.g., natural-killer cells or cytotoxic
lymphocytes).
Drugs and chemicals can produce adverse health effects by influencing the immune system in one
of three ways:
1. Causing a Hypersensitivity Reaction. There are four basic types of hypersensitivity reactions
(types I–IV), each with a different mechanism. Depending on the type of reaction, symptoms may be
immediate or delayed, mild or severe, and involve different organs and tissues. Allergic reactions can
cause considerable discomfort in the workplace, and some types (e.g., a severe type I reaction, or
anaphylaxis) can be life-threatening.
2. Suppressing the Immune System. Normal function of the immune system requires participation
by many components, and disruption of any of these could conceivably result in impaired capability.
If impairment is sufficient, the individual is at increased risk of infection and cancer. This has been
clearly demonstrated by patients on immunosuppressive therapy (e.g., transplant patients) and in
animal studies involving a variety of chemicals. Although there are few clear examples of immunosuppression
from occupational or environmental exposure in humans, there is no reason to expect that
this effect cannot occur under these circumstances as well.
3. Causing or Exacerbating Autoimmune Disease. By producing a dysregulation of the immune
system, drugs and chemicals are capable of causing the immune system to attack normal body
constituents. This has been clearly demonstrated for several drugs, and a number of reports suggest
that it may also occur from occupational and environmental exposures.
The potential for a chemical to produce immunotoxicity can be assessed through a variety of in vivo
and in vitro tests. Most of these tests focus on effects on a very specific aspect of the immune system.
The immune system possesses considerable functional redundancy and extra capacity, and alterations
(or “abnormalities”) in one or a few parameters may not necessarily result in diminished overall
functional of the immune system. Consequently, the results of these tests must be interpreted carefully.
REFERENCES AND SUGGESTED READING
10.8 SUMMARY 205
Burleson, G. R., J. H. Dean, and A. E. Munson, Methods in Immunotoxicology, Wiley-Liss, New York (1995).