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Rachel's Environmental & Health Weekly
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Statement on Immune Toxins
[Here we present, verbatim, a consensus statement about toxic chemicals and the immune system written by 18 scientists[1] and published in the summer of 1996.[2] The scientists met at a workshop in Racine, Wisconsin, February 10-12, 1995, to discuss the issue "because of the pervasive contamination of the environment by compounds... [having] the potential to disturb the immune system of wildlife and humans.... introduced into the environment by human activity...."[2] The statement is not easy reading, so we have added a few clarifications and commentaries of our own inside square brackets.]
Consensus Statement
The following consensus was reached by participants[1] at the workshop.
A) We are certain of the following--
A competent immune system is essential for health.
Experimental lab studies demonstrate that certain synthetic chemicals affect the immune system (e.g., aromatic hydrocarbons; carbamates [a class of pesticides]; heavy metals [for example, mercury]; organohalogens [for example, many chlorine-containing compounds]; organophosphates [a class of pesticides]; organotins [chemicals containing tin and carbon atoms]; oxidant air pollutants, such as ozone and nitrogen dioxide; and polycyclic aromatic hydrocarbons [often produced by combustion of coal, oil, gasoline, garbage, medical waste]). These effects are manifested as alterations in the immune system that may lead to a decreased quality of life. These alterations include immune modulation [changes in the immune system] expressed as an increase or decrease in measured immune parameters [for example, the number of T cells or B cells in blood], hypersensitivity, and autoimmunity.
[In other words, from experiments on laboratory animals, it is known with certainty that many classes of common chemicals can change the immune system and can cause hypersensitivity and autoimmune diseases. In humans, hypersensitivity is often expressed as an allergic reaction. [3,pgs.81-106] Autoimmune diseases include diabetes, multiple sclerosis, rheumatoid arthritis, lupus, and a dozen other diseases. [3,pg.123]]
Changes in the characteristics of the immune system in humans and certain wildlife species have been associated with both therapeutic and environmental exposure to synthetic chemicals, e.g., diethylstilbestrol (DES), dioxin, polychlorinated biphenyls (PCBs).
Impairment of the immune system can result from alterations in the development [before and shortly after birth or hatching] of the immune system and may be long-lasting. The effects may not be manifested at hatching or birth and may not be expressed until the animal or human reaches adulthood.
Life-long capacity for immune response [i.e., healthy functioning of the immune system] is determined early in development, during prenatal and early postnatal development in mammals and prehatching and early posthatching development in egg-laying species.
Alterations in the developing and mature immune systems may not be recognized as an adverse health effect until long after the exposure.
Some wildlife and human populations are exposed to elevated levels of certain synthetic chemicals.
The widespread exposure of populations of humans and wildlife to many man-made chemicals has made it difficult, if not impossible, to find control populations that have no exposure level. True control populations for human and wildlife epidemiological studies are thus lacking. [In other words, we are all now exposed to many chemicals that can change our immune systems, so it is not possible to find a "control group" of people who have truly healthy, unaffected immune systems that can be studied.]
B) We estimate with confidence that--
Certain synthetic chemicals, such as those listed above, released or reintroduced into the environment act upon the developing and mature immune systems in humans and other vertebrates.
Prenatal and early postnatal mammals and the immature and early life stages of amphibians, reptiles, fishes, and birds are likely to be the most vulnerable life stages to immunomodulation [changes in the immune system].
Vulnerability upon exposure varies among gender, species, and stages of the life cycle. In addition to embryos, fetuses, and the newborn, children, the very old, and certain populations (e.g., chronically ill, poorly nourished, HIV positive) are also likely to be more at risk. [Naturally, this makes it difficult to study the effects of chemicals on the immune system because the effects vary greatly, depending on the stage of life of the person or animal being studied.]
In certain instances, humans and wildlife are experiencing immune alterations. Data suggest that immune alterations seen in wild animals and humans are consistent with those produced by synthetic chemicals identified as immunotoxic in studies with laboratory animals.
Immunotoxic effects expressed in individuals could therefore be expressed at the population level thus affecting biodiversity at the community or ecosystem level. [In other words, so many individuals might be affected that entire populations could have their immune systems degraded.]
Immune system effects reported in wildlife, in parallel with IN VITRO [test tube] and IN VIVO [living animal] experimental studies, support the possibility for qualitative prediction of human effects.
Current predictive capability for immunomodulation is limited to identification of qualitative changes not quantitative changes.
C) Based on our current understanding we predict--
Certain synthetic chemicals can cause alterations of the developing immune system.
Alterations in immunologic function whether occurring prenatally or embryologically or later in life can translate into altered host resistance and susceptibility to disease, including autoimmune disease. Disease patterns are thus likely to be affected by immune modulation induced by immunological toxicants.
D) There are uncertainties in our understanding because--
More needs to be learned about how the immune system develops.
Few well-controlled human or wildlife ecoepidemiological studies that document immune modulation [immune system changes] have been completed.
The lack of sensitive tests and the uncertainty about exposure have been impediments in many of these studies. Exposure is well known for some wildlife studies.
Information on exposure is limited. Little is known about the effects of long-term, low-level exposure.
Little is known about the effects of exposure to chemical mixtures. Most published studies use single agents when testing for the effects of environmental exposure. The specific components of environmental mixtures are rarely defined.
The pharmacokinetics of many immunotoxic compounds in target organs is understood in experimental animals but not in humans and wildlife. [Pharmacokinetics refers to the precise details, at the level of the cell, of how chemicals affect living things.]
Data are lacking about the persistence of the effects of immunomodulators.
For regulatory purposes, the current lack of knowledge about the mechanisms leading to immunomodulation makes cause-and-effect linkages extremely difficult.
Uncertainty exists about whether the right questions have been asked concerning the mechanisms of immune modulation.
E) Our judgment is that--
The potential exists for widespread immunotoxicity in humans and wildlife species because of the worldwide lack of appropriate protective standards. This is based on documented immune effects from high-level exposure, plus a large amount of anecdotal data on humans and wildlife, and strong experimental animal data.
Although exposure is widespread, it varies from region to region and individual to individual. Based on anecdotal information, it is presumed that exposure is greater in Eastern Europe and the former Soviet Union and especially in developing countries because of lack of adequate environmental regulations and enforcement.
The lack of human epidemiological studies in the developing world makes it impossible to determine the scale of immune modulation and/or autoimmune disease among these populations. The consequences of chemical exposure in developing countries may be severe because of multiple confounders such as poverty, malnutrition, and poor medical care. The consequences will be difficult to identify because of the lack of adequate control cohorts.
The risk of exposure to known immunomodulators is sufficient to warrant regulatory approaches that would limit exposure. [In other words, we already know enough to justify taking regulatory action.]
F) To improve our predictive capacity--
More basic research is needed on the development of the immune system of diverse animal species and the factors that drive its maturation and senescence [loss of power with age]. Further study is needed to understand the mechanistic role of synthetic chemicals in the alteration of these processes.
Priority needs to be given to developing assays [tests] predictive of disease resistance for a variety of species. It is important to know how immune modulation affects increased prevalence of infectious diseases among humans and wildlife.
More emphasis must be placed on developmental immunotoxicology. This can be accomplished through collaborative research efforts to standardize protocols, share specimens, and to develop inexpensive, rapid biomarkers of immunotoxicity. The use of the Internet and other online systems to apprise researchers of planned and ongoing experiments will increase collaborative opportunities.
Models based on "real world" situations (dose, duration of exposure, timing) that include metabolism, pharmacokinetics, route of exposure, and target effects in a number of indicator species should be developed for extrapolation to humans and other species.
Ecoepidemiological criteria that include dose-response, time order (exposure precedes effect), specificity, strength of association, coherence, and predictability combined with laboratory validation are needed to improve the level of certainty in epidemiological studies.
More epidemiological research among susceptible populations, especially in developing countries, is needed. [End of consensus statement.]
--Peter Montague (National Writers Union, UAW Local 1981/AFL-CIO)
[1] Authors of the statement include: Dr. John B. Barnett, Department of Microbiology and Immunology, West Virginia University, Morgantown, West Virginia; Dr. Theo Colborn, World Wildlife Fund, Washington, D.C.; Dr. Michael Fournier, Laboratoire de Rescherche en Toxicologie de l'Environnement, Universite du Quebec, Montreal, Quebec, Canada; Dr. John Gierthy, Department of Environmental Health and Toxicology, State University of New York, Albany, N.Y.; Dr. Keith Grasman, Department of Biological Sciences, Wright State University, Dayton, Ohio; Dr. Nancy Kerkvliet, Department of Agricultural Chemistry, Oregon State University; Corvallis, Oregon; Mr. Garet Lahvis, University of Maryland, School of Medicine, Baltimore, Md.; Dr. Michael Luster, Environmental, Immunological, and Neurobiological Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; Dr. Peter McConnachie, Immunotransplant Lab, Southern Illinois University, School of Medicine, Springfield, Illinois; Dr. J. Peterson Myers, W. Alton Jones Foundation, Charlottesville, Va.; Dr. A.D.M.E. Osterhaus, Erasmus University, Rotterdam, The Netherlands; Dr. Robert Repetto, World Resources Institute, Washington, D.C.; Dr. Rosalind Rolland, World Wildlife Fund, Washington, D.C.; Dr. Louise Rollins-Smith, Vanderbilt University, Nashville, Tenn.; Dr. Ralph Smialowicz, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; Dr. Michael Smolen, World Wildlife Fund, Washington, D.C.; Dr. Sarah Walker, University of Missouri, Department of Internal Medicine, Columbia, Mo.; Dr. David Watkins, University of Wisconsin, Medical School, Madison, Wisconsin.
[2] "Statement of the Work Session on Chemically-Induced Alterations in the Developing Immune System: The Wildlife/Human Connection," ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 104 Supplement 4 (August, 1996), pgs. 807-808.
[3] William R. Clark, AT WAR WITHIN; THE DOUBLE-EDGED SWORD OF IMMUNITY (New York: Oxford University Press, 1995).
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