Autoimmunity By Pesticides: Multiple Exposures & Increased Susceptibility
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Autoimmunity By Pesticides: Multiple Exposures & Increased
Susceptibility
Date:
Sun, 25 Aug 2002 12:34:05
-400
From:
Stephen Tvedten <steve@getipm.com>
Organization: Get Set Inc. (www.getipm.com)
To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of California, Department of Pesticide
Regulation
cc: Christine Whitman whitman.christine@epa.gov
Autoimmunity by pesticides: multiple exposures &
increased susceptibility
Date: Sat, 24 Aug 2002 20:22:56 -0500
Enhanced adverse-effects of multiple exposures (eg, too many pesticides, arsenic in wood, physician-injected ethylmercury, toxic sludge in our food) will be increasingly appreciated. Note that the first citation an article by a Dow employee. I used PubMed's "related articles" function and found that "susceptibility" did not occur in the titles of any related articles. Nor was Dale Hattis cited -- despite his important articles about inter-individual susceptibility and the subgroups of individuals with increased susceptibility (eg, 6-12). Several other citations are provided (2-5).
Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
1: Toxicol Lett 2002 Feb 28;127(1-3):101-9
Autoimmunity by pesticides: a critical review of the state of the science.
Holsapple MP.
Toxicology and Environmental Research and Consulting, 1803 Building, Midland,
MI 48674, USA.
<mholsapple@dow.com>
The goals of this paper will be to present a critical review of the state of the science of pesticides and autoimmunity, and to discuss research that addresses the potential links between environmental chemicals and autoimmune disease. To date, the science of immunotoxicology has primarily focused on immunosuppression and hypersensitivity/allergy, and test methods are available to address these outcomes. So much progress has been made to address immunosuppression and contact sensitization that there are regulatory guidelines in the U.S. included in the registration of pesticides. In contrast, there are no validated approaches to assess autoimmunity. The overall objective of this paper will be to use pesticides as an important class of environmental chemicals to critically evaluate the state of the science for addressing chemical-induced autoimmunity. Specific examples of studies with pesticides will be discussed in the context of the following types of approaches: animal studies using standard immunotoxicological parameters; animal studies using specialized models of autoimmunity; human studies after environmental or occupational exposure; and human studies after accidental poisoning.
Publication Types:
- Review
- Review, TutorialPMID: 12052647
[PubMed - indexed for MEDLINE]
2: J Toxicol Environ Health A 1999 Jun 25;57(4):225-36
Prevalence of antinuclear antibodies in a rural population.
Rosenberg AM, Semchuk KM, McDuffie HH, Ledingham DL, Cordeiro DM, Cessna AJ,
Irvine DG, Senthilselvan A, Dosman JA.
Department of Pediatrics, Centre for Agricultural Medicine, College of
Nursing, University of Saskatchewan and National Water Research Institute,
Saskatoon, Canada.
Exposure to environmentally and occupationally encountered toxicants can be associated with the development of certain autoimmune diseases and with the induction of antinuclear antibodies (ANA). Some chemicals used in the agricultural industry are known to affect immune function but their roles in the induction of autoimmunity in general, and ANA in particular, have not been reported previously. This study was undertaken to establish the prevalence of ANA in a rural population and to determine environmental and occupational exposures with which they are associated. This cross-sectional study represented one component of an interdisciplinary project (Prairie Ecosystem Study [PECOS], Eco-Research Program, Tri-Council Secretariat of Canada) designed to explore, in a rural population, the roles of environmental exposures as determinants of human health status. Information regarding lifetime, current, and main occupational exposures in the rural-dwelling study population was derived from a self-administered questionnaire. Sera from consenting subjects, collected during the months of February and March 1996, were assayed for ANA by indirect immunofluorescence on HEp-2 cells. The study population comprised 322 adult subjects (mean age 49.3+/-14.7 yr; range 16-87 yr). Statistical analyses adjusted for age and sex revealed that the presence of ANA among the participants was associated with a current agricultural occupation that included oilseed production, hog production, or poultry production. There was a significant association between ANA positivity and a current main farming operation of crop production. There was also an association among individual participants between lifetime exposure to the insecticide class of pesticides and the presence of ANA. In this rural study population, ANA positivity was significantly associated with lifetime exposure specifically to carbamate, organochlorine (including aldrin, chlordane, dieldrin, endrin, heptachlor, and lindane, but excluding DDT and methoxychlor), and pyrethroid insecticides and to phenoxyacetic acid herbicides, including 2,4-D. After adjustment for age, sex, and other insecticide exposures, multivariate analyses indicated that ANA positivity was associated with current oilseed production and with lifetime exposure to pyrethroid insecticides. In a rural population, ANA were associated with production of certain crops and certain animals and exposure to specific pesticides. The data indicate that some occupational exposures related to the agricultural industry are associated with the presence of ANA, a serologic expression of autoimmunity.
PMID: 10406347 [PubMed - indexed for MEDLINE]
3: Environ Health Perspect 1998 Feb;106 Suppl 1:85-109
Integrated defense system overlaps as a disease model: with examples for
multiple chemical sensitivity.
Rowat SC.
Grantham's Landing, British Columbia, Canada.
<steven_rowat@sunshine.net>
The central nervous, immune, and endocrine systems communicate through multiple common messengers. Over evolutionary time, what may be termed integrated defense system(s) (IDS) have developed to coordinate these communications for specific contexts; these include the stress response, acute-phase response, nonspecific immune response, immune response to antigen, kindling, tolerance, time-dependent sensitization, neurogenic switching, and traumatic dissociation (TD). These IDSs are described and their overlap is examined. Three models of disease production are generated: damage, in which IDSs function incorrectly; inadequate/inappropriate, in which IDS response is outstripped by a changing context; and evolving/learning, in which the IDS learned response to a context is deemed pathologic. Mechanisms of multiple chemical sensitivity (MCS) are developed from several IDS disease models. Model 1A is pesticide damage to the central nervous system, overlapping with body chemical burdens, TD, and chronic zinc deficiency; model 1B is benzene disruption of interleukin-1, overlapping with childhood developmental windows and hapten-antigenic spreading; and model 1C is autoimmunity to immunoglobulin-G (IgG), overlapping with spreading to other IgG-inducers, sudden spreading of inciters, and food-contaminating chemicals. Model 2A is chemical and stress overload, including comparison with the susceptibility/sensitization/triggering/spreading model; model 2B is genetic mercury allergy, overlapping with: heavy metals/zinc displacement and childhood/gestational mercury exposures; and model 3 is MCS as evolution and learning. Remarks are offered on current MCS research. Problems with clinical measurement are suggested on the basis of IDS models. Large-sample patient self-report epidemiology is described as an alternative or addition to clinical biomarker and animal testing.
Publication Types:
- Review
- Review, Academic
PMID: 9539008 [PubMed - indexed for MEDLINE]
4: J Toxicol Environ Health 1996 Jun 28;48(3):215-29
Clinical immunotoxicity of pesticides.
Vial T, Nicolas B, Descotes J.
Department of Pharmacology and Medical Toxicology, INSERM U80, Laennec
Faculty of Medicine, Lyon, France.
Because of the wide use of pesticides for domestic and industrial purposes, the evaluation of their immunotoxic effects is of major concern for public health. Despite the large amount of experimental data describing pesticide-induced immunosuppression, evidence that pesticides may severely impair immune functions in humans is lacking or scarce. Contact hypersensitivity is a well-identified immunotoxic effect of pesticides but remains a rare complaint in pesticide-exposed workers. By contrast, immunologically mediated systemic reactions have been described only as debatable case reports. The association between autoimmune diseases and pesticide exposure has more recently been suggested. Despite the lack of convincing human data, a potential risk for the immune system should not be excluded, especially during chronic exposure to pesticides or in otherwise (immuno) compromised patients (malnutrition, children, old patients). Epidemiological studies including markers of exposure and the assessment of immune competence in exposed individuals, or registries of sentinel diseases related to immunosuppression (e.g., non-Hodgkin's lymphoma, opportunistic infections) or autoimmunity (e.g. lupus erythematosus, rheumatoid arthritis), are warranted.
Publication Types:
- Review
- Review, Tutorial
PMID: 8656446 [PubMed - indexed for MEDLINE]
5: Arch Environ Health 1993 Mar-Apr;48(2):89-93
Immunologic abnormalities in humans exposed to chlorpyrifos: preliminary
observations.
Thrasher JD, Madison R, Broughton A.
Department of Health Science, California State University, Northridge.
Twelve individuals who were exposed to chlorpyrifos were studied 1-4.5 y
following exposure to determine changes in the peripheral immune system. The
subjects were found to have a high rate of atopy and antibiotic
sensitivities, elevated CD26 cells (p < .01), and a higher rate of
autoimmunity, compared with two control groups. Autoantibodies were directed
toward smooth muscle, parietal cell, brush border, thyroid gland, myelin, and
ANA. Chlorpyrifos exposure was implicated in the immunologic abnormalities
reported. The immunologic changes were similar to those reported for other
pesticides.
PMID: 7682805 [PubMed - indexed for MEDLINE]
6: Hattis D, Russ A, Goble R, Banati P, Chu M.
Human interindividual variability in susceptibility to airborne
particles.
Risk Anal. 2001 Aug;21(4):585-99. Review.
7: Hattis D, Banati P, Goble R, Burmaster DE.
Human interindividual variability in parameters related to health
risks.
Risk Anal. 1999 Aug;19(4):711-26. Review.
8: Hattis D, Banati P, Goble R.
Distributions of individual susceptibility among humans for toxic
effects. How much protection does the traditional tenfold factor provide
for what fraction of which kinds of chemicals and effects?
Ann N Y Acad Sci. 1999;895:286-316.
9: Hattis D.
Human interindividual variability in susceptibility to toxic
effects: from annoying detail to a central determinant of risk.
Toxicology. 1996 Jul 17;111(1-3):5-14. Review.
10: Hattis D.
The challenge of mechanism-based modeling in risk assessment for
neurobehavioral end points.
Environ Health Perspect. 1996 Apr;104 Suppl 2:381-90. Review.
11: Hattis D, Glowa J, Tilson H, Ulbrich B.
Risk assessment for neurobehavioral toxicity: SGOMSEC joint report.
Environ Health Perspect. 1996 Apr;104 Suppl 2:217-26. Review.
12: Hattis D, Silver K.
Human interindividual variability--a major source of uncertainty in
assessing risks for noncancer health effects.
Risk Anal. 1994 Aug;14(4):421-31. Review.
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