Veterans and Agent Orange Update 2002 (2003) / Chapter Skim
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2. Considerations in Evaluating the Evidence
2. Considerations in Evaluating the Evidence
Pages 20-29
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From page 20... ...
Determining whether an observed association between an exposure and a health outcome is "real" requires additional scn~tiny because there may be alternative explanations for the observed association. Those explanations include error in the design, conduct, or analysis of the investigation; bias, a systematic tendency to distort the measure of association so that it may not represent the true relation between exposure and outcome; confounding, distortion of the measure of association because of failure to recognize or account for another factor related to both exposure and outcome; and chance, the effect of random variation, which produces spurious associations that can, with a known probability, sometimes depart widely from the true relation.
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From page 21... ...
As with the epidemiologic evidence, the chapter concentrates on studies publishedin200~2002 but considers all relevant studies in drawing conclusions. Theissueof whether a relationship between a particular chemical exposure and a particular health outcome reflects a true association in humans is addressed in the context of research regarding the mechanism of interaction between the chemical and biologic systems, evidence from animal studies, and evidence of an association between exposure and the occurrence of a health outcome in humans, including evidence from occupational and environmental chemical exposures.
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From page 22... ...
It is generally accepted that genetic susceptibility plays a key role in determining the adverse effects of environmental chemicals. Genetic susceptibility is central in the assessment of biologic plausibility because if polymorphisms of the gene encoding the AhR exist in humans as they do in laboratory animals, some people would be at greater risk or at lesser risk for the toxic and carcinogenic effects of TCDD.
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From page 23... ...
For instance, the analytic data available on people known to have been exposed to herbicides during the Vietnam War constitute a valuable resource for the study of TCDD-related disease; documented TODD body burdens provide a quantitative bridge between experimental studies and epidemiology. Taken together, experimental studies and epidemiologic investigations provide complementary perspectives from which to view human health effects of exposure to herbicides.
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From page 24... ...
Evaluations of disease-exposure associations that are based solely on the published literature, therefore, could be biased in favor ofpositiveassociations.In reviewing reports of overall associations with exposure, however, the committee clid not consider the risk of publication bias to be high among studies of herbicide exposure and health risks, because numerous published studies show no positive association, it examined a substantial amount of unpublished matenal, and it felt that publicity surrounding exposure to herbicides, particularly of Vietnam veterans, has been so intense that studies that show no association would! be unlikely to be viewed as unimportant by the investigators that is, the pressure to publish such "negative" findings would be considerable.
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From page 25... ...
Those aspects of the commiRee's review required thoughtfill consideration of alternative approaches at several points and could not be accomplished by adherence to a narrowly prescribed formula. The approach described here therefore evolved throughout the committee process and was determined, to a large extent, by the nature of the evidence, exposures, and health outcomes examined.
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From page 26... ...
, Veterans and Agent Orange: Update 1998 (TOM, 1999; hereafter, Update 19989, and Veterans and Agent Orange: Updlate 2000 (IOM, 2001; hereafter, Update 20029, this review summarizes the recent experimental data that serve as a scientific basis of assessment of the biologic plausibility of health outcomes reported in epidemiologic studies. Efforts to establish the biologic plausibility of effects of herbicide exposure in the laboratory strengthen the evidence of the herbicide effects suspected to occur In humans.
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From page 27... ...
Most, if not all, of TCDD's effects are mediated through the ary} hydrocarbon receptor (AhR) , which interacts with other proteins, binds to DNA and results in biochemical effects, including enzyme induction.
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From page 28... ...
Mechanisms of Toxic Action Mechanisms Related to Genotoxic Effects Several studies reviewed in Update 2000 indicate a relatively weak or no genotoxic potential of 2,4-D. Two studies published since then are consistent with a lack of genotoxicity.
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From page 29... ...
Two studies examined the ability of 2,4-D to increase heat-shock proteins in bacteria and a human cell line. 2,4-D exposure induced several heat-shock proteins in bacteria (Cho et al., 2000)
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