cleaning). Finally, background documents and reviews of experimental evidence were retrieved and examined.

The literature search resulted in the retrieval of about 30,000 titles. As the titles and abstracts were reviewed, it became apparent that many of the studies were not relevant to the committee’s task. The committee therefore developed inclusion criteria for the studies to be reviewed; for example, there had to be an examination of the agents under consideration, the study design had to be appropriate for the committee’s task of weighing evidence, and the publication had to be an original study rather than a review or meta-analysis. Results of the studies also had to demonstrate persistent rather than short-term effects. Applying those criteria helped the committee to narrow the 30,000 titles and abstracts to about 3000 peer-reviewed studies that were carefully reviewed. The studies were primarily occupational studies of workers exposed chronically to insecticides or solvents, including studies of Gulf War veterans that specifically examined insecticide and solvent exposure. Examples of studies excluded from review were those which focused solely on the efficacy of insecticide use in mitigating the effects of insect infestation or examined pesticide ingestion and suicide. Similarly, studies of occupations with exposure to multiple agents and those without specificity of agent (for example, farming and agricultural work) were excluded in that it was difficult to determine the agent responsible for an outcome. Case studies of acute poisonings or short-term outcomes were also excluded.

It should be noted that animal studies had a limited role in the committee’s assessment of association between exposure and health outcome. Animal data were used for making assessments of biologic plausibility; they were not used as part of the weight-of-evidence approach to determining likelihood that an exposure to a specific agent might have a specific long-term outcome. The animal studies were, however, used as evidence to support the epidemiologic data.

The committee did not collect original data or perform secondary data analysis. It did, however, calculate confidence intervals, when a study did not provide them, on the basis of the number of subjects (cases and controls), the relative risk or odds ratio, or the p value.


As noted, the committee adopted a policy of using only published, peer-reviewed literature to draw its conclusions. Although the process of peer review by fellow professionals enhances the likelihood that a study has reached valid conclusions, it does not guarantee validity. Accordingly, committee members read each study and considered its relevance and quality.

The committee classified the evidence of association between exposure to a specific agent and a specific health outcome into five previously established categories, as set forth below. The categories closely resemble those used by several IOM committees that have evaluated vaccine safety, herbicides used in Vietnam, and indoor pollutants related to asthma. The first three categories imply a statistical association. The committee’s conclusions are based on the strength and coherence of the findings in the available studies. The conclusions represent the committee’s collective judgment. The committee endeavored to express its judgment as clearly and precisely as the available data allowed. It used the established categories of association from previous IOM studies because they have gained wide acceptance over more than a decade by Congress, government agencies, researchers, and veterans groups.

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