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Gulf War and Health: Insecticides and Solvents, Volume 2
studies on exposure to pesticides and cancer outcomes are limited by sample size and lack of exposure specificity, the committee reviewed these studies and provides a brief discussion of their strengths and limitations at the end of each cancer section. However, the studies on exposure to pesticides are not considered primary evidence for the committee’s conclusions and are not included in the data analysis tables in the cancer sections.
It should be noted that for cancer sites on which no published studies of exposure to insecticides were available, the committee acknowledged the lack of data and did not draw a conclusion regarding association. Conclusions were drawn for all cancers in which a body of literature was available.
The committee focused its review of cancer outcomes on human studies that had comparison or control groups (cohort and case-control studies). Case reports, case series, review articles, and meta-analyses related to cancer were excluded from the committee’s review. Studies that by design could not provide valid exposure assessment information or estimates of risk—such as ecologic, cross-sectional, proportionate mortality ratio (PMR), and mortality odds ratio studies—were reviewed by the committee but were not considered critical to its conclusions. The committee describes those studies in the relevant sections of Chapter 5 as supplementary evidence and identifies the limitations related to drawing conclusions about associations. However, the studies are not identified in the tables that accompany each cancer section, because they were not critical to the committee’s conclusions. The specific limitations of ecologic, cross-sectional, PMR, and mortality odds ratio studies are described in Chapter 2.
Toxicity and Carcinogenicity
Toxicologic studies examine the direct effects of various agents on natural processes in organisms. They can determine whether a specific chemical is carcinogenic in animals (such as rodents or other animals). Some studies in rodents have demonstrated carcinogenic and tumorigenic effects following long-term or high-dose oral exposure to several insecticides under review in this report, although some have inconsistent results. For example, exposure to dichlorvos has led to leukemia, pancreatic adenoma, and squamous cell papilloma of the forestomach in certain experimental studies (ATSDR, 1997). The International Agency for Research on Cancer (IARC)2, which is charged with evaluating and determining whether a chemical agent is carcinogenic in humans on the basis of evidence from studies on both humans and animals, has determined that dichlorvos is “possibly carcinogenic to humans.” That classification is based on IARC’s finding of “inadequate evidence” in humans and “sufficient evidence” in experimental animals of the carcinogenicity of dichlorvos (IARC, 1991).
With regard to malathion and lindane, hepatic cancers have been observed in studies on animals exposed to each (ATSDR, 1999, 2001a). IARC has reviewed hexachlorocyclohexanes, which include the gamma isomer known as lindane, and has determined that the insecticide is “possibly carcinogenic to humans” on the basis of “inadequate evidence” in humans and “limited evidence” in animals. IARC also found
It is important to note the differences in the objective of the IARC program and the charge of this committee. The objective of the IARC program is to determine whether agents or occupational exposures are carcinogenic, whereas this committee is charged with determining whether or not there is an association between exposure to a specific agent or agents and a specific health outcome, such as a particular cancer.