IARC assembles a panel of experts covering the appropriate range of scientific expertise, including epidemiology, toxicology, and exposure assessment, to evaluate the literature on
chemical toxicity based on animal data and to determine whether there is sufficient evidence
for harm in humans. To date, they have identified one pesticide—arsenic—and one
contaminate—dioxin—to be known human carcinogens. There was a general association
between insecticides and an elevation of human cancers, but the studies were deemed
insufficient at the time to determine which specific chemicals were associated with the
elevated cancer risk.
The risk of melanoma is potentially increased with pesticide use, particularly the chemical carbaryl (used primarily in insecticides). The risks of nonmelanoma skin cancers are difficult to assess, as state cancer registries generally do not collect information on these cancers.
Birth defects or developmental abnormalities might be faster indicators of toxicity than
carcinogenesis. Dr. Fenton’s studies of the mammary gland provide a compelling model for
identifying toxicities in a rapid manner. The prostate is also an informative model for early developmental effects. NIEHS, a collaborator with the Agricultural Health Study, is looking
at adverse reproductive outcomes from the study data.
Future toxicology studies should focus on metabolite data. A number of the metabolites of DDT have been evaluated, but the metabolite data for most other compounds are unknown—
especially chlorotriazines, where several parent compounds all form the same metabolites.
The way a person metabolizes various compounds will have a major effect on their
susceptibility to both toxicity and carcinogenesis.
The Agricultural Health Study is approaching its second generation of studies and until their previous results are replicated, inconsistencies based on pesticide ratings by the EPA and
IARC will remain. These agencies’ ratings do not take into account the possibility that the
mechanism of action of pesticides is non-genotoxic.
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The number of cases occurring in cancer clusters is typically too small to launch a detailed investigation; the purpose of statewide studies is to detect patterns to help determine the
causes of these clusters.
Data concerning childhood cancer are still in their infancy, and the disparities facing Latino and socioeconomically disadvantaged children are particularly difficult to assess. However,
half of the children enrolled in the Northern California Childhood Leukemia Study are
Latino, which should provide a sufficient number of cases to identify the factors that predict risk in these different groups of children.
There is an increased incidence of prostate cancer related to the combination of
organophosphate exposure and a predisposed genetic history. Family history plays an
important role in cancer risk and multiple efforts are under way to identify the interplay
between genetic susceptibility and environmental exposures.
The National Children’s Study will follow early-life exposures and evaluate pubertal timing from the beginning of breast development through completion of puberty. Also, NIEHS is
sponsoring the Breast Cancer and the Environmental Research Center, which has a human
component that evaluates young girls going through puberty and studies the effects of early
life exposures on breast development. These data, along with specific chemical information,
will facilitate a faster evaluation of the risk factors for breast cancer.
Stomach cancer is still important worldwide, but rates have decreased in the U.S. since the introduction of refrigeration in the twentieth century. Nitroso compounds and Helicobacter pylori infection at an early age are known risk factors.
A concern of large epidemiologic studies, such as the Agricultural Health Study, is
enrollment bias. At the design stage, the expectation was that 10,000 African Americans
would be enrolled into the study, but actual enrollment was only 1,500. Migrant workers were
left out of the study, as they cannot be captured using a state cancer registry.
Epidemiologic studies are presently being conducted at the molecular level to understand
mechanisms and modes of action of chemicals. Occupational and environmental studies are
an ideal area to use these new technologies to uncover the gene-environment interactions
involved in carcinogenesis. These emerging technologies can also be applied to exposure
assessment and intermediate biologic endpoints.
Agricultural policy in the U.S. has encouraged the extensive use of nitrate fertilizers, which has resulted in the contamination of water supplies and vast ecologic effects. Nitrogen
fertilizers and pesticides are largely fossil fuel-derived chemicals; their use might be reduced as a result of market forces if oil prices continue to increase. Reduced use can also be
encouraged through changed agricultural policies, i.e., better crop rotation and management.