may play in carcinogenesis are described above; overall, increased rates of cell proliferation can contribute to an increased likelihood of carcinogenesis. For example, polycyclic aromatic hydrocarbons and aflatoxin B1, produce liver tumors when administered to newborn rodents but not when administered to older animals, presumably because the liver proliferates rapidly in the developing organism but slowly in older animals. Differing metabolic capabilities may contribute to greater susceptibility if the developing organism has less competent detoxifying or conjugating abilities than the adult. Conversely, less competent activating enzymes may protect the developing animal from chemicals that require metabolic activation to their reactive forms to elicit effects. Ethylnitrosourea, which does not require metabolic activation, is very effective as a carcinogen in neonatal rodents as compared to adults, whereas diethylnitrosamine, which requires activation, is not (Vesselinovitch et al., 1979). In addition, there may be age-related differences in DNA repair abilities and in the fidelity of DNA replication.
Epidemiologic studies of the effects of age on susceptibility to carcinogenesis are conflicting. The risk of bladder cancer associated with employment in a ''hazardous occupation" (e.g., an industry believed to be associated with an increased risk of bladder cancer, such as the rubber or leather industries, or work with dyestuffs, paint, and other organic chemicals) was greater in younger people (Hoover and Cole, 1973), whereas the risk of nasal cancer among nickel workers increased in proportion to age at beginning of exposure (Doll et al., 1970). Tucker et al. (1987) demonstrated that chemotherapeutic treatment of children with cancer using alkylating agents, which can form adducts with DNA and induce mutations, resulted in a significantly elevated risk of secondary leukemia. No study has been performed to determine whether similar treatment of adults has the same outcome, however, so it is not possible to conclude that children are more susceptible to chemically induced carcinogenesis on the basis of these limited data. Evidence from epidemiologic studies is thus inadequate to demonstrate a consistent increased susceptibility to carcinogenesis among children, nor would one assume that children would regularly be more susceptible to toxic end points in pesticide toxicity. These data emphasize the need to evaluate each pesticide specifically for age-related toxicity. The incidence of most cancers in humans increases with age, with the exception of certain tumor types that are associated with childhood and that are suspected to result from inborn genetic alterations or prenatal genetic damage. An example of a childhood tumor is retinoblastoma, in which a mutation occurs in the retinoblast population resulting from