Children as a sensitive subpopulation for the risk assessment process.
For cancer risk assessment purposes, it is necessary to consider how to incorporate sensitive subpopulations into the process to ensure that they are appropriately protected. Children represent one such potentially sensitive subpopulation that is of quite considerable magnitude. The data needs include sensitivity to the induction of childhood cancers compared to adult cancers and relative sensitivity of early-life exposures for the formation of tumors in adults. These needs as far as human data are concerned are best met for ionizing radiations, for which it has been shown in the atomic bomb survivors that early-life exposures are more effective at inducing cancers later in life. The risk assessment approach for ionizing radiations, however, is based on tumor data itself for total population exposures so that there is no requirement to consider specifically the impact of early-life exposures. In the case of environmental chemicals, the majority of the tumor data used for risk assessments are from rodent bioassays. There is a paucity of data that allow for a comparison of the response to early-life exposures compared to that for adult-only exposures. This presents a fairly difficult challenge to the identification of a general sensitivity factor or a chemical-specific sensitivity factor for early-life exposures. The U.S. Environmental Protection Agency (EPA) has not, until recently, incorporated a general adjustment for early-life exposure to carcinogens into its risk assessment guidelines. The Agency has relied on the fact that, in the absence of specific data to the contrary, the linear extrapolation for rodent tumor data provided appropriate protection. When specific data are available, then an adjustment can be calculated. In its most recent draft guidelines, however, a general adjustment has been proposed for mutagenic chemicals. A 10-fold risk adjustment is recommended for the first 2 years of life, a 3-fold adjustment for years 3-15, and no adjustment for exposures after age 15. For chemicals that do not have a mutagenic mode of action, no adjustment is recommended because the data for deriving such an adjustment are simply not available. Clearly, this is an interim position that is dependent on more pertinent data being collected. A significant component of this is to conduct cancer bioassays that include early-life exposures.
Preston
R Julian
RJ
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. preston.julian@epa.gov
D000328:Adult; D000375:Aging / Q000502:physiology; D002273:Carcinogens / Q000633:toxicity; D002648:Child; D004781:Environmental Exposure; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology; D018570:Risk Assessment
D002273:Carcinogens