For carcinogenic effects, the committee proposed new methods of cancer risk assessment designed to take such differences into account. Preliminary analyses conducted by the committee suggest that consideration of such differences can lead to lifetime estimates of cancer risk that can be higher or lower than estimates derived with methods based on constant exposure. However, underestimation of risk assuming constant exposure was limited to a factor of about 3- to 5-fold in all cases considered by the committee. Because these results are based on limited data and specific assumptions about the mechanisms by which carcinogenic effects are induced, the applicability of these conclusions under other conditions should be established.

Currently, most long-term laboratory studies of carcinogenesis and other chronic end points are based on protocols in which the level of exposure is held constant during the course of the study. To facilitate the application of risk assessment methods that allow for changes in exposure and susceptibility with age, it would be desirable to develop bioassay protocols that provide direct information on the relative contribution of exposures at different ages to lifetime risks. Although the committee does consider it necessary to develop special bioassay protocols for mandatory application in the regulation of pesticides, it would be useful to design special studies to provide information on the relative effects of exposures at different ages on lifetime cancer and other risks with selected chemical carcinogens.

In addition to pharmacodynamic models for cancer risk assessment, the committee recommends the development and application of physiologically based pharmacokinetic models that describe the unique features of infants and children. For example, differences in relative organ weights with age can be easily described in physiologic pharmacokinetic models; special compartments for the developing fetus may also be incorporated. Physiologically based pharmacokinetic models can be used to predict the dose of the proximate toxicant reaching target tissues, and may lead to more accurate estimates of risk.

In summary, better data on dietary exposure to pesticide residues should be combined with improved information on the potentially harmful effects of pesticides on infants and children. Risk assessment methods that enhance the ability to estimate the magnitude of these effects should be developed, along with appropriate toxicological tests for perinatal and childhood toxicity. The committee's recommendations support the need to improve methods for estimating exposure and for setting tolerances to safeguard the health of infants and children.



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