18 years of age, the point when all biological systems have essentially matured.

CONCLUSIONS

Age-Related Variation in Susceptibility and Toxicity

A fundamental maxim of pediatric medicine is that children are not ''little adults." Profound differences exist between children and adults. Infants and children are growing and developing. Their metabolic rates are more rapid than those of adults. There are differences in their ability to activate, detoxify, and excrete xenobiotic compounds. All these differences can affect the toxicity of pesticides in infants and children, and for these reasons the toxicity of pesticides is frequently different in children and adults. Children may be more sensitive or less sensitive than adults, depending on the pesticide to which they are exposed. Moreover, because these processes can change rapidly and can counteract one another, there is no simple way to predict the kinetics and sensitivity to chemical compounds in infants and children from data derived entirely from adult humans or from toxicity testing in adult or adolescent animals.

The committee found both quantitative and occasionally qualitative differences in toxicity of pesticides between children and adults . Qualitative differences in toxicity are the consequence of exposures during special windows of vulnerability—brief periods early in development when exposure to a toxicant can permanently alter the structure or function of an organ system. Classic examples include chloramphenicol exposure of newborns and vascular collapse (gray baby syndrome), tetracycline and dysplasia of the dental enamel, and lead and altered neurologic development.

Quantitative differences in pesticide toxicity between children and adults are due in part to age-related differences in absorption, metabolism, detoxification, and excretion of xenobiotic compounds, that is, to differences in both pharmacokinetic and pharmacodynamic processes. Differences in size, immaturity of biochemical and physiological functions in major body systems, and variation in body composition (water, fat, protein, and mineral content) all can influence the extent of toxicity. Because newborns are the group most different anatomically and physiologically from adults, they may exhibit the most pronounced quantitative differences in sensitivity to pesticides. The committee found that quantitative differences in toxicity between children and adults are usually less than a factor of approximately 10-fold.

The committee concluded that the mechanism of action of a toxicant—how it causes harm—is generally similar in most species and across age



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