Differential sensitivity of children and adults to chemical toxicity

Children, particularly neonates, can be biologically more sensitive to the same toxicant on a body weight basis than adults. Current understanding of the rates of maturation of metabolism and evidence from case studies indicate that human infants up to 6 months of age typically lack the capacity to detoxify and eliminate substances as readily as adults. For most chemicals, the infant physiologic systems usually produce higher blood levels for longer periods. The newborn's metabolic capacity rapidly matures and, by 6 months of age, children are usually not more sensitive than adults based on their pharmacokinetic competence. Whether children are at greater risk from chemical exposures is another question. Drawing conclusions about the ability of the U.S. Environmental Protection Agency's intraspecies (UFH) and database (UFD) uncertainty factors to protect children on the basis of the modest data available is challenging. However, virtually all studies available suggest that a high percentage of the population, including children, is protected by using a 10-fold UFH or by using a 3.16-fold factor each for toxicokinetic and toxicodynamic variability. Based on specific comparisons for newborns, infants, children, adults and those with severe disease, the population protected is between 60% and 100%, with the studies in larger populations that include sensitive individuals suggesting that the value is closer to 100%. UFD is likewise protective when used with databases that are missing substantive studies.