Differential sensitivity of children and adults to chemical toxicity. II. Risk and regulation.
Animals can be useful predictors of chemical hazards to humans. Growth and development are compressed into a shorter period in animals, which makes interpretation of animal testing inherently more difficult. However, similar events occur in both humans and laboratory animals and testing that covers the full period of animal development can reasonably be considered an appropriate surrogate for human development. Some have proposed an additional 10-fold factor for the extra protection of children when estimating safe exposures. Use of such an additional factor, as required by the Food Quality Protection Act (FQPA), is meant to address the same issues covered by the EPA's database uncertainty factor, UF(D), and additional issues related to exposure uncertainty. Thus, when UF(D) has already been deployed, the EPA modifies its use of the FQPA factor. Based on our analysis, we agree with the EPA. Drawing conclusions about the adequacy of UF(H), the uncertainty factor used to account for intrahuman variability, in terms of its ability 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 uncertainty factor for human variability 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%.
Toxicology Excellence for Risk Assessment, Cincinnati, Ohio 45223, USA.
Michael
M
Dourson
Gail
G
Charnley
Robert
R
Scheuplein
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002648:Child; D002675:Child, Preschool; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015262:Xenobiotics / Q000633:toxicity*
D015262:Xenobiotics