Differential sensitivity of children and adults to chemical toxicity. I. Biological basis.
Children, particularly neonates, can be biologically more sensitive to the same toxicant exposure on a body weight basis than adults. Current understanding of the rates of maturation of metabolic capability and evidence from case examples on pharmaceuticals, drugs of abuse, environmental contaminants, and dietary and endogenous agents indicate that human infants up to approximately 6 months of age are typically--but not always--more sensitive to chemical toxicity than adults. For most chemicals, the immaturity of infant biotransformation, elimination, and other physiologic systems usually produces higher blood levels for longer periods. There is metabolic capacity for most tested substances in the newborn, although it is quite low and immature for some chemicals. For some chemicals, unique metabolic pathways not available in the adult human can also be utilized by the newborn. The newborn's metabolic capacity rapidly matures and, by about 6 months of age, children are usually not more sensitive to chemical toxicity than adults. By then, most metabolic systems are reasonably mature, becoming almost completely capable by 1 year of age. In many cases children are less sensitive than adults. Whether children are at greater risk from chemical exposures is another question. Risk depends on both inherent sensitivity and exposure conditions. If chemical exposure levels remain below those capable of overwhelming a child's metabolic detoxification systems and producing toxicity, children will be at no greater risk than are adults. Children of all ages are still developing so even if they are exposed to chemicals at levels below those of adults, they may be at greater risk than adults. However, as long as those exposure levels are still below those required to produce toxicity, children will not be at greater risk.
Keller and Heckman, Stafford, Virginia 22554, USA.
Robert
R
Scheuplein
Gail
G
Charnley
Michael
M
Dourson
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018675:Toxicity Tests; D015262:Xenobiotics / Q000633:toxicity*
D015262:Xenobiotics