Age-dependent developmental changes in toxicokinetics occur in both ra
ts and humans, particularly in relation to renal function and hepatic
xenobiotic metabolism. These processes are immature in humans at birth
, especially in the pre-term neonate, but mature rapidly oiler the fir
st months of life. In consequence the duration of immaturity primarily
corresponds to the period of suckling. Similar developmental changes
occur in the neonatal rat over the first weeks of life. Rat pups start
to consume some of the adult diet in the third week of life, prior to
weaning, so that there is a potential for consumption of the adult di
et during the period of immaturity. There is an extensive database on
the pharmacokinetics of therapeutic drugs in infants and children. The
elimination/clearance of many drugs is higher in children than in adu
lts and this difference would apply to other xenobiotics. In consequen
ce, children frequently will have lower body burdens than adults for t
he same daily intake of a chemical when this is expressed on a body we
ight basis, as used to describe the ADI (Acceptable Daily Intake) or T
DI (Tolerable Daily Intake) (e.g. mg/kg body weight/day). Therefore, a
n increased safety or uncertainty factor for post-suckling infants and
children is not required in relation to age-related differences in to
xicokinetics. Indeed the higher clearance of many xenobiotics (toxicok
inetics) by children compared with adults may compensate, at least in
part, for increased organ sensitivity (toxicodynamics) during developm
ent.