Toxicokinetics in infants and children in relation to the ADI and TDI

Area of Science:

• Toxicology
• Developmental Biology
• Pharmacokinetics

Background:

• Toxicokinetic processes like renal function and hepatic metabolism are immature at birth, particularly in preterm neonates.
• These processes mature rapidly in early life, with the period of suckling corresponding to this developmental immaturity.
• Similar age-related changes occur in neonatal rats, with potential exposure to adult diets during immaturity.

Purpose of the Study:

• To evaluate age-related differences in toxicokinetics between infants/children and adults.
• To determine if increased safety factors are needed for children regarding chemical intake.
• To assess how developmental toxicokinetics influence risk assessment for xenobiotics.

Main Methods:

• Review of existing pharmacokinetic databases for therapeutic drugs in infants and children.
• Comparison of xenobiotic elimination and clearance rates in children versus adults.
• Analysis of body burden differences based on body weight for chemical intake (e.g., Acceptable Daily Intake).

Main Results:

• Children exhibit higher elimination/clearance rates for many xenobiotics compared to adults.
• For a given daily intake, children often have lower body burdens of chemicals relative to body weight.
• Immature organ sensitivity (toxicodynamics) during development may be offset by higher xenobiotic clearance (toxicokinetics).

Conclusions:

• An increased safety or uncertainty factor for post-suckling infants and children is not warranted due to age-related toxicokinetic differences.
• Higher xenobiotic clearance in children can partially compensate for potential increases in organ sensitivity during development.
• Risk assessments for chemical exposure in children should consider these developmental toxicokinetic variations.