Kids are different: developmental variability in toxicology

Data on the impact of many environmental compounds to human health is often lacking, particularly when considering the risk to the unborn and developing child. The stage of development of the individual at the time of exposure to a toxicant has not always been considered. For example, a higher percentage of ingested lead is absorbed from the gastrointestinal tract of infants than adults. Renal elimination also follows a developmental pattern, being very limited during the newborn period, increasing during infancy and childhood, and declining gradually after puberty. Genetic polymorphisms in metabolic enzyme activity add another dimension of variability. Depending on the particular chemical, this may serve as a protective factor or increase susceptibility to toxic effects (e.g. epoxide hydrolase and fetal hydantoin syndrome). Children also have distinctive behaviors and target organ susceptibilities that warrant special consideration. The consequences of developmental changes are well-known in medical practice, and many drug doses are modified based on age, liver, and renal function, and other factors that may influence pharmacokinetic behavior of drugs. There is a sizable body of such information available, in part, in the pediatric and clinical pharmacology and toxicology literature. The concept of the significance of developmental stage is becoming increasingly important in toxicological risk assessment as well.