The Role of Toxicokinetics and Toxicodynamics in Developmental and Translational Toxicology

Abstract

Toxicokinetics and toxicodynamics vary depending on dose, developmental stage and exposure timing. The embryo is the developmental stage most susceptible to toxicants. Many birth defects occur only as a result of first trimester exposures when organogenesis is occurring and the formation of new organs and structures (e.g., limbs) can be disrupted. The Absorption, Distribution, Metabolism and Elimination (ADME) of toxicants changes dramatically as the embryo grows from a single-celled organism into a fetus with multiple organ systems. Before birth the mother’s behavior and body largely determines the toxicokinetics of chemicals. Immediately after birth the newborn’s organs must suddenly function independently of the mother. Birth itself is a major trigger causing widespread changes in gene and protein expression patterns. The average infant doubles in size in under a year’s time, the first of roughly four doublings in size after birth. Toddlers’ mobility and mouthing behavior put them at greatest risk for accidental poisonings. Older children’s growth and development makes their metabolism unpredictable. Adolescents develop adult metabolic capacity but adolescent behavior can make them more likely to abuse some toxicants (e.g., inhalants). ADME changes as pregnancy progresses for adolescents and adults. In general adults are the least susceptible to toxicants but occupation becomes a major risk factor for exposure. Elderly adults become somewhat more susceptible to toxicants as organ function declines with age. Beer’s list, unit doses of iron, and the X classification system are examples of translational toxicology designed to protect elderly patients, toddlers and embryos respectively.