Approaches to acrylamide physiologically based toxicokinetic modeling for exploring child-adult dosimetry differences.

Dietary exposure to acrylamide is common as a result of its formation during the cooking of carbohydrate foods. This leads to widespread human exposure in adults and children alike. Acrylamide is neurotoxic and is metabolized by cytochrome P-450 (CYP) 2E1 to a mutagenic epoxide, glycidamide.

Pharmacokinetic and pharmacodynamic factors that can affect sensitivity to neurotoxic sequelae in elderly individuals.

Early-life exposure to agents that modulate neurologic function can have long-lasting effects well into the geriatric period. Many other factors can affect neurologic function and susceptibility to neurotoxicants in elderly individuals. In this review we highlight pharmacokinetic and pharmacodynamic factors that may increase geriatric susceptibility to these agents.

Age-related differences in susceptibility to carcinogenesis: a quantitative analysis of empirical animal bioassay data.

In revising cancer risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) analyzed animal cancer bioassay data over different periods of life.

Physiologically based pharmacokinetic (PBPK) modeling of caffeine and theophylline in neonates and adults: implications for assessing children's risks from environmental agents.

Children's risks can differ from those in adults for numerous reasons, one being differences in the pharmacokinetic handling of chemicals. Immature metabolism and a variety of other factors in neonates can affect chemical disposition and clearance. These factors can be incorporated into physiologically based pharmacokinetic (PBPK) models that simulate the fate of environmental toxicants in both children and adults.

Differences in pharmacokinetics between children and adults--II. Children's variability in drug elimination half-lives and in some parameters needed for physiologically-based pharmacokinetic modeling.

In earlier work we assembled a database of classical pharmacokinetic parameters (e.g., elimination half-lives; volumes of distribution) in children and adults.

Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature.

Pharmacokinetics (PK) of xenobiotics can differ widely between children and adults due to physiological differences and the immaturity of enzyme systems and clearance mechanisms. This makes extrapolation of adult dosimetry estimates to children uncertain, especially at early postnatal ages. While there is very little PK data for environmental toxicants in children, there is a wealth of such data for therapeutic drugs.