Health & Environmental Research Online (HERO)


Print Feedback Export to File
625124 
Journal Article 
Review 
Incorporating children's toxicokinetics into a risk framework 
Ginsberg, G; Slikker, W, Jr; Bruckner, J; Sonawane, B 
2004 
Yes 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
112 
2 
272-283 
English 
14754583 
WOS:000189149800044 
Children's responses to environmental toxicants will be affected by the way in which their systems absorb, distribute, metabolize, and excrete chemicals. These toxicokinetic factors vary during development, from in utero where maternal and placental processes play a large role, to the neonate in which emerging metabolism and clearance pathways are key determinants. Toxicokinetic differences between neonates and adults lead to the potential for internal dosimetry differences and increased or decreased risk, depending on the mechanisms for toxicity and clearance of a given chemical. This article raises a number of questions that need to be addressed when conducting a toxicokinetic analysis of in utero or childhood exposures. These questions are organized into a proposed framework for conducting the assessment that involves problem formulation (identification of early life stage toxicokinetic factors and chemical-specific factors that may raise questions/concerns for children) ; data analysis (development of analytic approach, construction of child/adult or child/animal dosimetry comparisons) ; and risk characterization (evaluation of how children's toxicokinetic analysis can be used to decrease uncertainties in the risk assessment) . The proposed approach provides a range of analytical options, from qualitative to quantitative, for assessing children's dosimetry. Further, it provides background information on a variety of toxicokinetic factors that can vary as a function of developmental stage. For example, the ontology of metabolizing systems is described via reference to pediatric studies involving therapeutic drugs and evidence from in vitro enzyme studies. This type of resource information is intended to help the assessor begin to address the issues raised in this paper. 
children; dosimetry; risk assessment; toxicokinetics