The question of differential susceptibility is dependent on an understanding of the mechanisms of toxicity. However because epidemiologic studies and animal experiments on susceptible populations are rare, risk assessments have seldom addressed susceptibility. The database for trichloroethylene (TCE) is relative rich in toxicity information. The evidence suggests that human responses to TCE exposure can vary (quantitatively or qualitatively) depending on certain factors that are intrinsic (e.g. genetic variation, age, sex), as well as other factors that are acquired (e.g., diet and nutrition, or background exposure to TCE and its metabolites). TCE's metabolism is important to overall toxicity, particularly by metabolites generated from via oxidative metabolism by cytochrome p450 (CYP2E1). Children may be particularly susceptible to TCE toxicity for several reasons. Differences in rates of individual metabolic pathways, ability to induce specific isozymes such as CYP2E1, as well as the presence or absence of enyzme polymorphisms may influence susceptibility. Differences in clearance of metabolites in children may alter their susceptibility compared to adults. TCE metabolites may also preferentially partition into the fetal compartment. Increased uptake and exposure in children may occur due to differences in breathing rate, volume-to mass ratio, and drinking water ingestion. Finally, exposure during critical periods of development may result in long-lasting effects. This presentation focuses on how EPA's the synthesis and characterization of TCE health risk assessment incorporates information concerning children's potential increased susceptibility.
Learning Objectives: Learning objectives: At the conclusion of the session the participant will be able to: 1. Recognize and discuss factors that alter susceptibility of children to an environmental chemical with widespread exposure and a relatively rich toxicological database (Trichloroethylene). 2. Use the assessment of the health risk of Trichloroethylene as a template to apply to risk assessments of chemicals with similar metabolic pathways or metabolites in terms of susceptibility to children
Keywords: Environmental Health Hazards,
Presenting author's disclosure statement:
Organization/institution whose products or services will be discussed: U.S. Environmental Protection Agency
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.