oxin-like compounds (DLCs), in spite of very large investments in data collection and research.

Variability among members of the population is an important consideration in understanding risks. Variability results from the wide range of environmental sources and human interactions with them, as well as from physiological and genetic differences that might influence the relative susceptibility of humans and other species to adverse health effects from exposure. For example, sources of variability associated with human health outcomes include the inherent genetic diversity of human populations, which currently remain difficult to address quantitatively. Abundant evidence demonstrates complex gene-environment interactions for many complex human diseases, immune system dysfunction, and other disorders in which TCDD, other dioxins, and DLCs might be implicated.

Adding more complexity, the risks from TCDD, other dioxins and DLCs continue to change over time because of changing exposures, and understanding of the risks continues to evolve with the collection of more data. Any assessment reflects the snapshot of the information available at that time, and analysts should recognize that additional information might later reveal evidence that differs from prior assumptions.

One of the charges to the committee emphasized reviewing the Reassessment1 “to assess whether EPA’s risk estimates are scientifically robust and whether there is a clear delineation of all substantial uncertainties and variability.” Risk assessment in the case of TCDD, other dioxins, and DLCs represents a formidable task because of the size of the available database and the complexity of numerous issues. EPA collated and presented a massive database on TCDD, other dioxins, and DLCs, on which the committee commented specifically in the chapters that follow. This chapter identifies the major categories of decisions that analysts generally make when developing risk estimates in the context of the four traditional steps of risk assessment: hazard identification and classification, exposure assessment, dose-response assessment, and risk characterization (NRC 1983). The Reassessment deals with complexities in the risk assessment of TCDD, other dioxins and DLCs by making specific choices as described in this chapter, but EPA could alternatively use a probabilistic approach. Typically, risk assessments should address uncertainties that derive from conceptualizations and fundamental choices among competing options in a way that clearly identifies the quantitative impacts of alternatives. When there are two or more plausible interpretations, a risk assessment should make clear


The Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds (EPA 2003a, Part I; 2003b, Part II; 2003c, Part III) is collectively referred to as the Reassessment.

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