Clearly adverse effects, including, perhaps, cancer, may not be detectable until exposures contribute to body burdens that exceed current backgrounds by one or two orders of magnitude (10 to 100 times). (Part III, p. 6-2, lines 11-13)

The rationale for those statements is not clearly defined, although the Reassessment states later that few clinically significant effects were detected in the small number of human cohorts studied, nearly all members of which had body burdens significantly above background levels.

The text considers species differences in sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, also referred to as dioxin), other dioxins, and dioxin-like compounds (DLCs) and concludes that “humans most likely fall in the middle rather than at either extreme of the range of sensitivity for individual effects among animals” (p. 6-2, lines 25-26). A general comparison across several species is not relevant to the focused issue of risk characterization. The comparisons of importance are those between humans and the species and strains used in the specific studies that revealed adverse effects at the lowest levels of exposure, the so-called critical effects (see below). This general statement on interspecies differences detracts from a critical and quantitative assessment of differences in sensitivity between humans and the species used in the key toxicological studies for risk characterization.

Overall the committee considered this introductory section to be reasonable but unfocused.

TCDD, Other Dioxins, and DLCs are Structurally Related and Elicit Their Effects Through a Common Mode of Action

Reassessment (Part III, pp. 6-4 to 6-5)

The text is uncontroversial and concludes that binding to the aromatic hydrocarbon receptor (AHR) appears to be necessary but is not sufficient to elicit the various TCDD-induced effects. The committee agrees with this conclusion.

EPA and the International Scientific Community Have Adopted Toxic Equivalency of TCDD, Other Dioxins, and DLCs as a Prudent Scientific Policy

Reassessment (Part III, pp. 6-5 to 6-6)

The text summarizes the current situation and is uncontroversial. Obviously, given the date of the Reassessment, the text has not considered planned updates to toxic equivalency factor (TEF) values and whether these



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