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Summary
Pages 11-27

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From page 11...
... A few industrial accidents and occupational exposures to substantial amounts of TCDD, other dioxins, and DLCs have provided opportunities 11
From page 12...
... , began collecting and evaluating scientific information about the sources, fate, and effects of the compounds. In 1985, EPA produced an initial assessment of the human health risks from environmental exposure to TCDD.
From page 13...
... in the risk assessment of complex mixtures of dioxins and the uncertainties associated with the use of TEFs. The committee will also review the uncertainty associated with the reassessment's approach regarding the analysis of food sampling and human dietary intake data and, therefore, human exposures, taking into consideration the Institute of Medicine's report Dioxin and Dioxin-Like Compounds in the Food Sup ply: Strategies to Decrease Exposure.
From page 14...
... Animal studies and mechanistic data provide additional support for classifying TCDD as a human carcinogen. The committee concludes that the distinction between those two qualitative categories of cancer risk classification depends more on semantics than on science and that the public health implications of the two terms appeared identical, and for these reasons the committee did not focus much attention on the issue of classification.
From page 15...
... ESTIMATING CANCER RISK Because nearly all data (both human epidemiological studies and experimental animal bioassays) relevant to cancer risk are for doses much higher than those to which the general human population is typically exposed, analysts must extrapolate below the doses observed when estimating risks.
From page 16...
... Specifically, the committee determined that the scientific evidence is consistent with receptormediated responses and favors the use of a nonlinear model over the default linear assumption to extrapolate below the POD for dioxin-related cancer risk. The committee recognizes that a linear response at doses below the POD cannot be entirely excluded, especially if background exposures are not orders of magnitude below the POD and additivity of risk from other types of chemicals is considered.
From page 17...
... assess risks to population groups, such as those with occupational exposures, and (3) estimate the risk contributions of the major food sources and other environmental sources for those individuals with high intakes.
From page 18...
... different assumptions for estimating historical exposures among subjects in the epidemiological studies. In the case of the noncancer risk estimates, EPA should characterize the uncertainty associated with (1)
From page 19...
... . The recent NTP studies on TCDD and several other dioxins and DLCs provide additional evidence in support of the TEF approach.
From page 20...
... For highly persistent chemicals like TCDD, other dioxins, and DLCs, substantial differences in the rates of elimination from the body will result in very different amounts of chemical accumulated in the body over time, even with the same daily dose rate expressed in body weight or body surface area units. In the 2003 Reassessment, EPA used an estimate of the total amount of chemical in the body at steady state for a defined rate of exposure, called the body burden, as the dose metric to adjust for differences in body weight (or surface area)
From page 21...
... models to estimate the differences between humans and rodents in the relationship between total body burden at steady state, as calculated from the intake, half-life, bioavailability, and tissue concentrations, and use the results to modify the estimated human equivalent intakes. The committee also recommends that EPA provide a clear evaluation of the impact of using body burden as the dose metric, relative to other possible options such as intake, on the final risk estimates.
From page 22...
... In light of the large database showing that TCDD, other dioxins, and DLCs produce immunotoxic responses in laboratory animal studies, combined with sparse human data, the committee agrees with EPA's conclusion that these compounds are potential human immunotoxicants. However, EPA's conclusion that dioxins, other than TCDD, and DLCs are immunotoxic at "some dose level" is inadequate.
From page 23...
... The committee agrees that EPA has in general adequately addressed the available data on the likelihood that exposure to TCDD, other dioxins, and DLCs is a significant risk factor for other toxic end points. EPA cautiously stated its overall conclusions about noncancer risks due to TCDD, other dioxins, and DLCs exposures and acknowledged the uncertainty of suspected relationships.
From page 24...
... EPA's sole use of the default assumption of linearity and selection of the ED01 as the only POD to quantify cancer risk does not provide an adequate quantitative characterization of the overall range of uncertainty associated with the final estimates of cancer risk. Because EPA decided not to derive an RfD, its traditional noncancer metric, or any other alternative for noncancer effects, the 2003 Reassessment does not provide important detailed risk characterization information about noncancer risks.
From page 25...
... The effects seen at the lowest body burdens that are the primary focus for any risk assessment -- the "critical effects." 2. The modeling strategy used for each noncancer effect modeled, paying particular attention to the critical effects, and the selection of a point of comparison based on the biological significance of the effect; if the ED01 is retained, then the biological significance of the response should be defined and the precision of the estimate given.
From page 26...
... The following points represent Summary recommendations to address the key concerns: · EPA should compare cancer risks by using nonlinear models consistent with a receptor-mediated mechanism of action and by using epidemiological data and the new NTP animal bioassay data. The comparison should include upper and lower bounds, as well as central estimates of
From page 27...
... · EPA should continue to use body burden as the preferred dose metric but should also consider physiologically based pharmacokinetic modeling as a means to adjust for differences in body fat composition and for other differences between rodents and humans.


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