Health Risks from Dioxin and Related Compounds Evaluation of the EPA Reassessment (2006) / Chapter Skim
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1 Introduction
1 Introduction
Pages 28-44
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From page 28... ...
Three years later, EPA, other federal agencies, and the scientific community began developing a broad research program to identify the biological response mechanisms and to explore other key scientific issues related to dioxin. In light of significant advances in the scientific understanding of the mechanisms of dioxin toxicity, new studies of dioxin's carcinogenic potential in humans, and increased evidence of other adverse health effects primarily after the 1985 assessment, EPA announced in 1991 that it would conduct a scientific reassessment of the health risks of human exposure to TCDD and related compounds, that is, dioxins, other than TCDD, and dioxin-like compounds (DLCs)
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From page 29... ...
EPA, with NIEHS, revised Chapter 8, developed a new Chapter 9 on TEFs, and revised the former Chapter 9 and renamed it as a free-standing report, "Part III -- Integrated Summary and Risk Characterization for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds." The dioxin report consisted of two other parts: "Part I -- Estimating Exposure to Dioxin-Like Compounds" and "Part II -- Health Assessment for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)
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From page 30... ...
Ultimately, the NRC review would seek to inform and assure the risk characterization of TCDD, other dioxins, and DLCs and to benefit EPA in finalizing its Reassessment. TCDD, OTHER DIOXINS, AND DLCS The Reassessment addresses a limited number of chemical compounds within three subclasses of the halogenated aromatic hydrocarbons (HAHs)
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INTRODUCTION 31 FIGURE 1-1 Benzene ring (a) with conjugated bonds and (b)
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However, of the several hundred HAH congeners, only 29 are considered to have significant toxicity and to induce a common battery of toxic responses through similar biological modes of action. The evaluation of dioxin-like congeners within the Reassessment focuses on dioxins and DLCs with TCDD-like toxicity and those generally considered the most associated with environmental and human health risks.
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TOXIC EQUIVALENCY FACTORS TCDD, other dioxins, and DLCs are generally present as complex mixtures in environmental, food, and biological matrices, including humans and other animals. To address the complexity of risk assessment for TCDD-related compounds, the concept of TEFs is used in the Reassessment.
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From page 34... ...
The team concluded that an additive TEF model served as the most feasible risk assessment method for complex mixtures of TCDD-like PCDDs, PCDFs, and PCBs. Although several TEF/TEQ schemes exist for TCDD-related compounds, the Reassessment recommends using the international WHO TEF scheme of values, proposed and published by WHO (IPCS 1998a)
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From page 35... ...
INTRODUCTION 35 TABLE 1-1 TEFs for Humans and Nonhuman Mammals PCDD Congeners WHO TEF 2,3,7,8-TCDD 1 1,2,3,7,8-PeCDD 1 1,2,3,4,7,8-HxCDD 0.1 1,2,3,7,8,9-HxCDD 0.1 1,2,3,6,7,8-HxCDD 0.1 1,2,3,4,6,7,8-HpCDD 0.01 1,2,3,4,6,7,8,9-OCDD 0.0001 PCDF Congeners WHO TEF 2,3,7,8-TCDF 0.1 1,2,3,7,8-PeCDF 0.05 2,3,4,7,8-PeCDF 0.5 1,2,3,4,7,8-HxCDF 0.1 1,2,3,7,8,9-HxCDF 0.1 1,2,3,6,7,8-HxCDF 0.1 2,3,4,6,7,8-HxCDF 0.1 1,2,3,4,6,7,8-HpCDF 0.01 1,2,3,4,7,8,9-HpCDF 0.01 1,2,3,4,6,7,8,9-OCDF 0.0001 PCB Congeners WHO TEF IUPAC Number Structure 077 3,3',4,4'-TCB 0.0001 081 3,4,4',5-TCB 0.0001 105 2,3,3',4,4'-PeCB 0.0001 114 2,3,4,4',5-PeCB 0.0005 118 2,3',4,4',5-PeCB 0.0001 123 2',3,4,4',5-PeCB 0.0001 126 3,3',4,4',5-PeCB 0.1 156 2,3,3',4,4',5-HxCB 0.0005 157 2,3,3',4,4',5'-HxCB 0.0005 167 2,3',4,4',5,5'-HxCB 0.00001 169 3,3',4,4',5,5'-HxCB 0.01 189 2,3,3',4,4',5,5'-HpCB 0.0001 Abbreviations: PeCDD, pentachlorodibenzo-p-dioxin; HxCDD, hexachlorodibenzo-p-dioxin; HpCDD, heptachlorodibenzo-p-dioxin; OCDD, octachlorodibenzo-p-dioxin; TCDF, tetrachlorodibenzofuran; PeCDF, pentachlorodibenzofuran; HxCDF, hexachlorodibenzofuran; HpCDF, heptachlorodibenzofuran; OCDF, octachlorodibenzofuran; TCB, tetrachlorobiphenyl; PeCB, pentachlorobiphenyl; HxCB, hexachlorobiphenyal; HpCB, heptachlorobiphenyl.
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From page 36... ...
However, the Reassessment recognizes that the contribution of reservoir sources to human exposure may be significant, perhaps contributing half or more of total background TEQ exposure. For any given time period, releases from both contemporary formation sources and from reservoir sources determine the overall amount of TCDD, other dioxins, and DLCs released to the accessible environment.
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From page 37... ...
Background exposure includes exposure via the commercial food supply, air, or soil but not any significant occupational exposure. Background exposure estimates are based on the monitoring of data from environmental sites and other media void of known contaminant sources and on pharmacokinetic models using body burden data from nonoccupationally exposed populations.
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From page 38... ...
Also, tissue concentrations are a function of age and year of birth. HEALTH EFFECTS On a global scale, exposure to TCDD, other dioxins, and DLCs resulting from accidental, occupational, or incidental exposure through dermal contact, inhalation, or ingestion has been associated with adverse effects on human health.
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From page 39... ...
. In response, the NRC formed the Committee on EPA's Exposure and Human Health Reassessment of TCDD and Related Compounds, a panel of 18 members that included experts in exposure assessment; food exposure pathways; pharmacokinetics; physiologically based pharmacokinetic modeling; benchmark dose modeling; dose-response modeling; molecular and cellular aspects of receptor-mediated responses; toxicology with specialties in cancer, reproduction, development, and immunology; epidemiology; reproductive physiology and medicine; pediatric biology and medicine; statistics; risk assessment (both qualitative and quantitative)
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40 Total PCBs Mean PCDD, PCDF, 11.6 3.3 5.8 0.12 Environmental in 1996 al.
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41 continued 0.014 2.2 0.57 0.00056 0.027 0.18 0.13 0.26 2000 al. from et.
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42 of soil, 4 for average Total PCBs statistically ed Chapter xcepte 2, Mean PCDD, PCDF, 0.29 0.094 0.093 from means.
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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.
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From page 44... ...
Chapter 5 reviews EPA's assessment of the carcinogenicity of TCDD other TCDD, other dioxins, and DLCs, including the qualitative characterization of their carcinogenicity, the validity of the nonthreshold linear dose-response model, and the use of the animal bioassay and epidemiological data to quantify the dose response. Chapter 6 reviews EPA's assessment of noncancer end points, including immune function, reproduction, and development.
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