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United States General Accounting Office: 
GAO: 

Report to Congressional Requesters: 

April 2002: 

Environmental Health Risks: 

Information on EPA's Draft Reassessment of Dioxins: 

GAO-02-515: 
		
Contents: 

Letter: 

Results in Brief: 

Background: 

EPA Used Data on the Presence of Dioxins, Toxicity, and Food 
Consumption to Estimate Human Dietary Exposure: 

EPA's and WHO's Specific Reassessment Objectives and Processes
Differed, but Their Analytical Methods and Conclusions on Dioxins' 
Health Risks Are Similar: 

EPA's Draft Dioxin Reassessment Report Generally Reflects the Views of 
Recent Peer Reviews: 

Observations: 

Agency Comments and Our Response: 

Scope and Methodology: 

Appendix I: Major Milestones in the EPA and WHO Dioxin Risk Assessment 
Efforts: 

Appendix II: Comparison of the Major Conclusions from EPA's and WHO's 
Dioxin Risk Assessments: 

Appendix III: Questions EPA Asked Peer Review Panels to Address: 

Appendix IV: EPA's Responses to Peer Review Panels: 

Appendix V: Comments from the Environmental Protection Agency: 

Appendix VI: GAO Contacts and Staff Acknowledgments: 

Tables: 

Table 1: EPA's Estimates of the Average U.S. Adult's Daily Exposure to 
Dioxins From Dietary Intake, Picograms per Day: 

Table 2: Numbers, Types, and Dates of Food Samples EPA Used in 
Estimating Dietary Exposure to Dioxins: 

Table 3: Numbers, Types, and Dates of Food Samples EPA Used in 
Estimating Dietary Exposure to PCBs in Four Food Categories: 

Table 4: EPA's Estimates of Toxic Concentrations of Dioxins in 10 Food 
Categories, Picograms per Gram: 

Table 5: Estimated Daily Dietary Intake of 10 Food Types for an 
American Adult Weighing 70 Kilograms (154 pounds): 

Table 6: Questions for the July 2000 Panel Review of EPA's Draft 
Dioxin Reassessment: 

Table 7: Questions for the November 2000 Science Advisory Board Panel: 

Table 8: EPA's Responses to July 2000 Panel's Report: 

Table 9: EPA's Responses to Science Advisory Board Panel's Comments: 

Abbreviations: 

CDD: polychlorinated dibenzo-p-dioxins: 

CDF: polychlorinated dibenzofurans: 

ED: effective dose: 

EPA: Environmental Protection Agency: 

IARC: International Agency for Research on Cancer: 

PCB: polychlorinated biphenyls: 

TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin: 

TEF: toxic equivalency factors: 

TEQ: toxic equivalency: 

USDA: Department of Agriculture: 

WHO: World Health Organization: 

[End of section] 

United States General Accounting Office: 
Washington, DC 20548: 

April 26, 2002: 

The Honorable John Breaux: 
The Honorable Thad Cochran: 
United States Senate: 

Some dioxins, which are chemical compounds that share certain 
structural and biological characteristics, have been linked to adverse 
human health effects, including cancer.[Footnote 1] Often the 
byproducts of combustion and industrial processes, complex mixtures of 
dioxins enter the food chain and human diet through emissions into the 
air that settle on soil, plants, and water. The Environmental 
Protection Agency (EPA) and other entities, such as the World Health 
Organization, began assessing the potential human health risks of 
dioxins in the 1970s, when animal studies on one of them-2,3,7,8-
tetrachlorodibenzo-p-dioxin, or TCDD—showed it to be the most potent 
cancer-causing chemical studied to date. EPA's initial assessment of 
dioxins was published in 1985. Since that time, there have been major 
advances in the scientific understanding of dioxin toxicity and 
significant new studies on dioxins' potential adverse health effects. 
As a result, in 1991 EPA decided to conduct a reassessment of the 
health risks of exposure to dioxins. A draft of this reassessment was 
reviewed by a scientific peer review panel in 1995, and three panels 
reviewed key segments of later drafts in 1997 and 2000. 

EPA plans to release its comprehensive reassessment report on the 
health risks of dioxins this year. According to EPA officials, the 
report will conclude that dioxins may adversely affect human health at 
lower exposure levels than previously thought and that most exposure 
to dioxins occurs from eating such American dietary staples as meats, 
fish, and dairy products, which contain minute traces of dioxins. 
These foods contain dioxins because animals eat plants and commercial 
feed, and drink water, contaminated with dioxins, which then 
accumulate in animals' fatty tissue. EPA plans to use its reassessment 
of the risks posed by dioxins to develop a risk management strategy to 
address the health risks identified and to determine whether the 
nation's current air, water, and hazardous waste cleanup programs need 
to be changed to protect the public health. EPA's reassessment will be 
considered by the National Academies[Footnote 2] in an ongoing study 
of the implications of dioxin in the food supply, which is examining, 
among other things, options to reduce dietary exposure to dioxins. 

Of the several hundred known dioxins, 29 are considered toxic to 
varying degrees. TCDD is the most widely studied dioxin and one of the 
most toxic. EPA's reassessment report on the human health risks posed 
by dietary exposure to dioxins evaluates the health effects of TCDD 
and the 28 other compounds with similar structural and biological 
characteristics and varying toxic effects. According to EPA, its 
evaluation of the effects of these compounds is sufficient to 
characterize the effects of environmental dioxins in general. 

Concerned about the potentially significant impact that EPA's dioxin 
risk assessment report could have on consumers and on the food and 
agriculture industries, you asked us to examine several aspects of 
EPA's reassessment of dioxins. As agreed with your offices, this 
report describes (1) the data EPA used to estimate human dietary 
exposure to dioxins in the United States; (2) how EPA's reassessment 
objectives, processes, analytical methods, and conclusions on the 
health risks posed by dioxins compare with those of the World Health 
Organization; and (3) the extent to which the draft dioxin 
reassessment report reflects the views of independent peer review 
panels that reviewed key aspects of the reassessment. Also as agreed 
with your offices, our report provides information on the relevant 
scientific issues but does not render an opinion on the scientific 
merits of the reassessment. This report is based primarily on EPA's 
draft reassessment report dated October 2001,[Footnote 3] which EPA 
circulated for internal agency review, and on the two most recent peer 
reviews of key segments of the draft reassessment in 2000. 

Results in Brief: 

EPA derived its estimates of human dietary exposure to dioxins in the 
United States from (1) various studies that chemically analyzed 
samples of 10 food types, (2) toxicity estimates of the various levels 
of the individual dioxins in these foods, and (3) estimates of the 
quantities of these foods consumed by Americans. To develop more 
reliable national estimates of dietary exposure, EPA incorporated into 
its analysis some food studies that were designed to be nationally 
representative. However, as EPA notes in its draft reassessment 
report, the food data were limited in several ways. In some cases, the 
food sampling methods, or the number of samples collected, were not 
sufficient to reliably estimate average, nationally representative 
exposures. In other cases, the studies did not analyze the food 
samples for the presence of all the dioxins that EPA was assessing. 
Further, most of the samples were collected 5 or more years ago; 
therefore, they may not reflect current exposures if, as EPA believes, 
emissions of dioxins have continued to decline in the United States 
since 1995 because of air quality regulations. Nonetheless, EPA 
believes that its estimate of average dietary exposure to dioxins is a 
reasonable characterization of current exposure because, for example, 
the emission reductions that have occurred since most of the food 
samples were collected are not believed to be as significant as 
earlier emission reductions. Regarding toxicity estimates, because 
sufficient data are not available on many of the individual dioxins, 
EPA used an approach that relies on data developed by the World Health 
Organization to estimate the toxicity of the various mixtures of 
dioxins identified in the 10 types of foods. Although this approach 
may overstate or understate the concentrations of dioxins in the 
foods, it is the internationally accepted scientific method for risk 
assessments of dioxins. 

While both EPA and the World Health Organization have taken steps 
during the past decade directed at the general objective of assessing 
the human health risks of dioxins, some of their specific objectives 
and processes have differed. Nonetheless, the analytical methods the 
organizations used and the conclusions they reached have much in 
common. EPA established a long-range objective of characterizing the 
potential human health risks posed by exposure to dioxins using a 
comprehensive, multiyear review process resulting in a reassessment 
report. In contrast, the World Health Organization conducted a series 
of individual reviews with more narrowly focused primary objectives, 
such as updating the estimated amount of dioxins to which a person 
could be exposed daily for a lifetime without appreciable health 
consequences. Regarding analytical methods and conclusions, both EPA 
and the World Health Organization: 

* Examined similar sets of human and animal study data, considered a 
similar range of health effects, and applied some analytical concepts 
that both entities determined were more appropriate to the assessment 
of dioxins than those often used in assessments of other chemicals. 

* Concluded that dioxins could adversely affect human health at lower 
exposure levels than previously thought and that some adverse 
noncancer effects, such as reproductive and developmental impairments, 
could occur at or near the levels to which the general population is 
now being exposed. 

A major difference in the organizations' assessments concerns whether 
there are threshold levels below which exposure to dioxins would pose 
a negligible risk of cancer. While EPA assumed there is no safe 
threshold level for cancer effects, the World Health Organization 
assumed there is. 

EPA's draft reassessment report largely reflects the recommendations 
and suggestions provided to the agency by the two most recent 
independent peer review panels, although some areas of disagreement on 
key scientific issues remain. The panels, one consisting of 12 
independent reviewers and the other convened by EPA's Science Advisory 
Board, concurred with many key assumptions and approaches that EPA 
used. In addition, the panels made recommendations on several issues 
and provided suggestions for EPA to consider. EPA generally addressed 
the panels' recommendations and suggestions by, for example, 
performing additional analyses or explaining that the data currently 
available are not yet sufficient to address the recommendation or 
suggestion. If EPA disagreed with the panels' recommendations or 
suggestions, it explained its position in the text. Additional changes 
are being made as EPA prepares the draft for external interagency 
review. Lack of consensus on some scientific issues, such as whether 
the weight of evidence supports EPA's classification of TCCD as a 
human carcinogen, reflects uncertainty in areas where data are 
limited. Accordingly, the Science Advisory Board views this 
reassessment report as an interim evaluation that will need to be 
updated and peer reviewed in the future as important data gaps are 
addressed. 

Background: 

Dioxins persist for a long time in the environment because they do not 
dissolve in water and are relatively immobile in soil and sediment. 
When animals consume plants, feed, and water contaminated with 
dioxins, they accumulate in the animals' fatty tissue. Similarly, when 
humans consume these animals, the dioxins then accumulate in human 
fatty tissue. According to EPA, because dioxins also persist in the 
body for years, recent significant reductions in dioxin emissions into 
the air are unlikely to reduce human health risks in the near term. 

While EPA estimates that most exposure to dioxins occurs from eating 
commonly consumed foods, the draft reassessment report also estimates 
that limited exposure to dioxins results from breathing air containing 
trace amounts of dioxins; inadvertently ingesting soil containing 
dioxins; and absorbing through the skin minute levels of dioxins 
present in the soil. Some people may experience higher exposure levels 
than the general population as a result of food contamination 
incidents; workplace exposures; industrial accidents; or consuming 
unusually high levels of fish, meat, or dairy products. When 
calculating human exposures, dioxins are measured in picograms—that 
is, trillionths (0.000000000001) of a gram. Highly sophisticated 
measurement techniques and technologies are required to test foods for 
the presence of the 29 dioxins identified as having toxic effects. 

The several hundred known dioxin compounds can be placed in one of 
three closely related families: polychlorinated dibenzo-p-dioxins 
(CDD), polychlorinated dibenzofurans (CDF), and polychlorinated 
biphenyls (PCBs). CDDs and CDFs are byproducts of combustion and some 
industrial processes. According to EPA, U.S. emissions of CDDs and 
CDFs into the environment declined by 75 percent between 1987 and 1995 
primarily as a result of reductions in emissions from municipal and 
medical waste incinerators. Some PCBs share certain characteristics 
with CDDs and CDFs and therefore are identified as "dioxin-like." PCBs 
were at one time manufactured for use in products such as lubricants 
and industrial transformers but have not been made in the United 
States since 1977. However, because dioxins break down so slowly, past 
emissions remain in the environment for years—even decades—before they 
diminish. Consequently, a large part of humans' current exposure to 
dioxins is due to releases of dioxins that were stored in soil and 
sediment, and to a lesser extent in vegetation and the atmosphere. 
These sources are called "reservoir sources." EPA believes that with 
the reduction in current emissions from combustion and incineration, 
these reservoir sources have taken on more significance. 

According to EPA, dioxins always occur in the environment and in 
humans as complex mixtures of individual compounds. However, the 
complex nature of the dioxin mixtures to which people are exposed 
(through foods or other sources) complicates evaluation of the health 
risks such mixtures might pose. Scientists therefore developed the
concept of toxic equivalency factors (TEFs) to facilitate risk 
assessment of exposure to these mixtures. Because TCDD is the best-
understood dioxin, it is used as a frame of reference for estimating 
the toxicity of the other dioxins, and its TEF is set at 1.0. Only 1 
of the other 28 dioxins included in EPA's reassessment has a TEF of 
1.0; most of the others have TEFs of 0.1 or less, meaning that they 
are considered less toxic to humans than TCDD. International experts 
review and periodically update the TEFs based on new data. For its 
reassessment of dioxins, EPA used the latest revisions that were made 
at an expert meeting organized by the World Health Organization in 
1997.[Footnote 4] 

Since 1991, EPA has been updating its initial 1985 report assessing 
the health risks of dioxins. The October 2001 draft reassessment 
report exceeds 3,000 pages. Part I of the draft report provides 
information on exposure to dioxins, including chapters on dietary 
intake; part II addresses health assessment methodologies and specific 
health effects; and part IA the Integrated Summary[Footnote 5] 
highlights information in parts I and II on exposure and health 
effects and provides a risk characterization—a statement summarizing 
EPA's assessment of the health risks associated with dioxins. In the 
reassessment, EPA studied the risks of cancer as well as noncancer 
health effects, such as neurological and reproductive impairments. 

Founded in 1948, the World Health Organization (WHO) is a specialized 
agency of the United Nations, with 191 member states. WHO's functions 
include giving worldwide guidance in the field of health and setting 
global standards for health. WHO carries out these functions through a 
variety of offices and programs that often collaborate with each other 
and with other public health entities of WHO's member states and 
nongovernmental organizations. The principal contributors to the WHO 
reassessments of dioxin risks that are discussed in this report have 
been (1) the International Agency for Research on Cancer, which 
coordinates and conducts both epidemiological and laboratory research 
into the causes of cancer; (2) the WHO European Centre for Environment 
and Health, which coordinates comprehensive efforts, in collaboration 
with the International Programme on Chemical Safety, to evaluate the 
possible health risks of dioxins as well as methods of prevention and 
control of environmental exposure of the general population to these 
chemicals;[Footnote 6] and (3) the Joint Expert Committee on Food 
Additives of the United Nations' Food and Agriculture Organization and 
WHO, which provides scientific evaluations as a basis for the 
development of food standards by the Codex Alimentarius (food code) 
Commission.[Footnote 7] 

EPA Used Data on the Presence of Dioxins, Toxicity, and Food 
Consumption to Estimate Human Dietary Exposure: 

To estimate dietary exposure to dioxins, EPA obtained and reviewed 
information on (1) the dioxins present in 10 types of foods[Footnote 
8] with high fat content, (2) the toxicity of individual dioxins 
contained in these food types, and (3) the quantities of these foods 
that people in the United States typically eat. EPA has incorporated 
new studies following improvements in analytical capabilities to 
detect dioxins in food during the 1990s. However, in its draft 
reassessment report, EPA identified a number of limitations with the 
food data used to estimate dietary exposure that add uncertainty to 
the agency's overall estimate of current average daily dietary 
exposure to dioxins. For example, in some cases, the studies available 
on the presence of dioxins in foods were not designed to estimate 
national averages. Further, while EPA used the accepted method for 
estimating the toxicity of the dioxins found in the 10 food types, EPA 
and others acknowledge that the method has limitations. Finally, EPA 
estimated the quantities of these foods consumed using U.S. Department 
of Agriculture (USDA) data on U.S. adults' food consumption based on 
surveys made between 1989 and 1991; however, EPA believes the dietary 
habits of Americans have changed very little over the course of the 
past decade. 

EPA Estimates That Most Human Exposure to Dioxins Occurs from Eating 
Certain Types of Foods: 

A body of scientific research on foods in Europe, North America, and 
other locations indicates that the primary source of human exposure to 
dioxins is the dietary intake of foods, especially those containing 
animal fat. According to EPA's October 2001 draft reassessment report, 
the average adult in the United States receives about 95 percent of 
his or her exposure to dioxins by eating commonly consumed foods, such 
as beef, pork, and poultry; fish; and dairy products. (EPA estimated 
small exposures to dioxins from the air and soil as well.) 

The 10 types of foods EPA analyzed for its reassessment are beef; 
pork; poultry; other meats, such as lamb and baloney; eggs; milk; 
dairy products, such as cheese and yogurt; freshwater fish and 
shellfish; marine fish and shellfish; and vegetable fat, such as corn 
and olive oils and margarine. These foods, only one of which is not of 
animal origin, are believed to be the major contributors to dietary 
exposure to dioxins. Even though vegetable fat products are estimated 
to contain low levels of dioxins, EPA included these foods in its 
analysis because they are high in fat and common in the American diet. 
EPA excluded fruits and vegetables from its analysis because data on 
dioxins in U.S. fruit and vegetable products, which generally contain 
little or no fat, are extremely limited. The existing data indicate 
that typically these products contain low levels of dioxins, which 
generally stem from residues—deposits on outer layers with little 
penetration to inner portions. 

Until recently, chemical analyses of dioxins in foods have focused 
primarily on two of the families of dioxins, the CDDs and CDFs, with 
less attention on identifying and measuring specific PCBs. The draft 
reassessment report includes an evaluation of PCB levels in the 10 
food types. The draft report identifies estimated exposures to CDDs 
and CDFs together and identifies the estimated exposure to PCBs 
separately. This approach provides information that can inform 
potential regulatory approaches, among other things, because CDDs and 
CDFs result primarily from combustion and industrial processes, 
whereas PCBs, which persist in the environment from the 1970s and 
earlier, are no longer being manufactured. 

As shown in table 1, EPA estimated that the average adult in the 
United States is exposed daily to about 63 picograms of dioxins 
through dietary intake, with the highest exposure coming from beef and 
freshwater fish and shellfish. According to EPA, this exposure level 
is close to the level that has caused adverse noncancer effects in 
animals, such as effects on the development of reproductive systems. 
It is important to note that EPA's dietary exposure estimates are 
averages, and they do not apply to adults with additional or unusual 
exposure to dioxins-for example, from diets unusually high in fat 
content or diets of foods high in dioxin content.[Footnote 9] 

Table 1: EPA's Estimates of the Average U.S. Adult's Daily Exposure to 
Dioxins From Dietary Intake, Picograms per Day: 

Food type: Beef; 
Dietary exposure to CDDs and CDFs: 9.0; 
Dietary exposure to PCBs: 4.2; 
Total dietary exposure to dioxins: 13.2. 

Food type: Freshwater fish and shellfish; 
Dietary exposure to CDDs and CDFs: 5.9; 
Dietary exposure to PCBs: 7.1; 
Total dietary exposure to dioxins: 13.0. 

Food type: Dairy products (cheese, yogurt, etc.); 
Dietary exposure to CDDs and CDFs: 6.6; 
Dietary exposure to PCBs: 3.2; 
Total dietary exposure to dioxins: 9.8. 

Food type: Other meats (lamb, baloney, etc.); 
Dietary exposure to CDDs and CDFs: 4.5; 
Dietary exposure to PCBs: 1.0; 
Total dietary exposure to dioxins: 5.5. 

Food type: Marine fish and shellfish; 
Dietary exposure to CDDs and CDFs: 2.5; 
Dietary exposure to PCBs: 2.4; 
Total dietary exposure to dioxins: 4.9. 

Food type: Milk; 
Dietary exposure to CDDs and CDFs: 3.2; 
Dietary exposure to PCBs: 1.5; 
Total dietary exposure to dioxins: 4.7. 

Food type: Pork; 
Dietary exposure to CDDs and CDFs: 4.2; 
Dietary exposure to PCBs: 0.2; 
Total dietary exposure to dioxins: 4.4. 

Food type: Poultry; 
Dietary exposure to CDDs and CDFs: 2.4; 
Dietary exposure to PCBs: 0.9; 
Total dietary exposure to dioxins: 3.3. 

Food type: Eggs; 
Dietary exposure to CDDs and CDFs: 1.4; 
Dietary exposure to PCBs: 1.7; 
Total dietary exposure to dioxins: 3.1. 

Food type: Vegetable fat (oils, margarine, etc.); 
Dietary exposure to CDDs and CDFs: 1.0; 
Dietary exposure to PCBs: 0.6; 
Total dietary exposure to dioxins: 1.6. 

Food type: Total; 
Dietary exposure to CDDs and CDFs: 40.7; 
Dietary exposure to PCBs: 22.8; 
Total dietary exposure to dioxins: 63.5. 

Notes: The average adult is assumed to weigh 70 kilograms (154 
pounds). A picogram is one-trillionth of a gram. 

Source: Derived from U.S. EPA, October 2001 draft dioxin reassessment 
report, chapter 4, tables 430 and 4-31. 

[End of table] 

The Food Samples EPA Studied to Identify the Presence of Dioxins Had a 
Variety of Limitations: 

To estimate any population's dietary intake of dioxins, the specific 
dioxins present in the various foods must be identified and measured 
through chemical analyses of the foods. However, reliable estimates of 
the average concentrations of dioxins in specific foods nationwide 
have only recently begun to be available. In the past, data were 
available only from studies of dioxin concentrations in a specific 
food product or products in a specific location or a few locations, 
and these data were not sufficient to reliably estimate average 
national exposure. During the 1990s, as analytical capabilities to 
detect dioxins at parts-per-trillion levels were developed, new 
studies of foods in the United States, some with broader scope than 
the earlier studies, became available. EPA has incorporated new studies	
into its analysis of dietary exposure to dioxins to try to develop 
more reliable national estimates of such exposure. As a result, the 
estimates presented in the October 2001 draft reassessment report are 
based on more food data than the drafts developed just a few years ago. 

Nevertheless, in its October 2001 draft reassessment report, EPA said 
that the amount and the representativeness of the food data it used to 
estimate the average U.S. adult's dietary exposure to dioxins vary. 
Further, EPA officials acknowledged that some of the available studies 
were not designed to estimate national average exposures. As discussed 
below, the food sample data are limited in part by the timing of the 
sampling, variations in the methods used to collect the samples, and 
the types of samples collected and analyzed. In commenting on a draft 
of this report, EPA officials said that these food data limitations do 
not represent major weaknesses in its estimates of dietary exposure to 
dioxins. 

* As reported in the draft reassessment, most of the food samples were 
collected between 5 and 8 years ago. Current samples would be expected 
to have lower dioxin levels because emissions containing dioxins 
declined by about 75 percent from 1987 to 1995, and EPA believes the 
downward trend is continuing.[Footnote 10] Nevertheless, EPA believes 
that the exposure estimates based on food data from the mid-1990s are 
representative of current dietary exposure for several reasons. First, 
EPA believes that because most of the food samples the agency used for 
its reassessment were collected after the 75-percent decrease in 
emissions, much of the decrease should already be reflected in the 
foods' dioxin concentration numbers. Second, EPA said that, because 
most municipal and medical waste incinerators are located far from and 
downwind of concentrated meat and dairy production areas, the impact 
of any emission reductions since 1995 on the commercial food supply 
should be proportionately less than on the environment in general. 
Third, EPA said that because reservoir sources of dioxins account for 
half or more of current exposure, and because some sources of dioxins 
are unknown, it is unlikely that emission reductions that occurred 
after most of the food samples were taken would significantly affect 
the current estimate of general population exposure from the 
commercial food supply. 

* According to EPA, while its analyses of some of the foods are based 
on national samples collected from food processing or food monitoring 
locations, such as federal slaughtering establishments, other analyses 
are based on limited "market basket surveys"—random purchases of 
selected products, such as eggs, direct from grocery stores—in a small 
number of U.S. and Canadian cities.[Footnote 11] Depending on their 
design, national surveys would generally be more representative of 
average dietary exposures to dioxins than limited surveys. 

* Some of the analyses of the foods were derived from individual food 
samples, while others were from composite samples. Using composites is 
more economical than using individual samples, and EPA believes they 
are appropriate for use in analyzing dioxin concentrations to 
establish average, or mean, exposure estimates. However, EPA 
acknowledges that data on the variability or range of results from 
individual samples typically are not available from studies analyzing 
composite samples. As a result, information that can provide insight 
into the reliability of the estimates is not available. Table 2 shows 
the number(s), type(s), and date(s) of the samples EPA used for each 
of the 10 food categories. 

Table 2: Numbers, Types, and Dates of Food Samples EPA Used in 
Estimating Dietary Exposure to Dioxins: 

Food type: Beef (back fat samples); 
Number/type of sample: 63 individual samples; 
Year(s) samples collected: 1994. 

Food type: Pork (belly fat samples); 
Number/type of sample: 78 individual samples; 
Year(s) samples collected: 1995. 

Food type: Poultry (abdominal fat samples); 
Number/type of sample: 78 individual samples; 
Year(s) samples collected: 1996. 

Food type: Milk; 
Number/type of sample: 8 composite samples; 
Year(s) samples collected: 1996 and 1997. 

Food type: Dairy products; 
Number/type of sample: 8 composite samples; 
Year(s) samples collected: 1996 and 1997. 

Food type: Eggs[A]; 
Number/type of sample: 15 composite samples (24 eggs each); 
Year(s) samples collected: 1997. 

Food type: Marine fish and shellfish[A]; 
Number/type of sample: 158 individual samples; 
Year(s) samples collected: 1995 and 1996. 

Food type: Freshwater fish and shellfish[A]; 
Number/type of sample: 222 samples (individual and composite); 
Year(s) samples collected: 1986-89; 1994; 1996-99. 

Food type: Vegetable fat (oils, margarine, etc.)[A]; 
Number/type of sample: 30 individual samples; 
Year(s) samples collected: 1995[B]. 

Food type: Other meats; 
Number/type of sample: [C]; 
Year(s) samples collected: [C]. 

[A] EPA used these samples to analyze CDDs and CDFs only. 

[B] Estimate based on 1996 study publication date. 

[C] EPA did not provide this information for other meats. 

Source: U.S. EPA, October 2001 draft dioxin reassessment report. 

[End of table] 

* According to the draft reassessment report, data from some of the 
food studies were sufficient to estimate exposure to total dioxins—the 
CDDs, CDFs, and PCBs. However, the report shows that in other cases, 
the data only provided support for estimating exposure to CDDs and 
CDFs. As a result, for four food categories, different studies are 
used for estimating exposure to CDDs and CDFs than those used for 
PCBs. As reported in the draft reassessment, these studies analyzed 
fewer samples, a number of which were collected 14 or more years ago 
and therefore provide data on dioxins that may not reflect current 
levels. Table 3 shows information on the four foods for which EPA used 
different samples to estimate exposure to PCBs than those used to 
estimate CDDs and CDFs. 

Table 3: Numbers, Types, and Dates of Food Samples EPA Used in 
Estimating Dietary Exposure to PCBs in Four Food Categories: 

Food type: Eggs; 
Number/type of sample: 18 individual samples; 
Year(s) samples collected: 1995. 

Food type: Eggs; 
Number/type of sample: 6 composite samples[A]; 
Year(s) samples collected: 1986-88[B]. 

Food type: Marine fish and shellfish; 
Number/type of sample: 1 composite of 13 samples; 
Year(s) samples collected: 1995. 

Food type: Marine fish and shellfish; 
Number/type of sample: 5 composites[A]; 
Year(s) samples collected: 1986-1988. 

Food type: Freshwater fish and shellfish; 
Number/type of sample: 1 composite of 10 samples; 
Year(s) samples collected: 1995. 

Food type: Freshwater fish and shellfish; 
Number/type of sample: 6 composites[A]; 
Year(s) samples collected: 1986-88[B]. 

Food type: Vegetable fat; 
Number/type of sample: 5 composites[A]; 
Year(s) samples collected: 1986-88. 

[A] The studies used in the analyses do not specify the number of 
individual samples in the composite samples. 

[B] The year that one of the composite samples was collected is not 
identified. The study was published in 1989. 

Source: U.S. EPA, October 2001 draft dioxin reassessment report. 

[End of table] 

* As EPA acknowledges in the draft report, its analyses of dioxins 
present in foods are based on uncooked foods, even though dioxin 
levels can be different in cooked and uncooked foods. According to 
EPA, while many studies indicate that foods have similar dioxin 
concentrations whether they are cooked or uncooked, the studies show 
that some foods have lower concentrations of dioxins when they are 
cooked, while others have higher levels when they are cooked. These 
differences reflect, in part, the fact that different cooking methods 
(frying, boiling, grilling, etc.) may have different effects on dioxin 
levels. On the basis of the available data, which it believes are not 
conclusive, EPA states in the draft reassessment report that uncooked 
food is a reasonable surrogate to use for identifying and quantifying 
dioxin concentrations in cooked food. 

* Because the primary focus of EPA's exposure assessment was on foods 
produced and consumed in the United States, EPA's analysis does not 
address imported food products that may vary from domestic sources in 
dioxin content. 

Despite these limitations, the data on dioxin levels in foods 
supporting the October 2001 draft report reflect a significant 
improvement compared with the data EPA had available for use in its 
1994 draft reassessment report, which was peer reviewed in 1995 by 
EPA's Science Advisory Board. Specifically, in the 1994 draft, EPA 
provided estimates of levels of CDDs and CDFs for seven food types; 
the October 2001 draft provided estimates for ten food types. With the 
exception of an estimate for fish that was based on 60 samples, the 
1994 draft estimates were developed from samples ranging in number 
from 2 to 14; as table 2 shows, the number of samples used for the 
2001 draft is greater. In addition, while EPA recognized that PCBs 
were being identified in foods, the agency did not have sufficient 
data at that time to develop estimates of the levels of specific PCBs 
in foods; the 2001 draft does include estimates of PCB levels in foods. 

The following sections describe in greater detail the samples EPA used 
to identify the level of dioxins in 9 of the 10 foods studied—beef, 
pork, and poultry; freshwater and marine fish; milk, dairy, and eggs; 
and vegetable fat—and any associated limitations or uncertainties. 
(The draft reassessment report does not provide any information 
supporting EPA's estimate of the types and amounts of dioxins in other 
meats, the tenth food type.[Footnote 12] In commenting on a draft of 
our report, EPA said that information on other meats would be provided 
in its final report.) 

Beef, Pork, and Poultry: 

In estimating exposure to dioxins from beef, pork, and poultry, EPA 
used data from the first statistically designed national surveys of 
dioxin levels in these foods sponsored by EPA and USDA. These surveys 
were designed to be representative of all U.S. regions and all classes 
of animals slaughtered in federally inspected slaughtering 
establishments. EPA believes the three surveys provide reasonable 
estimates of the average national concentrations of dioxins in beef, 
pork, and poultry. Nonetheless, information EPA provided in the draft 
reassessment report about these samples identifies some limitations 
and uncertainties about these studies. 

* The samples are now between 6 and 8 years old and therefore may not 
reflect current exposures. To address this data gap, EPA and USDA are 
conducting a follow-up study on dioxin levels in beef, pork, and 
poultry that will commence in 2002 and provide updated information. 
However, EPA officials said the results of this survey will likely not 
be available for incorporation into the dioxin reassessment report 
that EPA plans to publish this year. 

* The animal samples for beef, pork, and poultry were not meat 
products sold in grocery stores but rather were cuts of fat generally 
not consumed—either back fat, abdominal fat, or belly fat from 
slaughtering establishments. Some uncertainty therefore surrounds the 
accuracy of EPA's estimates of dietary intake of dioxins because of 
comparability concerns. EPA used this approach because USDA federal 
inspectors could obtain the samples with little disruption to the 
slaughtering establishments and because the samples' high fat content 
would enable more accurate measurement of dioxins, since the analysis 
would be of highly concentrated fat samples. However, this approach 
assumes that edible meat products sold in grocery stores contain the 
same types and amounts of dioxins as the fat samples (adjusted for 
differences in percentages of fat). According to EPA, this assumption 
is supported by a well-developed understanding of the manner in which 
dioxins distribute across fat reservoirs in vertebrates. Therefore, 
EPA concluded that the fat samples for all three foods were comparable 
to the edible meat samples. EPA also based its conclusion on its 
analysis of beef samples—comparing five back fat samples with other 
cattle parts, including muscle tissue, which could be representative 
of edible beef products.[Footnote 13] For the five samples, the ratios 
of CDDs and CDFs in muscle fat to CDDs and CDFs in back fat varied by 
up to 300 percent, ranging from 0.58 to 1.7; and the ratios for PCBs 
varied by up to 50 percent, from 1.0 to 1.5.[Footnote 14] Although 
some of the variation may result from imprecision inherent in 
measuring picograms, this limited analysis indicates that using fat 
samples may overstate or understate to some extent the dioxin levels 
in beef, pork, and poultry products. 

* EPA reported that it excluded 2 of the 80 samples of abdominal fat 
from poultry because they had significantly higher concentrations of 
certain dioxins than the other samples. EPA, USDA, and the Food and 
Drug Administration investigated the cause of these elevated dioxin 
levels and determined that it stemmed from contaminated animal feed 
that had been distributed to poultry, fish, hog, and cattle producers 
in several southern and southwestern states!' EPA considered the two 
poultry fat samples inappropriate for the dioxins study, which was 
aimed at identifying typical exposures to dioxins. However, it is not 
clear that the poultry samples with high concentrations of dioxins 
were anomalies because the incidence of dioxin contamination in animal 
feeds is not known. For example, this instance of contaminated animal 
feed was discovered by the first national poultry sample, which tested 
only 80 samples nationwide. 

* In response to suggestions from a peer review panel, when the data 
were sufficient to do so, EPA presented a standard deviation—the 
typical amount of variability around the mean—on its estimates of the 
average levels of dioxins in the foods, as well as the range of the 
levels of dioxins identified in the samples. For beef, pork, and 
poultry, EPA was able to provide this information for the CDDs and 
CDFs. These data indicated considerable variability in the levels of 
CDDs and CDFs in the foods. For example, the estimated level of 0.28 
picograms of dioxins in a gram of pork has a standard deviation of 
plus or minus 0.28. In other words, the standard deviation is equal to 
or greater than the mean. Accordingly, the estimated dioxin level is 
subject to a wide range of uncertainty. 

* Because EPA did not have sufficient information to develop a 
standard deviation for PCBs, the agency could not develop a standard 
deviation for total dioxins (the combination of CDDs, CDFs, PCBs) in 
beef, pork, and poultry. As a result, EPA could not state with any 
degree of certainty that exposure to total dioxins or to PCBs would 
fall within specified levels. EPA believes this limitation is a minor 
one because it considers the average exposure level, rather than the 
more limited extreme exposures, to be of greater public health 
interest. Nonetheless, this additional analysis, if available, would 
enable policymakers, scientific peer reviewers, and other users to 
better evaluate the extent to which the data may be representative of 
average national exposures. 

Freshwater and Marine Fish and Shellfish: 

Though EPA analyzed more fish samples for the current reassessment 
draft than for earlier drafts, the current draft report acknowledges 
that the levels of dioxins in fish are more uncertain than those in 
the other foods for two reasons. First, the data lack the "geographic 
coverage and statistical power" of the other food surveys. That is, 
while the sample sizes for CDDs and CDFs in fish are considerably 
larger than those used for the analyses of other foods, they do not 
provide data that are nationally representative because of the 
diversity of fish and bodies of water. Specifically, there are a 
significant number and variety of freshwater and marine fish species 
living in numerous bodies of water that contain differing types and 
levels of dioxins. Moreover, fish consumed in the United States 
include both farm-raised and wild fish. Second, EPA based its 
estimates for levels of PCBs in fish on a much smaller data set than 
it used for CDDs and CDFs. EPA used 222 samples to estimate the levels 
of CDDs and CDFs in freshwater fish and shellfish and 158 samples for 
marine fish and shellfish compared with 7 and 6 composite samples for 
PCBs for freshwater and marine fish, respectively. Further, most of the 
samples for PCBs were from Canadian rather than U.S. cities, and the 
analyses of levels of PCBs in them did not evaluate all of the PCBs 
identified as being toxic. For example, according to the report, only 
one of the composite samples for marine fish and shellfish, collected 
between 1984 and 1986, was analyzed for the presence of the most 
common and toxic PCB, referred to as PCB-126. For these reasons, EPA 
acknowledges in the draft report that the resulting estimates are not 
representative of the level of dioxins in fish nationally. We note 
that the limitations of the data used to estimate the levels of PCBs 
in fish are particularly significant because in the report, EPA 
estimates that freshwater fish contains the highest levels of PCBs 
(and total dioxins) of all the foods studied. 

The samples EPA used to estimate the levels of dioxins in fish were 
derived from EPA's National Bioaccumulation Study[Footnote 16] and 
three market basket surveys in the United States and Canada. Samples 
for the bioaccumulation study were collected between 1986 and 1989, 
whereas the samples for the market basket surveys were collected about 
a decade later, between 1995 and 1999. Some of the limitations and 
uncertainties associated with these samples that EPA acknowledged in 
the draft report are highlighted below. 

* Most of the fish samples used for the reassessment draft were 
collected 5 or more years ago; some are between 13 and 16 years old. 

* EPA did not have sufficient data to estimate exposure to PCBs from 
eating freshwater or marine shellfish. 

* Some of the estimates for freshwater fish, such as trout, are based 
on samples from the bioaccumulation study that may be more 
representative of wild fish (i.e., fish caught in recreational 
fishing) than fish typically purchased by the general population at 
grocery stores, which is largely farm-raised. Specifically, in cases 
in which EPA did not have data on farm-raised freshwater fish or fish 
purchased in grocery stores, the agency used the concentration of CDDs 
and CDFs from samples of wild caught fish from the bioaccumulation 
study. This use of older data on wild fish increases the uncertainty 
about the representativeness of EPA's exposure estimate. 

* For some fish species, such as mullet and mackerel, estimates were 
based entirely on samples collected in the Mississippi area and 
therefore may not be representative of levels seen in other locations. 

* EPA did not have sufficient data to estimate a standard deviation 
for the average levels of dioxins in freshwater or marine fish. As a 
result, EPA cannot state with any degree of certainty what the related 
dietary exposure to dioxins is. 

Milk, Dairy, and Eggs: 

The milk samples upon which both the milk and dairy estimates are 
based came from a national survey. In this survey, samples were 
collected during the four seasons, providing information on seasonal 
(temporal) variations. The milk samples were collected from 51 
sampling stations, located in a majority of the states, that support 
EPA's Environmental Radiation Ambient Monitoring System.[Footnote 17] 
In contrast, the estimates for CDDs and CDFs in eggs are based on Food 
and Drug Administration market basket surveys in 1997 in California, 
Georgia, Minnesota, New York, Ohio, Oregon, Pennsylvania, and 
Wisconsin. The estimates for PCBs in eggs are based on market basket 
surveys in San Diego, California; Atlanta, Georgia; Binghamton, New 
York; and five major Canadian cities. EPA used composite samples of 
milk and eggs to identify and measure the presence of specific dioxins 
in milk, dairy, and eggs. Information provided in the draft report 
identifies some limitations associated with these data. 

* Most of the milk samples were collected 6 years ago. 

* The egg samples used to support the analyses for CDDs and CDFs were 
collected 5 or more years ago. The estimates for PCBs in eggs are 
based, in part, on samples obtained in five Canadian cities between 14 
and 16 years ago. 

* Only one of the six composite samples used to estimate the level of 
PCBs in eggs was analyzed for the presence of the most common and 
toxic PCB. 

Vegetable Fat: 

According to EPA, its estimates of CDDs and CDFs in vegetable fat were 
developed from a market basket survey that was not representative of 
edible oil consumption in the United States. The 30 samples of various 
oils, solid shortening, margarine, and an oil spray were obtained from 
grocery stores in nine U.S. cities or metropolitan areas: Chicago, 
Illinois; Cincinnati, Ohio; Denver, Colorado; Miami, Florida; 
Minneapolis, Minnesota; Salt Lake City, Utah; San Antonio, Texas; San 
Francisco, California; and the Washington, D.C., metropolitan area. 
Although neither the reassessment report nor the study (published in 
1996) states when the samples were collected, there is typically at 
least a 1-year lag between collection and publication, indicating that 
the samples were collected 8 or more years ago. EPA used limited data 
to estimate the level of PCBs in vegetable fat. This estimate is 
derived from five composite samples of cooking fats and salad oils, 
each of which was obtained 14 or more years ago from one of five major 
(unidentified) Canadian cities. As a result of these limitations that 
EPA identified in the draft report, the estimate for dietary exposure 
to dioxins from eating vegetable fats is unlikely to reflect current 
average dietary exposure in the United States. 

Method EPA Used to Estimate Toxicity of Dioxins in the 10 Food Types 
Is Accepted by Experts but Has Limitations: 

After using the chemical analyses discussed previously to identify the 
types and quantities of dioxins present, EPA estimated the toxicity of 
the dioxins in the 10 types of foods, using measures called toxic 
equivalency factors. (As noted earlier, these measures—called TEFs—are 
used to create a frame of reference by comparing the potential 
toxicity of individual dioxins in a sample with the toxicity of the 
most toxic and best understood dioxin, TCDD, which is assigned a TEF 
of 1.) EPA used the TEFs that were updated by WHO in 1997. For each of 
the types of foods, EPA multiplied the measured types and amounts of 
the dioxins present by the related TEFs to arrive at a "dioxin toxic 
equivalence value" for that particular food category/dioxin 
combination.[Footnote 18] For each food category, the total dioxin 
toxic equivalency is the sum of these products—that is, the sum of the 
toxic equivalence values for (1) CDDs and CDFs and (2) PCBs. This 
provides an indicator of the relative toxic concentration of dioxins 
in each food category. As table 4 shows, EPA estimated that freshwater 
fish and shellfish had the largest per-gram concentration of dioxins 
with toxic effects. 

Table 4: EPA's Estimates of Toxic Concentrations of Dioxins in 10 Food 
Categories, Picograms per Gram: 

Food category: Freshwater fish and shellfish; 
Dioxin toxic equivalence values for CDDs and CDFs: 1.00; 
Dioxin toxic equivalence values for PCBs: 1.20; 
Total dioxin equivalence values: 2.20. 

Food category: Marine fish and shellfish; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.26; 
Dioxin toxic equivalence values for PCBs: 0.25; 
Total dioxin equivalence values: 0.51. 

Food category: Pork; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.28; 
Dioxin toxic equivalence values for PCBs: 0.01; 
Total dioxin equivalence values: 0.29. 

Food category: Beef; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.18; 
Dioxin toxic equivalence values for PCBs: 0.08; 
Total dioxin equivalence values: 0.26. 

Food category: Other meats; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.18; 
Dioxin toxic equivalence values for PCBs: 0.04; 
Total dioxin equivalence values: 0.22. 

Food category: Eggs; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.08; 
Dioxin toxic equivalence values for PCBs: 0.10; 
Total dioxin equivalence values: 0.18. 

Food category: Dairy; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.12; 
Dioxin toxic equivalence values for PCBs: 0.06; 
Total dioxin equivalence values: 0.18. 

Food category: Poultry; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.07; 
Dioxin toxic equivalence values for PCBs: 0.03; 
Total dioxin equivalence values: 0.10. 

Food category: Vegetable fats; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.06; 
Dioxin toxic equivalence values for PCBs: 0.04; 
Total dioxin equivalence values: 0.10. 

Food category: Milk; 
Dioxin toxic equivalence values for CDDs and CDFs: 0.02; 
Dioxin toxic equivalence values for PCBs: 0.01; 
Total dioxin equivalence values: 0.03. 

Note: The toxic equivalence values are estimated on a whole (wet) 
weight basis, as opposed to a dry weight basis. 

Source: Derived from U.S. EPA, October 2001 draft dioxin reassessment 
report. 

[End of table] 

The toxic equivalence approach using TEFs has evolved over the last 20 
years and is the internationally accepted scientific approach for risk 
assessments of dioxins. This approach has been formally adopted by 
several countries and as guidance by international organizations, such 
as WHO. TEFs are used to decrease the overall uncertainty in assessing 
the health risks of dioxins because they provide a framework for 
addressing the complex mixtures of dioxins to which people are most 
often exposed. Nonetheless, a number of uncertainties are involved in 
the use of the TEF concept. As a result of these uncertainties, 
estimates of the concentrations of dioxins in foods based on this 
approach may be overstated or understated. 

The draft reassessment report acknowledges that there are still many 
questions about the use of the TEF method and the validity of some of 
the underlying assumptions. The report states that many assumptions 
are necessary because of lack of data. Specifically, the derivation of 
TEFs is limited by the amount of available data on the relative 
potency of different dioxins compared with TCDD. For many dioxins, the 
available data on relative potency may be limited to only a few 
experimentally observed effects. Some of these effects may not be 
considered toxic by themselves, but they still might provide evidence 
that exposure to dioxins led to biological or chemical effects in 
experimental subjects. For example, EPA noted that only TCDD and one 
mixture of certain dioxins have been tested for carcinogenicity. 
Therefore, in order to develop a TEF that estimates the cancer potency 
of a mixture including other dioxins, scientists have assumed that the 
relative potencies observed for noncancer effects approximate those 
for cancer. In other words, once derived, TEFs apply to all effects, 
not just those for which relative potency data were available. 

Nonetheless, after considering a number of the uncertainties and 
limitations of this approach, the international experts who derived 
the current TEFs concluded that the TEF concept is still the most 
plausible and feasible approach for risk assessment of dioxins. 
Furthermore, the TEF values for individual dioxins are reevaluated and 
updated periodically to reflect the available evidence. When WHO 
established the most recent TEFs in 1998, it suggested that the toxic 
equivalency scheme be reevaluated every 5 years and that the TEFs and 
their application to risk assessment be reanalyzed to account for 
emerging scientific information. 

Daily Dietary Intake Estimates Are Primarily Based on Food Surveys of 
U.S. Adults Administered Between 1989 and 1991: 

To develop its estimate of the daily dietary intake of dioxins by the 
average adult in the United States, EPA needed to calculate the amount 
of food containing dioxins that Americans typically eat. EPA obtained 
this information for the 10 food types from USDA food intake surveys. 
The USDA survey data include information on the amounts of specific 
foods consumed in a day by an average person weighing 70 kilograms 
(154 pounds). 

USDA obtained its data from detailed food surveys prepared by 
thousands of individuals selected from statistical samples. In these 
surveys, individuals generally provided detailed information on food 
consumption for 2 days. The surveys used statistical sampling to 
ensure that all seasons, geographic regions of the United States, and 
demographic and sociodemographic groups were represented. EPA's 
analysis of these data tabulated intake rates for the major foods, as 
well as for individual food items. The total quantity of each food 
eaten by the survey population in a survey day was tabulated and 
weighted to represent the quantity eaten by the entire U.S. population 
in a typical day. For the draft reassessment report, EPA averaged 
USDA's data for three age groups of adults ranging from ages 20 to 70 
and over. Table 5 provides EPA's estimates of the daily dietary intake 
of 10 food types by adults in the United States. 

Table 5: Estimated Daily Dietary Intake of 10 Food Types for an 
American Adult Weighing 70 Kilograms (154 pounds): 

Food: Milk; 
Estimated dietary intake (grams per day): 175.0. 

Food: Dairy; 
Estimated dietary intake (grams per day): 55.0. 

Food: Beef; 
Estimated dietary intake (grams per day): 50.0. 

Food: Poultry; 
Estimated dietary intake (grams per day): 35.0. 

Food: Other meats; 
Estimated dietary intake (grams per day): 25.0. 

Food: Eggs; 
Estimated dietary intake (grams per day): 17.0. 

Food: Vegetable fats; 
Estimated dietary intake (grams per day): 17.0. 

Food: Pork; 
Estimated dietary intake (grams per day): 1.5. 

Food: Marine fish and shell fish; 
Estimated dietary intake (grams per day): 9.6. 

Food: Freshwater fish and shellfish; 
Estimated dietary intake (grams per day): 5.9. 

Source: Derived from U.S. EPA, October 2001 draft dioxin reassessment 
report. 

[End of table] 

While EPA prefers to use USDA food data from the 1989-91 USDA 
Continuing Survey of Food Intake By Individuals because it has 
conducted a statistical analysis of these data and includes them in 
the agency's Exposure Factors Handbook,[Footnote 19] the draft 
reassessment report uses other data for fish and does not provide 
information on the basis for its estimates of dietary intake of other 
meats. Specifically, the draft reassessment report derived its 
estimates of the daily dietary intake of beef, pork, poultry, milk, 
dairy products, vegetable fats, and eggs from USDA's Continuing Survey 
Food Intake By Individuals conducted from 1989 through 1991. In 
contrast, the daily dietary intake of freshwater and marine fish and 
shellfish were derived from a March 2000 report on the consumption of 
fish prepared by EPA's Office of Water. This report used data from 
USDA's Continuing Survey of Food Intakes By Individuals conducted in 
1994, 1995, and 1996. In this report, EPA weighted its estimates of 
exposure to dioxins from fish by the species-specific concentrations 
according to species-specific fish consumption rates for the U.S. 
population. However, in cases where species-specific concentration 
data were not available, EPA used default values. For example, EPA 
used data from the bioaccumulation study as the default for certain 
freshwater fish. The use of various default assumptions adds
uncertainty to the exposure estimates. 

EPA officials said that EPA did not use more current dietary intake 
data from USDA in the October 2001 draft reassessment because EPA has 
not yet fully reviewed surveys subsequent to the 1989-91 surveys that 
it uses in its Exposure Factors Handbook. EPA officials told us that 
they did not believe it was necessary to use more current data because 
the dietary habits of Americans have changed very little over the 
course of the past decade. These officials cited data collected in 
surveys conducted between 1994 and 1996 that show little change in the 
intake of the 10 foods compared with surveys conducted between 1989 
and 1991. 

EPA's and WHO's Specific Reassessment Objectives and Processes 
Differed, but Their Analytical Methods and Conclusions on Dioxins' 
Health Risks Are Similar: 

EPA and WHO have undertaken extensive efforts to reassess the health 
risks of exposure to dioxins. EPA's comprehensive dioxin reassessment 
objective has been to characterize the potential human health risks 
posed by exposure to dioxins. To do this, EPA used an extensive, 
multiyear review process. In contrast, WHO had more narrowly focused 
primary objectives and conducted its reassessments of dioxins through 
a succession of individual reviews and meetings. Nonetheless, EPA and 
WHO used very similar analytical methods to identify the types of 
potential human health hazards associated with exposure to dioxins and 
assess the probability and severity of harm given different levels of 
exposure. Moreover, the conclusions EPA and WHO reached on the basis 
of their respective reassessments also reflected much agreement. 
However, there were some significant issues on which EPA and WHO 
differed, such as whether there are threshold doses of dioxins to 
which humans could be exposed over a lifetime without significant risk 
of cancer and whether dioxins other than TCDD are human carcinogens. 

EPA Undertook a Comprehensive Assessment, While WHO Used a Succession 
of Individual Reviews and Meetings: 
In general, both EPA and WHO focused their evaluations of the health 
effects and risks associated with dioxins on TCDD and 28 other related 
chemical compounds (including 12 dioxin-like PCBs) for which consensus 
toxic equivalency factors had been established through a 1997 meeting 
organized by WHO.[Footnote 20] However, there were important 
differences in some of the specific objectives of EPA's and WHO's 
dioxin reassessments and the processes used by EPA and WHO to develop 
the reassessments. 

EPA's overall objective has been very broad: to characterize the 
available scientific information on the potential health risks posed 
by exposures to dioxins. EPA therefore addressed each of the four 
major components of a chemical risk assessment: hazard identification, 
dose-response assessment, exposure assessment, and risk 
characterization.[Footnote 21] The resulting characterization of risks 
posed by dioxins can be used to inform risk management decisions, such 
as whether and where to set or revise regulatory standards, but other 
information and factors would also enter into such decisions.[Footnote 
22] The process by which EPA has undertaken this task has been a 
comprehensive, multiyear review. Moreover, the EPA reassessment has 
included multiple independent scientific peer reviews of various draft 
reports by EPA's Science Advisory Board and others. EPA has also 
solicited public review and comments on its draft reassessment. 

WHO's reassessment objective also addressed a broad range of data and 
issues regarding the potential exposures and health risks associated 
with dioxins, but the specific reports and evaluations WHO produced on 
dioxins generally had more narrowly focused primary objectives than 
EPA's reassessment report. In addition, rather than a comprehensive, 
integrated process such as EPA's, WHO's process consisted of 
individual evaluations and meetings for each of those particular 
objectives.[Footnote 23] 

* In 1997, the International Agency for Research on Cancer (IARC), a 
chief contributor to WHO's dioxin risk assessments, published 
monographs covering TCDD and 16 other dioxins. (This agency publishes 
the results of its evaluations of specific chemicals in its series 
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. In 
the rest of this report, we call the monographs covering TCDD and 
other dioxins the 1997 cancer monographs.) The primary objective 
leading to these monographs was to classify TCDD and other specific 
dioxins under a standard scheme that identifies whether and under what 
circumstances substances are human carcinogens.[Footnote 24] 
Essentially, this objective corresponds to the hazard identification 
step of EPA's four-step risk assessment process. 

* Under its activities related to the European Centre for Environment 
and Health, WHO organized two meetings of experts addressing issues on 
the health effects of dioxins. In June 1997, WHO convened experts in 
Stockholm, Sweden, to derive consensus toxic equivalency factors for 
29 dioxins that could be used for human, fish, and wildlife risk 
assessments. In May 1998, WHO convened 40 experts from 15 countries in 
Geneva, Switzerland, to evaluate scientific data on the health risks 
and exposures of dioxins with the principal objective of updating the 
estimated amount of dioxins to which humans can be exposed daily 
without appreciable harm. In the rest of this report, we call these 
efforts, respectively, the 1997 TEF meeting and the 1998 consultation. 

* At the 57th meeting of the Food and Agriculture Organization of the 
United Nations/WHO Joint Expert Committee on Food Additives in June 
2001 in Rome, Italy, the committee for the first time evaluated the 
risks associated with the presence of dioxins in food. The 
participants specifically evaluated dioxins (among other specific food 
additives and contaminants), with the view toward recommending 
acceptable intakes for dioxins contained in foods. The committee used 
the 1998 consultation's assessment as the starting point for its 
evaluation but took into account newer studies. In the rest of this 
report, we call this evaluation the 2001 food additives meeting. 

Appendix I highlights some of the major milestones in the EPA and WHO 
assessments of dioxin risks, with a particular focus on the 
reassessment efforts that both entities began in the 1990s. 

EPA and WHO Used Similar Analytical Methods: 

Despite differences in some of the specific objectives and processes 
of their respective reassessment efforts, EPA and WHO used similar 
analytical methods to identify and assess the potential health risks 
of dioxins. Through these analyses, EPA and WHO identified the types 
of potential hazards that might be associated with exposure to 
dioxins, the circumstances under which these substances could cause 
adverse effects, and the probability and severity of expected effects 
given different levels of exposure to dioxins. Specifically, both EPA 
and WHO: 

* reviewed available scientific data from many studies of humans and 
animals covering a variety of effects potentially associated with 
exposure to dioxins; 

* continued to consider cancer risks, as in the original dioxin risk 
assessments, but also paid increasing attention to noncancer health 
effects, such as changes in reproductive and developmental functions 
and the immune and nervous systems, as well as other health problems, 
such as chloracne (a chronic and disfiguring skin disease) and 
alterations in liver enzyme levels; 

* reviewed evidence regarding other biochemical, molecular, or 
cellular effects that have been observed in various studies, agreeing 
that these effects might be precursors to subsequent adverse effects; 
and; 

* considered a range of analytical methods, models, and approaches to 
assess the dose-response relationships for exposure to dioxins. 

EPA and WHO also used some analytical concepts and methods that they 
agreed were more appropriate to the analysis of dioxins than those 
that are often used for risk assessments of other chemicals. For 
example, both entities used body burden—the concentration of dioxins 
in the body—instead of other dose measures, such as daily intake, to 
compare risks between humans and animals and determine doses that 
would be of equivalent risk in humans and animals. The organizations 
also concurred that the concept of toxic equivalency should be used to 
facilitate risk assessment of dioxins and complex mixtures of dioxins. 
Furthermore, in contrast to chemical risk assessments in general, EPA 
and WHO often had sufficient data to focus on the dose level 
associated with a 1-percent increase in a particular effect (rather 
than being limited to the level associated with a 10-percent increase) 
and seldom had to extrapolate outside the observed doses or exposures 
from the studies that they used to prepare the reassessments. 

Much of the scientific data available to EPA and WHO on the potential 
effects of exposure to dioxins came from animal studies, mainly 
studies of TCDD on a variety of species. (According to WHO, most other 
dioxins and dioxin-like compounds are "relatively poorly studied" 
compared with TCDD.[Footnote 25]) However, EPA's and WHO's recent 
reassessment efforts also benefited from the increasing quantity and 
quality of data on the effects of dioxins in humans that became 
available during their reassessments. Among the sources of these human 
data were studies of occupational exposure of people who produce and 
apply herbicides; residents in a contaminated area of Seveso, Italy 
(where an accident at a chemical factory had released a cloud of toxic 
chemicals, including dioxins, in 1976); and noncancer effects in 
infants and children. 

EPA and WHO Had Similar Overall Conclusions but Differed on Some 
Important Issues: 

The conclusions EPA and WHO reached on the basis of their respective 
dioxin reassessments were frequently similar, but some significant 
differences also emerged. With respect to the major areas of 
agreement, both EPA and WHO concluded that TCDD is a human carcinogen 
and that: 

* dioxins can cause a variety of both cancer and noncancer health 
effects, 

* dioxins act in the same way within the body to cause the effects 
observed in animals and humans, 

* dioxins adversely affect human health at lower exposure levels than 
previously thought, and, 

* some effects could occur at or near the levels to which the general 
population is now being exposed. 

EPA and WHO not only concurred at the broad level of these conclusions 
but also on many of the supporting details. For example, both entities 
had similar reasons for concluding that TCDD is a human carcinogen: 
the combination of sufficient evidence that TCDD causes cancer in 
animals, more limited evidence of carcinogenicity from human data, and 
strong evidence that TCDD operates through the same mode, or 
mechanism, of action in animals and humans.[Footnote 26] 

The major differences of opinion between EPA and WHO concerned whether 
(1) there is a threshold below which exposure to dioxins would not be 
expected to cause cancer, (2) it is useful to calculate a "tolerable" 
dose of dioxins or estimate a dose without appreciable risk of 
deleterious effects to which humans can be exposed over a lifetime, 
and (3) both mixtures of dioxins and dioxins other than TCDD are 
likely human carcinogens. In addition, EPA quantified the general 
population's possible additional risk of developing cancer from 
exposure to dioxins, while WHO did not. Such differences may make it 
more difficult for interested parties to compare the results of EPA 
and WHO dioxin risk assessments. The following sections provide 
additional information on each of these differences. 

Cancer Threshold: 

EPA and WHO disagreed about whether there is a threshold below which 
exposure to dioxins would not cause cancer. EPA concluded that 
available evidence was insufficient for the agency to depart from its 
default linear cancer risk assessment approach, which is based on an 
assumption that no threshold exists regarding adverse effects (i.e., 
any exposure to carcinogenic substances, no matter how small, poses 
some risk of developing cancer).[Footnote 27] In contrast, WHO 
concluded that there is a threshold for all adverse effects, including 
cancer. Specifically, WHO concluded that dioxins do not initiate 
cancer through a direct effect on genetic material (that is, they are 
non-genotoxic carcinogens) and, therefore, do not warrant a linear (no 
threshold) assessment of risk. WHO also concluded that noncancer 
health effects occurred at lower body burdens (concentrations) of 
dioxins than the body burdens at which cancer occurred in animals. 
Accordingly, WHO determined that establishing a tolerable intake based 
on estimated thresholds for noncancer effects would also address any 
cancer risks (that is, if the intake were set to avoid appreciable 
noncancer health consequences, it should also avoid appreciable 
consequences concerning cancer). 

Estimating a "Tolerable" Dose or One Without Appreciable Risk: 

WHO programs estimated a tolerable daily intake for dioxins in 1998 
and a tolerable monthly intake in 2001. These measures represent the 
amounts of dioxins that the WHO experts believe a human could ingest 
daily or monthly for a lifetime without appreciable health 
consequences. Expressing these estimates as "tolerable" intakes 
generally does not connote that such intakes are acceptable or risk 
free, but rather that any health consequences would be judged to be 
tolerable while exposure is continuing to be reduced.[Footnote 28] 
EPA's related (but not identical) measure is the reference dose, which 
would estimate a daily exposure to the human population, including 
sensitive subgroups, that is likely to be without an appreciable risk 
of deleterious effects during a lifetime.[Footnote 29] EPA, however, 
chose not to calculate a reference dose for dioxins, as it generally 
does for noncancer health assessments of other substances. According 
to EPA, it did not do so because any reference dose that it would 
recommend for dioxins would likely be below (perhaps considerably 
below) the current background intake levels and body burdens of the 
U.S. population. EPA pointed out that reference doses are typically 
calculated to address the risks of incremental exposures over 
background exposure.[Footnote 30] In the case of dioxins, however, 
background exposure is a significant component of total exposure. 
Therefore, in EPA's opinion, a reference dose would be uninformative 
to risk managers for safety assessment. EPA also noted that, if it 
were to set a reference dose, its estimate likely would be more 
stringent than the tolerable intake levels for dioxins proposed by WHO 
because EPA's traditional approach for setting a reference dose gives 
more weight to scientific uncertainties than the approach WHO used in 
setting its tolerable intake level. 

EPA chose instead to use an alternative approach, the margin of 
exposure, to characterize noncancer risks. The margin of exposure is a 
ratio that shows how far the actual (or estimated) total human 
exposure to a particular substance is from levels at which adverse 
effects have been demonstrated to occur in human or animal studies. 
The margin of exposure is an alternative way of characterizing the 
likelihood that noncancer effects may be occurring in the human 
population at environmental exposure levels. A reference dose, on the 
other hand, estimates a level of exposure below which EPA considers it 
unlikely that any adverse effects will occur. EPA generally considers 
margins of exposure of 100 or more as adequate to rule out the 
likelihood of significant effects occurring in humans. However, for 
the most sensitive effects identified with dioxins (i.e., those that 
occurred at the lowest doses of exposure), the margins of exposure 
ranged from 15 to less than 1. 

Characterizing Cancer Risks Posed by TCDD, Other Individual Dioxins, 
and Mixtures of Dioxins: 

EPA and WHO both characterize TCDD as carcinogenic to humans. While 
EPA further characterizes other individual dioxins and mixtures of 
dioxins as "likely to be human carcinogens," WHO does not. 
Specifically, WHO states that the carcinogenicity of dioxins other 
than TCDD cannot be determined because of insufficient data. This 
difference of opinion largely reflects the specific objectives and 
scopes of EPA's and WHO's assessments. EPA's conclusion reflects a 
"weight of the evidence" judgment—that is, it is based on EPA's entire 
reassessment of dioxins (resting, in particular, on the conclusion 
that all dioxins share a similar mode of action and using evidence 
from both animal and human studies). In contrast, WHO's cancer 
monographs looked only at individual dioxins, focusing on whether they 
met specific criteria. Consequently, WHO's conclusions reflected a 
narrower data set and did not address the risks posed by mixtures of 
dioxins. However, because most human exposure is to mixtures rather 
than individual dioxins, and both EPA and WHO advocate using the same 
toxic equivalency factors for assessing the dioxins in such mixtures, 
any differences in the carcinogenicity classifications may have little 
practical impact. 

Quantifying Cancer Risks: 

Quantifying the lifetime cancer risk to the general population from 
exposure to dioxins was an important component of EPA's dioxin 
reassessment. EPA estimated that the upper bound on the general 
population's lifetime risk for all cancers from dioxins might be on 
the order of 1 in 1,000 or more (i.e., people might experience a 1 in 
1,000 increased chance of developing cancer over their lifetime 
because of exposure to dioxins). EPA's reassessment also states that 
the vast majority of the population is expected to have less risk per 
unit of exposure and some may have zero risk. WHO did not carry out 
such a quantitative assessment of the general population's cancer risk 
for two main reasons. First, calculations of population risk are 
beyond the scope of WHO's IARC cancer monographs, which evaluate 
whether and under what circumstances particular substances could pose 
a cancer risk to humans but generally do not provide quantitative risk 
estimates.[Footnote 31] Second, as noted previously, WHO's conclusion 
about a cancer threshold for dioxins led it to focus on noncancer 
effects when deriving tolerable intake levels for dioxins. However, 
WHO did explore the calculation, through modeling, of a cancer 
"benchmark dose," the dose or body burden estimated to result in a 1-
percent increase in cancer mortality. But WHO noted that its estimates 
for this benchmark dose ranged quite widely and strongly depended on 
the assumptions made during the modeling. 

Appendix II provides a more detailed comparison of the EPA and WHO 
conclusions regarding a number of major issues covered by the 
entities' dioxin risk assessments. 

EPA's Draft Dioxin Reassessment Report Generally Reflects the Views of 
Recent Peer Reviews: 

Two independent peer review panels, including an EPA Science Advisory 
Board[Footnote 32] panel, reviewed major sections of EPA's draft 
dioxin reassessment report in 2000. Both panels generally agreed with 
a number of key assumptions and approaches that EPA used to develop 
its updated health risk assessment of dioxins. Each of the peer review 
panels had a number of recommendations and suggestions for EPA to 
address or consider, most of which focused on the approaches and 
methodologies used to depict the health risks associated with dioxins. 
EPA made a number of revisions to its draft report in response to 
these recommendations and comments. The peer review panels disagreed 
with EPA on a few major points, and the Science Advisory Board panel 
emphasized the need for additional research to bridge gaps in data. 

Two Peer Review Panels Reviewed the Draft Dioxin Reassessment Report 
in 2000 and Concurred on Many Key Aspects: 

Both an independent expert peer review panel and one convened by EPA's 
Science Advisory Board reviewed the draft reassessment report on 
dioxins in 2000. These reviews resulted in part from the Board's 
review of an earlier version of EPA's draft reassessment report. In 
1995, a Board panel had reviewed the draft reassessment and requested 
that EPA make substantive revisions to the chapter on dose-response 
modeling[Footnote 33] and to the Integrated Summary. The Board had 
also requested that EPA develop a separate chapter on toxicity 
equivalence factors and submit the revised dose-response and new 
toxicity chapters to external peer review before the next Board review 
of these sections. In response, EPA revised the chapter on dose-
response modeling and had it peer reviewed in 1997. Similarly, EPA 
wrote a chapter on toxicity equivalence factors and had it peer 
reviewed as part of the July 2000 review. 

July 2000 External Peer Review Panel: 

In July 2000, EPA organized an independent peer review panel to review 
the revised Integrated Summary and the new chapter on toxicity 
equivalence factors. To obtain an objective critique, EPA had a 
contractor select 12 independent individuals with expertise in several 
technical fields, including risk characterization and communication; 
toxicology; epidemiology; sources of, and population exposure to, 
dioxins and related compounds; mechanisms and mode of action; and 
toxic equivalency. The panel addressed 20 questions about the 
reassessment report regarding exposure to and the health risks of 
dioxins. Table I of appendix III lists the questions the July 2000 
panel addressed in its review. 

The panel generally agreed with the approaches and methodologies EPA 
used in its reassessment, and noted, among other things, the following: 

* Body burden—the concentration of dioxins in the body—is an 
appropriate "dose metric" (measure) for comparing health risks across 
species. 

* The use of margin of exposure—a ratio that shows how far actual or 
estimated human exposure is from levels at which adverse effects have 
been demonstrated to occur in human or animal studies— is a more 
logical approach to characterizing noncancer risk of dioxins than 
comparing exposure to a reference dose. 

* The report's information on noncancer effects in animals and humans 
was adequately assembled, and the explanation of why dioxins' effects 
observed in animals are of concern to humans was also sufficient. 

* The history, rationale, and support for the toxicity equivalence 
approach, which is used to assess risks posed by dioxins and complex 
mixtures of dioxins on the basis of their toxicity relative to an 
equivalent dose of TCDD, were adequately presented. 

As discussed further below, the July 2000 panel also provided several 
recommendations and suggestions and identified the topics of greatest 
concern for finalizing the Integrated Summary. 

The Board Panel: 

Once the July 2000 panel published its recommendations and suggestions 
in August 2000, EPA addressed them and sent its revised draft to the 
Science Advisory Board's dioxin reassessment review subcommittee panel 
in September 2000. The panel comprised several professors and 
directors employed by medical institutions and representatives of 
industry-affiliated research organizations, consulting firms, and 
state health agencies. The Board panel met to review the revised 
sections of the draft reassessment report in November 2000. The Board 
agreed to answer 20 questions on the reassessment report regarding 
exposure to and the health risks of dioxins. Most of these questions 
were similar to those asked of the July 2000 panel. The Board panel 
completed its review and published a report in May 2001. Table 2 of 
appendix III lists the questions the Board panel addressed in its 
review. 

The Board panel, as the July 2000 panel before it, endorsed several 
key aspects of the reassessment, noting that, among other things, EPA 
had: 

* used appropriate dose metrics, such as body burden, to equate risks 
across species; 

* assembled and distilled a large and diverse body of literature on 
noncancer effects into a coherent document; 

* properly chosen the margin-of-exposure approach to characterize 
noncancer risks; 

* used toxicity equivalence factors to effectively address the joint 
effects of complex mixtures of dioxins on human health; and; 

* compiled an outstanding inventory of dioxin sources and effectively 
characterized the estimates of background exposure to dioxins using 
the available scientific data. 

The Board panel stated that, overall, EPA had prepared a thorough and 
objective summarization of the data and had addressed the key issues 
the Board had set forth in its 1995 review of the draft. The Board 
panel concluded that there was no need to submit further revisions of 
the reassessment report and that EPA should proceed to complete and 
release the document. However, as discussed in the following section, 
the Board panel provided several recommendations and suggestions for 
EPA to improve the draft document before its release. The Board panel 
also recognized the need for additional research to bridge gaps in 
data that limit EPA's ability to determine the magnitude of the health 
risks associated with dioxins. In essence, the Board panel viewed this 
reassessment as an interim assessment, recognizing that the data gaps 
are not likely to be addressed in the foreseeable future. 

EPA's Draft Reassessment Report Reflects Changes Made in Response to 
Recommendations and Suggestions of Peer Reviews: 

While the peer review panels generally agreed with the methodologies 
and approaches used by EPA, they made a number of recommendations and 
suggestions, and the Board asked specifically that the agency either 
address them before this reassessment is released in 2002 or in a 
future assessment of dioxins. The panels' recommendations generally 
reflected either a consensus of the panelists or the opinion of a 
majority. EPA generally addressed the panels' recommendations and 
suggestions by performing additional analyses, adding or revising 
text, identifying the recommendations or suggestions as related to 
EPA's long-term research goals, or indicating that the data currently 
available are not adequate to address the recommendation or 
suggestion. Additional changes are now being made as EPA prepares the 
draft for external interagency review. 

Four of the five recommendations by the July 2000 panel regarded 
improvements EPA could make to the section on health risks associated 
with dioxins. The July 2000 panel recommended that EPA: 

* explicitly explain the relationship between body burden and daily 
intake, serum levels, and tissue dose; 

* include a table in the final reassessment report summarizing the 
various noncancer effects observed in animals and humans at low-level 
exposures; 

* improve the methodologies used in determining the cancer risks of 
dioxins—such as requesting more detail on exactly how the cancer slope 
factor[Footnote 34] for estimating cancer risks of the general 
population was derived; and; 

* reexamine the basis for its estimate of the upper bound cancer risks 
to the general population. 

The fifth recommendation of the July 2000 panel involved the use of 
specific terminology in the exposure section. In addition, this panel 
had several suggestions regarding the health risks associated with 
dioxins, including that EPA: 

* provide more detail in the Integrated Summary on the implications of 
using the margin-of-exposure approach rather than comparing exposure 
with reference doses; 

* more clearly describe the significance of the upper bound cancer 
risks to the public; and; 

* add discussion of the uncertainties associated with using various 
dose metrics specifically for evaluating childhood risks. 

Ten of the 13 recommendations made by the Board panel also focused on 
the need to improve the section on health risks associated with 
dioxin. These recommendations included that EPA: 

* calculate a reference dose to evaluate risk in addition to using the 
margin-of-exposure approach to provide information on the minimum dose 
that humans can receive without suffering harm, 

* improve its margin-of-exposure approach by more clearly explaining 
its choice to use dose levels associated with a 1-percent increase in 
a particular effect and also by calculating a dose level associated 
with the 10-percent increase more commonly used in chemical risk 
assessments, and; 

* provide better justification for using a specific dose metric and 
identify the important data gaps that could affect the results of 
those choices. 

Three of 13 recommendations asked that EPA improve the section on 
exposure to dioxins by evaluating the sources that contribute most to 
dioxins in the food chain, discussing all "special population" 
exposure in more detail, and extending breast-feeding exposure 
scenarios beyond 1 year. 

EPA made many additions and changes to the draft reassessment in 
response to the peer review reports by both panels. For example, in 
response to recommendations from both panels, EPA revised and added 
text in several places to better explain the variety of dose metrics 
available and why body burden is the best choice for assessing 
dioxins, while acknowledging that EPA will need to address data gaps 
on body burden in the future as further research is completed. Tables 
1 and 2 in appendix IV highlight the actions EPA took to address both 
panels' recommendations, suggestions, and concerns. 

EPA and Peer Reviewers Do Not Agree on a Few Scientific Issues, and 
Uncertainties Remain Because Data Are Lacking: 

Overall, the peer review panels agreed with EPA's approach to the 
reassessment, and EPA generally addressed the recommendations, 
suggestions, and concerns of the peer review panels. In a few cases, 
EPA disagreed with the panels' recommendations or suggestions. In 
these cases, the agency explained its position in the text and, in the 
case of the July 2000 panel, addressed it in a separate written 
document. For example, although the Board panel had recommended that 
EPA calculate a reference dose and add it to the text, EPA chose to 
continue to use only the margin-of-exposure approach and not calculate 
a reference dose. EPA stated in the revised draft report that a 
calculated reference dose would be lower than most people's daily 
exposure and added a more detailed explanation of why it chose to use 
the margin-of-exposure approach. 

In addition to disagreeing with EPA on a few key scientific issues, 
the peer review panels could not agree among themselves in some cases 
on EPA's findings. In such cases, the panels refrained from making 
recommendations or suggestions to the agency. For example, members of 
both peer review panels did not reach consensus on the strength of 
evidence used by EPA to support the classification of TCDD as a human 
carcinogen and other dioxin compounds as likely human carcinogens. 

EPA officials believe that the weight of scientific evidence on human 
and animal exposure supports classifying TCDD as a known human 
carcinogen, a view also held by WHO and the U.S. Department of Health 
and Human Services. 

Although neither panel specifically recommended that EPA change its 
classification of TCDD as a human carcinogen to a lesser category, 
such as a likely human carcinogen, for various reasons most of the 
peer reviewers did not endorse EPA's classification. For example, 
while the July 2000 panel agreed that TCDD is clearly a potent 
carcinogen in many species of animals, most of the panel thought that 
human epidemiology studies were too limited, and the results not 
consistent enough, to serve as a basis for showing increased cancer 
mortality. As a result, the majority felt that the characterization of 
TCDD as a known human carcinogen was not justified. Similarly, the 
Board panel also noted limitations in the scientific data, questioning 
the epidemiological data that indicated dioxins are carcinogens in 
humans, as well as the data that supported similar modes of action 
occurring in both animals and humans. Almost one-half of the Board did 
not support classification of TCDD as a known human carcinogen for 
various reasons. Those who did support the classification believed 
that the results from studies of TCDD-exposed workers were persuasive 
and that the variety of studies from researchers in different 
countries provided limited but convincing evidence of TCDD's 
carcinogenicity in humans. 

Observations: 

A decade in the making, EPA's draft reassessment report on dioxins was 
both improved and limited by the passage of time, particularly in 
estimating the daily dietary intake of dioxins by the typical American 
adult. That is, EPA was able to include new food studies in the 
reassessment as they became available. At the same time, however, 
these and earlier studies that EPA relied on became less current with 
the passage of time. Overall, while EPA's draft reassessment report 
has advanced the state of knowledge on dietary exposure to dioxins in 
the United States, the extent to which the estimate accurately 
reflects current average daily exposure is not known. EPA acknowledges 
the need for additional research on dietary intake, identifying a 
number of data limitations associated with the estimates it developed 
in its October 2001 draft report. Future efforts could eliminate most 
of the food data limitations of the reassessment. Such efforts could 
include periodic, comprehensive food surveys that analyze samples of 
the most commonly eaten food products in each type of food studied, 
with samples collected within the same time frames and analyses 
performed using standardized methodologies. Further, when they become 
available, the results of the ongoing EPA/USDA follow-up study on 
dioxin levels in beef, pork, and poultry should provide quantitative 
information on the changes, if any, in dioxin levels in these foods 
from the mid-1990's to the present. 

Agency Comments and Our Response: 

We provided EPA with a draft of this report for its review and comment 
and the draft segment comparing EPA's and WHO's assessments of dioxins 
to WHO. In commenting on the draft report, EPA's assistant
administrator, Office of Research and Development, said that the 
report was well researched and written and provided a balanced 
treatment of the information. However, EPA believed that additional 
information on some of the data limitations discussed in the section 
on EPA's estimates of the dietary intake of dioxins would better 
enable readers to evaluate the impact of the data limitations. Where 
appropriate, we revised the report to reflect the views EPA presented 
in its comments. For example, we added information concerning the 
strength of the food concentration data used in estimating national 
mean levels of exposure to dioxins, the sampling of animal fat rather 
than meat and poultry products sold in grocery stores, and the 
likelihood that current dioxin levels in food have significantly 
declined since the mid-1990s. EPA's comments and our evaluation of 
them are provided in appendix V. 

In commenting on the draft segment comparing EPA's and WHO's analyses, 
a senior advisor of health and environment, the Department of 
Protection of the Human Environment, World Health Organization, said 
the report was well written and accurate. 

Scope and Methodology: 

To describe the types and extent of data EPA used to reassess human 
dietary exposure to dioxins in the United States, we reviewed the 
relevant portions of the October 2001 draft reassessment, the 1994 and 
2000 drafts that were peer reviewed, and the initial 1985 health risk 
assessment. We also reviewed EPA documents and journal articles on the 
agency's national sampling of beef, pork, and poultry samples, and 
information about the other samples used for milk, eggs, fish, dairy 
products, and vegetable fats. We discussed the samples and methodology 
issues about them with EPA officials and contractor staff. We did not 
validate or verify EPA's estimates of dietary exposure to dioxins. 

To compare EPA's objectives, processes, analytical methods, and 
conclusions with those of WHO, we analyzed EPA's October 2001 draft 
reassessment report and various WHO publications on its objectives, 
analyses, and conclusions. We discussed the similarities and 
differences with EPA and WHO officials. 

To determine the extent to which EPA's draft dioxin reassessment 
reflects the views of two independent peer review panels, we analyzed 
the recommendations, suggestions, and concerns in the reports by the 
EPA Science Advisory Board's dioxin reassessment review subcommittee 
panel—on reviews performed in 1994 and 2000—and a report from another 
independent peer review panel on its July 2000 review. Recommendations 
of the Board panel were noted in bold print in the executive summary, 
and we considered other statements to be "suggestions" when they were 
the consensus opinion of the panelists or the opinion of a majority or 
of some of the panelists. We considered the July 2000 panel's 
statements to be "recommendations," "suggestions," or "concerns," when 
those particular words were used in the executive summary and where 
the statements reflected either a consensus or the opinion of a 
majority or of some of the panelists. We also reviewed EPA 
documentation to determine the changes EPA has made to its draft 
reassessment as a result of being peer reviewed, including comparing 
the agency's previous drafts of the reassessment with each other and 
reviewing the written responses to the July 2000 panel's 
recommendations and suggestions. We also met with EPA officials to 
identify the agency's responses to the panels' recommendations, 
suggestions, and concerns, including discussing those with which it 
disagreed. 

We conducted our work from July 2001 through March 2002 in accordance 
with generally accepted government auditing standards. 

We will send copies of this report to the administrator, EPA, and make 
copies available to others who request them. This report will also be 
available on GAO's Web site [hyperlink, http://www.gao.gov]. 

If you or your staff have questions about this report, please call me 
on (202) 512-3841. Key contributors to this report are listed in 
appendix VI. 

Signed by: 

David G. Wood: 
Director, Natural Resources and Environment: 

[End of section] 

Appendix I: Major Milestones in the EPA and WHO Dioxin Risk Assessment 
Efforts: 

1977: 
WHO publishes initial cancer monograph that includes evaluation of 
some dioxins. 

Late 1970's-1984: 
EPA performs initial risk assessments of the dioxin TCDD. 

1985: 
EPA releases first comprehensive health assessment document on dioxins. 

1985-1987: 
EPA reviews and adopts proposal to use interim toxic equivalency 
factor (TEF) procedures for estimating risks associated with exposures 
to mixtures of dioxins. 

1987: 
WHO updates previously released monographs on carcinogenicity of some 
dioxins. 

1988: 
EPA completes external review draft on estimating cancer risks posed 
by dioxins. Science Advisory Board completes review of external review 
draft. 

1990: 
Experts at meeting in Bilthoven, Netherlands, establish a tolerable 
daily intake for TCDD (WHO effort). 

1991: 
EPA begins current dioxin reassessment. 

1991-1993: 
EPA holds public meetings and workshops. 
* 1991-92 - EPA holds public meetings. 
* 1992 - EPA convenes two peer review workshops. 
* 1993 - EPA holds a third peer review workshop. 

1994: 
EPA provides opportunities for public comment on draft report on human 
health risks of dioxins (150-day comment period and 11 public 
meetings). EPA submits draft report for Science Advisory Board review. 

1995: 
Science Advisory Board completes review of draft report, approving 
most chapters but recommending revisions to some parts (EPA effort). 

1997: 
Dose-response chapter undergoes peer review (EPA effort). 
WHO publishes new monographs, based on reassessments, on the evidence 
for carcinogencity of TCDD and several other dioxins. Experts at 
meeting in Stockholm, Sweden, derive consensus TEFs for dioxins for 
human, fish, and wildlife risk assessments. 

1998: 
WHO publishes the consensus TEFs from the Stockholm meeting. Experts 
meeting in Geneva, Switzerland, reevaluate the risks to human health 
from dioxins and revise the tolerable daily intake for dioxins. 

2000: 
Science Advisory Board and an independent panel of peer reviewers review
major segments of EPA’s revised draft report (EPA effort). 

2001: 
EPA completes final internal review draft report, which incorporates 
revisions in response to Science Advisory Board and peer review panel 
recommendations and comments. 
Experts at meeting in Rome, Italy, evaluate risks associated with 
dioxins in foods and establish a provisional tolerable monthly intake 
for dioxins (WHO effort). 

2002: 
Dissemination of final dioxin reassessment report for review by other 
federal agencies is pending. Publication of final dioxin reassessment
report is pending (EPA effort). 

[End of section] 

Appendix II: Comparison of the Major Conclusions from EPA's and WHO's 
Dioxin Risk Assessments: 

Effects associated with exposure to dioxins: 

EPA conclusions: 
Exposure to dioxins can produce a wide variety of effects in animals 
(including cancer and noncancer health effects) and might produce many 
of the same effects in humans. 
EPA characterizes dioxin and related compounds as carcinogenic and 
developmental, reproductive, immunological, and endocrinological 
hazards and makes the following specific points.[A] 
* Exposure to TCDD leads to an increased risk of generalized cancers 
at multiple organ sites, including lung cancer. 
* Long-term noncancer consequences of exposure to TCDD in adults 
include chloracne, elevated gamma glutamyl transferase levels, and 
altered testosterone levels.' Among the possible noncancer 
consequences of exposure to TCDD or other dioxin and dioxin-like 
compounds are dermatological conditions such as chloracne; liver 
diseases; and kidney, nervous system, and lung disorders. 
* Although available data suggest an association between TCDD exposure 
and other adverse outcomes, further study is required of circulatory 
and heart disease, diabetes and glucose metabolism, reproductive and 
developmental outcomes, and immunologic disorders. 

WHO conclusions: 
Exposure to dioxins may be linked to a variety of adverse effects. 

* Short-term human exposure to high levels of dioxins may result in 
skin lesions (such as chloracne) and altered liver function.
* Long-term exposure is linked to impairment of the immune system, the 
developing nervous system, the endocrine system, and reproductive 
functions.
* Chronic animal exposure to dioxins has resulted in several types of 
cancer. Human data from occupational or accidental exposure has 
produced evidence of increased risks for all cancers combined, along 
with less strong evidence of increased risks for cancers of particular 
sites. 

Mode of action through which exposure to dioxins can lead to adverse 
effects: 

EPA conclusions: 
Dioxins are structurally related and elicit their effects through a 
common mode of action—binding of dioxins to a cellular protein called 
the aryl hydrocarbon receptor. Binding to the aryl hydrocarbon 
receptor appears to be necessary for all well-studied effects of 
dioxins but is not sufficient, in and of itself, to elicit these 
responses. 

TCDD and related compounds have a common mode of action in animals and 
humans. Therefore, there is no reason to expect, in general, that 
humans would not be similarly affected as animals at some dose. 

WHO conclusions: 
A broad variety of data has shown the importance of the aryl 
hydrocarbon receptor in mediating the biological effects of dioxins. 
The precise chain of molecular events by which the receptor elicits 
these effects is not yet fully understood. However, alterations in key 
biochemical and cellular functions are expected to form the basis for 
dioxin toxicity. 

Experimental data indicate that TCDD and probably other 
polychlorinated dibenzo-p-dioxins (CDD) and polychlorinated 
dibenzofurans (CDF) are not direct-acting genotoxic agents (i.e., do 
not directly affect genetic material).
Dioxins act through the same mode of action in animals and humans. 

Use of the toxicity equivalency (TEQ) concept: 

EPA conclusions: 
EPA and the international scientific community have adopted TEQ of 
dioxins as prudent science policy. 

(EPA recommended that the TEFs derived by WHO in 1997—published in 
1998—be used to assign TEQ to complex environmental mixtures for 
assessment and regulatory purposes.) 

WHO conclusions: 
The complex nature of CDD, CDF, and polychlorinated biphenyls (PCB) 
mixtures complicates the risk evaluation for humans. The concept of 
TEFs has been developed to facilitate risk assessment and regulatory 
control of exposure to these mixtures. 

(WHO derived updated consensus TEFs for 29 dioxins in 1997, with the 
results of the meeting published in 1998. Subsequent WHO assessments 
of dioxins used this updated set of TEFs for their calculations.) 

Whether dioxins are human carcinogens: 

EPA conclusions: 
Complex mixtures of dioxins are highly potent, "likely" human 
carcinogens. 
* A weight-of-the-evidence evaluation suggests that mixtures of 
dioxins are strong cancer promoters and weak direct or indirect 
initiators and are likely to present a cancer hazard to humans.[C] 
* Because dioxins and related compounds always occur in the 
environment and in humans as complex mixtures of individual congeners, 
it is appropriate that the characterization apply to the mixture. 

Individual congeners can also be characterized as to their 
carcinogenic hazards. 
* TCDD is best characterized as "carcinogenic to humans." Based on the 
weight of all evidence (human, animal, and mode of action), TCDD meets 
the criteria that allow EPA and the scientific community to accept a 
causal relationship between TCDD exposure and cancer hazard. 
* Other individual dioxin-like compounds are characterized as "likely 
to be human carcinogens" primarily because of the lack of 
epidemiological evidence associated with their carcinogenicity, 
although the inference based on TEQ is strong that they would behave 
in humans as TCDD does. Other factors, such as the lack of compound-
specific chronic animal studies, also support this characterization. 

WHO conclusions: 
TCDD is a human carcinogen (group 1), considering limited evidence in 
humans, sufficient evidence in experimental animals, and evidence of a 
mode of action that functions the same way in humans as in 
experimental animals.[D] 

Other dioxins are not classifiable as to their carcinogenicity to 
humans (group 3). Depending on the specific compound evaluated, the 
International Agency for Research on Cancer (IARC) noted that the 
available data provided inadequate evidence for carcinogenicity in 
humans or limited evidence, inadequate evidence, or evidence 
suggesting lack of carcinogenicity in experimental animals. 

Whether there appears to be a "threshold" or safe dose of dioxins that 
would not cause adverse effects: 

EPA conclusions: 
The supposition of a response threshold for receptor-mediated effects 
(such as those associated with dioxins' binding to the aryl 
hydrocarbon receptor ) is a subject for scientific debate. The same 
receptor occupancy assumption of the classic receptor theory is 
interpreted by different parties as support for and against the 
existence of a threshold. 

Empirical dose-response data from cancer studies do not provide 
consistent or compelling support for threshold models and are 
insufficient to move from EPA's default policy of linear extrapolation 
(an approach that assumes there is no threshold of exposure without 
risk). 

Threshold levels of lifetime exposure to dioxins that would cause 
toxic noncancer effects may be below the current level of background 
exposure and body burdens, and, therefore, the potential exists for 
noncancer risk at background exposure. 

WHO conclusions: 
TCDD does not affect genetic material, and there is a level of 
exposure below which cancer risk would be negligible. 

Although TCDD is classified by IARC as a human carcinogen, it is not 
considered to be a direct acting carcinogen. Therefore, a threshold 
approach could be used in the hazard assessment approach. 

A tolerable intake can be established for TCDD on the basis of the 
assumption that there is a threshold for all effects, including 
cancer. Because cancer occurred in animals at higher body burdens than 
other toxic effects, establishing a tolerable intake on the basis of 
noncancer effects would also address any carcinogenic risk. 

Whether it is useful to set a dose or exposure level that the public 
could experience for a lifetime without expectation of harm: 

EPA conclusions: 
EPA did not calculate reference dose or reference concentration values 
in this reassessment as it generally does for noncancer effects in 
other assessments. Instead, EPA chose to characterize the margins of 
exposure between estimated actual human exposure and the exposure 
levels at which studies indicated various adverse noncancer effects 
could occur. 

WHO conclusions: 
The WHO 1998 consultation set daily limits on exposure levels of 
dioxins for non-cancer effects, a tolerable daily intake. 

The Joint Expert Committee on Food Additives of the United Nation's 
Food and Agriculture Organization and WHO set a provisional tolerable 
monthly intake limit on exposure levels to dioxins, again focusing on 
noncancer effects. The Committee participants felt that it was more 
appropriate to express the tolerable intake on a monthly rather than a 
daily basis because of the long half-life of dioxins (i.e., the body's 
stored dioxins decline slowly, with only half of the accumulated 
dioxins disappearing over about 7 years). 

Human exposure to dioxins: 

EPA conclusions: 
Human exposure to dioxins has occurred through background exposure, 
contamination of foods, occupational exposure, and exposure associated 
with industrial accidents. An increased background exposure can result 
from either a diet that favors consumption of foods high in dioxin 
content or a diet that is disproportionately high overall in animal 
fats.	 

Most (more than 95 percent) background exposure results from the 
presence of minute amounts of dioxins in dietary fat, primarily from 
the commercial food supply. 

The average dioxin tissue level for the general U.S. adult population 
appears to be declining. 

Five compounds account for most (about 80 percent) of the toxicity in 
human tissue concentrations. 

WHO conclusions: 
Human exposure to dioxins may occur through background (environmental) 
exposure and accidental and occupational contamination. 

Over 90 percent of human background exposure is estimated to occur 
through the diet, with food from animal origin being the predominant 
source. 

Recent studies show decreasing levels of dioxins in food and 
consequently a significantly lower dietary intake of these compounds. 

Risks of adverse health effects at the general public's current levels 
of exposure to dioxins: 

EPA conclusions: 
In general, EPA's assessments indicated that dioxins pose risks at 
lower levels of exposure than previously estimated and that the 
general public's current levels of exposure are at or near those that 
have been observed to cause harm. 

EPA estimates that the upper bound cancer risk at average current 
background body burdens exceeds 10-3 (i.e., the upper bound on general 
population lifetime risk for all cancers might be on the order of 1 in 
1,000 or more). However, this is an upper bound estimate, so the true 
risks are likely less than that and may be zero for most people. 
* In 1985, EPA's estimate of the cancer slope factor based on exposure 
to TCDD was 1.6 x 10-4 per picogram of TCDD per kilogram of body 
weight per day (pgTCDD/kgBW/day).[E] 
* EPA's current upper bound slope factor for estimating human cancer 
risk on the basis of human data is 1 x 10-3 per pgTCDD/kgBW/day. 
* EPA's current upper bound slope factor for estimating human cancer 
risk on the basis of animal data is 1.4 x 10-3 per pgTCDD/kgBW/day. 

EPA estimated that U.S. residents are exposed daily to about 1 
picogram of dioxins per kilogram of body weight, which is close to the 
level that caused biological changes in animals. EPA noted that the 
margins of exposure between estimated actual human exposure and the 
exposure levels at which studies indicated adverse noncancer health 
effects could occur were "considerably less than typically seen for 
environmental contaminants of toxicologic concern." 

WHO conclusions: 
In general, WHO's assessments also indicated that dioxins pose risks 
at lower levels of exposure than previously estimated and that the 
general public's current levels of exposure are at or near those that 
have been observed to cause harm. 

In 1990, WHO experts had established a tolerable daily intake for TCDD 
of 10 picograms per kilogram of body weight. In 1998, the WHO 
consultation established a tolerable daily intake for dioxins at a 
range of 1-4 TEQ picograms per kilogram of body weight and noted that 
subtle effects may already occur in the general population at current 
background levels of 2 to 6 picograms per kilogram of body weight. The 
consultation stressed that the ultimate goal is to reduce human intake 
levels below 1 picogram TEQ per kilogram of body weight per day. 

In 2001, Joint Expert Committee on Food Additives of the United 
Nation's Food and Agriculture Organization of the United Nations and 
WHO determined that a monthly tolerable intake level made more sense 
than a daily level and established a provisional tolerable monthly 
intake of 70 picograms per kilogram of body weight per month 
(equivalent to 2.33 picograms per day) for dioxins. 

The various WHO entities did not calculate quantitative cancer risk 
estimates for the additional cancer risk that dioxins might pose to 
the general population. However, WHO did explore the calculation of a 
cancer "benchmark dose" (the dose or body burden estimated to result 
in a 1-percent increase in cancer mortality) through various models. 
On the basis of data from three industrial exposure studies, WHO 
estimated that the body burden of dioxins associated with a 1-percent 
excess cancer risk over a lifetime was 3 to 13 nanograms per kilogram 
of body weight, which is associated with a daily dose of dioxins in 
the range of 2 to 7 picograms per kilogram of body weight per day. 

Risks to population subgroups: 

EPA conclusions: 
Children's risks from dioxins and related compounds may be greater 
than that of adults, but more data are needed to fully address the 
issue. 

There may be individuals in the population who might experience a 
higher cancer risk on the basis of genetic factors or other 
determinants of cancer risk not accounted for in epidemiologic data or 
animal studies. In particular, a very small percentage of the 
population (less than 1 percent) may experience risks that are 2 to 3 
times higher than the general population estimate if their individual 
response is at the upper bound and they are among the most highly 
exposed based on dietary intake of dioxins. 

WHO conclusions: 
Certain population subgroups are at greater risk from dioxins. Fetuses 
are most sensitive to dioxin exposure, and newborns may also be more 
vulnerable to certain effects. Some individuals or groups of 
individuals may be exposed to higher levels of dioxins because of 
their diets or occupations. 

[A] Endocrinological hazards are those related to the system of 
ductless glands that secrete hormones directly into the blood stream 
for distribution throughout the body, such as the pituitary, thyroid, 
and adrenal glands. 

[B] Elevated gamma glutamyl transferase levels are among the changes 
in liver function and structure that have been observed using human 
data. 

[C] According to EPA's revised proposed guidelines for carcinogen risk 
assessment, the descriptor "likely to be a human carcinogen" is 
appropriate when the available tumor effects and other key data are 
adequate to demonstrate carcinogenic potential to humans, yet not 
sufficient to infer a cause and effect relationship. 

[D] For additional information on WHO-International Agency for 
Research on Cancer's (IARC) evaluation categories and the definitions 
of degrees of evidence, see the Preamble to the IARC Monographs 
available on the IARC Internet site [hyperlink, http://www.iarc.fr/]. 

[E] The cancer slope factor is an upper bound of the probability of 
cancer risk in the population. According to EPA, the slope factor 
generally approximates or exceeds a 95-percent confidence limit, 
meaning that there is a greater than 95-percent chance that cancer 
risks will be less than the upper bound. 

Source: GAO review of EPA and WHO documents on dioxin reassessment 
efforts. 

[End of table] 

[End of section] 

Appendix III: Questions EPA Asked Peer Review Panels to Address: 

EPA sought expert opinions from both a July 2000 panel of independent 
peer reviewers and a November 2000 Science Advisory Board expert panel 
on several key questions that pertain to the content of the documents 
under review. The questions are classified into 11 general topics. 
Most of the questions are the same for both panels. However, according 
to usual Science Advisory Board practice, EPA staff, Board staff, and 
the chair of the Board's dioxin reassessment review subcommittee 
jointly developed additional questions for the Board's review. Table 6 
and table 7 show the topics and questions addressed by the July 2000 
panel, and Board panel, respectively. 

Table 6: Questions for the July 2000 Panel Review of EPA's Draft 
Dioxin Reassessment: 

Topic: Body burden; 
Question: 1. Did EPA adequately justify its use of body burden as a 
dose metric for inter-species scaling? Should the document present 
conclusions based on daily dose? 

Topic: Use of margin-of-exposure approach; 
Question: 2. How might the rationale be improved for EPA's decision 
not to calculate a reference dose/reference concentration, and for the 
recommended margin-of-exposure approach for conveying risk 
information? Is a margin-of-exposure approach appropriate, as compared 
to the traditional reference dose/reference concentration? Should the 
document present a reference dose/reference concentration? 
Question: 3. Are the calculations of a range of effective dose (ED)01 
body burden for noncancer effects in rodents responsive and clearly 
presented? Please comment on the weight of evidence interpretation of 
the body burden data associated with a 1 percent response rate for 
noncancer effects that is presented in Chapter 8, appendix I and 
figure 8-1 (where EPA considers that the data best support a range 
estimate for ED01 body burdens from lOnh/kg to 50 ng/kg). 

Topic: Mechanisms and mode of action; 
Question: 4. How might the discussion of mode of action of dioxin and 
related compounds be improved? 
Question: 5. Despite the lack of congener-specific data, does the 
discussion in the Integrated Summary and Risk Characterization support 
EPA's inference that these effects may occur for all dioxin-like 
compounds, based on the concept of toxicity equivalence? 

Topic: TEFs; 
Question: 6. Is the history, rationale, and support for the TEQ 
concept, including its limitations and caveats, laid out by EPA in a 
clear and balanced way in Chapter 9? Did EPA clearly describe its 
rationale for recommending adoption of the 1998 WHO TEFs? 
Question: 7. Does EPA establish clear procedures for using, 
calculating, and interpreting toxicity equivalence factors? 

Topic: Noncancer effects: 
Question: 8. Have the available human data been adequately integrated 
with animal information in evaluating likely effect levels for the 
noncancer endpoints discussed in the reassessment? 
Question: 9. Do reviewers agree with the characterization of human 
developmental, reproductive, immunological, and endocrinological 
hazard? What, if any, additional assumptions and uncertainties should 
EPA embody in these characterizations to make them more explicit? 

Topic: Cancer effects; 
Question: 10. Do you agree with the characterization in this document 
that dioxin and related compounds are carcinogenic hazards for humans? 
Question: 11. Does the document clearly present the evolving 
approaches to estimating cancer risk (e.g. margin of exposure and the 
lower limit on ED01 as a point of departure) as described in EPA's 
April 1996 "Proposed Guidelines for Carcinogenic Risk Assessment"? Is 
this approach equally as valid for dioxin-like compounds? 
Question: 12. Please comment on the presentation of the range of upper 
bound risks for the general population based on this reassessment. 
What alternative approaches should be explored to better characterize 
quantitative aspects of potential cancer risk? Is the range that is 
given sufficient, or should more weight be given to specific data 
sources? 

Topic: Background and population exposures; 
Question: 13. Have the estimates of background exposures been clearly 
and reasonably characterized? 
Question: 14. Has the relationship between estimating exposure from 
dietary intake and estimating exposure from body burden been clearly 
explained and adequately supported? 
Question: 15. Have important "special populations" and age-specific 
exposures been identified and appropriately characterized? 

Topic: Children's risk; 
Question: 16. Is the characterization of increased or decreased 
childhood sensitivity to possible cancer and noncancer outcomes 
scientifically supported and reasonable? Is the weight-of-evidence 
approach appropriate? 

Topic: Relative risks of breast feeding; 
Question: 17. Has EPA adequately characterized how nursing affects 
short-term and long-term body burdens of dioxins and related compounds? 

Topic: Risk characterization summary statement; 
Question: 18. Does the summary and analysis support the conclusion 
that enzyme induction, changes in hormone levels, and indicators of 
altered cellular function seen in humans and laboratory animals 
represent effects of unknown clinical significance, but they may be 
early indicators of toxic response? 
Question: 19. Has the short summary statement in the risk and hazard 
characterization on page 107 adequately captured the important 
conclusions and the areas where further evaluation is needed? What 
additional points should be made in this short statement? 

Topic: Sources; 
Question: 20. Are these sources adequately described and are the 
relationships to exposure adequately explained? 

Source: EPA. 

[End of table] 

Table 7: Questions for the November 2000 Science Advisory Board Panel: 

Topic: Body burden; 
Question: 1. Did EPA adequately justify its use of body burden as a 
dose metric for inter-species scaling? Should the document present 
conclusions based on daily dose? 

Topic: Use of margin-of-exposure approach. 
Question: 2. Has EPA's choice of the margin-of-exposure approach to 
risk assessment adequately considered that background levels of 
dioxins have dropped dramatically over the past decade and are 
continuing to decline? How might the rationale be improved for EPA's 
decision not to calculate a reference dose/reference concentration, 
and for the recommended margin-of-exposure approach for conveying risk 
information? Is a margin-of-exposure approach appropriate, as compared 
to the traditional reference dose/reference concentration? Should the 
document present a reference dose/reference concentration? 
Question: 3. Are the calculations of a range of ED01 body burden for 
noncancer effects in rodents responsive and clearly presented? Please 
comment on the weight-of-evidence interpretation of the body burden 
data associated with a 1-percent response rate for noncancer effects 
that is presented in chapter 8, appendix I and Figure 8-1 (where EPA 
considers that the data best support a range estimate for ED01 body 
burdens from lOnh/kg to 50 ng/kg). 

Topic: Mechanisms and mode of action; 
Question: 4. How might the discussion of mode of action of dioxin and 
related compounds be improved? 
Question: 5. Despite the lack of congener-specific data, does the 
discussion in the Integrated Summary and Risk Characterization support 
EPA's inference that these effects may occur for all dioxin-like 
compounds, based on the concept of toxicity equivalence? 

Topic: TEFs: 
Question: 6. Is the history, rationale, and support for the TEQ 
concept, including its limitations and caveats, laid out by EPA in a 
clear and balanced way in Chapter 9? Did EPA clearly describe its 
rationale for recommending adoption of the 1998 WHO TEFs? 
Question: 7. Does EPA establish clear procedures for using, 
calculating, and interpreting toxicity equivalence factors? 

Topic: Noncancer effects; 
Question: 8. Have the available human data been adequately integrated 
with animal information in evaluating likely effect levels for the 
noncancer endpoints discussed in the reassessment? Has EPA 
appropriately defined noncancer adverse effects and the body burdens 
associated with them? Has EPA appropriately reviewed, characterized, 
and incorporated the recent epidemiological evidence for noncancer 
risk assessment for human population? 
Question: 9. Do reviewers agree with the characterization of human 
developmental, reproductive, immunological, and endocrinological 
hazard? What, if any, additional assumptions and uncertainties should 
EPA embody in these characterizations to make them more explicit? 
	
Topic: Cancer effects; 
Question: 10. Do you agree with the characterization in this document 
that dioxins and related compounds are carcinogenic hazards for 
humans? Does the weight of the evidence support EPA's judgment 
concerning the listing of environmental dioxins as a likely human 
carcinogen? 
Question: 11. Does the document clearly present the evolving 
approaches to estimating cancer risk (e.g., margin of exposure and the 
lower limit on ED01 as a point of departure) as described in EPA's 
1996 "Proposed Guidelines for Carcinogenic Risk Assessment"? Is this 
approach equally as valid for dioxin-like compounds? Has EPA 
appropriately reviewed, characterized, and incorporated the recent 
epidemiological evidence for cancer risk assessment for human 
populations? 
Question: 12. Please comment on the presentation of the range of upper 
bound risks for the general population based on this reassessment. 
What alternative approaches should be explored to better characterize 
quantitative aspects of potential cancer risk? Is the range that is 
given sufficient or should more weight be given to specific data 
sources? 

Topic: Background and population exposures; 
Question: 13. Have the estimates of background exposures been clearly 
and reasonably characterized? 
Question: 14. Has the relationship between estimating exposure from 
dietary intake and estimating exposure from body burden been clearly 
explained and adequately supported? Has EPA adequately considered 
available models for the low-dose exposure-response relationships 
(liner, threshold, "J" shaped)? 
Question: 15. Have important "special populations" and age-specific 
exposures been identified and appropriately characterized? 

Topic: Children's risk; 
Question: 16. Is the characterization of increased or decreased 
childhood sensitivity to possible cancer and noncancer outcomes 
scientifically supported and reasonable? Is the weight-of-evidence 
approach appropriate? 

Topic: Relative risks of breast feeding; 
Question: 17. Has EPA adequately characterized how nursing affects 
short-term and long-term body burdens of dioxins and related compounds? 

Topic: Risk characterization summary statement; 
Question: 18. Does the summary and analysis support the conclusion 
that enzyme induction, changes in hormone levels, and indicators of 
altered cellular function seen in humans and laboratory animals 
represent effects of unknown clinical significance, but they may be 
early indicators of toxic response? 
Question: 19. Has the short summary statement in the risk and hazard 
characterization on page 107 adequately captured the important 
conclusions and the areas where further evaluation is needed? What 
additional points should be made in this short statement? 

Topic: Sources;	
Question: 20. Are these sources adequately described and are the 
relationships to exposure adequately explained? 

Source: EPA. 

[End of table] 

[End of section] 

Appendix IV: EPA's Responses to Peer Review Panels: 

EPA generally addressed the peer review panels' comments by performing 
additional analyses, adding or revising text, or identifying comments 
as related to EPA's long-term research goals. In some instances, EPA 
thought that the reassessment already addressed the panel's comment. 
The panels classified their recommendations, suggestions, and 
concerns, and EPA responded to each. Tables 8 and 9 show the comments 
made by the panels and EPA's response or action taken. 

Table 8: EPA's Responses to July 2000 Panel's Report: 

Recommendation: 
1. Use terminology such as "ambient exposures" or "general population 
exposures," rather than the term "background exposure," which implies 
normal and acceptable. 
EPA response or action: 
EPA prefers to use "background exposure" as it appropriately 
recognizes the ubiquitous nature of trace amounts of dioxins in the 
environment and food supply even when no sources are identified 
nearby. EPA added a definition to its glossary. 

Recommendation: 
2. Present more detail (e.g., sample calculations) in the Integrated 
Summary on exactly how the cancer slope factor was derived. 
EPA response or action: 
Additional information has been added to Section 5 of the Integrated 
Summary to clearly illustrate how the cancer slope factors were 
derived. 

Recommendation: 
3. The panel thought that the upper bound cancer risk of 10-3 to 10-2 
in the general population, implying an additional 3,000 to 30,000 
deaths per year, was alarmist, not warranted and not realistic. 
EPA response or action: 
Recommended that EPA should present "reality check" on the risk 
estimates relative to highly exposed past cohorts. 
EPA states its estimates were derived from the best data sets 
available. 

Recommendation: 
4. Include a table to summarize the various noncancer effects observed 
in animals and humans at low-level exposures. 
EPA response or action: 
EPA has added a table (table 2-2) to the Integrated Summary of the 
September 2000 draft. While not extensive, it illustrates the low 
range of margins of exposure that is calculated for a variety of 
effects in several species, including humans. 

Recommendation: 
5.The panel thought body burden was an appropriate dose metric. 
However, the panel recommended that EPA explicitly explain the 
relationship among daily intake, serum levels, tissue dose, and body 
burden. 
EPA response or action: 
Additional discussion of alternative dose metrics has been included in 
the Health Assessment of TCDD and Related Compounds (Part II), Chapter 
1: Disposition and Pharmocokinetics. This discussion has also been 
carried over to Section 1.3 of the Integrated Summary. The utility, 
strengths, and weaknesses of each are presented, and in a number of 
cases the relationships of one to another are discussed. 

Suggestion: 
1. Data presented on dioxin levels in food are an improvement over 
earlier drafts, but need more specific information on the number of 
samples collected, sampling locations, and standard deviations of 
observed levels presented in tables 4-6 and 4-8. 
EPA response or action: 
This additional information was included in Estimating Exposure to 
Dioxin-Like Compounds (Part I), Vol. 3, Chapter 4, and has been now 
added to the Integrated Summary (see table 4-5). This table presents 
dioxin levels in environmental media and food, along with number of 
samples, mean, range, and standard deviation. 

Suggestion: 
2. Revise and expand discussion of dioxin levels in food, identifying 
levels of dioxins in other food sources for which data are available; 
listing food sources that have not been extensively characterized 
(i.e., fish); commenting on changing rate of dioxins in food sources 
over the years; and addressing the effects of cooking practices. 
EPA response or action: 
Several new paragraphs have been added/edited in the Integrated 
Summary, Section 4, to address these comments. 

Suggestion: 
3. Reviewers thought EPA adequately derived approaches to estimate 
average daily dose from both dietary intake and body burden. Suggested 
revisions included (a) providing a clear definition of body burden and 
explaining how body burden relates to tissue levels; (b) presenting 
equations and sample calculations in the Integrated Summary to 
illustrate how average daily dose can be estimated from dietary intake 
or from body burden; (c) considering other sources of data for 
characterizing trends in body burden levels; and (d) providing 
additional detail on the variability in the distribution of estimated 
average daily intakes. 
EPA response or action: 
(a) EPA added a definition of body burden, and an explanation of how 
body burden relates to tissue levels, to the glossary in the 
Integrated Summary; (b) equations illustrating how average daily dose 
can be estimated from dietary intake or from body burden were in Part 
I, Vol. III, Chapter 4, but were not included in the Integrated 
Summary in the interest of brevity; (c) although body burden trends 
(e.g., differences in age) in the reassessment document are not 
statistically based, a current modeling study is underway to more 
fully understand body burden trends; (d) section 4.4.3 in the 
Integrated Summary on variability in intake levels has been expanded 
to include key references and a new discussion on the Center to 
Disease Control and Prevention blood study to further support the 
findings on variability. EPA is also currently investigating the 
possibility of using probability methods to further study variability 
of dioxin exposure. 

Suggestion: 
4. Reviewers thought EPA identified important "special populations" of 
highly exposed individuals and suggested that the agency consider 
including others, such as people who lose weight rapidly, fetuses, and 
people who eat large amounts of potentially contaminated food sources 
not explicitly considered in the reassessment (e.g., lamb). 
EPA response or action: 
In Part I, Vol. III, Chapter 5, EPA analyzed a large amount of 
available data on these special populations: nursing infants (Section 
5.2), people who fish (Section 5.3), people living near sources of 
dioxin release (Section 5.4), and cigarette smokers (Section 5.5). 
Other populations (such as exposed workers or those living in Seveso) 
were discussed in detail in Part II. 

Suggestion: 
5. Reviewers thought EPA may have overstated upper bound risks and 
suggested EPA more clearly describe the basis of the current cancer 
slope factor and significance of upper bound cancer risks to public. 
EPA response or action: 
The text has been revised to put the upper bound estimate of risk in 
better perspective. The previous range of upper bound risks was 
apparently confusing and has been removed. 

Suggestion: 
6. Most reviewers agreed that developmental, reproductive, 
immunological, and endocrinological noncancer effects could be seen in 
humans, given sufficient dose. Reviewers suggested EPA improve the 
justification for the conclusion that human epidemiological data 
suggest that noncancer effects occur at ambient exposures. 
EPA response or action: 
Additional discussion has been added to Sections 2,5, and 6 of the 
Integrated Summary to address this issue. 

Suggestion: 
7. The panel thought the Integrated Summary presented a reasonable 
argument that cancer risk associated with breastfeeding is likely low 
and suggested EPA provide similar argument for noncancer effects. 
EPA response or action: 
EPA asserts that the argument that noncancer risk associated with 
breastfeeding is also low is already in the report, although it is not 
broken out into a separate section. EPA agrees with WHO that on 
balance, the benefits of breastfeeding outweighed risks of dioxin 
exposures. 

Suggestion: 
8. The panel agreed that the Integrated Summary needs additional 
discussion on the uncertainties associated with using various dose 
metrics specifically for evaluating childhood risks. Some reviewers 
continued to have reservations about EPA's selection of the body 
burden dose metric for children, especially considering that 
children's (especially nursing infants') doses can be much higher than 
those of adults, even though their body burdens often are not. 
EPA response or action: 
See recommendation above relating to selection of a dose metric. 
Figures 4-4 and 5-2 were added to the Integrated Summary to help 
illustrate the rationale for selecting body burden as the dose metric 
using a nursing scenario, and expanded discussion can be found in 
Section 4. Nonetheless, uncertainty remains regarding the most 
appropriate dose metric for any given effect. 

Suggestion: 
9. Most of the reviewers agreed with the use of margin of exposure to 
express exposures rather than comparing exposures with reference dose 
given the assumptions made in the assessment, but they suggested the 
implication of these assumptions be more clearly defined. 
EPA response or action: 
Additional discussion regarding the concept of margin of exposure has 
been included in Sections 5 and 6 of the Integrated Summary. A table 
has been added to illustrate the concept for several cancer and 
noncancer endpoints. Additional details have been added to the 
discussion regarding the decision to use a margin of exposure rather 
than calculate a reference dose. 

Suggestion: 
10. The reviewers thought the Integrated Summary clearly presented the 
entire data set of dose response data that met EPA's selection 
criteria, but that presentation should be improved. Many thought that 
EPA should attempt to differentiate effects that are "frank 
manifestations of toxicity" from effects with unknown clinical 
significance. 
EPA response or action: 
Additional discussion has been added to the text to provide this 
differentiation, as suggested by the peer reviewers. EPA believes 
differentiating effects is inherently difficult since the 
manifestations of toxicological response lie along a continuum and 
biochemical changes may serve as a biomarker of the potential for 
frank response. 

Suggestion: 
11. The reviewers generally agreed that Chapter 9 on TEQs in Part II, 
presented the history, rationale and support for the TEQ approach for 
evaluating dioxin toxicity, but they were concerned that this approach 
attributes dioxin toxicity to compounds for which few toxicologic data 
are available. Though the reviewers felt that Chapter 9 establishes 
clear procedures for using, calculating, and interpreting TEQs, they 
stated certain topics needed to be described more clearly and 
suggested EPA concisely state why it selected WHO's 1998 TEFs over 
previously used TEFs, present example TEQ calculations as an appendix, 
and should stress that risk assessors should characterize fate and 
transport of individual dioxins separately. 
EPA response or action: 
Chapter 9 on TEQs has been revised in response to peer reviewers' 
comments. Additional discussion has been added to the Chapter to focus 
on 5 compounds that make up greater than 70 percent of human exposure 
and body burden on a TEQ basis. While several of the minor compounds 
have limited toxicologic data supporting their TEF values, the major 
compounds have robust data sets. This discussion has been carried over 
to the Integrated Summary in Section 1.2. 

Source: EPA. 

[End of table] 

Table 9: EPA's Responses to Science Advisory Board Panel's Comments: 

Recommendation: 
1. Carry out additional work on the exposure assessment section to 
evaluate sources that make the greatest contribution to dioxins in the 
food chain, and make the text consistent with the tables. 
EPA action or response: 
This is a long-term research goal of EPA. EPA officials stated that 
they interpret the Science Advisory Board recommendation as basically 
endorsing what EPA plans to do in the future—linking sources of 
dioxins with exposures. The minor issue regarding making the table and 
text consistent was resolved by EPA. 

Recommendation: 
2. Include discussion of all "special population" exposures in the 
summary document.	
EPA action or response: 
EPA added additional information regarding "special population" 
exposures (i.e., some Native American subsistence fishers could be 
highly exposed to dioxins depending on the amount of fish they catch 
and where). According to EPA officials, the agency now addresses this 
issue in the Integrated Summary—Sections 4 (exposure) and Section 6 
(risk characterization) and specifically mentions Native Americans in 
the text. 

Recommendation: 
3. Extend breastfeeding exposure scenarios beyond 1-year. 
EPA action or response: 
According to EPA officials, they performed additional analysis and 
revised the related text. See Integrated Summary, Section 6. 

Recommendation: 
4. For human carcinogen designation, better understanding and 
interpretation of epidemiological data are needed. Add expected 
differences in results between epidemiological studies of genotoxic 
agents and cancer promoters. 
EPA action or response: 
EPA added text in Part II and the Integrated Summary regarding the 
expectations for epidemiological studies for strong cancer promoters 
and will be including a discussion of new cancer studies in the 
reassessment to provide the latest on this issue. 

Recommendation: 
5. Methodology: Agree with use of margin-of-exposure approach, but in 
addition calculate a reference dose. 
EPA action or response: 
EPA disagreed and chose not to calculate a reference dose, but 
explanation of why it did not explained in more detail. See pp. 118-
122 in the Integrated Summary. 

Recommendation: 6. 
Methodology: In future reevaluations develop quantitative estimates of 
noncancer risk-—similar to those developed for cancer—-to the extent 
methods become feasible. 
EPA action or response: 
EPA's opinion is that to some extent it is already merging cancer and 
noncancer methods using margin-of-exposure analysis for both cancer 
and noncancer effects. The text tries to balance the discussion of 
cancer and noncancer risks, but noncancer risks cannot be done 
quantitatively. 

Recommendation: 
7. Further investigation of noncancer hazards is needed. They receive 
insufficient attention on pp. 7 and 11. About half of the panel 
believes that the current draft assessment may overestimate the likely 
cancer hazard. 
EPA action or response: 
EPA revised the text to put noncancer effects into better perspective, 
but officials acknowledged that the tools used to describe cancer 
risks are easier for people to understand. In the text of the report, 
EPA is providing more discussion on noncancer effects by providing 
examples where possible. 

Recommendation: 
8. The panel agreed with using body burden as the dose metric; 
however, better justification for using a specific dose metric such as 
body burden is needed. Provide more explicit examples of how different 
dose metrics might apply to specific toxic endpoints. 
EPA action or response: 
EPA officials said that the agency has revised and added text in 
several places to better explain the variety of dose metrics available 
and why body burden is the best choice for assessing dioxin. EPA 
revised Part II, Chapter 1 on dose metrics and it also made changes to 
Chapter 8 and added text in the Integrated Summary, Sections 1,5, and 
6. EPA recognized the need to better explain that using other dose 
metrics rather than body burden in certain situations is also 
acceptable. 

Recommendation: 
9. EPA should identify important data gaps on body burden (i.e., how 
it varies with age and in females depending on number of offspring) to 
highlight research opportunities. 
EPA action or response: 
EPA officials stated that research opportunities in the future will 
address this issue. EPA will be incorporating new studies in future 
dioxin assessments, particularly those that look at population 
dynamics (i.e., younger people starting now with lower intake levels/ 
body burdens than in past) as they become available. Currently, there 
is major work under way at the Center for Disease Control and 
Prevention looking at serum levels regarding dioxins and other health 
issues that will give insight/data on body burdens. First-year data of 
3-year study have been collected. 

Recommendation: 
10. There is some evidence that very low doses of dioxins may result 
in some decreases in adverse responses but can produce other adverse 
effects at the same or similar doses. Evaluate the totality of the 
evidence for non-monotonic dose response as studies become available, 
particularly evidence for any "U-shaped" dose response curve. 
EPA action or response: 
EPA officials stated that the agency will continue to work on the dose 
response chapter. The possibility that dioxins are anti-carcinogen is 
reflected in the Integrated Summary, Section 2 with three Kayajanian 
references. However, EPA does not have data on where or if it occurs 
on the dose response curve—above or below body burdens. 

Recommendation: 
11. Calculate ED using definitions other than that used for ED01 and 
for comparison purposes present values of ED10 (since its been applied 
to other chemicals by the agency). 
EPA action or response: 
EPA has done additional analysis using other effective dose values 
(e.g., ED10). EPA officials stated that it differed from the original 
calculation using ED01 in only a few instances. See pp. 118-122, in 
Integrated Summary and Part II, Chapter 8. 

Recommendation: 
12. Give additional consideration to its justification of method 
selection for condensing these effective doses into a recommended 
range. 
EPA action or response: 
See #11 above. 

Recommendation: 
13. The agency's description of its calculation of ED01 was not	
sufficiently detailed to permit the calculations to be repeated.
Describe calculation of ED01 more clearly and completely. 
EPA action or response: 
More explanation provided for use of ED01. See #11 above. 

Suggestion: 
1. The agency's calculation of the cancer potency factor is not 
prominently featured in the reassessment. Highlighting this 
calculation would significantly improve the transparency and 
accessibility of the reassessment. 
EPA action or response: 
EPA officials disagreed with the comment that cancer potency factor 
not prominently featured. EPA officials stated that figure (5-2) on 
cancer potency estimates for animal studies with full page footnote 
provided in version reviewed by the Science Advisory Board. Text has 
been added in Part II, Section 5 discussing sensitivity of 
calculations. 

Suggestion: 
2. The panel suggested that the agency consider making greater and 
more systematic use of parametric methods in calculations. This 
approach would help readers to develop a better sense of how the 
results presented depend upon specific analytical assumptions. 
EPA action or response: 
EPA does not plan to perform additional analysis. This is mostly 
intended as a recommendation to do further research. 

Concern: 
1. The majority of panel members have concerns about Agency cancer 
risk estimates associated with current population exposures and feel 
that it was not appropriate for the agency to characterize the risks 
in such a quantitative manner without providing a similar quantitative 
estimate of uncertainty. 
EPA action or response: 
EPA has added text on what EPA can say about quantifying uncertainty. 
EPA officials agree with the Science Advisory Board that there needs 
to be improvements in methodology (i.e., it will require more/better 
data sets). However, this will require further research in the future. 
It is a generic concern, not just regarding dioxins. 

Source: EPA. 

[End of table] 

[End of section] 

Appendix V: Comments from the Environmental Protection Agency: 

Note: GAO comments supplementing those in the report text appear at 
the end of this appendix. 

United States Environmental Protection Agency: 
Office Of Research And Development: 
Washington, D.C. 20460: 

April 17 2002: 

Ms. Christine Fishkin: 
Assistant Director: 
Natural Resources and Environment: 
United States General Accounting Office: 
Washington, DC 20548: 

Dear Ms. Fishkin: 

I am writing in response to an April 5, 2002 letter from David G. 
Woods to EPA Administrator Christine Todd Whitman transmitting the 
draft General Accounting Office (GAO) report entitled, Environmental 
Health Risks: Information on EPA's Draft Reassessment of Dioxins (GAO-
02-515) for Agency review. Thank you for the opportunity to provide 
our comments on this report before it is issued in final form. I 
realize that this report is the culmination of a significant effort by 
you and your colleagues. You should be commended for your thorough 
researching of the questions posed to you and your balanced treatment 
of the information at your disposal. This 67 page report deals with 
technically complex issues which you have succeeded in presenting in a 
concise and logical document. Your involvement of Agency experts in 
the information gathering and drafting phases of this report has no 
doubt added to its success and I compliment their efforts as well. 

While the Agency is very pleased with this draft report. Some of the 
points made by the Agency have not found their way into this review 
draft. The Comments provided below represent a series of issues where 
additional Agency comment is considered necessary. We have also 
provided a mark-up noting minor or editorial corrections for your 
consideration. These comments are not meant to detract from the 
overall quality of the report but are presented for clarification and 
completeness. 

1) Apparent inconsistencies among different components of the Draft 
Reassessment Documents: The GAO was supplied with internal working 
copies of all components of the draft EPA dioxin reassessment. [See 
comment 1] Each of these components was undergoing revision in 
response to comments from an independent peer review panel and the EPA 
Science advisory Board (SAB). At the time of the GAO review, different 
components were at different stages of revision. The exposure 
information contained in the Risk Characterization is a summary of 
information and analysis presented in the Exposure and Health Volumes. 
Since the development of the working draft of Characterization follows 
development of the working draft of the Exposure and Health Volumes, 
some inconsistences are inevitable. Among the changes made in the 
Exposure Volume that were identified as inconsistences by the GAO are 
the refinement of the fat content of ingested products, and the 
introduction of an additional category of consumption called "other 
meats". Clearly, it is EPA's intent to make the documents fully 
consistent at publication. In identifying these inconsistencies 
without clearly explaining the sequential nature of the revision 
process, the GAO report could lead some readers to interpret these as 
significant flaws rather than simply an issue of the draft 
Characterization not yet reflecting the updated Exposure Volume. The 
locations and text in question follows: 

a. Footnote on p. 8: "EPA's Integrated Summary (Table 4-7) presents 
information on exposure to 9 foods...." Table 4-7 in the draft 
Integrated Summary had not been updated yet. 

b. p. 19: The Integrated Summary does not reflect the newer and more 
valid percentages of fat in the food products found in the Exposure 
Volume. 

c. p. 22: The Integrated Summary does not include corrected average 
percent fat in milk found in the Exposure Volume. 

2) Characterizing potential sources of uncertainty in the draft 
Reassessment's dietary exposure estimate: The GAO draft correctly 
identifies several sources of potential uncertainty in the 
reassessment's estimate of dietary exposure. Each of these 
uncertainties is also identified in the draft reassessment. In our 
view, this point is not emphasized sufficiently in the GAO draft 
report. [See comment 2] More importantly, the GAO report does not 
provide the reader with enough perspective to judge the relative 
significance of these uncertainties to the overall calculation of 
dietary exposure. Without such a discussion, many readers would 
reasonably conclude that the uncertainties are of significance; 
otherwise, GAO would not have emphasized them. This is not
the case. Three issues are of particular importance are: a. The 
strength of the food concentration data for deriving national mean 
levels of exposure; b. The sampling of adipose tissue rather than 
muscle tissue in the meat surveys; and, c. The likelihood that current 
dioxin levels in food have significantly declined since the mid-
nineties. [See comment 3] EPA does not believe that these three issues 
raised are major weakness in the dietary exposure calculation. EPA has 
discussed in detail each of these issues with the GAO review team. 
However, the current draft of the GAO report does not adequately 
capture the depth of those discussions. A more detailed discussion of 
these issues follows. 

a. The draft GAO report states on p. 11, [Now on p. 10, See comment 4] 
1st sentence in second paragraph: "... dioxins vary and acknowledged 
that the available studies generally were not designed to estimate 
national exposures." This is incorrect. The reassessment's dietary 
estimate for beef, pork, and poultry are all based on joint EPA/USDA 
studies which incorporated a rigorous statistical design specifically 
intended to derive a representative national mean concentration.
Estimates for milk and dairy were based on an EPA milk survey that had 
broad national coverage. Although not a statistically based sampling, 
the study was specifically intended to gather milk samples that were 
representative of typical milk consumed in the US. Fish and shellfish 
accounted for an additional 26% of national exposure and this analysis 
relied on data from a wide variety of sources not intended to develop 
a national mean. Data on eggs, which the GAO study reviews in detail, 
account for only 4% of the total and were not part of a formal 
national survey. Together beef, pork, poultry, milk and dairy account 
for 66% of total estimated exposure; consequently, a majority of the 
dietary exposure estimated by EPA was derived from studies 
specifically designed to estimate national exposures. Fish is the one 
major food category, not based on sampling, designed to generate a 
national exposure mean. 

b. p 12, 2nd bullet and p. 17, 1st bullet: Concern is expressed about 
the comparability of grocery store samples and the fat reservoir 
samples taken for beef/pork/poultry in the national surveys: "Some of 
the samples are of edible food products sold in grocery stores, while 
others are of inedible cuts of fat, such as back fat on cattle...." 
The three national surveys obtained back fat from cattle, leaf fat 
from poultry, and belly fat from pork for the reasons this report 
cites on p.17. "EPA used this approach because USDA federal inspectors 
could obtain the samples with little disruption to the slaughtering 
establishments and because the samples' high fat content would enable 
more accurate measurement of dioxins, since the analysis would be of 
highly concentrated fat samples....EPA concluded that the fat samples 
for all three foods were comparable." [Now on p. 14; See comment 5] 

The use of the term 'inedible fat' may be misleading to some readers. 
The term, as used in the reassessment, refers more to the 
marketability of the fat rather than its physiological or nutritional 
status. For example, the back fat taken from beef carcasses is the 
same fat reservoir that extended to the ribs, which is considered 
edible fat. The critical issue is whether the lipid-adjusted 
concentrations of dioxin-like compounds of the sampled adipose tissues 
are good indicators of the lipid adjusted concentrations found in 
muscle tissues regularly consumed in the US diet. EPA has concluded 
the answer to this question is an unequivocal yes. There is a well 
developed understanding of distributional behavior of dioxin-like 
compounds in vertebrate tissues. In general, dioxin-like compounds 
distribute readily across the fat reservoirs of an organism, based on 
tissue lipid concentration. This understanding served as an essential 
component of support to the reassessment's broader conclusion that 
body burden is the best dose metric for estimating risk. This position 
was endorsed by the EPA, SAB and is also the position adopted by the 
WHO. 

EPA chose to further support this understanding by specifically 
examining dioxin distribution in beef cattle. The GAO draft report 
discuses this study on p. 17, [Now on p. 16; See comment 6] stating 
that "For the five samples, the ratios of CDDs. and CDFs in muscle fat 
to CDDs and CDFs in back fat varied by up to 300 percent, ranging from 
0.58 to 1.7; and the ratios for PCBs varied by up to 50 percent, from 
1.0 to 1.5. This variability indicates that using fat samples
may overstate or understate dioxin levels in beef, pork, and poultry 
to some extent." This GAO interpretation fails to adequately take into 
consideration the inherent variability that comes from trying to 
measure 0.000000000001 grams of dioxin in a gram of fat. Given the 
complexities of dioxin laboratory analysis, back fat concentrations 
ranging from 1/2 to 2 times the concentration in edible fat is best 
characterized as indistinguishable from each other. The full weight of 
evidence provides strong support for the use of back fat data to 
calculate dietary intakes for beef. 

c. The Draft GAO review correctly reports that most of the food 
concentration data used in the reassessment were collected between 5 
and 8 years ago and that since that time emissions from regulated 
sources are anticipated to have declined (P11 first bullet and 
footnote 10, p 44 observations). On page 45, [Now on p. 37; See 
comment 7] the draft report concludes that "the extent to which 
estimates accurately reflect current average daily exposure is not 
known". EPA believes that sufficient information is available to 
support a conclusion that, in spite of the emission reduction of the 
late 1990's, the exposure estimates of the draft reassessment are a 
reasonable characterization of contemporary exposure. The dioxin 
reassessment emissions inventory estimates that, from 1987 to 1995, 
overall quantifiable releases to the environment decreased by 75%. 
Most of this reduction was from municipal and medical waste
incinerators and from pulp and paper facilities use of chlorine 
bleach. These reductions were, in large part, in anticipation of EPA's 
promulgation of regulations scheduled for the last half of the 1990's. 
EPA has projected that full implementation of these rules would result 
in an overall decrease in quantifiable emission from the 1987 baseline 
of 90% or an additional 15% increment over the 1995 decline level. 
Most of the food samples were taken after the initial 75% decrease had 
occurred and therefore much of the decrease should already be 
reflected in the food concentration numbers. Additionally, most of the 
municipal and medical waste incinerators are located far from, and 
down-wind from, concentrated meat and dairy production areas; 
consequently, the impact of these emissions reduction on the 
commercial food supply should be less than directly proportional to 
their reduction in overall environmental release. Finally, reservoir 
sources of dioxin-like compounds (old releases that have been stored 
in soil and sediment and then reintroduced to the environment) are 
estimated to account for half or more of current exposure. This, 
combined with the unquantified sources of dioxin that cannot be 
accounted for in the inventory estimate, tend to reduce the likelihood 
of emission reduction in the late 90's significantly affecting the 
current estimate of general population exposure via the commercial 
food supply. EPA has concluded that, looking at the full weight of the 
evidence, exposure estimates based on food concentrations for the mid-
1990's should be representative of current dietary exposure. 

3) Variability in dairy concentration data: On p. 22 GAO, correctly 
describes the variability in dairy products reported in the Oct. 
draft. EPA has reviewed this number and concluded that since dairy 
lipid-adjusted concentration is derived directly from the milk data it 
should not have a separately derived standard deviation. The milk 
values are as reported in the GAO review (0.18 plus or minus 0.0012). 
This change was verbally reported to the GAO review team. [See comment 
8] 

4) Exclusion of elevated poultry samples form mean concentration 
calculation: Page 18 of the draft GAO report reads: [Now on p. 15; See 
comment 9] "EPA considered the two poultry fat samples inappropriate 
for the dioxins study, which was aimed at identifying typical 
exposures to dioxins. However, it is not clear that the poultry 
samples with high concentrations of dioxins were anomalies because the 
incidence of dioxin contamination in animals feeds is not known." EPA 
has reported to the GAO review team that the cause of the high poultry 
samples was specifically determined to be because of localized use of 
ball clay as an anti-caking agent in soybean meal. That ball clay is 
no longer being used (voluntarily removed after a FDA request to feed 
manufacturers). EPA concluded it was inappropriate to extrapolate the 
ball clay samples nationally to describe current background exposures 
via consumption of poultry. EPA is currently drafting a new section on 
animal feed contamination episodes, to include more details of this 
episode. 

5) Percentage of fat in consumed product: On p. 15, 2nd bullet, GAO 
states that, "...specific information on the assumptions and analyses 
EPA used in estimating these average fat percentages is not provided 
in the draft reassessment report." On p. 19, this same point is made, 
but in more critical detail. This is not correct. On p. 3-73 of the 
draft Exposure Volume, EPA provides the following explanation for 
their procedure for estimating percentage fat in consumed beef: [See 
comment 10] 

The percentage of fat in beef was estimated using food consumption 
data and fat content data for various beef products provided by David 
Haytowitz, USDA, to Linda Phillips, Versar, Inc., by personal 
communication, January 2001. USDA obtained food consumption data from 
the 1994-96 Continuing Survey of Food Intake Among Individuals 
(CSFII). The total quantity (in grams) of each food item eaten by the 
survey population in one survey day was tabulated and weighted to 
represent the quantity eaten by the entire U.S. population in one day. 
The fat content of each of these food items was also reported. To 
estimate the weighted mean percent of fat in beef products that are 
typically consumed by the U.S. population, the total amount of each 
beef item was first multiplied by the fraction of fat reported for 
that item to calculate the amount of beef fat consumed from each beef 
item. Next, the total amount of beef fat consumed (in grams) was 
calculated by summing the beef fat intakes for the individual beef 
items. The total amount of beef consumed was also estimated by summing 
the beef intake for the individual beef items. Finally, the weighted 
fraction of beef was estimated by dividing the total beef fat intake 
by the total beef intake. An abbreviated (i.e., the total number of 
beef items included in the analysis was 146; only a few beef items 
were included in the example to demonstrate the methodology) example 
of this calculation is provided in Table 3-39. 

It was also stated that the same source of data and procedure was 
followed for poultry and pork, though without this much detail. EPA is 
considering adding this information as an appendix to the Exposure 
Volume. 

6) Comparison of dietary intakes with body burden: The GAO report 
focuses on the reasonableness of the dietary intake estimates by 
examining the uncertainties in national food level data and dietary 
intake assumptions. There is, however, an additional analytic approach 
provided in the reassessment to assess the reasonableness of dietary 
estimates that is not acknowledged by the GAO. This is the comparison 
of projected intake levels to body burden measurements. For persistent 
bioaccumulating compounds, scientists can use human tissue 
measurements (blood serum) and pharmacokinetic modeling to estimate 
cumulative exposure. Using this approach, the reassessment concludes 
that when past elevated environmental levels are taken into 
consideration there is strong agreement between current measured serum 
levels and current estimated dietary exposure. 

7) Instances of data not supplied in the draft report: 

a. Other meats: On p. 13 and the footnote on p. 15, it is stated that 
EPA did not provide data on the concentration and composition for 
"other meats". The footnote on Table 430 from the October 2001 draft 
states that the concentration of 0.18 ppt assigned to "other meats" 
was, "estimated as the average of beef, pork, and poultry." The 
justification and exact procedure for doing this will be included in 
the final draft of the Exposure Volume. 

b. Number of samples in composite for PCB analysis: On p. 14, it is 
noted that, "The draft reassessment report does not specify the number 
of individual samples in the composite samples" for egg, fish, 
freshwater fish and shellfish, and vegetable. All these data was from 
two publications from Mes, and Mes and Weber. These individuals did 
not specify in their publication how many samples were in the 
composites. A sentence will be added to the description of the data 
stating that they did not identify how many samples were in the 
composite. 

8) Peer Review Process: Page 4, para 2, line 4 of the draft GAO report 
reads "12 reviewers assembled by EPA" . The reviewers are not chosen 
by EPA, but by an independent contractor (as noted by GAO later). It 
is important to be clear that in all instances, peer reviewers were 
chosen by an outside party, not EPA, in keeping with EPA's Peer Review 
Guidance. [See comment 11] 

9) TEF Values: The TEF for 2,3,4,7,8-PeCDF is 0.5. Therefore, the 
statement in the 4th line from the end of the middle paragraph on page 
6 of the draft GAO report needs correction to note that PeCDD has a 
TEF of 1.0, PeCDF has a TEF of 0.5; all the others have TEFs of 0.1 or 
lower. [Now on p. 6; See comment 12] 

On p.25, last line of 1st paragraph, the GAO Report suggests that TEFs 
for cancer rely on non-cancer endpoints. TEFs are relative potency 
factors which are independent of endpoint. This is a basic 
underpinning of the entire TEF approach. All data are considered, 
according to a weighting scheme derived by international consensus and 
based on scientific judgment, in setting TEFs. While EPA recognizes 
that there are few long term carcinogenesis studies for
other dioxins, there are many studies of tumor promotion data 
demonstrating that the TEFs work for that endpoint. GAO, EPA and peer 
reviewers of the EPA reassessment have recognized that further 
research on TEFs for dioxin and related compounds is needed. Some of 
this work is ongoing and will provide input into future TEF updates. 
[Now on pp.20-21; See comment 13] 

In conclusion, I want to reiterate that the above mentioned discussion 
is meant to provide clarification and completeness to a well 
researched and written report Thank you for the opportunity for the 
Agency to provide these comments as the GAO moves toward finalizing 
its Report. 

Sincerely yours, 

Signed by: 

Paul Gilman: 
Assistant Administrator: 

Attachment: 

The following are GAO's comments on EPA's letter dated April 17, 2002. 

1. The discrepancies we identify between the Integrated Summary and 
supporting chapters appear in the October 2001 reassessment documents 
that EPA distributed for internal agency review. We identified them 
primarily to inform readers of our report of the source of the 
information we cite. For example, a reader of the Integrated Summary 
would find (outdated) information on 9 food types, whereas we are 
citing information on 10 food types that is provided in the supporting 
chapters of EPA's reassessment documents and that EPA officials told 
us is correct. 

2. Throughout the section of our report on EPA's estimate of dietary 
exposure to dioxins, we attribute the identification of the 
limitations to EPA's draft reassessment report. 

3. Our report did not characterize the significance of the limitations 
EPA identified in its reassessment documents. We have added to the 
report EPA's opinion that these limitations do not represent major 
weaknesses in its estimates of dietary exposure to dioxins. 

4. The statement in our report that the available studies generally 
were not designed to estimate national exposures is derived from page 
76 of EPA's October 2001 Integrated Summary draft. In this document 
EPA says: "The amount and representativeness of the data vary, but in 
general these data were derived from studies that were not designed to 
estimate national background means." In its written comments, EPA says 
that most of the dietary exposure it estimated was derived from 
studies specifically designed to estimate national exposures. In 
support of this point, EPA says that 66 percent of the estimated 
exposure to dioxins is from eating beef, pork, poultry, milk, and 
dairy products, and that these studies were designed to estimate 
national exposures. (We note that these studies cover 5 of the 10 food 
types on which EPA based its exposure estimates.) Importantly, our 
draft report stated that the studies on beef, pork, and poultry were 
based on the first statistically designed national surveys of dioxin 
levels in these foods and that the milk samples upon which both the 
milk and dairy estimates were based came from a national survey with 
samples collected from sampling stations in a majority of the states. 
However, while our review of EPA's milk survey design plan indicated 
the milk samples were intended to assess the levels of dioxins in the 
general milk supply of the United States, the survey design document 
also stated that (1) the milk would be collected from dairy plants 
around the United States that represent approximately 20 percent of 
the nation's milk supply and (2) the survey was not designed to be 
statistically rigorous—that is, it was not intended to randomly sample 
milk in such a way that the results could be generalized to the full 
milk supply with a known degree of precision. Thus, we concluded that 
EPA's statement in the Integrated Summary—that the studies covering 
the 10 food types generally were not designed to estimate national 
exposures—was accurate. In light of EPA's comments and the fact that 
the milk samples used to estimate milk and dairy exposures did have 
national coverage, we have revised the report to indicate that EPA 
acknowledges that some of the available studies were not designed to 
estimate national average exposures. 

5. We revised the description of the fat samples from "inedible fat 
samples" to cuts of fat, such as back fat on cattle, that generally 
are not consumed by the U.S. public. 

6. We understand that there is variability associated with 
measurements at the picogram level. Nonetheless, we continue to 
believe that the variability identified among the five samples studied 
indicates that using fat samples not consumed by the public may 
overstate or understate to some extent dioxin levels in beef, pork, 
and poultry products sold to the public. 

7. In its comments, EPA stated that it believes that sufficient 
information is available to support a conclusion that, in spite of the 
emission reduction of the late 1990s, the exposure estimates of the 
draft reassessment are a reasonable characterization of contemporary 
exposure. We have revised the report to include EPA's opinion and the 
reasons it cited in support of its view that the emission reduction in 
the late 1990s does not significantly affect the current estimate of 
general population exposure. However, because EPA does not have data 
on dioxin emissions after 1995, we cannot evaluate EPA's conclusion. 

8. EPA stated that it plans to delete information on the variability 
in dairy concentration data from the reassessment report, and we have 
therefore deleted this point from our report. 

9. We understand that the contamination of the two samples eliminated 
from EPA's estimate was found to stem from a localized ball clay 
contamination. However, we continue to believe that because of the 
lack of information on the incidence of dioxin contamination in animal 
feeds as well as on the potential sources of such contamination, it is 
not clear that the poultry samples with high concentrations of dioxins 
were anomalies. For example, this animal feed contamination problem 
was identified as a result of the first national survey of only 80 
poultry fat samples. We acknowledge that a decision to exclude 
apparently anomalous information entails professional judgment. 
However, because the incidence of contamination of animal feed is 
unknown, we believe that it is important for users of the dioxin 
reassessment to understand the judgments EPA made in estimating 
dietary exposure. 

10. In the draft report, EPA does not provide information on the 
assumptions and analyses used to estimate the average fat percentages 
for pork and poultry. However, EPA does provide some information on 
how it estimated the fat percentage for beef. The fat percentage 
estimates affect the exposure estimates, and we believe this 
information should be included in the reassessment report. In its 
comments to us, EPA stated that the agency is considering adding 
information about the pork and poultry estimates to the report. We are 
therefore deleting references to this point in our report. 

11. We deleted the phrase "assembled by EPA" to be consistent with 
information we provide in the body of the report that the peer review 
panelists were selected by an independent contractor. 

12. We have revised this statement to reflect the fact that most 
(rather than all) of the other dioxins have TEFs of 0.1 or lower.
13. We clarified that TEFs apply to all effects, not just those for 
which relative potency data were available. 

[End of section] 

Appendix VI: GAO Contacts and Staff Acknowledgments: 

GAO Contacts: 

David G. Wood, (202) 512-3841: 
Christine Fishkin, (202) 512-6895: 

Staff Acknowledgments: 

Other key contributors to this report include Timothy Bober, Greg 
Carroll, Nancy Crothers, Greg Wilmoth, and Carrie Wheeler. 

[End of section] 

Footnotes: 

[1] In this report, unless otherwise indicated, we use the term 
"dioxins" to refer to the three closely related families of chemical 
compounds (dioxins, furans, and polychlorinated biphenyls) that EPA 
evaluates in its reassessment of dioxins. In the scientific 
literature, these compounds may be referred to as "dioxins and dioxin-
like compounds." 

[2] The National Academies consist of four organizations: the National 
Academy of Sciences, the National Academy of Engineering, the 
Institute of Medicine, and the National Research Council. 

[3] The September 2000 draft reassessment report is posted on EPA's 
Web page. While the October 2001 draft reflects a number of revisions 
to the September 2000 version on the Web page in response to public 
and peer review comments, the drafts are substantially the same. 

[4] The World Health Organization (WHO) met in Stockholm in June 1997 
to update earlier TEFs on dioxins for human risk assessment. As of 
2002, both EPA and WHO use the TEFs adopted by WHO in 1997, and 
published by Van den Berg et al. in 1998. 

[5] The full title of part III is Integrated Summary and Risk 
Characterization for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and 
Related Compounds. 

[6] The International Programme on Chemical Safety, established in 
1980, is a joint program of three cooperating organizations: the 
United Nations Environment Programme, the International Labour 
Organisation, and WHO. The International Programme on Chemical 
Safety's main roles are to establish the scientific basis for safe use 
of chemicals and to strengthen national capabilities and capacities 
for chemical safety. 

[7] The Food and Agriculture Organization of the United Nations was 
founded in 1945 with responsibilities covering nutrition and 
associated international food standards. Among its activities, the 
Organization approves international standards and helps frame 
international conventions and agreements. 

[8] EPA's Integrated Summary (table 4-7) presents information on 
exposures to 9 foods, while the detailed exposure chapters, chapters 3 
and 4, present information on 10 foods. However, the estimated total 
exposures from foods in both parts of the reassessment are almost 
identical. 

[9] The reassessment report addresses variability in general 
population exposure, indicating it results primarily from differences 
in dietary choices that individuals make. EPA estimates that dietary 
intake of dioxins for the general population may extend to levels two 
to three times higher than the mean estimate. 

[10] EPA does not have information on dioxin emissions reductions post-
1995. However, EPA's air toxics regulations are expected to result in 
further reductions. For example, EPA expects that its 1995 air toxics 
rule for large municipal waste combustors—associated with more than 60 
percent of total dioxin emissions—and its 2000 air toxics rule for 
small municipal waste combustors will reduce dioxin emissions from 
these entities to less than 1 percent of 1990 levels. 

[11] Some of the market basket surveys cited by EPA were conducted 
under the auspices of the Food and Drug Administration. 

[12] The report's references to this category of food are limited to 
several tables in the chapters on dietary exposure in which the 
estimates are provided, while the Integrated Summary cites nine foods, 
excluding other meats. 

[13] U.S. Environmental Protection Agency, Matthew Lorber et al, 
Distribution of Dioxins, Furans, and Coplanar PCBs in Different Fat 
Matrices in Cattle (Washington, D.C., 1997). 

[14] EPA also excluded other beef samples from its analysis on the 
basis that the source animals had unusually high levels of dioxin 
exposure. However, the analysis does not explain why the ratios (and 
thus the overall comparability) would vary with levels of exposure. 

[15] U.S. General Accounting Office, Food Safety: Agencies' Handling 
of a Dioxin Incident Caused Hardships for Some Producers and 
Processors, [hyperlink, http://www.gao.gov/products/GAO/RCED-98-104], 
Washington, D.C.: Apr. 10, 1998). 

[16] EPA's National Bioaccumulation Study, published in 1992, 
investigated the prevalence of selected bioaccumulative pollutants, 
including dioxins, in fish. 

[17] EPA's Environmental Radiation Ambient Monitoring System is a 
national network of monitoring stations that regularly collect air, 
water, precipitation, and milk samples for analysis of radioactivity. 
The samples were collected from 51 stations located in 41 states, 
Puerto Rico, and Panama. 

[18] For beef, pork, poultry, milk, and dairy products, the toxic 
concentrations are also based on EPA's estimates of the average 
percentage of fat in these foods--17, 19, 9, 1.8, and
12 percent, respectively. 

[19] EPA's August 1997 Exposure Factors Handbook provides data on 
standard factors needed to calculate human exposure to toxic 
chemicals, including the estimated average daily intake of foods that 
EPA program offices are encouraged to use in exposure assessment 
activities. 

[20] Because the results of this expert meeting were not published 
until 1998, EPA refers to this international consensus scheme as the 
TEQ-WHO. update. See Martin Van den Berg, et al., "Toxic Equivalency 
Factors (TEFs) for PCBs, PCDDs, PCDFs for Humans and Wildlife," 
Environmental Health Perspectives (1998): Vol. 106, No. 12: 775-792.) 

[21] See U.S. General Accounting Office, Chemical Risk Assessment: 
Selected Federal Agencies' Procedures, Assumptions, and Policies, 
[hyperlink, http://www.gao.gov/products/GAO-01-810] (Washington, D.C.: 
Aug. 6, 2001) for a more detailed description of the four-step process 
and other chemical risk assessment procedures that may be used by EPA. 

[22] See U.S. General Accounting Office, Environmental Protection 
Agency: Use of Precautionary Assumptions in Health Risk Assessments 
and Benefits Estimates, [hyperlink, 
http://www.gao.gov/products/GAO-01-55] (Washington, D.C.: Oct. 16, 
2000) and [hyperlink, http://www.gao.gov/products/GAO-01-810]. 

[23] EPA experts participated in all of these international meetings 
and evaluations convened by WHO on dioxins. 

[24] Group 1 is the classification for chemical agents or mixtures 
that WHO's reviewers determine are carcinogenic to humans. Group 2A is 
the classification for those probably carcinogenic, and Group 2B for 
those possibly carcinogenic. Group 3 includes those not classifiable 
as to human carcinogenicity, and Group 4 covers those probably not 
carcinogenic. 

[25] EPA's reassessment also noted that there is a broad range in the 
quality and quantity of data available for individual dioxins. 
However, EPA pointed out that five dioxins (including TCDD) contribute 
approximately 80 percent of the total toxic equivalence of dioxin in 
humans and characterized these five chemicals as "well studied." 
Nevertheless, EPA's reassessment relied primarily on TCDD studies. 

[26] The National Toxicology Program of the Department of Health and 
Human Services also listed TCDD as a known human carcinogen in the 
2001 addendum to its Report on Carcinogens (9th edition) on the basis 
of a similar combination of epidemiological (human) and mechanistic 
information, supported by experimental animal studies. 

[27] EPA's risk assessment guidelines set forth "default" assumptions—
generic approaches based on general scientific knowledge and policy 
judgment that are applied to various elements of the risk assessment 
process when specific scientific information is not available. 

[28] Although the experts participating in WHO's 1998 consultation 
established a tolerable daily intake range of 1 to 4 picograms per 
kilogram of body weight, they also stressed that the ultimate goal 
should be to reduce human intake levels below that range and 
recommended that every effort should be made to reduce exposure to the 
lowest possible level. 

[29] The Agency for Toxic Substances and Disease Registry in the 
Department of Health and Human Services uses a similar measure known 
as the minimal risk level. Minimal risk levels are estimates of the 
daily human exposure to a hazardous substance that are likely to be 
without appreciable risk of adverse noncancer health effects over a 
specified duration of exposure. These substance-specific estimates are 
intended to serve as screening levels to identify contaminants and 
potential health effects that may be of concern at hazardous waste 
sites. In 1999, the Agency for Toxic Substances and Disease Registry 
set a minimal risk level for dioxins and related compounds of 1.0 
picogram TEQ per kilogram of body weight per day, but did not use body 
burden as a dose metric. 

[30] Background exposure to chemicals is the exposure that regularly 
occurs to members of the general population from media such as food, 
air, and soil that have concentrations of these chemicals within 
normal background range. 

[31] WHO's IARC working groups may do some quantitative evaluations of 
human data in the monographs, but without extrapolation beyond the 
range of data available. Quantitative extrapolation of cancer risks 
from experimental (animal) data to the human situation is not 
undertaken. 

[32] EPA's Science Advisory Board reviews key scientific studies and 
methodologies used by the agency in formulating rules to protect the 
environment and public health. The Board comprises nongovernment 
experts and provides technical advice directly to the EPA 
administrator primarily on the basis of its peer reviews—that is, 
critical evaluations by panels of independent experts. 

[33] Dose-response modeling is used to estimate the health risks 
associated with various exposure levels (dose). 

[34] A cancer slope factor is an upper bound estimate of the increased 
cancer risk from a lifetime of exposure to an agent, generally 
approximating or exceeding the 95 percent confidence limit. This 
estimate is generally reserved for use in the low-dose region of the 
dose-response relationship. 

[End of section] 

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