Technical Report: Interpreting the 2005
CDC Biomonitoring Data for Dioxins

July 21, 2005

Summary

• Studies continue to demonstrate falling dioxin levels in humans, food, soils, and sediments. Dioxin levels in blood are declining in people of all birth years. Today, the youngest of the U.S. population begin life at a time when environmental levels--and exposures--have fallen significantly compared to their parents' and grandparents' exposures.
• As noted by the U.S. Centers for Disease Control and Prevention (CDC) in their Third National Report on Human Exposure to Environmental Chemicals, the levels of dioxins and furans found in humans as part of its study ". have decreased by more than 80% since the 1980s." and "... are below those associated with the occupational or unintentional exposures that produce health effects." (CDC, 2005)
• Government data show that dioxin emissions have dropped dramatically. CDC reports that "Releases from industrial sources have decreased approximately 80% since the 1980s. Today, the largest releases of these chemicals occurs as a result of the open burning of household trash and municipal trash, landfill fires, and nagricultural and forest fires." (CDC, 2005)
• Dioxins have never been intentionally manufactured for commercial purposes. They are trace by-products from a variety of combustion processes including natural (e.g., forest fires) and human-generated burning (e.g., burning of trash, automobile fuels), industrial combustion (e.g., energy generation, manufacturing, and incineration) and other sources.

Introduction

In its 2005 National Report on Human Exposure to Environmental Chemicals, CDC has released the third report documenting measured levels of a variety of environmental chemicals in samples of blood and urine taken from persons in the general U.S. population around the country. To aid in the interpretation of the CDC data on dioxin blood¹ levels in the U.S, the following summary provides key information regarding exposure to dioxins and health effects. In their National Reports, the CDC noted that:

Finding a measurable amount of one or more of the polychlorinated dibenzo-p-dioxins, dibenzofurans, coplanar or mono-ortho-substituted biphenyls in serum does not mean that the level of one or more of these causes and adverse health effect (CDC, 2005).

The measurement of an environmental chemical in a person's blood or urine does not by itself mean that the chemical causes disease. Advances in analytical methods allow us to measure low levels of environmental chemicals in people, but separate studies of varying exposure levels and health effects are needed to determine which blood or urine levels result in disease. (CDC, 2003)

Substantial human and animal data exist to permit interpretation of the measured levels of dioxins in blood samples from adults and children in the U.S. population.

Scope of this Document

"Dioxins" is the general term used to refer to groups of compounds known as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and a small subset of polychlorinated biphenyls for which toxicity equivalency factors have been established (TEFPCBs).² There are 75 dioxins, 135 furans, and 209 PCBs (U.S.EPA, 2004a). Within these large classes of compounds, 7 PCDDs, 10 PCDFs, and 12 PCBs have toxicity equivalency factors (TEF) assigned to them. This summary focuses on seven PCDD compounds and ten PCDF compounds because these compounds exhibit "dioxin-like" toxicity (U.S.EPA, 2004a).³ Although these 17 PCDD/F compounds share certain physical and chemical characteristics, their toxicities vary greatly. In fact, the least toxic of these compounds is estimated to be about 10,000 times less toxic than the most toxic compound, which is also the most well-studied compound--2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

To interpret the biomonitoring data for PCDD/Fs in human blood, the toxicity of each of the 17 compounds must be understood. Public health assessments for PCDD/Fs are usually based on an assessment of total toxic equivalency (TEQ). TEQs are obtained by multiplying the concentration of each PCDD and PCDF compound by its relative potency (its "toxic equivalency factor," or TEF) compared to the compound TCDD and summing up the results for all of the PCDD/F compounds (Attachment 1). For public health assessments, it is of interest to know both the mean (or average) level and some measure of the upper range of levels in the population, e.g., the 95th percentile.

CDC's Third National Report

CDC's Third National Report on Human Exposure to Environmental Chemicals presents the analytical results for samples collected as part of the 2001-2002 National Health and Nutrition Examination Survey (NHANES). NHANES is a CDC program in which questionnaires, physiological measurements, and analytical measurements from blood and urine samples are collected from a large, statistically-representative sampling of the U.S. population in an effort to gain an understanding of the health and nutritional status of the U.S. population (CDC, 2003).

In CDC's 2003 Second National Report (based on data from the 1999-2000 NHANES Survey), CDC reported data for 15 of the 17 PCDD/F compounds. CDC reported that fifty percent of the U.S. population aged 12 years and older had levels of PCDD/Fs below the limit of detection (LOD). This may have been due, in part, to the small volume of blood samples available to the CDC to analyze PCCD/F compounds. Limits of detection depend upon the volume of the individual blood samples available for testing. The larger the sample volume, the lower the limit of detection.

To improve its ability to detect these low concentrations, CDC increased the amount of blood it used for quantifying PCDD/Fs for the individual samples in the 2001-2002 NHANES Survey. Additionally, CDC analyzed pooled blood samples each made up of a small amount of blood from multiple (34) individuals. CDC used the results from these pooled samples to estimate the mean, or the average, level of PCDD/F compounds (Needham, 2005a).

Thus, in the Third National Report, CDC reported data as percentiles from the analysis of individual blood samples, the 'mean' (average) from the pooled samples, and an estimate of the TEQs for the 50th and 95th percentiles.

Other differences between CDC's Second and Third National Reports include:

• In its 2003 Report, CDC reported data for 15 of the 17 PCDD/F compounds; in its 2005 Report, CDC reports data for all 17 PCDD/F compounds.
• In its 2003 Report, CDC reported data for the U.S. population aged 12 years and older; in 2005, it provided data for sampled population aged 20 years and older.

Results -- Dioxin Levels Have Fallen in the U.S. Population

The CDC's Third National Report continues to confirm the trend of falling levels of PCDD/Fs in the U.S. population and that today's levels remain low. "The generally low values reported here support the observation that human serum levels of polychlorinated dibenzo-p-dioxins, dibenzofurans, and PCBs have decreased by more than 80% since the 1980s." (CDC 2005).

CDC's report gives us the first picture of a statistically representative sampling of PCDD/Fs in the U.S population; smaller studies of people in the U.S. have allowed estimates of PCDD/F levels.

These CDC data indicate that 1) the extensive efforts to control dioxin emissions have been successful in reducing exposure levels for the general population, and 2) current mean (average) PCDD/F levels in the general population (19.2 ppt-TEQ⁴) continue to decrease from the estimated mean PCDD/F TEQ levels of the 1970s, which were about 50 - 80 ppt-TEQ (Lorber, 2002).

Using the data from measured levels of individual PCDD/F compounds in blood samples from each person sampled as part of the NHANES program, The Chlorine Chemistry Division of the American Chemistry Council calculated a TEQ for the 50th and 95th percentiles of the U.S. population.⁵ The 50th percentile blood lipid level of PCDD/F compounds for the population samples (age 20 years and older) was 13.6 ppt-TEQ. Ninety five percent of the sampled population had less than or equal to 52.5 ppt-TEQ in their blood lipid. The mean (average) blood lipid level of PCDD/F compounds for the population samples (age 20 years and older) was 19.2 ppt-TEQ (Attachment 1). Based on the CDC data released in 2005, the levels for 95 percent of today's U.S. population are about half the 1970s levels.

CDC's data show that PCDD/F levels are going down in all age groups in the U.S. population. Younger people have lower PCDD/F levels in their blood than older people. The CDC data confirm the findings of other studies--PCDD/F levels in blood are related to the year in which a person was born. That is, older Americans were exposed to higher environmental levels and, as a result, have higher blood levels than their children and their grandchildren. The good news is that with the progress made in reducing environmental levels, PCDD/F levels in blood are declining in people of all birth years. Today, the youngest of the U.S. population begin life at a time when environmental levels-and exposures-are lower than when their parents' and grandparents' were infants. This leads some to speculate that today's babies will likely never reach the PCDD/F body levels of their grandparents.

Voluntary and governmental controls have reduced levels in the environment and in the food supply, which result in lower exposures and intake levels than in the past. To predict PCDD/F levels in the future, The Chlorine Chemistry Division of the American Chemistry Council performed modeling using the 2001-2002 NHANES data. The model suggests that PCDD/F levels in all age groups are predicted to continue the downward trend. The model suggests that people are eliminating PCDD/F compounds from the body faster than they are taking them in (intake levels).⁶ Moreover, by using conservative modeling factors⁷, levels of PCDD/F in the environment and in humans will continue to decline and that the higher body levels reported from the 1970's will not be seen in the future.

Historically PCDD/F TEQ Levels in Humans Have Fallen for the Past 40 Years	Looking Ahead PCDD/F TEQ Levels For Each Age Group Are Projected to Continue Falling
Data Sources: Information for 1965 1985 and 1995 are modeled average PCDD/F - TEQ for ages 20 to 70 (Lorber, 2002) Information for 1996-2001 is the measured average TEQ from indivuals age 15 to over 60 from LA, MO, NC and NY (558 people) and includes 4 PCBs (Patterson et. al., 2004). If PCBs were not included, this TEQ would be lower. The Chlorine Chemistry Division of the American Chemistry Council calculated the TEQ from the CDC 1999-2000 NHANES data for ages 20 and over. The small blood volume of indivual samples resulted in a high number of non detects, which influenced the TEQ calculations. Attachment 1. The Chlorine Chemistry Division of the American Chemistry Council calculated the TEQ from the 2001-2002 NHANES data for ages 20 and over. CDC used blood samples with a larger volume, which lowered the limits of detection resulting in fewer non-detects. The Chlorine Chemistry Division of the American Chemistry Council modeled the future body levels starting with the mid point measurement for the average (mean) PCDD/F ppt-TEQ for each reported age group (20 years and older) reported in the Third National Exposure Report (2001-2002 NHANES dataset) CCC based projections for the age group 15 years on CDC's 2001-2002 pooled samples (Needham, 2005a). *Range for governmental exposure guidelines is 8 - 32 ppt (Attachment 2)

PCDD/F levels have been declining since the early 1970s; modeling predicts a continuation of the declining levels. Some may ask whether there is an increase in dioxin levels between the 2003 and 2005 Reports. This analysis concludes that there is NOT an increase for a number of reasons:

• Additional congeners: The 2005 Report included data for two additional congeners for the first time. These added a small amount to the overall PCDD/F.
• Missing data: In the 1999-2000 NHANES data for PCDD/F, there were more missing congener data than in the 2001-2002 NHANES data. Of the expected 29,880 individual PCDD/F congener data in the 1999-2000 NHANES data, nearly 23% were missing. In contrast, the 2001-2002 NHANES data was more robust-only 11% of the 18,768 congener data were missing. Missing data included those samples that were lost due to spillage, mislabeling, and many other factors. In the calculation of the TEQ, The Chlorine Chemistry Division of the American Chemistry Council treated each of these missing congener data as 'zero.' Thus, missing data may have lowered the reported mean ppt-TEQ for 1999-2000 NHANES.
• Small blood sample volume: The small blood sample volume available to the CDC for the 1999-2000 NHANES hampered CDC from measuring low levels of PCDD/Fs in blood. With the larger blood sample volumes in the 2001-2002 NHANES, CDC was able to measure lower levels.

With the larger volume blood samples, the smaller number of missing data, and the inclusion of the full set of 17 PCDD/F congeners, overall, one might reasonably conclude that the 2001-2002 NHANES data represent a more realistic and representative profile of PCDD/F levels of the U.S. population.

U. S. Government and International Guidelines

The World Health Organization (WHO), the U.S. Agency for Toxic Substances and Disease Registry (ATSDR), the Joint Expert Committee on Food Additives of the World Health Organization (JECFA/WHO), and the European Commission Scientific Committee on Foods (ECSCF) have recently examined the body of human and laboratory animal health effects data for PCDD/Fs and those PCB compounds for which a TEF has been assigned and made recommendations for average daily intake limits.⁸ Based on their evaluations of the human and animal health effects data, these agencies have recommended that the average daily intake of PCDD/Fs and TEF-PCBs be limited to 1 to 4 pg-TEQ per kg body weight per day⁹ (usually written as TEQ/kg bw/day). These governmental guidelines ensure that daily intake of this level over a person's lifetime does not approach the levels for health concerns estimated from the available scientific data.

Current average intake of PCDD/Fs is less than most health protective intake levels set by U.S. and international health agencies (see Attachment 2). The U.S. Environmental Protection Agency (U.S.EPA) estimated average intakes of 0.61 pg-TEQ/kg bw/day (U.S.EPA, 2004c). The U.S. Food and Drug Administration reports estimated intakes of PCDD/Fs to be 0.39 pg-TEQ/kg bw/day (U.S.FDA, 2004). Some people in the U.S. with high fat diets or who consume large amounts of fatty fish may exceed these recommended governmental guidelines.¹⁰ The government guidelines include TEF-PCBs, which have been reported to account for approximately 40-50% of the overall TEQ in humans.

Overall, levels of these chemicals in humans in the U.S. are decreasing over time (Needham et al., 2005). Studies continue to demonstrate falling dioxin levels in human tissue, food, and sediments.

Exposure and Distribution in the Body

PCDD/F compounds are persistent, fat-soluble compounds, which bioaccumulate from the environment in the food chain, with storage in animal fats, including human body fat. Human exposure occurs primarily through the diet, with the main sources of PCDD/Fs being animal fats from beef, dairy products, pork, poultry, and fish. Fluctuations in short-term intake rates (for periods as long as weeks or months) do not have significant effects on the levels of PCDD/Fs in the body.

PCDD/Fs can be measured in the lipid portion of blood, and these measurements provide a good indication of the levels of these compounds throughout the body. Scientists have predicted that several PCDD/F compounds have very long half-lives of elimination in humans (more than 5 years to as much as 20 years). New research suggests that PCDD/Fs are eliminated from the human body at variable rates depending upon their levels in the body (Aylward et al., 2005) and that half-lives of elimination actually range from approximately 1 year to 10 years and are inversely related to the levels in the body and age (Aylward et al., 2005; Lorber, 2002).

Health Effects

Specific human populations have been exposed to relatively high levels of PCDD/Fs in a variety of situations, including exposure during manufacturing of pesticides that contained certain PCDD/F compounds as contaminants, during spraying of herbicides in agriculture or during the Vietnam War, and from accidents at chemical manufacturing plants in which some PCDD/F compounds were released into the surrounding area.

The one health effect clearly linked to high levels of exposure to PCDD/Fs is a reversible skin condition called chloracne. It appears that chloracne is only associated with levels in humans of at least 800 ppt lipid although levels in the thousands of PG/G of lipid do not always produce the effect (Mocarelli et al., 1991 as cited in CDC, 2003 and CDC, 2005). Some studies of industrial worker groups have suggested a small increase in cancer rates in persons with exposure levels hundreds of times higher than those found in the general population. Studies of high-level exposure also indicate that some biochemical parameters, including levels of serum enzymes, hormone levels, and immune system parameters, may be altered by exposure to PCDD/Fs.

As noted by CDC (2003), "Levels in this Report are far below those associated with the occupational and unintentional exposures that produce health effects."

Sources of PCDD/Fs

PCDD/Fs have never been intentionally manufactured for commercial purposes. They are trace by-products from a variety of combustion processes including natural (e.g., forest fires) and human-generated burning (e.g., burning of trash, automobile fuels [diesel, leaded, and unleaded]), industrial processes (e.g., incineration, energy generation, manufacturing, and other sources).

*With the exception of forest fire data, dioxin emissions source data are based on EPA projections for 2002/4, assuming full compliance with regulatory levels and the closure of a copper smelter (personal communication, Dwain Winters, US EPA, 9-9-02). #The dioxin contribution from forest fires was calculated using National Interagency Fire Center acreage burned in year 2004 wildland fires; an emission factor of 20 ng-TEQ/kg biomass burned [Gullett and Touati (2003)]; and a biomass consumption rate of 9.43 metric tons/acre in areas consumed by wildfires from Ward et al. (1976), as cited in the EPA Draft Dioxin Reassessment (September, 2000).

Historically, PCDD/F compounds were produced inadvertently in larger quantities as trace by-products during the manufacture of certain pesticides, the operation of incinerators without current emission controls, and in various industrial processes.

Because PCDD/Fs are persistent in the environment, they are ubiquitous in both urban and rural areas in soil and sediment.

EPA data show that over time quantified emissions from sources in its Dioxin Source Inventory¹¹ have decreased. As a result of reductions in some source categories, a shift has occurred in leading sources of PCDD/Fs. For example, industrial, municipal and medical incineration, once significant sources of dioxins, are currently smaller sources as a result of the combination of regulatory activities, improved emission controls, voluntary actions on the part of industry, and the closing of a number of facilities. Today, EPA reports that the largest quantified uncontrolled source of dioxin is the backyard burning of trash.¹² CDC reports that the largest releases of PCDD/Fs occur from open burning of household and municpal trash, landfill fires and agricultural and forest fires (CDC, 2005).

Sources: Data for 1987 and 1995 are from the "US Environmental Protection Agency Inventory of Sources of Dioxin-Like Compounds in the United States-1987 and 1995" http://cfpub.epa.gov/ncea/cfm/dioxindb.cfm?ActType=default. Year 2000 data are from EPA's "External Review Draft: The Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States: The Year 2000 Update," released in March 2005. (EPA, 2005). http://www.epa.gov/NCEA/pdfs/dioxin/2k-update/pdfs/Dioxin_Frontmatter.pdf The 2002/4 data are based on EPA projections assuming full compliance with regulatory levels by this period and the closure of a copper smelter (personal communication, Dwain Winters, US EPA, 9-9-02).

References

Aylward L.L., Brunet R.C., Carrier G., Hays S.M., Needham L.L., Patterson D.G., Gerthoux P.M, Brambilla P. and Mocarelli P. (2005). Concentration-dependent TCDD elimination kinetics in humans: Toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy and Vienna, Austria and impact on dose estimates for the NIOSH cohort. Journal of Exposure Analysis and Environmental Epidemiology 15(1):51-65.

CDC (2005). Third National Report on Human Exposure to Environmental Chemicals, Atlanta, GA., NCEH Pub. No. 05-0570. July 2005. See http://www.cdc.gov/exposurereport/

CDC (2003). Second National Report on Human Exposure to Environmental Chemicals, Atlanta, GA., NCEH Pub. No. 02-0716. Revised March 2003. See http://www.cdc.gov/exposurereport/

Gullett, B.K. and Touati, A. (2003). PCDD/F emissions from forest fire simulations, Atmospheric Environment 37, p. 803-13.

Lorber, M. (2002). A pharmacokinetic model for estimating exposure of Americans to dioxin-like compounds in the past, present, and future. Science of the Total Environment. 288, 81-95.

Mocarelli P, Needham LL, Marocchi A, Patterson DG Jr, Brambilla P, Gerthoux PM, Meazza L, Carreri V. (1991). Serum concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. Journal of Toxicology Environmental Health. 32(4), 357-66.

Needham, L.L., Barr, D.B., Caudill, S.P., Pirkle, J.L., Turner, W.E., Osterloh, J., Jones, R.L., Sampson, E.J. (2005). Concentrations of environmental chemicals associated with neurodevelopmental effects in U.S. population. NeuroToxicology. Available online 9 March 2005.

Needham, L.L. (2005a). Exposure Levels as Determined by Serum Levels from Control Data Sets and National Health and Nutrition Examination Survey (slides show preliminary data), presentation to the National Academy of Sciences, Expert Panel on Review EPA's Exposure and Human Health Reassessment of TCDD and Related Compounds, Project BEST-K-03-08-A. February 2, 2005. Slides are available by contacting NAS staff. http://www4.nas.edu/cp.nsf/Projects+_by+_PIN/BEST-K-03-08-A?OpenDocument.

NHANES (2001-2001) NHANES 2001-2002 Data Files Data, Docs, Codebooks, SAS Code. Web site accessed May 2005. http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.htm

NHANES (1999-2000) NHANES 1999-2000 Data Files Data, Docs, Codebooks, SAS Code. Web site accessed May 2005. http://www.cdc.gov/nchs/about/major/nhanes/nhanes99_00.htm

Patterson, D.G., Canady, R., Wong, L-Y., Lee, R., Turner, W., Caudill, S., Needham, L., Henderson, A. (2004). Age specific dioxin TEQ reference range. Organohalogen Compounds 66, 2878-2883.

United States Environmental Protection Agency (U.S.EPA). Database of Sources of Environmental Releases of Dioxin-Like Compounds in the United States, EPA website http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?PrintVersion=True&deid=20797, accessed March 29, 2005.

U.S. Environmental Protection Agency (2005). External Review Draft: The Inventory of Sources and Environmental Releases of Dioxin-like Compounds in the United States: The Year 2000 Update. Available March, 2005 at http://www.epa.gov/ncea/pdfs/dioxin/2k-update/

United States Environmental Protection Agency (U.S.EPA). (2004a). Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. National Academy Sciences (NAS) Review Draft. Part I: Estimating Exposure to Dioxin-Like Compounds. Volume 1: Sources of Dioxin-Like Compounds in the United States. Chapter 1: Background and Summary. Page 1-4. Washington, D.C.: National Center for Environmental Assessment, U.S. Environmental Protection Agency. http://www.epa.gov/ncea/pdfs/dioxin/nas-review/

United States Environmental Protection Agency (U.S.EPA). (2004b). Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. National Academy Sciences (NAS) Review Draft. Part I: Estimating Exposure to Dioxin-Like Compounds. Volume 1: Sources of Dioxin-Like Compounds in the United States. (2005). Chapter 11: Sources of Dioxin-Like PCBs. Page 11-2. Washington, D.C.: National Center for Environmental Assessment, U.S. Environmental Protection Agency. http://www.epa.gov/ncea/pdfs/dioxin/nas-review/

United States Environmental Protection Agency (U.S.EPA). (2004c). Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. National Academy Sciences (NAS) Review Draft. Part I: Estimating Exposure to Dioxin-Like Compounds. Volume 2: Properties, Environmental Levels, and Background Exposures. Chapter 4: Human Exposure to CDD, CDF, and PCB Congeners. Page 4-46. Washington, D.C.: National Center for Environmental Assessment, U.S. Environmental Protection Agency. http://www.epa.gov/ncea/pdfs/dioxin/nas-review/

U.S. Environmental Protection Agency (September, 2000). Exposure and human health reassessment of 2,3,7,9-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds (Draft).

United States Food and Drug Administration. (2004). PCDD/PCDF Exposure Estimates. Center for Food Safety and Applied Nutrition/Office of Plant & Dairy Foods. July 2004; Updated November 2004. http://www.cfsan.fda.gov/~lrd/dioxee.html

Van den Berg, M., L. Birnbaum, A.T. Bosveld, B. Brunstrom, P. Cook, M. Feeley, J.P. Giesy, A. Hanberg, R. Hasegawa, S.W. Kennedy, T. Kubiak, J.C. Larsen, F.X. van Leeuwen, A.K. Liem, C. Nolt, R.E. Peterson, L. Poellinger, S. Safe, D. Schrenk, D. Tillitt, M. Tysklind, M. Younes, F. Waern, and T. Zacharewski. (1998). Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environmental Health Perspectives 106(12), 775-792.

Ward et al., 1976 An update on particulate emissions from forest fires. Presented at: 69th Annual Meeting of the Air Pollution Control Association, Portland, OR June 27-July 1, 1976] as cited in the EPA Draft Dioxin Reassessment, September, 2000.

Attachment 1: Calculation of PCDD/F-TEQ

To interpret the biomonitoring data for PCDD/Fs in human blood, the toxicity of each of the 17 compounds must be understood. Although these 17 PCDD/F compounds share certain physical and chemical characteristics, their toxicities vary greatly. In fact, the least toxic of these compounds is estimated to be about 10,000 times less toxic than the most toxic compound, which is also the most well-studied compound--2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Public health assessments for PCDD/Fs are usually based on an assessment of total toxic equivalency (TEQ). TEQs are obtained by multiplying the concentration of each PCDD and PCDF compound by its relative potency (its "toxic equivalency factor," or TEF) compared to the compound TCDD and summing up the results for all of the PCDD/F compounds. For public health assessments, it is of interest to know both the mean (or average) level and some measure of the upper range of levels in the population, e.g., the 95th percentile.

In the Second National Report on Human Exposure to Environmental Chemicals (CDC, 2003), CDC reported data for individual congeners of PCDD/Fs but did not report data as TEQs. To determine the 50th and 95th percentile PCDD/F-TEQs, the Chlorine Chemistry Council calculated TEQs for each of the sampled individuals from the NHANES database (sampling years 1999-2000) for which PCDD/F data were available (1,992 individuals). Similarly, for the Third National Report on Human Exposure to Environmental Chemicals (CDC, 2005), The Chlorine Chemistry Division of the American Chemistry Council accessed the 2001-2002 NHANES data set to calculate the corresponding 50th and 95th percentile PCDD/F-TEQs for the sampled population (1,244 individuals).

TEQs were calculated by multiplying the concentration in blood (lipid adjusted) of the PCDD/F compounds for each individual compound by the respective toxic equivalency factors (TEFs) (Table 1), and then summing the adjusted concentrations of the PCDD/Fs for each individual. Next, the 50th and 95th percentiles for the individuals were calculated (Tables 2 and 3, respectively). Table 4 presents the mean (average) PCDD/F-TEQs.

A range of values for each of these percentiles is given because there are several methods for addressing values below the limit of detection (LOD), including:

(i) If a chemical concentration is below the detection limit, its value is set at zero. This method produces the lower end of the range of the 50th and 95th percentiles.

(ii) Values for chemicals below the detection limit are set equal to the LOD divided by two, which gives the intermediate value for the percentiles.

(iii) Values for chemicals below the detection limit are set equal to the LOD divided by the square root of 2. This method gives the highest end of the range of the 50th and 95th percentiles.

Where PCDD/F concentrations were missing from the NHANES data, the Chlorine Chemistry Division of the American Chemistry Council set concentrations equal to zero.

Table 1: Toxic equivalency factors (TEFs) for PCDDs and PCDFs (Van den Berg et al., 1998).

Table 2. Estimated Values for for PCDD/F TEQs for individuals from NHANES data (ppt, blood - lipid adjusted).

Table 2a. Estimated 50^th percentiles

Table 2b. Estimated 95^th percentiles

Table 2c. Mean PCDD/F TEQs

^* ND is non detect, meaning the concentration for a chemical was below the analytical limit of detection.
¹ Estimated percentile based upon the Chlorine Chemistry Division of the American Chemistry Council's analysis of the 1999-2000 NHANES data.
² Estimates are higher for ages 20 and over as compared to the entire population because older individuals tend to have higher levels of PCDD/Fs in their blood than younger people (Patterson et al., 2004).
³ Estimated percentile based upon the Chlorine Chemistry Division of the American Chemistry Council's analysis of the 2001-2002 NHANES data.
⁴ CDC's estimates of the 95^th percentiles differ from the Chlorine Chemistry Division of the American Chemistry Council estimates because CDC weighted the data by race, gender, age and other population factors.

References for Attachment 1

CDC (2005). Third National Report on Human Exposure to Environmental Chemicals, Atlanta, GA., NCEH Pub. No. 05-0570. July 2005. See http://www.cdc.gov/exposurereport/

CDC (2003). Second National Report on Human Exposure to Environmental Chemicals, Atlanta, GA., NCEH Pub. No. 02-0716. Revised March 2003. See http://www.cdc.gov/exposurereport/

NHANES (1999-2000) NHANES 1999-2000 Data Files Data, Docs, Codebooks, SAS Code. Web site accessed May 2005. http://www.cdc.gov/nchs/about/major/nhanes/nhanes99_00.htm

NHANES (2001-2002). NHANES 2001-2002. Data Files Data, Docs, Codebooks, SAS Code. Web site accessed May 2005. http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.htm

Patterson, D.G., Canady, R., Wong, L-Y., Lee, R., Turner, W., Caudill, S., Needham, L., Henderson, A. (2004). Age specific dioxin TEQ reference range. Organohalogen Compounds 66, 2878-2883.

Van den Berg, M., L. Birnbaum, A.T. Bosveld, B. Brunstrom, P. Cook, M. Feeley, J.P. Giesy, A. Hanberg, R. Hasegawa, S.W. Kennedy, T. Kubiak, J.C. Larsen, F.X. van Leeuwen, A.K. Liem, C. Nolt, R.E. Peterson, L. Poellinger, S. Safe, D. Schrenk, D. Tillitt, M. Tysklind, M. Younes, F. Waern, and T. Zacharewski. (1998). Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environmental Health Perspectives 106(12), 775-792.

Attachment 2:
Background Information on International Tolerable Intake Limits of Dioxin-like Compounds and Conversion to Levels in Human Blood.

Tolerable Intake Limits have been set by various U.S. and international agencies for PCDD/Fs and PCBs with a TEF (Table 3). These agencies include the Agency for Toxic Substances and Disease Registry (ATSDR), the Joint Expert Committee on Food Additives (JECFA), the European Commission Scientific Committee for Food (ECSCF), and the World Health Organization (WHO).

Table 3: U.S. Government and International Acceptable Exposure Guidelines for Dioxin-Like Compounds (2,3,7,8-substituted PCDD/Fs, and PCBs with a TEF) (TEQs)*

The agencies listed in Table 3 have approximated the toxicokinetics of PCDDs and PCDFs using a one-compartment model, where the relationship between intake and the level of chemicals in a body tissue ("Body Level") is described using the following equation:

where:

t1/2 = half-life of PCDDs/PCDFs in the human body = 7.5 years or 2738 days (7.5 × 365)

f = 0.5 (50% of PCDDs/PCDFs are absorbed from the diet and are available to be distributed throughout the body)

ln(2) = the natural log 2 is 0.69

Half-life can also be described as a function of months (7.5 × 12 = 90) or weeks (7.5 × 52 = 390) for the intakes corresponding to the JECFA and ECSCF tolerable intakes. It should be noted that each agency uses a slightly different value for half-life (either 7.5 or 7.6 years).

PCDD/Fs partition into the lipid fraction of the body and blood. Concentrations of PCDD/s reported in biomonitoring studies (including the results reported by CDC) are in units of ng/kg lipid or ppt. Concentrations in the body can be converted to the equivalent blood lipid concentration by dividing by the fraction of lipid in the average human. Most agencies use the assumption that the average human has a percent fat/lipid content of 25% (U.S.EPA, 2004b). Using this information, the tolerable daily intake guidelines established by each agency can be converted to equivalent concentrations in the body and equivalent blood lipid concentrations (Table 4).

Table 4: U.S. and International Agencies' Tolerable Intakes and Equivalent Body and Blood Lipid Concentrations for PCDD/Fs and PCBs with TEFs

Uncertainties with Converting Tolerable Intakes into Blood Concentrations

This method of calculating concentrations in the body and equivalent blood lipid concentrations based on the regulatory agency tolerable intake limits contains several uncertainties and limitations. These include:

1) The pharmacokinetic parameters for 2,3,7,8-TCDD are used as representative for all PCDD/F congeners or total TEQ. It is known that each congener has a different half-life, half-lives may depend upon dioxin body concentrations, and little is known about the bioavailability of each congener.

2) Because of the long half-lives of PCDD/Fs, the blood lipid concentrations found in people today represent intake from decades ago. Recent modeling efforts indicate that historical exposures to PCDD/Fs were low in the early part of the century, peaked between 1950 and 1970 and have declined sharply over the past 30 years (Aylward and Hays, 2002; Lorber, 2002). Therefore, people who are older than approximately 30 years of age have blood lipid concentrations that are largely a result of their exposures 10 to 30 years ago rather than their recent (past 10 years) exposures. As a result, the intake that would be calculated for a person's given blood lipid concentration, assuming no historically higher exposures, would be an overestimate of their actual current intake. Simply stated, today's children experience lower exposures to PCDD/Fs than their parents/grandparents did when they were children.

References for Attachment 2

ATSDR (Agency for Toxic Substances and Disease Registry) (1998). Toxicological Profile for Chlorinated Dibenzo-p-dioxins (CDDs). December 1998. Chapter 7. Available at http://www.atsdr.cdc.gov/toxprofiles/tp104.html

Aylward, L.A. and Hays, S.M. (2002). Temporal trends in human TCDD body burden: Decreases over three decades and implications for exposure levels. Journal of Exposure Analysis and Environmental Epidemiology 12:319-328.

European Commission Scientific Committee on Food (ECSCF). (2001). Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-Like PCBs in Food. Update Based on New Scientific Information Available Since the Adoption of the SCF Opinion of 22nd November 2000. Adopted on 30 May 2001. CS/CNTM/DIOXIN/20 final http://europa.eu.int/comm/food/fs/sc/scf/out90_en.pdf

Lorber, M. (2002). A pharmacokinetic model for estimating exposure of Americans to dioxin-like compounds in the past, present, and future. Science of the Total Environment 288, 81-95.

United States Environmental Protection Agency (U.S.EPA). (2004a) Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. National Academy Sciences (NAS) Review Draft. Part I: Estimating Exposure to Dioxin-Like Compounds. Volume 2: Properties, Environmental Levels, and Background Exposures. Chapter 4: Human Exposure to CDD, CDF, and PCB Congeners. Page 4-46. Washington, D.C.: National Center for Environmental Assessment, U.S. Environmental Protection Agency. http://www.epa.gov/ncea/pdfs/dioxin/nas-review/

United States Environmental Protection Agency (U.S.EPA). (2004b) Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Related Compounds. National Academy Sciences (NAS) Review Draft. Part II: Health Assessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. Chapter 8: Dose-Response Modeling for 2,3,7,8-TCDD. Page 8-13. Washington, D.C.: National Center for Environmental Assessment, U.S. Environmental Protection Agency. http://www.epa.gov/ncea/pdfs/dioxin/part2/drich8.pdf

Joint FAO/WHO Expert Committee on Food Additives (JECFA). (2001). Summary and Conclusions. Fifty-seventh meeting. Rome, 5-14 June 2001. Section 3: Polychlorinated dibenzodioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls http://www.who.int/ipcs/food/jecfa/summaries/en/summary_57.pdf

WHO (World Health Organization). (1998). Assessment of the health risk of dioxins: re-evaluation of the Tolerable Daily Intake (TDI). Executive Summary. May 25-29, 1998 Geneva, Switzerland. Available at http://www.who.int/ipcs/publications/en/exe-sum-final.pdf

End Notes

¹CDC performs its analyses on the liquid part of the blood, called serum. For the purposes of this summary, we will refer to serum as "blood."

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² This document uses the terms PCDD, PCDF, and TEF-PCBs rather than the more general terms, "dioxins," "furans," or "dioxin-like compounds." TEF refers to "toxicity equivalency factors" published in Van den Berg, et al., 1998.

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³This Summary does not address the interpretation of the PCB compounds for the following reasons: (i) The sources of PCDD/Fs are very different from the sources of PCBs (for example, PCDD/Fs were never intentionally produced, while PCBs were manufactured in the U.S. for almost 50 years) (U.S.EPA, 2004b). (ii) Methods used to reduce releases of PCDD/Fs differ from PCBs. (iii) The applicability of TEQs to PCBs is subject to scientific uncertainty.

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⁴ A ppt stands for 'part per trillion;' ppt-TEQ reflects the combined estimated/calculated value for PCDD/Fs.

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⁵See Attachment 1 for a description of the methodology used by the Chlorine Chemistry Division of the American Chemistry Council to calculate the 50th and 95th percentiles for dioxin-TEQs.

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⁶Intake of PCDD/F compounds is mostly via the diet.

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⁷CCC started with the 2001-2002 estimated average PCDD/F ppt-TEQ for a representative age in each CDC age grouping and projected the future body levels for each age grouping by applying conservative assumptions in a simple model. The assumptions included 1. current FDA intake levels (7 pg/kg/mo) stay constant; 2. intake has an 80% absorption rate; and 3. elimination rates decline linearly through age (half life assumption: 5 yrs for 10 yr olds; 15 years for 70 yr old). The starting data for 15 year olds are from the pooled data; data for other age groups are from CCC calculated TEQ for a representative, mid-point age in the age group.

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⁸Tolerable Daily Intake, or TDI, is the estimated amount of a contaminant, based upon scientific data and the application of uncertainty factors, in food or drinking water that can be ingested daily over a lifetime without appreciable health risk. The WHO reported, ".that occasional short-term excursions above the TDI would have no health consequences provided that the averaged intake over long periods is not exceeded." (WHO, 1998). See Attachment 2 for additional information on international recommendations for average daily intakes of dioxin-like compounds, and the conversion of those intakes to levels of PCDD/F compounds in humans.

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⁹ A "pg" is one picogram, one trillionth of a gram, also noted as 0.000000000001g. Note that one gram is approximately 0.035 ounces. Intake levels, in this case pg-TEQ, are related to the size of the person in kilograms body weight per day, also shown as kg bw/day.

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¹⁰Governmental public health agency safe exposure levels include built-in safety margins to account for variations in the human population as well as the uncertainties associated with drawing health conclusions for humans from data obtained in studies using laboratory animals. These safe exposure levels were derived from extensive reviews of health effects studies that considered relevant non-cancer end points including reproductive (e.g., sperm count declines, endometriosis), developmental (e.g., learning, cognitive), and neurological (e.g., behavioral) effects.

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¹¹EPA's Dioxin Source Inventory presents a compilation of the sources and environmental releases in the United States. The draft inventory of year 2000 data is available at: http://www.epa.gov/ncea/pdfs/dioxin/2k-update/.

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¹²EPA does not quantify dioxins from forest fires in its Dioxin Source Inventory.

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