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Petitioned Health Consultation
Public Comment Release
Dioxin Contamination in the Tittabawassee River Floodplain South of Midland, Michigan
TITTABAWASSEE RIVER
MIDLAND, MIDLAND COUNTY, MICHIGAN
EPA FACILITY ID: MID980994354
MARCH 4,2002
Public Comment Ends: May 15,2002
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service
Agency for Toxic Substances and Disease Registry Division of Health Assessment and Consultation
Atlanta, Georgia 30333
Health ConsuItation: A Note of Explanation
An ATSDR health consultation is a verbal or written response From ATSDR to a specific request for information about health risks related to a specific site, a chemical release, or the presence of hazardous material. In order to prevent or mitigate exposures, a consultation may lead to specific actions, such as restricting use of or replacing water supplies; intensifying environnlental sampling; restricting site access; or removing the contaminated nlateriai '- in addition, consultations may recornnlend additional public health actions, such as conducting health surveillance activities to evaluate exposure or trends in adverse health outcomes; conducting biological irldicators of exposure studies to assess exposure; and providing health education for health care providers and comn~unity members.
The Public Comment Period is an opportuni~y for the general public to corlllnerlt on Agency findings 01-
proposed activities for this written consultation. The purposes of the commerlt period arc to 1 ) provide the public, particularly the community associated with a site, the opportunity to comment on the public health findings, 2) evaluate whether the co~tlntunity health concerns have been adequately addressed, and 3) provide ATSDR with addition4 information.
The conclusions and reconlmendations presented in this health consultation are the resul: of site specific analyses and are not to be cited or quoted for other evaluations or health consultations.
You May Contact ATSDR TOLL FREE at 1 -888-42ATSDR
or Visit out- Home Page at: http://www.atsdr.cdc.gov
PETITIONED HEALTH CONSULTATION
PUBLIC COMMENT RELEASE
Dioxin Contamination in the Tittabawassee River Floodplain South of Midland, Michigan.
TITTABAWASSEE RNER
MIDLAND, MIDLAND COUNTY, MICHIGAN
EPA FACILITY ID: MID980994354
Prepared by:
Michigan Department of Communit)l Health Under a Cooperative Agreement with the
Agency for Toxic Substances and Disease Regis:]-y
Table of Contents
....................................................................................................................................... Summary 1
Purpose and Statement of Health Issues ............................................................................... 1
................................................................................................................................ Background 2
.................................................................................................................................... Discussion 3
Dioxin Contamination in Floodplain Soil ........................................................................... 3 ................................................................................................... Michigan Fish Advisories 5
Human Exposure Pathways ............................................................................................... 6 Denlographics ...................................................................................................................... 7 Toxicological Evaluation .................................................................................................... 7
......................................................................................... ATSDR Child I-Iealth Initiative 10 ................................................................................................................................ Co~lclusio~~s 10
.................................................................................................................... Reconul~endations 10 Public Health Action Plan .................................................................................................. 11
.......................................................................................................... Contact Information 12 .................................................................................................................................. References 13
................................................................................ ........................... Preparers of Report ..-. IS
List of Figures
................................................... Figure 1 . Tittabawassee River from Midland to Saginaw 14
Figure 2 . Phase I Sampling Locations .................................................................................. 15
Figure 3 . Phase 11 Sampling Locations ................................................................................. 16
List of Tables
Table 1 . Total Dioxin TEQ Concentrations Detected in Soil Samples Collected from the Mitigation Site .................. .- ..................................................................................... 3
Table 3- . Total Dioxin TEQ Concentrations Detected in Soil Samples Collected in the ...................... Tittabawassee River ~ l o o d ~ l a i n Upstream from the Mitigation Site 4
.................................................. Table 3 . Exposure Pathway for Dioxin-Contaminated Soil 6
Table 4 . ATSDR's Decision Framework for Sites Contaminated with Dioxin and Dioxin- ..................................................................................................... Like Compounds S
List of Attachments
Attachment A. Petition Letter to ATSDR dated May 1,2001
Attachment B. Petition Scoping Report for Dow Chemical Company Midland
Attachment C. ATSDR Letter to Petitioners for Dow Midland site dated November 2,2001
Attachment D. Dioxin and Dioxin-Like Compounds in Soil, Part 1: ATSDR Interim Policy Guideline
Attachment E. Dioxin and Dioxin-Like Compounds in Soil, Part 2: Technical Support Document for ATSDR Interim Policy Guideline
Summary
A Midland resident and two Michigan-based environmental organizations petitioned the Agency for Toxic Substances and Disease Registry (ATSDR) to conduct a public health assessment of dioxin contamination in Midland, Michigan, and adjacent communities. The present public health consultation addresses floodplain soil contamination in the Tittabawassee River watershed downstream from the city of Midland. The data necessary to determine if dioxin-contaminated floodplain soil in the Tittabawassee River watershed poses a public health risk are not available; therefore, the site poses an indeterminate public health hazard.
Dioxin was detected at concentrations exceeding the ATSDR action level at several locations in the floodplain near the confluence of the Tittabawassee and Saginaw Rivers. Additional soil sampling is necessary to deternine if nearby residential properties are similarly contaminated with dioxin.
A soil sampling study conducted by the Michigan Department of Environmental Quality (MDEQ) indicates that floodplain soil in Tittabawassee River watershed near and upstream of the confluence of the Tittabawassee and Saginaw Rivers is contaminated with dioxin. These data, along with dioxin levels detected in fish, indicate that dioxin contamination may be widespread throughout the Tittabawassee River watershed below Midland. ~dditionai soil sampling is necessary to determine the extent and severity of dioxin contamination in these areas.
The Michigan Department of Community Health (MDCH) recommends that the MDEQ implement sampling plans to determine if dioxin contamination is present in the Tittabawassee River watershed between the city of Midland and the confluence of the Tittabawassee and Saginaw Rivers. MDCH specifically recommends soil sampling at residential properties in closest proximity to previously identified areas of concern. These plans should include contingencies for potential public health actions if dioxin is detected at concentrations greater than the ATSDR action level, and a comprehensive evaluation of site-specific exposure factors if dioxin is found at concentrations greater than the ATSDR screening level. The MDCH will request ATSDR collaboration and support for health education and an Exposure Assessment for affected communities if indicated by the results of soil studies.
Purpose and Statement of Health Issues
On May 1,200 1, a Midland resident and two Michigan-based environmental organizations petitioned the federal Agency for Toxic Substances and Disease Registry (ATSDR) to conduct a public health assessment of dioxin contamination in communities adjacent to Midland, Michigan, where contamination originating from the Midland area has been "transported ... via air and water" (Attachment A). The petitioners stated that the "likely source of this contamination is the Dow Chemical Companjl" (Petitioners for the Dow Midland site 2001). The petitioners specifically noted that dioxin contamination found in fish i n the Tittabawassee River below Midland has been and continues to be chronically high.
ATSDR and the Michigan Department of Community Health (MDCH) have a cooperative agreement for conducting assessments and consultations for potential health hazards at sites of environmental contamination within the state of Michigan. On July 30,2001, MDCH staff and a representative from the ATSDR Region 5 office visited the Midland area, and toured both the Tittabawassee River floodplain and the Dow Chemical Company @ow) plant site. The MDCH completed a "Petition Scoping Report" and provided the information obtained from these activities to ATSDR on August 3 1,2001. A copy of the report is provided in Attachment B. MDCH met with the petitioners on October 3,2001 to discuss the health assessment process and to provide an opportunity for exchange of additional information.
ATSDR responded in writing (Attachment C) to the petitioners on November 2,2001, stating that, "After reviewing the public health issues and community concerns about potential dioxin contamination and the Dow Midland facility, ATSDR has found a reasonable basis to prepare public health consultations to address the concerns associated with the Dow facilityW(ATSDR 2001). MDCH has agreed to prepare these public health consultations. ATSDR will review MDCH's work and provide technical support as needed.
The present consultation addresses concerns related to dioxin contamination found in soil samples taken from the floodplain of the Tittabawassee River below Midlapd. Additional consultations for Midland and affected adjacent conlmunities that address other contaminated media may be developed in the future with the ultimate goal of providing a full multimedia, multipathway public health assessment.
Background
The Dow Chemical Company, founded in 1897, operates a chemical manufacturing plant in the city of Midland, Michigan. The Dow plant encompasses approximately 1,900 acres on the southern perimeter of the city (Figure 1). The Tittabawassee River forms the southern boundary of the plant site and flows east to the Saginaw Bay of Lake Huron.
Chemicals that have been produced at the Dow plant include: styrene, butadiene, picric acid, mustard gas, Saran Wrap, Styrofoam, Agent Orange, napalm, and various pesticides including Chlorpyrifos, Dursban and 2,4,5-trichlorophenol (2,4,5-T). Chlorophenol production began in 1915. Wastes generated from this process were initially disposed of in 600 acres of on-site waste ponds. During high flow periods in the early 1900s, wastes from these ponds would be intentionally released to the Tittabawassee River (Brandt 1997). Dow currently operates its own on-site wastewater treatment plant.
In 1986 the State of Michigan experienced a significant flood event that incapacitated the Dow wastewater treatment plant and flooded areas of the plant where soils were contaminated with dioxins. Run-off from 10 feet of floodwaters overwhelmed containment systems, overflowed dikes and entered the river (Wilkerson 1986). Untreated or partially treated chemical wastes entered the Tittabawassee River before plant operations were shut down (Schmidt 1986). Chemical odors associated with the Dow plant were noticed 7 miles downstream from the Dow plant site.
Discussion
Dioxin Contamination in Floodplain Soil
In April 2000, soil samples were collected under the direction of the Michigan Department of Environmental Quality (MDEQ) in an area near the confluence of the Tittabawassee arid Saginaw Rivers (Figure 2) as part of a wetland mitigation project (MDEQ 2001a). This project was required by the United States Army Corps of Engineers to replace the shallow water habitat that would be lost through implementation of proposed fill and containment response activities at a site of environmental contamination located downstream on the Saginaw River in Bay City.
Soil samples were collected by the responsible party to ensure that the selected Mitigation Site on the north side of the Tittabawassee River did not contain contaminant concentrations that would pose an unacceptable risk to terrestrial and aquatic organisms that would be expected to inhabit the new wetland resource. A sampling grid was established over the entire sample area and surface soil was
. cornposited from nine locations located from within each grid area. At the request of the MDEQ, two of the composite samples were randomly selected for dioxin analysis and concentrations of 1,474 and 2,199 parts per trillion (ppt) total dioxin toxicity equivalents (see box) were
Table 1. Total Dioxin Toxic Equivalent (TEQ) Concentrations Detected in Soil Samples Collected from the Mitigation Site
Range of DEQ Residential ATSDR ATSDR
Soil Samples Date TEQ Screening Action Detected Cleanup Location Sampled Criterion Level Level
(FP~) ( P P ~ ) (PP~) (PP~)
Mitigation Site April 2000 1,474 - 2,199 90 50 1,000 Composite Samples Mitigation Site Discrete Dee. 2000
338 - 7,261 90 50 1,000 Samples De Rosa et al. 1997a ; MDEQ 2000,2001a.
No immediate local source could be identified to explain the presence of the high concentrations of dioxin at the Mitigation Site. The only known upstream source of significant concentrations of dioxin is the Dow plant in the city of Midland, approximately 20 miles upstream of the Mitigation Site.
To further define the extent and level of dioxin contamination, the MDEQ developed a Phase I soil sampling prosran to achieve the follow in^:
Confirm the Mitigation Site sampling results. Identify whether other areas of the Tittabawassee River floodplain in the vicinity of the Mitigation Site contain dioxin above the MDEQ residential soil criterion of 90 ppt for dioxin.
Generate sufficient information to make determinations regarding the necessity of implementing a Phase I1 soil investigation within the Tittabawassee River floodplain.
In December 2000, MDEQ staff collected and analyzed five discrete surface soil samples from the Mitigation Site. Concentrations of dioxin ranged from 338 to 7,261 ppt total dioxin TEQs (Table 1). These data confirmed the previous composite sample results and also indicated that dioxin contamination was present throughout Mitigation Site soils at concentrations exceeding the MDEQ Residential Cleanup Criterion.
Based on the sampling results for the Mitigation Site, three upstream locations were selected to assess whether other areas of the Tittabawassee River floodplain in the near vicinity contained dioxin (Figure 2).
1. A site of environmental contamination, located 1 mile upstream along the north bank of the river.
2. A forested area within the Shiawassee National Wildlife Refuge (SNWR), located 1% miles upstream along the south bank of the river.
3. An open, upland area within the SNWR, located slightly less than 1% miles upstream along the south bank of the river.
Four discrete surface soil samples were collected near the site of environmental contamination upstream of the Mitigation Site, two were collected upstream of the site from an adjacent farm field and two downstream from an adjacent golf course. All sample results identified total dioxin TEQ concentrations above the MDEQ Residential Cleanup Criterion of 90 ppt (Table 2).
Table 2. Total Dioxin TEQ Concentrations Detected in Soil Samples Collected in the Tittabawassee River Floodplain Upstream from the Mitigation Site.
- --
Range of DEQ Residential ATSDR ATSDR
Soil Samples Date TEQ Screening Action Cleanup Location Sampled Detected Criterion Level Level ( P P ~ ) (ppt) ( P P ~ ) ( P P ~ )
Farm field May 2001 180 - 424 90 50 1,000 Golf course May 2001 2,529 - 2,588 90 50 1,000 SNWR Forested Area Ma\. 2001 90 50 1,000
< 6 inches 35 - 134 90 50 1,000 < 12 inches 57 - 1,055 90 50 1,000
ShTVR Upland Area June 200 1 90 50 1,000 0-3 inches 3-6 inches
12- 15 inches 58 - 275 90 50 1,000 De Rosa et al. 1997a : XIDEQ 2 0 0 0 , 2 0 0 1 ~
Five locations were sampled at two depths' from within the forested area of the SNWR. Sample depths varied somewhat from one location to another due to root mass, leaf litter, and other location-specific factors. Five of the 10 samples contained total dioxin TEQ concentrations above the MDEQ Residential Cleanup Criterion (Table 2).
Five locations were sampled at three depths from within the SNWR Upland Area. Samples were collected from the 0-3 inch, 3-6 inch, and 12-15 inch soil strata. .The five sampling locations were selected from the higher ground elevations found within the open upland area. Thirteen of the 15 samples contained total dioxin TEQ concentrations above the MDEQ Residential Cleanup Criterion (Table 2).
Based upon the soil sampling results described above, the MDEQ proposed a Phase II sampling plan in October 2001 (MDEQ 2001b). Phase 11 soil samples would be collected from three locations within the 12mile stretch of the Tittabawassee River located between the city of Freeland and Center Road in Saginaw Township (Figure 3). The selected sampling locations are Freeland Festival Park, Imerman Park, and West Michigan Park. The Freeland Festival Park is located approximately 7 miles downstream of the city of Midland and is operated by the community of Tittabawassee Township. Imerman Park is located 4% miles downstream of the Freeland Festival Park. Irnerman Park is a large, heavily utilized park that is operated by Saginaw County. West Michigan Park is operated by the community of Saginaw Township and is located just over 6 miles downstream of he rman Park and approximately 4 miles upstream of the confluence of the Tittabawassee and Saginaw Rivers. The objectives of the Phase II sampling program are to:
Identify whether dioxin has come to be located throughout the Tittabawassee River floodplain in Saginaw County.
Identify whether dioxin contamination in the Tittabawassee River floodplain soil located within Saginaw County is consistently above the MDEQ Residential Cleanup Criterion.
Identify if dioxin contamination found in floodplain soil varies between upstream and downstream locations.
a Observe dioxin distribution with respect to soil depth.
Begin to make determinations regarding the source or sources for the observed dioxin concentrations.
Make determinations regarding the need to implement a Phase III investigation and assessment program for residential properties within the Tittabawassee River floodplain.
The Phase I1 sampling plan has not been implemented to date. No additional information concerning dioxin concentrations in the Tittabawassee River floodplain is available at this time.
Michigan Fish Advisories The Tittabawassee River flows southeast from Midland to the confluence of the Saginaw and Shiai~assee Rivers near the Mitigation Site. From there, the Saginaw River flows northeast to the Saginaw Bay of Lake Huron. The MDCH has issued fish advisories for the Tittabawassee River below Midland based on detected levels of dioxins and polychlorinated biphenyls (PCBs). The advisories recommend no consumption of carp, channel catfish, or ivhite bass, and limited
consumption of smallmouth bass and all other species (one meal per week for the general population and one meal per month for children and women of childbearing age). Similar advisories have been issued for the Saginaw River. Advisories for the Saginaw Bay recommend no consumption of carp and channel catfish based on detected dioxin levels. The advisory for .Lake Huron, based on detected dioxin levels, recommends that women of childbearing age and children limit consumption of rainbow and steelhead trout to one meal per month, smaller whitefish (less than 18 inches in length) to one meal per week, and recommends no consumption of larger whitefish (MDCH 2001).
Human Exposure Pathways To determine whether people are or could be exposed to contaminants associated with a property, ATSDR and MDCH evaluate the environmental and human components that lead to human exposure. An exposure pathway contains five major elements: 1) a source of contamination, 2) contaminant transport through an environmental medium, 3) a point of exposure, 4) a route of human exposure, and 5) a receptor population. An exposure pathway is considered a complete pathway if there is evidence that all five of these elements are, have been, or will be present at the property.
Table 3. Exposure Pathway for Dioxin-Contaminated Soil in the Tittabawassee River Floodplain
Chemicals Exposure Exposure !hurce Transport and of Concern point Exposed
Route Time Status
Population Frame Media Residents Past Complete Soil in
The Dow Deposition of river residential Incidental in the
Chlorinated yards. farm ingestion, Chemical sediments in the Dioxins Titfabawassee Current Complete fields, and Dermal contact, Floodplain, Company, Tittabawassee
Midland River Floodplain and Furan' public Inhalation farmers, recreational Future Complete
access sites visitors
The MDEQ Phase I sampling program has conclusively shown that elevated levels of total dioxin TEQ concentrations are present in the Tittabawassee River floodplain near the confluence with the Saginaw River. Human use of the floodplain increases upstream of the Phase I sampling area. Numerous residential properties a r i located within the floodplain, the majority located in the city of Shields and in Saginaw Township, but also scattered along the stretch of the river. Some agricultural operations are also located within the floodplain and as are several public parks.
The likely source of these contaminants is chemical manufacturing activities at the Dow plant site in Midland. The likely mechanism of transport is deposition of contaminated river sediments in the Tittabawassee River floodplain. People living within the floodplain, farmers, and recreation users of the Tittabawassee River could be exposed to dioxins and furans in floodplain soil through incidental ingestion, direct dermal contact, and inhalation of soil and dust. Chlorinated dioxins and furans are very persistent in soil, therefore, exposure is likely to have occurred in the past and will continue in the absence of any remedial action.
Demographics Human use of the Tittabawassee River floodplain increases upstream of the Phase I sample area. Numerous residential properties are located within the floodpkn, the majority being within the communities of Shields and Saginaw Township. Of particular concern are approximately 12 homes located adjacent to the river less than half a mile upstream from the Mitigation Site where total dioxin TEQs were detected at concentrations up to 7,261 ppt. Agricultural operations also occur within the floodpIain as well as a variety of public recreational facilities including parks, boat launches and public access sites.
Toxicolopical Evaluation
Health Effects Dioxins are a group of 210 chlorinated chemicals with similar structures and chemical properties. This group of chemicals, which includes chlorinated dioxins, furans, and some polychlorinated biphenyls, is often referred to collectively as simply "dioxins" or "dioxin-like compounds." When found in the environment, dioxins are usually a mixture of several of these chemicals. Dioxins are not intentionally produced and have no known use. Not all dioxins have the same toxicity or ability to cause illness and adverse health effects. However, it is assumed that dioxins and dioxin-like compounds cause advene health effects through a similar biological mechanism of action. Further, the available science indicates that the health effects resulting from exposure to multiple dioxin-like compounds are additive, meaning that the health effects are greater than would be expected for a single compound.
The most toxic chemical in the group is 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Toxic equivalency factors have been developed to compare the relative toxicity of other dioxins and dioxin-like compounds to that of 2,3,7,8-TCDD. The levels of other dioxin-like compounds measured in the environment are multiplied by a TEF to produce a 2,3,7,8-TCDD toxic equivalent or TEQ concentration. The resulting TEQs for all dioxin-like compounds measured in a sample are then added together to determine the total dioxin TEQ concentration for that sample.
People who have been exposed to high levels of dioxins have developed chloracne, a skin disease with severe acne-like pimples. Chioracne can persist for years, sometimes clearing only to recur several years later. Changes in blood and urine that may indicate liver damage have also been seen in some people. Exposure to high concentrations of dioxins may cause long-term alterations in glucose (blood sugar) metabolism and slight changes in hormone levels (ATSDR 1998).
Exposure to low levels of dioxins in study animals has resulted in a wide variety of adverse health effects, such as cancer, liver damage, and disruption of the endocrine system. In many species of animals, dioxins weaken the immune system and cause a decrease in the system's ability to fight infection. In other animal studies, exposure to dioxins has caused reproductive damage and birth defects. Some animal species, including monkeys, exposed to dioxins during pregnancy had miscarriages. The offspring of animals exposed to dioxins during pregnancy often had birth defects including skeletal deformities. kidney defects, weakened immune rssy onscs, and neurodeveloprnental effects (ATSDR 1998).
It is not known whether people exposed to low levels of dioxins will experience the same health effects seen in animal studies. However, based on the available information, dioxins are believed to have the potential to cause a wide range of adverse effects in humans, including cancer. The U.S. Environmental Protection Agency (EPA) (EPA 2000) has characterized the mixture of dioxins to which people are commonly exposed as "likely h u m carcinogens." The EPA has also characterized 2,3,7,8-TCDD as a "human carcinogen" (EPA 2000). The U.S. Department of Health and Human Services, National Toxicology Program 9& Report on Carcinogens (NTP 2001) lists 2,3,7,8-TCDD as a substance "know12 to be a human carcinogen."
ATSDR Interim Guidance Because of the potential for adverse health effects in human populations exposed to environmental levels of dioxins, the ATSDR has developed interim policy guidelines to assist health assessors in identifying soil concentrations of potential concern (Attachments D and E). The guidelines recommend the tiered approach shown in the table below to evaluate dioxin concentrations in soil.
Table 4. ATSDR's Decision Framework for Sites Contaminated with Dioxin and
5 50 ppt TEQs Health effects are unlikely and further evaluation is not .
necessary, unless there are community health concerns.
Dioxin-Like Compounds.
> 50 ppt but < 1,000 ppt TEQs Evaluation of site-specific factors, such as
Bioavailability Ingestion rates Pathway analysis Soil cover Climate Other contaminants Community concerns Demogiaphics Background exposure
Screening Level
2 1,000 ppt TEQs Potential public health actions considemd, such as
Surveillance Research Health studies Community education Exposure investigations
+Evaluation Level. . Action Level
(De Rosa et al. 1997a)
The screening level of 50 ppt total dioxin TEQ is the environmental media evaluation guide (EMEG) for 2,3,7,8-TCDD. The EMEG was developed from the ATSDR minimum risk level (MRL) based on neurodevelopmental effects observed in the offspring of female rhesus monkeys exposed during pregnancy (ATSDR 1998). EMEGs are very conservative and protective values. Generally, if soil concentrations do not exceed the EMEG, ATSDR assumes that exposure is not likely to result in adverse health effects. However, if soil concentrations exceed the EMEG, this does not mean that adverse human health effects will always occur. Instead, soil concentrations greater than 50 ppt total dioxin TEQ indicate further site-specific evaluation is necessary (De Rosz. et al. 1997a).
The action level of 1,000 ppt TEQ is a concentration of dioxin in soil at which various actions may be considered to prevent or limit exposure. The action level is based on the 1984 analysis by Kimbrough et al. of the carcinogenic potential of 2,3,7,8-TCDD. ATSDR recommends that the action level for soil be used in full consideration of site-specific factors that may affect total exposure to dioxins through all media and exposure pathways (De Rosa et al. 1997b).
ATSDR recommends that the action level be compared to the "maximum concentrations identified at the site" (De Rosa et al. 1997b). Total dioxin TEQ concentrations greater than 1,000 ppt have been detected at several locations in the Tittabawassee River floodplain including: the Mitigation Site (up to 7,261 ppt), an upstream golf course (up to 2,588 ppt), and the forested area of the SNWR (up to 1,055 ppt).
Soil concentrations of dioxin TEQs that fall between the screening level and the action level warrant further site-specific study @e Rosa et al. 1997b). Many factors, such as those shown in the table above, can affect how much dioxin people are exposed to, how much is absorbed into the body, and whether or not adverse health effects will result. All of the soil samples collected from the Mitigation Site, the upstream golf course and farm field, the upland area of the S M , and some of the samples from the SNWR forested area fall within 50 and 1,000 ppt.
. . Background Ex~osure to Dioxins An important.consideration when evaluating dioxin levels in soil is the level of exposure from all sources of dioxin, or the "background exposure." People c k be exposed to dioxins from many sources other than contaminated soil. The general population is mainly exposed to dioxins through their diet by eating plants and animals that contain dioxins. People that live near or work at hazardous waste sites containing dioxins, waste incinerators, or manufacturing facilities that produce dioxins as a by-product may have additional dioxin exposures beyond their diet. When people are exposed to and absorb dioxins, they are stored in fatty body tissues where they may persist for months or years. The half-life (the time needed for the body to rid itself of half the contaminants absorbed) for dioxins in humans is 5 to .14 years. Because they remain for a long time, dioxins accumulate in the body and can cause health effects long after exposures have ended. The amount of dioxins accumulated over time is referred to as the "body burden." The best available science suggests that body burden levels of dioxins are closely associated with the likelihood of health effects. Therefore, many scientists recommend comparing dioxin body burden levels in at-risk populations to those associated with health effects observed in animal and human studies (EPA 2000, De Rosa et al. 1997b).
Because people may be exposed to dioxins from a variety of sources, and because all these exposures contribute to the body burden of dioxin accumulated over time, ATSDR recommends evaluation of the contribution of soil exposures tb total exposures from all sources (De Rosa et al. 1997b). Evaluation of soil exposures would require sufficient knowledge of dioxin concentrations in soil, bioavailability of dioxin in site soils, and human behaviors that can affect exposures. Additionally, evaluation of all other sources of dioxin exposure would be required to evaluate the incremental contribution of soil exposures to the total body burden of dioxins in the at-risk population. This information is not currently available for residents, farmers, and recreational users of the Tittabawassee River floodplain area.
ATSDR Child Health Initiative Children may be at greater risk than adults from certain kinds of exposure to hazardous substances at sites of environmental contamination. They engage in activities such as playing outdoors and hand-to-mouth behaviors that increase their exposure to hazardous substances. They are shorter than adults, which means they breathe dust, soil, and vapors close to the ground. Their lower body weight and higher intake rate result in a greater dose of hazardous substance per unit of body weight. The developing body systems of children can sustain permanent damage if toxic exposures are high enough during critical growth stages. PrenataI exposures and those that occur in the first few years of life are more likely to cause permanent damage.
Fetuses, infants, and children may be especially sensitive to dioxin exposure because of their rapid growth and development. In animal studies, exposure to dioxin has caused reproductive damage and birth defects. Some animal species exposed to dioxins during pregnancy had miscarriages. The offspring of animals exposed to dioxins during pregnancy often had birth defects including skeletal deformities, kidney defects, weakened immune responses, and neurodevelopmental effects (ATSDR 1998).
Conclusions
The data necessary to determine if floodplain soil throughout'the Tittabawassee River floodplain poses a public health risk are not available, therefore the site poses an indeterminate public health hazard. ATSDR classifies sites of environmental contamination into the indeterminate category when the data to make a final decision are lacking.
The levels of total dioxin TEQs detected at concentrations exceeding the ATSDR action level at the Mitigation Site (7,261 ppt), the golf course (2,588 ppt), and some areas of the SNWR (1,055 ppt) would pose an urgent public health hazard if people were routinely exposed to soil at these locations. The level of exposure on these properties is currently not known. In addition, soil sampling is necessary to determine if nearby residential properties are contaminated with dioxin.
The results of the MDEQ Phase I sampling study indicate that floodplain soil samples collected from the confluence of the Tittabawassee and Saginaw Rivers at the Mitigation Site, the upstream golf course and farm field, and the forested and upland areas of the SNWR are contaminated with dioxin. These data, along with dioxin levels detected in fish, indicate that dioxin contamination may be widespread throughout the Tittabawassee River watershed below Midland. Additional soil sampling is necessary to determine the extent and severity of dioxin contamination.
Recommendations
'3 Implement the MDEQ Phase I1 soil-sampling plan to determine if dioxin contamination is present in floodplain soil in the Tittabawassee River watershed between the Phase I sampling locations and the city of iMidiand.
Design and implement a soil-sampling plan for the residential properties adjacent to the Tittabawassee River and in closest proximity to the Mitigation Site and other identified areas of concern. The plan should include contingencies for potential public health actions if total dioxin TEGs are detected at these properties at concentrations greater than the ATSDR action level, consistent with evaluation of site-specific exposure factors.
@ Allow the sampling plans for the residential areas to be reviewed and commented upon by MDCH, ATSDR, and U.S. EPA prior to finalization and implementation. Feedback from MDCH and ATSDR will be provided to assess whether the sampling plan will be adequate to collect the information necessary to better characterize the public health implications.
Design a comprehensive evaluation of site-specific exposure factors for residents of the properties in closest proximity to the Mitigation Site and any other areas of concern identified in the Phase I and II studies including biological sample analysis if feasible. Implement the exposure evaluation if total dioxin TEQs are detected at these properties at concentrations greater than the ATSDR screening level.
Design and implement a sampling plan to address residential properties throughout the Tittabawassee River watershed contingent upon the results of the Phase II soil sampling study.
Public Health Action Plan
* The MDEQ should implement the Phase 11 sampling plan for the Tittabawassee River watershed, and design and implement a sampling plan for at-risk residential properties, including contingencies for potential public health actions if necessary, consistent with evaluation of site-specific exposure factors.
* The MDEQ should implement additional soil studies as indicated by the results of Phase I1 sampling.
The MDCH will request ATSDR collaboration and support for health education and an exposure assessment for the affected communities if soil studies indicate an evaluation of site-specific exposure factors is necessary to determine the level of public health hazard posed by dioxin contamination in the watersheds.
The MDCH in cooperation with the appropriate local health departments will undertake health educa~ion activities to define and respond to the information needs of the affected communities.
The MDCH i n cooperation with the appropriate local health departments will be available to consult on the appropriateness and efficacy of future remedial actions.
Contact Information
If any citizen has additional information or health concerns regarding the Tittabawassee River Floodplain consultation or the Dow Chemical Company Midland petitioned health assessment, please contact the Michigan Department of Community Health, Division of Environmental and Occupational Epidemiology, at 1-800-648-6942.
References
ATSDR (Agency for Toxic Substances and Disease Registry). 1998. Toxicological Profile for Chlorinated Dibenzo-p-Dioxins. December 1998.
ATSDR (Agency for Toxic Substances and Disease Registry). 2001. Letter to Petitioners for Dow Midland site dated November 2,2001.
Brandt, E. N., 1997. Growth Company: Dow Chemical's First Century, Michigan State University Press, East Lansing, MI.
De Rosa, Christopher T. et al. 1997a. Dioxin and Dioxin-Like Compounds in Soil, Part 1: ATSDR Interim Policy Guideline. Toxicology and Industrial Health, Vol. 13, No. 6, 1997. pages 759-768.
De Rosa, Christopher T. et al. 1997b. Dioxin and Dioxin-Like Compounds in Soil, Part 2: Technical Support Document for ATSDR Interim Policy Guideline. Toxicology and Industrial Health, Vol. 13, No. 6, 1997. pages 769-804.
EPA (United. States Environmental Protection Agency). 2000. Draft Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. September 2000.
MDCH (Michigan Department of Community Health). 2001. Michigan 2001 Fish Advisory.
MDEQ (Michigan Department of Environmental Quality). 2000. Part 201 Generic Cleanup Criteria Tables. June 7,2000.
MDEQ (Michigan Department of Environmental Quality), Environmental Response Division. 2001a. Unpublished: Greenpoint - Tittabawassee River Dioxin Study Area, Phase I Sampling Study Report. October 2001.
MDEQ (Michigan Department of Environmental Quality), Environmental Response Division. 2001b. Unpublished: Greenpoint - Tittabawassee River Dioxin Study Area Phase II Sampling Progam. October 200 1.
NTP (National Toxicology Program). 2001. 9th ~ e ~ o r t on Carcinogens. U.S. Department of Health and Human Services. Public Health Service. January 200 1.
Petitioners for Dow Midland site. 2001. Petition letter to ATSDR. May 1, 2001
Schmidt, Wayne. Pollution rising to dangerous levels, experts say. Eay City Times. September 13, 1986.
U. S. Census Bureau (United States Census Bureau). 1990. Census of Population and Housing.
Wilkerson, Isabel. 1986. Tainting of Fish Feared After Michigan Floods. The New York Times. September 23, 1986.
P H A S E I1 S A M P L I N G L O C A T I O N S
Preparers of Report
Michigan Department of Community Health
Linda D. Larsen, Ph.D. Toxicologist, Principal Investigator
Robin Freer, M.S. Geographic Information System Specialist
ATSDR Regional Representative
Mark Johnson Office of Regional Operations, .Region V
ATSDR Technical Project Officer
Alan W. Yarbrough Division of Health Assessment and Consultation
Superfund Site Assessment Branch
Attachment A
Petition Letter to ATSDR dated May 1, 2001
May 1,2001
Dr. H m y Falk Assistant Administrator Agcncy fbr Toxic Substanus and Disease Registry (ATSDR) 1600 Clifton Road, NE ( E 2 S ) l - 9 ~ fff14 s&oL/ Atlanta, GA 30333 ' f
Dear Dr. Falk,
W e are writjag on behalf of our organi;ations to petition f ~ r a puXic health assessment of the population of Midland, Michigan, becrrusc of chronic and sexious dioxin contamination. Thc primary .
sourcc of this-qntamiuation is the Dow Chemical Company. -- Our petition is prompted by the following fk&, which have emerged ovcr thc last two dccades:
+ Results of soil sampling by rhe state Department of Environmental QuaIity (DBQ) in Midland have been surprising, and alarming- Although the state's residcntid cleanup criteria for djoxins in soiI i s 90 pa-rts per trillion, of 37 samples taken in the comnunity in 1996, almost a third had dioxin above that level. The areas that exceeded the rcsidmtial cleanup standard included two elementary schools, an intrrmediate school, a high school and parks. These are areas where the public hns access and children play. After release OF these rd ts , 'DEQ promised to mampIe community area and determine potentid human a p o w e s -
* Instead of carrying through on its commitment, DEQ agreed with Dow's suggestion to use soils inside Dow's corporate center as a c c s ~ g a t e ? ' for the c~nimunity. Lcvcls found in 1998 sampling at the corporate center ranged &om 66 to 476 parts per n-iIIion, with an werage of 136 parts pet billion One paticuitarly high dioxin .hot spot was adjacent: to a residentizl area east of the Dow facility.
PEQ and DOW still r c h c to kecp commirmen$ to characterize human exposures to dioxins and take appropriate protective actions - more than four years after the k t samphg was done.
I. There are other routes of e.qosure to dioxins in Midland. Dioxin contamination offish jll ht Titkbawaee River below -Midland is chronically high- According to the Michigan Fish Contaminant Monifon'rzg Program: ,2000 Aruluai Xeport issued by DEQ t J i s h t e r , dio;ulr! TEQ conmtrzdons exceeded the "trigger level" for fish c o w p t i o n warnings iii all 10 CTJ,~;,
collected in 1999 and Itl all I I catp coIIected since 1992, and in 2 of 5 smallmourh bsss. As a nl-ulr, the state h a t i$ t t~ed i~ advisory to warn a - ~ n s t ~ b g more thm 1 me.: PCP a ~2
for smallmouth bass from the river due to dioxin, and advises that women and cfiiidn cat no srnalhnauth basis fiom the river due to elevated levds of dioxins and PCBs.
This data is simply the latest in a long line of disclosures about dioxin contamination of the community. For exampIe, a 1985 multi-media risk asscsiiment by the U.S. Eavironmental P r o t d a A p c y pointed to birth defects and cancer data suggesting elevated h d t h dfkds in thc Midland community, noted that the highest levels of dioxin in thc nation were found in Tittabawasee River fish, and called for a comprehensive health study. To date, no such study has - ever bmn done. Fuahcr, n&a than hkin,a action to protect the public from the serious soil conknination documented in the two most recent rounds of soil testing, the Statc of Michigan has continued to engage in private discussions with Dow Chemical Company about how to manage public relations. Despite repeated requests &om our ~ r g ~ z a r i o n s for an independently- f u n d 4 swe-commissioned hsalth study md a plan to protect citizens from exposure to excessive levels of dioxins, the state has t a . no such action.
It is abundantly clear that significant levels of dioxins and other hazardous materials, including PCBs, are present in the Midland community and in adjacent communities, where contamhaxlts are transported h r n Dow via water and air. These conmiaants may be ingested through hh, consumed in other food, absorbed rhrough dermal contact with soils, and inhaled. The scicncc supporting the link between dioxins and human health effects is strong and growing. Ir: is t ime for a public health assessment by ATSDR and appmprkate protective actions by fcdaal, state and local agencia KO prevent M a exposures to dioxin and to study hcalth impacts in the c o r n m ~ t y .
Sincerely,
Attachment B
Petition Scoping Report for Dow Chemical Company Midland
Petition Scoping Report A u g u s t 31, 2001
~ i t ~ / ~ i t y / S t . a t e : Dow C h a m i c a l ~om~an~/Midlad/Michiqan Region: 5 Scoping Team:
A. Peti tionerr s C o n c e r n (s)
Dioxins, reported as total equivalent concentrations (TEQs) of 2,3,7,8-TCDD, have been detected in soil in Midland at concentrations above the Michigan Department of Environmental Quality residential cleanup criterion. Levels of dioxins detected in soil adjacent to the eastern perimeter of the Dow plant site and along a road-way (haul route) in the community exceed 1 ppb.
r Dioxins have been detected in fish taken from the Tittabawassee River. Levels detected exceed the State of Michigan trigger levels for fish consumption warnings. In 1985, the U.S. EPA noted that the highest national levels of dioxins in fish were found in the Tittabawassee River. In 1985, the U.S. EPA "called for a comprehensive health study" of dioxin exposures and the resulting health effects in the Midland community. No such comprehensive study has ever been performed.
B. B r i e f Site Background
The Dow Chemical, founded in 1897, operates a chemical manufacturing facility in the city of Midland, Michigan. The facility encompasses approximately 1900 acres on the southern perimeter of the city. The Tittabawassee River forms the southern boundary of the facility and flows east to the Saginaw Bay of Lake Huron.
Chemicals produced at the Midland plant include; styrene, butadiene, picric acid, mustard gas, Saran wrap, Styrofoam, Agent Orange, napalm, and various pesticides including Dursban and 2,4,5-T. Chlorophenol production began in 1915. Wastes generated from this process were initially disposed of in 600 acres of on-site waste ponds. During high flow periods in the early 1900rs, wastes from these ponds would be released to the Tittabawassee River. Dow currently operates it's own wastewater treatment plant on-site.
Two rotary kiln incinerators are used for treatment of liquid and solid hazardous and non-hazardous wastes generated from manufacturing activities at the facility. Ambient air dispersion modeling and monitoring indicates that the north-eastern quadrant of the city of Midland have been affected by emissions from the incinerators.
C. Key Previous Actions Related To The Site
The Dow property is currently part of the RCRA corrective action program delegated by the U.S. EPA to the MDEQ Waste Management Division. The-EPA sampled soil in the city of Midland in the 1980's and found elevated concentrations of 2,3,7,8-TCDD. The EPA recommended additional sampling in the future to monitor levels of dioxins in the community. In 1996, the MDEQ took additional soil samples from public properties such as parks and school yards and found total dioxins (TEQ) at concentrations exceeding the Michigan residential cleanup criterion for soil. The Dow plant site, it's northeastern perimeter, and a community road-way leading from the Dow plant to a landfill were also sampled. Concentrations at the plant perimeter and on the road-way excoeded 1 ppb. in 1998, as a follow-up alternative to additional community sampling, the Dow Company and the DEQ agreed co sa:.?le ~ h ? Dow Corporate Center property as a surrogate for the community. Levels of TEQs detecced at the Corporate Center ranged from 77-583 parts per trillion (ppt).
NO p u b l i c h e a l t h a s ses smen t has been c o n d u c t e d by e i t h e r t h e MDCH o r t h e ATSDR.
D. Public Health Issue (s)
Table 1. Levels of total dioxins detected i n s o i l i n the city of Midland.
Midland 1 1 1 I 1
P e r i m e t e r Road-Wa y (Haul Route) Dow Corpora t e C e n t e r Nor theas t Quadran t o f
ATSDR Action
Level for TCDD
1000
Soi l Samples Location
Nor theas t P l a n t
10 - 2663
77 - 583
22 - 598
Table 2 . Levels of total dioxins (TEQ) detected i n f i s h in the Tittabawassee River downstream of Midland.
Demographics
ATSDR Chronic
So i l EMEMG f o r
a Child in ppt
50
2000 -
The c i t y o f Midland i s t h e coun ty s e a t o f Midland County, Michigan and encompasses a n a r e a approximate1.y 28 squa re m i l e s . The p o p u l a t i o n of Midland w a s a p p r o x i m a t e l y 38,090 i n 1990. Twenty f i v e p e r c e n t of t h e p o p u l a t i o n i n 1990 were c h i l d r e n unde r t h e age of 17 y e a r s .
Range of TEQ
detected i n ppt
6 - 1068
ATSDR Chronic
S o i l EMEMG for an Adult
i n ppt
700
90
9 0
90
Date
1976 - 1980
Previous H e a l t h Studies
DEQ Cleanup
Criterion i n ppt
9 0
Range of 2,3,7,8- TCDD in ppt
3 - 695
Range o f TEQ i n PPt
NA
Data pend ing
A t t h e r e q u e s t o f t h e MDEQ A i r Q u a l i t y D i v i s i o n (AQD) and i n s u p p h r t o f t h e AQD.review of a n a p p l i c a t i o n made by t h e Dew Company f o r a n a i r q u a l i t y p e r m i t f o r a new i n c i n e r a t o r , t h e MDCH per formed a s t a t i s t i c a l a n a l y s i s o f c a n c e r i n c i d e n c e f o r z i p c o d e s 48640 and 4 8 6 4 2 , Midland County, a n d Bay County. T h i s a n a l y s i s showed t h a t t h e 1994 through 1998 a g e - a d j u s t e d i n c i d e n c e r a t e f o r a l l c a n c e r s combined i n z i p code 48640, which i n c l u d e s t h e Dow p l a n t s i t e , was s i g n i f i c a n t l y h i g h e r t h a n t h e c o r r e s p o n d i n g r a t e s f o r a l l whi te r e s i d e n t s i n Midland County, Bay County, a n d t h e S t a t e o f Michigan . I n c i d e n t r a t e s were a l s o e l e v a t e d i n t h i s z i p code f o r l u n g and p r o s t a t e c a n c e r . NO e l e v a t i o n s i n cance r r a t e s were i n d i c a t e d f o r z i p code 48642. ( s e e a t t a c h m e n t )
5 0
5 0
MDCEi Advisory Trigger i n ppt
10
Data p e n d i n g I 10
700
700
1000
1000
50 I 7 00 1000
E. Exposure Pathways
Level of Community Interest (Difficult to gauge at this time. The Michigan Environmental Council, a well-organized environmental group is one of Che petitioners. However, Midland is a corporate town and support for the company is high)
X High Large numbers of inquiries about the site/release; well attended meetings about a site/release; the involvement of national, state, and local environmental activist groups, and community groups that . are well-organized; extensive environmental, health and/or political interest and extensive national, state and local media coverage.
Pathway
Direct Contact with Soil
Fish Consumption
X Medium Involvement of the petitioner and community groups without the involvement of national, and state environmental activist groups; some national or state environmental, health and/or political interest; only local media coverage.
Contaminant and h v e l
Dioxins and Furans 6 - 2663 PPt
Dioxins and Furans
Source of .
ont tam in ant
Incinerator Emissions
Release to Surface Water
Low Involvement of the petitioner; no community, environmental, health, or political interest; no media coverage.
F. Decision Criteria
Environmental Media
Soil
Fish - , 3 .
PPt
2.1 Are the location, concentration, and toxicity of the hazardous substances, related to the petition, site, or release possibly of public health concern?
Exposure Point
soil in the city of Midland
Tittabawassee River
Exposure Route
Incidental Ingestion Derma 1 Contact Particulate Inhalation
Ingestion
Yes, levels of dioxins detected in soil in the city of Midland and in fish in the Tittabawassee fiver downstream of Midland exceed health-based comparison values. Dioxin and related compounds are believed to cause both carcinogenic and noncarcinogenic human health effects at extremely low levels of exposure.
2.2 Is there an exposed or potentially exposed population as indicated in the petition and as determined by evaluating the human exposure pathways for the hazardous substance release (s) ?
Exposed Population
Residents of Midland
Anglers and their families
Yes, dioxins are present in soil throughout the city of Midland. Moze t h m 38,000 people live in the city, 25% of which are children under the age of 17. The Tittabawassee River is a valuable State of Michigan fishery resource and is heavily utilized both by the residents of Midland and by other communities down river.
Time Frame Past
.presen
Future
past-
. Future
2 . 3 1s there a plausible relacionship between possible human e:<possrs to a role?s? cf hazardous substances and co~-i~unicy health concerns or adverse healtb. ol~tco-es?-
Yes, the U . S . EPA, the In ternat ional A g e n q f o r ~esearch on Cancer, and the National Toxicology Program have determined t h a t exposure t o dioxins is associated with elevated rates of a l l cancers combined as w e l l as several p a r t i c u l a r cancers including lung and s o f t t i s sue sarcoma. Elevated incidence rates of a l l cancers combined, lung and pros ta te cancer have been detected i n the c i t y of Midland. Additional information i s needed t o determine if exposure t o dioxins i s re la ted t o other hea l th effects i n the population of Midland and the surrounding communities.
G. Recommendation:
The scoping team recommends:
No further action Further characterization
X Public Health Consultation/SRU X Public Health Assessment
X Health Education X Exposure Investigation
"Refer as a Public Health Consultation to a toxicologist, epidemiologist or physician for determination of plausible relationship between possible human exposure to a release of hazardous substances and community health concerns or adverse health outcomes, if relationships are not readily available utilizing the tox. profiles.
Referral to :
Attachment C
ATSDR Letter to Petitioners for Dow Midland site dated November 2,2001
DEPARTMENT OF HEALTH & H U M A N SERVICES Public Health Service
Agency for Toxic Substances and Disease Registry
Atlanta GA 30333
November 2,2001
In May 2001, you wrote to the Agency for Toxic Substances and Disease Registry (ATSDR), about the Dow Chemical Company, Midland, Michigan and dioxin contamination- ATSDR acknowledged your letter to be a petition for a public health assessment. The following outlines ATSDR's response to your petition.
After reviewing the public health issues and community concerns about potential dioxin contamination and the Dow Midland fkility, ATSDR has found a reasonable basis to prepare public health consultations to address the concerns associated with the Dow facility. The public health consultations will review and summarize the existing environmental and health data for dioxin concentrations in soils in the Midland community a d in fish found in commurrity streams. The co~ultajions will evaluate possible ways that people could be exposed to h&l substances, document and evaluate community health concerns, state health-based conclusions, and make recommendatiow. We believe that the health consultations will provide timely, appropriate responses to the concerns.
ATSDR maintains a cooperative agreement with the Micbigan Department of Community Health (MDCH), under which MDCH conducts public health assessments and other environmental health activities in Michigan. ATSDR has requested that MDCH complete the public health consultations and release them for public review in fiscal year 2002, which began October 1,200 1. MDCH has a talented stafT with a good track record for successfdly conducting public heaith evaluations, and they understand the needs of Michigan communities. ATSDR will review MDCH's work and provide technical support as needed. We have enclosed a fact sheet about public health consultations.
Thank you for referring your concerns to ATSDR We welcome your comments about this response and the pIanned public health consultations. If you have questions about our proposed plan of action, please contact Dr. Mark Johnson, ATSDR Senior Regional Representative, at telephone (3 12) 886-0840, or AIan Yarbrough, ATSDR Technic. Project Officer, at teIephone (404) 498-0427. Dr. Linda Larsen, MDOH, may be contacted at (5 17-335-8566). Community members may also contact ATSDR by calling our toll-free telephone number, 1-88892-ATSDR (1-888-422-8737).
Sincerely yours,
Robert C. Williams, P.E., DEE Assistant Surgeon General
Director, Division of Health Assessment and Consultation
Enclosure
CC -
Linda D. Larsen, Ph.D. blichigan Department of Community Health NOV S - 2001
El\l~llhu~u~~;!, I . ~ L ,:~,LJcI;II~LUGY DIVISION
Attachment D
Dioxin and Dioxin-Like Compounds in Soil, Part 1: ATSDR Interim Policy Guideline
_- ._- -, I. - U.S. DEPARTMENT OF HEALTH AND NUMAN SERV~CES /#J-SDR
Public HealUl Service 4- .O..'a.C --I.. --..-
DIOXIN AND DIOXIN-LIKE COMPOUNDS IN SOIL, PART I: ATSDR INTERIM POLICY GUIDELME
CHRISTOPHER T. DE ROSA, DAVID BROWN,' ROSALINE DHAKA, WOODROW GARRETT, HUGH HANSEN, JAMES HOLLER, DENNIS JONES,
DENISE JORDAN-IZAGUIRRE, RALPH O'CONNOR, HANA POHL, AND CHARLES XINTARAS
Agency for Toxic Substances and Disease Registry US. Department of Health and Human Services
Atlanta, Georgia
PURPOSE
The Agency for Toxic Substances and Disease Registry (ATSDR) has adopted this interim policy auideline to assess the public health implications of dioxin and dioxin-like compounds in residential s
soils near or on hazardous waste sites. These compounds include
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) .Related chlorinated dibenzo-p-dioxins (CDDs) Chlorinated dibenzofurans (CDFs) - Other suuccurally related groups of chemicaIs from the family of halogenated aromatic hydrocarbons.
These substances are defined under the Comprehensive Environmental Response, Compensation. and Liability Act of 1980 (CERCLA). as amended. commonly known as Superfund, This interim policy guideline will provide a clear and consistent understanding of ATSDR's current approaches and j u d p e n t s resarding hazards posed by the presence of TCDD and in less toxic dioxin-like congeners, the CDDs and CDFs, in residential soils. Likely users of this interim policy guid,eline include:
a ATSDR and staie-based health assessors ATSDR partners including relevant federal, state, and local health and environmen~l entities Concerned community sroups.
L
I. Address 311 correspondence to: Christopher T. De Rosa. Ph.D., Director. Division of Toxicolo:y. Agency for Toxic Substances and Disease Rc:i>try. hfailstop E-79, 1600 Clifion Road. NE. Atlanta. G.3\ 30333. Tei.:(404)629-6300. Fas:(40?)639-63 15. E-~nail:[email protected]\,.
7.Abbreuiatious: ATSDR.A:cncy for Toxic Subsrclnces and Diseasc Regist?: CDDs. chlonnatrd dibcnro- p-dioxins: CDFs. chlorinated dibenzofuranr;: CERCLA. Comprehensive En\.ironrnencal Responss. Cornpensarion, and Liabiliry 4.ct of 1980: EhIEG. cn\.ironmcnial media evaluarion guide: FDA. U.S. Fcod and Drus Administation: I\\.?!?!-. minimal risk l?\.?i:?CDD. 7.3.7.8-rerrachlorodibenzo-p-dio.\;in:TEF. toxiii:! equi\.slrncy facior. T E Q j . io,:.ici:)- eql~i \ -~!cni ;
3. Ksy \voids: diosin. h c n m exposure. ~ j k ajicjsntsnc. soil Ievrls. TCDD. TEQs. 4. Nore: '65 Bulkley .4\'snue Xorth. h'esc?nn. CT 06S80. 5 . Rrprinrsd from rhs Jo!in:cl of Clecn Trci :~~nlog~: E ~ r r . i r n ~ ~ r ~ l e ~ i r a l To.i-icolc>g?.n,id Occ~c~~(7iinnc:l;Lf.ledic~~:,~,
h(. 5. Ho. 7. 1997.
- ! o s i c o l o ~ . and Indusrr in l Health. Val. 13. No. 6. pp. 359-76s Cop! righr Q 1997 Princeton Scientific Publ ishing Co.. Inc.
iSSS: u:-tS-1237
1:
INTERIM POLICY GUIDELINE
This interim policy guideline is based on a current understanding of rhe toxicology and epidemiology associated with TCDD and its congeners (see "Background" section) and on exposure potential when soil is the prirna~y medium of interest.
This guidance is consistent with the Dioxin and Dioxin-Like Compounds in Soil. Part 11: Technical Support Document for ATSDR Interim Policy Guideline (De Rosa et al.. 1997) and with the ATSDR Public Health Assessment Guidance Manual (ATSDR. 1992). They explain how to use comparison values to select contaminants for further evaluation and then draw conclusions abour ttie public health implications of the contaminants. Assessments of public health implications are based on considerations of site-specific factors affecting the extent and characteristics of exposure and on the toxicology and epidemiology of the compounds selected for evaluation.
This guidance for dioxin and dioxin-like compounds is unique because of the potency of TCDD itself, and the need to consider the total potency of all dioxin and dioxin-like compounds detected in soil. The toxicity of a dioxin-like compound is commonly referred to in terms of its dioxin toxicity equivalency Factor (TEF). See "Back~round" section for further information.
These guidelines and procedures apply to human exposure for direct ingestion of soils contaminated with dioxin and dioxin-like compounds in residential areas and may not be appropiiate for other exposure scenarios. The guidance will be evaluated in view of new data that may become available. The science basis for the guidance is outlined in the "Back, uround'. discussion.
Steu 1. Screenin? for contaminants of concern
Review soil sampling data and compare levels against dioxin comparison values (environmentai media evaluation guide or EMEG for children) that are not site-specific. If one or more soil samplin? values exceed the screening value of 50 parts per trillion (ppt) of toxicity equivalents (TEQs), funher site-specific evaluatians are needed as described next and in Table I.
If samples exceed this screening value, then ATSDR generally assumes that further evaluation is required. Howeuer, even if samples are below these values, ATSDR policy states that i t may still be necessary to conduct a more detailed site-specific etfaluation under the follou~ing conditions:
conrnunityhealthconcems hea!th assessor's concerns about other combinations of contaminants.
Toricolocp~ arid I~~dtrsrr-ial Hecrlrh, Vol. 1.3, No. 6. 1997 76 1
Ster, 2. Evaluatinc ~otential exposure ~athwavs
Further evaluation includes the most critical aspect of health hazard evaluations. char is. the determination of likelihood, extent, and duration of exposure of populations. Thus. the health assessor uses the following to determine the existence of a potential or completed exposure pathway-past, present, or future:
site visits and observations . * detailed review of data packages for land use scenarios, contaminant locations, and site
locations
evaluation of receptor populations and potential points of contact.
If a completed or potentially completedexposure pathway is identified. then the extent of exposure and public health implications are further evaluated.
Site-specific exposure scenarios based on site-specific factors are evaluated in conjunction with relevant toxicologic. epidemiologic. and medical information. This involves assessing site-specific information about the likelihood, frequency, routes. and levels of exposure to contaminants. and the populations that are likely to be exposed.
Where estimated levels of exposure in soil fall in the range of greater than 50 ppt to less than I part per billion (ppb) TEQs CTable 1). a weight-of-evidence approach is recommended to evaluate the exposure and the public health implications of the exposure.
Health assessors must ask the following questions:
How extensive is the contamination?
Is the contamination isolated or widespread?
Is the contamination in surface soils or areas easily accessible to children or adults? Is it i n areas with no ve~etation or in any orher areas?
At dlis site, how often (daily, weekly, monthly) and for what length of time (months. years, Iifetimes) would exposures be likely to occur?
Many of these esrima~es depend on professional judgment and experience regardins the likelihood of exposures from soils in different kinds of sites. For further information on the evaluation process see ATSDR ( 1 992).
Irlrc~prernfion ofHenlr11 Giridrrnce Iblrres The ~ o l i c y incorporates information on exposure potential from residential soils and residential exposure scenafios. Ir should be noted that the levels (in TEQs) I 5 0 ppt (0.05 ppb). > 0.05 ppb bet < I ~ p b . 2nd 2 I ppb in r ~ s i d r n c i a l soils are suidance values and should nar bz consrned to
indicate rnat acxal h e a l t h effects will occur. The policy provides a protective framework for
ei-z!uating :he healrh irnplicarions of exposures to dioxin and dioxin-like compounds in resideniizi
soi!j on a jirr-specific basis.
762 De Rosn et al.
TABLE 1. ATSDR's Decision Framework for Sites Contaminated with Dioxin a n d Dioxin-Like Compounds
Because the toxicity of dioxin and dioxin-like compounds is assumed to be eIaborated through a common receptor-mediated mechanism, levels greater than 50 ppt (0.05 ppb) TEQs* are used to determine whether further site-specific evaluation for dioxins is to occur based on the maximum soil concentrations identified at the site. A level of 1 ppb TEQs is used to determine the poten~ial need for public health actions on a site-specific basis and on the basis of adequate sampling and measured or projected human exposure-past, present, or future-as determined by the health assessor.
SCREENING LEVEL EVALUATION LEVELS ACTION LEVEL" 5 50 ppt (0.05 ppb) TEQs > 0.05 ppb but < I ppb TEQs 2 1 ppb TEQs The EMEG for TCDD is Evaluation of site-specific Potential public health actions 50 PPr factors, such as: considered, such as:
This is based on an MRL of Bioavailability I poA$day for TCDD * Ingestion rates (ATSDR, 1989). Pathway analysis
Surveillance Research
Health studies
For screening purposes - Soil cover Community education 50 ppt TCDD is assumed to Climate Physician education be equivalent to 50 ppt TEQs Other contaminants Exposure investigations
Community concerns Derno,pphics .
Background Exposures 'The toxicity equivalent W Q ) of TCDD is calculated by multiplying the exposure level of a particular
- - dioxin-like compound by its toxicity equivalency factor (TEF). TEFs are bas& on congener-specific data and the assumption that Ah receptor-mediated toxicity of dioxin-lih chemicals is additive. The TEF scheme compares the relative toxicity of individual dioxindike compounds to that of TCDD. which is the most toxic halogenated arpmatic hydrocarbon.
'-A concentration of chemicals at which consideration of action to interdict/prevent exposure occurs. such as surveillance, research. health studies. community education. physician educa~ion. or exposure insesdgations. Altemad\.ely. based on the evaluation by the health assessor. none of these actions may be
Step 3. Definin? pubIic health im~lications/actions
Where exposures to concentrations in residential. soirs exceeding 1 ppb TEQs are significant, ATSDR healch assessors should consider judging the site a public health hazard and consider site-specific public health recomrnendacions/actions to prevent or interdicr exposures (Table 1).
BACKGROUND FOR wTERIRI POLICI' GUIDELINE
Djosirl and Diosirz-Like Conzporrrzds Dioxin and dioxin-like compounds are structurally related goups of chemicals from [he family of halozenated aromatic hydrocarbons. Dependinp on h e nurnbeiof chlorine-substituted positions. there are several congeners in each p u p . The most toxic and the most studied conZener is
TCDD.
TEFs were developed to compare rhe relative toxicity of individual dioxin-like cot~lpounds to that of TCDD (Tables 2 and 3). This comparison is based on the assumption thal dioxin and dioxin-like compounds act throush the same mechanism of action. TheTEF for TCDD is defined as one. whereas TEF values for all other dioxin-like compounds are less than one- TEQs are used to assess the risk of exposure to a mixture of dioxin-like compounds. A TEQ is defined as the product of the concentration. Ci. of an individual "dioxin-like compound" in a complex environmental mixture and the correspondins TCDD TEFi for that compound. The total TEQs is the sum of [he TEQs for each of the congeners in a ziven mixture:
Total TEQs = (ci TEFi ) i=I
Adverse Healrl~ Effecfs
Studies in animals demonsu-aced a wide range of effects associated with dioxin exposure including death, cancer, and wasting. as well as hepatic, irnrnunoIo,oic, neurologic, reproductive, and developmental effects. In contrast to laboratory results, direct exposure information is not available in human studies; therefore, body burden is used as a surrogate. Body burdens in some animal studies were in the same range as those associated with adverse health effects in human studies. For more informarion, see Technical Support Document for ATSDR Interim Policy Guideline: Dioxin and Dioxin-Like Compounds in Soil (ATSDR, 1997). These results underscore the need for research to elucidate the toxicity at low doses to human populations and to evaluate exposures in at-risk populations (see Apperldix 1) in view of total body burdens of dioxin and dioxin-like compounds.
TABLE 1. Recommended Toxicity Equivalency Factors (TEFs) for CDDs and CDFs
EPA cumen[ EPA current CDDs recommended values CDFs recommended values rnonoCDDs 0 monoCDFs 0 diCDDs 0 diCDFs 0 triCDDs 0 triCDFs 0 2.3,7,S-TCDD I 2.3.7.8-cemCDF 0.1 other tetraCDDs 0 orher tetraCDFs 0 2.3,7.8-pentaCDDa 0.5 1.2.3.7.8-pencaCDF 0.05 ocher pencaCDDs 0 2.3.4.7.8-pentaCDF 0.5
other pentaCDFs 0 . 2.3.7.8-hexaCDDS 0.1 2.3.7,s-hexaCDP 0.1 other hexaCDDs 0 orher hexaCDFs 0 2,3,7,8-heptaCDDX 0.0 l 2.3.7.S-hcptaCDP 0.0 1 o ~ h r r hepraCDDs 0 other hepraCDFs 0 ocraCDD 0.00 1 ocraCDF 0.00 1 'Any isomer char conrains chlorine in the 2.3.7.8-positions CDDs = chlonnarzd dibenzo-p-dioxins: CDFs = chlorinated dibenzofurnas: TCDD = reu~chlorodibenzo-p-dioxins. S-crce. derivs:! from EPA (19S9).
TABLE 3. Recommended Toxicity Equivalency Factors (TEFsf for Diosin-Like PCBs
WHO proposed WHO proposed PCB interim value9 PCB interim valuesa
3.Y.4.4'-TCB 0.0005 2.3.3'4.4'5-HxCB 0.0005 3.3'.4.4',5-PeCB 0. I 2.2.3'.4.4',5'-HxCB 0.0005 3.3'.4.4'.5.5'-HxCB 0.0 1 2.3'.4.4'.55'-HxCB 0.0000 1 2.3.Y.4.4'-PeCB 0.0001 2.3.3'.4.4'5$'-HpCB 0.000 1 2.3.4,4'.5-PeCB 0.0005 2,2'.3.3:4.a'5-HpCB 0.000 1 2.3',4,4'5-PeCB 0.000 1 2.2'$,4.4'5.5'-HpCB 0.0000 1 2'.3.4.4'.4-P~CB 0.000 1 'Interim values proposed by World Health Orsanizacion/Intema~onal Programme on Chemical Safety PCB = polychlorinated biphenyl: TCB = terrachlorinated biphenyl: PeCB = pencachlorinated biphenyl: HxCB = hexachlorinaced biphenyl: HpCB = heptachiorinated biphenyl Source: derived from Ahiborg et al. (1994).
Screening Level for Diosirz and Diosin-Like Comporrnds in Soil While identifyin2 levels of potential concern to human health, ATSDR considers a spectrum of contaminant concentrations. In general, screening levels are concenmtions used to select contaminants of concern at hazardous waste sites that are taken forward in the health assessment process for further evaluation (screenins levels are aiso called comparison values see Appendix I - Glossary).
A minima1 risk level (MRL) is an estimate of the daily human exposure to a hazardous substance that is Iikely to be without appreciable risk of adverse noncancer health effects oirer a specified duration and route of expQsure. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and others to identify contaminants and .
potential healch e f f e c ~ that may be of concern at hazardous waste sites. The intermediate-duration oral MRL of 1 picogam/kilogram/day or pz_/g/day for TCDD (ATSDR, 1989) was based on reproductive effects in rats. The intermediateduration oral MRL was also adopted as a chronic oral MRL. Based on this value. an EMEG of 50 ppt (0.05 ppb) TCDD, which is equivalent to 50 ppt (0.05 ppb) TEQs, was derived for exposure from contaminated soil. Uncenainty factors of 1000 (total) were used in the calculations of the MRL (for further details, see Appendix 3 of the Technical Support Documenr). Based on a review of more recent literature, ATSDR scientists conclude char the MRL of 1 pgkaJday is approximately two orders of rnzgnitude below the noncancer health effect levels observed in recent studies. This is also true for cancer effect levels.
El~airtariotr Levels for Diorirl and Dio.\-il~-Like Co~~zpourzds irr Soi/ El.olliaiioi~ ievelr are concenrrations > 50 ppt (0.05 ppb) bur < 1 ppb TEQs at yhich sire-specific. factors, includin,a. but not limited to, bioavailability, insescion rates, pathway analysis. soil cover. climate, other contaminants. community concerns, demo~raphics. and background exposure, are considered in a deliberative process ro assess the nature and extent of conraminarion and its irnpacf on the community. Such an evaluation process may prompt further assessment at the nexr level where actions are considered. The e1:aluation levels arc to be used as a framework to guide procedures far that judsmenr process. Thus, judsments i n the evaluative phase are linked to actioils iiihs:: considsratio:l is $\.en to interventions from z ~ u b l i c healrh perspecrive.
Acfion L e ~ ~ e l f o r Dioxin and Dioxiil-Like Corl~po~c~tds iri Soil Acriorr lel*els are concenuations of chemicals at which consideration of action to interdict exposure occurs: I ppb TCDD in residential soil was identified by Kirnbrouzh et al. (1984) as a "level of concern," and recommended as "a reasonable level to beein consideration of action to iimir exposure." Kimbrough et al.'s (1 984) conclusions were derived in pan from an evaluation of the carcinogenic potential of TCDD. based on a 2-year oral chronic toxicity and oncogenicity study in rats (Kociba et al.. 1978). With the advancement of knowledge about dioxin-like chemjcals and their assumed common mechanism of toxicity. the TEQs were introduced into the risk assessment process. Since then, 1 ppb of totaI dioxins (expressed as TEQs) in soil has been used as an accion level by ATSDR.
The Kociba et ai. (1 978) study also served as the basis for the Food and Drug Administration's (FDA's) derivation of a risk-specific dose of 0.057 pgkg/day dioxin for a 1 in a million upper-bound risk estimate for cancer (FDA. 1990). Usin: a typical default value of 70 kg for average body weight and 100 miIligrams/day (mg/day) for soil consumption, FDA's 0.057 pgkglday risk-specific dose corresponds co a soil concentration of 40 ppt. This value is marginally luwer. but from a risk assessment perspective. it is essentially equivalent to the ATSDR media-specific screening levellcomparison value (EMEG) of 50 ppt.
As noted previously. ATSDR's EMEG is based on the M U of I p@g/day TCDD, which is approximately two orders of magnitude below any health effect I e d s demonstrated either experimentally or in epidemiologic studies for both cancer and noncancer health end points. The conservative (i.e., protective) nature of both the MRL and the EMEG reflects adjustments made for recognized areas of uncertainty, perhaps spanning two to three orders of magnitude. As such, the EMEG and the MRL, on which the EMEG is based, are below levels of exposures associated with demonstrated health effects and are therefore considered to be protective of human health. The EMEG of 50 ppt (0.05 ppb) is at the low end of the range reflecting currently recopized areas of scientific uncertainty; this range is 50-50 000 ppt (or 0.05-50 ppb), which is based on the 1000-fold uncertainty factor used to derive the MRL.
CONCLUSIONS
ATSDR concludes that the action level of 1 ppb (TEQ) for dioxin and dioxin-like compounds, when coupled to a site-specific context of evaluation for the range > 50 ppt (0.05 ppb) to < 1 ppb TEQs in residential soil, is proceccive of public health and continues to represent a level ac which consideration of health action to interdict exposure, includins cleanup, should occur. This conclusion is based on ATSDR's review and evaluation of
more recenr experimental and epiderniolocjc research findinzs ATSDR's historical use of the [ e m "action level" [he range of heal& guidance values developed by ATSDR includinz the MRL and EbIEG
. . - a the lirnications and uncertainties of ATSDR's healrh rruidance values and the sclen:!:::
d a : ~ on which these valu-s zre based.
ATSDR considers this action level to be both reasot~able and protective for tHd following reasons:
- ATSDR's MRL is approximately two orders of magnitude below effect levels in experimental and epidemiologic studies.
Cancer risk-specific doses and screening values for end points other than cancer are essentidly equivalent from a risk assessment perspective,
WHERE TO FIND MORE INFORMATION
For more information on the historical and scientific background of dioxin in soil values, their proper use, and data on limitations associated with these numbers, please refer to Dioxin and Dioxin-Like Compounds in Soil. Part TI: Technical Support Document for ATSDR Interim Policy
Guideline (De Rosa et al-. 1997).
REFERENCES
AHLBORG. U.G.. BECKING. G.C., BIRNBAUM, L.S.. et a1. (1994). "Toxic equi\dency facton for dioxin- like PCBs." Chernosphere 28(6): 104967.
AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY (ATSDR) (1989). Toxicological Profile for 2.3.7.8- Terrachlorodibenzo-p-dioxin. U.S. Depamnent of Healch and Human Services, Public Healch Service. Agency for. Toxic Substances and Disease Registry. AtIanm. GA.
AGENCY.FOR TOXIC S u e n m c s AND ~ ~ S E A S E REGIZTRY (ATSDR) (1992). Public Health Assessment Guidance Manual. U.S. Department of Health and Human Senlices, Public Health Senlice. Agency for Toxic sibstances and Disease Registry. NTIS PB 92-147164- AtIanra, GA.
AGEKCY FOR TOXIC SUBSTAKCES AND DISEASE REGISTRY (ATSDR) (1997)- Technical Suppbrt Document for ATSDR Interim Policy Guideline: Dioxin and Dioxin-Like Compounds in Soii. U.S. Department of Health and Human Sen-ices. PubIic Health Service, Asency for Toxic Substances and Disease R g i s p . Atlanta. GA.
KIMBROUGH. R.D.. FALK. H.. STEHR. P.. ct ai. (1984). "Health implications of 7.3.7.8- tea-achlomdibenzo-p-dioxin (TCDD) contamination of residential soil." J. Toxicol. En\,iron. Hedh I4:47-93.
KOCIBA. R.J., KEYES. D.G., BEYER, J.E., er al. (1978). "Resulrs of a two-year chronic toxicity and oncogenicity study of 3.3.7.8-TCDD in rats." Toxicol. Appl. Pharmacol. 4628 1-787.
U.S. ENVIRON~ENTAL P R O T E ~ O S AGESCY (EPA) (1989). In~erim Procedures for Esrirnatins Risks Associated wich Exposure to Mixtares of Chlorinated Dibenzo-p-dioxins and Dibenzofurans (CCIDs and CDFs) and 1989 Update. Risk Assessment Forum. U.S. Environmental Protection Agency. EPA 6313-891 01 6. NTIS PB90-145756. Washington, DC.
U.S. FOOD AND DRUG AD~~[KISTR.%TION (FDA) (1990). Carcinogenic Risk Assessment for Dioxins and Furans in Fish Conraminated by Bleached-Paper Mills. Reporr of h e Quantiradve Risk Assessmenr Committee. Food and Dmg Adrninistrarion. Washinzron, DC.
APPENDIX I - GLOSSARY
Action leve! A concentration of chemicals at which consideration of action re interdicdprevent exposure occurs, such as surueiilance. researck.
heaith smdies. community education, physician educarion, or exposu;: investigations. Alternarively. based on the e\,aluacion by ihr hea1:h
assessor. none o f these acrions may be necessary.
To.\-icolo,q?. or~d Ind~cslriol Health. Vol. 13. No. 6. 1997 767
"At-risk" population A population ar a potentially ele\(ared risk hue to physiological sensitivity andlor increased exposure to a hazardous chemical.
B DDs Brominated dibenzo-p-dioxins
BDFs Brominated dibenzofurans
CDDs
CDFs
Chlorinated di benzo-p-dioxins
Chlorinated di benzdfurans
Comparison value A concentration used to select contaminants of concern at hazardous waste sites that are taken forward in the health assessment process for further evaluation (The terms comparison value and screeninp IeveI are often used synonymously.)
Dioxin A term used interchangeably with 2.3.73-tetrachlorodibenzo-p-dioxin or TCDD
Dioxin-like compounds Compounds from a group of halosenated aromatic hydrocarbons that have molecuIes shaped like TCDD and produce similar toxic effects. such as certain other chIorinated dibenzo-p-dioxins (CDDs) and certain chlorinated dibenzofurans (CDFs), poiychlorinated biphenyls (PCBs). polybrorninated biphenyls (PBBs). brominated dibenzo-p-dioxins (BDDs). and brominated dibenzofurans (BDFs).
Dioxins
EMEG
HazDar
MRL
PBBs
PCBs
A term used interchangeably with chlorinated dibenzo-p-dioxins
An environmental media evaluation suide (EMEG) is a media-specific comparison value that is used to select contaminants of concern at hazardous waste sites.
,2TSDRVs Hazardous Substance Release/Health Effects Database
A minimal risk level (MRL) is an estimate of the daily human exposure to a hazardous substance that is likely to be without an appreciable risk of adverse noncancer health efiecrs over a specified route and durarion of exposure.
Polybrominared biphznyls
Polychlorinated biphenyls
768 De Rosa er al.
Screenin:
TCDD
TEFs
TEQs
The process of initially identifying potentially important chemical contaminants and exposure pathways by climinatin: those of known lesser significance.
Toxicity equivalency factors (TEFs) are based on congener-specific data and the assumption that the toxicity of dioxin and dioxin-like compounds is mediated by the Ah receptor and is additive. The TEF scheme compares the relative toxicity of individual dioxin-like compounds to that of TCDD, which is the most toxic halogenated aromatic hydrocarbon.
Toxicity equivalent (TEQ) is defined as the product of the concentration, Ci, of an individual "dioxin-like compound" in a
complex environmental mixture and the correspond in^ TCDD toxicity equivalency factor (TEFi) for that compound. The total TEQs is the sum of the TEQs for each of the congeners in a given mixture:
n
To tal TEQs = 2 (c, TEF, ) - i=l
Attachment E
Dioxin and Dioxin-Like Compounds in Soil, Part 2: Technical Support Document for ATSDR Interim Policy Guideline
To.vicoioSx ntrd I~~drtsr~-ini Hecrlrh. Vol. 13, No. 6. 1997 769
DIOXIN AND DIOXIN-LIKE COMPOUNDS IN SOIL, PART 11: TECHNICAL SUPPORT DOCUMENT FOR ATSDR INTERIM
POLICY GUIDELINE
CHRISTOPHER T. DE ROSA, DAVID BROWN,' ROSALINE DHARA, WOODROW GARRETT, HUGH HANSEN, JAMES HOLLER, DENNIS JONES,
DENISE JORDAN-IZAGUIRRE, RALPH O'CONNOR, HANA POHL, AND CHARLES XINTARAS
Agency for Toxic Substances and Disease Registry U.S. Department of Health and Human Services
Atlanta, Georgia
TABLE OF CONTENTS
List of tzbles ......................................................................................................................... 770 List of appendices ................................................................................................................. 77 I
............................................................................................................... Acknowledgments 772
................................................................................................................ INTRODUCTION 772
. ................................................ ............................... DISCUSSION ......... 773
..... ...................... Issue 1 : Relationship between ATSDR's action level and EMEGs. ....- 773
................................................................ Comparison values ... 773 Exposure evaIuation and interdiction stracezies ............................................................ 774 Action levels, EMEGs. and MRLs ................................................................................ 774 Liniiarions, assumptions. and uncenainries ................................................................. 775 '
....................................................................... Issue 2: ,Analytic and samplin: techniques 775
.................................................................................................... Analyiic techniques 773 ........ .... .................... S2maIino techniques .. .. .... 775 . -
I . Address a11 correspondence to: Christopher T. De Rosa. Ph.D.. Director, Division of Toxicolog. Agency far Toxic Subsiances and Disease Resistry. Mailstop E-29. 1600 Clifton Road. NE. Atlanta. GA 30333. Tei.:(?W)639-6300. Fax:(J01)6?9-63 15. E-rnail:[email protected].
7. Abbreitiations: ATSDR. Azency for Tosic Substances and Disease Eesisrry; AUC. area under the cunle: CD25. chlorinared dibenzo-p-dioxins: BDDs. brominated dibenzo-p-dioxins: BDFs. brorninaled dibenzofu-zs: CCEHRP. The Public Health Service Committee LO Coordinate Environrnenral Health and Related P;:grams: CDDs. chlorinared dibenzo-p-dioxins: CDFs. chlorinated dibenzofurans: EMEGs. cnvironn:::::! media evaluation zuides: EPA. U.S. En\,ironrnental Protection A~enc).: FD.4. U.S. Food and Dm: .~.6;ninisrnrion: LOAEL. louesr-obsened-adverse-etiecr level: MRL, minimal risk level: NOAEL. no -obsc r~~ . s i -~dv f i s e - e f f e~~ level: PB Bs. polybrominted biphenyls: PCBs. polychlorinared biphzny1s:TCDD. ~.~~.?.S-t~:r:::-~ior~dibenzo-p-dioninl;: TEF. toxicity equivaient facror: TEQs, to~iciry equivalents.
j. K.; .;, .srds: dioxin. human exposure. risk asscismrnr. soil levels. TCDD. TEQs. < >'..> - '- -. ,.. . 3-i Bu1i.i-y A\-snuc Socth. \Vestport. CT 06SSO. 5. !?:z-.::sd from ih? Jo~tr i : ( r l ( { c / c ( i i ~ p ~ / r ~ f ~ ~ / o ~ > - , E i ~ \ . i r o ~ ~ , r ~ o , ~ : o / f i ~ . ~ - j ~ - ? : o ; ~ . , ( l i r ( 1 o ~ ~ ~ ~ ! i p i l l i O l l ~ l ~
,!,'c~~c;,:<. \.'I.:. 6. ~ J o . 2 . !997.
Tuzicolog!. a n d !ndustrial Hexlth. TioI. 13. No. 6, pp. 7 6 9 4 0 4 Cop!.righ[ Q 1997 Princeton Scienlific Publishing Co.. I n i .
ISSS: 07-18-7337
770 De Rosa el a /
issue 3: One part per billion of dioxin and dioxin-like con~pounds as an action level for cleanup ....................................................................................... 775
Historical background ...................... .. ...... .. .......................................................... 775 . .
Lrm~tations of soil action level .................................... .... .............................................. 776 .................................................................. Carcinogenic versus other health outcomes 776
........................................................................ ................................... CONCLUSIONS .. 778
Protection of public health ......................................................................................... .. 778 Si te-specific parameters ............................................................................................. 778 Evaluation of recent literature ...................................................................................... 778 Health guidance values ................................................................................................ 779
..................................................................................................... RECOMMENDATIONS 779
Evaluation of hazardous waste sites .............................................................................. 779 ATSDR draft profile for CDDs ................... .. ............................................................. 780 Further evaluation of dioxin and dioxin-like compounds ........................................... 780
LIST OF TABLES
Table I . ATSDR's decision framework for sites contaminated with dioxin and dioxin-Iike compounds ............................................................... 776
Tables in the appendices
Table 2- 1 . Recornmended toxicity equivalency factors (TEFs) for CDDs and CDFs ....................... .. ........................................................ .:. . 783
Table 2.2 . Recommended roxicity equivaIency factors (TEFs) for dioxin-like PCBs ....................................................................................... 785
............................................................................................. . Table 3- I MRLs for TCDD 790
. lable 3.22 . EMEGs (in ppb) based on 1989 TCDD MRLs ............................................ 790
Tzble 3.3b . EMEGs ( i n ppb) based on 1994 TCDD MRLs ........................................... 790
. 1 able 3-! . Health effects associated with exposure to TCDD
2nd body burdens in humans .......................................................................... 793
Table 4.2 . Breast milk levels of total TEQs associated with health effects in human infants ................... ......- ....... -. ...................... 795
Table 4.3 . Human body burdens and animal body burdens associated with health effects ..................... .....--..... ........................................ 796
LIST OF APPENDICES
Appendix 1 . ' Glossary ....................... ... ........-...........-............................................. 781
Appendix 2 . Assumptions . limitations. and uncertainties in developing health guidance values ............................................................................. 783
Minimal risk level (MRL) ....................................................................... 783 .................................... Environmental media evaluation guide (EMEG) 783
....................................................... Exposure to dioxin-Iike compounds 784 Bioavailabilify ..................... ....... ....--...--........................................ 785 Soil ingestion ........................................................................................... 786 Background exposure ...........................................................................- 786
.................................................... Exposure from soil by different routes 787 Use of body burdens to compare health effects in humans and animals ......................................................................................... 787
................................ ..................... . Appendix 3 MRLs and EMEGs for TCDD .... 788
Current MRLs ..................... ... ............................................................ 788 Proposed MRLs ................................. .. ...... .. ...................................... 788
Appendix 4 . Recent health effects studies ................................................................... 791
Introduction .............................................................................................. 791 Mechanism of action ................................................................................ 791 Human studies ................... .. ................................................................. 791 Animal studies ................... .. ................................................................. 792 Body burdens and associated healih effects ............................................ 792
Appendix 5 . Chronolosy for dioxin and dioxin-like compounds: hzalch ~uidance values and policy statenznts ......................................... 798
~ ~ ~ e n d i x 6 . References 800
772 De Rosa er 01.
ACKNOWLEDGMENTS
The agency-wide ATSDR Dioxin Workgroup collaborated in developing this technical suppon document and are named as authors on this publication. The workgroup thanks the following people for their valuable contributions: Allan Susten. Frank Schneli. and Dana Abouelnasr for constructive discussions and organizing the focus group-John Crellin. David Fowler. Todd Going, Buck Grissom, Jack Hanley, and Susan Moore; Sharon Wilbur for her review; Nancy Haynie-Mooney and Anne Olin, editorial reviews; and Emma Julian and Mary Knox, technical typing.
INTRODUCTION
Dioxin remains at the forefront of public heaIth concerns in the United States and throughout the world. Over the past 20 years, a wide range of federal agencies and other organizations have been involved in developing policy statements. strategies, and assessment methods to address the public health implications of dioxin exposure. These positions were developed in response to issues confronted by thdse organizations iri pursuing their missions. often as a direct function of Ie~islative mandates. Because of distinct differences in perspective. policy, and p ~ c t i c e , dictated by the mandated activities of these organizations and the evolving understanding of dioxin toxicity. apparently divergent positions may be reflected in their conclusions.
In pursuing its mandated responsibilities, the Azency forToxic Substances and Disease Registry (ATSDR) must address public health concerns associated with exposure to dioxin and dioxin- like compounds in the context of all available relevant information. This information includes both technicai data and science policy positions adopted by ATSDR and others that are germane to the public health assessment of dioxin and dioxin-like compounds.
The issues outlined previously, coupled with requests from the public. other agencies. the private sector. and agency staff for a statement reflecting the agency's position on science and science policy issues related to dioxin and dioxin-like compounds, prompted the development of this technical support document. This document is intended to serve as technical backzround and support for the agency inerim policy guideline on dioxin and dioxin-like compounds in soil and to harmonize such efforrs with those of other federal agencies and relevant organizations to the extent praccicable. This document reflects an assessment of current practice within the azency and defines the appropriate roles of professional judgment and emerging scientific principles in ATSDR's public health assessments of exposures to dioxin and dioxin-like compounds.
This docun~ent is not intended to supplant [he Environmental Protection Agency's (EPA) on~oing reassessment of dioxin and dioxin-like compounds or ATSDR's toxicolo~ical profile on chlorinated dibenzo-/I-dioxins (CDDs). but it will provide technical background supporr for ATSDR's public health practice at sites contaminated by dioxin and dioxin-like compounds. A cencrai theme of this documenr is the use of health guidance values in the broader context of biomedical and other scientific juzi~ment to define exposures of concern rather than sin,oIe numerical conclusions thar may ~ o n \ ~ e y an artificial sense of precision (ATSDR. 1993: CEQ. 1989).
To.ricalog~ nltd Indrisrrinl Henlrh, C'ol. 13, No. 6, 1997 773
After reviewins the previously cited issues. ATSDR further considered three specific issues:
o Issue I : The relationship between the ATSDR action level of 1 pan per billion @pb) dioxin and dioxin-like compounds in residential soil and ATSDR's environmental media evaluation guides (EMEGs)
o Issue 2: That current analytic and sampling techniques employed for soil contaminared with dioxin and dioxin-like compounds may not be sufficiently sensitive
o Issue 3: That ATSDR's action level of 1 ppb dioxin and dioxin-like compounds in residential soil is too high.
Each of these issues is addressed in subsequent sections of this paper. To facilitate its review of these issues ATSDR has
o developed a glossary of critical terms and concepts to facilitate a consistent use and understanding of terminology in this support document (Appendix I )
o identified and evaluated key assumptions underlying the review and evaluation of the ATSDR action level of 1 ppb of dioxin and dioxin-like compounds in residential soil, the ATSDR minimal risk level (MRL), and the ATSDR EMEG (Appendix 2)
o reviewed and evaluated the documentation for the ATSDR action level of 1 ppb for dioxin and dioxin-like compounds in residential soils, the MRL of I pico~ram/kilob& day [p,aAg/day) 2.3.7,8-temchlorodibenzo-p-dioxin (TCDD). and the EMEG of 50 parts per trillion (ppt) (Appendix 3)
o revieisfed and evaluated ATSDR's use of an action level of 1 ppb (HazDat) for dioxin and dioxin-like compounds. given recent insights into the toxicologic and human health effecrs of such compounds, particularly those associated with reproductive and de\felopmencaI toxicities (Appendix 4).
DISCUSSION
Issue 1: Relationship between ATSDR's action level and EMEGs
Co~7rparisoil Ihllres EMEGs are comparison values used by ATSDR health assessors ro select contaminants for further evaluation based on concerns about end points ocher than cancer. As such. EMEGs represent a stanin? poinr for che health assessor to make an initial decerminacion of whether or not a specific conraminarion level merits further evaluation as a potenrial health concern. EMEGs are based orl ,4TSDR's MRLs or ana1o:ous health zuidance vaiues that are thousht to be without appreciable r;sk fo: a ~ i v s 2 route and duration of exposcre.
774 De Rosa er al.
Generally, if a on cent ration of a chemical at a site is less than the EMEG, A ~ ~ D R assumesthere is little likelihood that the chemical presents a health hazard at the site via a particular environmental medium. In some instances, ATSDR may further consider contaminants present at levels below the EMEG, based on community health concerns. However, if the concentration of a chemical meets or exceeds the EMEG, this does not mean there is a chemical health hazard; instead. this meaos that the situation merits further evaluation of site-specific information (for example, bioavailability. demographics, on-site activities, climatic conditions. or soil cover). Follow-up evaluation of all available site-specific information may reveal that there is no healch threat at the site even though the media concentrations may exceed theEMEG.
fiposure Evaluarion and Interdiction Srrategies Levels greater than the EMEG of 50 ppt (0.05 ppb) TCDD in soil are used to determine whether further site-specific evaluation for dioxin is to occur. Because the toxicity of dioxin and dioxin- like compounds is assumed to be elaborated through a common receptor-mediated mechanism, the EMEG is expressed i n total toxicity equivalents (total TEQs). An action level of 1 ppb (also expressed as total TEQs) is used to determine the need for public health actions on a site-specific basis and on the basis of the maximum concentration identified at the site.
For these reasons, P;TSDR considers source-specific contributions to total exposure and associated body burdens of dioxin and dioxin-like compounds expressed as TEQs in evaluating sites. This requires insight into not onIy contamination levels in soil, but also into other media as well. In this way the' contribution of each potential source of exposure is evaluated and viewed in the context of total exposure and associated body burdens for a given at-risk population.
ATSDR also evaluates exposure levels and potential body burdens in at-risk populations in the context of current howIedge regardins effect levels as identified in both experimental studies and epidemiologic investigations (DeVito et ai., 1995; Appendix 4). A fulI range of strategies to interdict exposures and reduce overall body burden are then considered. These exposure interdiction strategies include restricted land use and access, health education, relocation, and remediation to reduce incremental contributions to body burdens and risks of potential health effects.
Acfion Levels, EMEGs, and MRLs ATSDR's health guidance values for dioxin or dioxin-like compounds (MRLs, EMEG, action level) each have their distinct application corresponding to screening, evaluation. or consideration of potential public health actions (Table I). The use of such a hierarchy or framework of quantitative conclusions for purposes of screening, evaluation, and consideration of action is not intended to-
serve as a surrogate for professional judgment. Parame~ers of exposure and toxicity that may serve to either increase or decrease health concerns for at-risk populations should be considered on a site-specific basis. ATSDR's approach is consistent with recommendations of the National Research Council (NRC, 1994) that a tiered or iterative approach be used in health assessment efforts, beginning with rslarively conservati~le screening techniques and subsequently relyin: on
"lore rigorous data-intensive efforts as su,a,oesced by public health concerns.
Toxicology arrd Imzd~tsrricr[ Henlri~. Voi. 13. No. 6, 1997 775
Lirnirario~~s, Assumrzprions, or~d Uncerrainries
Health guidance values reflect the application of a range of dcfault assumptions that are conservative (i-e., protective) and which are believed. in aggregate, to result in protective health guidance values. These assumptions include bioavailability of dioxin and dioxin-like compounds from test vehicles, soil ingestion rates for different at-risk populations (i-e.. children, geophagic children, adults), and the use of animal data in the absence of adequate epiderniolosic data addressing the health effects in human populations (Appendix 2). Additionally. to account for recognized areas of uncertainty regarding species variability in effect(s) and effect levels. sensitive human populations. and iowdose extrapolation, uncertainty factors are used in developing health guidance values. The application of such uncertainty factors concributes further to the protective nature of health guidance values.
The limitations, assumptions, and uncertainties inherent in health risk assessment are addressed in the National Academy of Sciences report "Science and Judgment in Risk Assessment" (NRC, 1994). In this report, the Academy states that "uncertainty analysis should be an iterative process, moving from the identification of generic uncertainties" to more refined analyses for chemical- specific or industrial plant-specific uncertainties. Implicit in this scenario are sire-specific applications addressed in this support document. ATSDR's practice in evaluating sites contaminated with dioxin and dioxin-like compounds is consistent with the position of the National Academy of Sciences (NRC, 1994) in terms of uncertainty analysis.
Issue 2: AnaIvtic and samoling techniques
Analpic Teclzniques The EF;A 8280 method is currently unable to provide analytical data for IeveIs between the screenins level of 50 ppt and the action leveI of I ppb TEQs (EPA. 1995). The EPA 8290 method can provide anaIytica1 data in the ranse of 50 ppt to I ppb. The detection limit of Method 8290 has a range of 1-5 ppt. Thus, in those instances where the health assessor has determined that it is necessary to evaluate the site-specific public health implications of exposure to soil levels of dioxin and dioxin-like compounds between 50 ppt and I ppb, it may be appropriate to implement the EPA 8290 (EPA, 1994) soil analytic method wirh the more sensitive detection limit. This decision should be made on a site-specific basis.
Sampling Teclzniques ATSDR's position regardin: soil samplin: strategies is germane to the discussions in this document. ATSDR recommends thar appropriate soil sarnplin: methods be determined on a site-
specific basis (Emmett and Jordan-Izaguirre, 1994).
776 De Rosa er al.
TABLE I. ATSDR's Decision Framework for Sites ~ o n t a m i n 2 t e d with Dioxin and Dioxin-Like Compounds
Because rhe toxicity of dioxin and dioxin-like compounds is assumed to be elaborated through a common receptor-mediated mechanism. levels greater than 50 ppt (0.05 ppb) TEQs* are used to determine whether further sire-specific evaluation for dioxins is to occur based on the maximum soil concentrations identified at the site. A level of 1 ppb TEQs is used to determine the potential need for public health actions on a site-specific basis and on the basis of adequate sampling and measured or projecred human exposure-past. present. or future---as determined by the health assessor.
SCREENING LEVEL EVALUATION LEVUS ACTION LEVEL" k 50 ppt (0.05 ppb) TEQs > 0.05 ppb but < I ppb TEQs 2 1 ppb TEQs The EMEG for TCDD is Evaluation of site-specific Potential public health actions 50 PPt facton. such as: considered, such as:
This is based on an MRL of Bioavailability Surveillance 1 pgfkg/day for TCDD Ingestion rates * Research (ATSDR, 1989). - Pathway analysis Health studies
For screening purposes Soil cover Community education 50 ppt TCDD is assumed to Climate Physician education be equivalent to 50 PPt TEQs Other contaminants Exposure investigations
* Communiry concerns
Backmund Exposures 'The toxicity equivalent CTEQ) of TCDD is calculated by multiplying the exposure level of a parricular
dioxin-Iike compound by its toxicicy equivalency factor 0 . T E F s are based on congener-specific data and the assurnpuon that Ah receptor-mediated toxicity of dioxin-like chemicals is additive. The TEF scheme compares the relati\le toxicity of individual dioxin-like cornpounds to that of TCDD, which is the most toxic halogenated aromatic hydrocarbon.
^'A concentration of chemicals at which consideration of action to interdict/prevent exposure occurs. such as surveillance, research. health studies. community education. physician education, or exposure investigations. Afternari\lely, based on the evaluation by the health assessor. none of these actions may be necessary.
Issue 3: One part per billion of dioxin and dioxin-like com~ounds as an action level for cleanup
The decision to derive standard action levels for individuaI chemicals and to fcrther use these values to drive clean-up activities is an EPA risk manage-meot decision. Risk management issues are outside the direct mandates ofATSDR.
Hisforical Backgrorci7d The 1 ppb level for dioxin has been described as a "reasonable level to besin consideration of action to limit exposure" (Kimbroush et al.. 1984): "a level of concern" (Kimbrouzh et at.. 1984; Pohl et al., 1995); and "a soil action le\.el" (Johnson. I992b). This action level of I ppb was orisinally used in reference LO TCDD in soil (see Appendix 5 for acomplece chronolo~y resardinz the use and epplicarion of rhese terms). More recenrly, i t has been used in reference to TCDD toxiciry equii'alents or TEQs (CCEHRP. 1992). The TEQ approach is based on the assumption of a common ixepcor-medizted mechanism of toxic action for dioxin and dioxin-like compounds (Binbaum. 1994; DeVito e: a ] . , 1995).
Limirarions of Soil Action Level A key limitation inherent in the use of any soil action level is the incomplete understanding of how such a soil action level would contribute to body burdens in at-risk populations. The extent of contribution of soil dioxin and dioxin-like compounds to body burdens of dioxin is a function of all media-specific levels of the contamination at a given site. Accordingly, a 1 ppb level of dioxin and dioxin-like compounds in residential soil could result in distinctly different contributions to overall body burdens in different populations. For this reason, ATSDR's use of 1 ppb has always been coupfed with the recommendation that full consideration be given to site-specific factors such as demographics, on-site activities, climatic conditions. and soiI cover.
These site-specific factors provide health assessors with valuable insight into how closely the assumptions associated with health guidance values actually reflect real site conditions. Moreover, such insight and understanding are essential to the determination of whether a site-specific action level other than 1 ppb might be appropriate. As noted by Kimbrough et al. (1984). exposure assessments used to project risk contain assumptions that are unlikely to be actually encountered. These assumptions include uniform levels of contamination, uniform land use patterns, lifetime exposure, and no degradation of dioxin and dioxin-like compounds.
Carcinogenic Versus Otlrer HealrJz Outcomes
A significant point to be considered in regard to 1 ppb as an action level for dioxin and dioxin- Like compounds in residential soil is the issue of carcinogenic versus other health outcomes. As discussed previously, 1 ppb dioxin in residential soil was identified by Kimbrough et aI. (1984) as a "levei of concern," and was recommended as "a reasonable level to begin consideration of action to limit exposure." It is important to note that Kirnbroush et al.3 (1984) conclusions were derived in part from an evaluation of the carcinogenic potential of TCDD, based on a 2-year oral chronic toxicity and oncogenicity study in rats (Kociba et aI,, 1978).
The Kociba et al. (1 978) study also served as [he basis for the Food and Drus Administration's (FDA's) derivation of a risk-specific dose of 0.057 p!&/day dioxin foi a 1 in a million upper- bound risk estimate for cancer (FDA, 1990). Using typical default values of 70 lcilogarns (kg) for averase body weieht, and 100 milligrams/day (m,o/day) for soiI consumption, FDA's 0.057 pzJkg/day risk-specific dose corresponds to a soil concentration of 40 ppt, a vaIue rnar,oinally lower than, bur essentially equivalent to ( h m a riskassessment perspective), the ATSDR screenins EMEG of 50 ppt (0.05 ppb). EPA's 0.006 p ~ J k g d a y risk-specific dose corresponds to a soil concentration of 4 ppt, a value about one order of rnaznitude below the FDA level. In conrrast, Paustenbach et al. (1992) reexamined human exposure to dioxin and dioxin-like compounds from soil. In residential areas, soils conraining 20 ppb ofTCDD were calcula&d to pose a lifetime cancer risk no :ream than 1 i n 10". Assumptions used for escimatins exposure from soil differed from previous evaIuations of soil ingestion, dermal contact, dust inhalation, fish consumption. and in the cancer slope fzctor for TCDD. Exposure throush dermal contact was discussed.
As noted previously. ATSDR's EMEG is based on the MRL of 1 pzkg/day TCDD, which is approximately two orders of ' r n a ~ n i t u d e be!ow any human effect levels demonsrra:sd either
expzrimzntaily or in epidemiolosjc srudies for both cancer and noncancer heaIch end points. The
conservative (i.e.. pl-elective) nature of both the MRL and the EMEG reflebts adjustments made for recognized areas of uncertainty perhaps spanning two to three orders of magnitude (Appendix 2). As such, the EMEG and the MRL (on which the EMEG is based) are below levels of exposures associated with demonstrated health effects and are therefore considered protective of human health. A 1000-fold uncertainty factor was used in the derivation of the MRL. reflecting the range of currently recognized areas of scientific uncertainty. The EMEG of 50 ppt is at the low end of this range, which is approximately 50-50 000 ppt (0.05-50 ppb). The level calculated by Paustenbach of 20 000 ppt (20 ppb) is closer to the mid-point of the range of scientific uncertainty.
In the case of the FDA's risk-specific dose, it should be noted that this dose is based on an upper- bound estimate of risk in the 95% confidence limit sense. This means that there is a 956 chance that actual risk is less (CCEHRP, 1992) and could be as low as zero. This places the low end of ATSDR's range of evaluation (> 0.05 ppb but < 1 ppb TEQs) approximately two orders of rnasnitude below health effect levels demonstrated experimentally or in epidemiologic studies.
CONCLUSIONS
Protection of Public Healrlr The issues discussed previously indicate that (I ) ATSDR's EMEG and MRL are approximately two orders of magnitude below effect levels in experimental and epidemiologic studies, (2) cancer risk-sptcific doses and screening values for end points other than cancer are essentially equivalent from a risk assessment perspective, (3) ATSDR's EMEG of 50 ppt (0.05 ppb) and action level of 1 ppb are not inconsistent, and (4) a 1 ppb action level for dioxin and dioxin-like compounds in residential soil, when coupled to a site-specific context of evduaiion for the range of greaterthan 50 ppt to less than 1 ppb (TEQs) in residential soil. is protective of public health. Similarly, a cleanup level of I ppb (TEQs) for dioxin and dioxin-like compounds in residentiai soil is considered to be generally protective of human health if coupled with a full evaluation of site specific factors.
Sire-Specific Parartrefers A range of site-specific parameters, e.:., soil type, soil cover, media-specific contamination levels, and demo-mphics, affect body burdens of dioxin and dioxin-like compounds in at-risk pophlations. Because these parameters vary on a site-specific basis, it is not currently feasible to identify, for all sites, a single numericaI value to appropriately guide cleanup or other public health actions. For this reason, ATSDR uses a hierarchy of health guidance values (Table 1) for purposes of screening, evaluation. and consideration of the potential need for further action to interdict exposures. exrending to and possibly includins cleanup. Alternative actions may include, but are not Iimiced to. health education, restricted access. deed restrictions. and relocation.
Evalrtnrion of Recent Lirernrrtre Based on ATSDR's evaluarion of more recenr literature (Appendix 4). ATSDR has deternlined rhar the azency's MRL of I p/k/day (ATSDR. 1989) is approximately two orders of masnitude below efiect levels in experimental and epiderniolo~ic scudies. Accordinsly, ATSDR concludes t:lar this MRL and the EMEG of 50 ppr, which is based on the MRL. continue to be reasonable and pro~ective, aIrhoush zeophazic children and those with elevaced body burdens of dioxin and
dioxin-like compounds may represent special at-risk populations. Such an approach is consistent with the current public health conclusions and practices reflected in a recent publication by the Health Council of the Netherlands (1996). in which a health-based exposure limit of 1 pflgkiay dioxin and dioxin-like compounds was also recommended based on the council's own independent reassessment of dioxin.
With specific reference to the issues outlined in this paper. ATSDR further concludes the following:
o ATSDR's action level of 1 ppb of dioxin and dioxin-like compounds (TEQs) in residential soil is consistent with ATSDR's EMEG. These values are used for distinctly different purposes in the evaluation of dioxin-contaminated sites (Table 1 ).
o Currently used soil analytic rnechods may not be sufficienrly sensitive. Determination of an appropriate analytic method should be made on a site-specific basis. Specific knowledze of different dioxin-like compounds at a given site is required to evaluate the adequacy of a soil sampling protocol.
o ATSDR's action level of 1 ppb for dioxin and dioxin-like compounds (TEQs) in residentiaI soil is not too high. Whether to use the 1 ppb action level should be decided on a site-specific basis in which residential soil levels ereater than 50 ppt and less than 1 ppb are further evaluated in the context of site-specific parameters.
Healrlr Guidance Valiies While health guidance values represent an important frame of reference in public health assessment, they are not surrogates for biomedical and other technical judgments in pubIic health assessments. For this reason. heaIth guidance values. including those used for screenins. evaIuation, and consideration of action, are used by ATSDR in the context of all relevant site- specific pararnecers. In this site-specific context of evaluation for levels of dioxins in soil sreater than 50 ppr and less than 1 ppb. ATSDR concludes that the 1 ppb level in residential soil continues to represent a level at urhichconsideration of health action to limit exposure should occur: ATSDR considers rhis action level to be both reasonabIe and protective.
The identification of a threshold body burdenhlood serum Ievel. below which adverse health effects are not anticipated. would heIp to better define potential health risks at sites contaminated with dioxin and dioxin-like compounds. However. since siznificant uncertainties remain regarding such levels, especiaIly for at-risk populations by virtue of exposure or physiolo~ic sensitivity,.a threshold levzl cannot be identified at present.
E\,olliarioii u,fHclzn~-doris M'crste Sires '4TSDR.s approach [o the evalliation of hazardous n.as[e sires. indudins thoss coniarninar-d iv i rh dioxir. 2nd dioxin-!ik: cor?oundi. places presminen~ emphasis on biomedical 2nd ocher
tzchnicz! judsrnent. I n [hr exercise of such a judzment. health suidance values serve as a frame
780 De Rosa er al.
of reference to guide agency practice at sites. In this frame of reference, values of 5 50 ppt (0.05 pp b) TEQs, > 50 ppt (0.05 ppb) but c1 ppb TEQs, and 2 1 ppb TEQs continue to be the agency's best estimate of appropriate health guidance values for purposes of screening. evaluation, and consideration of health action to limit exposure, respectively (Table I) .
Based on the foregoing frame of reference. the dioxin workgroup's recommendations are as follows:
h u e I : Relarionship between ATSDR1s action level and EMEGs
o That ATSDR continue to use the EMEG of 50 ppt as TEQs for soil contaminated with dioxin and dioxin-like compounds for purposes of screening
o That 1 ppb dioxin and dioxin-like compounds expressed as TEQs in soil continue to be used by ATSDR as an "action level" (Johnson, 19925), which has been characterized as "a reasonable level to begin consideration of action to Iimit exposure" (Kimbrough et al., 1984) to dioxin from residential soil.
Issue 2: Analvtic and sarn~linc. techni~ues
o That ATSDR and EPA continue their effom to assure earlier consultation at sites
o That the adequacy of analytic and sampling techniques be assessed on a site-specific basis.
Issue 3: One part per billion of dioxin and dioxin-like comuounds as an action level for cleanup
o That ATSDR continue to consult with EPA resarding the appropriateness of 1 ppb of dioxin and dioxin-like compounds as an action level for cleanup or other actions to interdict exposure and protect human health on a site-specific basis.
ATSDR Drafr Projiie for CDDs Ir is recommended that ATSDK complete ics draft profile on CDDs in coordination with EPA's dioxin reassessment.
F~lrriler- Elwllinrion of Dioxin and Dioxin-Like Corrrporrnds Finally, once ATSDR's toxicoIogica1 profile has been completed, the health guidance values for dioxin and dioxin-like compounds should be further evaluated when new informacion becomes available.
Toxicology and lnditsrrial Healrlr, Val. 13, No. 6. I997 78 1
APPENDICES FOR TECHNICAL SUPPORT DOCUMENT FOR ATSDR INTERIM POLICY GUIDELINE
APPENDIX I - GLOSSARY
Action level A concentration'of chemicals ar which consideration of action to interdictlprevent exposure occurs, such as surveillance, research, health studies, community education, physician education, or exposure investigations. Alternatively, based on the evaluation by the health assessor. none of these actions may be necessary.
"At-risk" population A population at a potentially elevated risk due to physiological sensitivity andlor increased exposure to a hazardous chemical.
BD3s Brominated dibenzo-p-dioxins
B DFs Brominated dibenzofurans
CDDs Chlorinated dibenzo-pdioxins
CDFs Chlorinated dibenzofurans
Comparison value A concentration used to select contaminants of concern at hazardous waste sites that are taken forward in the health assessment process for further evaluation (The terms comparison value and screening level are often used synonymously.)
Dioxin A term used interchangeably with 2.3.7.8-tetrachlorodibenzo-p-dioxin or TCDD
Dioxin-like compounds Compounds from a group ofha10,oenated aromatic hydrocarbons that have molecuIes shaped like TCDD and produce similar toxic effects, such as cenain other chlorinated dibenzo-p-dioxins (CDDs) and certain chlorinated dibenzofurans (CDFs). polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), brominated dibenzo-p-dioxins (BDDs), and brominated dibenzofurans (BDFS~.
Dioxins
EMEG
A term used interchangeably with chlorinated dibenzo-p-dioxins
An environmental media evaluation p i d e (EMEG) is a media-specific comparison value that is used to select- conran~inant-s of concern zt
hazardous waste sices.
ATSDR's Hazardous Subsrznce ReleasdHcalrh Effects Database
782 De Rosa er (11.
MRL
PBBs
PCB.s
Screening
TCDD
TEFs
TEQs
A minimal risk level (MRL) is an estimate 7f thedaily human exposure to a hazardous substance that is likely to be without an appreciable risk of adverse noncancer health effects over a specified route and duration of exposure.
Potybrominated biphenyls
Polychlorinated biphenyls
The process of initiaIly identifying potentially important chemical contaminants and exposure pathways by eliminating those of known lesser significance.
Toxicity equivalency factors (TEFs) are based on congener-specific data ar~d the assumption that the toxicity of dioxin and dioxin-like compounds is mediated by the Ah receptor and is additive. The TEF scheme compares the relative toxicity of individual dioxin-like compounds co that of TCDD, which is the mos: toxic halogenated aromatic hydrocarbon.
Toxicity equivalent (TEQ) is defined as the product of the concentration. C, of an individual "dioxin-like compound" in a complex environmental mixture and the corresponding TCDD toxicity equivalency factor (TEF,) for that compound. The total TEQs is the sum of the TEQs for each of the congeners in a given mixture:
n
Total TEQs = 1 (c, TEF, ) i=l
Tu.ricoloSy and I~~dlisrricrI Health. Vol. 13. No. 6. 1997 763
APPENDIX 2 - ASSUMPTIONS, LIMITATIONS, AND UNCERTAINTIES IN DEVELOPING HEALTH GUIDANCE VALUES
Regulatory and policy decisions regarding contaminant levels must constantly be made in the face of scientific and technical uncertainties. In establishing health-based benchmarks such as
minimal risk levels (MRLs) and environmental media evaluation guides (EMEGs). multiple assumptions are made about the nature of these uncertainties, depending on the specific question or.issue being addressed. In interpreting and using health-based benchmarks to make general and/or site-specific decisions, these assumptions must be identified and addressed to avoid underestimating or overestimating actual risks. Some of these assumptions are made routinely during the development of health-based guidance values. and the conservatism they introduce into the final estimate is explicitly prescribed in the appropriate guidance documents.
Minimal Risk Level An ATSDR MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects for a specified route and duration of exposure. These substance-specific estimates, which are intended to serve as screening levels. are used by ATSDR health assessors and other responders to identify contaminants and potentid health effects that may be of concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or action levels for ATSDR o r other agencies.
MRLs are intended to serve as a screening tool to help public health professionals decide where to further evaluate the potential for health effects. They may also be viewed as a mechanism to identify those hazardous waste sires that are not expected to cause adverse health effects. MRLs contain some desgee of uncertainty because of the lack of precise toxicologicaI information on the peopie who might be most sensitive (e.g.. infants, elderly, individuaIs with liver disease. and nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR uses a consekative (i.e., protective) approach to address these uncertainties consistent with the public health principle of prevention. Although human data are preferred, MRLs often must be based on animal studies because relevant human studies are lackin,a- In the absence of evidence to the contrary. ATSDR assumes that humans are more sensitive than animals to the effects of hazardous substances and that certain persons may be particularly sensitive. Thus, the resultins MRL may be as much as two orders of magnitude below levels shown to be effect levels in laboratory animals.
E~n~irortmer~ral Media El~alttoriorz GiiiC? The EMEG is a media-specific concentration below which exposure is unlikely to pose a health threat. The EMEG is calculated by multiplyins the MRL by the body weight and dividin~ by the
ingestion rate. No site-specific assumptions are used in deriving the EMEGs. Because they are
no( site-specific, they are not clean-up Isvels.
Assumptions used in developing the ATSDR EMEGs include (1 ) exposure occurs 24 hours a day for every day of the exposure period, (2) body weight. 10 kilograms for a child (22 pounds) and 70 kilograms for an adult (154 pounds), (3) inzestion rate for drinking water is 2 l i~ers per day for adults and 1 liter for chiIdren, and (4) ingestion rate for soil is 100 milligrams per day for adults. 200 milligrams per day for children, and 5 grams per day for the geophagic child.
EMEGs should not be used to suggest or predict adverse health effects or to set clean-up levels. Their purpose is to provide health assessors with a means of selecting environmental contaminants for further evaluation (ATSDR, 1992).
. Exposure to Dioxin-like Compo~tnds Dioxin-like compounds or "related chemicals" are other compounds containing chlorine or bromine whose moIecules are shaped like TCDD and produce similar toxic effects. including some other dioxin congeners, some furan compounds, some poIychIorinated biphenyls (PCBs),
and some polybrominated biphenyls (PBBs) (Schierow, 1995). (See also Table 2-1 and Table 2-
2.) As explained in Appendix 1, TEQs are used to estimate toxicity of dioxin-like compounds.
TABLE 2-1. Recommended Toxicity Equivalency Factors (TEFs) for CDDs and CDFs
EPA current EPA current CDDs recommended values CDFs recommended values mocoCDDs 0 monoCDFs 0 diCDDs 0 diCDFs 0 triCDDs 0 triCDFs 0 2.3 J.8-TCDD 1 2.3.7.8-tecraCDF 0.1 other tetraCDDs 0 other tetraCDFs 0 2,3,7,8-pencaCDDJ 0.5 I dJ.7,X-pentaCDF 0.05 other pentaCDDs 0 2.3.4,7.8-pentaCDF 0.5
orher pentaCDFs 0 2,3.7,8-hexaCDD3 0.1 2.3.7.8-hexaCDP 0.1 ocher hexaCDDs 0 ocher hexaCDFs 0 2,3.7,8-heptaCDD3 0.0 1 2.3.7.8-hepcaCDP 0.0 1 other heptaCDDs 0 other heptaCDFs 0 octaCDD 0.00 1 octaCDF 0.00 1 "ny isomer that contains chlorine in the 2.3.7.8-positions CDDs = chlorinared dibenzo-p-dioxins: CDFs = chlorinated dibenzofurans: TCDD = tetrachlorodibenzo-p-dioxin. Source: derived from EPA ( 1989a).
Some of rhe assumptions for usin? the TEQ approach include a well-defined ,oroup of chemicals,
a broad database of information, consistency across end points. addi~ivity of the effects, and a common mechanism of action (EPA. 1989~). Accordins to EPAguidelines for risk assessment of complex rnirrrilres. porency-weighted addiri\.ity is assumed for mixtures in the absence o f
inf~rrnation to the contrary (EPA. 19S7).
Toxicolog~~ arzd li~drtsrrinl Healfh. VoL lj, No. 6. J997 785
The limitations associated with the use ofTEQs must be considered in developing health guidance values. TEQs are derived using toxicity equivalency factors mFs) that are constants determined from experimental studies for each congener. Although TEFs are considered a constant, they are dependent on the specific study (end point. dose. and duration of exposure). As defined, TEQs are assumed to be additive and not synergistic or antagonistic. In actual mixtures of dioxin and dioxin-like compounds, competitive inhibition may occur at sufficiently high doses. As with MRLs and EMEGs. biomedical judgment must be used in considering site-specific conditions that would reasonably modify estimates applicable for an individual site.
TABLE 2-2. Recommended Toxicity ~~uiva iency Factors (TEFs) for Dioxin-Like PCBs
WHO proposed WHO proposed PCB interim values PCB inteArn values"
3.3',4.4'-TCB 0.0005 2.3.3'4.4.5-HxCB 0.0005 3.3',4.4'.5-PeCB 0.1 2,2.3'.4.4',5'-HxCB 0.0005 3,3',4,4'.5.5'-HxCB 0.0 1 2,3',4,4'.5.5'-HxCB 0.0000 1 2.3.3',4,4'-PeCB 0.000 1 2.3,3'.4.4.5,5'-HpCB 0.000 1 2.3.4.4.5-PeCB 0.0005 2.2'.3,3'.4.4'5-HpCB 0.000 1 2,3',4,4'5-PeCB 0.000 1 2.2'.3.4.4',5 5'-HpCB 0.00001 2'.3.4,4',4-PeCB 0.0001 'Interim values proposed by World Health Organization/internationaI Programme on Chemical Safety PCB = polychlorinated biphenyl; TCl3 = tetracldotinated biphenyl; PeCB = pentachlorinated biphenyl; HxCB = hexachiorinated biphenyl; HpCB = heptachlorinated biphenyl Source: derived from Ahlborg et aI. (1994).
Bioa~~ailabilir)l Bioavailabiiity is an integral factor in the estimation of the internal dose (or dose at tarset tissue) of the chemical. The gasuointestind absorption of TCDD and reIated compounds is \miable, incomplete, and congener- and vehicle-specific. More lipid-soluble congeners. such as 2.3.7.8- tetrachIorodibenzofuran, are almost completely absorbed, while the extremely insofuble octachlorodibenzodioxin is less well absorbed depending on the dosin: rezimen; high doses may be absorbed at a lower rate, whereas low repetitive doses may he absorbed at a = oreater rate. The only study of TCDD bioavaiIability in humans was reported by Poiger and Schlatter (1986) and was based on a single maIe in which the zastrointestinal absorption was > 87% when TCDD was administered in corn oil.
Laboratory data suggest hat there are no major interspecies differences in ihe ,aastrointestinal absorption of CDDs and CDFs. However, absorption of TCDD is dependent on conditions and characteristics of the soil medium; in animals. absorption of TCDD from different soiIs ranged from 0.5% (Urnbreit et a]., 1986a, 1986b) to 50% (Lucier er al., 1986). Absorption from a diet was 50% [to 63% in rais (Fries and Marrow, 1975). Therefore, exposure with food as a vehicle, rather than wirh oil as a vehicle, relaces more closely to exposure from soil. Bioa~~ailability has to be considered when calculatins the hypothetical in~estion dose.
786 De Rosa cr al.
I f assumed that 100% of TCDD is bioavailable, risk may be overestimated. The health assessor should recoyize that others used various assumptions in their calculations. Kimbrough et al. ( 1984) assumed 308 bioavailability from ingestion of soil, but pointed out that animal studies with contaminated Missouri soil indicated absorption up to 30% to 50% (McConnell et al.. 1984). Pohl et al. (1995) assumed 408 bioavailability from soil. In contrast, Paustenbach et aI. (1986) estimated bioavailability of 10% to'30%. Unless toxicokinetic studies that use soil samples from the specific site are available, it is difficult to speculate on how rnuchTCDD and related compounds will be absorbed. Therefore. the estimate of the actual intake has limitations.
1 The chronic MRL is based on studies where food was the vehicle. Resuits from animal studies indicate that bioavailability of TCDD from soil varies between sites because dioxin and dioxin- like compounds bind tightly to soil, and increasingly so with the passage of time fGouph, 1991) and clay content of soil. Therefore. TCDD content aIone may not be indicative of the potential for human health hazard from contaminated environmental materials, and site-specific evaluation is essential.
Soil I17gestio11 Soil ingestion rates are assumptions included in the derivation of EMEGs (see previous section). ATSDR (1992) uses assumptions based on consumption of 100 mglday for adults and 200 mgfday for children. The soil ingestion for children is based on a number of studies (Binder et al.. 1986; Clausino et al.; 1987) estirnatiiig the average soil ingestion in populations of normal children. Kirnbrough et a!. ( 1 984) assumed in their calculations that children between 1.5 and 3.5 years of aze ingest abour 10 of soil daily. and their risk assessment was based on "extreme total daily dose estimates." This estimate was later disputed. and several studies were conducted to evaluate he daily intake of soil by children. One of the reports suggested that an average child ingests only about 2 5 3 0 mg of soil daily (Gough, 1991). However, about 1% to 2% of children are geophasic and ingest from 5 g to 10 g of soil daily (EPA. 1989b). Uncertainties associated -141i[h this issue are acknowled,oed, but ATSDR (1992) views ingestion rates of 100 rng/day and 200 mgday for adults and children. respectively, to be reasonable. In the event that geophasic children are ar risk, ATSDR considers this issue further in the public health assessment. .
Bnck,oi-ortrrd Erposrire EMEGs represent an esiirnation of exposure dose from one source only. A11 relevant sources of exposure from the hazardous waste site and all possible background exposures should be included in the finat evaluation of actual exposure.
Dioxin and dioxin-like compounds are known to readily enter the food chain. It'has been estimated chat abour 984 of exposure occurs rhrouzh food. It should be nored that the average background intake of dioxin and dioxin-like compounds and of all TEQs of TCDD for adults in rhe zeneral popularion w:re estimated as 0.35 p ~ k ~ l d a y and 1.9 pg/kg/day, respectively (IVHO. 199 1 ).
Further. i t is irxporranr to consider the background level ofdioxin and dioxin-like compounds in conraminaicd soil. The U.S. backsround TCDD soil levels ranzed from nonderecred rn I0 ppc in
. . . j n d u s t r ~ a l ! ~ ? ~ ::?zj of groups of rnidwesrzrn and mid-Aclanric states (Nestrick er a!.. 1986).
Toxicology and f~rdrrrrrial Healrlr. Vol. 13. No. 6. 1997 787
Exposure froiir Soil by Diferenr Routes
Kirnbrough et al. (1984) estimated that the lifetime uptake of TCCID from soil will consist of 95% from soil ingestion, 3% from soiI dermal exposure (assurnins 1% dermal absorption). and 2% from inhalation. Paustenbach et al. (1986) indicated chat the 1 % dermal absorption proposed for TCDD-contaminated soil may be too high. Similarly, he further lowered the estimates of inhalation intake, specularing that 2% from inhalation may be too high.
Unless indicated otherwise by the specific on-site circumstances, exposure by routes other than oral can be considered insignificant.
Use o fBody Burdens ro Compare Health Effecrs in Humans and Anirnals Levels of exposure to dioxin and dioxin-like compounds that produce toxicity in experimental animals cannot be directly compared with levels associated with adverse health effects in humans because most epidemiologic studies do not provide adequate data to estimate the exposures in the studied cohort. However, body burden history can sometimes be estimated from reported serum or adipose concentrations and empirically based assumptions regarding whole-body elimination kinetics. Comparisons between estimated body burdens of dioxin and dioxin-like compounds associated with adverse health effects in experimental animals and humans have shown that humans and animals appear to respond to similar body burdens (DeVito et al., 1995).
By definition, the body burden of a chemicd is the tot'al amount of chemical present in the whole body at a particular time (Hodgson et al., 1988). Body burden of a chemical is determined by its toxicokinetics. It has been demonstrated that absorption, disuibution, and eIimination of dioxin and dioxin-like compounds are congener-specific (Flesch-Jays et al., 1996; Van den Berg et al., 1994). Further, parameters such as increased age of the exposed individual, increased body fat, and srnokin: may influence toxicokinetics (Resch-Janys et al.. 1996). Assumptions made regardins roxicokinetics of dioxin and dioxin-like compounds may result in limitations of the body burden method.
ATSDR acknowledges chat other approaches may be used to estimate internal dose such as the area-under-the-curve (AUC) approach (Aylward et al.. 1996). AUC is the total area under the curve that describes the concentration of a chemical in the systemic circulation as a function of time (from zero to infinity). AUC is equal to external dose divided by clearance (i-e., elimination rate divided by concentration in body fluid). As some authors have speculated (DeVito er al., 1995), i t is possible that, in addition to dose and body burden, length of exposure may also play a sisnificant role in the toxicity of dioxin and dioxin-like compounds. As such, i t may be advanca,oeous in some instances to use the AUC method. However, since information abour length of exposure and exrernal dose is often missins or inaccurate, the use of body burdens remains the merhod of choice to describe dose-response relationship. The body burden approzch is employed by other ATSDR prosrams (e.g., in epidemiolo2ic scudies executed by the Division of Health Studies), by other U.S. ~overnrnental a~encies (EPA, FDA), and by international agencics (%'KO, IARC).
788 De Rnscr ef al.
APPENDIX 3 - MRLs AND EMEGs FOR TCDD
CURRENT MRLs
ATSDR published the Toxicologicai Profle for TCDD (ATSDR. 1989). Minimal risk levels (MRLs) listed in the profile were for acute, intermediate-duration, and chronic on1 exposures (see Table 3-1).
Acrtre Oral MRL The acute orai MRL of 100 pglkg/day was based on hepatotoxic effects in guinea pigs that were observed following administration of a single gavage dose of 0. I pg&gTCDD (Turner and Collins, 1983).
An uncertainty factor of 10 was used for extrapolation from animals to humans, a factor of I0 for human variability, and a factor of 10 for the use of a lowesc-obsen~ed-adverse- effect level (LOEL) .
lnrernrediare Oral MRL The LOAEL of 0.001 pgkglday was considered for derivation of the intermediate- duration oral MRL of 1 p@g/day. At this exposure level, dilated pelvises and changes in gestational index were observed in rats (Murray et al., 1979) and abortions were reported in monkeys (Allen et al., 1979).
An uncertainty factor of 10 was used for extrapolation from animals to humans, a factor of 10 for human variability, and a factor of 10 for the use of a LOAEL.
C/zronic Oral MRL The intermediate-duration oral MRL of 1 p~Jklday was also adopted as the chronic oral RIRL.
PROPOSED MRLs
The Toxicolo,oica! Prujle for CDDs ulas i n a drafr staze in 1993/I 993. The internal MRL workgroup proposed oral MRLs for TCDD (see Table 3-1 ).
Acrue Otnl MRL The acute oral MRL of 20 ps/kg/day was based on the LOAEL. of 0.01 pg/k:/day- TCDD chat induced suppressed serum complement activity in B6C3F1 mice exposed to 14 daily doses administered by gavase-in-oil vehicle (White er a]., 1986).
An uncerrainty facror of 10 was used for extrapolation from animals to humans. a facror of 10 for human variabiliry. and a facror of 10 for thc use of a LOAEL. Furthermort. a
modifying factor of 0.5 was applied [o adjust for ihc difference in higher bioavailability of TCDD from ~avase-in-oil vehicle than from focd or soi I.
To.\-icolagy arrd Indurrr-ial Hea ltlz, Val. 13. . . No. 6. 1997 789
fnrertnediate Oral MRL The intermediate-duration oral MRL of 7 pgkglday was based on a no-observed- adverse-effect level (NOAEL) of 0.0007 pgkdday TCDD for decreased thymus weizht in guinea pigs exposed for 90 days in their feed (DeCzprio et al.. 1986). The LOAEL in the study was 0.005 W d a y .
An uncertainty factor of 10 was used for interspecies extrapolation and a factor of 10 for human variability. The NOAEL for deriving an intermediate-duration exposure MRL is also supported by the same level NOAEL for liver effects in the DeCaprio et al. study. The liver effects reported at higher levels consisted of hepatocelIular incIusions and hypertriglyceridemia.
Chronic Oral MRL A chronic oral MRL, of 0.7 pgkgfday was based on a LOAEL of 0.0002 pgkglday
TCDD in the feed of monkeys that resulted in mild learnin: and behavioral impairment in their offspring (Bowman et al., 1989).
An uncertainty factor of 3 was used for the use of a minimal LOAEL, a factor of 10 was used for interspecies extrapolation, and a factor of 10 for human variability.
Environmental media evaluation guides (EMEGs) are media-specific comparison values that are used to select contaminants of concern at hazardous waste sites.
EMEGs are derived for air, water, and soil environmental media. They are based on inhalation and oral MRLs for air and waterlsoil exposures. respectively. The methodology and formula for derivation of EMEGs are described in ATSDR's PubIic Health Assessment Guidance Manual (ATSDR. 1992).
EMEGs are estimates of external dose. They do not provide data on how much of the dose is actually absorbed. No E m G s are available for the dermal exposure route.
EMEGs based on these MRLs are presented in Tables 3-2a and 3-2b.
790 De Rosa el a!.
TABLE 3-1. I\IRLs' for TCDD
MRL' [n UF UF
Exposure p:Ag LOAEL inter- UF Year duration /day MOAEL species sensitivity h l F ' End point Study 1989 acute 100 10 10 10 LOAEL for heparoroxicity Turner and
guinea pigs Collins. 1983
1989 inter- I 10 10 10 LOAEL for abortions and Murray el
mediate orher reproductive, al., 1979
developmental effects rats, Allen et al., monkeys 1979
1989 chronic 1 10 LO 10 LOAEL for abonions and Murray et other reproductive, a!., 1979 developmental effecls rats, Allen et al.. monkeys 1979
1994 acute 20 10 10 10 0.5 LOAEL for suppressed White et al., serum complement activity I986 mice
1994 inter- 7 10 10 - NOAEL for decreased DeCaprio er rnediaie thymus weightl liver a]., 1986
toxicity guinea pigs 1994 chronic 0.7 3 10 10 LOAEL for mild learning Bowman et
and behavioral impairment al.. I989 monkey offspring
'The MRL is calculated as MRL = (HOAEL or LOAEL)/(UF x MF), where MRL = minimal risk level (mglkgiday). NOAEL = no-oiserved-adverse-effect IeveI (rnflgday). LOAEL = lowesc-obsenfed- adverse-effect level (rn/lt$day), UF = uncertainty facror (unicless). MF = modifyins factor (unitless) -'MF for bioa\~ailabiIitg was used in the derivarion of an acute MRL (1 991)
TABLE 3-2a. EMEGs (in ppb) Based on I989 TCDD MRLs
Exposure durarion Child Adulr acute 5 70 inremediate 0.05 0.7 chronic 0.05 0.7
TABLE 3-2b. EMEGs (in ppb) Based on 1991 TCDD hlRLs
Exposure durztion Child Adulr acute 1 I ? intrrmediats 5 3
chronic 0.04 0.5 'The EMEG is calculated as EMEG = (MRL)tB\i')AR. ushere EhEG = en\-ironmen~a! ~ ? - ~ i u a t i o ~ ~ u i d e (rng/l;s). BLi '= body u:eizhl i n k: (adulr = 70 k ~ : child = I0 ks). IR =soil i n Z z s [ i o n ra:s (mu~d2:j)
(zdult = iW ndday : child = 200 mziday)
Toxicology arrd l~ldrcm-inl Healrh. VoL 13. No. 6, 1997 79 1
APPENDIX 4 - RECENT HEALTH EFFECTS STUDIES
Inrroducrion A significant number of tcxicological studies have been conducted since the development of [he 1 ppb action level for dioxin and dioxin-like compounds in residential soil. Many of these studies have examined human health effects after known or suspected exposure. In addition. in these intervening years. analytical techniques have been perfected to pennit determination of very low
levels of dioxin and dioxin-like compounds in environmental and biologic media. Significant advances have also been made in assessing possible health effects associated with exposure. This appendix is a synopsis of this more recent information.
Mechanism pfAction Recent studies have indicated that dioxin and dioxin-like compounds act through the same mechanism of action mediated by the Ah receptor, and that responses to their toxicity have been shown to be similar in several species Pirnbaum, 1994; ~ e ~ t o et al., 1995).
Human Studies Direct exposure information is generally not available in human studies, and so body burden is used as.a surrogate. In this approach, the exposure is estimated from measured body burden, the elimination rate for humans, and the time since the exposure incident. Positive correlations have been observed between dioxin exposure and cancer (Fingerhut e t aL. 1991; Zober et al., 1990; Manz e t al., 1991). More recent studies on cohorts investigated previously confirmed the association between dioxin exposure and higher cancer morrality (Flesch-Janys et al., 1995; Becher et al.. 1996; Ott and Zober, 1996). The correlation was dose-dependent and increased with the latency period. IARC (1997) classified TCDD as a Group 1 carcinosen (carcinogenic to humans).
For healch end poinrs other than cancer, epidernio10,aic studies suggest a positive correlation between exposure to TCDD and development of chloracne (MocareIii et al., 1986; ~azderova- Vejlupkava et al., 1981; Regsani, 1980: Zober et al., 1990). dermal hyperpigmentation and hirsutisrn (Poland er al., 1971; Jirasek et aL, 1974). elevated hepatic enzymc levels, rnairlty y-,alutamyI transferase (Mocarelli et al, 1986; May, 1982), and increased risk of diabetes (Sweeney et al.. 1992; Table 4-1).
Other studits showed an association between development of subtle health effects (e.2.. lower vitamin K Ievels, mild chanses in liver enzymes, decreased neurologic optimality, and subtle changes in hormonal levels) i n infants and their exposure to dioxin and dioxin-like chemicals from rnacsrnal milk (Pluirn el al., 1992. I991.a. 1991.b: Huisrnan et al., 1995; Koopman-Esseboom er al., 1993; Table 4-71. It is important to note that in reviewing the issues surroundins breastfeedinz, the World Health Orzanization has concluded that the risks to infants do not
ou~weigh positive biolo~ic and psychologic aspects of breastfeeding (Johnson, 1992a).
792 De Rosa et a/.
I t has been suggested that dioxin and dioxin-like chemicals have the ability to disrupt endocrine function at low levels of exposure. A recent study of the cohort of people exposed during the Seveso accident indicated an alteration of the human sex ratio in their offspring (Mocarelli er al., 1996). In the 7-year period foIlowing the exposure, 26 males versus 48 females were born, bur the study was limited by not providing information on sex-related spontaneous abortions in the cohort. A study of occupationally exposed worken reported altered reproductive hormone levels (Egeland et al., 1992). Other studies indicate low-exposure contamination of maternal milk with dioxin and dioxin-like compounds may have an impact on the hypothalamic-pituitary-thyroid regulatory system in newborns (Pluim et al., 1992; Koopman-Esseboom et aL. 1994).
Animal Studies Studies in animals demonstrated a wide range of effects associated with CDDs exposure including mcrcality, cancer, wasting, and hepatic, immunologic. neurologic, reproductive, and developmental effects (ATSDR, 1989). In support of the findings that showed endocrine system disruption in humans, studies in animals reponed that TCDD affects the adrenal (DiBartolomeis et al.. 1987; Gorski et al.. 1988a. 1988b) and thyroid glands (Hermansky et al.. 1988; Honget al.. 1987; Lu et al., 1986; Henry and Gasiewicz, 1987; Rozman et aI., 1985) and also alters estradiol (Umbreit et al., 1987), testosterone, and dihydrotestosterone levels (Mebus et al., 1987; Moore et al., 1985).TCDD decreased responsiveness of the ventral prostate to testosterone in male offspring of exposed femaIe rats and inhibited sexual differentiation in the central nervous system without altering sexual dimorphism in estrogen-receptor concentrations (Bjerke et aI., 1994; Bjerke and Peterson, 1994). In animal studies, effects have been seen with the lowest doses evaluated, with the most sensitive end point being neurobehaviord changes in the offspring of dioxin-exposed monkeys (Schann et al.? 1992). A summary of critical study results and observed effect levels is presented in Table 4-3.
Body Burdens and Associared Healrk Effects Health effects reported from human studies and associated body burdens of TCDD are listed in TabIe 4- 1; these body burdens ranse from concentrations of 18 to 2,357 n&. As can be seen from a comparison of animal and human studies shown in Table 4-3, body burden concentrations calculated for effect dosage rates in animal studies are in the same range as body burden concentrations associated with healrh effects in human studies. These results underscore the need for research to elucidate the toxicity of dioxin at low doses to human populations (CCEHRP. 1992) and to evaluate exposures in at-risk popuiarions in view of total body burdens of dioxin and dioxin-like compounds.
Based on this review of more recent data, ATSDR has determined that its MRL of I ps/kz/day for TCDD is approximacelg two orders of magnitude below the health effect le\gels observed in recent studies. This is also true of cancer effect levels (Kociba ec al.. 1978). Independently. the Healrh Council of the Nerherlands (1996) reassessed the risk associated with dioxin and dioxin- liks compounds based on recent studies and recommended a health-based exposure limit equal ro I p~ikgldap [oral TEQs.
To.ricology and Indrcstriaf Health, Vol. 13. No. 6, 1997 793
ATSDR concludes that chechronic oral MRL of 1 pgkglday TCDD is protective of public health based on the fact that the MRL is approximately two orders of magnitude below the effect levels demonstrated experimentally and in epidemiologic studies.
TABLE 4-1. Health Effects Associated with Exposure to TCDD and Body Burdens in Humans
Duration Body burdens of exposure System Effect . ng/kg body weight Reference < I year Dermal Chloracne in children 2357' Mocarelli et al..
< l year
2 15 years
2 IS years
Not specified
11 yean'
6.5 years
2 15 years
1 15 years
Not specified
2 1 year
2 70 yean
Reproductive
Gastrointestinal
Hepatic
Dermal
Dermal
Immunologic
Neurologic
Reproductive
Genotoxicity
Cancer
Cancer
No increased risk of > 24b spontaneous abortion No increased risk of clinical 41gC gastrointestinal disease No increased risk of clinical 418' hepatic disease Chloracne in 517 subjecn 80Sd 1 8C
Chloracne 646*
No increased risk for 418c peripheral neuropathy Increased prevalence of 3 lh hizh luteinizing hormone and low test&terone levels No chromosome aberrarions 63-833' or sister chromatid exchanges Increased cancer mortality 124-459 risk Increased cancer mortality 69-46 1';
199 1 WoIfe et a!.. 1995 Calverr et al.. 1992 Calveit ct al.. 1997- Schecter.et al., 1993 Jansing and Korff. 1994 Tonn et al.. 1996 Sweeney et al., 1993 Eo,eland et al.. 1991
Zober et ai., 1993 Fingerhut a al., I991 Manz et a!..
rate 1991
796 De Rosa et al.
TABLE 4-3. Human Body Burdens a n d Animal Body Burdens Associated with HeaIth Effects
Body burdens Duration of ngkg body exposure System Effect weieht Reference Studies in humans c 1. year Dermal Chloracne in 2357'
children Nor specified Dermal Chloracne in 5/7 80Sb 18'
subjects
11 years Dermal Chloracne 646d
6.5 years Immunologic Immunosuppression 156-176'
1 15 yean Reproducrive Increased prevalence 3 1' of high iuteinizing hormone and low testosterone levels
Mocarelli er al., 199 1 Schecter et al.. 1993
Jansing and Kotff. 1994
Tonn et al.. 1996 Egeland et al., 1994
2 1 year Cancer Increased cancer 124-459g Fingerhut et d., mortaliry risk I991
r 20 years Cancer Increased cancer 69-46 I h. Manz ec al.. 1991 mortaIity rate
Studies in animals
14 days Immunologic Suppressed serum 74' complement in mice
90 days Reproductive Decreased litter size 26 in rats
'White et a!., 1986 'Murray et al.. 1979
90 days IrnmunoIogic Decreased thymus 164' 'DeCaprio et al., weight in guinea 1986 pigs
16 months De\-elopmental Behavioral 3 2' Schanu: et al.. alterations in 1997- offspring in monkeys
2 years Cancer Liver, lung 2976" Kociba et al..
carcinoma in rars 1978 2 years Cancer Liver carcinoma in 9W N T P . 1973,
mice
Toxicology and Ir~dlcsfricrl Healrh. Val. 13. No. 6. 1997 797
TABLE 4-3. Human Body Burdens and Animal Body Burdens Associated with Health
Effects (cont'd)
*Studies which serve as the basis for ATSDR's health guidance values - 'Calculated using serum TCDD levels measured shanly after exposure. Body burdens were calculated using body weights of 13 kg for 1-3 year olds. 20 kg for 4-6 year oldz. 28 kg for 7-10 year olds. 45 kg for 1 I-year-old males. and 55 kg f ~ r 16year-old f e d e s and body fat percentages of 15% for 0-10 year olds. 15% for 1 I-year-old males, and 20% for 16-year-old females (ICRP, 198 1). bCdculated by averaging the reported individual body burdens divided by the reference body weight of 75 kg for males and 65 kg for femalcs. The authors calculated half-life adjusted serum TCDD levels using the assumption of 75 kg and 65 kg body weights for male and female workers, respeaiveIy, and a half-life of 5 years. CSarne as footnote d but using a half-life of 10 years. dCalculated using the reported mean half-life adjusted serum TCDD level of 2935 pg/g blood fat and assuming the average worker weighed 70 kg with 22% body fat @cVito et d. 1995). The authors calculated the haif- life adjusted serum TCDD level using a half-life of 7 years. eCaIculated using the reported mean current serum TCDD level of 3295 pglg blood lipid, Half-life adjusted serum TCDD level was calculated using a half-life of 11.6 years (Wolfe et al.. 1994). backggund TCDD concenrracion of 5 ngkg lipid, and 13-15 ycan eiapsed time. Body burdens were calculated assuming the average worker weighed 70 kg with 22% body fat (DeVito t t al., 1995). fCalcuiaced using the reported half-life adjusted serum TCDD level of > 140 p$g blood lipid and assuming the average worker weighed 70 kg wich 22% body fat (DeVito et al., 1995). The authors calculated the adjusted serum dioxin level using a dioxin half-life of 7.1 yean and background dioxin level of 6.08 pg/g blood lipid. gcalculated using the reported mean current serum TCDD ievel of 233 pglg lipid Half-Iie adjusted serum TCDD levels were caIculattd using a half-life of 11.6 years (Wolfe et al.. 1994). back,oround TCDD concentration of 5 n&.g lipid, and 35 years of elapsed time. Body burdens were calculated assuming the average worker weighed 70 kg with 22% body fat (DeVito et al., 1995). hCalculated using the repotted mean current adipose tissue TCDD level of 296 ngkg. Half-life adjusted adiposeTCDD levels were cdculated usins a half-life of 1 1.6 years (Wolfe et al., 1994), back-mund TCDD concentration of 5 ngkg lipid, and 1-33 years of elapsed time. Body burdens were calculated assuming the avenge worker weighed 70 kg with 228 body fat (DeVito et aI.. 1995). ' Acure exposure study in mice (White et al.. 1986). Assumed parameter values a: = 0.8 (Curtis et aL, 1990). ,, = 11 days (Birnbaurn. 1986). J Intermediate-duration exposure study in rats (Murray et al.. 1979) Assumed paramerer values a: = 0.8 (Curris c t al., 1990). t,, = 24 days (Van den Berg er al.. 1994).
Assumed parameter values for guinea pigs in DeCaprio ec al. (1986) study: a = 0.5 (Van den Ber: ct al.. 1994), t,, = 94 days (Olson, 1986). 'The lowest effect level in the current database for chronic-duration exposure- Assumed parameter values for monkeys in Schantz et aI. (1992) study: a = 0.8 (value for rats from Van den Berg et aL. 1994). t,, = 391 days (Bowman et ai.. 1989). "A cancer study in rats. Body burdens calculated in De VXO er al., 1995. "A cancer study in mice. Body burdens calculated in De Vito ct al.. 1995-
Toxicologv nrrd ~ r~dr r~ r l - id Hea!th, VO~. 13, No. 6. 1997 79 1
APPENDIX 4 - RECENT HEALTH EFFECTS STUDIES
Inrroduction
A significant number of toxicological studies have been conducted since the development of the 1 ppb action level for dioxin and dioxin-like compounds in residential soil. Many of these studies have examined human health effects after known or suspected exposure. In addition, in these intervening years, analyrical techniques have been perfected to permit determination of very low levels of dioxin and dioxin-like compounds in environmental and biologic media. Significant advances have also been made in assessing possible health effects associated with exposure. This appendix is a synopsis of this more recent information.
Mechanism pfAcrion Recent studies have indicated that dioxin and dioxin-like compounds act through the same mechanism of action mediated by the Ah receptor, and that responses to their toxicity have been shown to be similar in several species (Birnbaurn. 1994; ~ e V i t o et al.. 1995).
Human Srudies Direct exposure information is generally not available in human studies, and so body burden is used as a surrogate. In this approach, the exposure is estimated from measured body burden, the e l i n a t i o n rate for humans, and the time since the exposure incident. Positive correlations have been observed between dioxin exposure and cancer (Fingerhut e t aL, 1991; Zober et al., 1990; Manz et al., 1991). More recent studies on cohorts investigated previously confirmed the association between dioxin exposure and hisher cancer mortaIiry (Flesch-Tanys et aI., 1995; Becher et al.. 1996; On and Zober, 1996). The correlation was dose-dependent and increased with the latency period. IARC (1997) classified TCDD as a Group 1 carcinogen (carcinogenic to humans ).
For health end points other than cancer, epidemiologic studies suggest a positive correlation between exposure to TCDD and development of chloracne (MocareIIi et al., 1986; ~azderova- Vejlupkova et al., 1981; Reggiani, 1980: Zober et al., 1990). dermal hyperpigmentation and hirsutisrn (Poland ec a\., 197 1; Jirasek et ai., 1974), elevated hepatic enzymc levels, mair11y y-glutamyl mnsferase (Mocarelli et aL, 1986; May. 1982). and increased riskof diabetes (Sweeney et al., 1992; Table 4-1).
Other studits showed an association between development of subtle health effects (e.2-. lowa vitamin K levels, mild chanses in liver enzymes, decreased neurologic optimality, and subtle changes in hormonal levels) in infants and their exposure to dioxin and dioxin-like chemicals from maternal miIk (Pluim et al., 1992. 1991a, 1994b: Huisrnan et al., 1995; Koopman-Esseboom e[ a[., 1994; Table 4-21. It is important to note that in reviewing the issues surround in^ brezstfeedins, the World Health 0r:anization has concluded that the risks to infants do nor ourweigh ds posicive biolosic and psychologic aspects of breastfeedins (Johnson. 1992a).
792 De Rosa er nl.
I t has been suggested that dioxin and dioxin-like chemicals have the ability to disrupt endocrine function at low levels of exposure. A recent study of the cohort of people exposed during the Seveso accident indicaced an alteration of the human sex ratio in their offspring (Mocarelli et al., 1996). In the 7-year period following the exposure, 26 males versus 48 females were born. but the study was limited by not providing information on sex-related spontaneous abortions in the cohort. A study of occupationally exposed workers reponed altered reproductive hormone levels (Egeland et al., 1992). Other studies indicate low-exposure contamination of maternal milk with dioxin and dioxin-like compounds may have an impact on the hypothalamic-pituitary-thyroid regulatory system in newborns (Pluim et al., 1992; Koopman-Esseboom et al.. 1994).
Animal Srudies Studies in animals demonstrated a wide range of effecu associated with CDDs exposure including mcrtality, cancer, wasring, and hepatic, immunologic, neurologic, reproductive, and developmental effects (ATSDR, 1989). In suppon of the findings that showed endocrine system disruption in humans, studies in animals reponed that TCDD affects the adrenal (DiBartolomeis et al-. 1987; Gorski et al., 1988a. I988b) and thyroid glands (Hermansky et al., 1988; Hong et al., 1987; Lu et al., 1986; Kenry and Gasiewicz, 1987; Rozman et al., 1985) and also alters estradiol (Umbreit et al., 1987), testosterone, and dihydrotestosterone levels (Mebus et al., 1987; Moore et al.. 1985).TCDD decreased responsiveness of the v e n d prostate to testosterone in male offspring of exposed female rats and inhibited sexual differentiation in the central nervous system without altering sexual dimorphism in estro~en-receptor concenuations (Bjerke et id., 1994; Bjerke and Peterson, 1994). In animal studies, effects have been seen with the lowest doses evaluated. with the most sensitive end point being neurobehaviord changes in the offspring of dioxin-exposed monkeys (Schantz et al.. 1992). A summary of critical study results and observed effect levels is presented in Table 4-3.
Body Brtrdens and Associared Heairk ERecrs Health effects reported from human studies and associated body burdens of TCDD are listed in Table 4 1; these body burdens range from concentrations of 18 to 2,357 risks. As can be seen from a comparison of animal and human studies shown inTable 4-3, body burden concentrations calculated for effect dosase rates in animaI studies are in the same range as body burden concentrations associated wich health effects in human studies. These results underscore the need for research to elucidate the toxicity of dioxin at low doses to human populations (CCEHRP, 1992) and to evaluate exposures in at-risk popularions in view of total body burdens of dioxin and dioxin-like compounds.
Based on this review of mare recent data, ATSDR has determined that its MRL of 1 pglk~lday for TCDD is approximately two orders of magnitude below the health effect levels observed in recent studies. This is also true of cancer effect levels (Kociba ec al., 1978). Independently. the
Health Council of the Nerherlands ( 1996) reassessed the risk associated with dioxin and dioxin- like compounds based on recent srudies and recommended a heaIth-based exposure Iirnit equal to I pgik,aida\: [oral TEQs.
To.ricology arrd Ind[csrrial Health, Vol. 13, No. 6, 1997 793
ATSDR concludes that the chronic oral MRL of 1 pskg/dayTCD~ is protective of public heal& based on the fact that the MRL is approximately two orders of magnitude below the effect levels demonstrated experimentally and in epidemiologic studies.
TABLE 4-1. Health Effects Associated with Exposure to TCDD and Body Burdens in Humans
Duration Body burdens of exposure System Effect ng/kg body weight Reference c I year Dermal Chloracne in children 2357' Mocarelli er al..
c 1 year
1 15 years
2 15 yean
Not specified
I1 years
6.5 years
2 I5 years
2 15 years
Not specified
2 1 year
2 20 years
Reproductive
Gastrointestinal
Hepatic
Dermal
Dermal
Irnmunolo~ic
Neurologic
Reproductive
Genotoxicity
Cancer
Cancer
No increased risk of > 24b spontaneous abortion No increased risk of clinical 4 1 gC gasomintestinal disease No increased risk of clinical 418' hepatic disease Chloracne in 5n subjects 80.Sd 1 8C
Chloracne 646'
Imrnunosupprcssion 156-1769
No increased risk for 41ac peripheral neuropathy Increased prevalence of 3 lh high luteinizjng hormone and low testosterone levels No chromosome aberrations 63-833' or sister chromatid exchanges Increased cancer mortality 124-459 risk Increased cancer rnowliry 69-46 1'; race
1991 Wolfe et al., 1995 Calverr et d., 1992 CalVerr et al.. 1997- Schecter et al., 1993 Jansing and KO*. 1994 Tonn et al., 1996 Sweeney et al.. 1993 Egeland et al.. 1994
Zober er at.. 1993 Fingerhut ct aI.. 1991 Manz et al.. 1991
796 De Rosa et al.
TABLE 4-3. Human Body Burdens and Animal Body Burdens Associated with Health Effects
Body burdens Duration of ngkg body exposure S yslern Effect weight Reference Studies in humans < 1. year DermaI Chloracne in 2357' Mocarelli et al..
children 199 1 Nor specified Dermal ChIoracne in 5/7 80Sb 18' Schecter et at.,
subjects 1993 1 I years DermaI Chloracne 646* Jansing and Korff,
1994 6.5 years Immunologic Immunosuppression 156-176' Tonn et al., 1996
2 15 years Reproductive Increased prevalence 3 1' of high Iuteinizing hormone and low testosterone levels
Egeland et al., 1994
Z 1 year Cancer Increased cancer 124-459' Fingerhut et al., mortality risk 1991
> 20 years Cancer Increased cancer 69-46 I Manz et a].. 1991 mortality rate
Studies in animals
14 days Immunologic Suppressed serum 74' -White et al., compIernent in mice 1986
90 days Reproductive Decreased litter size 26 'Murray et al.. in rats 1979
90 days IrnmunoIogic Decreased thymus 1 6?L -DeCaprio et al.. weight in guinea 1986 pigs
16 months Developmental Behavioral 3 2' . Schanrz et al., alterations in 1997 offspring in monkeys
2 years Cancer Liver, lung 2976" Kociba et d., carcinoma in racs 1978
2 years Cancer Liver carcinoma in 944" NTP, 1972 mice
Toxicologv and I,~dirsrrinl Healrh. Vol. 13, No. 6. 1997 797
TABLE 4-3. Human Body Burdens and Animal Body Burdens Associated with Health
Effects (cont'd)
*Studies which serve as the basis for ATSDRS health guidance values - 'Calculated using serum TCDD levels measured shortly after exposure. Body burdens were calculated wing body weights of 13 kg for 1-3 year olds. 20 kg for 4-6 year ol&. 28 kg for 7-10 year olds, 45 kg for I I-year-old males. and 55 kg f ~ r 16-year-old females and body fat percentages of 15% for 0-10 year olds. 15% for I 1 -year-old males, and 20% for 16-year-old females (ICRP, 198 1). bCaldulated by averaging the reported individual body burdens divided by the reference body weight of 75 kg for males and 65 kg for females. The authors calculated half-life adjusted serum TCDD levels using the assumption of 75 kg and 65 kg body weights for male and female workers, respectively. and a half-life of 5 years. 'Same as footnote d but using a half-life of 10 years. dCalcuIatcd using the reported mean half-Iife adjusted serum TCDD level of 2935 pgfg blood fat and assuming the average worker weighed 70 kg with 22% body fat (De-to et al., 1995). The authors calculated the half- life adjusted serum TCDD level using a half-life of 7 years. 'Calculated using the reported mean current serum TCDD level of 3295 pg/g blood lipid. Half-life adjusted serum TCDD level was calculated using a half-life of 11.6 years (Wolfe et al.. 1994). back,mund TCDD c o n c e n ~ o n of 5 ngYkg lipid, and 13-15 years elapsed time. Body burdens were calculated assuming the average worker weighed 70 kg with 22% body fat (DeVito et al., 1995). *Caiculated using the reported half-life adjusted serum TCDD level of > 140 pgg blood lipid and assuming the average worker weighed 70 kg with 22% body fat (DeVito et al., 1995). The authors calculated the adjusted serum dioxin level using a dioxin half-life of 7.1 years and background dioxin level of 6.08 pgg blood lipid. gcalculated using the reported mean cumnt serum TCDD Ievel of 233 pdg lipid Half-life adjusted serum TCDD levels were caIculated using a half-life of 11.6 years (Wolfe et al., 1994). background TCDD concentration of 5 ngkg lipid, and 35 years of dapsed ame. Body burdens were calculated assuming the averaie worker weighed 70 kg with 22% body fat @eVico et a!.. 1995). hCalculated using the reporred mean current adipose tissue TCDD level of 296 n&. Half-life adjusted adiposeTCDD levels were calculated using a half-life of 1 1.6 years (Wolfe et al.. 1994). back-mund TCDD concentration of 5 lipid, and 1-33 years of elapsed time. Body burdens were calculated assuming the average worker weighed 70 kg with 22% body fat (DeVito et a]., 1995). ' Acute exposure study in mice (White et al.. 1986). Assumed parameter values a: = 0.8 (Curtis et aL. 1990). F,, = 11 days (Birnbaum. 1986). J Intermediate-duration exposure study in mts (Murray et al.. 1979) Assumed parameter values a: = 0.8 (Curtis et al., 1990), t,, = 24 days (Van den Berg ec al.. 1994). '; Assumed parameter values for guinea pigs in DeCaprio et al. (1986) study: a = 0.5 (Van den Bers et al.. 1994). t,, = 94 days (Olson, 1986). 'The lowest effect level in the current database for chronic-duration exposure. Assumed parameter values for monkeys in Schantz et al. (1992) study: a = 0.8 (value for rars from Van den Berg et aL. 1994). t,, = 39 1 days (Bowman et al., 1989). "A cancer study in rats. Body burdens calculated in De Vico ct al.. 1995. "A cancer study in mice. Body burdens calculated in De Vito cr al.. 1995.
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