Click for next page ( 18


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 17
A Summary of Dioxin Reports, Assessments, and Regulatory Activity This chapter begins with a brief summary of evaluations from several gov- ernmental bodies on the toxicity of chlorinated dibenzo-p-dioxins (CDDs) and related compounds, including chlorodibenzofurans (CDFs) and polychlorinated biphenyls (PCBs) with dioxin-like activity, and on the potential human health effects from exposure to these compounds. For brevity, these compounds will be referred to in this report collectively as "dioxin-like compounds" (DLCs), except when there is a need to refer to one of the specific compounds. This chapter also contains information on DLC-related regulations and guidelines that have been established in the United States, a number of European countries, Japan, and Australia for the environment, feeds, and foods. The chapter concludes with discussions on DLC monitoring and research programs and on methods of chemi- cal analysis for DLCs in feeds and foods. EVALUATIONS BY GOVERNMENTAL BODIES This section presents information about the toxicity of DLCs. For CDDs and CDFs, dioxin-like activity requires chlorination of the parent compounds at the 2, 3, 7, and 8 positions; for PCBs, this activity requires chlorination at four or more positions (with at most one ortho substitution). While there are 75, 135, and 209 different CDDs, CDFs, and PCBs, respectively, only 7, 10, and 12 of them are considered to have dioxin-like activity (Figure 2-1~. This section begins with a description of toxicity equivalency factors and toxic equivalencies, which are systems that have been developed to compare the potential toxicities of various dioxin congeners (i.e., compounds that have similar 17

OCR for page 17
18 (A) Cl5,~~ OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 19 . . . . . . The Agency for Toxic Substances and Disease Registry's (ATSDR) Toxi- cological Profile for Chlorinated Dibenzo-p-dioxins (ATSDR, 1998~. This report primarily covers the toxicity of CDDs. It alludes to CDFs and PCBs generally only in discussions of contaminant concentrations in environmental media and foods since these compounds (particularly CDDs and CDFs) are commonly analyzed simultaneously. (ATSDR has published separate toxicological profiles on CDFs and PCBs [ATSDR 1994, 20001.) A report prepared for the European Commission DO Environment, Evalu- ation of the Occurrence of PCDD/PCDF and POPs in Wastes and Their Potential to Enter the Foodchain (Fiedler et al., 2000~. This report pro- vides a cursory discussion of toxicity, body burdens, and intakes and focuses on the occurrence of persistent organic pollutants (POPs) in envi- ronmental media, animal feeds, and pathways of contamination. It ad- dresses only about a dozen POPs, but CDDs and CDFs are discussed thoroughly because of the relatively large databases for these compounds. A report prepared for the European Commission DO Environment and the U.K. Department of the Environment and Transport and the Regions, Compilation of EU Dioxin Exposure and Health Data (AEA Technol- ogy, 1999~. This report contains a thorough review of exposure and health effects data. An initial report and an update from the Scientific Committee on Food of the European Commission, Health and Consumer Protection Directorate- General, Opinion of the Scientific Committee on Food on the RiskAssess- ment of Dioxins and Dioxin-like PCBs in Food (Scientific Committee on Food, 2000, 2001~. The initial report focuses on dietary exposure and toxicity of DLCs; it does not address pathways of contamination. The update, based on scientific information made available after release of the initial report, includes new toxicity and tolerable intake information only. The International Agency for Research on Cancer's (IARC) IARC Mono- graphs on the Evaluation of Carcinogenic Risks to Humans. Volume 69: Polychlorinated Dibenzo-para-dioxins and Polychlorinated Dibenzo- furans (IARC, 1997~. The focus of this report is assessment of the poten- tial human carcinogenicity of CDDs and CDFs, but other issues, such as other types of toxicity, environmental occurrence, and human exposure, are also covered. The U.S. Environmental Protection Agency's (EPA) draft Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds (EPA, 2000~. This draft reassessment is the most extensive compilation of data on the environmental occur- rence and toxicity of DLCs and the consequent human exposures and risks.

OCR for page 17
20 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY Toxicity Equivalents and Toxicity Equivalency Factors The biological activities of DLCs vary and, since humans are usually ex- posed to mixtures of DLCs, the toxicity of an exposure depends on the particular composition of the mixture. It is desirable to express the expected biological activity of mixtures using a common metric. The biological activities of the various dioxin congeners are compared to the activity of 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD). TCDD is the most biologically potent of the DLCs, and the greatest amount of toxicity information has been gathered for this dioxin congener. The toxic potency of a mixture of DLCs is therefore expressed in TCDD toxicity equivalents, or TEQs. As an example, exposure to a mixture of DLCs with a potency of 2 ng TEQ/kg means that the total mixture is expected to have the potency of an exposure equal to 2 ng TCDD/kg. The TEQ value for a mixture is calculated by multiplying the mass or concentration of each DLC by a toxicity equivalency factor (TEF) and summing across all DLCs present. TEFs are calculated as a way to express the activity of DLCs in relation to TCDD as determined by various biochemical or toxicological assays. A sample TEQ calcu- lation is shown in Table 2-1. (For further discussion of the derivation and use of TEQs and TEFs see EPA, 2000.) Any mixture that yields a certain TEQ concentration is assumed to have the same toxic potential as another mixture with the same TEQ. Although the TEF system is useful for determining toxicity in mixtures of DLC congeners, it cannot be used to simplify environmental fate and transport analyses of DLCs because individual congeners differ in their physical and chemical properties, an impor- tant consideration in fate modeling. Several TEF schemes have been developed over the years; they differ regarding the inclusion of dioxin-like PCBs and TEFs TABLE 2-1 Sample Toxicity Equivalents (TEQ) Calculation for a Mixture of Dioxin-like Compounds Compound Mass Concentration (ng/kg) Toxicity Equivalency Factor TEQ Concentration (ng TEQ/kg) TCDD 2 1 2 1,2,3,4,7,8-HxCDD 35 0.1 3.5 1,2,3,4,6,7,8,9-OCDF 12 0.001 0.012 3,3',4,4',5-penta-CB (PCB-126) 46 0.1 4.6 2,3,4,4',5-penta-CB (PCB-114) 186 0.0005 0.093 Total 281 10.205 NOTE: TCDD = 2,3,7,8-tetrachlorodibenzo-p-dioxin, HxCDD = hexachlorodibenzo-p-dioxin, OCDF = octachlorodibenzofuran, CB = chlorinated biphenyl, PCB = polychlorinated biphenyl.

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 21 for certain compounds. The biological activity of a mixture of DLCs may be estimated differently depending on the TEF system used and the particular com- pounds analyzed. Appendix Tables A-1 and A-2 present the common TEF sys- tems. Although the use of TEFs provides a convenient method for assessing the toxicity of mixtures of DLCs, there are limitations to this method. These limita- tions include uncertainties associated with the TEF values assigned to each DLC congener; whether TEF values are constant across all responses and ranges of dose; whether all effects of DLCs, including TCDD and PCB congeners, are mediated via the arylhydrocarbon receptor; whether a TEQ for a DLC mixture is the sum of the toxicity of each DLC present in mixture; and whether all mixtures with the same TEQ have the same toxicity. Potential Human Health Effects from Exposure to DLCs Chemical dose is typically measured as an intake in units of mass per unit of body weight, such as 2 mg of calcium/kg. However, for compounds that are cleared slowly from the body, such as DLCs, intakes are not very useful for understanding toxicity profiles, dose-response modeling, or interspecies com- parisons. In the case of DLCs, a given intake can create very different internal concentrations in the species and target organs of interest, depending on the duration of dosing and toxicokinetic and toxicodynamic parameters (e.g., the fat content of the target tissue and the half-life of the specific dioxin congener in an organism). Reviews of DLC toxicity generally refer to an internal exposure met- ric, such as body burden, or to concentration in a particular tissue when such data are available. Different body burden definitions may be used, such as steady state, lifetime average, or peak concentrations. Because DLCs are preferentially associated with lipids, body burden concentrations are frequently given in units of mass per mass of lipid. Various reports cited in this chapter provide different measurement units. No conversions to other units were made for any of these values to ensure the accuracy of the values as presented by the study author. Effects Observed in Humans at General Exposures General exposure is defined here as that received through everyday life. The general population, breastfeeding infants, and consumers of contaminated fish are considered to have general exposures to DLCs. Occupationally exposed work- ers and victims of unintentional releases are not included. An exception is made for the Times Beach, Missouri investigations, since body burdens of TCDD in exposed subjects were similar to those of the general population, despite wide- spread soil contamination. The reports cited earlier (AEA Technology, 1999; ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; IARC, 1997; Scientific Committee on Food, 2000,

OCR for page 17
22 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY 2001) consider all human data, regardless of dose, or focus on high-dose popula- tions because of the greater probability of observing an effect. These reports describe certain populations as "poisoned" or "highly exposed," including those in pesticide manufacturing studies, the Ranch Hand studies, the Seveso reports, and the Yusho and Yu-cheng investigations (see below). There are several stud- ies of cancer in pesticide applicators, but they are confounded by lack of specific exposure information. Studies of Swedish (Axelson and Sundell, 1974, as cited in EPA, 2000) and Finnish (Riihimaki et al., 1982, 1983, as cited in EPA, 2000) applicators that used both 2,4-D (2,4-dichlorophenoxyacetic acid) and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) showed a slight increase in relative risk for cancer, but exposure to TCDD or other DLCs was not quantified. A study of 1,261 Air Force veterans known as Ranch Hands, who were responsible for aerial herbicide spraying in Vietnam, showed that the men had a median TCDD blood serum level that was 12.4 ppt (range 0-618 ppt) compared with 4.2 ppt in controls (Air Force veterans engaged in cargo transport), with the greatest exposure in the nonflying ground personnel (median value 23.6 ppt) (Wolfe et al., 1990, as cited in EPA, 2000~. Follow-up studies through the early l990s suggested that this group did not have an increased risk of cancer death, although it was noted that in general the Ranch Hands did not have elevated TCDD levels significantly above background and were still a relatively young group, taking into account a 20-year cancer latency period (EPA, 2000~. In 1976, an unintended industrial release in Seveso, Italy, exposed a large population of people to TCDD. At the time of the release, serum levels of TCDD were as high as 56,000 ppt for the most highly exposed children, who developed severe chloracne (Mocarelli et al., 1991, as cited in EPA, 2000~. Twenty years after the release, tissue plasma levels of TCDD were measured in randomly selected residents. Those from the area with the greatest initial exposure had geometric mean TCDD levels of 53.2 ppt (n = 7; range 1.2-89.9 ppt); those with the next greatest exposure had 11.0 ppt (n = 51~; and those with the lowest exposure had 4.9 ppt (n = 52) (Landi et al., 1996, 1998, as cited in EPA, 2000~. In a 15-year follow-up, the overall cancer mortality in the residents did not appear to be increased compared with a control group from outside the exposed area, although significant excess mortality risks occurred in the lowest exposure group for esophageal cancer in males and bone cancer in females (Bertazzi et al., 1997, 1998, as cited in EPA, 2000~. EPA reports that the cancer data appear to be contradictory and are difficult to interpret because of the small number of cases, problems with exposure classification, and a 15-year rather than a 20-year fol- low-up (EPA, 2000~. Two significant occurrences of poisoning of food oils with PCBs and furans have been reported in Japan. The first occurred in 1968 in the Yusho incident, in which 1,900 people unintentionally consumed up to 2 g of rice oil that contained a 1:250 ratio of furans to PCBs. Tissue studies indicated that both the furans and

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 23 the PCBs were retained for many years. There was a significantly increased risk of liver cancer in males 15 years after the incident, although determination of rice oil as the culprit was problematic (Kuratsune et al., 1988, as cited in EPA, 2000~. Noncancer effects included acneform eruptions, hyperpigmentation, and hyper- keratosis and ocular lesions. The second incident (Yu-chen) was a contamination of cooking oil in Taiwan in 1979 that affected 2,000 people and resulted in similar noncancer effects. Six months after the incident, blood PCB levels ranged from 11 to 720 ppb with a mean value of 49 ppb and most values less than 100 ppb (Chen et al., 1980, as cited in EPA, 2000~. There have been few epidemiological investigations of the health effects of DLCs in populations with no extraordinary exposure circumstances. A large population of children from an industrial region in the Netherlands is currently being studied for a variety of health outcomes in relation to exposure to DLCs (Vreugdenhil et al., 2002), and Koopman-Esseboom and colleagues (1994a) ex- amined DLC levels in blood and human milk in two cohorts, one industrial and one rural, in the Netherlands (see below). Cancer. Epidemiological studies on carcinogenicity from general exposures to DLCs are sparse, but experimental animal studies provide strong support of carcinogenicity. The IARC monographs (1997) include no cancer epidemiology studies regarding general exposures to CDDs and express no opinion about the potential for carcinogenicity from such exposures. All of the investigations de- scribed in the monographs are cohort studies of workers with known, inferred, or presumed exposure to CDDs (usually TCDD); cohort studies of the Seveso popu- lation with unintentional TCDD exposure; or case-control studies in which sub- jects had known or expected contact, usually on the basis of occupation, with chlorophenoxy herbicides that likely contained TCDD. The monograph on CDFs describes a few studies of cancer in humans, including investigations that showed a moderate increase in cancer incidence and mortality in Swedish fishermen and consumers of Baltic Sea fish. Stomach cancer incidences in the Swedish consum- ers were 2.2 (1.3-3.5) and 1.6 (1.0-2.4) per thousand, compared with consumers of Atlantic Ocean fish and regional referents, respectively. Squamous-cell skin cancer rates were 1.9 (1.2-3.1) and 2.3 (1.5-3.5) per thousand compared with Atlantic Ocean fish consumers and the referent group, respectively (IARC,1997~. EPA (2000) includes no cancer epidemiology studies regarding general ex- posures to DLCs, but it does provide dose-response data for populations that are highly exposed to DLCs. The relative risk for total cancer for the lowest-exposed stratum in the epidemiological studies cited by EPA ranged from 0.9 to 1.24 (see Appendix Table A-3~. However, as reported by EPA (2000), in some exposed populations such as those in Seveso, Italy, the calculated relative risk for specific cancers was considerably higher (e.g., the relative risk for connective and soft tissue sarcoma in males was 2.8~. In studies that have identified specific cancers

OCR for page 17
24 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY arising after DLC exposure, the evidence is equivocal. However, the cumulative evidence of all studies is consistent with the possibility that DLC exposure is . . carclnogemc. None of the evaluations reviewed by the committee (AEA Technology, 1999; ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; IARC, 1997; Scientific Commit- tee on Food, 2000, 2001) derives a conclusion about the carcinogenic potential of DLCs to humans solely from general exposures. Noncancer Effects. Several potential noncancer health effects from general exposures to DLCs have been reported in recent evaluations of DLC toxicity (ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; IARC,1997~. These evaluations indicate that there are possible adverse neurobehavioral effects and changes in the distribution of thyroid hormone concentrations in breastfed infants compared with formula-fed infants. Koopman-Esseboom and colleagues (1994b) found a negative correlation between extended DLC exposure and thyroid hormone lev- els in infants and mothers. The Scientific Committee on Food (2000, 2001) also reports neurobehavioral effects and changes in thyroid hormone status in breastfed infants, but stated that these adverse effects were "subtle, within the normal range, and considered without clinical relevance," whereas Weisglas-Kuperus and coworkers (2000) and Patandin and coworkers (1998) concluded that DLCs have a negative effect on neurodevelopment, birth weight, and immunity. EPA (2000) identifies one study that found changes in the distribution of alanine aminotransferase and aspartate aminotransferase concentrations in breastfed in- fants. Adverse effects on infant birth weight, neurodevelopment, neurobehavior, thyroid hormone status, and the immune system in children have been reported (AEA Technology, l999~. These observations were made in infants in the general population and in children whose mothers ate DLC-contaminated fish from Lake Michigan. Neurodevelopmental delays in breastfed infants in a Dutch study were also reported (Huisman et al., 1995~. A negative correlation was found between neurodevelopment in infants and breast-milk concentrations of PCBs. At 42 months of age, the cognitive decrement remained (Patandin et al., 1999), al- though the psychomotor deficits seen at younger ages had disappeared (Lanting et al., 1998~. A study of early learning in school-age Dutch children found that prenatal exposures to DLCs resulted in impaired cognitive and motor abilities, which could persist when the home environment was less than optimal, but no long-term impairment could be measured in children raised in more optimal environments (Vreugdenhil et al., 2002~. One evaluation (AEA Technology, 1999) notes that people with exposure to TCDD from the Times Beach contami- nation showed reduced immune response and changes in T-lymphocyte differen- tiation, and people eating relatively large amounts of Baltic Sea fish showed changes in T-cell lymphocytes, but IARC (1997) reports contradictory findings about cell-mediated immunity in the Times Beach subjects. EPA (2000) consid-

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 25 ers the data about immunological effects from exposures to DLCs to be inconclu- sive. Effects Observed in Humans at Higher Exposures Cancer. The IARC (1997) evaluation discusses the body of epidemiological literature on CDDs, but it focuses on the high-exposure cohorts with documented TCDD exposure (all occupational exposures) in its evaluation of whether CDDs are carcinogenic to humans. It concludes that the overall standardized mortality rate for all cancer types combined was 1.4 per thousand (95 percent confidence interval, 1.2-1.6) for the most highly exposed subgroups in these occupational cohorts; statistically significant dose-response trends in two of the studies strengthen that opinion. IARC also concludes, however, that the epidemiological data provide "lim- ited evidence" of a carcinogenic effect of TCDD in humans, although the IARC monographs (1997) upgrade 2,3,7,8-TCDD from classification 2A, Probably Carcinogenic to Humans, to 1, Carcinogenic to Humans. In its monograph on the carcinogenicity of CDFs, IARC notes that male victims of the Yusho incident had a threefold excess of liver cancer mortality, but that no such excess occurred in victims of the Yu-cheng incident, and finds the evidence for the carcinogenicity of CDFs in humans to be inadequate. The reports of the Scientific Committee on Food (2000,2001) rely largely on the IARC (1997) evaluation and state that TCDD should be regarded as a human carcinogen, though not a direct-acting genotoxin. The report prepared by Fiedler and colleagues (2000) repeats the IARC (1997) evaluation of the carcinogenicity of CDDs. AEA Technology (1999) concludes that the epidemiological data sug- gest that TCDD exposure increases the rates of all cancers. On the basis of the epidemiological and animal studies, ATSDR (1998) concludes that TCDD may be a human carcinogen. EPA (2000) considers TCDD to be a human carcinogen and that other DLCs are likely to be human carcinogens, based on a combination of epidemiological and animal cancer studies and mechanistic information. The epidemiological data alone do not demonstrate a causal association between exposure and cancer, but suggest that the compounds are multisite carcinogens, increasing cancer at all sites, lung cancer, and perhaps other particular cancers. EPA (2000) describes TCDD as a nongenotoxic carcinogen and a potent promoter. Noncancer Effects. A number of noncancer human health effects have been associated with high exposures to DLCs. These effects are listed below. . Chloracne and other dermal effects (ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; IARC, 1997~.

OCR for page 17
26 Estimates of Tolerable Intakes DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY Changes (AEA Technology, 1999; ATSDR, 1998; Fiedler et al., 2000; IARC, 1997) or possible changes (EPA, 2000; Scientific Committee on Food, 2000, 2001) in glucose metabolism and in diabetes risk. Alterations (ATSDR, 1998) or possible alterations (EPA, 2000) in thy- roid function. Alterations in growth and development (AEA Technology, 1999; IARC, 1997; Scientific Committee on Food, 2000, 2001), neurodevelopment (AEA Technology, 1999; IARC, 1997), and neurobehavior (AEA Tech- nology, 1999; IARC, 1997; Scientific Committee on Food, 2000, 2001~. EPA (2000) considers postnatal developmental effects on neurobehavior to be possibly related to exposures to DLCs. Fiedler and colleagues (2000) note that there was an altered sex ratio among births after the Seveso unintended exposure. Increased gamma-glutamyl transferase concentrations (EPA, 2000; Sci- entific Committee on Food, 2000, 2001~. Altered concentrations of reproductive hormones in men (EPA, 2000~. Alterations in liver function (Fiedler et al., 2000; IARC, 1997) and he- patic effects (ATSDR, 1998~. Possibly altered serum lipid (EPA, 2000; Scientific Committee on Food, 2000, 2001) and cholesterol concentrations (EPA, 2000~. Possibly altered alanine aminotransferase and aspartate aminotransferase concentrations (EPA, 2000~. Alterations in the immune system (Fiedler et al., 2000; IARC, 1997~. Possible ocular changes (ATSDR, 1998; IARC, 1997~. Increased mortality from cardiovascular disease (AEA Technology, 1999; Scientific Committee on Food, 2000, 2001~. Toxicity Benchmarks Several governmental bodies have derived or recommended acceptable daily intakes or similar parameters for TCDD or DLCs as a group (AEA Technology, 1999; ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; Scientific Committee on Food, 2000, 2001~. These guidance levels are summarized in Table 2-2. ATSDR (1997) defines a minimal risk level (MRL) for a hazardous sub- stance (e.g., DLCs) as an estimate of daily human exposure that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration and route of exposure. For 2,3,7,8-TCDD, ATSDR (1998) derives MRLs for oral exposure to over three intervals: acute (14 days or less), intermediate (15-364 days), and chronic (1 year or more). An MRL is "an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse non-cancer health effects over a specified duration of exposure"

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGULATORYACTIVITY TABLE 2-2 Estimates of Tolerable Intakes of Dioxins and Dioxin-like Compounds Reference Cancer Noncancer ATSDR, 1998 None given Acute oral MRL: 200 pa/kg/d (TCDD) Intermediate oral MRL: 20 pa/kg/d (TCDD) Chronic oral MRL: 1 pa/kg/d (TCDD) EPA, 2000 1 x 10-3 pa/kg/d (TCDD) None given or 0.001 pa/kg/d at a 1 in 1 million excess risk level Scientific Committee on Food, 2000, 2001 AEA Technology, 1999; Fiedler et al., 2000 14 pg TEQ DFp wHog8lkglwk 1-4 pg TEQ/kg/d (CDDs, CDFs, PCBs) NOTE: MRL = minimal risk level, TCDD = 2,3,7,8-tetrachlorodibenzo-p-dioxin, TEQ = toxicity equivalents, CDD = chlorinated dibenzo-p-dioxin, CDF = chlorodibenzofuran, PCB = polychlori- nated biphenyl. (ATSDR, 1998~; the MRL does not pertain to cancer. The MRLs for TCDD are, respectively, 0.0002 ,ug/kg/d (200 pg/kg/d), 0.00002 ,ug/kg/d (20 pg/kg/d), and 0.000001,ug/kg/d (1 pg/kg/d). The acute MRL is based on immunological effects in female mice, the intermediate MRL on immunological effects in guinea pigs, and the chronic MRL on developmental effects in rhesus monkeys. In each case, uncertainty factors are applied to address animal-to-human extrapolation, inter- individual variation in response, and (if necessary) a low-effect to no-effect dose extrapolation. The report by Fiedler and colleagues (2000) reiterates the World Health Organization (WHO)-recommended tolerable daily intake (TDI) of DLCs of 1 to 4 pg TEQ/kg/d and also WHO's recommendation that exposures should be re- duced as much as possible. Similarly, the AEA Technology (1999) report encour- ages member states of the European Union to adopt the recent WHO recommen- dation, and notes that PCBs contribute about half of dietary TEQ exposure. The Scientific Committee on Food (2000, 2001) derived a tolerable weekly intake (TWI) of DLCs based on TCDD body burdens associated with sensitive effects in experimental animals: developmental and reproductive effects in rats and mon- keys and endometriosis in monkeys. Body burdens associated with the lowest- observed-adverse-effect levels in the relevant studies ranged from about 30 to 100 ng TCDD/kg. The estimated human dietary intakes needed to produce these body burdens were then calculated, and safety factors (ranging from 3 to 10) were applied. The lowest TDI thus calculated was 2 pg TCDD/kg, corresponding to a

OCR for page 17
42 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY environmental and food monitoring programs are summarized in Appendix Tables A- 17 and A- 18, respectively. Environmental, Feed, and Food Monitoring. FDA currently uses a subsample of between 200 and 300 food items from the Total Diet Study (TDS) to analyze for DLCs. This analysis is conducted separately from the analysis in the TDS (see Chapter 5~. The sampling is conducted once per year and has been completed up to 2001. The food samples typically chosen are those that have not previously been analyzed for DLCs or those that may contain animal fats. In addition to TDS sampling, FDA conducts a targeted sampling study aimed at foods that are potentially variable in contaminant levels, such as fish, vegetable oils, and dietary supplements. For example, a number of different fish varieties may be sampled rather than just one species in order to understand the sources of DLCs and the variability across species. This sampling is conducted on a yearly basis and generally includes 500 to 1,000 samples. FDA also follows up on any unusually high values in any of their studies to determine sources of DLCs in the food supply. FDA does not target any specific imported foods, but it tries to create a representative sample of the diet of the general U.S. population, which may include imported foods. When FDA does investigate an imported food, it tends to look at imports from the top three countries for that product. USDA and EPA conducted a joint program of three surveys for DLCs in beef, pork, and poultry, using 60 to 80 samples in each survey taken from feder- ally inspected slaughterhouses in the United States. These studies were not re- peated or continuous studies, but rather one-time events. Sixty-three beef samples were collected in May and June 1994 and examined for CDDs and CDFs. The sampling for the pork survey took place in August and September 1995 and yielded 78 final samples. It was the first survey for CDDs and CDFs in pork in the United States. Sampling was conducted in September and October 1996 for poultry, with a final sample size of 80. This poultry survey was also the first of its kind in the United States to survey for CDDs and CDFs (see later section, "Con- centrations of DLCs in Foods". Human Biomonitoring. The Centers for Disease Control and Prevention's (CDC) National Health and Nutrition Examination Surveys (NHANES) are a series of studies that have collected data on the health and nutritional status of the U.S. population since the early 1960s. Between 1998 and 2001, the dietary component of NHANES and the USDA/Agricultural Research Service Continu- ing Survey of Food Intakes by Individuals merged; NHANES also became a continuous and annual survey. The sampling plan for each year follows a com- plex, stratified, multistage, probability cluster design to select a representative sample (approximately 5,000 individuals) of the noninstitutionalized, civilian U.S. population.

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 43 The NHANES protocol includes a home interview followed by a standard- ized physical examination in a mobile examination center. As part of the exami- nation protocol, blood is obtained by venipuncture from participants aged 1 year and older, and urine specimens are collected from people aged 6 years and older. The venipuncture is performed to obtain laboratory results that provide preva- lence estimates of disease, risk factors for examination components, and baseline information on the health and nutritional status of the population. Recently in- cluded among the NHANES laboratory measures are serum dioxins, furans, and coplanar PCBs. CDC's National Center for Environmental Health, Division of Laboratory Sciences, performs the environmental chemical analysis of the blood or urine specimens collected in NHANES. The first National Report on Human Exposure to Environmental Chemicals (CDC, 2001) did not include DLC measurements. The second national report (NCEH, 2003), using data from the 1999-2000 NHANES survey, included DLC results, along with other environmental chemi- cal analyses; data for people older than 12 years, including major demographic attributes (e.g., race and sex); and approximately 2,500 samples (from approxi- mately 10,000 participants for the 2-year period, 5,000 participants per year). Unfortunately, none of these data were available in time for inclusion in this report. Human exposure data from the 2001-2002 NHANES survey on DLCs (and other environmental chemicals) is estimated to be released in fall 2003. It is anticipated that all four years of the NHANES data (1999-2002) will be com- bined for a more refined demographic analysis; it is not known when these data will be released. Monitoring Programs of Other Countries and Organizations EC. Appendix Table A-l9 summarizes the nationally funded monitoring programs' research activities that were underway as of 1999 in each EC member state. Programs that were completed by 1999 are not included in this list. Currently, there are several additional on-going DLC surveys in the United Kingdom, including cow's milk studies, wild and farmed fish studies, total diet studies, and a baby food study that is about to be launched (Personal communica- tion, M. Gem, U.K. Food Standards Agency, May 3, 2002~. Beginning in July 2002, EC member states are required to conduct food surveillance studies. In 2002, the United Kingdom will collect 62 food samples, concentrating on foods containing fat; the number of samples will be doubled in 2003 (Personal commu- nication, M. Gem, U.K. Food Standards Agency, May 3, 2002~. These results will be published in Food Safety Information Sheets. Several countries, including Austria, Belgium, Denmark, Finland, Germany, the Netherlands, Spain, Sweden, and the United Kingdom, have also participated in the WHO assessment of DLC concentrations in human breast milk.

OCR for page 17
44 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY WHO/FAD. WHO is involved in several monitoring studies of human breast milk and food. Through its European Center for Environment and Health in Bilthoven, the Netherlands, WHO conducts periodic studies on concentrations of DLCs in human breast milk, predominately in European countries. Since 1976, WHO has been responsible for the Global Environment Moni- toring System's Food Contamination Monitoring and Assessment Program. This program provides information on levels and trends of contaminants in food through its network of participating laboratories in over 70 countries around the world. The main objectives of the program are to collect data on levels of certain priority chemicals (including DLCs) in foods, to provide technical coordination with countries wanting to implement monitoring studies on foods, and to provide information to JECFA on contaminant levels to support its work on international standards on contaminants in foods. Australia. DLCs are not routinely monitored in Australia, and there are very few data on the levels of DLCs in either the environment or in food. However, a survey of DLC levels in foods is currently being conducted by the Department of Health and Aging, the Australia New Zealand Food Authority, and the Australian Government Analytical Laboratories. Japan. Japan's Law Concerning Special Measures Against Dioxins requires that businesses conduct surveillances of DLC concentrations in emission gas, effluent, ash, dust, and other compounds at least once a year. These results are to be submitted to prefectural governors. Beyond the regulatory requirements, it appears that there are not any ongoing surveillance programs in Japan (see Ap- pendix Table A-20. However, several studies were conducted in 1998 and 1999 in order to identify DLC concentrations in blood, air/indoor air/soil, dust and soot/water, and food. These studies include: . . . The State of Dioxin Accumulation in the Human Body, Blood, Wildlife, and Food: Findings of the Fiscal 1998 Survey. Sponsored by the Ministry of the Environment: Environmental Health and Safety Division, Environ- mental Health Department, Environment Agency of Japan (cited in Tran et al., 2002~. Survey on the State of Dioxin Accumulation in Wildlife: Findings of the Fiscal 1999 Survey. Sponsored by the Ministry of the Environment: En- vironmental Risk Assessment Office, Environmental Health Department, Environment Agency of Japan (cited in Tran et al., 2002~. Detailed Study of Dioxin Exposure: Findings of the Fiscal 1999 Survey. Sponsored by the Ministry of the Environment: Environmental Risk As- sessment Office, Environmental Health Department, Environment Agency of Japan (cited in Tran et al., 2002~.

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 45 Canada. The Feed Program in the Canadian Food Inspection Agency (CFIA) routinely monitors for contaminants in livestock feeds as part of their National Feed Inspection Program. In a preliminary survey conducted by CFIA in 1998- 1999, 24 fishmeals and feeds and 9 fish oils were sampled across Canada and tested for dioxins, furans, and PCBs. The results are summarized in Appendix Table A-21. CFIA is currently utilizing these results to develop a continuing monitoring plan for dioxin, furans, and PCBs and future regulatory approaches. Research Programs in the United States While significant academic and industrial research on DLCs exists, many governmental organizations also have an active role in promoting and conduct- ing research on DLCs. Much of this research is in complement to on-going monitoring and surveillance programs and includes a variety of modeling stud- ies to evaluate the behavior of DLCs in the air, how they move through the environment, and how they become part of the food supply. The U.S. govern- ment has also been conducting research into the effects of exposure to DLCs on humans and examining historical data to determine how DLC levels change through time. Representative federal research programs are summarized in Ap- pendix Table A-22. Research Programs in Other Countries and Organizations European Commission. Appendix Table A-23 summarizes the nationally funded research activities that were underway as of 1999 in each EC member state. Programs that were completed by 1999 are not included in this list. WHO/FAD. WHO is involved in several research studies. The major re- search endeavor includes working with the United Nations Environmental Pro- gramme to provide risk assessments of POPs, including DLCs. Chemical Methods for Analysis of DLCs in Feeds and Foods Not all feeds or food products have been found to be at equal risk for DLC contamination. While commonly associated with feeds and foods containing ani- mal fats, DLCs can, however, also be found in vegetables, fruits, and cereals. The need for detection of DLCs at these low levels makes the current quantitative methods of analysis expensive and challenging to perform, which limits the number of laboratories available to conduct these tests (Hess and Stevens, 2001~. In order to efficiently develop a reliable picture of DLCs in the food supply, both screening methods (which can be used to analyze a large number and variety of feed and food samples), and trace analysis (which can quantify low levels of DLCs in follow-up to a positive screening result) can be useful.

OCR for page 17
46 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY Both current screening and trace analysis methods follow a two-part proce- dure: extraction/separation of the sample, where the compounds of interest are isolated from the matrix; and instrumental analysis, where DLCs are detected. The major challenge with regard to food samples is the extraction/separation of DLCs from other compounds in the food matrix. Techniques for DLC extraction from fruits, hard vegetables, soft vegetables, grains, dairy products, fish, and meats are very different, and composite foods and food additives are especially challenging. Screening Methods Because of their speed and cost efficiency, significant efforts have been made in recent years to develop screening assays for determining DLC and PCB contamination. However, screening assays provide speed and cost savings at the expense of specificity and a lower level of detection (Has s and Stevens, 2001~. They do provide the sensitivity of conventional assays and, most importantly, minimize false negatives. Although to quantify contamination levels, trace analy- sis must follow a positive screening result, screening methods can be very useful in detecting a contamination event or identifying critical control points in a potential contamination pathway. Two cost-effective approaches have been developed for screening purposes: instrumental methods and biotechnology approaches. Both approaches rely on the same basic extraction methods used in trace analysis, while reducing the cost of the analytical measurement. Of the two screening methods, the development of the CALUX method was supported under a Small Business Innovation Research Grant from the National Institute of Environmental Health Sciences. FDA's Center for Veterinary Medi- cine, Arkansas Regional Laboratory, has a licensing agreement to use the CALUX method for its DLC research. Instrumental Methods Instrumental methods of screening for the presence of DLCs respond to the physical properties of the compounds. Interfering compounds that were not re- moved during the initial extraction procedure and may cause an overestimate of DLC contamination levels can be identified in an initial analysis. A secondary clean-up of the sample can be performed and the sample can be reanalyzed, reducing the number of false positives that this methodology produces. Biotechnology Approach The biotechnology approach is based on the chemical reactivity of com- pounds and uses immunoassay-type tests and arylhydrocarbon receptor-type tests.

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 47 In comparison studies, the biotechnology approach has been found routinely to overestimate DLC content in the presence of interfering compounds, which re- sults in false positives (Hess and Stevens, 2001~. While some interfering com- pounds are removed during the extraction phase of the test, the residual presence of these compounds is not detectable during a biotechnology-based assay. Even more seriously, this approach also can have a problem with false negatives due to analyte loss during the extraction phase (Hess and Stevens, 2001~. Assays of duplicate aliquots from a single sample can minimize this problem, but this doubles the cost of analysis. Analytical Methods for Analysis of DLCs in Feeds and Foods Trace Analysis The analytical approach used most frequently to detect DLCs in feeds and foods relies on isotopic dilution. This method is isomer specific, very sensitive, and robust, although expensive and demanding. Following the extraction phase, a known amount of the isotope i3C iS added to the sample, which creates a mixture of forms of the compound of interest that are chemically identical, yet distin- guishable by mass spectrometry. Using a combination of gas chromatography and high-resolution mass spectrometry allows determination of the ratio between each analyte and its associated isotonically labeled standard, leading to accurate quantification of analyte concentration. The overall accuracy of the assay de- pends on the ability to spike the sample with the isotope accurately, weigh the sample, and measure the ratio. The effects of interfering compounds and minor sample losses due to handling are detectable and correctable. The analytical cost estimates associated with the standard analytical method for DLCs obtained from a number of sources are summarized in Appendix Table A-24. EPA-Approved Method for Analysis of Dioxins and Furans in Wastewater In 1997, to augment less sensitive methods approved earlier, EPA Method 1613: Tetra- Through Octa-Chlorinated Dioxins and Furans by Isotope Dilution High Resolution Gas Chromatography/High Resolution Mass Spectrometry (HRGC/HRMS), EPA 821-B-94-005, was approved. Method 1613 is the most sensitive analytical test procedure approved under the Clean Water Act for the analysis of CDDs and CDFs and was developed to meet the need for more stringent pollutant monitoring and control. Method 1613 also allows determina- tion of the 17 terra- through octa-chlorinated, 2,3,7,8-substituted CDDs and CDFs. Method 1613 extends minimum levels of quantitation of CDDs and CDFs into the low parts-per-quadrillion range for aqueous matrices and the low parts- per-trillion range for solid matrices. Furthermore, the use of isotope dilution

OCR for page 17
48 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY techniques, internal standard calibration, and the 1600 series method quality control protocol results in improved sensitivity, precision, and accuracy. These improvements have been validated through both intra- and interlaboratory valida- tion studies. Method 1613 is also intended to encourage advances in technology and reductions in the cost of analysis by allowing the use of alternate extraction and clean-up techniques. The analyst is permitted to modify the method to over- come interferences or to lower the cost of measurements, provided that all method equivalency and performance criteria are met. Concentrations of DLCs in Foods This section presents recent data (1990 or later) regarding the concentrations of DLCs in European and North American foods, as provided by AEA Technol- ogy (1999), ATSDR (1998), EPA (2000), Fiedler and colleagues (2000), IARC (1997), and the Scientific Committee on Food (2000, 2001~. Recent Contamination Levels in Foods Appendix Table A-25 provides DLC values for foods other than breast milk. The data are very heterogeneous with regard to collection date, the number of samples of a particular food, sampling method (individual versus composite samples), the compounds analyzed, the unit of analysis (e.g., fat, fresh weight, dry weight), and the state of the food (e.g., raw or cooked). Numbers in the table may represent means, ranges of means, or ranges of observations. Temporal Trends Evidence of temporal trends in the data on DLC contamination levels in foods is presented in some reviews, if only indirectly, in decreasing estimates of dietary intakes of DLCs. EPA (2000) reports, specifically that: Concentrations of dioxins and furans in U.K. cows' milk declined from 1.1 to 3.3 pg I-TEQDF/g of lipid in 1990 to 0.67 to 1.4 pg I-TEQDF/g of lipid in 1995. The mean pg I-TEQDF/g of lipid in German milk declined by about 25 percent between 1990 and 1994. Examination of U.S. foods preserved over the last several decades sug- gests that dioxin and furan concentrations were two to three times higher in the 1950s to 1970s than at present, while PCB concentrations were ten times higher. IARC (1997) states that PCDD/PCDF in milk, dairy products, eggs, poultry, and "fatty food composites" in the United Kingdom decreased markedly during

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGU~TORYACTIVITY 49 the 1980s. Fiedler and colleagues (2000) cite a decrease in the level of contam~ nation of German foods, most markedly for dairy products, meat, and fish. In 1998, an EPA study compared the DLC concentration in historic samples to current DLC concentrations derived from post-1993 national food surveys for beef, pork, poultry, and milk (Winters et al., 1998~. The surveys' principal objec- tive was to determine the national average concentration of DLCs in the lipids of these animal-fat products. National mean TEQ concentrations from these surveys are shown in Appendix Table A-26. Appendix Table A-27 presents the PCDD/PCDF and PCB TEQ concentra- tions of the 14 historical samples, as well as TEQ concentrations normalized and expressed as a percent of current concentrations for the most similar food type. For example, the 1908 beef ration percentage of 38 percent means that the 0.34 pg TEQ/g of lipid PCDD/PCDF (calculated at nondetects = I/2 limit of detection) is 38 percent of the current beef concentration of 0.89 pg TEQ/g of lipid (at nondetects = i/: limit of detection), as determined by the recent national EPA beef survey. . Although not necessarily representative of these food types or their respec- tive time period, it should be noted that all 10 samples from 1957 to 1982 were higher in PCDD/PCDF TEQ than the current mean concentrations (at nondetects = i/: limit of detection), and that 12 of the 13 samples taken from 1945 through 1983 were higher for PCB TEQ. If the samples are indicative of past concentra- tions of DLCs, normalized TEQ suggests a PCDD/PCDF concentration two to three times higher during the period of peak environmental loading, while PCB TEQ may have been over 10 times current concentrations. EPA plans to con- tinue analyzing historic meat and dairy products as additional samples become available. Contribution of Food Groups to DLC Exposure According to the Scientific Committee on Food (2000), the major sources of dietary exposure to PCDD/PCDF intakes in Europe are milk and dairy products (16 to 39 percent), meat and meat products (6 to 32 percent), and fish and fish products (11 to 63 percent). Fish was a particularly large contributor in Finland and Sweden, fruits and vegetables in Spain, and cereals in the United Kingdom. In Germany, milk, meat, and fish contributed 31 percent, 23 percent, and 17 percent, respectively, of dietary I-TEQ from PCDD/PCDF (Scientific Committee on Food, 2000~. Temporal Trends Several of the reviewed reports describe data that suggest a decrease in DLC intakes over recent decades. AEA Technology (1999) reports three time trend-

OCR for page 17
so DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY analyses of DLC intake. Dutch data on DLC in foods gathered in 1978, 1984 to 1985, and 1994 indicate a statistically significant decreasing trend in adult intake over time, with a 50 percent decrease in I-TEQ/kg/d over each 5.5-year interval in that penod. Dietary studies conducted in Germany in 1989 and 1995 indicate a 45 percent decrease in I-TEQ intake. Diet studies in the United Kingdom in 1982, 1988, and 1992 suggest a 45 percent decrease in intake at each time point com- pared to the preceding point. All of these estimates likely pertain to the average consumer. Independent of changes over time in the DLC content of food and in dietary intake, it is generally recognized that body burdens of DLCs increase with age due, in part, to the long half-lives of these compounds. Summary This chapter summarizes reports on the toxicity and risk of DLCs and on regulatory activity in the United States and other countries that are widely recog- nized to reflect current status and knowledge of these compounds (AEA Technol- ogy, 1999; ATSDR, 1998; EPA, 2000; Fiedler et al., 2000; IARC, 1997; Scien- tific Committee on Food, 2000, 2001~. The risks from exposure to DLCs outlined in these documents are based on population groups that received exposures ex- ceeding the daily exposures estimated for the general population, so risks to the general population are not known. Efforts to regulate DLCs range from exposure limits and environmental emission regulations to guidelines and recommenda- tions to limit DLC levels in feed and food. Efforts in the United States and other countries to monitor DLCs and gather more current data are descnbed. Research on DLC levels in human foods indicates that the greatest contribution to exposure from the food supply is from animal fats in meat, dairy products, and fish. REFERENCES AEA Technology. 1999. Compilation of EU Dioxin Exposure and Health Data. Prepared for the European Commission DO Environment. Oxfordshire, England: AEA Technology. ATSDR (Agency for Toxic Substances and Disease Registry). 1994. Toxicological Profile for Chlo- rinated Dibenzofurans (CDFs). Atlanta, GA: ATSDR. ATSDR. 1998. Toxicological Profile for Chlorinated Dibenzo-p-dioxins. Atlanta, GA: ATSDR. ATSDR. 2000. Toxicological Profile for Polychlorinated Biphenyls (PCBs). Atlanta, GA: ATSDR. Axelson O. Sundell L. 1974. Herbicide exposure, mortality and tumor incidence. An epidemiological investigation on Swedish railroad workers. Scand J Work Environ Health 11:21-28. Bertazzi PA, Zocchetti C, Guercilena S. Consonni D, Tironi A, Landi MT, Pesatori AC. 1997. Dioxin exposure and cancer risk: A 15-year mortality study after the "Seveso accident." Epide- miology 8:646-652. Bertazzi PA, Bernucci I, Brambilla G. Consonni D, Pesatori AC. 1998. The Seveso studies on early and long-term effects of dioxin exposure: A review. Environ Health Perspect 106:625-633. CDC (Centers for Disease Control and Prevention). 2001. National Report on Human Exposure to Environmental Chemicals. Atlanta, GA: CDC.

OCR for page 17
A SUMMARY OF DIOXIN REPORTS, ASSESSMENTS, AND REGULATORYACTIVITY 51 Chen PH, Gaw JM, Wong CK, Chen CJ. 1980. Levels and gas chromatographic patterns of polychlo- rinated biphenyls in the blood of patients after PCB poisoning in Taiwan. Bull Environ Contam Toxicol 25:325-329. EPA (U.S. Environmental Protection Agency). 2000. Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds. Draft Final Report. Washington, DC: EPA. FDA (U.S. Food and Drug Administration). 2000. Guidance for industry: Dioxin in anticaking agents used in animal feed and feed ingredients; Availability. Fed Regist 65:20996-20997. Fiedler H. Hutzinger O. Welsch-Pausch K, Schmiedinger A. 2000. Evaluation of the Occurrence of PCDD/PCDF and POPs in Wastes and Their Potential to Enter the Foodchain. Prepared for the European Commission DG Environment. Bayreuth, Germany: University of Bayreuth. Hass RJ, Stevens FM. 2001. Dealing with dioxin: The state of analytical methods. Food Safety Mag Dec 2000/Jan 2001. Huisman M, Koopman-Esseboom C, Fidler V, Hadders-Algra M, van der Paauw CG, Tuinstra LGM, Weiglas-Kuperus N. Sauer PJJ, Touwen BCL, Boersma ER. 1995. Perinatal exposure to poly- chlorinated biphenyls and dioxins and its effect on neonatal neurological development. Early Human Development 41:111-127. IARC (International Agency for Research on Cancer). 1997. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 69: Polychlorinated Dibenzo-para-Dioxins and Poly- chlorinated Dibenzofurans. Lyon, France: World Health Organization. IOM (Institute of Medicine). 1991. Nutrition During Lactation. Washington, DC: National Academy Press. Jacobson JL, Fein GG, Jacobson SW, Schwartz PM, Dowler JK. 1984. The transfer of polychlori- nated biphenyls (PCBs) and polybrominated biphenyls (PBBs) across the human placenta and into maternal milk. Am J Public Health 74:378-379. Koopman-Esseboom C, Huisman M, Weislas-Kuperus N. Van der Paauw CG, Tuinstra LGM, Boersma ER, Sauer PJJ. 1994a. PCB and dioxin levels in plasma and human milk of 418 Dutch women and their infants. Predictive value of PCB congener levels in maternal plasma for fetal and infant's exposure to PCBs and dioxins. Chemosphere 28:1721-1732. Koopman-Esseboom C, Morse DC, Weisglas-Kuperus N. Lutkeschipholt IJ, Van der Paauw CG, Tuinstra LG, Brouwer A, Sauer PJ. 1994b. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res 36:468-473. Kuratsune M, Ikeda M, Nakamura Y. Hirohata T. 1988. A cohort study on mortality of Yusho patients: A preliminary report. In: Miller RW, Wantanabe S. Fraumeni JF, eds. Unusual Occur- rences as Clues to Cancer Etiology. Tokyo: Japan Scientific Societies Press. Pp. 61-68. Landi MT, Bertazzi PA, Consonni D. 1996. TCDD blood levels, population characteristics, and individual accident experience. Organohalogen Compd 30:290-293. Landi MT, Consonni D, Patterson DG Jr, Needham LL, Lucier G. Brambilla P. Cazzaniga MA, Mocarelli P. Pesatori AC, Bertazzi PA, Caporaso NE. 1998. 2,3,7,8-Tetrachlorodibenzo-p- dioxin plasma levels in Seveso 20 years after the accident. Environ Health Perspect 106:273- 277. Lanting CI, Fidler V, Huisman M, Boersma ER. 1998. Determinants of polychlorinated biphenyl levels in plasma from 42-month-old children. Arch Environ Contam Toxicol 35:135-139. Mocarelli P. Nee&am LL, Marocchi A, Patterson DG Jr, Brambilla P. Gerthoux PM, Meazza L, Carreri V. 1991. Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. J Toxicol Environ Health 32:357-366. NCEH (National Center for Environmental Health). 2003. Second National Report on Human Expo- sure to Environmental Chemicals. NCEH Pub. No. 02-0716. Atlanta, GA: CDC. Patandin S. Koopman-Esseboom C, de Ridder MA, Weisglas-Kuperus N. Sauer PJ. 1998. Effects of environmental exposure to polychlorinated biphenyls and dioxins on birth size and growth in Dutch children. Pediatr Res 44:538-545.

OCR for page 17
52 DIOXINS AND DIOXIN-LIKE COMPOUNDS IN THE FOOD SUPPLY Patandin S. Dagnelie PC, Mulder PG, Op de Coul E, van der Veen JE, Weisglas-Kuperus N. Sauer PJ. 1999. Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adult- hood: A comparison between breast-feeding, toddler, and long-term exposure. Environ Health Perspect 107:45-51. Riihimaki V, Asp S. Herberg S. 1982. Mortality of 2,4-dichlorophenoxyacetic acid and 2,4,5- trichlorophenoxyacetic acid herbicide applicators in Finland: First report of an ongoing pro- spective study. Scand J Work Environ Health 8:37-42. Riihimaki V, Asp S. Pukkala E, Hernberg S. 1983. Mortality and cancer incidence among chlori- nated phenoxyacid applicators in Finland. Chemosphere 12:779-784. Scientific Committee on Food. 2000. Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food. European Commission, Health and Consumer Protection Directorate-General. SCF/CS/CNTM/DIOXIN/8 Final. Brussels: Euro- pean Commission. Scientific Committee on Food. 2001. Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food. Update. European Commission, Health and Consumer Protection Directorate-General. CS/CNTM/DIOXIN/20 Final. Brussels: Euro- pean Commission. Tran N. Wells C, Daniels C. 2002. A White Paper on Existing Dioxin Regulations and Monitoring Program. Prepared for the Committee on the Implications of Dioxin in the Food Supply. Washington DC: Novigen Sciences. Vreugdenhil HI, Slijper FM, Mulder PG, Weisglas-Kuperus N. 2002. Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age. Environ Health Perspect 110:A593-A598. Weisglas-Kuperus N. Patandin S. Berbers GA, Sas TC, Mulder PG, Sauer PJ, Hooijkaas H. 2000. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Environ Health Perspect 108:1203-1207. Winters DL, Anderson S. Lorber M, Ferrario J. Byrne C. 1998. Trends in dioxin and PCB concentra- tions in meat samples from several decades of the 20th century. Organohalogen Compd 38:75- 78. Wolfe WH, Michalek JE, Miner JC, Rahe A, Silva J. Thomas WF, Grubbs WD, Lustik MB, Karrison TG, Roegner RH, Williams DE. 1990. Health status of Air Force veterans occupationally exposed to herbicides in Vietnam. I. Physical health. JAm Med Assoc 264:1824-1831.