Polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-BDEs) are endocrine disrupting compounds prevalent in human serum and breast milk. Retention of PBDEs and OH-BDEs in humans may be affected by differences in PBDE metabolism due to variants in cytochrome P450 2B6 (CYP2B6). The objectives of this study are to assess the partitioning profiles of PBDEs and OH-BDEs in forty-eight paired human serum and milk samples, and to evaluate the relationship between variants in CYP2B6 genotype and PBDE and OH-BDE accumulation in humans. Results show that the geometric mean (GM) concentrations of PBDEs are similar in serum (GM = 43.4 ng/g lipid) and milk samples (GM = 52.9 ng/g lipid), while OH-BDEs are retained primarily in serum (GM = 2.31 ng/g lipid), compared to milk (GM = 0.045 ng/g lipid). Participants with CYP2B6*6 genotype had a greater relative retention of PBDEs in serum and milk, and significant relationships (p < 0.05) were also observed for PBDE-47, 5-OH-BDE-47 and 6-OH-BDE-47 concentrations relative to CYP2B6*5 and CYP2B6*6 genotypes. These results are the first to show that CYP2B6 genotype is significantly related to the relative retention of PBDEs in humans, which may have direct implications for variability in the susceptibility of individuals to the potential adverse effects of these contaminants.

Electronic waste (E-waste) has rapidly increased in recent decades, especially in developing nations. Recycling and reclamation of certain chemicals is frequently performed in low and middle income countries including Vietnam where relatively unregulated home based e-waste recycling is common. In 2012, a pilot study was conducted in 2 villages in northern Vietnam, with 10 women who conducted home-based recycling in one and 10 matched controls in another. This was followed in 2013, with a study of 40 recycling women vs 20 non-recyclers. Whole blood, serum, and urine were collected and analyzed at the US Centers for Disease Control for metals, persistent pesticides, PCBs, and both chlorinated and brominated dioxins and furans. PBDEs 47, 99, 100, 153, 154, 183, and 209 were elevated in the recycling women. PCBs 138/158 and 153 were elevated in the younger recyclers. Certain chlorinated dioxins (1,2,3,6,7,8-HxCDD) and furans (1,2,3,6,7,8-HxCDF and 1,2,3,4,6,7,8-HpCDF) as well as 1,2,3,7,8-PeBDD and 2,3,7,8-TBDF were also elevated in the recycling women. Surprisingly, p,p'-DDE was higher in the control women. Lead was elevated in the recycling women, while methyl mercury was higher in the non-recyclers. Of interest, arsenic, methyl mercury, and lead were elevated in both groups of Vietnamese women as compared to women of similar age in the US monitored in NHANES. Further study is indicated to understand not only exposure in a larger group of women doing home recycling, but the potential for adverse health effects from lead, PBDEs, PCBs, and dioxins as all these compounds appear to have neurodevelopmental, endocrine disrupting, carcinogenic, and others in multiple animal species and people. The high levels of arsenic and methyl mercury, as well as lead, in all the northern Vietnamese women is also of concern.

Objective: Electronic waste is increasing. It is frequently recycled in developing countries. This is the first study to report metals, polybrominated diphenyl-ethers (PBDEs), polychlorinated biphenyls (PCBs), 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p’-DDT), and p,p’-DDE concentrations in female e-waste workers. Methods: Female Vietnamese recyclers and non-recyclers were studied. Metals and halogenated organics were measured in blood and urine, and compared with levels in women in the US National Health and Nutrition Examination Survey (NHANES). Results: Recyclers had higher serum PBDE than nonrecyclers. PCB-138/158 and PCB-153 were higher in 18 to less than 38-year-old nonrecyclers. Median urinary arsenic in both cohorts was six to seven-fold higher than NHANES. Median lead in blood and urine was 40% to 60% higher in recyclers than nonrecyclers. Lead in nonrecyclers was four to six-fold higher than NHANES. Both cohorts had higher arsenic and mercury than NHANES. Conclusion: Occupational exposure to PBDEs and lead occurred in recyclers. Environmental exposure to arsenic, lead, and mercury occurred in both cohorts. Occupational and environmental remediation are recommended.

The presence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-BDE) and methoxylated (MeO-BDE) analogs in humans is an area of high interest to scientists and the public due to their neurotoxic and endocrine disrupting effects. Consequently, there is a rise in the investigation of the occurrence of these three classes of compounds together in environmental matrices and in humans in order to understand their bioaccumulation patterns. Analysis of PBDEs, OH-BDEs, and MeO-BDEs using liquid chromatography-mass spectrometry (LC-MS) can be accomplished simultaneously, but detection limits for PBDEs and MeO-BDEs in LC-MS is insufficient for trace level quantification. Therefore, fractionation steps of the phenolic (OH-BDEs) and neutral (PBDEs and MeO-BDEs) compounds during sample preparation are typically performed so that different analytical techniques can be used to achieve the needed sensitivities. However, this approach involves multiple injections, ultimately increasing analysis time. In this study, an analytical method was developed for a "one-shot" analysis of 12 PBDEs, 12 OH-BDEs, and 13 MeO-BDEs using gas chromatography with tandem mass spectrometry (GC-MS/MS). This overall method includes simultaneous extraction of all analytes via pressurized liquid extraction followed by lipid removal steps to reduce matrix interferences. The OH-BDEs were derivatized using N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide (TBDMS-MTFA), producing OH-TBDMS derivatives that can be analyzed together with PBDEs and MeO-BDEs by GC-MS/MS in "one shot" within a 25-min run time. The overall recoveries were generally higher than 65%, and the limits of detection ranged from 2 to 14 pg in both breast milk and serum matrices. The applicability of the method was successfully validated on four paired human breast milk and serum samples. The mean concentrations of total PBDEs, OH-BDEs, and MeO-BDEs in breast milk were 59, 2.2, and 0.57 ng g(-1) lipid, respectively. In serum, the mean total concentrations were 79, 38, and 0.96 ng g(-1) lipid, respectively, exhibiting different distribution profiles from the levels detected in breast milk. This "one-shot" GC-MS/MS method will prove useful and cost-effective in large-scale studies needed to further understand the partitioning behavior, and ultimately the adverse health effects, of these important classes of brominated flame retardants in humans. (C) 2015 Elsevier B.V. All rights reserved.

Bisphenol A (BPA) is a high-volume, synthetic compound found in epoxy resins and plastics used in food packaging. Food is believed to be a major source of BPA intake. In this study, we measured the concentration of BPA in convenience samplings of foodstuffs purchased in Dallas, Texas. Sampling entailed collection of 204 samples of fresh, frozen, and canned foods in two rounds in 2010. BPA was positive in 73% of the canned food samples, while it was found in only 7% of non-canned foods at low concentrations. The results of this food sampling program were used to calculate adult dietary intakes of BPA. A pathway approach combined food intakes, a "canned fraction" parameter which described what portion of total intake of that food came from canned products, and measured food concentrations. Dietary intakes were calculated as 12.6 ng/kg-day, of which 12.4 ng/kg-day was from canned foods. Canned vegetable intakes alone were 11.9 ng/kg-day. This dietary intake was compared to total intakes of BPA estimated from urine measurements of the National Health and Nutrition Examination Survey (NHANES). Total adult central tendency intakes ranged from 30 to 70 ng/kg-day for NHANES cycles between 2005 and 2010. Three possibilities were explored to explain the difference between these two approaches for intake estimation. Not all foods which may have been canned, particularly canned beverages such as soft drinks, were sampled in our food sampling program. Second, non-food pathways of exposure may be important for adults, including thermal paper exposures, and dust and air exposures. Finally, our canned food concentrations may not be adequately representative of canned foods in the United States; they were found to be generally lower compared to canned food concentrations measured in six other worldwide food surveys including three in North America. Our finding that canned food concentrations greatly exceeded non-canned concentrations was consistent with other studies, and underscores the importance of canned foods in the overall exposure of adults of BPA.

Persistent organic pollutants (POPs) are environmental chemicals that persist in the environment for long periods of time. The UN, under the Stockholm Convention, has regulated many of these POPs. However, because of their long half-lives, human exposure persists for decades even after production has been stopped. The health effects are varied and range from skin rashes to developmental delays to cancer, depending on the level of exposure. This review is meant as a primer for practicing clinicians to help identify acute exposure, to provide guidance to questioning patients, and be well-informed with regards to policy changes. It touches upon human exposure, current regulations, and health effect of the persistent organic pollutants, including: dioxin, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and the endocrine disruptor bisphenol A (BPA).

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) have been measured in surplus serum collected in 2009 from a convenience sample of 300 Texas children (boys and girls) in the birth to 13 years of age range. Serum concentrations of traditional persistent organic pollutants such as 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and p,p'-DDE did not change consistently with age. By contrast, serum concentrations of tetra-, penta-, and hexa-BDEs were lowest in the youngest children (birth to two year old) and increased 3.0 to 7.9 times, depending on the analyte, for children in the >4 to 6 years of age group. From the apex concentration to the 10 to 13 years of age group, concentrations decreased significantly except for 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE-153), which also had a longer apex concentration of >4 to 8 years of age. This concentration trend for PBDE-153 is most likely due to a longer half-life of PBDE-153 than of other PBDE congeners. The observed PBDEs concentration patterns by age may be related, at least in part, to ingestion of residential dust containing PBDEs through hand-to-mouth behavior among toddlers, preschoolers, and kindergarteners. Further studies to characterize young children's exposure to PBDEs are warranted and, in particular, to determine the lifestyle factors that may contribute to such exposures.

We wish to comment on the article by Tai et al .1 This article suggests that the dioxin contaminant of Agent Orange may be responsible for neurological abnormalities in Vietnamese infants. The characteristic and toxic dioxin contaminant of Agent Orange, 2,3,7,8-tetrochlorodibenzodioxin (TCDD), was reported at very low levels for those potentially exposed. TCDD levels were only slightly higher in the potentially contaminated (1.4 pg/g) than in the comparison …

BACKGROUND:Phthalates have been found in many personal care and industrial products, but have not previously been reported in food purchased in the United States. Phthalates are ubiquitous synthetic compounds and therefore difficult to measure in foods containing trace levels. Phthalates have been associated with endocrine disruption and developmental alteration. OBJECTIVES:Our goals were to report concentrations of phthalates in U.S. food for the first time, specifically, nine phthalates in 72 individual food samples purchased in Albany, New York, and to compare these findings with other countries and estimate dietary phthalate intake. METHODS:A convenience sample of commonly consumed foods was purchased from New York supermarkets. Methods were developed to analyze these foods using gas chromatography-mass spectroscopy. Dietary intakes of phthalates were estimated as the product of the food consumption rate and concentration of phthalates in that food. RESULTS:The range of detection frequency of individual phthalates varied from 6% for dicyclohexyl phthalate (DCHP) to 74% for di-2-ethylhexyl phthalate (DEHP). DEHP concentrations were the highest of the phthalates measured in all foods except beef [where di-n-octyl phthalate (DnOP) was the highest phthalate found], with pork having the highest estimated mean concentration of any food group (mean 300 ng/g; maximum, 1,158 ng/g). Estimated mean adult intakes ranged from 0.004 μg/kg/day for dimethyl phthalate (DMP) to 0.673 μg/kg/day for DEHP. CONCLUSIONS:Phthalates are widely present in U.S. foods. While estimated intakes for individual phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, cumulative exposure to phthalates is of concern and a more representative survey of U.S. foods is indicated.

Children have unusual patterns of exposure to environmental chemicals, and they have vulnerabilities that are quite distinct from those of adults. Increasingly, children's exposures to chemicals in the environment are understood to contribute to the causation and exacerbation of certain chronic, disabling diseases in children including asthma, cancer, birth defects, and neurobehavioral dysfunction. The protection of children against environmental toxins is a major challenge to modern society. Dioxins in organic eggs: a review M. De Vries1, 2, R.P. Kwakkel2 and A. Kijlstra1, * 1 Animal Sciences Group, Wageningen University and Research Centre, P.O. Box 65, NL-8200 AB Lelystad, The Netherlands 2 Animal Nutrition Group, Wageningen University, Wageningen, The Netherlands * Corresponding author (e-mail: aize.kijlstra@wur.nl) Received 19 July 2006; accepted 9 August 2006 Abstract Eggs contribute for about 4% to the daily dioxin intake of humans. Research among layer farms in the Netherlands and other EU countries has shown that organic eggs contain more dioxin than conventional Eggs contribute for about 4% to the daily dioxin intake of humans. Research among layer farms in the Netherlands and other EU countries has shown that organic eggs contain more dioxin than conventional ones and that a significant number of organic farms produce eggs with a dioxin content that exceeds the EU standard. The hens’ intake of dioxins from various sources leads to an increase in the dioxin content of organic eggs. These sources include plants, feed, soil, worms and insects, and compared with hens on conventional and free-range farms, organic hens make more use of these sources due to better access to the outdoor run. Plants appear to be relatively unimportant as a source of dioxins. Also commercial organic feed generally has very low dioxin contents, but not much is known about non-commercial feed. Consumption of worms and insects and particularly ingestion of soil are important causes of high dioxin levels in eggs. Management interventions, like a reduction of the time the hens spend outside, may decrease the dioxin levels in organic eggs but at the same time may interfere with the image of the organic production system. *** Steven Lester, Science Director for The Center for Health, Environment & Justice, points out “that the average backgrond exposure of the American public to dioxin in food is very close to or above he EPA new reference dose.”

This chapter contains sections titled: Introduction History of Military Use of Herbicides Exposed and Potentially Exposed Populations in Vietnam Dioxin Contamination and “Hot Spots” Early Studies Postwar International Research Cooperation Dioxin “Hot Spots” Mitigation Efforts Remediation at the DA Nang Base U. S. Government Support at DA Nang Bien HOA and its Airbase PHU Cat Airbase Agent Orange in Cambodia, Laos, and Vietnam Health Impacts of Agent Orange/Dioxin Veterans and Agent Orange Vietnamese and Health Studies Support for Vietnamese Believed to be Affected by Agent Orange/Dioxin Conclusions References

PREFACE xi ACKNOWLEDGMENT xvi ABOUT THE EDITOR xvii CONTRIBUTORS xix LIST OF TABLES AND FIGURES xxiii 1 PERSISTENT ORGANIC POLLUTANTS: AN OVERVIEW 1 Daniele Wikoff, Lauren Fitzgerald, and Linda Birnbaum 2 TOXICITY EQUIVALENCE FACTORS FOR DIOXIN AND RELATED COMPOUNDS 37 Michael DeVito 3 HISTORIC AND NEWER PERSISTENT ORGANIC POLLUTANTS IN FOOD 53 Janice Huwe 4 FLAME RETARDANTS: POLYBROMINATED DIPHENYL ETHERS AND THEIR REPLACEMENTS 89 Thomas F. Webster and Heather M. Stapleton 5 PHARMACOKINETICS OF 2,3,7,8-TETRACHLORODIBENZO-AND RELATED COMPOUNDS P-DIOXIN 109 James R. Olson 6 IMMUNOMODULATION BY PERSISTENT ORGANIC POLLUTANTS 171 Robert W. Luebke, Jamie C. DeWitt, Dori R. Germolec, Keith D. Salazar, and Nancy I. Kerkvliet 7 DEVELOPMENTAL NEUROTOXICITY OF DIOXINS 193 G. Jean Harry and Pamela J. Lein 8 EPIDEMIOLOGICAL EVIDENCE ON THE HEALTH EFFECTS OF PERFLUOROOCTANOIC ACID 229 Kyle Steenland, Tony Fletcher, and David A. Savitz 9 POLYBROMINATED P-DIOXINS AND DIBENZO-DIBENZOFURANS 255 Kurunthachalam Kannan, Chunyang Liao, and Hyo-Bang Moon 10 EPIDEMIOLOGICAL STUDIES ON CANCER AND EXPOSURE TO DIOXINS AND RELATED COMPOUNDS 303 Lennart Hardell and Mikael Eriksson 11 REPRODUCTIVE AND DEVELOPMENTAL EPIDEMIOLOGY OF DIOXINS 359 Anne Sweeney, Deborah J. del Junco, Marcella Warner, and Brenda Eskenazi 12 BISPHENOL A 381 Thaddeus T. Schug, Sarah A. Vogel, Laura N. Vandenberg, Joe M. Braun, Russ Hauser, Julia A. Taylor, Frederick S. vom Saal, and Jerold J. Heindel 13 PHTHALATES: HUMAN EXPOSURE AND RELATED HEALTH EFFECTS 415 John D. Meeker and Kelly K. Ferguson 14 THE SEVESO ACCIDENT 445 Angela Cecilia Pesatori and Pier Alberto Bertazzi 15 AGENT ORANGE: HEALTH AND ENVIRONMENTAL ISSUES IN VIETNAM, CAMBODIA, AND LAOS 469 Susan Hammond and Arnold Schecter 16 THE YUSHO AND YUCHENG RICE OIL POISONING INCIDENTS 521 Yoshito Masuda and Arnold Schecter 17 THE BINGHAMTON, NEW YORK, ELECTRICAL TRANSFORMER FIRE INCIDENT OF 1981 553 Nancy Kim and Arnold Schecter 18 THE YUSHCHENKO DIOXIN POISONING: CHRONOLOGY AND PHARMACOKINETICS 567 John Jake Ryan 19 POPs AND HUMAN HEALTH RISK ASSESSMENT 579 David T. Szabo and Anne E. Loccisano INDEX 619

BACKGROUND:Hexabromocyclododecane (HBCD) is a brominated flame retardant used in polystyrene foams in thermal insulation and electrical equipment. The HBCD commercial mixture consists mainly of α, β, and γ stereoisomers. Health concerns of HBCD exposure include alterations in immune and reproductive systems, neurotoxic effects, and endocrine disruption. Stereoisomer-specific levels of HBCD have not been measured previously in U.S. food. OBJECTIVES:We measured HBCD stereoisomer levels in U.S. foods from Dallas, Texas, supermarkets. METHODS:Convenience samples of commonly consumed foods were purchased from supermarkets in Dallas in 2009-2010. Food samples included a wide variety of lipid-rich foods: fish, peanut butter, poultry, pork, and beef. Thirty-six individual food samples were collected in 2010 and analyzed for α-, β-, and γ-HBCD stereoisomers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Ten pooled food samples previously collected in 2009 for a study of total HBCD levels using gas chromatography-mass spectrometry (GC-MS), were reanalyzed for α-, β-, and γ-HBCD stereoisomers using LC-MS/MS. RESULTS:Of the 36 measured individual foods, 15 (42%) had detectable levels of HBCD. Median (ranges) of α- and γ-HBCD concentrations were 0.003 (< 0.005-1.307) and 0.005 (< 0.010-0.143) ng/g wet weight (ww), respectively; β-HBCD was present in three samples with a median (range) of 0.003 (< 0.005-0.019) ng/g ww. Median levels (range) for α-, β-, and γ-HBCD, in pooled samples were 0.077 (0.010-0.310), 0.008 (< 0.002-0.070), and 0.024 (0.012-0.170) ng/g ww, respectively. CONCLUSIONS:α-HBCD was detected most frequently and at highest concentrations, followed by γ-, and then β-HBCD, in food samples from Dallas, Texas. Food may be a substantial contributor to the elevated α-HBCD levels observed in humans. These data suggest that larger and more representative sampling should be conducted.