Children Show Highest Levels of Polybrominated Diphenyl Ethers in a California Family of Four: A Case Study

Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants, are ubiquitous environmental contaminants with particularly high concentrations in humans from the United States. This study is a first attempt to report and compare PBDE concentrations in blood drawn from a family. Serum samples from family members collected at two sampling occasions 90 days apart were analyzed for PBDE congeners. Concentrations of the lower-brominated PBDEs were similar at the two sampling times for each family member, with children’s levels 2- to 5-fold higher than those of their parents. Concentrations of, for example, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) varied from 32 ng/g lipid weight (lw) in the father to 60, 137, and 245 ng/g lw in the mother, child, and toddler, respectively. Decabromodiphenyl ether (BDE-209) concentrations differed significantly between the two samplings. September concentrations in the father, mother, child, and toddler were 23, 14, 143, and 233 ng/g lw, respectively. December concentrations (duplicate results from the laboratory) were 2 and 3, 4 and 4, 9 and 12, and 19 and 26 ng/g lw, respectively. Parents’ ∑PBDE concentrations approached U.S. median concentrations, with children’s concentrations near the maximum (top 5%) found in U.S. adults. The youngest child had the highest concentrations of all PBDE congeners, suggesting that younger children are more exposed to PBDEs than are adults. Our estimates indicate that house dust contributes to children’s higher PBDE levels. BDE-209 levels for all family members were 10-fold lower at the second sampling. The short half-life of BDE-209 (15 days) indicates that BDE-209 levels can decrease rapidly in response to decreased exposures. This case study suggests that children are at higher risk for PBDE exposures and, accordingly, face higher risks of PBDE-related health effects than adults

Global Gene Expression Analysis in the Livers of Rat Offspring Perinatally Exposed to Low Doses of 2,2′,4,4′-Tetrabromodiphenyl Ether

BACKGROUND: Polybrominated diphenyl ethers are a group of flame-retardant chemicals appearing increasingly in the environment. Their health effects and mechanisms of toxicity are poorly understood. OBJECTIVES: We screened for the sensitive effects and mechanisms of toxicity of 2,2 ,4,4 -tetra-bromodiphenyl ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses comparable to human exposure. METHODS: Wistar dams were exposed to vehicle or BDE-47 (0.002 and 0.2 mg/kg body weight) every fifth day from gestation day 15 to postnatal day 20 by injections to caudal vein. Total RNA was extracted from the livers of pups and hybridized to the whole-genome RNA expression micro-arrays. The list of genes 2-fold differentially expressed was exported to PANTHER and Ingenuity Systems for analysis of enriched ontology groups and molecular pathways. RESULTS: Oxidoreductase and transferase protein families were enriched in exposed rats as were these biological process categories: carbohydrate metabolism; electron transport; and lipid, fatty acid, and steroid metabolism. Four signaling pathways (cascades of activation of drug-metabolizing enzymes) and 10 metabolic pathways were significantly enriched. Drug-metabolizing enzymes appear to be regulated by BDE-47 through an aryl hydrocarbon receptor-independent mechanism. Direct interaction with retinoid X receptor or its upstream cascade may be involved. The main metabolic effects consisted of activation of metabolic pathways: alpha- and omega-oxidation of fatty acids, glycolysis, and starch hydrolysis. CONCLUSIONS: Altered expression of genes involved in metabolic and signaling pathways and functions of the organism occurs after perinatal exposure of rat offspring to BDE-47 at doses relevant for the general population

Polybrominated Diphenyl Ethers: A Case Study for Using Biomonitoring Data to Address Risk Assessment Questions

The use of biomonitoring data holds promise for characterizing exposure and informing risk assessment. Biomonitoring data have been used successfully to track population trends, identify susceptible populations, and provide indications of emerging environmental health issues. However, there remain challenges associated with interpreting biomonitoring data for risk assessment. An international biomonitoring workshop was convened in September 2004 to explore the use of biomonitoring data in the context of risk assessment. Six compounds were examined as case studies for this workshop, including polybrominated diphenyl ethers (PBDEs). The PBDE case study was developed to provide an example of a persistent compound for which relatively few data are available for human exposure, biomonitoring, and health outcomes. PBDEs are used in hard plastics, electronics, textiles, and polyurethane foam products. The congener pattern downstream of production facilities often resembles the commercial mixture. However, because these compounds persist in the environment and in biota, the patterns of congeners evolve. PBDEs partition into body lipids, and direct measurement of bromodiphenyl ether congeners in biologic specimens provides a good marker of exposure. Data indicate significant variability (> 100-fold range) in lipid-adjusted levels for PBDEs in the general population. It is hypothesized that both exposure and pharmacokinetics may play a role in observed congener profiles. Significant gaps in our ability to interpret PBDE biomonitoring data to address public health and risk assessment questions include limited knowledge of environmental fate and transport of PBDE congeners, limited population-based data for adults, and lack of data for potentially vulnerable populations such as children

Developmental Exposure to Low-Dose PBDE-99: Effects on Male Fertility and Neurobehavior in Rat Offspring

In utero exposure to a single low dose of 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) disrupts neurobehavioral development and causes permanent effects on the rat male reproductive system apparent in adulthood. PBDEs, a class of flame retardants, are widely used in every sector of modern life to prevent fire. They are persistent in the environment, and increasing levels of PBDEs have been found in biota and human breast milk. In the present study we assessed the effects of developmental exposure to one of the most persistent PBDE congeners (PBDE-99) on juvenile basal motor activity levels and adult male reproductive health. Wistar rat dams were treated by gavage on gestation day 6 with a single low dose of 60 or 300 μg PBDE-99/kg body weight (bw). In offspring, basal locomotor activity was evaluated on postnatal days 36 and 71, and reproductive performance was assessed in males at adulthood. The exposure to low-dose PBDE-99 during development caused hyperactivity in the offspring at both time points and permanently impaired spermatogenesis by the means of reduced sperm and spermatid counts. The doses used in this study (60 and 300 μg/kg bw) are relevant to human exposure levels, being approximately 6 and 29 times, respectively, higher than the highest level reported in human breast adipose tissue. This is the lowest dose of PBDE reported to date to have an in vivo toxic effect in rodents and supports the premise that low-dose studies should be encouraged for hazard identification of persistent environmental pollutants

Apparent Half-Lives of Hepta- to Decabrominated Diphenyl Ethers in Human Serum as Determined in Occupationally Exposed Workers

The aim of the present study was to model apparent serum half-lives of polybrominated diphenyl ethers (PBDEs) with 7–10 bromine substituents. Workers with occupational exposure to PBDEs have elevated serum levels of PBDEs, but these substances are also found in the general population and are ubiquitous environmental contaminants. The calculations were based on exposure assessments of rubber workers (manufactured flame-retarded rubber compound) and electronics dismantlers who donated blood during a period with no work-related exposures to PBDEs, and referents without any known occupational exposure (clerks, cleaners, and abattoir workers). The workers had previously been found to have elevated levels of high- and medium-brominated diphenyl ethers compared with the referent populations. We performed nonlinear mixed-effects modeling of kinetics, using data from previous and present chemical analyses. The calculated apparent half-life for decabromodiphenyl ether (BDE-209) was 15 days (95% confidence interval, 11–18 days). The three nona-BDEs and four octa-BDE congeners were found to have half-lives of 18–39 and 37–91 days, respectively. BDE-209 has a short half-life in human blood. Because BDE-209 is commonly present in humans in general, the results of this study imply that humans must be more or less continuously exposed to BDE-209 to sustain the serum concentrations observed. BDE-209 is more readily transformed and/or eliminated than are lower brominated diphenyl ether congeners, and human health risk must be assessed accordingly

Polybrominated Diphenyl Ether (PBDE) Levels in an Expanded Market Basket Survey of U.S. Food and Estimated PBDE Dietary Intake by Age and Sex

OBJECTIVES: Our objectives in this study were to expand a previously reported U.S. market basket survey using a larger sample size and to estimate levels of PBDE intake from food for the U.S. general population by sex and age. METHODS: We measured concentrations of 13 polybrominated diphenyl ether (PBDE) congeners in food in 62 food samples. In addition, we estimated levels of PBDE intake from food for the U.S. general population by age (birth through ≥60 years of age) and sex. RESULTS: In food samples, concentrations of total PBDEs varied from 7.9 pg/g (parts per trillion) in milk to 3,726 pg/g in canned sardines. Fish were highest in PBDEs (mean, 1,120 pg/g; median, 616 pg/g; range, 11.14–3,726 pg/g). This was followed by meat (mean, 383 pg/g; median, 190 pg/g; range, 39–1,426 pg/g) and dairy products (mean, 116 pg/g; median, 32.2 pg/g; range, 7.9–683 pg/g). However, using estimates for food consumption (excluding nursing infants), meat accounted for the highest U.S. dietary PBDE intake, followed by dairy and fish, with almost equal contributions. Adult females had lower dietary intake of PBDEs than did adult males, based on body weight. We estimated PBDE intake from food to be 307 ng/kg/day for nursing infants and from 2 ng/kg/day at 2–5 years of age for both males and females to 0.9 ng/kg/day in adult females. CONCLUSION: Dietary exposure alone does not appear to account for the very high body burdens measured. The indoor environment (dust, air) may play an important role in PBDE body burdens in addition to food

Diet Contributes Significantly to the Body Burden of PBDEs in the General U.S. Population

BACKGROUND. Exposure of the U.S. population to polybrominated diphenyl ethers (PBDEs) is thought to be via exposure to dust and diet. However, little work has been done to empirically link body burdens of these compounds to either route of exposure. OBJECTIVES. The primary goal of this research was to evaluate the dietary contribution to PBDE body burdens in the United States by linking serum levels to food intake. METHODS. We used two dietary instruments-a 24-hr food recall (24FR) and a 1-year food frequency questionnaire (FFQ)-to examine food intake among participants of the 2003-2004 National Health and Nutrition Examination Survey. We regressed serum concentrations of five PBDEs (BDE congeners 28, 47, 99, 100, and 153) and their sum (ΣPBDE) against diet variables while adjusting for age, sex, race/ethnicity, income, and body mass index. RESULTS. ΣPBDE serum concentrations among vegetarians were 23% (p = 0.006) and 27% (p = 0.009) lower than among omnivores for 24FR and 1-year FFQ, respectively. Serum levels of five PBDE congeners were associated with consumption of poultry fat: Low, medium, and high intake corresponded to geometric mean ΣPBDE concentrations of 40.6, 41.9, and 48.3 ng/g lipid, respectively (p = 0.0005). We observed similar trends for red meat fat, which were statistically significant for BDE-100 and BDE-153. No association was observed between serum PBDEs and consumption of dairy or fish. Results were similar for both dietary instruments but were more robust using 24FR. CONCLUSIONS. Intake of contaminated poultry and red meat contributes significantly to PBDE body burdens in the United States.National Institute of Environmental Health Sciences (R01ES015829, T32ES014562

Serum Polybrominated Diphenyl Ether (PBDE) Levels Are Higher in Children (2–5 Years of Age) than in Infants and Adults

Background: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many products and have been detected in human samples worldwide. Limited data show that concentrations are elevated in young children. Objectives: We investigated the association between PBDEs and age with an emphasis on young children from Australia in 2006–2007. Methods: We collected human blood serum samples (n = 2,420), which we stratified by age and sex and pooled for analysis of PBDEs. Results: The sum of BDE-47, -99, -100, and -153 concentrations (Σ4PBDE) increased from 0–0.5 years (mean ± SD, 14 ± 3.4 ng/g lipid) to peak at 2.6–3 years (51 ± 36 ng/g lipid; p 60 years (p = 0.894). The mean Σ4PBDE concentration in cord blood (24 ± 14 ng/g lipid) did not differ significantly from that in adult serum at ages 15–30 (p = 0.198) or 31–45 years (p = 0.140). We found no temporal trend when we compared the present results with Australian PBDE data from 2002–2005. PBDE concentrations were higher in males than in females; however, this difference reached statistical significance only for BDE-153 (p = 0.05). Conclusions: The observed peak concentration at 2.6–3 years of age is later than the period when breast-feeding is typically ceased. This suggests that in addition to the exposure via human milk, young children have higher exposure to these chemicals and/or a lower capacity to eliminate them. Key words: Australia, children, cord blood, human blood serum, PBDEs, polybrominated diphenyl ethers. Environ Health Perspect 117:1461–1465 (2009). doi:10.1289/ehp.090059