Richard S. Jones

Prenatal exposure to PBDEs and neurodevelopment.

Background Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds that are persistent and bioaccumulative and therefore have become ubiquitous environment contaminants. Animal studies suggest that prenatal PBDE exposure may result in adverse neurodevelopmental effects. Objective In a longitudinal cohort initiated after 11 September 2001, including 329 mothers who delivered in one of three hospitals in lower Manhattan, New York, we examined prenatal PBDE exposure and neurodevelopment when their children were 12–48 and 72 months of age. Methods We analyzed 210 cord blood specimens for selected PBDE congeners and assessed neurodevelopmental effects in the children at 12–48 and 72 months of age; 118, 117, 114, 104, and 96 children with available cord PBDE measurements were assessed at 12, 24, 36, 48, and 72 months, respectively. We used multivariate regression analyses to evaluate the associations between concentrations of individual PBDE congeners and neurodevelopmental indices. Results Median cord blood concentrations of PBDE congeners 47, 99, and 100 were 11.2, 3.2, and 1.4 ng/g lipid, respectively. After adjustment for potential confounders, children with higher concentrations of BDEs 47, 99, or 100 scored lower on tests of mental and physical development at 12–48 and 72 months. Associations were significant for 12-month Psychomotor Development Index (BDE-47), 24-month Mental Development Index (MDI) (BDE-47, 99, and 100), 36-month MDI (BDE-100), 48-month full-scale and verbal IQ (BDE-47, 99, and 100) and performance IQ (BDE-100), and 72-month performance IQ (BDE-100). Conclusions This epidemiologic study demonstrates neurodevelopmental effects in relation to cord blood PBDE concentrations. Confirmation is needed in other longitudinal studies.

Low Dose of Some Persistent Organic Pollutants Predicts Type 2 Diabetes: A Nested Case–Control Study

Background Low doses of some persistent organic pollutants (POPs) associate cross-sectionally with type 2 diabetes, whereas associations with high POP exposures are inconsistent. Objectives We investigated whether several POPs prospectively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Methods Participants in this nested case–control study were diabetes free in 1987–1988. By 2005–2006, the 90 controls remained free of diabetes, whereas the 90 cases developed diabetes. Using serum collected in 1987–1988, we measured 8 organochlorine pesticides, 22 polychlorinated biphenyl congeners (PCBs), and 1 polybrominated biphenyl (PBB). We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey (NHANES) in 2003–2004. We computed odds ratios (ORs) for incident diabetes using logistic regression analysis. Results Chlorinated POPs in CARDIA in 1987–1988 were much higher than corresponding NHANES 2003-2004 concentrations. POPs showed nonlinear associations with diabetes risk. The highest risk was observed in the second quartiles of trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB153—a finding that suggests low-dose effects. We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum. The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index ≥ 30 kg/m2. Conclusions Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity.

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 (∑4PBDE) 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 < 0.001) and then decreased until 31–45 years (9.9 ± 1.6 ng/g lipid). We observed no further significant decrease among ages 31–45, 45–60 (p = 0.964), or > 60 years (p = 0.894). The mean ∑4PBDE 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.

Determinants of Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenyl Ethers (PBDEs) in an Urban Population

Background Recent studies have reported blood levels of polybrominated diphenyl ethers (PBDEs) in the U.S. population. Information about neonatal levels and about the relationship to polychlorinated biphenyls (PCBs) exposures is limited. Objectives The objective was to characterize levels and determinants of fetal exposure to PBDEs and PCBs among newborns from Baltimore, Maryland. Methods We analyzed umbilical cord blood for eight PBDEs and 35 PCBs from infants delivered at the Johns Hopkins Hospital. Maternal and infant characteristics were abstracted from medical records. Results Ninety-four percent of cord serum samples had quantifiable levels of at least one PBDE congener, and > 99% had at least one detectable PCB congener. PBDE concentrations in cord blood were similar to those reported in other studies from North America. Strong correlations were observed within but not across PCB and PBDE classes. Multivariate models showed that many factors independently predicted exposure to BDE-47, BDE-100, and BDE-153 and CB-118, CB-138/158, CB-153, and CB-180. Generally, infants of Asian mothers had lower PBDE and PCB levels, and infants of smokers had higher levels. Increased maternal body mass index was associated with lower levels of PCBs but not PBDEs. Levels of PCBs but not PBDEs were lower in births from married and multiparous mothers. Increased maternal age was associated with higher PCB levels but lower PBDE levels. Conclusions Although many of the factors we investigated were independent predictors of both PBDE and PCB levels, in some cases the direction of associations was different. More research is needed to better understand the sources and pathways of PBDE exposure.

Individual Characteristics Associated with PBDE Levels in U.S. Human Milk Samples

Background Reported polybrominated diphenyl ether (PBDE) concentrations in human samples in the United States have been higher than in Europe and Asia. Little is known about factors that contribute to individual variability in body burden. Objective In this large study we measured PBDE concentrations in human milk from the United States during 2004–2006. We assessed characteristics associated with concentrations in milk and change in milk concentration between 3 and 12 months postpartum. Methods We analyzed 303 milk samples obtained 3 months postpartum for PBDEs. A second sample was analyzed for 83 women still lactating 12 months postpartum. PBDE concentrations in milk and variability by individual characteristics such as age, parity, and prepregnancy body mass index (BMI) were evaluated using generalized linear models. Results PBDE congeners BDEs 28, 47, 99, 100, and 153 were detected in > 70% of samples. BDE-47 concentrations were the highest, ranging from below the limit of detection to 1,430 ng/g lipid, with a median of 28 ng/g lipid. Concentrations of most individual PBDE congeners and the sum of BDEs 28, 47, 99, 100, and 153 (∑PBDE) were lower among mothers > 34 years of age compared with those 25–29 years of age and higher among mothers with high compared with normal BMI, after adjustment for other covariates. Parity was not associated with PBDE concentration. The change in ∑PBDE concentration in milk between 3 and 12 months postpartum was highly variable (median increase, 14%; interquartile range, −26% to 50%). Conclusions PBDEs were detected in nearly all human milk samples, varying by maternal weight and age and over the course of breast-feeding.

Polybrominated Diphenyl Ether Levels in the Blood of Pregnant Women Living in an Agricultural Community in California

Background Recent studies have raised concerns about polybrominated diphenyl ether (PBDE) flame retardant exposures to pregnant women and women of child-bearing age in the United States. Few studies have measured PBDEs in immigrant populations. Objectives Our goal was to characterize levels of seven PBDE congeners, polychlorinated biphenyl (PCB)-153, and polybrominated biphenyl (PBB)-153 in plasma from 24 pregnant women of Mexican descent living in an agricultural community in California. Results The median concentration of the sum of the PBDE congeners was 21 ng/g lipid and ranged from 5.3 to 320 ng/g lipid. Consistent with other studies, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) was found at the highest concentration (median = 11 ng/g lipid; range, 2.5–205) followed by 2,2′,4,4′,5-pentabromobiphenyl (BDE-99) (median = 2.9 ng/g lipid; range, 0.5–54), 2,2′,4,4′,5-pentaBDE (BDE-100) (median = 1.8 ng/g lipid; range, 0.6–44), and 2,2′,4,4′,5,5′-hexaBDE (BDE-153) (median = 1.5 ng/g lipid; range, 0.4–35). Levels of PCB-153 (median= 4.4 ng/g lipid; range, < 2–75) were lower than U.S. averages and uncorrelated with PBDE levels, suggesting different exposure routes. Conclusions The overall levels of PBDEs found were lower than levels observed in other U.S. populations, although still higher than those observed previously in Europe or Japan. The upper range of exposure is similar to what has been reported in other U.S. populations. PBDEs have been associated with adverse developmental effects in animals. Future studies are needed to determine the sources and pathways of PBDE exposures and whether these exposures have adverse effects on human health.

Body burdens of polybrominated diphenyl ethers among urban anglers

Polybrominated diphenyl ethers (PBDEs) have been widely used in the United States and worldwide as flame retardants. Recent PBDE production figures show that worldwide use has increased. To determine whether fish consumption is a source of PBDE exposure for humans, a cross-sectional epidemiologic study of New York and New Jersey urban anglers was conducted during the summers of 2001–2003. Frequency of local fish consumption was assessed by questionnaire, and blood samples for PBDE analysis were collected from 94 anglers fishing from piers on the lower Hudson River and Newark Bay. We analyzed PBDEs by gas chromatography–isotope dilution–high-resolution mass spectrometry. The congeners found in anglers’ serum at the highest concentrations were, by International Union of Pure and Applied Chemistry numbers, BDE-47, BDE-153, and BDE-99. Anglers reporting consumption of local fish had higher, but nonstatistically significantly different, concentrations of PBDEs than did anglers who did not eat local fish. For some congeners (BDE-100 and BDE-153), we observed moderate dose–response relationships between serum PBDE levels and frequency of reported fish intake. These findings suggest that consumption of locally caught fish is not a major route of human exposure for this study population.

Body burdens of brominated flame retardants and other persistent organo-halogenated compounds and their descriptors in US girls

BACKGROUND Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. OBJECTIVE Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. METHODS Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. RESULTS Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had higher GMs than in Ohio for the pesticides and most PCB congeners, but the opposite for CB-99 and -118. CONCLUSIONS Several of these potential HAAs were detected in nearly all of these young girls, some at relatively high levels, with variation by geographic location and other demographic factors that may reflect exposure pathways. The higher PBDE levels in California likely reflect differences in fire regulation and safety codes, with potential policy implications.

Determinants of Serum Polybrominated Diphenyl Ether (PBDE) Levels among Pregnant Women in the CHAMACOS Cohort

We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ≥3 pieces of stuffed furniture in their homes (p < 0.05). Womens total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ≥3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in womens serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.

A method for rapid, non-targeted screening for environmental contaminants in household dust

Household dust can be a major source of human exposure to environmental contaminants such as polybrominated diphenyl ethers, pesticides, and other compounds. This work shows a screening technique that may be used to identify components in an environmental sample as xenobiotics based on mass spectral characteristics of classes of compounds that may be expected to be present in the environment. Household dust (SRM-2585) from the National Institute of Standards and Technology (NIST) was extracted with hexane using accelerated solvent extraction. Large molecules, such as triglycerides and fatty acids were removed with gel permeation chromatography. The extract was then concentrated and analyzed by comprehensive two dimensional gas chromatography coupled to a time of flight mass spectrometer. The resulting peak table was automatically filtered to identify compound classes such as phthalates, polycyclic aromatic hydrocarbons and their heterocyclic analogs, chlorinated compounds, brominated compounds, and nitro compounds. While phthalates can be identified by abundances at specific masses, the identification of the remaining classes is based on the identification of the molecular ion and identification of isotope clusters or other spectral characteristics. The technique detected compounds identified and quantified by NIST as well as compounds not identified by NIST in the sample. By comparison with concentrations determined by NIST for the analytes found, the technique is able to identify analytes in these compound classes at concentrations as low as 10-20 ng/g dust.