Human exposure to polybrominated diphenyl ethers and endocrine disruption

Thesis (Ph.D.)--Boston UniversityPolybrominated diphenyl ethers (PBDEs) are a class of flame retardant chemicals that have been added to consumer products such as foam furniture and electronic equipment since the 1970s. Human exposure can occur when PBDEs are released to the environment. North Americans are among the most highly exposed populations, with median serum concentrations about an order of magnitude higher than European or Asian populations. Multiple animal studies have shown PBDEs to be thyroid hormone disruptors that may also adversely affect reproductive success. Limited human studies exist on the human health effects of PBDEs or their persistence in human tissues. We investigated exposure to PBDEs in a longitudinal cohort of 52 healthy adults within the Boston metropolitan area, hereafter referred to as the Flame Retardant Exposure (FlaRE) cohort. We followed individuals for approximately one year and collected serum samples and questionnaire data at three sampling intervals: Winter 2010, Summer 2010, and Winter 2011. Serum samples were analyzed for 11 PBDE congeners, thyroid function, and reproductive function tests. We used these data to assess the stability of PBDEs in serum measures, determine potential temporal trends in PBDE serum concentrations over 1 year, and assess the relationship between PBDE exposure and thyroid and reproductive function tests over time. In the FlaRE cohort, geometric mean sum concentrations of the five most prevalent PBDE congeners (BDE 28, 47, 99, 100, 153) were 21.8 ng/g lipid in Winter 2010, 22.8 ng/g lipid in Summer 2010, and 18.7 ng/g lipid in Winter 2011. We found that a single PentaBDE serum measurement is a stable estimate, either continuously or categorically, of a participant's blood concentration over the one-year study period. After adjustment of important confounders, we found that serum PentaBDE congeners were inversely associated with Total T4, which is consistent with animal experiments and some previous epidemiology studies. Among men 40 years or older, increased exposure to PentaBDEs was associated with a decrease in inhibin-B, an increase in follicular stimulating hormone, and decreases in the inhibin-B/FSH ratio thus indicating PBDE exposure may decrease testicular function in men

Temporal Variability of Polybrominated Diphenyl Ether (PBDE) Serum Concentrations over One Year

Polybrominated diphenyl ethers (PBDEs) are flame retardant chemicals used in consumer products. They are common contaminants in human serum and associated with adverse health effects. Our objectives were to characterize PBDE serum concentrations in a New England cohort and assess temporal variability of this exposure biomarker over a one-year period. We collected three repeated measurements at six-month intervals from 52 office workers from the greater Boston (MA, United States) area from 2010 to 2011. The intraclass correlation coefficient for BDEs 28, 47, 99, 100, and 153 ranged from 0.87 to 0.99, indicating that a single serum measurement can reliably estimate exposure over a one-year period. This was true for both lipid adjusted and nonlipid adjusted concentrations. The kappa statistics, quantifying the level of agreement of categorical exposure classification, based on medians, tertiles, or quartiles ranged from 0.67 to 0.90. Some congeners showed nonsignificant increases from sampling round 1 (winter) to round 2 (summer) and significant decreases from round 2 to round 3 (winter). This study highlights the high reliability of a single serum PBDE measurement for use in human epidemiologic studies

Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations

Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007–2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population

Investigating a Novel Flame Retardant Known as V6: Measurements in Baby Products, House Dust, and Car Dust

With the phase-out of polybrominated diphenyl ether (PBDE) flame retardants, the use of new and alternate flame retardants has been increasing. 2,2-bis­(chloromethyl)­propane-1,3-diyltetrakis­(2-chloroethyl) bisphosphate, known as V6, is a flame retardant applied to polyurethane foam commonly found in furniture and automobile foam. However, to the authors’ knowledge, no research has been conducted on V6 levels in the environment. The intention of this study was to measure the concentration of V6 in foam collected from baby products where it was recently detected and measure levels in dust samples collected from homes and automobiles in the Boston, MA area. To accomplish this, a pure V6 commercial standard was purchased from a Chinese manufacturer and purified (>98%). An analytical method to measure V6 in dust samples using liquid chromatography tandem mass spectrometry (LC/MS-MS) was developed. Extraction was conducted using accelerated solvent extraction (ASE) and extracts were purified using an ENVI-Florisil SPE column (500 mg, 3 mL). V6 was measured in foam samples collected from baby products with a concentration ranging from 24 500 000 to 59 500 000 ng/g of foam (<i>n</i> = 12, average ± sd: 46 500 000 ± 12 000 000 ng/g; i.e., on average, 4.6% of the foam mass was V6). V6 was also detected in 19 of 20 car dust samples and 14 of 20 house dust samples analyzed. The concentration of V6 in the house dust ranged from <5 ng/g to 1110 ng/g with a median of 12.5 ng/g, and <5 ng/g to 6160 ng/g in the car dust with a median of 103.0 ng/g. Concentrations in car dust were significantly higher than in the house dust potentially indicating higher use of V6 in automobiles compared to products found in the home. Furthermore, tris (2-chloroethyl) phosphate (TCEP), a known carcinogen, was found in the V6 commercial mixture (14% by weight) as an impurity and was consistently detected with V6 in the foam samples analyzed. A significant correlation was also observed between V6 and TCEP in the dust samples suggesting that the use of V6 is a significant source of TCEP in the indoor environment

Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States

During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris­(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis­(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10^β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes