Identifying predictors of human exposure to brominated and organophosphate flame retardants in the indoor environments

Thesis (Ph.D.)--Boston UniversityFlame retardants are chemical additives used to meet flammability standards for many materials including high impact polystyrene used in consumer electronics and polyurethane foam used in furniture. To date, research in the U.S. has primarily focused on polybrorninated diphenyl ethers (PBDEs), which have been shown to escape from products over time and accumulate in the dust of indoor environments as well as in our bodies. Due to growing concerns regarding its persistence and toxicity, PBDEs began to be phased out of production in the U.S. in 2005. Since then, other flame retardants such as hexabromocyclododecane (HBCD), tetrabromobisphenol-A (TBBP-A) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) have potentially increased in use. Therefore, our objectives were to characterize human exposure to these flame retardants and assess predictors of exposure. We investigated exposure to target flame retardants in three potentially susceptible and highly exposed populations: HBCD and TBBP-A in breast milk of first-time mothers, the primary metabolite of TDCPP in urine from office workers, and PBDEs in serum from collegiate gymnasts. The target flame retardants were identified in 100% of samples, with the exception of TBBP-A (35%). Body burdens of HBCD and TBBP-A were similar to reports from other parts of the world. HBCD exposure was positively associated with the number of stereo and video electronics in the home and lower in participants who regularly chose organic foods compared to those who did not. Our measurements of TDCPP metabolite in urine are among the first in the world. Participants who worked in a new office building had urinary concentrations of TDCPP metabolite that were 26% of those who worked in older office buildings. Finally, the geometric mean (GM) concentration of BDE153 in serum from gymnasts was four times higher than in the general U.S. population and similar to the GM concentration measured in foam recyclers and carpet installers. Concentrations of flame retardants in gym air and dust were orders of magnitude higher than previously found in residences. Overall, our results suggest that the indoor environment contributes to flame retardant exposure in our target populations

Potential Exposure to Arsenic from Infant Rice Cereal

Background: Rice is known to be high in arsenic, including in infant rice cereal. Although arsenic in drinking water is currently regulated, there are currently no US regulations regarding arsenic concentrations in food. Objective: We used published values to estimate arsenic exposure via rice cereal relative to breast milkor formula for 6- to 12-month-old infants in the general US population. Results: We found that arsenic exposure from 3 servings of rice cereal exceeded that of formula made with water containing arsenic at 10 μg/L, the US Environmental Protection Agency maximum contaminant level. Conclusions: Our findings suggest that rice cereal can markedly increase arsenic exposure among US infants relative to breast milk and formula

Estimated Exposure to Arsenic in Breastfed and Formula-Fed Infants in a United States Cohort

Background: Previous studies indicate that concentrations of arsenic in breast milk are relatively low even in areas with high drinking-water arsenic. However, it is uncertain whether breastfeeding leads to reduced infant exposure to arsenic in regions with lower arsenic concentrations. Objective: We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. population. Methods: We measured arsenic in home tap water (n = 874), urine from 6-week-old infants (n = 72), and breast milk from mothers (n = 9) enrolled in the New Hampshire Birth Cohort Study (NHBCS) using inductively coupled plasma mass spectrometry. Using data from a 3-day food diary, we compared urinary arsenic across infant feeding types and developed predictive exposure models to estimate daily arsenic intake from breast milk and formula. Results: Urinary arsenic concentrations were generally low (median, 0.17 μg/L; maximum, 2.9 μg/L) but 7.5 times higher for infants fed exclusively with formula than for infants fed exclusively with breast milk (β = 2.02; 95% CI: 1.21, 2.83; p \u3c 0.0001, adjusted for specific gravity). Similarly, the median estimated daily arsenic intake by NHBCS infants was 5.5 times higher for formula-fed infants (0.22 μg/kg/day) than for breastfed infants (0.04 μg/kg/day). Given median arsenic concentrations measured in NHBCS tap water and previously published for formula powder, formula powder was estimated to account for ~ 70% of median exposure among formula-fed NHBCS infants. Conclusions: Our findings suggest that breastfed infants have lower arsenic exposure than formula-fed infants, and that both formula powder and drinking water can be sources of exposure for U.S. infants

Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts

Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n = 53 urine samples total). We identified a 50% increase in the TPHP biomarker (p = 0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p = 0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S.Accepted versio

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

Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing in Vitro Fertilization

Background: Evidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes. Objectives: We evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic. Methods: This analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman. Results: Detection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ΣPFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%). Conclusions: Using IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP102

Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing in Vitro Fertilization

Background: Evidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes. Objectives: We evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic. Methods: This analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman. Results: Detection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ΣPFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%). Conclusions: Using IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP102

Predictors of Tetrabromobisphenol‑A (TBBP-A) and Hexabromocyclododecanes (HBCD) in Milk from Boston Mothers

Tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecanes (HBCDs) are brominated flame retardants that have been found in human milk and serum throughout the world, but have received comparatively little attention in the United States. The objective of this study is to determine concentrations of these analytes in samples of breast milk collected from first-time mothers in the Greater Boston, Massachusetts area and to explore predictors of exposure. Human milk samples were analyzed by LC-ESI-MS/MS for TBBP-A, HBCDs (the α, β, and γ diastereomers), and HBCD degradation products: pentabromocyclododecanes (PBCDs) and tetrabromocyclododecadienes (TBCDs). HBCD diastereomers were detected in all samples with α-HBCD present in the highest proportion. TBBP-A, PBCDs, and TBCDs were detected in 35%, 42%, and 56% of the analyzed samples, respectively. Self-reported demographic, dietary and behavioral data were examined as predictors of HBCD levels. Levels of HBCD were significantly, positively associated with the number of stereo and video electronics in the home (17% increase/item; 95% Confidence Interval (CI) = 4–31%) and reduced in participants who regularly chose organic foods compared to those who did not (0.51, 95% CI = 0.32–0.82). These results suggest that lifestyle factors are related to body burdens of HBCD and that domestic electronics may be an important source of HBCD exposure in the indoor environment

Flame Retardant Exposure among Collegiate United States Gymnasts

Gymnastics training facilities contain large volumes of polyurethane foam, a material that often contains additive flame retardants such as PentaBDE. While investigations of human exposure to flame retardants have focused on the general population, potentially higher than background exposures may occur in gymnasts and certain occupational groups. Our objectives were to compare PentaBDE body burden among gymnasts to the general United States population and characterize flame retardants levels in gym equipment, air, and dust. We recruited 11 collegiate female gymnasts (ages 18–22) from one gym in the eastern United States. The geometric mean (GM) concentration of BDE-153 in gymnast sera (32.5 ng/g lipid) was 4–6.5 times higher than in the general United States population groups. Median concentrations of PentaBDE, TBB, and TBPH in paired handwipe samples were 2–3 times higher after practice compared to before, indicating the gymnasts contacted these flame retardants during practice. GM concentrations of PentaBDE, TBB, and TBPH were 1–3 orders of magnitude higher in gym air and dust than in residences. Our findings suggest that these collegiate gymnasts experienced higher exposures to PentaBDE flame retardants compared to the general United States population and that gymnasts may also have increased exposure to other additive flame retardants used in polyurethane foam such as TBB and TBPH

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