Centurial Persistence of Forever Chemicals at Military Fire Training Sites.

Drinking water contamination by per- and polyfluoroalkyl substances (PFAS) is widespread near more than 300 United States (U.S.) military bases that used aqueous film-forming foams (AFFF) for fire training and firefighting activities. Much of the PFAS at these sites consist of precursors that can transform into terminal compounds of known health concern but are omitted from standard analytical methods. Here, we estimate the expected duration and contribution of precursor biotransformation to groundwater PFAS contamination at an AFFF-contaminated military base on Cape Cod, Massachusetts, United States, by optimizing a geochemical box model using measured PFAS concentrations from a multidecadal time series of groundwater and a soil survey in the source zone. A toolbox of analytical techniques used to reconstruct the mass budget of PFAS showed that precursors accounted for 46 ± 8% of the extractable organofluorine (a proxy for total PFAS) across years. Terminal PFAS still exceed regulatory limits by 2000-fold decades after AFFF use ceased. Measurements and numerical modeling show that sulfonamido precursors are retained in the vadose zone and their slow biotransformation into perfluoroalkyl sulfonates (half-life > 66 yr) sustains groundwater concentrations of perfluorobutane sulfonate (PFBS) and perfluorohexane sulfonate (PFHxS). The estimated PFAS reservoir in the vadose zone and modeled flux into groundwater suggest PFAS contamination above regulatory guidelines will persist for centuries without remediation.

The association of urinary phosphorous-containing flame retardant metabolites and self-reported personal care and household product use among couples seeking fertility treatment.

BACKGROUND: Phosphorous-containing flame-retardants (PFRs) are widely detected. They are used both as a flame retardant as well as plasticizer. METHODS: A subset of 230 women and 229 men were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. At each visit, participants completed a questionnaire of personal care product (PCP) and household product (HP) use. Metabolites [bis(1,3-dichloro-2-propyl) phosphate, diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate and bis(1-chloro-2-propyl) phosphate] were measured in urine (1-5 samples; n = 638 women, n = 335 men). Associations were assessed using generalized mixed models, adjusted for SG, age, BMI, smoking, education, and season. RESULTS: In women, moisturizer (60%), nail polish remover (77%), and nail polish (134%) use were associated (p < 0.05) with an increase in DPHP concentrations, while ip-PPP concentrations increased 21-27% with conditioner, cosmetics, deodorant, and hair product use. Mouthwash and vinyl glove use were associated with a respective 31% and 92% increase in DPHP among men. CONCLUSIONS: Our exploratory analysis suggests PFRs may be used as a plasticizer in consumer products, and nail polish use contributes to internal DPHP exposure. Further research is needed to understand how PFRs are used in these products and how it relates to exposure.

Identification of Beta-Carotene Degradation Compounds and Their Structural Elucidation by High-Resolution Accurate Mass Spectrometry.

Beta-carotene (BC) degradation was studied by liquid chromatography coupled to a quadrupole time of flight mass spectrometer. Throughout/After 21 days of dark storage, 56 nonvolatile degradants were chromatographically separated from pure BC crystal and their molecular formulas were identified. Their structure information was gained by comparing the fragments to a different, but structure-related compound. For example, a newly formed double bond position in dehydrogenated BC was determined by comparing the fragments between BC and dehydrogenated BC. One of their chemical structures was confirmed by comparing its precursor ion mass, retention time, isotopic ratio, and fragmentation to a pure trans-beta-apo-8'-apocarotenal. BC cleavage was observed on double bonds as well as single bonds in BC conjugation chain. PRACTICAL APPLICATION: As evidenced in this study, beta-carotene (BC) degradation is a spontaneous process initiated when the compound is exposed to air. The stoichiometric ratio of BC to oxygen is 1:0.03 at the first oxidation, therefore, only 0.3 mg oxygen or 1.2 mL air will degrade 10 mg BC, an average daily recommended intake. Not like in enzymatic BC degradation, spontaneous BC oxidation did not produce provitamin A, either in retina C20H38O or retinol C20H40O forms. For BC application in vitamin A deficiency, spontaneous BC oxidation should be avoided.

Prioritizing potential endocrine active high resolution mass spectrometry (HRMS) features in Minnesota lakewater.

Liquid chromatography high-resolution mass spectrometry (LC-HRMS) shows great potential for expanding our understanding of relevant unknown chemical components present within complex environmental mixtures. This study identified potentially endocrine active components within Minnesota lakewater by prioritizing LC-HRMS features uniquely present at sunfish spawning habitats where male fish showed signs of estrogen agonism. Porewater samples from four locations within the same lake were analyzed using liquid chromatography quadrupole time of flight mass spectrometry (LC-QToF/MS) with positive (ESI+) and negative (ESI-) electrospray ionization. Plasma vitellogenin concentrations of captured male sunfish was used to designate sites as either endocrine active (ACT; 2 sites) or reference (REF; 2 sites). Assuming unique chemical presence at active sites contributed to endocrine activity, features at significantly higher intensities (p-value < 0.05, t-value > t-critical, log-fold change > 0.1; equal variance t-test of log2 transformed data) in ACT sites were then compiled into a suspect search list for feature identification. Adducts and isotopes of prioritized features were deprioritized using pattern recognizing algorithms using mass, retention time, and intensity. Feature identities were reported according to established confidence metrics using spectral libraries and elemental composition algorithms. This LC-HRMS approach identified a number of features omitted by targeted analysis with higher relative abundances in ACT sites, including plant essential oils, fatty acids, and mycotoxins. Multivariate analysis determined whether features were either present at both sites (AB) or unique to individual ACT sites (A or B). Detection frequency across datasets indicated bias in feature prioritization influenced by the chosen sampling method and sample acquisition mode. The majority of features prioritized by this workflow remain tentatively identified or unidentified masses of interest, reflective of current limitations in shared spectral libraries for soft ionization analyses. Strategies similar to this workflow have the potential to reduce bias in database-driven toxicological prioritization frameworks.

Organophosphate flame-retardant metabolite concentrations and pregnancy loss among women conceiving with assisted reproductive technology.

OBJECTIVE: To evaluate whether urinary concentrations of organophosphate flame retardant (PFR) metabolites are associated with pregnancy loss among women conceiving with assisted reproductive technology (ART). DESIGN: Prospective preconception cohort of subfertile women. SETTING: Academic hospital fertility center in Boston, Massachusetts. PATIENT(S): A total of 155 women conceiving 179 pregnancies with ART. INTERVENTION(S): None. Mean exposure to each of five PFR metabolites was estimated by averaging the specific-gravity adjusted natural log concentrations from two urine samples collected during the ART cycle of conception. MAIN OUTCOME MEASURE(S): Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for biochemical and total pregnancy loss (all losses <20 weeks' gestation) by quartiles of PFR metabolite concentrations were estimated using a repeated measures log-binomial model, accounting for multiple pregnancies per woman. RESULT(S): Of the 179 pregnancies, 31% ended in pregnancy loss (12% in biochemical loss). Among the three metabolites with high detection frequency [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), and isopropylphenyl phenyl phosphate (ip-PPP)], an increased risk of biochemical loss was observed for women with DPHP concentrations in the fourth vs. first quartile (RR 1.64; 95% CI 0.61-4.39). Also found was an elevated risk of biochemical pregnancy loss among women in the highest quartile of the molar sum of urinary PFR metabolites compared with the lowest (RR 1.89; 95% CI 0.64-5.58). Urinary concentrations of ip-PPP and BDCIPP were not associated with either outcome. CONCLUSION(S): Among subfertile women, urinary DPHP metabolite concentrations measured during the ART cycle of conception may be associated with early pregnancy loss. Although this study is uniquely designed to investigate early markers of pregnancy success and maintenance, the small sample size likely contributed to imprecision. Given their increasing use as replacement chemicals for traditional flame retardants, exposure to PFRs may increase, and more studies will be needed to investigate their potential to impact pregnancy and reproduction.

The association between urinary concentrations of phosphorous-containing flame retardant metabolites and semen parameters among men from a fertility clinic.

BACKGROUND: The use of PFRs has steadily increased as brominated compounds have been or are being phased out. Human exposure is widespread and animal studies have shown adverse impacts on male reproduction, but human data are lacking. OBJECTIVE: To study the associations between urinary concentrations of phosphorous-containing flame retardant (PFR) metabolites and semen parameters. METHODS: A subset of 220 men from an existing longitudinal cohort of couples were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. Semen parameters included sperm count, concentration, motility, and morphology; some men had samples measured from multiple clinic visits (up to five visits; n = 269 semen samples). 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)] were measured in urine samples (between one and five urine samples per participant; n = 355 urine samples). Semen parameters were evaluated continuously and dichotomized for models. Metabolites were assessed for associations with semen parameters as continuous and categorized into quartiles using multivariable generalized mixed models, adjusted for specific gravity, age, BMI, smoking, and abstinence period. RESULTS: Metabolites BDCIPP, DPHP, and ip-PPP were detected in a high proportion of urine samples (85%, 86%, and 65% respectively). Concentrations varied by season of collection, particularly for BDCIPP where samples collected in the summer were approximately 2-fold higher than concentrations of other seasons (p < 0.0001). The odds of having a sperm count less than 39 mil/ejaculate decreased by 20% for increasing BDCIPP concentrations (p = 0.04). When regressing semen parameters on PFR metabolite quartiles, some negative associations were observed for individual quartiles among sample volume and morphology, but overall associations were weak and inconsistent. CONCLUSION: Detection rates were high for BDCIPP, DPHP, and ip-PPP. We did not observe consistent associations between PFR metabolites and semen parameters. Due to the high prevalence of exposure, further investigation of other potential health effects should be conducted.

Prenatal exposure to organophosphates and associations with birthweight and gestational length.

Organophosphate esters (OPEs) are often used as flame retardants and plasticizers. Animal data suggest exposure to OPEs could impact children's growth and development, yet impacts on human birth outcomes are understudied. We evaluate impacts of OPE exposure on the timing of delivery and infant's birthweight in the Pregnancy Infection and Nutrition Study (PIN). North Carolina women enrolled in PIN in early pregnancy and participated in follow-up through delivery. Analyses were limited to mothers recruited from 2002 to 2005, whose children participated in additional follow-up in early childhood (n = 349). Mothers collected urine samples in which OPE metabolites were assessed and birth outcomes were abstracted from medical records. Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) were detected in >80% of samples. Average birthweight and gestational age were 3326 g and 39.1 weeks, respectively. As data suggest that the mechanisms of action by which OPEs impact birth outcomes may be fetal sex dependent, we conducted sex-stratified statistical analyses. Women with the highest ip-PPP concentrations delivered girls 1 week earlier than women with lower levels (95% Confidence Interval (CI): -1.85, -0.15). Women with BDCIPP levels above the median had 3.99 (95% CI: 1.08, 14.78) times the odds of delivering their daughters preterm. Similarly, higher ip-PPP levels were associated with lower birthweight, but not after standardizing for gestational age. Among males, maternal ip-PPP was associated with decreased odds of preterm birth (OR = 0.21, 95% CI: 0.06, 0.68). DPHP and BCIPHIPP levels were not associated with outcomes in either sex. Results indicate that prenatal OPE exposure may impact timing of birth, though results are imprecise. Given widespread OPE exposure and the urgent need to identify and mitigate causes of preterm birth, further investigation is warranted.

Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo.

Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone (TH) homeostasis through multiple mechanisms, including inhibition of enzymes that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The placenta plays a critical role in helping to maintain TH levels during fetal development and expresses SULTs. This is concerning given that disruption of TH regulation within the placenta could potentially harm the developing fetus. In this study, we investigated the effects of two polybrominated diphenyl ethers (PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed to BFR concentrations up to 1 µM for 1-24 h to investigate changes in basal SULT activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the most potent inhibitor of basal 3,3'-T2 SULT activity at all exposure durations, decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE-47, and 6-OH BDE-47 also decreased 3,3'-T2 SULT activity by 23-42% at concentrations of 0.5 µM and 1.0 µM following 24 h exposures. BDE-47 had no effect on SULT activity, and there was no observed effect of any BFR exposure on expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research demonstrates that total TH SULT activity in placental cells are sensitive to BFR exposure; however, the mechanisms and consequences have yet to be fully elucidated.

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.

BACKGROUND: Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. METHODS: This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, 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). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. RESULTS: Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). CONCLUSIONS: Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes.

Size-resolved particle measurements of polybrominated diphenyl ethers indoors: Implications for sources and human exposure.

Polybrominated diphenyl ethers (PBDEs) are flame retardant polymer additives that are widely detected in outdoor and indoor environments. Release of PBDEs from consumer products leads to high concentrations indoors, but mechanisms of release are poorly understood. Although ingestion of dust is a well-studied indoor PBDE exposure route, the importance of inhalation exposure is uncertain. To address these unknowns, dust was collected from household vacuum cleaners, and suspended particulate matter was collected from the same homes in St. John's, Newfoundland, Canada, using a cascade impactor. Size-fractionated particulate matter samples (0.01-18 µm diameter) were analyzed for PBDEs. The sum of PBDEs in all particulate matter ranged from 8.7 ± 0.5 to 15.7 ± 0.5 pg/m3 , with >50% of PBDE mass in respirable particulate matter (<1 µm). Mass loadings as a function of particle size suggested that both abrasion and off-gassing led to the presence of PBDEs in particulate matter. Variability in the particulate matter mass loadings indicated that emission mechanisms were both product- and location-dependent. Congener profiles in colocated vacuum dust and particulate matter samples were different, indicating that vacuum dust cannot accurately predict PBDE congeners in respirable particulate matter. A calculated lower limit inhalation exposure to PBDEs (0.19 ng/d) is lower than exposure via diet or ingestion of dust, although the different biochemical pathways for inhalation compared with ingestion may have different biological effects. The present study highlights the importance of contaminant analysis in size-fractionated particulate matter to assess human exposure via inhalation compared with traditional vacuum dust methods. Environ Toxicol Chem 2018;37:481-490. © 2017 SETAC.

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

[This corrects the article DOI: 10.1289/EHP1021.].

Current-use flame retardants: Maternal exposure and neurodevelopment in children of the CHAMACOS cohort.

Flame retardants are commonly used in consumer products found in U.S. households. Restrictions on the use of polybrominated diphenyl ether flame retardants have resulted in increased use of replacement chemicals, including Firemaster 550® (FM 550®) and organophosphate flame retardants (PFRs): tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). Animal research suggests that PFRs may affect neurodevelopment through noncholinergic mechanisms similar to some organophosphate (OP) pesticides. Despite the widespread presence of these compounds in home environments, and their structural similarity to neurotoxic OP pesticides, understanding of human exposure and health effects of PFRs is limited. We measured four urinary PFR metabolites from pregnant women in the CHAMACOS birth cohort study (n = 310) and assessed neurodevelopment of their children at age 7. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in >75% of urine samples, and isopropylphenyl phenyl phosphate (ip-PPP), a metabolite of one component of FM 550®, was detected in 72% of urine samples. We observed decreases of 2.9 points (95% Confidence Interval (CI): -6.3, 0.5) and 3.9 points (95% CI: -7.3,-0.5) in Full-Scale intelligence quotient and Working Memory, respectively, for each ten-fold increase in DPHP in adjusted regression models (n = 248). Decreases in Full-Scale IQ and Working Memory were greater in models of the molar sum of the PFR metabolites compared to the DPHP models. This is the first study to examine PFR and FM 550® exposures and potential neurodevelopmental outcomes in pregnant women and children. Additional research is warranted.

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/EHP1021.

Exposure to flame retardant chemicals and occurrence and severity of papillary thyroid cancer: A case-control study.

BACKGROUND: Thyroid cancer is the fastest increasing cancer in the U.S., and papillary thyroid cancer (PTC) accounts for >80% of incident cases. Increasing exposure to flame retardant chemicals (FRs) has raised concerns about their possible role in this 'epidemic'. The current study was designed to test the hypothesis that higher exposure to FRs is associated with increased odds of PTC. METHODS: PTC patients at the Duke Cancer Institute were approached and invited to participate. Age- and gender-matched controls were recruited from the Duke Health System and surrounding communities. Because suitable biomarkers of long-term exposure do not exist for many common FRs, and levels of FRs in dust are significantly correlated with exposure, relationships between FRs in household dust and PTC were evaluated in addition to available biomarkers. PTC status, measures of aggressiveness (e.g. tumor size) and BRAF V600E mutation were included as outcomes. RESULTS: Higher levels of some FRs, particularly decabromodiphenyl ether (BDE-209) and tris(2-chloroethyl) phosphate in dust, were associated with increased odds of PTC. Participants with dust BDE-209 concentrations above the median level were 2.29 times as likely to have PTC [95% confidence interval: 1.03, 5.08] compared to those with low BDE-209 concentrations. Associations varied based on tumor aggressiveness and mutation status; TCEP was more strongly associated with larger, more aggressive tumors and BDE-209 was associated with smaller, less aggressive tumors. CONCLUSIONS: Taken together, these results suggest exposure to FRs in the home, particularly BDE-209 and TCEP, may be associated with PTC occurrence and severity, and warrant further study.

Associations between flame retardant applications in furniture foam, house dust levels, and residents' serum levels.

Polyurethane foam (PUF) in upholstered furniture frequently is treated with flame retardant chemicals (FRs) to reduce its flammability and adhere to rigorous flammability standards. For decades, a commercial mixture of polybrominated diphenyl ethers (PBDEs) called PentaBDE was commonly applied to foam to fulfill these regulations; however, concerns over toxicity, bioaccumulation, and persistence led to a global phase-out in the mid-2000s. Although PentaBDE is still detected in older furniture, other FR compounds such as tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and Firemaster® 550 (FM550) have been increasingly used as replacements. While biomonitoring studies suggest exposure is widespread, the primary sources of exposure are not clearly known. Here, we investigated the relationships between specific FR applications in furniture foam and human exposure. Paired samples of furniture foam, house dust and serum samples were collected from a cohort in North Carolina, USA and analyzed for FRs typically used in PUF. In general, the presence of a specific FR in the sofa of a home was associated with an increase in the concentration of that FR in house dust. For example, the presence of PentaBDE in sofas was associated with significantly higher levels of BDE-47, a major component of PentaBDE, in house dust (10ß=6.4, p<0.001). A similar association was observed with a component of FM550, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), with levels that were approximately 3 times higher in house dust when FM550 was identified in the sofa foam (p<0.01). These relationships were modified by dust loading rates in the living room and the ratio of sofa size to room size. Interestingly, levels of TDCIPP and tris(1-chloro-2-isopropyl) phosphate (TCIPP) were also higher in dust with detections in sofa foam; however, these associations were not statistically significant and may suggest there are other prominent sources of these compounds in the home. In addition, the presence of PentaBDE in sofa foam was associated with significantly higher levels of BDE-47 in serum (p<0.01). These results suggest that FR applications in sofas are likely major sources of exposure to these compounds in the home.

Closing the Mass Balance on Fluorine on Papers and Textiles.

Papers and textiles that are treated with per- and polyfluoroalkyl substances (PFASs) are sources of human and environmental exposure. Data for individual PFASs, such as perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), are not placed into the context of total fluorine for papers and textiles. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to quantify volatile and ionic PFASs, respectively, and the total oxidizable precursor (TOP) assay was used to quantify precursors that form perfluoroalkyl carboxylates. Molar sums of PFASs obtained by GC-MS, LC-MS/MS, and precursors were compared to total fluorine (nmol F/cm2) determined by particle-induced gamma ray emission (PIGE) spectroscopy, measured before and after extraction. Volatile and ionic PFASs and unknown precursors accounted for 0-2.2%, 0-0.41%, and 0.021-14%, respectively, of the total nmol F/cm2 determined by PIGE. After extraction, papers and textiles retained 64 ± 28% to 110 ± 30% of the original nmol F/cm2 as determined by PIGE, indicating that the majority of fluorine remains associated with the papers and textiles. The sum of PFASs in the volatile, ionic, and precursor fraction, and total fluorine after extraction indicate that mass balance was achieved (within analytical error) of the initial total fluorine measured by PIGE.

Serum perfluoroalkyl acids (PFAAs) and associations with behavioral attributes.

The ubiquitous use of poly- and perfluoroalkyl substances (PFASs) in a variety of industrial and consumer products has resulted in chronic exposure in most industrialized nations, and led to measurable concentrations in blood and other tissues in humans across all life stages; however, behavioral attributes that relate to exposure are not well studied. To further investigate how behavior may relate to PFAS exposure, 37 adults were recruited from central North Carolina. Participants provided blood samples and behavioral questionnaires were administered, asking questions about a variety of household, dietary, and behavioral outcomes. Six PFAAs, including PFHxA (geometric mean: 0.14 ng/mL), PFOA (1.57 ng/mL), PFNA (0.67 ng/mL), PFDA (0.28 ng/mL), PFHxS (3.17 ng/mL) and PFOS (4.96 ng/mL) were detected in >50% of the samples. Generally, males had higher serum levels than females across all chemicals, and levels were very similar to NHANES levels; however, PFHxS and PFDA levels were higher in our study population. Several personal characteristics and behaviors were associated with serum PFAS levels. Reported use of filtration devices was associated with lower levels of PFOA (28% lower, p = 0.03), but higher levels of PFHxA (122% higher, p = 0.04). Serum PFHxS levels were also elevated in individuals that vacuumed less often, and in individuals that reported consuming more microwavable foods. These results suggest that personal behaviors may be important determinants of PFAS exposures.

Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation.

The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and ß-tetrabromoethylcyclohexane (ß-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC50 of 160 nM; no statistically significant inhibition of SULT activity was observed. ORD inhibition of 3,3'-T2 formation from rT3 was also observed (IC50 ∼ 100 nM). The kinetics of T4 O and IRD were also investigated, although a definitive mechanism could not be identified as the Michaelis-Menten parameters and maximal rate constants were not significantly different. Concentrations tested were intentionally above expected environmental levels, and this study suggests that these NBFRs are not potent human liver DIO and SULT inhibitors. To our knowledge, DBDPE is the first example of a nonhydroxylated contaminant inhibiting DIO activity, and further study of the mechanism of action is warranted.

Influence of storage vial material on measurement of organophosphate flame retardant metabolites in urine.

Use of organophosphate flame retardants (PFRs) has increased over the past decade with the phase out of polybrominated diphenyl ethers. Urinary metabolites of PFRs are used as biomarkers of exposure in epidemiologic research, which typically uses samples collected and stored in polypropylene plastic cryovials. However, a small study suggested that the storage vial material may influence reported concentrations. Therefore, we aimed to examine the influence of the storage vial material on analytical measurement of PFR urinary metabolites. Using urine samples collected from participants in the Environment and Reproductive Health (EARTH) Study, we analyzed the PFR metabolites in duplicate aliquots that were stored in glass and plastic vials (n = 31 pairs). Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP) and isopropyl-phenyl phenyl phosphate (ip-PPP) were detected in 98%, 97% and 87% of duplicates. We observed high correlations between glass-plastic duplicates for BDCIPP (rs = 0.95), DPHP (rs = 0.79) and ip-PPP (rs = 0.82) (p < 0.0001). Urinary ip-PPP was an average of 0.04 ng/ml (p = 0.04) higher among samples stored in glass, with a mean relative difference of 14%. While this difference is statistically significant, it is small in magnitude. No differences were observed for BDCIPP or DPHP, however future research should seek to reduce the potential for type II error (false negatives). We conclude that storing urine samples in polypropylene plastic cryovials may result in slightly reduced concentrations of urinary ip-PPP relative to storage in glass vials and future research should seek to increase the sample size, reduce background variability and consider the material of the urine collection cup.

Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort).

Organophosphate flame retardants (PFRs), used in consumer products since the 1970s, persist in the environment. Restrictions on penta-polybrominated diphenyl ether (PBDE) flame retardants resulted in increased use of Firemaster® 550 (FM® 550), and the organophosphate triesters: tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). The objectives of this study were to (1) identify determinants of flame retardants (4 PFRs, PentaBDEs and FM® 550) in house dust, (2) measure urinary PFR metabolites in pregnant women, and (3) estimate health risks from PFR exposure. We measured flame retardants in house dust (n = 125) and metabolites in urine (n = 310) collected in 2000-2001 from Mexican American women participating in the CHAMACOS birth cohort study in California. We detected FM® 550 and PFRs, including two (TCEP and TDCIPP) known to the state of California to cause cancer, in most dust samples. The maximum TCEP and TDCIPP dust levels were among the highest ever reported although the median levels were generally lower compared to other U.S. cohorts. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in 78% and 79% of prenatal urine samples, respectively. We found a weak but positive correlation between TPHP in dust and DPHP in 124 paired prenatal urine samples (Spearman rho = 0.17; p = 0.06). These results provide information on PFR exposure and risk in pregnant women from the early 2000's and are also valuable to assess trends in exposure and risk given changing fire safety regulations and concomitant changes in chemical flame retardant use.