Thomas F Webster

Boston University, Boston, Massachusetts, United States

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Publications (104)435.61 Total impact

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    ABSTRACT: Background While adult exposure to PCE is known to have toxic effects, there is little information on the long-term impact of prenatal and early childhood exposure. We undertook a retrospective cohort study to examine the effects of their early life exposure to PCE-contaminated drinking water. This retrospective cohort study examined whether prenatal and early childhood exposure to PCE-contaminated drinking water influenced the risk of a variety of chronic conditions among adults who were born between 1969 and 1983 in the Cape Cod area of Massachusetts. Methods Eight hundred and thirty-one participants with prenatal and early childhood PCE exposure and 547 unexposed participants were studied. Individuals completed questionnaires to gather information on demographic characteristics, chronic conditions, and other sources of solvent exposure. The location of residences from birth through 1990 were used to estimate PCE exposure with U.S. EPA’s water distribution system modeling software (EPANET) modified to incorporate a leaching and transport model. Results No associations were observed between early life PCE exposure and current occurrence of obesity, diabetes, cardiovascular disease, hypertension, color blindness, near- and far sightedness and dry eyes. In contrast, a 1.8-fold increased risk of cancer (95% CI: 0.8, 4.0) was seen among individuals with any early life exposure. These results were based on 31 participants (23 exposed and 8 unexposed) who reported cancers at a variety of anatomical sites, particularly the cervix. A 1.5-fold increase in the risk of epilepsy (95% CI: 0.6, 3.6, based on 16 exposed and 7 unexposed participants) was also observed among individuals with any early life exposure that was further increased to 1.8 (95% CI: 0.7, 4.6) among those with exposure at or above the sample median. Conclusions These results suggest that the risk of epilepsy and certain types of cancer such as cervical cancer may be increased among adults who were exposed to PCE-contaminated drinking water exposure during gestation and early childhood. These findings should be interpreted cautiously because of the study limitations and confirmed in follow-up investigations of similarly exposed populations with medically-confirmed diagnoses. This relatively young study population should also be monitored periodically for subsequent changes in disease risk.
    Environmental Health 04/2015; 14(1). DOI:10.1186/s12940-015-0021-z · 2.71 Impact Factor
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    ABSTRACT: 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 (USA) 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 non-lipid 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 non-significant 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.
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    ABSTRACT: Background: Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator activated receptor γ (PPARγ) nuclear receptor. Objectives: Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated. Methods: A commercially available fluorescence polarization ligand binding assay (PolarScreenTM PPARγ-competitor assay kit, Invitrogen) was used to investigate the binding potency of flame retardants and dust extracts to human PPARγ LBD. Rosiglitazone was used as a positive control. Results: Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate (TB-MEHP), halogenated bisphenol/phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE47, with an IC50 of 0.24 μM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3–16% increase in PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions. Conclusion: Our results suggest that several flame retardants are potential PPARγ ligands, and that metabolism may lead to increased binding affinity. The PPARγ binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.
    Environmental Health Perspectives 10/2014; DOI:10.1289/ehp.1408522 · 7.03 Impact Factor
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    ABSTRACT: Alternative flame retardant use has increased since the phase out of pentabromodiphenyl ethers. One alternative, Firemaster(®) 550 (FM550), induces obesity in rats. Triphenyl phosphate (TPP), a component of FM550, has a structure similar to organotins, which are obesogenic in rodents.
    Environmental Health Perspectives 07/2014; DOI:10.1289/ehp.1408111 · 7.03 Impact Factor
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    ABSTRACT: In this discussion paper, the transition from long-chain poly- and perfluorinated alkyl substances (PFASs) to fluorinated alternatives is addressed. Long-chain PFASs include perfluoroalkyl carboxylic acids (PFCAs) with 7 or more perfluorinated carbons, perfluoroalkyl sulfonic acids (PFSAs) with 6 or more perfluorinated carbons, and their precursors. Because long-chain PFASs have been found to be persistent, bioaccumulative and toxic, they are being replaced by a wide range of fluorinated alternatives. We summarize key concerns about the potential impacts of fluorinated alternatives on human health and the environment in order to provide concise information for different stakeholders and the public. These concerns include, amongst others, the likelihood of fluorinated alternatives or their transformation products becoming ubiquitously present in the global environment; the need for more information on uses, properties and effects of fluorinated alternatives; the formation of persistent terminal transformation products including PFCAs and PFSAs; increasing environmental and human exposure and potential of adverse effects as a consequence of the high ultimate persistence and increasing usage of fluorinated alternatives; the high societal costs that would be caused if the uses, environmental fate, and adverse effects of fluorinated alternatives had to be investigated by publicly funded research; and the lack of consideration of non-persistent alternatives to long-chain PFASs.
    Chemosphere 06/2014; DOI:10.1016/j.chemosphere.2014.05.044 · 3.50 Impact Factor
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    ABSTRACT: Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met CPAI-84 standards by analyzing 11 samples of tent fabrics for chemical flame retardant additives. Furthermore, we investigated potential exposure by collecting paired samples of tent wipes and hand wipes from 27 individuals after tent setup. Of the 11 fabric samples analyzed, 10 contained flame retardant additives, which included tris(1,3-dichloroisopropyl) phosphate (TDCPP), decabromodiphenyl ether (BDE-209), triphenyl phosphate, and tetrabromobisphenol-A. Flame retardant concentrations were discovered to be as high as 37.5 mg/g (3.8% by weight) in the tent fabric samples, and TDCPP and BDE-209 were the most frequently detected in these samples. We also observed a significant association between TDCPP levels in tent wipes and those in paired hand wipes, suggesting that human contact with the tent fabric material leads to the transfer of the flame retardant to the skin surface and human exposure. These results suggest that direct contact with flame retardant-treated textiles may be a source of exposure. Future studies will be needed to better characterize exposure, including via inhalation and dermal sorption from air.
    02/2014; 1(2):152-155. DOI:10.1021/ez400185y
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    ABSTRACT: Polybrominated diphenyl ether (PBDE), flame retardants (FRs) have been ubiquitously detected at high concentrations in indoor environments; however, with their recent phase-out, more attention is being focused on measurements of exposure to alternative FRs such as organophosphate FRs (OPFRs). In our previous research, we found that PBDE residues measured on children's handwipes were a strong predictor of serum PBDE levels. Here we build upon this research to examine longitudinal changes in PBDEs in indoor dust and children's handwipes, and explore the associations between handwipes and dust for alternative FRs. Children from our previous study were re-contacted after approximately two years and new samples of indoor dust and handwipes were collected. PBDE dust-levels were significantly correlated between two different sampling rounds separated by two years; however, PBDE levels in handwipes were not correlated, perhaps suggesting that the sources of PBDEs remained relatively constant in the home, but that behavioral differences in children are changing with age and influencing handwipe levels. OPFRs [i.e. tris(1,3-dichloroisopropyl) phosphate (TDCPP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP)], 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, also known as TBB), di(2-ethylhexyl) tetrabromophthalate (BEH-TEBP, also known as TBPH), and 1,2,5,6,9,10-hexabromocyclododecane (HBCD) were also ubiquitously detected in house dust samples and geometric mean levels were similar to PBDE levels, or higher in the case of the OPFRs. Significant associations between handwipes and house dust were observed for these alternative FRs, particularly for EH-TBB (rs=0.54; p<0.001). Increasing house dust levels and age were associated with higher levels of FRs in handwipes, and high hand washing frequency (>5timesd(-1)) was associated with lower FR levels in handwipes. Overall these data suggest that exposure to these alternative FRs will be similar to PBDE exposure, and the influence of hand-to-mouth behavior in children's exposure needs to be further examined to better estimate exposure potential.
    Chemosphere 01/2014; 116. DOI:10.1016/j.chemosphere.2013.12.100 · 3.50 Impact Factor
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    ABSTRACT: 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 U.S. 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 U.S. The geometric mean (GM) concentration of BDE-153 in gymnast sera (32.5 ng/g lipid) was 4-6.5 times higher than general U.S. 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 U.S. population and that gymnasts may also have increased exposure to other additive flame retardants used in polyurethane foam such as TBB and TBPH.
    Environmental Science & Technology 11/2013; DOI:10.1021/es4037868 · 5.48 Impact Factor
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    ABSTRACT: We aimed to characterize levels of polyfluorinated compounds (PFCs) in indoor dust from offices, homes, and vehicles; to investigate factors that may affect PFC levels in dust; and to examine the associations between PFCs in dust and office workers' serum. Dust samples were collected in 2009 from offices, homes, and vehicles of 31 individuals in Boston, MA and analyzed for nineteen PFCs, including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), fluorotelomer alcohols (FTOHs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant and analyzed for eight PFCs including PFOA and PFOS. Perfluorononanoate, PFOA, perfluoroheptanoate, perfluorohexanoate, PFOS and 8:2 FTOH had detection frequencies >50% in dust from all three microenvironments. The highest geometric mean concentration in office dust was for 8:2 FTOH (309ng/g), while PFOS was highest in homes (26.9ng/g) and vehicles (15.8ng/g). Overall, offices had the highest PFC concentrations, particularly for longer-chain carboxylic acids and FTOHs. Perfluorobutyrate was prevalent in homes and vehicles, but not offices. PFOA serum concentrations were not associated with PFC dust levels after adjusting for PFC concentrations in office air. Dust concentrations of most PFCs are higher in offices than in homes and vehicles. However, indoor dust may not be a significant source of exposure to PFCs for office workers. This finding suggests that our previously published observation of an association between FTOH concentrations in office air and PFOA concentrations in office workers was not due to confounding by PFCs in dust.
    Environment international 09/2013; 60C:128-136. DOI:10.1016/j.envint.2013.08.012 · 5.66 Impact Factor
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    ABSTRACT: Increased use of flame-retardants in office furniture may increase exposure to PBDEs in the office environment. However, partitioning of PBDEs within the office environment is not well understood. Our objectives were to examine relationships between concurrent measures of PBDEs in office air, floor dust, and surface wipes. We collected air, dust, and surface wipe samples from 31 offices in Boston, MA. Correlation and linear regression were used to evaluate associations between variables. Geometric mean (GM) concentrations of individual BDE congeners in air and congener specific octanol-air partition coefficients (Koa) were used to predict GM concentrations in dust and surface wipes and compared to the measured concentrations. GM concentrations of PentaBDEs in office air, dust, and surface wipes were 472pg/m(3), 2411ng/g, and 77pg/cm(2), respectively. BDE209 was detected in 100% of dust samples (GM=4202ng/g), 93% of surface wipes (GM=125pg/cm(2)), and 39% of air samples. PentaBDEs in dust and air were moderately correlated with each other (r=0.60, p=0.0003), as well as with PentaBDEs in surface wipes (r=0.51, p=0.003 for both dust and air). BDE209 in dust was correlated with BDE209 in surface wipes (r=0.69, p=0.007). Building (three categories) and PentaBDEs in dust were independent predictors of PentaBDEs in both air and surface wipes, together explaining 50% (p=0.0009) and 48% (p=0.001) of the variation respectively. Predicted and measured concentrations of individual BDE congeners were highly correlated in dust (r=0.98, p<0.0001) and surface wipes (r=0.94, p=002). BDE209 provided an interesting test of this equilibrium partitioning model as it is a low volatility compound. Associations between PentaBDEs in multiple sampling media suggest that collecting dust or surface wipes may be a convenient method of characterizing exposure in the indoor environment. The volatility of individual congeners, as well as physical characteristics of the indoor environment, influence relationships between PBDEs in air, dust, and surface wipes.
    Environment international 06/2013; 59C:124-132. DOI:10.1016/j.envint.2013.06.001 · 5.66 Impact Factor
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    ABSTRACT: 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 (n = 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.
    Environmental Science & Technology 04/2013; 47(9). DOI:10.1021/es400032v · 5.48 Impact Factor
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    Thomas F Webster, Heather M Stapleton
    Environmental Health Perspectives 04/2013; 121(4):a110-1. DOI:10.1289/ehp.1206470R · 7.03 Impact Factor
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    ABSTRACT: Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a flame retardant widely used in furniture containing polyurethane foam. It is a carcinogen, endocrine disruptor, and potentially neurotoxic. Our objectives were to characterize exposure of adult office workers (n=29) to TDCPP by measuring its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in their urine; measuring TDCPP in dust from their homes; offices and vehicles; and assessing possible predictors of exposure. We identified TDCPP in 99% of dust (GM=4.43μg/g) and BDCPP in 100% of urine samples (GM=408pg/mL). Concentrations of TDCPP were significantly higher in dust from vehicles (GM=12.5μg/g) and offices (GM=6.06μg/g) than in dust from the main living area (GM=4.21μg/g) or bedrooms (GM=1.40μg/g) of worker homes. Urinary BDCPP concentrations among participants who worked in a new office building were 26% of those who worked in older buildings (p=0.01). We found some evidence of a positive trend between urinary BDCPP and TDCPP in office dust that was not observed in the other microenvironments and may be related to the timing of urine sample collection during the afternoon of a workday. Overall our findings suggest that exposure to TDCPP in the work environment is one of the contributors to the personal exposure for office workers. Further research is needed to confirm specific exposure sources (e.g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways.
    Environment international 03/2013; 55C:56-61. DOI:10.1016/j.envint.2013.02.004 · 5.66 Impact Factor
  • Thomas F Webster
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    ABSTRACT: Must molecular mechanisms be the same for concentration addition to predict the effect of a mixture or is it sufficient for compounds to affect similar pathways or common outcomes? Does concentration addition provide a closer approximation to observations than alternative models such as independent action? Suppose effects are mediated by hormone A through receptor R, synthesis of A is reduced by compound B, and that C is a competitive antagonist to A. Both B and C reduce levels of the receptor-ligand complex AR but via different specific mechanisms. Are combinations of B and C concentration additive? We used simple pharmacodynamic models, deriving mathematical models using equilibrium binding and mass balance. Assume A binds the receptor at one site of R with effects proportional to the concentration of AR. Let C act as a competitive antagonist via the Gaddum equation. Let B affect synthesis of A via a function g(B). We derive a model describing the joint response surface of B and C, and a function describing its isoboles. Under concentration addition, the isoboles must be negatively sloped straight lines. We show that linearity of the isoboles depends crucially on g(B). The mixture is concentration additive if g"(B), the second derivative of g(B) with respect to B, is always zero. Responses are greater than concentration additive if g"(B) is always positive and less than concentration additive if g"(B) is always negative. We describe functions g(B) that lead to all three cases as well as one that is greater than concentration additive in some regions and less than concentration additive in others. At least in this simple model, concentration addition cannot be assumed: mixtures of competitive antagonists and compounds that alter hormone synthesis can lead to results that are concentration additive, greater than concentration additive or less than concentration additive. Nevertheless, concentration addition appears to provide a closer approximation to the pharmacodynamic model examined here than independent action. Care needs to be taken in extrapolating to other situations, but analysis of simple pharmacodynamic models appears to be a useful strategy.
    Toxicology 01/2013; 313(2-3). DOI:10.1016/j.tox.2013.01.009 · 3.75 Impact Factor
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    ABSTRACT: Background: Perfluorooctanoic acid (PFOA) has been linked to cancer in occupational mortality studies and animal toxicologic research. Objective: We investigated the relationship between PFOA exposure and cancer among residents living near the DuPont Teflon-manufacturing plant in Parkersburg, West Virginia (WV). Methods: Our analyses included incident cases of 18 cancers diagnosed from 1996 through 2005 in five Ohio (OH) counties and eight WV counties. For analyses of each cancer outcome, controls comprised all other cancers in the study data set except kidney, pancreatic, testicular, and liver cancers, which have been associated with PFOA in animal or human studies. We applied logistic regression models to individual-level data to calculate adjusted odds ratios (AORs) and confidence intervals (CIs). For the combined analysis of OH and WV data, the exposure of interest was resident water district. Within OH, geocoded addresses were integrated with a PFOA exposure model to examine the relationship between cancer odds and categories of estimated PFOA serum. Results: Our final data set included 7,869 OH cases and 17,238 WV cases. There was a positive association between kidney cancer and the very high and high serum exposure categories [AOR = 2.0 (95% CI: 1.0, 3.9) n = 9 and 2.0 (95% CI: 1.3, 3.2) n = 22, respectively] and a null association with the other exposure categories compared with the unexposed. The largest AOR was for testicular cancer with the very high exposure category [2.8 (95% CI: 0.8, 9.2) n = 6], but there was an inverse association with the lower exposure groups, and all estimates were imprecise because of small case numbers. Conclusions: Our results suggest that higher PFOA serum levels may be associated with testicular, kidney, prostate, and ovarian cancers and non-Hodgkin lymphoma. Strengths of this study include near-complete case ascertainment for state residents and well-characterized contrasts in predicted PFOA serum levels from six contaminated water supplies.
    Environmental Health Perspectives 01/2013; 121(3). DOI:10.1289/ehp.1205829 · 7.03 Impact Factor
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    ABSTRACT: California's furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on the market. Given these results, and the potential for human exposure to FRs, health studies should be conducted on the types of FRs identified here.
    Environmental Science & Technology 11/2012; 46(24). DOI:10.1021/es303471d · 5.48 Impact Factor
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    ABSTRACT: Background/Aims: Our limited understanding of how polyfluoroalkyl chemicals (PFCs) may impact on human health suggests the potential for a protective impact on brain health. This study was designed to explore the association between PFCs and cognitive ability in older adults. Methods: We assessed the association between four PFCs, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS), and self-reported limitation due to difficulty remembering or periods of confusion using data from participants aged 60-85 years from the 1999-2000 and 2003-2008 National Health and Nutrition Examination Surveys. We also considered whether diabetic status or diabetic medication use modifies this association in light of in vitro evidence that PFCs may act on the same receptors as some diabetic medications. Results: In multivariable adjusted models, point estimates suggest a protective association between PFCs and self-reported cognitive limitation (odds ratio, OR; 95% confidence interval, CI) for a doubling in PFC concentration: PFOS (OR, 0.90; 95% CI, 0.78, 1.03), PFOA (OR, 0.92; 95% CI, 0.78, 1.09), PFNA (OR, 0.91; 95% CI, 0.79, 1.04) and PFHxS (OR, 0.93; 95% CI, 0.82, 1.06). The protective association was concentrated in diabetics, with strong, significant protective associations in nonmedicated diabetics. Conclusions: This cross-sectional study suggests that there may be a protective association between exposure to PFCs and cognition in older adults, particularly diabetics.
    Neuroepidemiology 10/2012; 40(2):125-132. DOI:10.1159/000342310 · 2.48 Impact Factor
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    ABSTRACT: Background: Bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a replacement for polybrominated diphenyl ethers (PBDEs) in commercial flame retardant mixtures such as Firemaster 550. It is also used in a commercial mixture called DP 45. Mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) is a potentially toxic metabolite. Objectives: We used in vitro and rodent in vivo models to evaluate human exposure and the potential metabolism and toxicity of TBPH. Methods: Dust collected from homes, offices, and cars was measured for TBPH by gas chromatography followed by mass spectrometry. Pregnant rats were gavaged with TBMEHP (200 or 500 mg/kg) or corn oil on gestational days 18 and 19, and dams and fetuses were evaluated histologically for toxicity. We also assessed TBMEHP for deiodinase inhibition using rat liver microsomes and for peroxisome proliferator-activated receptor (PPAR) α and γ activation using murine FAO cells and NIH 3T3 L1 cells. Results: TBPH concentrations in dust from office buildings (median, 410 ng/g) were higher than in main living areas in homes (median, 150 ng/g). TBPH was metabolized by purified porcine esterases to TBMEHP. Two days of TBMEHP exposure in the rat produced maternal hypothyroidism with markedly decreased serum T3 (3,3´,5-triiodo-l-thyronine), maternal hepatotoxicity, and increased multinucleated germ cells (MNGs) in fetal testes without antiandrogenic effects. In vitro, TBMEHP inhibited deiodinase activity, induced adipocyte differentiation in NIH 3T3 L1 cells, and activated PPARα- and PPARγ-mediated gene transcription in NIH 3T3 L1 cells and FAO cells, respectively. Conclusions: TBPH a) is present in dust from indoor environments (implying human exposure) and b) can be metabolized by porcine esterases to TBMEHP, which c) elicited maternal thyrotoxic and hepatotoxic effects and d) induced MNGs in the fetal testes in a rat model. In mouse NIH 3T3 L1 preadipocyte cells, TBMEHP inhibited rat hepatic microsome deiodinase activity and was an agonist for PPARs in murine FAO and NIH 3T3 L1 cells.
    Environmental Health Perspectives 09/2012; 120(12). DOI:10.1289/ehp.1204932 · 7.03 Impact Factor
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    Gregory J Howard, Thomas F Webster
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    ABSTRACT: Background: Epidemiologists and toxicologists face similar problems when assessing interactions between exposures, yet they approach the question very differently. The epidemiologic definition of interaction leads to the additivity of risk differences (RDA) as the fundamental criterion for causal inference about biological interactions. Toxicologists define interaction as departure from a model based on mode of action: Concentration addition (CA, for similarly-acting compounds) or independent action (IA, for compounds that act differently). Objectives: We compare and contrast theoretical frameworks for interaction in the two fields. Methods: The same simple thought experiment has been used in both fields to develop the definition of non-interaction, with nearly opposite interpretations. In epidemiology, the "sham combination" leads to a requirement that non-interactive dose-response curves be linear. In toxicology, it results in the model of concentration addition. We apply epidemiologic tools to mathematical models of concentration-additive combinations to evaluate their utility. Results: RDA is equivalent to CA only for linear dose-response curves. Simple models demonstrate that concentration-additive combinations can result in strong synergy or antagonism in the epidemiologic framework at even the lowest exposure levels. For combinations acting through non-similar pathways, RDA approximates independent action at low effect levels. Conclusions: While epidemiologists have argued for a single logically consistent definition of interaction, the toxicologic perspective would consider this approach less biologically informative than a comparison with CA or IA. We suggest methods for analysis of concentration-additive epidemiologic data. The two fields can learn a great deal about interaction from each other.
    Environmental Health Perspectives 09/2012; DOI:10.1289/ehp.1205889 · 7.03 Impact Factor
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    ABSTRACT: Tetrabromobisphenol-A (TBBP-A) and hexab-romocyclododecanes (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 alpha, beta, and gamma diastereomers), and HBCD degradation products: pentabromocyclododecanes (PBCDs) and tetrabromocyclododecadienes (TBCDs). HBCD diastereomers were detected in all samples with alpha-HBCD present in the highest proportion. TBBP-4, 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.
    Environmental Science and Technology 09/2012; DOI:10.1021/es302638d · 5.48 Impact Factor

Publication Stats

3k Citations
435.61 Total Impact Points

Institutions

  • 2002–2014
    • Boston University
      • Department of Environmental Health
      Boston, Massachusetts, United States
  • 2009–2013
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2012
    • Dickinson College
      Carlisle, Pennsylvania, United States
  • 2010
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States