As a result of the polybrominated diphenyl ether (PBDE) ban in the mid-2000s, the chemical flame retardant market has moved toward alterative compounds including chlorinated alkyl and nonchlorinated ...aryl organophosphate flame retardants (OPFRs) as well as aromatic brominated compounds such as Firemaster 550 (FM550). Recent studies have shown that the OPFRs and Firemaster 550 components are frequently detected in polyurethane foams and in indoor dust. Some OPFRs are considered carcinogenic and/or neurodevelopmental toxicants, and children’s exposure to these compounds is a concern. OPFRs are readily metabolized and excreted in the urine as their dialkyl and diaryl compounds which function as biomarkers for OPFR exposure. Limited research has shown that adults are broadly exposed to OPFRs, but nothing is known about children’s exposure. Similarly, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), a FM550 component, is metabolized to tetrabromobenzoic acid (TBBA). The current study measured levels of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(1-chloro-2-propyl) phosphate (BCIPP), diphenyl phosphate (DPHP), 2 alkylated DPHPs, and TBBA in urine collected in 2013 from 21 US mother-toddler pairs. BDCIPP, DPHP, and ip-DPHP were detected in 100%, 98%, and 96% of all individuals, whereas BCIPP and tert-butyl-DPHP (tb-DPHP) were only detected in 8% and 13%. Further, TBBA was detected in 27% of adults but 70% of children. Overall, children had higher urinary levels of BDCIPP, DPHP, ip-DPHP, and TBBA as compared to their mothers, suggesting higher exposure. For example, on average, BDCIPP levels in children were 4.9 times those of mothers. BDCIPP and DPHP levels in mother’s urine were also significantly correlated with levels in children’s urine, suggesting similar exposure routes, likely in the home environment. Various potential predictors of OPFR exposure were assessed using a questionnaire. In children some predictors of hand-mouth exposure were associated with elevated BDCIPP and DPHP levels (e.g., less frequent hand washing for BDCIPP). Overall, these trends are consistent with higher flame retardant levels in children as a result of increased hand-mouth behavior and elevated dust exposure.
Triphenyl phosphate (TPHP) is primarily used as either a flame retardant or plasticizer, and is listed as an ingredient in nail polishes. However, the concentration of TPHP in nail polish and the ...extent of human exposure following applications have not been previously studied. We measured TPHP in ten different nail polish samples purchased from department stores and pharmacies in 2013–2014. Concentrations up to 1.68% TPHP by weight were detected in eight samples, including two that did not list TPHP as an ingredient. Two cohorts (n=26 participants) were recruited to assess fingernail painting as a pathway of TPHP exposure. Participants provided urine samples before and after applying one brand of polish containing 0.97% TPHP by weight. Diphenyl phosphate (DPHP), a TPHP metabolite, was then measured in urine samples (n=411) and found to increase nearly seven-fold 10–14h after fingernail painting (p<0.001). To determine relative contributions of inhalation and dermal exposure, ten participants also painted their nails and painted synthetic nails adhered to gloves on two separate occasions, and collected urine for 24h following applications. Urinary DPHP was significantly diminished when wearing gloves, suggesting that the primary exposure route is dermal. Our results indicate that nail polish may be a significant source of short-term TPHP exposure and a source of chronic exposure for frequent users or those occupationally exposed.
•Some nail polishes contain the plasticizer triphenyl phosphate (TPHP).•Urinary metabolites of TPHP increased 7-fold following nail polish application.•TPHP exposure from nail polish appears to occur via dermal exposure.•TPHP may be a replacement for phthalates in nail polish.
Many halogenated organic contaminants (HOCs) are considered endocrine disruptors and affect the hypothalamic–pituitary–thyroid axis, often by interfering with circulating levels of thyroid hormones ...(THs). We investigated one potential mechanism for TH disruption, inhibition of sulfotransferase activity. One of the primary roles of TH sulfation is to support the regulation of biologically active T3 through the formation of inactive THs. We investigated TH sulfotransferase inhibition by 14 hydroxylated polybrominated diphenyl ethers (OH BDEs), BDE 47, triclosan, and fluorinated, chlorinated, brominated, and iodinated analogues of 2,4,6-trihalogenated phenol and bisphenol A (BPA). A new mass spectrometry-based method was also developed to measure the formation rates of 3,3′-T2 sulfate (3,3′-T2S). Using pooled human liver cytosol, we investigated the influence of these HOCs on the sulfation of 3,3′-T2, a major substrate for TH sulfation. For the formation of 3,3′-T2S, the Michaelis constant (K m) was 1070 ± 120 nM and the V max was 153 ± 6.6 pmol min–1 (mg of protein)−1. All chemicals investigated inhibited sulfotransferase activity with the exception of BDE 47. The 2,4,6-trihalogenated phenols were the most potent inhibitors followed by the OH BDEs and then halogenated BPAs. The IC50 values for the OH BDEs were primarily in the low nanomolar range, which may be environmentally relevant. In silico molecular modeling techniques were also used to simulate the binding of OH BDE to SULT1A1. This study suggests that some HOCs, including antimicrobial chemicals and metabolites of flame retardants, may interfere with TH regulation through inhibition of sulfotransferase activity.
Poly- and perfluorinated organic compounds (PFCs) are ubiquitous in the Arctic environment. Several modeling studies have been conducted in attempt to resolve the dominant transport pathway of PFCs ...to the arctic—atmospheric transport of precursors versus direct transport via ocean currents. These studies are generally limited by their focus on perfluorooctanoate (PFOA) fluxes to arctic seawater and thus far have only used fluorotelomer alcohols (FTOHs) and sulfonamide alcohols as inputs for volatile precursors. There have been many monitoring studies from the North American and European Arctic, however, almost nothing is known about PFC levels from the Russian Arctic. In general, there are very few measurements of PFCs from the abiotic environment. Atmospheric measurements show the widespread occurrence of PFC precursors, FTOHs and perfluorinated sulfonamide alcohols. Further, PFCAs and PFSAs have been detected on atmospheric particles. The detection of PFCAs and PFSAs in snow deposition is consistent with the volatile precursor transport hypothesis. There are very limited measurements of PFCs in seawater. PFOA is generally detected in the greatest concentrations. Additional seawater measurements are needed to validate existing model predications. The bulk of the monitoring efforts in biological samples have focused on the perfluorinated carboxylates (PFCAs) and sulfonates (PFSAs), although there are very few measurements of PFC precursors. The marine food web has been well studied, particularly the top predators. In contrast, freshwater and terrestrial ecosystems have been poorly studied. Studies show that in wildlife perfluorooctane sulfonate (PFOS) is generally measured in the highest concentration, followed by either perfluorononanoate (PFNA) or perfluoroundecanoate (PFUnA). However, some whale species show relatively high levels of perfluorooctane sulfonamide (PFOSA) and seabirds are typically characterized by high proportions of the C
11–C
15 PFCAs. PFOA is generally infrequently detected and is present in low concentrations in arctic biota. Food web studies show high bioaccumulation in the upper trophic-level animals, although the mechanism of PFC biomagnification is not understood. Spatial trend studies show some differences between populations, although there are inconsistencies between PFC trends. The majority of temporal trend studies are from the Northern American Arctic and Greenland. Studies show generally increasing levels of PFCs from the 1970s, although some studies from the Canadian Arctic show recent declines in PFOS levels. In contrast, ringed seals and polar bears from Greenland continue to show increasing PFOS concentrations. The inconsistent temporal trends between regions may be representative of differences in emissions from source regions.
Legacy environmental contaminants such as polybrominated diphenyl ethers (PBDEs) are widely detected in human tissues. However, few studies have measured PBDEs in placental tissues, and there are no ...reported measurements of 2,4,6-tribromophenol (2,4,6-TBP) in placental tissues. Measurements of these contaminants are important for understanding potential fetal exposures, as these compounds have been shown to alter thyroid hormone regulation in vitro and in vivo. In this study, we measured a suite of PBDEs and 2,4,6-TBP in 102 human placental tissues collected between 2010 and 2011 in Durham County, North Carolina, USA. The most abundant PBDE congener detected was BDE-47, with a mean concentration of 5.09ng/g lipid (range: 0.12–141ng/g lipid; detection frequency 91%); however, 2,4,6-TBP was ubiquitously detected and present at higher concentrations with a mean concentration of 15.4ng/g lipid (range:1.31–316ng/g lipid; detection frequency 100%). BDE-209 was also detected in more than 50% of the samples, and was significantly associated with 2,4,6-TBP in placental tissues, suggesting they may have a similar source, or that 2,4,6-TBP may be a degradation product of BDE-209. Interestingly, BDE-209 and 2,4,6-TBP were negatively associated with age (rs=−0.16; p=0.10 and rs=−0.17; p=0.08, respectively). The results of this work indicate that PBDEs and 2,4,6-TBP bioaccumulate in human placenta tissue and likely contribute to prenatal exposures to these environmental contaminants. Future studies are needed to determine if these joint exposures are associated with any adverse health measures in infants and children.
•A suite of PBDEs and 2,4,6-TBP were measured in 102 placenta tissue samples.•BDE-209 was detected in more than 50% of the samples.•2,4,6-TBP was found in the highest concentrations in placenta tissue.•2,4,6-TBP was significantly correlated with PBDEs.•BDE-209 and 2,4,6-TBP were suggested to be negatively associated with maternal age.
The use of alternative chemical flame retardants in consumer products is increasing as the result of the phase-out of polybrominated diphenyl ethers. Today, the most commonly detected alternatives in ...residential furniture include the organophosphate flame retardants (PFRs) and the Firemaster (R) 550 mixture (FM550). Urinary levels of dialkyl and diaryl phosphate esters, and 2-ethylhexyl tetrabromobenzoate (EH-TBB) have been used as biomarkers of human exposure to PFRs and FM550, respectively. In a previous study, we demonstrated that toddlers had significantly higher levels of PFRs relative to their mothers in a cohort from New Jersey; however, it is unclear if there are regional differences in exposure. It is possible that exposure to PFRs may be higher in California relative to other US States due to the California flammability standard, as was seen previously observed for PBDEs. In the current study, we examined urinary levels of PFR metabolites and TBBA in 28 mother-child pairs from California, USA, collected in 2015, and compared them with levels measured in our previous study from New Jersey. Urine samples were extracted using solid-phase extraction and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1,3-dichloro-2propyl) phosphate (BDCIPP) and BCIPHIPP conjugates were detected in 100% of mother and child urine samples, while bis(1-chloro-2-propyl) phosphate (BCIPP), tert-butyl-phenyl phenyl phosphate (tb-PPP) and TBBA were detected in <50% of samples. Interestingly, BCIPHIPP conjugates were detected in 100% of the urine samples, suggesting ubiquitous exposure to the parent compound, tris(1-chloro-2-propyl) phosphate (TCIPP). The current study found significantly higher BDCIPP levels in California toddlers and higher and ip-PPP levels in mothers as compared to the New Jersey cohort, which may be reflective of California's furniture flammability standard. For example, BDCIPP levels in California children were 2.4 times higher than those in New Jersey children. Consistent with our previous work, the current study showed higher PFR and EH-TBB exposure in children, likely due to increased hand-mouth behavior. Children's DPHP and BDCIPP levels, on average, were 5.9 times and 15 times those of their mothers. Positive correlations between paired mothers and their children were shown for DPHP and BCIPHIPP conjugates but not BDCIPP or ip-PPP. In the children, several predictors of hand-mouth behavior were associated with BDCIPP, DPHP and ip-PPP urine levels, but no associations were observed with BCIPHIPP conjugates.
•Urinary BDCIPP levels higher in California children than New Jersey children.•Regional differences in exposure may be driven by California flammability standard.•Urinary DPHP and BCIPHIPP were correlated between mother-child pairs.•Hand-to-mouth frequencies were significantly associated with exposure.
Infant products containing polyurethane foam are commonly treated with organophosphate flame retardants (PFRs), including tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and triphenyl phosphate ...(TPHP). Infants may have greater exposure due to greater contact with these products, yet little is known about levels of exposure or the factors contributing to higher exposure. We recruited children age 2–18 months from North Carolina to investigate PFR exposure (n = 43; recruited 2014–2015). Parents provided information on potential sources and modifiers of exposure, and reported whether they owned common infant products. We measured five PFR metabolites in urine samples collected from children. TDCIPP and TPHP metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP)) were most commonly detected (>93% detect). Other metabolites were detected infrequently (<35% detect). Although we did not observe a clear age trend for infants, BDCIPP levels were substantially higher than those reported for adults (geometric mean = 7.3 ng/mL). The number of infant products owned was strongly associated with BDCIPP; children with >16 products had BDCIPP levels that were 6.8 times those with <13 (p = 0.02). Infants attending daycare centers also had higher BDCIPP levels (3.7 times those of others; p = 0.07), suggesting time spent in this microenvironment contributes to higher exposure. In contrast, DPHP levels were not related to products owned, time in different microenvironments, or behavior.
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.
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.
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).
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.
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•Preconception cohort of couples undergoing IVF as a model of human reproduction•Measured concentrations of urinary organophosphate flame retardant metabolites•No associations were observed for implantation, clinical pregnancy, or live birth.•Fertilization declined with increasing paternal exposure to TDCIPP.
Halogenated contaminants, particularly brominated flame retardants, disrupt circulating levels of thyroid hormones (THs), potentially affecting growth and development. Disruption may be mediated by ...impacts on deiodinase (DI) activity, which regulate the levels of active hormones available to bind to nuclear receptors. The goal of this study was to develop a mass spectrometry-based method for measuring the activity of DIs in human liver microsomes and to examine the effect of halogenated phenolic contaminants on DI activity. Thyroxine (T4) and reverse triiodothyronine (rT3) deiodination kinetics were measured by incubating pooled human liver microsomes with T4 or rT3 and monitoring the production of T3, rT3, 3,3′-diiodothyronine, and 3-monoiodothyronine by liquid chromatography tandem mass spectrometry. Using this method, we examined the effects of several halogenated contaminants, including 2,2′,4,4′,5-pentabromodiphenyl ether (BDE 99), several hydroxylated polybrominated diphenyl ethers (OH-BDEs), tribromophenol, tetrabromobisphenol A, and triclosan, on DI activity. The Michaelis constants (K
M) of rT3 and T4 deiodination were determined to be 3.2 ± 0.7 and 17.3 ± 2.3μM. The V
max was 160 ± 5.8 and 2.8 ± 0.10 pmol/min.mg protein, respectively. All studied contaminants inhibited DI activity in a dose-response manner, with the exception of BDE 99 and two OH-BDEs. 5′-Hydroxy 2,2′,4,4′,5-pentabromodiphenyl ether was found to be the most potent inhibitor of DI activity, and phenolic structures containing iodine were generally more potent inhibitors of DI activity relative to brominated, chlorinated, and fluorinated analogues. This study suggests that some halogenated phenolics, including current use compounds such as plastic monomers, flame retardants, and their metabolites, may disrupt TH homeostasis through the inhibition of DI activity in vivo.
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