Physiologically based pharmacokinetic (PBPK) modeling of BDE-209 following oral exposure in Chinese population.

The wide usage of decabromodiphenyl ether (BDE-209) as additive brominated flame retardant has caused its widespread occurrence in the environment and high exposure risk in humans. Estimating its internal exposure dose and reconstruction of external exposure dose using physiologically based pharmacokinetic (PBPK) modelling approach is a key step in the risk assessment of BDE-209. However, the PBPK model for BDE-209 is currently unavailable. This study has established two oral permeability-limited PBPK models of BDE-209 without enterohepatic recirculation (EHR) (model 1) and with EHR (model 2) for Chinese population. Using the in vitro experiments, the average binding of BDE-209 to human plasma protein (99.64% ± 2.97%) was obtained. Moreover, blood sample analysis and systematic literature review were performed to obtain internal and external exposure data of BDE-209 used for model calibration and validation. The predictions of both models were within 2-fold of the observed, and a longer half-life of serum BDE-209 was observed in model 2 than model 1. Based on the models, a human biomonitoring guidance value (HBM-GV) of 93.61 µg/g lw was derived for BDE-209, and there is no health risk found for Chinese population currently. This study provides new quantitative assessment tools for health risk assessment of BDE-209.

A PBPK model describing the pharmacokinetics of γ-HBCD exposure in mice.

The brominated flame retardant, hexabromocyclododecane (HBCD), is added-but not bound-to consumer products and is eventually found in the environment and human tissues. Commercial-grade HBCD mixtures contain three major stereoisomers, alpha (α), beta (ß), and gamma (γ), that are typically at a ratio of 12%:6%:82%, respectively. Although HBCD is widely used, the toxicological effects from its exposure in humans are not clearly understood. Using a physiologically based pharmacokinetic (PBPK) model could help improve our understanding of the toxicity of HBCD. The aim of this work was to develop a PBPK model, consisting of five permeability limited compartments (i.e., brain, liver, adipose tissue, blood, and rest of the body), to evaluate the pharmacokinetics of γ-HBCD in C57BL/6 mice. Physiological parameters related to body size, organ weights, and blood flow were taken from the literature. All partition coefficients were calculated based on the log Kow. The elimination in urine and feces was optimized to reflect the percent dose eliminated, as published in the literature. Compared with data from the literature for brain, liver, blood, and adipose tissue, the model simulations accurately described the mouse data set within 1.5-fold of the data points. Also, two examples showing the utility of the PBPK model supplement the information regarding the internal dose that caused the health effects observed during these studies. Although this version of the PBPK model expressly describes γ-HBCD, more efforts are needed to clarify and improve the model to discriminate between the α, ß, and γ stereoisomers.

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish.

Tetrabromobisphenol A (2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol, CAS no. 79-94-7) (TBBPA) is an effective brominated flame retardant present in many consumer products whose effectiveness is attributable to its ability to retard flames and consequently save human lives. Toxicokinetic studies revealed that TBBPA when absorbed via the gastrointestinal tract is rapidly metabolized to glucuronide or sulfate metabolites which are rapidly eliminated by the kidney. TBBPA does not accumulate in the body and there is no evidence that the parent compound is present in the brain. Although this brominated flame retardant was detected in human breast milk and serum, there was no evidence that TBBPA reached the brain in in vivo animal studies as reflected by the absence of neuropathological, neurotoxic, or behavioral alterations indicating that the central nervous system is not a target tissue. These animal investigations were further supported by use of the larval/embryo observations that TBBPA did not produce behavioral changes in a larval/embryo zebrafish a model of chemical-induced neurotoxicity. Although some protein expressions were increased, deceased or not affected in the blood-brain barrier indicating no evidence that TBBPA entered the brain, the changes were contradictory, or gender related, and behavior was not affected supporting that this compound was not neurotoxic. Taken together, TBBPA does not appear to target the brain and is not considered as a neurotoxicant.

Computational evaluation of interactions between organophosphate esters and nuclear hormone receptors.

Organophosphate esters (OPEs) have gained considerable interest from many environmental chemists and toxicologists due to their frequent detection in the environment and potential adverse effects on health. Nuclear hormone receptors (NHRs) were found to mediate many of their adverse effects. However, our knowledge regarding the direct binding and interaction between OPEs and NHRs is limited. In this study, Endocrine Disruptome, an online computational tool based on the technique of inverse docking, was used to calculate the binding affinity score of 25 individual OPEs with 12 different human NHRs. Results showed that 20% of potential binding interactions between the OPEs and NHRs had medium-to-high probabilities. The accuracy, sensitivity and specificity of the predictions were 78.8, 60.0 and 80.9%, respectively. OPEs with a benzene ring were more active than those without, among which, tri-o-tolyl phosphate and tri-m-tolyl phosphate displayed the highest activities, suggesting that they might pose the greatest potential risks for interference with endocrine functions. In addition, the antagonistic conformations of androgen receptor and estrogen receptor ß were found to be the two most vulnerable NHR conformations. Our findings can further the understanding about the health risk(s) of OPEs.

Exposure to Polybrominated Diphenyl Ethers and a Polybrominated Biphenyl and Risk of Thyroid Cancer in Women: Single and Multi-Pollutant Approaches.

BACKGROUND: Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone-disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend. METHODS: We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures. RESULTS: In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest (

Evaluating hexabromocyclododecane (HBCD) toxicokinetics in humans and rodents by physiologically based pharmacokinetic modeling.

Hexabromocyclododecane (HBCD) is a flame retardant largely found in textiles, electrical equipment and building materials. The potential exposure associated with adverse effects described in animals make HBCD a substance of interest. To better characterize the risk in humans, it is important to understand the dose-response relationship using available data concerning the exposure and toxicity of environmental contaminants such as HBCD. For this reason, a physiologically-based pharmacokinetic (PBPK) model was developed to describe the disposition of α-HBCD after a single oral administration. The results showed that the model can appropriately predict blood and tissue concentration in rodents. The model described that lipoproteins play a key role in the distribution of α-HBCD in the body even though its lipophilic nature would suggest preferential storage in adipose tissue. The model was also adapted to humans to predict plasma exposure to α-HBCD and showed reasonable estimates when compared against estimated diet levels and biomonitoring measures. As part of a larger study on integrating new toxicity data for human health risk assessment, the present PBPK model will serve as a supporting tool to help extrapolate and interpret in vitro and in vivo kinetics of flame retardants such as HBCD.

Halogenated and organophosphorus flame retardants in cetaceans from the southwestern Indian Ocean.

PBDEs, HBCD, DBDPE, PBEB and HBB, dechloranes and OPFRs, as well as natural MeO-PBDEs were monitored in muscle tissue of three dolphin species from the southwestern Indian Ocean (Delphinus delphis, Sousa plumbea and Tursiops aduncus) collected between 2012 and 2015. The mean PBDE concentration was 416 ±â€¯333 ng g-1 lw. BDE-47 was found in all samples and was almost half the total PBDE contamination. BDE-209, BDE-100 and BDE-99 were present in ≥85% of the samples. HBCD was detected in just two samples at 20 and 330 ng g-1 lw. PBEB and HBB were not detected, while DBDPE was in all samples but always below its limit of quantification. Dec 602 was the only quantifiable dechlorane at 232 ±â€¯549 ng g-1 lw. Mean OPFR concentration was 10452 ±â€¯11301 ng g-1 lw. TBOEP was found in all samples making up most of the total OPFR contamination. MeO-PBDEs were detected in all samples at 114 ±â€¯137 ng g-1 lw. Data on flame retardants in biota and environmental samples from the southwestern Indian Ocean are scarce and, as a result, comparisons are difficult. However, data from other marine predators in the region, such as penguins, suggest that further studies are needed to determine if these concentrations are the consequence of a high local contamination or widespread thoughout the Indian Ocean.

1,3,5-Tris-(2,3-dibromopropyl)-1,3,5-triazine-2,4,6-trione: kinetic studies and phototransformation products.

1,3,5-Tris-(2,3-dibromopropyl)-1,3,5-triazine-2,4,6-trione (TDBP-TAZTO) is an emerging brominated flame retardant which is widely used in several plastic materials (electric and electronic equipment, musical instruments, automotive components). However, until today, no photochemical studies as well as the identification of possible phototransformation products (PTPs) were described in literature. Therefore, in this study, UV-(C) and simulated sunlight irradiation experiments were performed to investigate the photolytic degradation of TDBP-TAZTO and to identify relevant PTPs for the first time. The UV-(C) irradiation experiments show that the photolysis reaction follows a first-order kinetic model. Based on this, the photolysis rate constant k as well as the half-life time t1/2 were calculated to be k = (41 ± 5 × 10-3) min-1 and t1/2 = (17 ± 2) min. In comparison, a minor degradation of TDBP-TAZTO and no formed phototransformation products were obtained under simulated sunlight. In order to clarify the photochemical behavior, different chemicals were added to investigate the influence on indirect photolysis: (i) H2O2 for generation of hydroxyl radicals and (ii) two quenchers (2-propanol, sodium azide) for scavenging oxygen species which were formed during the irradiation experiments. Herein, nine previously unknown PTPs of TDBP-TAZTO were detected under UV-(C) irradiation and identified by HPLC-(HR)MS. As a result, debromination, hydroxylation, and dehydrobromination reactions could be presumed as the main degradation pathways by high-resolution mass spectrometry. The direct as well as the OH radical-induced indirect photolysis were observed. Graphical abstract .

Bioconcentration and biotransformation of organophosphorus flame retardants (PFRs) in common carp (Cyprinus carpio).

Understanding the bioaccumulation and biotransformation of xenobiotic compounds is critical for evaluating their fate and potential toxicity in vivo. In the present study, the tissue specific accumulation and depuration of seven organophosphorus flame retardants (PFRs) in common carp (Cyprinus carpio) were investigated after exposing the fish to an environmental relevant level of PFRs. The log Kow of PFRs was significantly negatively correlated to the percentages of individual PFRs to the total PFRs in serum (p < 0.04), whereas significantly positive correlations were observed in all other tissues (p < 0.02). Significant correlations (p < 0.01) between the log Kow of PFRs and their log bioconcentration factor (BCFww) were also found in all investigated tissues except for serum. This suggests that the hydrophobicity of PFRs played a significant role in the distribution and body compartment accumulation of PFRs in common carp. The bioaccumulation potential of PFRs in serum was different from the other tissues, probably due to its specific properties. Dialkyl and/or diaryl phosphate esters (DAP) and hydroxylated PFRs (HO-PFRs) were quantified as the major metabolites. Their levels in liver and intestine were significantly higher than in other tissues. Biotransformation processes also played a crucial role in the accumulation of PFRs in fish. Our results provide critical information for further understanding the bioconcentration, tissue distribution and metabolism of PFRs in fish.

2,4,6-Tribromophenol Disposition and Kinetics in Rodents: Effects of Dose, Route, Sex, and Species.

2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with approximately 61% of the dose recovered after 4 h, and 89%-94% in 24 h; 5% was recovered in feces; and 1%-2% in blood/tissues. TBP administered to female SD rats (0.1-1000 µmol/kg) by gavage was well absorbed, with approximately 25% eliminated via urine after 4 h and approximately 88% after 24 h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin with between 55% and 85% of a 100 nmol/cm2 passing into or through skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP whereas bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23%-27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data, we conclude that humans are likely to have significant systemic exposure when TBP is ingested or dermal exposure occurs.

Biomonitoring Equivalents (BEs) for tetrabromobisphenol A.

Tetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed by measuring TBBPA in the blood of humans. Here, we derive Biomonitoring Equivalents (BEs) for TBBPA to interpret these, and future biomonitoring results for TBBPA in humans. The available toxicity risk values (TRVs) for TBBPA were all based on toxicology studies in rats. Several studies have been conducted in which TBBPA in blood of rats were measured following controlled oral doses of TBBPA. These data provide a robust relationship from which to derive BEs. BEs of 5.6 and 13.0 µg total TBBPA/L plasma were calculated for available cancer and non-cancer TRVs, respectively. Several studies have measured TBBPA in serum, with median concentrations less than 0.1 µg/L, indicating considerable margins of safety (MOS) for TBBPA based on the currently available biomonitoring studies.

TBBPA disposition and kinetics in pregnant and nursing Wistar Han IGS rats.

Tetrabromobisphenol-A (TBBPA) is a brominated flame retardant (BFR) commonly used in electronics to meet fire safety standards and has the largest worldwide production of any BFR. TBBPA has been detected in human breast milk and maternal/cord serum, indicating exposure to mothers, fetuses, and breastfeeding newborns although exposure to fetuses and newborns is poorly understood. Pregnant or nursing Wistar Han IGS rats were administered [14C]-TBBPA in a single dose (25 mg/kg, 2.5 µCi/kg) and euthanized between 0.5&24 h post dose to determine disposition in pregnant and nursing rats and their pups. Systemic exposure was largely unchanged between 1&8 h post dose in pregnant rats; [14C]-radioactivity in blood varied only slightly between 0.5&8 h (2.6 ± 0.6 â†’ 2.6 ± 0.8 nmol-eq/mL) but was below the limit of detection at 24 h with an absorption half-life of 16min and elimination half-life of 17 h. Cmax was observed at 30min in lactating rats and concentrations fell steadily through 8 h. Plasma from pregnant rats contained a mixture of TBBPA and TBBPA-conjugates at 30min but only metabolites in subsequent samples. TBBPA was not detected in lactating dam plasma in this study. Placental concentrations increased through 8 h while whole-fetus Cmax occurred at 2 h post dose. In lactating animals, liver, uterus, and mammary time-concentration curves lagged slightly behind blood-concentration curves. It was clear from these studies that TBBPA is available to both the developing fetus and nursing pup following maternal exposure, and nursing pups are continuously exposed via contaminated milk produced by their mother. This research was supported in part by the Intramural Research Program of NIH/NCI.

Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio).

In silico and in vivo approaches were combined in an aggregate exposure pathway (AEP) to assess accumulation and effects of waterborne exposures of early life stages of zebrafish (Danio rerio) to tetrabromobisphenol A (TBBPA). Three metabolites, two of which were isomers, were detected in fish. Two additional metabolites were detected in the exposure solution. Based on kinetics modeling, proportions of TBBPA that were bioaccumulated and metabolized were 19.33% and 8.88%, respectively. Effects of TBBPA and its metabolites were predicted by use of in silico, surflex-Dock simulations that they were capable of interacting with ThRα and activating associated signaling pathways. TBBPA had a greater toxic contribution than its metabolites did when we evaluated the toxicity of these substances based on the toxicity unit method. The half of the internal lethal dose (ILD50) was 18.33 µg TBBPA/g at 74 hpf. This finding was further confirmed by changes in expressions of ThRα and other NRs as well as associated genes in their signal pathways. Specifically, exposure to 1.6 × 102, 3.3 × 102 or 6.5 × 102 µg TBBPA/L significantly down-regulated expression of ThRα and associated genes, ncor, c1d, ncoa2, ncoa3, and ncoa4, in the AR pathway and of er2a and er2b genes in the ER pathway.

Persistent organic pollutants in fat of three species of Pacific pelagic longline caught sea turtles: Accumulation in relation to ingested plastic marine debris.

In addition to eating contaminated prey, sea turtles may be exposed to persistent organic pollutants (POPs) from ingesting plastic debris that has absorbed these chemicals. Given the limited knowledge about POPs in pelagic sea turtles and how plastic ingestion influences POP exposure, our objectives were to: 1) provide baseline contaminant levels of three species of pelagic Pacific sea turtles; and 2) assess trends of contaminant levels in relation to species, sex, length, body condition and capture location. In addition, we hypothesized that if ingesting plastic is a significant source of POP exposure, then the amount of ingested plastic may be correlated to POP concentrations accumulated in fat. To address our objectives we compared POP concentrations in fat samples to previously described amounts of ingested plastic from the same turtles. Fat samples from 25 Pacific pelagic sea turtles [2 loggerhead (Caretta caretta), 6 green (Chelonia mydas) and 17 olive ridley (Lepidochelys olivacea) turtles] were analyzed for 81 polychlorinated biphenyls (PCBs), 20 organochlorine pesticides, and 35 brominated flame-retardants. The olive ridley and loggerhead turtles had higher ΣDDTs (dichlorodiphenyltrichloroethane and metabolites) than ΣPCBs, at a ratio similar to biota measured in the South China Sea and southern California. Green turtles had a ratio close to 1:1. These pelagic turtles had lower POP levels than previously reported in nearshore turtles. POP concentrations were unrelated to the amounts of ingested plastic in olive ridleys, suggesting that their exposure to POPs is mainly through prey. In green turtles, concentrations of ΣPCBs were positively correlated with the number of plastic pieces ingested, but these findings were confounded by covariance with body condition index (BCI). Green turtles with a higher BCI had eaten more plastic and also had higher POPs. Taken together, our findings suggest that sea turtles accumulate most POPs through their prey rather than marine debris.

Metals and Organohalogen Contaminants in Bald Eagles (Haliaeetus leucocephalus) from Ontario, 1991-2008.

We examined the degree of exposure of lead (Pb), mercury (Hg), and several organohalogen contaminants and its potential impact on survival of bald eagles in Ontario from 1991 to 2008. Overall, results for 43 dead or dying bald eagles collected in the province indicate that 23% (10/43) of birds died of Pb poisoning and 9% (4/43) died of suspected Hg poisoning. Pb poisoning was diagnosed based on exceedances of toxicity thresholds in liver and kidney and supported by clinical observations, necropsy results, and histology findings when available. Evidence for Hg poisoning in eagles was limited; however, Hg concentrations exceeded the toxicity threshold in kidney. Pb concentrations ranged widely in liver and kidney. Total Hg concentrations were relatively higher in kidney compared with liver and were significantly correlated with selenium (Se) concentrations in both tissues. Concentrations of p,p'-DDE and sum PCBs in livers of 12 bald eagles collected from 2001 to 2004 were likely below concentrations associated with adverse effects. Hepatic concentrations of total polybrominated diphenyl ethers were generally higher in birds collected from southern Ontario compared with northern Ontario. Potential impacts of exposure to these flame retardants and others are not known. Elevated metal exposure appears to influence survivorship and may affect the recovery of bald eagles in the province, particularly in southern Ontario and along the Great Lakes where a disproportionate number of poisoned eagles were collected. Increased efforts are needed to identify sources of exposure and develop measures to reduce metal exposure in this top predator.

Influence of seasonality and vegetation on the attenuation of emerging contaminants in wastewater effluent-dominated streams. A preliminary study.

Treated wastewater from small communities is discharged into rivers or streams with a high biodiversity value. This is particularly important in Mediterranean countries, where most of the streams are dry almost all year round. This preliminary study assessed the occurrence and attenuation of 23 emerging contaminants (ECs) in 4 wastewater-dominated streams in which treated wastewater accounted for the entire stream flow. The concentration of ECs was monitored in the warm and cold seasons in the wastewater treatment plant (WWTP) effluent and at 6 downstream locations. The concentration of ECs in the WWTP effluents ranged from undetected to 12 µg L-1. The attenuation of ECs 1 km downstream ranged from no removal to up to 80% (48% on average). The half-lives of ECs in the 4 streams ranged from 0.4 to 20 h (3.9 ± 3.5 h on average). Compounds such as benzodiazepine drugs and flame retardants were the most recalcitrant (half-lives >5 h). The highest attenuation of ECs and ammonia was observed in the stream completely covered by vegetation. The cumulative hazardous quotient 1 km downstream was reduced on average by more than 60%. Therefore, the results suggest that both seasonality and vegetation play an important role in in-stream attenuation of ECs.

Probing the relationship between external and internal human exposure of organophosphate flame retardants using pharmacokinetic modelling.

Human external exposure (i.e. intake) of organophosphate flame retardants (PFRs) has recently been quantified, but no link has yet been established between external and internal exposure. In this study, we used a pharmacokinetic (PK) model to probe the relationship between external and internal exposure data for three PFRs (EHDPHP, TNBP and TPHP) available for a Norwegian cohort of 61 individuals from 61 different households. Using current literature on metabolism of PFRs, we predicted the metabolite serum/urine concentrations and compared it to measured data from the study population. Unavailable parameters were estimated using a model fitting approach (least squares method) after assigning reasonable constraints on the ranges of fitted parameters. Results showed an acceptable comparison between PK model estimates and measurements (<10-fold deviation) for EHDPHP. However, a deviation of 10-1000 was observed between PK model estimates and measurements for TNBP and TPHP. Sensitivity and uncertainty analysis on the PK model revealed that EHDPHP results showed higher uncertainty than TNBP or TPHP. However, there are indications that (1) current biomarkers of exposure (i.e. assumed metabolites) for TNBP and TPHP chemicals might not be specific and ultimately affecting the outcome of the modelling and (2) some exposure pathways might be missing. Further research, such as in vivo laboratory metabolism experiments of PFRs including identification of better biomarkers will reduce uncertainties in human exposure assessment.

Risk assessment and Biomonitoring Equivalent for 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) and tetrabromobenzoic acid (TBBA).

2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) is used as a flame retardant. Biomonitoring for TBB exposures include the metabolite, tetrabromobenzoic acid (TBBA), in urine. We derived a Reference Dose (RfD) for TBB and a Biomonitoring Equivalent (BE) for TBBA in urine. Three longer-term studies of oral gavage dosing of a commercial mixture BZ-54 (which includes 70% TBB) in rats were evaluated for deriving the RfD. The 95% lower confidence limits on the BMD associated with a 1 SD change from the mean (BDMLSD) values ranged from 77 to 134 mg/kg-day. The mean BMDLSD value of 91 mg/kg-day for maternal body weight changes was selected as the appropriate point of departure (POD), corresponding to a human equivalent dose (PODHEC) of 25 mg/kg-day. A total composite uncertainty factor (UF) of 300 yields an RfD of 0.08 mg/kg-day. A urinary mass excretion fraction (Fue) of 0.6 for TBBA following oral doses of TBB in rats was used to calculate BEs for TBBA in urine of 2.5 mg/L and 2.5 mg/g cr. Mean (5.3 × 10-6 mg/L) and maximum (340 × 10-6 mg/L) levels of TBBA measured in urine from human volunteers reported in the literature indicates margins of safety (MOS) are approximately 450,000 and 7,000, respectively.

Polybrominated diphenyl ethers (flame retardants) in mother-infant pairs in the Southeastern U.S.

Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants in foams, building material, electronics, and textiles. These chemicals leach into the environment, where they persist, and are found today in virtually every population worldwide. Several studies in recent years have detected the presence of PBDEs in maternal and infant samples. However, few of these studies were conducted in the U.S., and few examined paired or matched mother blood-cord blood samples. We analyzed serum from 10 mother-infant pairs for the presence of PBDEs in a patient population in the Southeastern U.S. Out of 35 measured PBDE congeners, five (BDE-28, -47, -99, -100, and -153) were present, with detection frequencies of 65-100 %. The total PBDE concentrations in maternal and infant sera were highly correlated (r2 = 0.710, p = 0.0043). The levels of BDE-47, -99, and -100 and of total PBDEs were higher in the infant cord sera when compared with those in maternal sera (p < 0.017), suggesting that fetuses and neonates might have higher circulating concentrations of these potentially neurotoxic and endocrine disrupting chemicals compared with their mothers. The primary focus henceforward should be whether there are any deleterious effects from exposure to these chemicals on human health.

Organophosphorus Flame Retardants in Pregnant Women and Their Transfer to Chorionic Villi.

The potential for prenatal exposure has recently raised concerns over the health risks of endocrine disruptors; however, knowledge about human prenatal exposure to organophosphorus flame retardants (OPFRs) is lacking. In this study, 2-ethylhexyl diphenyl phosphate (EHDPP), tributyl phosphate (TBP), triphenyl phosphate (TPHP), and tris(2-chloroethyl) phosphate (TCEP) were detected in the majority of chorionic villus samples, with median concentrations of 13.6, 18.8, 11.1, and 0.51 ng/g of dry weight (dw), respectively, significantly higher than those in the matching maternal decidua samples (5.96, 10.8, 1.44, and 0.26 ng/g of dw, respectively). The ratios of concentrations in chorionic villi (containing embryos) to those in maternal deciduae (CMRs) were 4.17, 3.82, 2.81, and 2.00 for EHDPP, TPHP, TBP, and TCEP, respectively, which correlated with their log Kow values (p = 0.003). The results of transthyretin (TTR) binding assays indicated that the stronger the binding ability to TTR, the higher the CMRs. The median concentrations of the metabolites diphenyl phosphate (DPHP), dibutyl phosphate (DBP), and bis(2-chloroethyl) phosphate (BCEP) were 4.11, 429, and 157 ng/g of dw in chorionic villi, higher than those in deciduae (1.64, 181, and 25.4 ng/g of dw, respectively). The ratios of DPHP/TPHP and DPHP/EHDPP were 0.20 and 0.43 in chorionic villi and 1.24 and 2.03 in deciduae, respectively, much lower than those of DBP/TBP and BCEP/TCEP (20.9 and 165.6 in chorionic villi and 13.1 and 35.3 in deciduae, respectively), suggesting that the difference in metabolism between the deciduae and chorionic villi would affect their maternal transfer.