BDE-47 exposure modulates cellular responses, oxidative stress and biotransformation related-genes in Mytilus galloprovincialis.

Polybrominated diphenyl ethers (PBDEs) are flame retardants, characterized by elevated stability in the marine environment, where are accumulated by organisms, inducing a wide panel of negative effects. In this study, some biochemical patterns related to toxicity, biotransformation and oxidative stress, were studied in the marine model system, Mytilus galloprovincialis, exposed to BDE-47. Mussels were fed with microalgae, previously treated with increasing concentrations of PBDEs (maximum dose 100 ng L-1 of BDE-47 per day). After 15 days of treatment, mussels were fed with the same diet without BDE-47, for additional 15 days. Gills and digestive glands were analyzed at T 0, at 15 and 30 days. Histopathological lesions were assessed in digestive glands of contaminated mussels, while expression of genes, related to cell cycle, multidrug resistance, oxidative stress and detoxification was evaluated on both gills and digestive glands. After 15 days, BDE-47 exposure significantly affected the cell activity in digestive gland and, at 30 days, only mussels exposed to the lower doses showed a certain recovery. Regarding the gene expression, both gills and digestive glands showed a significant down-regulation of the target genes at 15 days, although most of them were up-regulated at 30 days in digestive gland. The results on BDE-47 accumulation in mussels revealed a dose-dependent concentration in tissues, which remained elevated after further 15 days of depuration. This trend supports the responses of the biomarkers, indicating that exposure, at environmentally realistic concentrations of BDE-47, strongly modulates oxidative stress and related patterns of gene expression, suggesting concerns for long-term effect in the biota.

AM fungi increase uptake of Cd and BDE-209 and activities of dismutase and catalase in amaranth (Amaranthus hypochondriacus L.) in two contaminants spiked soil.

Soil co-contaminated with cadmium (Cd) and decabromodiphenyl ether (BDE-209) is a widespread environmental problem, especially in electronic waste contaminated surroundings. Accumulation of Cd and BDE-209 in crops has possibly harmful effects on local human health. In order to assess the potential of arbuscular mycorrhizal (AM) fungi and amaranth (Amaranthus hypochondriacus L.) in remediation of soil co-contaminated with Cd and BDE-209, pot trials were performed to investigate interactive effects of AM fungi, Cd and BDE-209 on growth of amaranth, uptake of Cd and BDE-209, distribution of chemical forms of Cd and activities of antioxidant enzymes in shoots and dissipation of BDE-209 in soil. The present results showed that shoot biomass of non-mycorrhizal plants was significantly inhibited by increasing of Cd addition (5-15 mg kg-1), but were only slightly declined with BDE-209 addition (5 mg kg-1). The interaction of Cd and BDE-209 reduced the proportions of ethanol- and d-H2O-extractable Cd in shoots, consequently alleviated Cd toxicity to plants and enhanced root uptake of Cd and BDE-209. Inoculation of AM fungi resulted in significantly greater shoot biomass as well as higher concentrations of Cd and BDE-209 compared with non-mycorrhizal treatment. Moreover, AM fungi played a beneficial role in relieving oxidative stress on amaranth by increasing the activities of dismutase (SOD) and catalase (CAT) in shoots and significantly improved the dissipation of BDE-209 in soil. The present study suggested that combination of AM fungi and amaranth may be a potential option for remediation of Cd and BDE-209 co-contaminated soils.

Ecological and human exposure assessment to PBDEs in Adige River.

The interest for environmental issues and the concern resulting from the potential exposure to contaminants were the starting point to develop methodologies in order to evaluate the consequences that those might have over both the environment and human health. Considering the feature of POPs, including PBDEs, such as bioaccumulation, biomagnification, long-range transport and adverse effects even long time after exposure, risk assessment of POPs requires specific approaches and tools. In this particular context, the MERLIN-Expo tool was used to assess the aquatic environmental exposure of Adige River to PBDEs and the accumulation of PBDEs in humans through the consumption of possible contaminated local aquatic food. The aquatic food web models provided as output of the deterministic simulation the time trend of concentrations for twenty years of BDE-47 and total PBDEs, expressed using the physico-chemical properties of BDE-47, in aquatic organisms of the food web of Adige River. For BDE-47, the highest accumulated concentrations were detected for two benthic species: Thymallus thymallus and Squalius cephalus whereas the lowest concentrations were obtained for the pelagic specie Salmo trutta marmoratus. The trend obtained for the total PBDEs, calculated using the physico-chemical properties of BDE-47, follows the one of BDE-47. For human exposure, different BDE-47 and total PBDEs concentration trends between children, adolescent, adults and elderly were observed, probably correlated with the human intake of fish products in the daily diet and the ability to metabolize these contaminants. In detail, for the adolescents, adults and elderly a continuous accumulation of the target contaminants during the simulation's years was observed, whereas for children a plateau at the end of the simulation period was perceived.

Species- and Tissue-Specific Profiles of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Derivatives in Cats and Dogs.

The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels, reported in the blood of domestic dogs and cats, are considered to be of great concern. However, the tissue distribution of PBDEs and their derivatives in these animals is poorly understood. This study determined the concentrations and profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in cats, with the dominant congener being BDE209. BDE207 was also predominant in cat tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was the dominant congener in dog bile, implying a species-specific excretory capacity of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47, possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6. Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and 2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood-brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their derivatives, particularly BDE209 and 6OH-BDE47.

The transepithelial transport mechanism of polybrominated diphenyl ethers in human intestine determined using a Caco-2 cell monolayer.

Oral ingestion plays an important role in human exposure to polybrominated diphenyl ethers (PBDEs). The uptake of PBDEs primarily occurs in the small intestine. The aim of the present study is to investigate the transepithelial transport characteristics and mechanisms of PBDEs in the small intestine using a Caco-2 cell monolayer model. The apparent permeability coefficients of PBDEs indicated that tri- to hepta-BDEs were poorly absorbed compounds. A linear increase in transepithelial transport was observed with various concentrations of PBDEs, which suggested that passive diffusion dominated their transport at the concentration range tested. In addition, the pseudo-first-order kinetics equation can be applied to the transepithelial transport of PBDEs. The rate-determining step in transepithelial transport of PBDEs was trans-cell transport including the trans-pore process. The significantly lower transepithelial transport rates at low temperature for bidirectional transepithelial transport suggested that an energy-dependent transport mechanism was involved. The efflux transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) and influx transporters (organic cation transporters) participated in the transepithelial transport of PBDEs. In addition, the transepithelial transport of PBDEs was pH sensitive; however, more information is required to understand the influence of pH.

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.

Differences in the mechanisms of action of BDE-47 and its metabolites on OVCAR-3 and MCF-7 cell apoptosis.

Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent tissues are limited. Our earlier studies showed that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) stimulated OVCAR-3 and MCF-7 cell proliferation, while its hydroxylated metabolites (5-OH-BDE-47 and 6-OH-BDE-47) increased estrogen receptors protein expression and extracellular signal-regulated kinase 1/2 and protein kinase Cα phosphorylation in these cell lines. In addition to cell proliferative disorder, a failure in the regulation of apoptosis can also lead to the formation and development of tumors. Therefore, in the present study, we investigated the effect of BDE-47 and its metabolites (2.5-50 ng ml-1 ) on the expression of apoptosis regulatory genes and proteins, caspase-8 and -9 activity and DNA fragmentation induced by extracellular signal-regulated kinase inhibitor (PD098059) and protein kinase Cα inhibitor (GÓ§ 6976) in ovarian (OVCAR-3) and breast (MCF-7) cancer cells. In OVCAR-3 cells, BDE-47 upregulated expression of most of the investigated genes and increased protein expression of tumor necrosis factor (TNF)-α, TNF receptor 1, caspase-6, Bcl-xl and caspase-8 activity. Whereas in MCF-7 cells, BDE-47 resulted in the downregulation of most of the investigated genes, and decreased caspase-8 and -9 activity. In both OVCAR-3 and MCF-7 cells, the expression of most of the investigated genes were downregulated by metabolites. Exposure of OVCAR-3 cells to 5-OH-BDE-47 corresponded with a decrease in the protein expression of caspase-6, caspase-9 and Bcl-xl and treatment with 6-OH-BDE-47 decreased Bcl-xl and TNF receptor 1 expression in OVCAR-3 cells and caspase-9 expression in MCF-7 cells. Hydroxylated metabolites of BDE-47 have strong inhibitory effects on apoptosis in ovarian and breast tumor cells and thus should be considered potential carcinogens in hormone-dependent cancers. Copyright © 2016 John Wiley & Sons, Ltd.

Enantioselective accumulation, metabolism and phytoremediation of lactofen by aquatic macrophyte Lemna minor.

Pesticides are frequently detected in water bodies due to the agricultural application, which may pose impacts on aquatic organisms. The enantioselective bioaccumulation and metabolism of the herbicide lactofen in aquatic floating macrophyte Lemna minor (L. minor) were studied and the potential L. minor phytoremediation was investigated. Ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS-MS) analysis for lactofen and its two known metabolites in L. minor was performed. The initial concentrations of racemic lactofen, R-lactofen and S-lactofen were all 30µgL-1 in the growth solution. The distribution of lactofen and its metabolites in growth solution and L. minor was determined throughout a 5-d laboratory trial. It was observed that S-lactofen was preferentially taken up and metabolized in L. minor. After rac-lactofen exposure, the accumulation amount of S-lactofen was approximately 3-fold more than that of R-lactofen in L. minor and the metabolism rate of S-lactofen (T1/2=0.92 d) was significantly faster than R-lactofen (T1/2=1.55 d). L. minor could only slightly accelerate the metabolism and removal of lactofen in the growth solution. As for the metabolites, desethyl lactofen was found to be the major metabolite in L. minor and the growth solution, whereas the metabolite acifluorfene was undetectable. No interconversion of the two enantiomers was observed after individual enantiomer exposure, indicating they were configurationally stable. The findings of this work represented that the accumulation and metabolism of lactofen in L. minor were enantioselective, and L. minor had limited capacity for the removal of lactofen and its metabolite in water.

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.

Evaluation of the Genotoxic and Physiological Effects of Decabromodiphenyl Ether (BDE-209) and Dechlorane Plus (DP) Flame Retardants in Marine Mussels (Mytilus galloprovincialis).

Dechlorane Plus (DP) is a proposed alternative to the legacy flame retardant decabromodiphenyl ether (BDE-209), a major component of Deca-BDE formulations. In contrast to BDE-209, toxicity data for DP are scarce and often focused on mice. Validated dietary in vivo exposure of the marine bivalve (Mytilus galloprovincialis) to both flame retardants did not induce effects at the physiological level (algal clearance rate), but induced DNA damage, as determined by the comet assay, at all concentrations tested. Micronuclei formation was induced by both DP and BDE-209 at the highest exposure concentrations (100 and 200 µg/L, respectively, at 18% above controls). DP caused effects similar to those by BDE-209 but at lower exposure concentrations (5.6, 56, and 100 µg/L for DP and 56, 100, and 200 µg/L for BDE-209). Moreover, bioaccumulation of DP was shown to be concentration dependent, in contrast to BDE-209. The results described suggest that DP poses a greater genotoxic potential than BDE-209.

Prenatal exposure to polybrominated diphenyl ethers and polyfluoroalkyl chemicals and infant neurobehavior.

OBJECTIVE: To assess the impact of prenatal exposure to polybrominated diphenyl ethers (PBDEs) and polyfluoroalkyl chemicals (PFCs) on early infant neurobehavior. STUDY DESIGN: In a cohort of 349 mother/infant pairs, we measured maternal serum concentrations during pregnancy of PBDEs, including BDE-47 and other related congeners, as well as 2 common PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid. When the infants were 5 weeks of age, we measured their neurobehavior by using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). RESULTS: Neither PBDE nor PFC exposures during gestation were associated with the 11 individual NNNS outcomes included in our study; however, when we used latent profile analysis to categorize infants into neurobehavioral profiles based on performance on the NNNS (social/easygoing, high arousal/difficult, or hypotonic), a 10-fold increase in prenatal PFOA concentrations significantly increased the odds of being categorized as hypotonic compared with social/easygoing (aOR 3.79; 95% CI 1.1-12.8). CONCLUSIONS: Infants of mothers with greater serum concentrations of PFOA during pregnancy were more likely to be categorized as hypotonic. No association between PBDE concentrations and hypotonia was found. Additional studies should further investigate possible associations of prenatal PFC exposure and muscle tone in infants and children.

Zebrafish (Danio rerio) eleutheroembryo-based procedure for assessing bioaccumulation.

This paper reports on the development and preliminary evaluation of a new bioaccumulation test based on the use of zebrafish (Danio renio) eleutheroembryos (72 h after hatching, corresponding to 144 h post fertilization, hpf) as an alternative to adult fish-based procedures for regulatory purposes regarding REACH application. The proposed test accomplished the OECD 305 guideline and consists of a 48 h uptake period followed by a 24 h depuration step. Bioaccumulation experiments were performed for a selected of hyper hydrophobic chemicals (log Kow> 7.6), that is, PCB 136 and PBDE 154 at two concentration levels corresponding roughly to 1% and 0.1% the chemicals LC50(nominal concentrations of 4.0 and 12.0 µg/L for PCB 136, and 1.0 and 5.0 µg/L PBDE 154, respectively). Toxicokinetic models were used to calculate the bioconcentration factors (BCFs) based on of the chemical concentrations found in the contaminated eleutheroembryos and their surrounding media. The experimentally determined accumulation profiles show bioaccumulation by zebrafish eleutheroembryos of both chemicals, and that the process is more complex than simple water-lipid partition. Calculated log BCFs using a first-order accumulation model(3.97 and 3.73 for PCB 136, and 3.95 and 4.29 for PBDE 154) were in the range of those previously reported in the literature. The suitability of this new nonprotected life stage bioaccumulation protocol for BCF estimation was evaluated by application to widely divergent micropollutants with different accumulation mechanisms. The results were compared with those in the MITE-NITE database for adult rice fish (Oryzias latipes).

Assimilation efficiency of PBDE congeners in Chinook salmon.

Polybrominated diphenyl ether (PBDE) flame retardants are environmental contaminants that can accumulate in biota. PBDE accumulation in an organism depends on exposure, assimilation efficiency, and elimination/metabolism. Net assimilation efficiency represents the fraction of the contaminant that is retained in the organism after exposure. In the present study, congener-specific estimates of net PBDE assimilation efficiencies were calculated from dietary exposures of juvenile Chinook salmon. The fish were exposed to one to eight PBDE congeners up to 1500 ng total PBDEs/g food. Mean assimilation efficiencies varied from 0.32 to 0.50 for BDE congeners 28, 47, 99, 100, 153, and 154. The assimilation efficiency of BDE49 was significantly greater than 100%, suggesting biotransformation from higher brominated congeners. Whole body concentrations of BDE49 significantly increased with both exposure to increasing concentrations of BDE99 and decreasing fish lipid levels, implying lipid-influenced debromination of BDE99 to BDE49. Excluding BDE49, PBDE assimilation efficiency was not significantly related to the numbers of congeners in the diets, or congener hydrophobicity, but was greater in foods with higher lipid levels. Estimates of PBDE assimilation efficiency can be used in bioaccumulation models to assess threats from PBDE exposure to Chinook salmon health and recovery efforts, as well as to their predators.

Increasing sample size in prospective birth cohorts: back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children.

Study sample size in prospective birth cohorts of prenatal exposure to persistent organic pollutants (POPs) is limited by costs and logistics of follow-up. Increasing sample size at the time of health assessment would be beneficial if predictive tools could reliably back-extrapolate prenatal levels in newly enrolled children. We evaluated the performance of three approaches to back-extrapolate prenatal levels of p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE) and four polybrominated diphenyl ether (PBDE) congeners from maternal and/or child levels 9 years after delivery: a pharmacokinetic model and predictive models using deletion/substitution/addition or Super Learner algorithms. Model performance was assessed using the root mean squared error (RMSE), R2, and slope and intercept of the back-extrapolated versus measured levels. Super Learner outperformed the other approaches with RMSEs of 0.10 to 0.31, R2s of 0.58 to 0.97, slopes of 0.42 to 0.93 and intercepts of 0.08 to 0.60. Typically, models performed better for p,p'-DDT/E than PBDE congeners. The pharmacokinetic model performed well when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives like p,p'-DDE and BDE-153. Results demonstrate the ability to reliably back-extrapolate prenatal POP levels from levels 9 years after delivery, with Super Learner performing best based on our fit criteria.

Facilitated Leaching of Additive-Derived PBDEs from Plastic by Seabirds' Stomach Oil and Accumulation in Tissues.

Our previous study suggested the transfer of polybrominated diphenyl ether (PBDE) flame retardants from ingested plastics to seabirds' tissues. To understand how the PBDEs are transferred, we studied leaching from plastics into digestive fluids. We hypothesized that stomach oil, which is present in the digestive tract of birds in the order Procellariiformes, acts as an organic solvent, facilitating the leaching of hydrophobic chemicals. Pieces of plastic compounded with deca-BDE were soaked in several leaching solutions. Trace amounts were leached into distilled water, seawater, and acidic pepsin solution. In contrast, over 20 times as much material was leached into stomach oil, and over 50 times as much into fish oil (a major component of stomach oil). Analysis of abdominal adipose, liver tissue, and ingested plastics from 18 wild seabirds collected from the North Pacific Ocean showed the occurrence of deca-BDE or hexa-BDEs in both the tissues and the ingested plastics in three of the birds, suggesting transfer from the plastic to the tissues. In birds with BDE209 in their tissues, the dominance of BDE207 over other nona-BDE isomers suggested biological debromination at the meta position. Model calculation of PBDE exposure to birds based on the results of the leaching experiments combined with field observations suggested the dominance of plastic-mediated internal exposure to BDE209 over exposure via prey.

Bioaccumulation, biotransformation, and toxicity of BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 in early life-stages of zebrafish (Danio rerio).

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), 6-hydroxy-tetrabromodiphenyl ether (6-OH-BDE-47), and 6-methoxy-tetrabromodiphenyl ether (6-MeO-BDE-47) are the most detected congeners of polybrominated diphenyl ethers (PBDEs), OH-BDEs, and MeO-BDEs, respectively, in aquatic organisms. Although it has been demonstrated that BDE-47 can interfere with certain endocrine functions that are mediated through several nuclear hormone receptors (NRs), most of these findings were from mammalian cell lines exposed in vitro. In the present study, embryos and larvae of zebrafish were exposed to BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 to compare their accumulation, biotransformation, and bioconcentration factors (BCF) from 4 to 120 hpf. In addition, effects on expression of genes associated with eight different pathways regulated by NRs were investigated at 120 hpf. 6-MeO-BDE-47 was most bioaccumulated and 6-OH-BDE-47, which was the most potent BDE, was least bioaccumulated. Moreover, the amount of 6-MeO-BDE-47, but not BDE-47, transformed to 6-OH-BDE-47 increased in a time-dependent manner, approximately 0.01%, 0.04%, and 0.08% at 48, 96, and 120 hpf, respectively. Expression of genes regulated by the aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and mineralocorticoid receptor (MR) was affected in larvae exposed to 6-OH-BDE-47, whereas genes regulated by AhR, ER, and the glucocorticoid receptor (GR) were altered in larvae exposed to BDE-47. The greatest effect on expression of genes was observed in larvae exposed to 6-MeO-BDE-47. Specifically, 6-MeO-BDE-47 affected the expression of genes regulated by AhR, ER, AR, GR, and thyroid hormone receptor alpha (TRα). These pathways were mostly down-regulated at 2.5 µM. Taken together, these results demonstrate the importance of usage of an internal dose to assess the toxic effects of PBDEs. BDE-47 and its analogs elicited distinct effects on expression of genes of different hormone receptor-mediated pathways, which have expanded the knowledge of different mechanisms of endocrine disrupting effects in aquatic vertebrates. Because some of these homologues are natural products, assessments of risks of anthropogenic PBDE need to be made against the background of concentrations from naturally occurring products. Even though PBDEs are being phased out as flame retardants, the natural products remain.

Human exposure to PBDE and critical evaluation of health hazards.

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives in a number of commercial products. Biomonitoring data show that, in recent years, PBDE concentrations have increased rapidly in the bodies of wildlife and humans. Usually, PBDE levels in North America have been reported to be higher than those in Europe and Asia. Moreover, body burden of PBDEs is three- to ninefold higher in infants and toddlers than in adults, showing these last two age groups the highest levels of these compounds, due to exposure via maternal milk and through dust. Tetra-, Penta-, and Hexa-BDEs are the isomers most commonly found in humans. Based on studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive changes, and even cancer. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or postnatal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly on motor activity and cognition. This paper is focused on reviewing the current status of PBDEs in the environment, as well as the critical adverse health effects based on the recent studies on the toxic effects of PBDEs.

Measurements of selected brominated flame retardants in nursing women: implications for human exposure.

We have examined several emerging brominated flame retardants (BFRs) including 2-ethyl-1-hexyl-2,3,4,5-tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), 4,5,6,7-tetrabromo-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-indane (OBIND), and decabromodiphenyl ethane (DBDPE) in paired human maternal serum (n = 102) and breast milk (n = 105) collected in 2008-2009 in the Sherbrooke region in Canada. Three legacy BFRs were also included in the study for comparison: decabromobiphenyl (BB-209), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), and 2,2',4,4',5,5'-hexabromodiphenyl ethers (BDE-153). TBB, BB-153, and BDE-153 had detection frequencies greater than 55% in both serum and milk samples. Their lipid weight (lw) adjusted median concentrations (ng g(-1) lw) in serum and milk were 1.6 and 0.41 for TBB, 0.48 and 0.31 for BB-153, and 1.5 and 4.4 for BDE-153, respectively. The detection frequencies for the other BFRs measured in serum and milk were 16.7% and 32.4% for TBPH, 3.9% and 0.0% for BTBPE, 2.0% and 0.0% for BB-209, 9.8% and 1.0% for OBIND, and 5.9% and 8.6% for DBDPE. The ratio of TBB over the sum of TBB and TBPH (fTBB) in serum (0.23) was lower than that in milk (0.46), indicating TBB has a larger tendency than TBPH to be redistributed from blood to milk. Overall, these data confirm the presence of non-PBDE BFRs in humans, and the need to better understand their sources, routes of exposure, and potential human health effects.

Hair as a biomarker of systemic exposure to polybrominated diphenyl ethers.

The efficacy of using hair as a biomarker for exposure to polybrominated diphenyl ether (PBDE) flame retardants was assessed in humans and an animal model. Paired human hair and serum samples were obtained from adult men and women (n = 50). In parallel, hair, serum, liver, and fat were collected from adult male Sprague-Dawley rats exposed to increasing doses of the PBDE mixture found in house dust for 70 days via the diet. All samples were analyzed by GC-MS for eight common PBDEs: BDE-28, -47, -99, -100, -153, -154, -183, and -209. Paired human hair and serum samples had five congeners (BDE-28, -47, -99, -100, and -154) with significant individual correlations (0.345-0.566). In rat samples, BDE-28 and BDE-183 were frequently below the level of detection. Significant correlations were observed for BDE-47, -99, -100, -153, -154, and -209 in rat hair, serum, liver, and fat across doses, with r values ranging from 0.803 to 0.988; weaker correlations were observed between hair and other tissues when data from the lowest dose group or for BDE-209 were analyzed. Thus, human and rat hair PBDE measurements correlate strongly with those in alternative matrices, validating the use of hair as a noninvasive biomarker of long-term PBDE exposure.

Toxicity reference values for polybrominated diphenyl ethers: risk assessment for predatory birds and mammals from two Chinese lakes.

PBDEs are persistent organic pollutants, and have the capability to produce adverse effects on organisms. Aquatic piscivorous species at higher trophic levels have the greatest exposure risk. Information on the toxic potency of a commercial PBDE mixture, DE-71, to mink and American kestrel was reviewed, and dietary- and tissue-based TRVs were derived and evaluated for ecological risk assessment of aquatic piscivorous species inhabiting wetland areas in China. The effect on mink thyroid function was identified as the most appropriate and protective endpoint for deriving the TRV s for mammals. The TRV was based on dietary exposure, and wa s0.1 mg DE-71/kg (wm) or 0.01 mg DE-71/kg (bm)/day (ADI); for liver of mammals,the TRV was 1.2 mg LPBDEslkg (lm). For birds, reproductive effects on American kestrels were used to derive the TRVs, in which an overall UF of 3.0 was used. The TRV was based on dietary exposure, and was 0.1 mg DE-71/kg (wm) or 0.018 mg DE-71/kg (bm)/day (ADI); for eggs of birds, the TRV was 2.35 jlgLPBDEs/g (lm). Reported concentrations of PBDEs in livers of aquatic mammals found dead, and in fish and bird eggs from Chinese wetland areas were compiled and compared to the corresponding criteria values. Results indicated that TRV values reported in this study can be used as indicators for screening-level risk assessment of piscivorous species in Chinese aquatic systems. Furthermore, based on monitoring concentrations of PBDEs in fishes from two lakes (DCL and TL) in China and the dietary-based TRV of 0.1 mg DE-71/kg (wm), a screening-level risk assessment of PBDEs was performed for predatory birds and mammals. The results suggest that concentrations of PBDEs in these two areas would not be expected to cause any adverse effects on the local fish-eating wild birds and mammals.