Search

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 K ow 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.

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.

Bioconcentrations of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in brain, gonad, and liver as well as effects on fecundity and development of zebrafish (Danio rerio) were determined. Zebrafish (1-month old) were exposed to environmentally relevant concentrations of 29 ± 2.1, 600 ± 21, or 6300 ± 130 ng TDCIPP/L. After 120 days of exposure, TDCIPP accumulated in the brain, gonad, and liver with bioconcentration factors of 460, 38, and 87 in females and 26, 55, and 110 in males, respectively. TDCIPP accumulated to a greater extent in brains of females than those of males. Exposure to 6300 ± 130 ng TDCIPP/L resulted in significantly (P < 0.05) fewer eggs being produced, but the histology of the gonad, plasma concentrations of estradiol and 11-ketotestosterone, and expression of genes involved in hypothalamic-pituitary-gonadal-liver axis were not significantly (P > 0.05) different between individuals exposed to TDCIPP and the unexposed control fish. Exposure to TDCIPP resulted in shorter body length, lighter body mass, and lower gonadal-somatic index in females. These effects were possibly due to down-regulation of expression of genes along the growth hormone/insulin-like growth factor (GH/IGF) axis. Correlations between the production of eggs and developmental parameters or expression of genes along the GH/IGF axis further suggested that environmentally relevant concentrations of TDCIPP could have adverse effects on reproduction, possibly due to the inhibition of the growth of females.

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.

Organophosphate flame retardants are emerging environmental contaminants, although knowledge of their health risks is limited. Here, thyroid hormone homeostasis and neuronal development was studied in the progeny of adult zebrafish exposed to tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Adult zebrafish were exposed to TDCPP (0, 4, 20, and 100 μg/L) for 3 months. Increased generation of reactive oxygen species and reduced survival rates was observed in exposed F1 larvae. We also observed a significant decrease in plasma thyroxine and 3,5,3'-triiodothyronine levels in F0 females and F1 eggs/larvae. The mRNA and protein expression of factors associated with neuronal development (e.g., α1-tubulin, myelin basic protein, and synapsin IIa) were significantly downregulated in exposed F1 larvae, as was the level of the neurotransmitters dopamine, serotonin, gamma amino butyric acid, and histamine. Larval locomotion was significantly decreased in exposed fish, but there was no effect on acetylcholinesterase activity. Bioconcentration of TDCPP was observed in F0 fish. TDCPP was also detected in F1 eggs following parental exposure, indicating maternal transfer of this compound. This study uniquely shows that TDCPP can be transferred to the offspring of exposed adults, causing thyroid endocrine disruption and developmental neurotoxicity.

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.

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.

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.

Highly hydrophobic organohalogen flame retardants (HHOFRs) are found ubiquitously in the environment; therefore, a better understanding of their bioavailability is needed. In the current study, bioaccumulation testing using the oligochaete, Lumbriculus variegatus, and passive sampling (solid-phase microextraction (SPME)) were performed to study the bioaccumulation potential of HHOFRs, including decabromodiphenyl ether (deca-BDE), decabromodiphenyl ethane (DBDPE), and dechlorane plus (DP), in laboratory-spiked and field-collected sediments. The HHOFRs were bioavailable to L. variegatus even though their biota-sediment accumulation factors were low (0.016 ± 0.002 to 0.48 ± 0.082 g organic carbon/g lipid, syn-DP > anti-DP > deca-BDE > DBDPE). Hydrophobicity and stereoisomerism affected HHOFR bioavailability. Meanwhile, HHOFR concentrations on the SPME fibers (Cf) correlated with those in biota (Cb), suggesting the potential application of SPME in bioavailability prediction for those compounds. The log Cf to log Cb correlation for deca-BDE and DP had a greater intercept than that for polychlorinated biphenyls (data obtained from the literature) although the slopes were similar, while data for DBDPE fell on the regression line for PCBs, implying some uncertainty in application of SPMEs across chemical classes. The increasing sorptive ability of proteins for HHOFRs in comparison to the less-brominated BDEs suggested that protein-binding should be considered when estimating bioaccumulation potential of HHOFRs in benthic invertebrates.

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.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is frequently present in indoor dust and can be detected in human milk. In order to evaluate the effects of TDCPP on vertebrate development, zebrafish embryos/larvae were used as an animal model to examine developmental phenotypes and explore possible mechanisms of toxicity by employing microarrays and iTRAQ labeling quantitative proteomics. The results demonstrated that treatment with TDCPP (3 μM) from 0.75 h postfertilization (hpf) inhibited cell rearrangement at 4 hpf, caused delay in epiboly at 5.7 and 8.5 hpf, and led to abnormal development (e.g., short tail, reduced body size) and lethality between 14 and 45 hpf, which might be related with altered expression of genes regulating embryogenesis. Furthermore, trunk curvature was observed as the main phenotype in 96 hpf zebrafish larvae exposed to 1 or 3 μM TDCPP, possibly by changing somite formation and expression of proteins related to fast muscle and cartilage development. Collectively, our results suggest that exposure to TDCPP causes developmental toxicity in vertebrates and warrant the need for studies to evaluate the potential health risks of TDCPP to developing human embryos/infants/children, due to its frequent presence in indoor dust and potential for human exposure.

Estimates of exposure to the flame-retardant polybrominated diphenyl ethers (PBDEs) in dust are very poor due to limited knowledge about dust ingestion. This study was undertaken to determine if PBDEs could be measured on hand wipes, and if so, to determine the distribution of levels present on the skin surface area to provide preliminary exposure estimates from hand-to-mouth contact. Hand wipes were collected from 33 individuals residing in the United States using sterile gauze pads soaked in isopropyl alcohol. The total PBDE residue collected on the wipes ranged from 2.60 to 1982 ng, with a median value of 130 ng, or normalized to hand surface area, a concentration of 135 pg/cm2. The fully brominated congener, BDE 209, was also detected and ranged from < DL to 270 ng with a median value of 26 ng. Congener patterns observed on the wipes were similar to patterns observed in house dust samples, consisting of congeners associated with the PentaBDE and DecaBDE mixtures, suggesting that the source of PBDEs to the hands may be dust particles. However, PBDE hand residues may also be a result of direct contact with PBDE-laden products, leading to adsorption to the skin surface oils. Repeated wipe sampling from three individuals suggests that sigmaPBDE levels on the hand may be relatively consistent for some individuals but not for others. Furthermore, levels of sigmaPBDEs were greater on the bottom of the hands relative to the top of the hands. Using these values we have calculated potential human exposure from hand-to-mouth contact. The median exposure estimates for children and adults are 1380 and 154 ng/day, respectively, whereas the 95th percentile exposure estimates were 6090 and 677 ng/day, respectively. These estimates are greater than dietary intake rates and suggest hand-to-mouth contact may be a key exposure route for PBDEs.

The present study investigated concentrations and patterns of brominated flame retardants, such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs), and persistent organochlorines (OCs) in liver and adipose tissues of raccoon dogs (RD: Nyctereutes procyonoides) collected from two metropolises and a local prefecture in Japan during 2001-2006. Relatively high concentrations of PBDEs were found in RD livers, while HBCD levels were the lowest among the measured organohalogen compounds. Among PBDE congeners, BDE 209 was predominant in RDs from all the regions, indicating that pollution derived from the technical decaBDE product is extensive across Japan. On the other hand, concentrations of tetra- to nona-BDE congeners in RDs from a metropolis were significantly higher than those from the other two regions, implying that there were regional differences in the past usage of the technical tetraBDE and octaBDE products. Such a regional difference was also observed for HBCD levels. Lipid-normalized concentration ratios of liver to adipose tissue (L/A ratio) for tri to hepta-BDE congeners were lower than 1.0 in the investigated eight RDs, suggesting lipid-dependent accumulation. However, the LA ratios of BDE 209 exceeded 1.0 in all the specimens, suggesting hepatic retention of this compound. In addition, lipid-dependent accumulation of a-HBCD was observed, but the L/A ratios of gamma-HBCD were greater than 1.0 in some specimens. These results indicate that Japanese RDs have been recently exposed to BDE 209 and gamma-HBCD and accumulated both these compounds preferentially in blood-rich organs, probably due to their binding to proteins and/or rapid biotransformation, as reported in experimental rodents.

Polychlorinated biphenyls (PCBs), DDTs, and polybrominated diphenyl ethers (PBDEs) were followed through the five life stages of a wild population of anadromous brown trout and related to variations in lipid content and exposure situations. Anadromous brown trout exhibits great variations in lipid content during its life cycle in the freshwater and marine environments. The results indicated substantial differences in PBDE and organochlorine exposure, with apparently more recent sources of PBDEs in the freshwater environment relative to the marine environment. Lipid and contaminant transfer were not always identical: The concentrations of PCBs, DDTs, and PBDEs (ng/g lipid weight) were about 15 times lower in the eggs compared to the muscle of their mother (e.g., 823 ng PCB/g Iw vs. 12,565 ng PCB/g lw, respectively). During the starving period from maiden to spawning trout the contaminant load increased by a higher factor than the lipid use. The data suggest a decoupling between lipid content and organohalogen concentrations for anadromous brown trout, which may contribute positively to reduce any potential negative effects of the transferred contaminants on eggs and fry.

The extent of bioaccumulation of the syn- and anti-isomers of Dechlorane Plus (DP) is assessed in archived food web samples from Lake Winnipeg and Lake Ontario. Concentrations of the isomers were determined using purified analytical solutions of individual isomers as opposed to the technical mixture. The syn-isomer was consistently detected in all samples from both lakes; the anti-isomer was detected in all Lake Ontario samples, but only 45% of the samples from Lake Winnipeg. The pattern of bioaccumulation was different for the isomers in Lake Winnipeg. The anti-isomer was dominant in higher trophic level (TL) organisms like walleye [arithmetic mean +/- 1 x standard error: 730 +/- 120 pg/g, lipid weight (1w)] and goldeye (760 +/- 170 pg/g, Iw) while the syn-isomer dominated the lower TL organisms like zooplankton (550 +/- 40 pg/g, Iw) and mussels (430 +/- 140 pg/g, Iw). In Lake Ontario, the extent of bioaccumulation of the isomers and concentrations was greatest in the lower TL benthic organism, Diporeia (syn, 1307 +/- 554; and anti, 3108 +/- 898 pg/g Iw) and also high in zooplankton (syn, 719; and anti, 1332 pg/g Iw). This suggests that the isomers are bioavailable in sediment and that, despite their molecular size, diffusion from the water column into zooplankton can occur. Differences in the mean fractional abundance of the anti-isomer (mean fanti = mean concentration of the anti-isomer divided by sum of mean syn- and anti-concentrations) were pronounced in sediments between lakes (Lake Winnipeg mean fanti = 0.610, Lake Ontario mean fanti = 0.860) and the extent of enrichment (anti-) and depletion (syn-) of the isomers were more marked in Lake Winnipeg biota. There were also differences in the biomagnification potentials, as measured bythe trophic magnification factor (TMF), between the isomers in the Lake Winnipeg food web; no statistically significant TMFs for either isomer were found for the

Decabromodiphenyl ether (BDE-209) isthe major component in the flame-retardant formulation DecaBDE which is incorporated into numerous consumer goods ranging from upholsteries to electronics. Because of the high volume of DecaBDE produced, its presence in consumer products and the environment, and the finding of BDE-209 in the blood of exposed workers, the extent of bioavailability, persistence, and potential debromination are important issues. To measure the bioconcentration, distribution, reductive debromination, and whole-body half-lives of BDE-209 after multiple low doses in an animal model, we dosed rats with a commercial DecaBDE (0.3 microg/g of diet) for 21 days and measured tissue polybrominated diphenyl ether levels during a 21 day withdrawal period. BDE-209, three nona-BDEs, and four octa-BDEs accumulated in the rats and distributed proportionately throughout the body. Only 5% of the total BDE-209 dose was present as parent compound in the rats after 21 days of dosing and <4% in the feces, suggesting extensive metabolism. A nona-BDE (BDE-207) and two octa-BDEs (BDEs-201 and -197) appeared to form via meta-debromination(s) of BDE-209 to a minimal extent (1% of the total BDE-209 dose). The wholebody half-lives tended to increase with decreasing bromination; however, two octa-BDEs, presumably forming from debromination, increased in the rats after 21 days of withdrawal and demonstrated the potential for BDE-209 to form more persistent lipophilic compounds in vivo.

The brominated flame retardants have been subject of a particular environmental focus in the Arctic. The present study investigated the congener patterns and levels of total hexabromocyclododecane (HBCD), polybrominated biphenyls, polybrominated diphenyl ethers (PBDEs), as well as methoxylated (MeO) and hydroxylated (OH) PBDEs in plasma samples of glaucous gulls (Larus hyperboreus) and polar bears (Ursus maritimus) from the Norwegian Arctic. The analyses revealed the presence of total HBCD (0.07-1.24 ng/g wet wt) and brominated biphenyl 101 (< 0.13-0.72 ng/g wet wt) in glaucous gull samples whereas these compounds were generally found at nondetectable or transient concentrations in polar bears. Sum (sigma) concentrations of the 12 PBDEs monitored in glaucous gulls (range: 8.23-67.5 ng/g wet wt) surpassed largely those of polar bears (range: 2.65-9.72 ng/g wet wt). Two higher brominated PBDEs, BDE183 and BDE209, were detected, and thus bioaccumulated to a limited degree, in glaucous gulls with concentrations ranging from < 0.03 to 0.43 ng/g wet wt and from < 0.05 to 0.33 ng/g wet wt, respectively. In polar bear plasma, BDE183 was < 0.04 ng/g wet wt for all animals, and BDE209 was only detected in 7% of the samples at concentrations up to 0.10 ng/g wet wt. Of the 15 MeO-PBDEs analyzed in plasma samples, 3-MeO-BDE47 was consistently dominant in glaucous gulls (sigmaMeO-PBDE: 0.30-4.30 ng/g wet wt) and polar bears (sigmaMeO-PBDE up to 0.17 ng/g wet wt), followed by 4'-MeO-BDE49 and 6-MeO-BDE47. The 3-OH-BDE47, 4'-OH-BDE49, and 6-OH-BDE47 congeners were also detected in glaucous gulls (sigmaOH-PBDE up to 1.05 ng/g wet wt), although in polar bears 4'-OH-BDE49 was the only congener quantifiable in 13% of the samples. The presence of MeO- and OH-PBDEs in plasma of both species suggests possible dietary uptake from naturally occurring sources (e.g., marine sponges and green algae), but also metabolically derived biotransformation of PBDEs such as BDE47 could be a contributing factor. Our findings suggest that there are dissimilar biochemical mechanisms involved in PCB and PBDE metabolism and accumulation/elimination and/or OH-PBDE accumulation and retention in glaucous gulls and polar bears.

Commercial hexabromocyclododecane (HBCD) is a high-production-volume flame-retardant applied in polystyrene foams. It contains three stereoisomers, of which gamma-HBCD always dominates. Here we report on the levels of HBCD in blubber of harbor porpoise and common dolphin from different European seas. The highest total (sigma)-HBCD levels were measured in harbor porpoises stranded on the Irish and Scottish coasts of the Irish Sea (median concentration 2.9 microg (g of lipid)(-1)) and the northwest coast of Scotland (median concentration 5.1 microg (g of lipid)(-1)). The median levels in other areas were, for the harbor porpoise south coast of Ireland, 1.2 microg (g of lipid)(-1), for the coasts of The Netherlands, Belgium, and France north of Calais (southern North Sea), 1.1 microg (g of lipid)(-1), for the east coast of Scotland (northern North Sea), 0.77 microg (g of lipid)(-1), and, for Galicia (Spain), 0.1 microg (g of lipid)(-1). The median levels for the common dolphin were, for west coast of Ireland, 0.9 microg (g of lipid)(-1), for the French coast of the English Channel between Normandy and Brest, 0.4 microg (g of lipid)(-1), and, for Galicia, 0.2 microg (g of lipid)(-1). A subset of 10 harbor porpoise and 9 common dolphin blubber samples representing all areas were analyzed by LC/MS to determine the diastereomeric composition of their HBCD residues. All samples showed exclusively the peak of alpha-HBCD. To test if biotransformation by the cytochrome P450 system could explain the observed compositional difference with technical HBCD mixtures, a number of in vitro assays with microsomal preparations of liver were carried out. We had to revert to material stored at -80 degrees C from laboratory rats and a fresh harbor seal found dead in the Dutch Wadden Sea, since such liver samples of cetaceans were not in our possession. The in vitro assays showed that beta- and gamma-HBCDs were indeed significantly metabolized when incubated in the presence of NADPH as electron donor, compared to a set of reference samples which were identical except for the addition of NADPH. In contrast, the peak of alpha-HBCD did not decrease significantly in the presence of NADPH. In separate microsomal assays with beta- and gamma-HBCDs, new peaks of brominated compounds (signal at m/z = 79 or 81) with masses of [M + 0] were formed only when NADPH was added. This confirms the process of cytochrome P450 mediated biotransformation. Although rat and harbor seal belong to different families of the mammalia than the cetaceans, we propose that biotransformation by the cytochrome P450 system is also the most likely process to explain the exclusive accumulation of alpha-HBCD in harbor porpoise and common dolphin.

Individual polybromodiphenyl ethers (PBDEs) were investigated in liver and muscle tissue of trout from 11 high mountain lakes in Europe and one in Greenland. Trouts in these lakes [brown trout (Salmo trutta), brook trout (Salvelinus fontinalis) and arctic char (Salvelinus alpinus)] are important sentinel species because they are located in the top of the food chain and pollution can only reach these ecosystems by atmospheric transport. The major PBDE congeners were BDE 47 and BDE 99, followed by BDE 100, BDE 153, BDE 154, and BDE 28. These compounds were found in all the samples examined. Their average concentrations [110-1300 and 69-730 pg g(-1) wet weight (ww) in liver and muscle or 2400-40000 and 2900-41000 pg g(-1) lipid weight (lw), respectively] were in the lower range when compared with those of fish from other less remote locations. The highest levels of PBDEs in liver and muscle are found in Lochnagar, Scotland: 11000 and 1200 pg g(-1) ww, respectively (366 000 and 177000 pg g(-1) lw, respectively). Male specimens exhibited higher PBDE concentrations in liver than female. The concentrations of most PBDEs in liver were correlated with fish age (p < 0.01) and, inversely, with condition factor (p < 0.01). Muscle PBDE concentrations did not correlate with age, and only some congeners showed significant positive correlations with condition factor (p < 0.05). The main differences between species were found in the accumulation of the more abundant PBDEs, brook trout showing the highest concentrations in muscle and the lowest in liver. No correlation between the occurrence of these compounds in high mountain fish and altitude, latitude, or temperature was observed. This fact and the lack of correlation between muscle concentrations and age suggest that the fluxes of PBDEs arriving at high mountain lakes are still not constant. In view of the present use of these compounds, they are probably increasing.

The congener 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE 209) is the primary component in a commonly used flame retardant known as decaBDE. This flame retardant constitutes approximately 80% of the world market demand for polybrominated diphenyl ethers (PBDEs). Because this compound is very hydrophobic (log K(ow) approximately 10), it has been suggested that BDE 209 has very low bioavailability, although debromination to more bioavailable metabolites has also been suggested to occur in fish tissues. In the present study, juvenile carp were exposed to BDE 209 amended food on a daily basis for 60 days, followed by a 40-day depuration period in which the fate of BDE 209 was monitored in whole fish and liver tissues separately. No net accumulation of BDE 209 was observed throughout the experiment despite an exposure concentration of 940 ng/day/fish. However, seven apparent debrominated products of BDE 209 accumulated in whole fish and liver tissues over the exposure period. These debrominated metabolites of BDE 209 were identified as penta- to octaBDEs using both GC/ECNI-MS and GC/HRMS. Using estimation methods for relative retention times of phenyl substitution patterns, we have identified possible structures for the hexa- and heptabromodiphenyl ethers identified in the carp tissues. Although exposure of carp to BDE 209 did not result in the accumulation of BDE 209 in carp tissues, our results indicate evidence of limited BDE 209 bioavailability from food in the form of lower brominated metabolites.

Several brominated flame retardants (BFRs) were analyzed in peregrine falcon eggs collected in 1987-1999, including the constituents of the technical polybrominated diphenyl ether (PBDE) products Penta (BDE-47, -99, -100, -153, -154), Octa (BDE-183), and Deca (BDE-209), hexabrominated biphenyl (BB-153), and hexabromocyclododecane (HBCD). The eggs represented females from three different breeding populations, northern Sweden, southwestern Sweden, and a captive breeding population. All BFRs analyzed for were found, including BDE-183 and -209, and concentrations were much higher in wild falcons (geometric mean sigmaPBDE, BB-153, and HBCD for northern/southern populations of 2200/2700, 82/77, and 150/250 ng/g lw, respectively) than in captive falcons (39, 8 ng/g lw, and not detected, respectively). This is the first time, to our knowledge, that BDE-183 and -209 have been quantified in high trophic level wildlife.

The flame retardant polybrominated diphenyl ethers (PBDEs) have become ubiquitous environmental pollutants. The environmental distribution of PBDEs is much less studied than that of the polychlorinated biphenyls (PCBs). To compare the environmental fate of the PCBs with their partial substitute, the PBDEs, common frogs (Rana temporaria)were collected along a approximately 1,500-km-long latitudinal gradient of the Scandinavian Peninsula and their livers analyzed for PCBs and PBDEs. Mean concentrations of total PCBs and BDE47 ranged from 9200 to 92 900 and 30 to 120 ng kg(-1) fresh weight, respectively, whereas BDE99 was detected in less than 50% of the frogs. PCB concentrations were higher than that of the PBDEs, and the differences decreased in the northern latitudes. Moreover, the pollutant concentrations in frog livers were negative functions of latitude. The observed scatter and regression slopes imply several influencing factors (such as habitat, exposure route, uptake, metabolism, excretion, etc.) and indicate release events instead of the grasshopper effect Biological variables such as gender, age, body size, and lipid content did not influence pollutant concentrations in the frog livers. The total PCB and BDE47 concentrations in frogs were highly correlated. Hence, their environmental fate is analogous and our results highlight the need to examine the potential role of xenobiotics on amphibian populations.

Geographical distribution of brominated diphenyl ether (BDE) flame retardants in the North American Great Lakes ecosystem in 2000 was determined by analysis of herring gull eggs (13 egg pools) from a network of 15 monitoring colonies scattered throughout the lakes and connecting channels. sigmaBDEs were found at concentrations ranging from 192 to 1,400 microg/kg, mean of 662 +/- 368 microg/kg (wet weight of egg contents). Highest concentrations were found in northern Lake Michigan and Toronto harbor (1,000-1,400 microg/kg) and lowest in Lake Huron and Lake Erie (192-340 microg/kg). The distribution suggested that input from large urban/ industrial areas through air or water emissions contributes local contamination to the herring gull food web in addition to background levels from regional/global transport. The congener composition was similar among sampling sites. Major congeners were BDE-47 (43%), BDE-99 (26%), BDE-100 (13%) BDE-153 (11%), BDE-154 (4%), BDE-183 (2%) and BDE-28 (1%). Temporal trends of BDE contamination, 1981-2000, were established by analysis of archived herring gull eggs (10 egg pools) from colonies in northern Lake Michigan, Saginaw Bay, Lake Huron and eastern Lake Ontario. BDE-47, -99 and -100, and BDE-153, -154 and -183 concentrations were grouped separately for analysis because these two groups had different trends and are primarily associated with the Penta BDE and Octa BDE flame retardant formulations, respectively. SigmaBDE47,99,100 concentrations were 5-12 microg/kg (wet weight) in 1981-1983 and then increased exponentially (p < 0.00001) at all three sites to 400-1,100 microg/kg over the next 17 years. Doubling times were 2.6 years in Lake Michigan, 3.1 years in Lake Huron and 2.8 years in Lake Ontario. SigmaBDE154,153,183 concentrations generally increased but varied in an erratic fashion among sites and decreased as a fraction of sigmaBDE over time. Concentrations of sigmaBDE154,153,183 were 100-200 microg/kg in eggs from all three colonies in 2000. Therefore, most of the dramatic increases in sigmaBDE concentrations observed over the past 20 years in the Great Lakes aquatic ecosystem seem to be connected with the Penta BDE formulation, which is mainly used as a flame retardant in polyurethane foam in North America. If present rates of change continue, concentrations of sigmaBDEs will equal or surpass those of sigmaPCBs in Great Lakes herring gull eggs in 10-15 years.

The levels of individual PBDE congeners were investigated in the invertebrate species whelk (Buccinum undatum), seastar (Asterias rubens), and hermit crab (Pagurus bernhardus), the gadoid fish species whiting (Merlangius merlangus) and cod (Gadus morhua), and the marine mammal species harbor seal (Phoca vitulina) and harbor porpoise (Phocoena phocoena). These species are all important representatives of different trophic levels of the North Sea food web. All six major PBDE congeners detected (BDEs 28, 47, 99, 100, 153, and 154) are most prevalent in the commercial Penta-BDE formulation. There is no evidence for the occurrence of the Octa-BDE formulation in the North Sea food web, since its dominant congener, BDE183, was never detected. BDE209, the main congener (> 97%) in the Deca-BDE formulation, was detected only in a minority of the samples and always in concentrations around the limit of detection. Since BDE209 is often the major BDE congener in sediments from the area, the main reason for its low concentrations in biota from the North Sea seems to be a relatively low bioaccumulation potential. This can either be due to a low uptake rate of the very large molecule or a relatively rapid excretion after biotransformation. Since all invertebrates investigated are sentinel species, they are highly representative for the area of capture. The highest lipid-normalized concentrations of PBDEs in the invertebrates occurred near the mouth of the river Tees at the East coast of the UK. The geographical distribution of the PBDEs can be explained by the residual currents in the area. The direction of these currents differs between the summer and the winter season as a result of the presence or absence of vertical summer stratification of the deeper waters north of the Dogger Bank. Summer stratification results in the development of a density-driven bottom water current formed after the onset of vertical stratification of the water column in May leaving the UK coast near Flamborough Head toward the Dogger Bank. In winter, the residual currents run in a more southerly direction and follow the UK coastline. The distribution pattern of the PCBs and p,p'-DDE in the invertebrates was entirely different from that of the PBDEs, which could be expected, since the use of these organochlorines in western Europe peaked in the 1960s and 1970s but has been forbidden more than two decades ago, whereas the production and use of the penta-BDE formulation is of a more recent origin. The higher trophic levels of the North Sea food web were represented by the predatory gadoid fish species whiting and cod and the marine mammal species harbor seal and harbor porpoise. The lipid-normalized levels of the six major PBDE congeners in fish were similar to the levels in the invertebrates, but a biomagnification step in concentrations of generally more than an order of magnitude occurred from gadoid fish to marine mammals. Based on the limited number of samples, no differences could be observed between harbor seal and harbor porpoise. In summary, the results in three species of sentinel invertebrates from a network of stations covering a major part of the North Sea basin showed that the estuary of the river Tees at the UK East coast is a major source for tri- to hexa-PBDEs. Throughout the food-chain, the most marked increase in (lipid-normalized) levels of all six PBDE congeners occurred from predatory (gadoid) fish to marine mammals, agreeing with the transition from gill-breathing to lung-breathing animals. This has serious consequences for the route of elimination of POPs, since their elimination from the blood into the ambient seawater via the gill-membrane is no longer possible.

A suite of 37 polybrominated diphenyl ether (PBDE) congeners and all of the homologue groups from mono- to deca-brominated were determined in ringed seal (Phoca hispida) blubber collected from subsistence hunts in the Canadian Arctic in 1981, 1991, 1996, and 2000. Total PBDE (sum(PBDE)) concentrations have increased exponentially over this period in male ringed seals aged 0-15 years. Penta- and hexa-BDEs are increasing at approximately the same rate (t2 = 4.7 and 4.3 years, respectively) and more rapidly than tetra-BDEs (t2 = 8.6 years) and tri-BDEs (t2 = infinity) in this age/sex grouping. In contrast to declining PBDE concentrations since 1997 in human milk from Sweden, sum(PBDE) concentrations in arctic ringed seals continue to increase exponentially similar to worldwide commercial penta-BDE production. PBDE congener profiles in male ringed seals aged 0-15 years from 1991 to 2000 also differ significantly from other aquatic organisms and semipermeable membrane devices collected from temperate coastal regions of British Columbia. While PBDE concentrations are 50 times lower than those of mono-ortho and non-ortho PCBs, and approxiamately 500 times higher than PCDD/Fs, our data indicate that, at current rates of bioaccumulation, PBDEs will surpass PCBs to become the most prevalent organohalogen compound in Canadian arctic ringed seals by 2050.

The temporal trends and influence of age and gender on levels of selected brominated flame retardants (BFRs) in human serum have been assessed by analyzing archived samples from Norway. Serum from 40 to 50 year old men collected at six time periods during 1977 to 1999 and from eight groups of differing age and gender sampled in 1998 were pooled into six and eight samples, respectively. The BFRs were isolated using solid-phase extraction (SPE) and the serum lipids decomposed bytreatmentwith concentrated sulfuric acid directly on the polystyrene-divinylbenzene SPE column, prior to elution of the BFRs. Following diazomethane derivatization, the samples were analyzed by gas chromatography-electron capture mass spectrometry. Eight BFRs were quantified in the serum samples: 2,4,4'-tribromodiphenyl ether (BDE-28), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153), 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154), 2,4,6-tribromophenol (TriBP), and tetrabromobisphenol A (TBBP-A). The serum concentrations of all the BFRs, increased during the entire period with the exception of TriBP, and the sum of the six polybrominated diphenyl ethers increased from 0.44 ng/g lipids in 1977 to 3.3 ng/g lipids in 1999. The BFR concentrations in the serum from the different age groups were relatively similar, except for the age group 0-4 years, which had 1.6-3.5 times higher serum concentrations. Women older than 25 years had lower serum concentrations of BFRs compared to the corresponding group of men. No trend related to age or gender, nor time during the period 1977 to 1999 was observed for TriBP. The present study indicates an ongoing increase in human exposure to BFRs, and the current body burden appears to be independent of age, except for infants (0-4 years old), who seem to experience elevated exposure.

Serum samples collected in 1988 from U.S. blood donors were analyzed for polybrominated diphenyl ethers (PBDEs) and polychlorinated and polybrominated biphenyls (PCBs and PBBs). The levels of the PBDEs are reported for the first time in serum from the U.S. population. The median concentrations and range of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153); 2,2',3,4,4',5',6-heptabromodiphenyl ether (BDE-183); and decabromodiphenyl ether (BDE-209) were 1.3 (<0.8-49); 0.54 (0.13-3.1); 0.24 (0.12-1.8); and <1 (<1-35) pmol/g lipid weight (l.w.), respectively. In addition we also measured detectable levels of nine additional PBDE congeners in many of the serum samples. The median concentrations and ranges of 2,2',4,4',5,5'-hexachloro- and hexabromobiphenyl (CB-153 and BB-153) were 190 (21-2600) and 19 (4.2-84) pmol/g l.w. The levels of PBDEs and CB-153 found in the U.S. samples were similar to background levels reported in the serum of Swedish hospital cleaners collected 10 years later, i.e., 1997. The BB-153 congener measured in the U.S. samples was not found in the Swedish samples. The difference in exposure to this congener could not be assessed in this study, although might be related to the 1973 BB-153 (FireMaster BP-6) animal and human contamination incident in the State of Michigan.