The authors' reply.
Environment Canada, Wildlife Research Centre, Ottawa, Ontario.Environmental Toxicology and Chemistry (Impact Factor: 2.83). 06/2012; 31(6):1185-6. DOI: 10.1002/etc.1846
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ABSTRACT: The absorption, disposition, metabolism and excretion study of orally administered 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) was studied in conventional and bile-duct cannulated male rats. In conventional rats, >70% of the radiolabelled oral dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, gastrointestinal tract, skin, liver and lungs. Urinary excretion of BDE-100 was very low (0.1% of the dose). Biliary excretion of BDE-100 was slightly greater than that observed in urine, i.e. 1.7% at 72 h, and glucuronidation of phenolic metabolites was suggested. Thiol metabolites were not observed in the bile as had been reported in other PBDE metabolism studies. Almost 20% of the dose in conventional male rats and over 26% in bile-duct cannulated rats was excreted in the faeces, mainly as the unmetabolized parent, although large amounts of non-extractable radiolabel were also observed. Extractable metabolites in faeces were characterized by mass spectrometry. Monohydroxylated pentabromodiphenyl ether metabolites were detected; mono- and di-hydroxylated metabolites with accompanying oxidative debromination were also observed as faecal metabolites. Tissue residues of [(14)C]BDE-100 in liver, gastrointestinal tract and adipose tissue contained only parent material. The majority of the 0-72-h biliary radioactivity was associated with an unidentified 79-kDa protein or to albumin.Xenobiotica 02/2006; 36(1):79-94. DOI:10.1080/00498250500491675 · 2.10 Impact Factor
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ABSTRACT: We evaluated the available pharmacokinetic data and human and animal toxicity data for 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) (CASRN 1163-19-5) with the objective of deriving a reference dose (RfD) based on the best available science. The available studies for deriving an RfD were first screened using the Klimisch criteria and further evaluated using the United States Environmental Protection Agency's general assessment factors for data quality and relevance (i.e., soundness, applicability and utility, clarity and completeness, uncertainty and variability, and evaluation and review). The chronic 2-year dietary feeding study conducted by the United States National Toxicology Program ( NTP, 1986 , Technical Report Series No. 309) was selected for RfD derivation. Hepatocellular degeneration in male rats was chosen as the critical endpoint in the development of an RfD. For dose-response characterization, we applied benchmark-dose modeling to animal data and determined a point of departure (the 95% lower confidence limit for a 10% increase in hepatocellular degeneration) of 419 mg/kg-day for oral exposures. Based on the similar pharmacokinetic characteristics of BDE-209 across species, this value was converted to a human equivalence dose of 113 mg/kg-day by applying a dosimetric adjustment factor based on body weight scaling to the (3/4) power. An oral RfD of 4 mg/kg-day was calculated by using a composite uncertainty factor of 30, which consisted of 10 for intraspecies uncertainty, 3 for interspecies uncertainty (i.e., 3 for toxicodynamics x 1 for toxicokinetics), and 1 for deficiencies with the database. We consider the RfD to be adequately protective of sensitive subpopulations, including women, their fetuses, children, and people with hepatocellular diseases.Critical Reviews in Toxicology 11/2009; 39 Suppl 3(s3):1-44. DOI:10.3109/10408440903279946 · 6.41 Impact Factor
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ABSTRACT: We report on the comparative bioaccumulation, biotransformation and/or biomagnification from East Greenland ringed seal (Pusa hispida) blubber to polar bear (Ursus maritimus) tissues (adipose, liver and brain) of various classes and congeners of persistent chlorinated and brominated contaminants and metabolic by-products: polychlorinated biphenyls (PCBs), chlordanes (CHLs), hydroxyl (OH-) and methylsulfonyl (MeSO(2)-) PCBs, polybrominated biphenyls (PBBs), OH-PBBs, polybrominated diphenyl ether (PBDE) and hexabromocyclododecane (HBCD) flame retardants and OH- and methoxyl (MeO-) PBDEs, 2,2-dichloro-bis(4-chlorophenyl)ethene (p,p'-DDE), 3-MeSO(2)-p,p'-DDE, pentachlorophenol (PCP) and 4-OH-heptachlorostyrene (4-OH-HpCS). We detected all of the investigated contaminants in ringed seal blubber with high frequency, the main diet of East Greenland bears, with the exception of OH-PCBs and 4-OH-HpCS, which indicated that these phenolic contaminants were likely of metabolic origin and formed in the bears from accumulated PCBs and octachlorostyrene (OCS), respectively, rather than being bioaccumulated from a seal blubber diet. For all of the detectable sum of classes or individual organohalogens, in general, the ringed seal to polar bear mean BMFs for SigmaPCBs, p,p'-DDE, SigmaCHLs, SigmaMeSO(2)-PCBs, 3-MeSO(2)-p,p'-DDE, PCP, SigmaPBDEs, total-(alpha)-HBCD, SigmaOH-PBDEs, SigmaMeO-PBDEs and SigmaOH-PBBs indicated that these organohalogens bioaccumulate, and in some cases there was tissue-specific biomagnification, e.g., BMFs for bear adipose and liver ranged from 2 to 570. The blood-brain barrier appeared to be effective in minimizing brain accumulation as BMFs were <or=1 in the brain, with the exception of SigmaOH-PBBs (mean BMF=93+/-54). Unlike OH-PCB metabolites, OH-PBDEs in the bear tissues appeared to be mainly accumulated from the seal blubber rather than being metabolic formed from PBDEs in the bears. In vitro PBDE depletion assays using polar bear hepatic microsomes, wherein the rate of oxidative metabolism of PBDE congeners was very slow, supported the probability that accumulation from seals is the main source of OH-PBDEs in the bear tissues. Our findings demonstrated from ringed seal to polar bears that organohalogen biotransformation, bioaccumulation and/or biomagnification varied widely and depended on the contaminant in question. Our results show the increasing complexity of bioaccumulated and in some cases biomagnified, chlorinated and brominated contaminants and/or metabolites from the diet may be a contributing stress factor in the health of East Greenland polar bears.Environment international 09/2009; 35(8):1118-24. DOI:10.1016/j.envint.2009.07.006 · 5.66 Impact Factor
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