Novel and distinct metabolites identified following a single oral dose of α- Or γ-hexabromocyclododecane in mice

Environmental Science and Technology

Volumn 46, Issue 24, 2012, Pages 13494-13503

  Hakk, Heldur ^a   Szabo, David T ^b   Huwe, Janice ^a   Diliberto, Janet ^c   Birnbaum, Linda S ^d  

^a U S DEPARTMENT OF AGRICULTURE   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^c U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^d NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOSE TISSUE; BIOMONITORING STUDIES; HEXABROMOCYCLODODECANES; HYDROXYLATED METABOLITES; IN-VIVO; METABOLIC PRODUCTS; METABOLITE LEVEL; ORAL DOSE; POST-EXPOSURE; TOXICOKINETICS;

BIOMOLECULES; BODY FLUIDS; ISOMERS; MAMMALS; METABOLISM; STEREOCHEMISTRY; TISSUE;

METABOLITES;

ALPHA HEXABROMOCYCLODODECANE; FAT; GAMMA HEXABROMOCYCLODODECANE; HEXABROMOCYCLODODECANE; LIPID; PROTEIN; TISSUE EXTRACT; UNCLASSIFIED DRUG;

ADULT; BIOMONITORING; BLOOD; BRAIN; FECES; LIPID; METABOLISM; METABOLITE; PROTEIN; RODENT; TOXIC SUBSTANCE; TOXICITY; URINE;

ADIPOSE TISSUE; ANIMAL TISSUE; ARTICLE; BILE; BLOOD; BRAIN; COVALENT BOND; FECES; FEMALE; ISOMER; LIQUID CHROMATOGRAPHY; LIVER; MASS SPECTROMETRY; METABOLISM; METABOLITE; MOUSE; NONHUMAN; STEREOISOMERISM; URINE;

ADMINISTRATION, ORAL; ANIMALS; BILE; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, LIQUID; CHROMATOGRAPHY, THIN LAYER; FECES; FEMALE; HYDROCARBONS, BROMINATED; MASS SPECTROMETRY; MICE; MICE, INBRED C57BL; TISSUE DISTRIBUTION;

MUS;

EID: 84871270337     PISSN: 0013936X     EISSN: 15205851     Source Type: Journal    
DOI: 10.1021/es303209g     Document Type: Article

References (41)

1. Covaci, A.; Gerecke, A. C.; Law, R. J.; Voorspoels, S.; Kohler, M.; Heeb, N. V.; Leslie, H.; Alchin, C. R.; de Boer, J. Hexabromocyclododecanes (HBCDs) in the environment and humans: A review Environ. Sci. Technol. 2006, 40, 3679-3688
2. Janák, K.; Covaci, A.; Voorspoels, S.; Becher, G. Hexabromocyclododecane in marine species from the western Scheldt estuary: Diastereomer- and enantiomer-specific accumulation Environ. Sci. Technol. 2005, 39, 1987-1994
3. Tomy, G. T.; Pleskach, K.; Oswald, T.; Halldorson, T.; Helm, P. A.; MacInnes, G.; Marvin, C. H. Enantioselective bioaccumulation of hexabromocyclododecane and congener-specific accumulation of brominated diphenyl ethers in an eastern Canadian Arctic marine food web Environ. Sci. Technol. 2008, 42, 3634-3639
4. Hiebl, J.; Vetter, W. Detection of hexabromocyclododecane and its metabolite pentabromocyclododecane in chicken egg and fish from the official food control J. Agric. Food Chem. 2007, 55, 3319-3324
5. Arnot, J.; McCarty, L.; Armitage, J.; Toose-Reid, L.; Wania, F.; Cousins, I. An Evaluation of Hexabromocyclododecane (HBCD) for Persistent Organic Pollutant (POP) Properties and the Potential for Adverse Effects in the Environment; submitted to European Brominated Flame Retardant Industry Panel (EBFRIP), May 26, 2009.
6. Palace, V.; Park, B.; Pleskach, K.; Gemmill, B.; Tomy, G. Altered thyroxine metabolism in rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane (HBCD) Chemosphere 2010, 80, 165-169
7. Saegusa, Y.; Fujimoto, H.; Woo, G. H.; Inoue, K.; Takahashi, M.; Mitsumori, K.; Hirose, M.; Nishikawa, A.; Shibutani, M. Developmental toxicity of brominated flame retardants, tetrabromobisphenol A and 1,2,5,6,9,10 hexabromocyclododecane, in rat offspring after maternal exposure from mid-gestation through lactation Reprod. Toxicol. 2009, 28, 456-67
8. Roze, E.; Meijer, L.; Bakker, A.; Van Braeckel, K.; Sauer, P. J. J.; Bos, A. F. Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age Environ. Health Perspect. 2009, 117, 1953-1958
9. Eriksson, P.; Fischer, C.; Wallin, M.; Jakobsson, E.; Fredriksson, A. Impaired behaviour, learning and memory, in adult mice neonatally exposed to hexabromocyclododecane (HBCDD) Environ. Toxicol. Pharmacol. 2006, 21, 317-322
10. Cantón, R. F.; Peijnenburg, A. A. C. M.; Hoogenboom, R. L. A. P.; Piersma, A. H.; van den Ven, L. T. M.; van den Berg, M.; Heneweer, M. Subacute effects of hexabromocyclododecan (HBCD) on hepatic gene expression profiles in rats Technol. Appl. Pharmacol 2008, 231, 267-272
11. Helleday, T.; Tuominen, K. L.; Bergman, Å.; Jenssen, D. Brominated flame retardants induce intragenic recombination in mammalian cells Mutat. Res., Genet. Toxicol. Environ. Mutagen. 1999, 439, 137-147
12. Stockholm Convention on Persistent Organic Pollutants website. http://chm.pops.int/Home/tabid/2121/mctl/ViewDetails/EventModID/1007/EventID/ 225/xmid/6921/Default.aspx#; accessed 11/29/11.
13. Riddell, N.; Becker, B.; Chittim, B.; Emmerling, F.; Köppen, R.; Lough, A. Preparation and X-ray structural characterization of further stereoisomers of 1,2,5,6,9,10-hexabromocyclododecane Chemosphere 2011, 84, 900-907
14. Kuromochi, H.; Suzuki, S.; Kawamoto, K.; Osako, M.; Sakai, S. Measurements of water solubility and 1-octanol/water partition coefficient of three hexabromocyclododecane diastereoisomers. In BFR 2010 Proceedings, April 7-9, 2010, Kyoto, Japan; pp 102-105.
15. Heeb, N. V.; Schweizer, W. B.; Kohler, M.; Gerecke, A. C. Structure elucidation of hexabromocyclododecanes-A class of compounds with a complex stereochemistry Chemosphere 2005, 61, 65-73
16. Morris, S.; Allchin, C. R.; Zegers, B. N.; Haftka, J. J. H.; Boon, J. P.; Belpaire, C.; Leonards, P. E. G.; van Leeuwen, S. P. J.; de Boer, J. Distribution and fate of HBCD and TBBPA brominated flame retardants in North Sea estuaries and aquatic food webs Environ. Sci. Technol. 2004, 38, 5497-5504
17. Tomy, G. T.; Budakowski, W.; Halldorson, T.; Whittle, D. M.; Keir, M. J.; Marvin, C.; MacInnes, G.; Alaee, M. Biomagnification of the α- and γ-isomers of hexabromocyclododecane (HBCD) in a Lake Ontario food web Environ. Sci. Technol. 2004, 38, 2298-2303
18. Zegers, B. N.; Mets, A.; van Bommel, R.; Minkenberg, C.; Hamers, T.; Kamstra, J. H.; Pierce, G. J.; Boon, J. P. Levels of hexabromocyclododecane in harbor porpoises and common dolphins from western European seas, with evidence for stereoisomer-specific biotransformation by cytochrome P450 Environ. Sci. Technol. 2005, 39, 2095-2100
19. Esslinger, S.; Becker, R.; Maul, R.; Nehls, I. Hexabromocyclododecane enantiomers: Microsomal degradation and patterns of hydroxylated metabolites Environ. Sci. Technol. 2011, 45, 3938-3944
20. Brandsma, S. H.; van der Ven, L. T.; de Boer, J.; Leonards, P. E. Identification of hydroxylated metabolites of hexabromocyclododecane in wildlife and 28-days exposed Wistar rats Environ. Sci. Technol. 2009, 43, 6058-6063
21. Szabo, D. T.; Diliberto, J. J.; Hakk, H.; Huwe, J. K.; Birnbaum, L. S. Toxicokinetics of the flame retardant hexabromocyclododecane gamma: Effect of dose, timing, route, repeated exposure and metabolism Toxicol. Sci. 2010, 117, 282-293
22. Szabo, D. T.; Diliberto, J. J.; Hakk, H.; Huwe, J. K.; Birnbaum, L. S. Toxicokinetics of the flame retardant hexabromocyclododecane alpha: Effect of dose, timing, route, repeated exposure and metabolism Toxicol. Sci. 2011, 121, 234-244
23. Yu, C. C.; Atallah, Y. H. Pharmacokinetics of HBCD in rats. Velsicol Chemicals, unpublished paper translated into English; cited in Hakk, H.; Letcher, R. L. Metabolism in the toxicokinetics and fate of brominated flame retardants-A review. Environ. Int. 2003, 29, 801-828.
24. Dean, W. P.; Leong, B. K. J. Acute Toxicity Studies in Rabbits and Rats; International Research and Development Corp.; Sponsor: Velsicol Chemical Corporation; Study no. 163-499. EPA/OTS 86-900000266; 1977
25. Ryuich, A.; Katsumi, M.; Shutoko, M. Test on chemical substances used in household items. Studies on pharmacodynamics of hexabromocyclododecane. Department of Pharmacy, Hokkaido University Hospital, 1983; (unpublished paper translated into English).
26. Huhtala, S.; Schultz, E.; Nakari, T.; MacInnis, G.; Marvin, C.; Alaee, M. Analysis of hexabromocyclododecanes and their hydroxyl metabolites from in vitro and environmental samples by LCMSMS Organohalogen Cmpd. 2006, 68, 1987-1990
27. Szabo, D. T.; Diliberto, J. J.; Huwe, J. K.; Birnbaum, L. S. Differences in tissue distribution of HBCD alpha and gamma between adult and developing mice Toxicol. Sci. 2011, 123, 256-263
28. Larsen, G. L.; Bergman, Å.; Klasson-Wehler, E. A methylsulphonyl metabolite of a polychlorinated biphenyl can serve as a ligand for α2u-globulin in rat and major-urinary-protein in mice Xenobiotica 1990, 20, 1343-1352
29. Hakk, H.; Diliberto, J. J.; Birnbaum, L. S. The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2 (-/-) knockout and C57BL/6N parental strains of mice Toxicol. Appl. Pharmacol. 2009, 241, 119-126
30. Hakk, H.; Larsen, G.; Bergman, Å.; Örn, U. Binding of brominated diphenyl ethers to male rat carrier proteins Xenobiotica 2002, 32, 1079-1092
31. Perry, J. J. Microbial metabolism of cyclic alkanes. In Petroleum Microbiology; Atlas, R. M., Ed.; Macmillan: New York, 1994; pp 61-98.
32. Kostichka, K.; Thomas, S. M.; Gibson, K. J.; Nagarajan, V.; Cheng, Q. Cloning and characterization of a gene cluster for cyclododecanone oxidation in Rhodococcus ruber SC1 J. Bacteriol. 2001, 183, 6478-6486
33. Fraas, S.; Steinbach, A. K.; Tabbert, A.; Harder, J.; Ermler, U.; Tittmann, K.; Meyer, A.; Kroneck, P. M. H. Cyclodexane-1,2-dione hydrloase: A new tool to degrade alicyclic compounds J. Mol. Catal. B: Enzym. 2009, 61, 47-49
34. Benedict, R. T.; Stapleton, H. M.; Letcher, R. J.; Mitchelmore, C. L. Debromination of polybrominated diphenyl ether-99 (BDE-99) in carp (Cyprinus carpio) microflora and microsomes Chemosphere 2007, 69, 987-993
35. Tang, A. H.; Tu, C. P. Biochemical characterization of Drosophila glutathione S-transferases D1 and D21 J. Biol. Chem. 1994, 269, 27876-27884
36. Stapleton, H. M.; Brazil, B.; Holbrook, R. D.; Mitchelmore, C. L.; Benedict, R.; Konstantinov, A.; Potter, D. In vivo and in vitro debromination of decabromodiphenyl ether (BDE 209) by juvenile rainbow trout and common carp Environ. Sci. Technol. 2006, 40, 4653-4658
37. Kuhn, E. P.; Suflita, J. M. Dehalogenation of pesticides by anaerobic microorganisms in soils and groundwater-a review. In Reactions and Movement of Organic Chemicals in Soils; Sawheny, B. L.; Brown, K., Eds.; Soil Science Society of America: Madison, WI, 1989; pp 111-180.
38. Vogel, T. M.; Criddle, C. S.; McCarty, P. L. Transformations of halogenated aliphatic compounds Environ. Sci. Technol. 1987, 21, 722-736
39. Szabo, D. T.; Richardson, V. M.; Ross, D. G.; Diliberto, J. J.; Kodavanti, P. R. S.; Birnbaum, L. S. Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat pups Toxicol. Sci. 2009, 107, 27-39
40. Harrad, S.; Abdallah, M. A-E.; Covaci, A. Causes of variability in concentrations and diastereomer patterns of hexabromocyclododecanes in indoor dust Environ. Int. 2009, 35, 573-579
41. Köppen, R.; Becker, R.; Jung, C.; Nehls, I. On the thermally induced isomerisation of hexabromocyclododecane stereoisomers Chemosphere 2008, 71, 656-662