Toxicokinetics of the flame retardant hexabromocyclododecane alpha: Effect of dose, timing, route, repeated exposure, and metabolism

Toxicological Sciences

Volumn 121, Issue 2, 2011, Pages 234-244

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

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^c U S DEPARTMENT OF AGRICULTURE   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Biotransformation; Brominated flame retardant; Endocrine disruptors; Hexabromocyclododecane; Lipophilic; Metabolism; Mixture; Persistent organic pollutants; Risk assessment; Toxicokinetics

Indexed keywords

FLAME RETARDANT; HEXABROMOCYCLODODECANE ALPHA; UNCLASSIFIED DRUG;

ABSORPTION; ANIMAL EXPERIMENT; ARTICLE; BIOTRANSFORMATION; DOSE RESPONSE; EXCRETION; FEMALE; HALF LIFE TIME; ISOMERIZATION; LIPOPHILICITY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLISM; MOUSE; NONHUMAN; RADIOACTIVITY; STEREOCHEMISTRY; THIN LAYER CHROMATOGRAPHY; TISSUE DISTRIBUTION; TOXICOKINETICS;

MAMMALIA; MUS;

EID: 79957878159     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfr059     Document Type: Article

References (38)

1. Arsenault, G., Chittim, B., McAlees, A., and McCrindle, R. (2007). Nuclear magnetic resonance spectral characterization and semi-empirical calculations of conformations of α- and γ-1,2,5,6,9,10-hexabromocyclododecane. Chemosphere 67, 1684-1694.
2. Chengelis, C. (2001). In A 90-day oral (gavage) toxicity study of HBCD in rats WIL-186012. 1527 p. WIL Research Laboratories, Inc., Ashland, OH.
3. Covaci, A., Gerecke, A. C., Law, R. J., Voorspoel, S., Kohler, M., Heeb, N. V., Leslie, H., Allchin, C. R., and de Boer, J. (2006). Hexabromocyclododecanes (HBCDs) in the environment and humans: a review. Environ. Sci. Technol 40, 3679-3688.
4. de Wit, C. A., Herzke, D., and Vorkamp, K. (2010). Brominated flame retardants in the Arctic environment-trends and new candidates. Sci. Total Environ 08, 2885-2918.
5. Diliberto, J. J., Burgin, D. E., and Birnbaum, L. S. (1999). Effects of CYP1A2 on disposition of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,2prime;,4,4prime;,5,5prime;-hexachlorobiphenyl in CYP1A2 knockout and parental (C57BL/6N and 129/Sv) strains of mice. Toxicol. Appl. harmacol 159, 52-64.
6. Eljarrat, E., Guerra, P., Martínez, E., Farré, M., Alvarez, J. G., López-Teijón, M., and Barceló, D. (2009). Hexabromocyclododecane in human breast milk: levels and enantiomeric patterns. Environ. Sci. Technol 43, 1940-1946.
7. Eriksson, P., Fischer, C., Wallin, M., Jakobsson, E., and Fredriksson, A. (2006). Impaired behaviour, learning and memory in adult mice neonatally exposed to hexabromocyclododecane (HBCDD). Environ. Toxicol. Pharmacol 21, 317-322.
8. Hakk, H., Diliberto, J. J., and Birnbaum, L. S. (2009a). 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 241, 119-126.
9. Hakk, H., Huwe, J. K., and Larsen, G. L. (2009b). Absorption, distribution, metabolism and excretion (ADME) study with 2,2prime;,4,4prime;,5,6prime;-hexabromodiphenyl ether (BDE-154) in male Sprague-Dawley rats. Xenobiotica 39, 46-56.
10. Heeb, N. V., Schweizer, W. B., Kohler, M., and Gerecke, A. C. (2005). Structure elucidation of hexabromocyclododecanes-a class of compounds with a omplex stereochemistry. Chemosphere 61, 65-73.
11. Heeb, N. V., Schweizer, W. B., Mattrel, P., Haag, R., Gerecke, A. C., Schmid, P., Zennegg, M., and Vonmont, H. (2008). Regio- and steroeselective isomerization of hexabromocyclododecanes (HBCDs): kinetics and mechanism of γ- to α-HBCD isomerization. Chemosphere 73, 1201-1210.
12. Hermanson, M. H., Isaksson, E., Forsström, S., Teixeira, C., Muir, D. C., Pohjola, V. A., and van de Wal, R. S. (2010). Deposition history of brominated flame retardant compounds in an ice core from Holtedahlfonna, Svalbard, Norway. Environ. Sci. Technol 44, 7405-7410.
13. International Life Sciences Institute (ILSI). (1994). ILSI Physiological Parameter Values for PBPK Models. ILSI, Washington, DC.
14. Janák, K., Covaci, A., Voorspoels, S., and Becher, G. (2005). Hexabromocyclododecane in marine species from the Western Scheldt Estuary: diastereoisomer- and enantiomer-specific accumulation. Environ. Sci. Technol 39, 1987-1994.
15. Kakimoto, K., Akutsu, K., Konishi, Y., and Tanaka, Y. (2008). Time trend of hexabromocyclododecane in the breast milk of Japanese women. Chemosphere 71, 1110-1114.
16. Law, K., Palace, V. C., Halldorson, T., Danell, R., Wautier, K., Evans, B., Alaee, M., and Marvin, C. (2006). Dietary accumulation of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss) I bioaccumulation parameters and evidence of bioisomerization. Environ. oxicol. Chem 25, 1757-1761.
17. Lilienthal, H., van der Ven, L. T., Piersma, A. H., and Vos, J. G. (2009). Effects of the brominated flame retardant hexabromocyclododecane (HBCD) on dopamine-dependent behavior and brainstem auditory evoked potentials in a one-generation reproduction study in Wistar rats. Toxicol. Lett 185, 63-72.
18. Lioy, P. J., Edwards, R. D., Freeman, N., Gurunathan, S., Pellizzari, E., Adgate, J. L., Quackenboss, J., and Sexton, K. (2000). House dust levels of selected insecticides and a herbicide measured by the EL and LWW samplers and comparisons to hand rinses and urine metabolites. J. Expo. Anal. Environ. Epidemiol 10, 27-340.
19. Meijer, L., Weiss, L., Van Velzen, M., Brouwer, A., Bergman, A., and Sauer, P. J. (2008). Serum concentrations of neutral and phenolic organohalogens in pregnant women and some of their infants in The Netherlands. Environ. Sci. Technol 42, 3428-3433.
20. Peck, A. M., Pugh, R. S., Moors, A., Ellisor, M. B., Porter, B. J., Becker, P. R., and Kucklick, J. R. (2008). Hexabromocyclododecane in white-sided dolphins: temporal trend and stereoisomer distribution in tissues. Environ. Sci. Technol 42, 650-655.
21. Pulkrabová, J., Hrádková, P., Hajslová, J., Poustka, J., Nápravníková, M., and Polácek, V. (2009). Brominated flame retardants and other organochlorine pollutants in human adipose tissue samples from the Czech Republic. Environ. Int 35, 63-68.
22. Roosens, L., Abdallah, M. A., Harrad, S., Neels, H., and Covaci, A. (2009). Exposure to hexabromocyclododecanes (HBCDs) via dust ingestion, but not diet, correlates with concentrations in human serum: preliminary results. Environ. Health Perspect 117, 1707-1712.
23. Ryan, J. J., Wainman, B. C., Schecter, A.,Moisey, J., Kosarac, I., and Sun, W. F. (2006). Trends of the brominated flame retardants, PBDEs and HBCD, in human milks from North America. Organohalogen Compounds 68, 778-781.
24. Schecter, A., Haffner, D., Colacino, J., Patel, K., Päpke, O., Opel, M., and Birnbaum, L. (2010). Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples. Environ. Health Perspect 118, 357-362.
25. Sellström, U., Bignert, A., Kierkegaard, A., Häggberg, L., de Wit, C. A., Olsson, M., and Jansson, B. (2003). Temporal trend studies on tetra- and pentabrominated diphenyl ethers and hexabromocyclododecane in guillemot egg from the Baltic Sea. Environ. Sci. Technol 37, 5496-5501.
26. Staskal, D. F., Diliberto, J. J., DeVito, M. J., and Birnbaum, L. S. (2005). Toxicokinetics of BDE 47 in female mice: effect of dose, route of exposure, and ime. Toxicol. Sci 83, 215-223.
27. Szabo, D. T., Diliberto, J. J., Hakk, H., Huwe, J., and Birnbaum, L. S. (2010). Toxicokinetics of the flame retardant hexabromocyclododecane gamma: effect of dose, timing, route, repeated exposure and metabolism. Toxicol. Sci 117, 282-293.
28. Thomsen, C., Molander, P., Daae, H. L., Janák, K., Froshaug, M., Liane, V. H., Thorud, S., Becher, G., and Dybing, E. (2007). Occupational exposure to hexabromocyclododecane at an industrial plant. Environ. Sci. Technol 41, 5210-5216.
29. Tomy, G. T., Budakowski, W., Halldorson, T., Whittle, D. M., Keir, M. J., Marvin, C., MacInnis, G., and Alaee, M. (2004). Biomagnification of alphaand gamma- hexabromocyclododecane isomers in a lake Ontario food web. Environ. Sci. Technol 38, 2298-2303.
30. UK Food Standards Agency. (2006). Brominated chemicals in farmed and wild fish and shellfish and fish oil dietary supplements. Available at: http://www.food.gov.uk/multimedia/pdfs/fsis0406.pdf. Accessed November 1, 2010. Accessed November 1, 2010.
31. van der Ven, L. T., van de Kuil, T., Leonards, P. E., Slob, W., Lilienthal, H., Litens, S., Herlin, M., Håkansson, H., Cantón, R. F., van den Berg, M., et al. (2009). Endocrine effects of hexabromocyclododecane (HBCD) in a onegeneration reproduction study in Wistar rats. Toxicol. Lett 185, 51-62.
32. van der Ven, L. T., Verhoef, A., van de Kuil, T., Slob, W., Leonards, P. E., Visser, T. J., Hamers, T., Herlin, M., Håkansson, H., Olausson, H., et al. (2006). A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in Wistar rats. Toxicol. Sci 94, 281-292.
33. Weiss, J., Meijer, L., Sauer, P., Linderholm, L., Athanasiadis, I., and Bergman, A. (2004). PBDE and HBCD levels in blood from Dutch mothers and infants. analysis of a Dutch Groningen infant cohort. Organohalogen Compounds 66, 2677-2682.
34. Wilford, B. H., Shoeib, M., Harner, T., Zhu, J., and Jones, K. C. (2005). Polybrominated diphenyl ethers in indoor dust in Ottawa, Canada: implications for sources and exposure. Environ. Sci. Technol 39, 7027-7035.
35. Wu, F., and Takaro, T. K. (2007). Childhood asthma and environmental interventions. Environ. Health Perspect 115, 971-975.
36. Xian, Q., Ramu, K., Isobe, T., Sudaryanto, A., Liu, X., Gao, Z., Takahashi, S., Yu, H., and Tanabe, S. (2008). Levels and body distribution of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in freshwater fishes from the Yangtze River, China. Chemosphere 71, 268-276.
37. Yu, C. C., and Atallah, Y. H. (1980). In Pharmacokinetics of HBCD in Rats; Report. Velsicol Chemical Corporation, Rosemont, IL.
38. Zegers, B. N., Mets, A., van Bommel, R., Minkenberg, C., Hamers, T., Kamstra, J. H., Pierce, G. J., and Boon, J. P. (2005). Levels of hexabromocyclododecane in harbor porpoises and common dolphins from Western European Seas, with evidence for stereoisomerspecific biotransformation by Cyt-450. Environ. Sci. Technol 39, 2095-2100.