Abstract
Until recently, pentabromodiphenyl (PentaBDE) and decabromodiphenyl (DecaBDE) ethers were commonly used as flame retardants in a wide array of products, mostly in the production of plastics utilized in the electric, electronic and textile industries. The aim of this study was to compare the toxicity of PentaBDE and DecaBDE after their repeated (7–28 days) intragastric administration to rats. The compounds were given at doses of 2, 8, 40 or 200 mg/kg/day (PentaBDE) and 10, 100 or 1,000 mg/kg/day (DecaBDE). The repeated administration of PentaBDE disturbed redox homeostasis, which was manifested by lower total antioxidant status and increased activity of glutathione reductase in serum and higher concentrations of glutathione reduced and malondialdehyde in the liver. The occurrence of these effects was not observed after DecaBDE administration. The results of histopathological examination showed fatty degeneration after administration of the highest dose of PentaBDE. The repeated administration of PentaBDE also caused the increase in relative liver mass, dose-dependent increase in the activity of CYP 1A (EROD) and CYP 2B (PROD), 7–12- and 2–8-fold, respectively, as well as enhanced level of CYP 1A1 (5–30-fold) and CYP 4A (2–4.5-fold). The administration of DecaBDE induced much less pronounced changes: a maximum 2.8-fold increase in the activity of CYP 1A, a twofold increase in CYP 2B, and no alterations in other parameters under study. Contrary to DecaBDE, PentaBDE disturbed redox homeostasis, and induced liver microsomal enzymes. Fatty degeneration in liver caused by this compound was also found.
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References
Barouki R, Morel Y (2001) Repression of cytochrome P450 1A1 gene expression by oxidative stress: mechanisms and biological implications. Biochem Pharmacol 61:511–516
Bartosz G (2006) A second face of oxygen. PWN, Warsaw (in Polish)
BSEF (Bromine Science and Environmental Forum). (2000) An introduction to bromine flame retardants
BSEF (Bromine Science and Environmental Forum). (2003) Major brominated flame retardants volume estimates total market demand by region in 2001, Brussels
Carlson GP (1980a) Introduction of xenobiotic metabolism in rats by brominated diphenyl ethers administered for 90 days. Toxicol Lett 6:207–215
Carlson GP (1980b) Introduction of xenobiotic metabolism in rats by short-term administration of brominated diphenyl ethers. Toxicol Lett 5:19–25
Choi J-W, Fujimaki S, Kitamura K, Hashimoto S, Ito H, Suzuki N, Sakai S, Morita M (2002) Polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs) and diphenyl ethers (PBDEs) in Japanese human adipose tissue. Organohalogen Comp 58:169–171
Christiansson A, Hovander L, Athanassiadis I, Rignell-Hydbom A, Jakobsson K, Bergman A (2008) Swedish researchers had increased PBDE-levels in serum after intercontinental flights—an exploratory study. Organohalogen Comp 70:1075–1078
Council Regulation (1993) EEC/793/93 of 23 March 1993, on the evaluation and control of the risk of existing substances
Darnerud PO, Thuvander A (1998) Studies on immunological effects of polybrominated diphenyl ether and polychlorinated biphenyl exposures in rats and mice. Organohalogen Comp 35:414–418
Darnerud PO, Eriksen GS, Johannesson T, Larsen PB, Viluksela M (2001) Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. Environ Health Persp 109(1):49–68
Darnerud PO, Aune M, Atuma S, Becker W, Bjerseliu R, Cnattingius S, Glynn A (2002) Time trend of polybrominated diphenyl ether (PBDE) levels in breast milk from Uppsala, Sweden, 1996–2001. Organohalogen Comp 58:233–236
Directive 2003/11/EC of the European parliament and of the council of 6 february 2003 amending for the 24th time council directive 76/769/EEC relating to restrictions on the marketing and use of certain dangerous substances and preparations (pentabromodiphenyl ether and octabromodiphenyl ether)
Dixon JB, Bhathal PS, O’Brien PE (2001) Nonalkoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121(1):91–100
EHC (Environmental Health Criteria). 162 (1994) Brominated diphenyl ethers. International Programme on Chemical Safety (IPCS), WHO, Geneva
EU (European Union Risk Assessment Report). (2000) Diphenyl ether, pentabromo derivative (pentabromodiphenyl ether). CAS No.: 32534-81-9, EINCES No.: 251-084-2. Risk assessment, United Kingdom
Fowles JR, Fairbrother A, Baecher-Steppan L, Kerkvliet NL (1994) Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6 J mice. Toxicology 86:49–61
Great Lakes Chemical Corporation (1976) Twenty-eight day toxicity study of pentabromodiphenyl ether in rats. Unpublished report, International Research and Development Corporation, Report no: 274-023 (cit. in: EU 2000)
Great Lakes Chemical Corporation (1984) 90-day dietary study in rats with pentabromodiphenyl oxide (DE-71) final report. Unpublished report, WIL Research Laboratories, project no: WIL-12011 (cit. in: EU 2000)
Guengerich PF (1994) Analysis and characterization of enzymes. In: Principles and Methods of Toxicology, 3rd ed. edn. Raven Press Ltd., New York
Guengerich PF (2000) Metabolism of chemical carcinogens. Carcinogenesis 21:345–351
Jones-Otazo HA, Clarke JP, Diamond ML, Archbold JA, Ferguson G, Harner T, Richardson GM, Ryan JJ, Wilford B (2005) Is house dust the missing exposure pathway for PBDEs? An analysis of the urban fate and human exposure to PBDEs. Environ Sci Technol 39:5121–5130
KEMl Report (1994) Risk assessment of polybrominated diphenyl ethers. No. 9/94. The Swedish National Chemicals Inspectorate
Kostka G, Palut D, Wiadrowska B (1997) Effect of permethrin and DDT on the activity of cytochrome P-450 1A and 2B molecular forms in rat liver. Rocz PZH 48(3):229–237 (in Polish)
Laemmli K, Favre M (1973) Maturation of the head of bacteriophage T4 DNA packing events. J Mol Biol 80:573–599
Law RJ, Allchin CR, deBoer J, Covaci A, Herzke D, Lepom P, Morris S, Troczynski J, de Wit CA (2006) Levels and trends of brominated flame retardants in the European environment. Chemosphere 64:187–208
Lorber M (2008) Exposure of Americans to polybrominated diphenyl ethers. J Exp Sci Environ Epidem 18:2–19
Lowry DH, Rosenbrough NJ, Farr RJ, Randal RJ (1951) Protein determination with the Folin phenol reagent. J Biol Chem 193:265–275
Lubet RA, Nims RW, Mayer RT, Cameron JW, Schechtman LW (1985) Measurement of cytochrome P-450 dependent dealkylation of alkoxophenoxazones in hepatic S9 s and hepatocyte homogenates: effects of dicumarol. Mutat Res 142(2):127–131
Lubet RA, Jones CR, Stockus DL, Fox SD, Nims RW (1991) Induction of cytochrome P450 and other drug metabolizing enzymes in rat liver following dietary exposure to Aroclor 1254. Toxicol Appl Pharmacol 108:355–365
Mercado-Feliciano M, Bigsby RM (2008) The polybrominated diphenyl ether mixture DE-71 is mildly estrogenic. Environ Health Persp 116(5):605–611
Muir T, Alaee M (2002) Costs and benefits of brominated flame retardants (PFRs) and alternatives. Organohalogen Comp 58:237–240
Omura T, Sato R (1964) The carbon monoxide-binding pigment of microsomes I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378
Otto S, Battacharya K, Jefcoate C (1992) Polycyclic aromatic hydrocarbon metabolism in rat adrenal ovary, and testis microsomes is catalyzed by the same novel cytochrome P-450 (P450RAP). Endocrinology 131(6):3067–3076
Pacyniak EK, Cheng X, Cunnungham ML, Crofton K, Klaassen CD, Guo GL (2007) The flame retandants, polybrominated diphenyl ethers, are pregnane X receptor activators. Toxicol Sci 91(1):94–102
Palut D, Kostka G, Wiadrowska B, Bańkowski R (2002) The effect of Diclofop on same drug metabolizing enzymes in the liver of Wistar rats. Roczn PZH 53(1):1–9 (in Polish)
Roach A, Symons R, Stevenson G, Manning T (2008) Levels of PBDEs in sediment fish and sea eagles from Sydney Harbour, Australia: spatial patterns and profiles. Organohalogen Comp 70:114–117
Safe S (2001) Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett 120:1–7
Sanders JM, Burka LT, Smith CS, Black W, James R, Cunningham ML (2005) Differential expression of CYP 1A, 2B, and 3A genes in the F344 rat following exposure to a polybrominated diphenyl ether mixture or individual components. Toxicol Sci 88(1):127–133
Schecter AJ, Päpke O, Harris TR, Tung KC, Musumba A, Olson J, Birnbaum L (2006) Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey of US food and estimated PBDE dietary intake by age and sex. Environ Health Persp 114(10):1515–1520
Schecter AJ, Harris TR, Shah NC, Musumba A, Päpke O (2008) Brominated flame retardants in US food. Mol Nutr Food Res 52:266–272
Sedlak T, Lindsay RH (1968) Estimation of total protein bound and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Bioch 25:192–205
Sjödin A, Thuresson K, Hagmar L, Klasson-Wehler E, Bergman A (1999) Occupational exposure to polybrominated diphenyl ethers at dismantling of electronics–Ambient air and human serum analysis. Organohalogen Comp 43:447–451
Sjödin A, Patterson DG, Bergman A (2003) A review on human exposure to brominated flame retardants–particularly polybrominated diphenyl ethers. Environ Int 29:829–839
Soderstrom G, Marklund S (2002) Fire of a flame retarded TV. Organohalogen Comp 41:269–272
Takigami H, Suzuki G, Hirai Y, Ishikawa Y, Sunami M, Sakai S (2008) Flame retardants in indoor air and dust of a hotel in Japan. Organohalogen Comp 70:186–189
Uchiyama M, Mihara M (1978) Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278
Van der Ven LTM, van de Kuil T, Leonards PEG, Slob W, Canton RF, Germer S, Visser TJ, Litens S, Hakansson H, Schenk D, ven den Berg M, Piersma AH, Vos JG, Opperhuizen A (2008a) A 28-day oral dose toxicity study in Wistar rats enhanced to detect endocrine effects of decabromodiphenyl ether (decaBDE). Toxicol Lett 179:6–14
Van der Ven LTM, van de Kuil T, Verhoef A, Leonards PEG, Slob W, Canton RF, Germer S, Hamers T, Visser TJ, Litens S, Hakansson H, Fery Y, Schenk D, ven den Berg M, Piersma AH, Vos JG (2008b) A 28-day oral dose toxicity study enhanced to detect endocrine effects of a purified technical pentabromodiphenyl ether (pentaBDE) mixture in Wistar rats. Toxicology 245:109–122
von Meyerinck L, Hufnagel B, Schmoldt A, Benthe HF (1990) Induction of rat liver microsomal cytochrome P450 by the pentabromo diphenyl ether Bromkal 70 and half-lives of it’s components in the adipose tissue. Toxicology 61:259–274
Vorkamp K, Frederiksen M, Thomsen M (2008) Polybrominated diphenyl ethers in the indoor environment–preliminary results from an exposure study in Denmark. Organohalogen Comp 70:859–862
Watanabe M, Kajiwara N, Takigami H, Noma Y, Kida A (2008) Formation and degradation behaviors of brominated organic compounds and PCDD/Fs during thermal treatment of waste printed circuit boards. Organohalogen Comp 70:78–81
Williams SN, Dunham E, Bradfield CA (2005) Induction of cytochrome P450 enzymes. In: Ortiz de Montellano PR (ed) (red.) Cytochrome P450: structure mechanism and biochemistry. Kluwer Academic, New York, Boston, Dordrecht, London, Moscow, pp 323–346
Zangar RC, Davydov DR, Verma S (2004) Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199:316–331
Zhou T, Ross DG, DeVito MJ, Crofton KM (2001) Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats. Toxicol Sci 61:76–82
Zhou T, Taylor MM, DeVito MJ, Crofton KM (2002) Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruption. Toxicol Sci 66:105–116
Zuurbier M, Leijs M, Schoeters G, Tusscher GT, Koppe JG (2006) Children’s exposure to polybrominated diphenyl ethers. Acta Pedriat 95(Suppl 453):65–70
Acknowledgments
The studies were funded by the State Committee for Scientific Research (Grant No. 2 POSF 006 30) and Join Project (No 502-13-482) of the Medical University of Lodz.
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Bruchajzer, E., Frydrych, B., Sporny, S. et al. Toxicity of penta- and decabromodiphenyl ethers after repeated administration to rats: a comparative study. Arch Toxicol 84, 287–299 (2010). https://doi.org/10.1007/s00204-009-0495-y
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DOI: https://doi.org/10.1007/s00204-009-0495-y