Toxicological effects of perfluorooctanoic acid in rats

랫드에서 Perfluorooctanoic Acid의 독성에 관한 연구

  • Kim, Yong-Hoon (College of Veterinary Medicine, Chungnam National University) ;
  • Cho, Eun-Sang (College of Veterinary Medicine, Chungnam National University) ;
  • Kim, A-Young (College of Veterinary Medicine, Chungnam National University) ;
  • Kim, Sung-Hwan (College of Veterinary Medicine, Chungnam National University) ;
  • Park, Min-Sik (College of Veterinary Medicine, Chungnam National University) ;
  • Cho, Sung-Whan (College of Veterinary Medicine, Chungnam National University) ;
  • Ryu, Si-Yun (College of Veterinary Medicine, Chungnam National University) ;
  • Jung, Joo-Young (College of Veterinary Medicine, Chungnam National University) ;
  • Son, Hwa-Young (College of Veterinary Medicine, Chungnam National University)
  • 김용훈 (충남대학교 수의과대학) ;
  • 조은상 (충남대학교 수의과대학) ;
  • 김아영 (충남대학교 수의과대학) ;
  • 김성환 (충남대학교 수의과대학) ;
  • 박민식 (충남대학교 수의과대학) ;
  • 조성환 (충남대학교 수의과대학) ;
  • 류시윤 (충남대학교 수의과대학) ;
  • 정주영 (충남대학교 수의과대학) ;
  • 손화영 (충남대학교 수의과대학)
  • Accepted : 2008.07.09
  • Published : 2008.12.01

Abstract

Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, is persistent organic pollutants widely spread throughout the environment and human population. But little is known about the adverse biological effects of the PFOA. In the present study, the toxicological effects of PFOA were investigated in rats. Sprague-Dawley rats (N = 10 in each group) were orally administered with PFOA in drinking water for 4 weeks (0, 100, 200, or 400 ppm in male, and 0, 200, 400, or 800 ppm in female). Three female rats given 800 ppm died during the study. PFOA treatment decreased the body weight gain and increased the liver weights in both genders. Serum biochemical investigations revealed significant increases in the aspartate aminotransferase, alanine transaminase, alkaline phosphatase, blood urea nitrogen, total cholesterol, and total bilirubin in male but in female. Serum estradiol (E2) levels were increased in all treated rats. Histopathologically, hepatocellular hypertrophy around central vein was noted in the liver of treated rats. No significant histopathological changes were noted in other organs. In conclusion, PFOA induced toxicological changes in the liver and increased serum E2 level which was not related to histopathological changes of endocrine and reproductive system.

Keywords

References

  1. 유승석, 김지영. 불소수지 코팅 주방기구의 안전성 평가. 식품의약품안전청연구보고서 2004, 8, 2276-2277
  2. Abbott BD, Wolf CJ, Schmid JE, Das KP, Zehr RD, Helfant L, Nakayama S, Lindstrom AB. Strynar MJ, Lau C. Perfluorooctanoic acid induced developmental toxicity in the mouse is dependent on expression of peroxisome proliferator activated receptor-alpha. Toxicol Sci 2007, 98, 571-581 https://doi.org/10.1093/toxsci/kfm110
  3. Aukawa A, Toyoshima M, Fujimiya M, Haralia K, Atlkl K, lunue K, Koizumi A. Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus. Int J Mol Med 2007, 19, 733- 739
  4. Ashby J, Brady A, Ekombe CR, Elliott BM, Ishmael J, Odum J, Thgwood JD, Kettle S, Purchase IFH. Mechanistically-based human hazard assessment of peroxisome proliferator-induccd hepatocarcinogenesis. Hum Exp Toxicol 1994, 13 (Suppl), S1-117 https://doi.org/10.1177/0960327194013001011
  5. Begley TH, White K, Houigfort P, Twaroski ML, Neches R, Walker RA. Perfluorochemicals: poIential sources of and migration from food packaging. Food Addit Contam 2005, 22, 1023-1031 https://doi.org/10.1080/02652030500183474
  6. Benninghoff AD, Field JA, Williams DE. Assessment of the estrogen activity of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and other structurally diverse perfluorinated chemicals in rainbow trout. Toxicologist 2007, 96, 110
  7. Biegel LB, Hurtt ME, Frame SR, Q'Connor JC, Cook JC. Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol Sci 2001, 60, 44-55 https://doi.org/10.1093/toxsci/60.1.44
  8. Biegei LB, Liu RCM, Hurtt ME, Cook Jc. Effects of ammonium perfluorooctanoate on Leydig cell function: In vitro, in vivo, and ex vivo studies. Toxicol Appl Pharmacol 1995, 134, 18-25 https://doi.org/10.1006/taap.1995.1164
  9. Butenhoff JL., Olsen GW, Pfahles-Hutchens A. The applicability of biomonitoring data for perllllOl'OOCtanesu lfonale to the environmental public health continuum. Environ Health Perspect 2006, 114, 1776-1782
  10. Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Tully JS, Needham LL. Serum concentrations of 11 polyfiuoroalkyl compounds in the U.S. population: data from the national health and nutrition examination survey (NHANES). Environ Sci Technol 2007, 41 , 2237-2242 https://doi.org/10.1021/es062686m
  11. Fei C, McLaughlin JK, Tarone RE, Olsen J Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect 2007, 115, 1677-1682 https://doi.org/10.1289/ehp.10506
  12. Ishibashi H, Ishida H, Matsuoka M, Tominaga N, Arizono K. Estrogenic effects of fluorotelomer alcohols for human estrogen receptor isoforms alpha and beta in virro. Biol Pharm Bull 2007, 30, 1358-1359 https://doi.org/10.1248/bpb.30.1358
  13. Kannan K, Corsolini S, Falandysn J, FiIlmann G, Kumar KS, Loganathan BG, Mohd MA, Olivero J, Van Wouwe N, Yang JH, Aldoust KM. Perfluorooctane sulfonate and related fluorochemicals in human blood from several countries. Environ Sci Technol 2004, 38, 4489-4495 https://doi.org/10.1021/es0493446
  14. Karrman A, Ericson I, van Ravel B, Darnerud PO, Aune M, Glynn A, Lignell S, Lindstrom G. Exposure of perfluorinated chemicals through lactation: levels of matched human milk and serum and a temporal trend, 1996-2004, in Sweden. Environ Health Perspect 2007, 115, 226-230 https://doi.org/10.1289/ehp.9491
  15. Kennedy GL Jr, Butenhoff JL, Olsen GW, O'Connor JC, Seacat AM, Perkins RG, Biegel LB, Murphy SR, Farrar DG. The toxicology of perfluorooctanoate. Crit Rev Toxicol 2004, 34, 351-384 https://doi.org/10.1080/10408440490464705
  16. kudo N, Katakura M, Sato Y, Kawashima Y. Sex hormone-regulated renal transport of perfluorooctanoic acid. Chem Biol Interact 2002, 139, 301-316 https://doi.org/10.1016/S0009-2797(02)00006-6
  17. Liu RC, Hahn C, Hurtt ME. The direct effect of hepatic peroxisome proliferators on rat Leydig cell function in vitro. Fundam Appl Toxicol 1996, 30,102-108 https://doi.org/10.1006/faat.1996.0047
  18. Liu RC, Hurtt ME, Cook JC, Biegel LB. Effect of the peroxisome proliferator, ammonium perfluorooctanoate (C8), on hepatic aromatase activity in adult male Crl:CD BR (CD) rats. Fundam Appl Toxicol 1996, 30, 220-228 https://doi.org/10.1006/faat.1996.0059
  19. Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS, Kidwell WR. Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: Estrogen induction of TGF alpha production. Mol Endocrinol 1987, 1, 683-692 https://doi.org/10.1210/mend-1-10-683
  20. Loos R, Locoro G, Huber T, WoUgast J, Chrisloph EH, de Jager A, Manfred Gawlik B, Hanke G, Umlaur G, Zaktivar JM. Analysis of pertluorooctanoate (PFOA) and other perfluorinated com!X'unds (PFCs) in the River Po watershed in N-ltaly. Chemosphere 2008, 71, 306-313 https://doi.org/10.1016/j.chemosphere.2007.09.022
  21. Maras M, Vanparys C, Muylle F, Robbens J, Berger U, Barber JL, Blust R, De Coen W. Estrogen-like propenies of fluorotelomer alcohols as revealed by mcf-7 breast cancer cell proliferation. Environ Health Perspect 2006, 114, 100-105 https://doi.org/10.1289/ehp.8149
  22. Olson er, Andersen ME. The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. Toxicol Appl Pharmacol 1983, 70, 362-372 https://doi.org/10.1016/0041-008X(83)90154-0
  23. Panaretakis T, Shabalina IG, Grander D, Shoshan MC, DePierre JW. Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid. Toxicol Appl Pharmacol 2001, 173, 56-64 https://doi.org/10.1006/taap.2001.9159
  24. Peden-Adams MM, EuDaly JG, Dabra S, EuDaly A, Heesemann L, Smythe J, Keil DE. Suppression of humoral immunity following exposure to the perfluorinated insecticide sulfluramid. J Toxicol Environ Health A 2007, 70, 1130-1141 https://doi.org/10.1080/15287390701252733
  25. Perkins RG. Investigation of ammonium perfluorooctanoate effect on hormone levels and peroxisomal proliferation in the rat. Toxicologist 1992, 12, 38
  26. Perkins RG, Butenhoff JL, Kennedy GL Jr, Palazzolo MJ. 13-week dietary toxicity study of ammonium perfluorooctanoate (APFO) in male rats. Drug Chem Toxicol 2004, 27, 361-378 https://doi.org/10.1081/DCT-200039773
  27. Takaes ML. Abbott BD. Activation of mouse and human peroxisome proliferator-activated receptors (alpha, beta/delta, gamma) by perfluorooctanoic acid and perfluorooctane sulfonate. Toxicol Sci 2007, 95, 108-117 https://doi.org/10.1093/toxsci/kfl135
  28. Takagi A, Sai K, Umemura T, Hasega.wa R, Kurokawa Y. Short-term exposure to the peroxisome proliferators, perfluorooctanoic acid and perfluoroclecanoic acid, causes significant increase of 8- hydroxydeoxyguanosine in liver DNA of rats. Cancer Lett 1991, 57, 55-60 https://doi.org/10.1016/0304-3835(91)90063-N
  29. Vanden Heuvel JP, Kuslikis BI, Van Rafdgbem MJ. Pelerson RE. Tissue distribulion, melabolism, and elimination of perfluorooctanoic acid in male and female rats. J Biochem Toxicol 1991, 6, 83-92 https://doi.org/10.1002/jbt.2570060202
  30. Yamasbila N, Kannan K, Taniyasu S. Horii Y, Petrick G, Gamo T. A global survey of perfluorinated acids in oceans. Mar Pollut Bull 2005, 51, 658-668 https://doi.org/10.1016/j.marpolbul.2005.04.026