Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Tissue Distribution and Toxicokinetics of 4-Tert-Octylphenol in Rats

4-Tert-Octylphenol의 랫드에서의 조직분포 및 독성동태에 관한 연구

  • 강미경 (국립독성연구원 독성연구부) ;
  • 안미령 (식품의약품안전청 의약품평가부) ;
  • 정혜주 (국립독성연구원 유효성연구부) ;
  • 최선옥 (국립독성연구원 유효성연구부) ;
  • 최홍석 (식품의약품안전청 의약품평가부) ;
  • 양지선 (식품의약품안전청 의약품평가부) ;
  • 이용복 (전남대학교 약학대학) ;
  • 유태무 (식품의약품안전청 의약품평가부) ;
  • 손수정 (국립독성연구원 유효성연구부)
  • Published : 2004.09.01
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Abstract

4-Tert-Octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues samples were taken at several time intervals after administration. Analysis of samples for OP was performed by column-switching high performance liquid chromatography (HPLC). In addition, we exam-ined tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg, single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days. After single oral administration of 200 mg/kg, Cmax of 213 $\pm$ 123 ng/ml was reached within the first 1.3 hr (Tmax) in the plasma. AUC was calculated for 1,333$\pm$484 ngㆍhr/ml. The final elimination half-life of plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues. OP was not accumulated in the liver following single oral application but 14-day oral treatments resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and these changes are closely related to the toxic and estrogenic effect of OP.

Keywords

References

  1. Badaiwi, A.F., Cavalieri, E.L. and Rogan, E.G. (2000): Effect of chlorinated hydrocarbons on expression of cytochrome P450 1A1, 1A2, and 1B1 and 2- and 4-hydroxylation of 17$\beta$-estradiol on female Sprague-Dawley rats. Carcinogen., 21, 1593-1599.
  2. Bolz, U., Kormer, W. and Hagermaier H. (2000): Development and validation of a GC/MS method for determination of phenolic xenoestrogens in aquatic samples. Cheoms., 40, 929-935
  3. Buhler, D.R., Miranda, C.L., Henderson, M.C., Yang, Y.H.,Lee, S.J. and Wang-Buhler, J.L. (2000): Effects of 17$\beta$-estradiol and testosterone on hepatic mRNA/protein levels and catalytic activities of CYP2M1, CYP2K1, and CYP3A27 in rainbow trout (Oncorhynchus mykiss). Toxicol. Appl, Pharmacol., 168, 91-101
  4. Certa, H., Fedtke, N., Wiegand, H.J., Muller, A.M.F. and Bolt, H.M. (1996): Toxicokinetics of p-ten-octylphenol in male Wistar rats. Arch. Toxicol., 71, 112-122
  5. Clark, L.B., Rosen, R.T., Hartman, T.G., Louis, J.B., Suffet, I.H., Lippincott, R.L. and Rosen, J.D. (1992): Determination of alkylphenol ethoxylates and their acetic-acid derivatives in drinking-water by particle beam liquidchromatography mass-spectrometry. Int. J. Environ. Anal. Chem., 47, 167-180 https://doi.org/10.1080/03067319208027027
  6. Ferguson, P.L., Iden, C.R. and Brownawell, B.J. (2000): Analysis of alkylphenol ethoxylate metabolites in the aquatic environment using liquid chromatography-electrospray mass spectrometry. Anal. Chem., 72, 4322-4330
  7. Ferreira-Leach, A.M.R. and Hill, M.E. (2001): Bioconcentration and distribution of 4-tert-octylphenol residues in tissues of the rainbow trout. Mar. Envioron. Res., 51, 75-89
  8. Hanioka, N., Jinno, H., Chung, Tanaka-Kagawa, T., Nishimura, T. and Ando, M. (1999): Inhibition of rat hepatic cyochrom P450 activates by biodegradation products of 4-tert-octylphenol ethoxylate. Xenobiotica, 29, 873-883 https://doi.org/10.1080/004982599238128
  9. Hanioka, N., Jinno, H., Chung, Y., Nishimura, T., TanakaKagawa, T. and Ando, M. (2000a): Effect of 4-tertoctylphenol on cytochrome P450 enzymes in rat liver. Arch. Toxicol., 73, 625-631
  10. Hanioka, N., Tanaka-Kagawa, T., Chung, Y, Nishimura, T., Jinno, H. and Ando, M. (2000b): Changes in hepatic cytochrome P450 enzymes by biodegradation products of 4tert- octylphenol polyethoxylate in rats. Bull. Environ. Contam. Toxicol., 64, 804-810
  11. Jobling, S., Nolan, M., Tyler, C.R., Brighty, G. and Sumpter, J.P. (1996): Inhibition of testicular growth in rainbow trout (Oncorhynchus mykiss) exposure to estrogenic alkylphenolic chemicals. Environ. Toxicol. Chem., 15, 194-202
  12. Muller, S., Schmid, P. and Schlatter, C. (1998): Distribution and pharmacokinetics of alkylphenolic compounds in primary mouse hepatocyte cultures. Environ. Toxicol. Pharmacol., 6, 45-48
  13. Pedersen, R.T. and Hill, E.M. (2000a): Identification of novel metabolites of the xenoestrogen 4-tert-octylphenol in primary rat hepatocytes. Chem. Biol. Interact., 128, 189-209
  14. Pedersen, R.T. and Hill, E.M. (2000b): Bioconcentration of the xenoestrogen 4-tert-octylphenol in hepatocytes of rainbow trout. Xenobiotica., 30, 867-879
  15. Petrovic, M. and Barcelo, D. (2001): Analysis of ethoxylated nonionic surfactants and their metabolites by liquid chromatography/atmospheric pressure inonzaton mass spectrometiry. J. Mass Spectro., 36, 1173-1185 https://doi.org/10.1002/jms.234
  16. Pottenger, L.H., Domoradzki, J.Y., Markham, D.A. and Hansen, S.C. (1997): Bioavailability of $^{14}C$-bisphenol A in fischer rats following oral, subcutaneous or intraperitoneal administration. Report K-001302-012A, Society of Plastics Industry Bisphenol A Task Group, 8 January
  17. Routledge, E.J. and Sumpter, J.P. (2000): Structural features of alkylphenolic chemicals associated with estrogenic activity. J. Biol. Chem., 272, 3280-3288 https://doi.org/10.1074/jbc.272.6.3280
  18. Saghir, S.A., Koritz, G.D. and Hansen L.G. (1999): Short-term Distribution, metabolism, and excretion of 2,2',5-tri-, 2,2',4,4'-tetra-, and 3,3',4,4'-tetrachlorobiphenyls in prepubertal rats. Arch. Environ. Contam. Toxicol., 36, 213-320
  19. Sohn, S.J., Kang, H.G., Yi, S.W., Suh, S.K., Park, I.S., Ahn, M.R., Choi, H.S., Cho, J.M., Shon, D.H., Yoo, T.M. and Yang, J.S. (2001): Toxicokinetics of 4-tert-octylphenol in rats. Environ. Mutagens Carcinogens, 21, 122-127
  20. Soto, A.M., Justicia, H., Wray, J.W. and Sonnenschein, C. (1991): p-Nonylphenol: an estrogenic xenobiotic released from "modified" poly-styrene. Environ. Health Persp., 92, 167-173
  21. Talmage, S.S. (1994): Environmental and human safety of major surfactants-alcohol ethoxylates and alkylohenol ethoxylates. The Soap and Detergent Association, Lewis, Boca Raton, FL
  22. Tsuda, T., Takino, A., Kojima, M., Harada, H. and Muraki, K. (1999); Gas chromatographic-mass spectrometric determination of 4-nonylphenols and 4-tert-octylphenol in biological samples. J. Chromatogr., 723, 273-279 https://doi.org/10.1016/S0378-4347(98)00524-6
  23. Upmeier, A., Degen, G.H., Schuhmacher, U.S., Certa, H. and Bolt, H.M. (1999): Toxicokinetics of p-tert-octylphnol in female DNHan rats after single i.v. and oral application. Arch. Toxicol., 73, 217-22
  24. White, R., Jobling, S., Hoare, S.A., Sumpter, J.P. and Parker, M.G. (1994): Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinol., 135, 175-182
  25. Yacobi, A., Skelly, J.P. and Batra, V.K. (1989): Toxicokinetics and new drug development, In Pergamon Press, Inc., pp.1-20
  26. Yoo, S.D., Shin, B.S., Kwack, S.J., Lee, B.M., Park, K.L., Han, S.Y and Kim, H.S. (2000): Pharmacokinetic dispostion and tissue distribution of bisphenol A in rats after intravenous administration. J. Toxicol. Environ. Health, 60, 131-139
  27. Yoo, S.D., Shin, B.S., Lee, B.M., Lee, K.C., Han, S.Y. Kim, H.S., Kwack, S.J. and Park, K.L. (2001): Bioavailability and mammary excretion of Bisophenol A in SpragueDawely rats. J. Toxicol. Environ. Health, 64, 417-426 https://doi.org/10.1080/152873901753170740