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Tissue Distribution and Toxicokinetics of 4-Tert-Octylphenol in Rats  

Kang Mi Kyung (국립독성연구원 독성연구부)
Ahn Mee Ryung (식품의약품안전청 의약품평가부)
Chung Hye Joo (국립독성연구원 유효성연구부)
Choi Sun Ok (국립독성연구원 유효성연구부)
Choi Hong Serk (식품의약품안전청 의약품평가부)
Yang Ji Sun (식품의약품안전청 의약품평가부)
Lee Yong Bok (전남대학교 약학대학)
Yoo Tae Moo (식품의약품안전청 의약품평가부)
Sohn Soo Jung (국립독성연구원 유효성연구부)
Publication Information
Toxicological Research / v.20, no.3, 2004 , pp. 195-203 More about this Journal
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
4-Tert-Octylphenol (OP); Toxicokinetic; Column-switching HPLC; Distribution;
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1 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
2 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
3 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
4 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
5 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
6 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   DOI   ScienceOn
7 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
8 Yacobi, A., Skelly, J.P. and Batra, V.K. (1989): Toxicokinetics and new drug development, In Pergamon Press, Inc., pp.1-20
9 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
10 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   DOI   ScienceOn
11 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.
12 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
13 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   DOI   ScienceOn
14 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
15 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
16 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
17 Pedersen, R.T. and Hill, E.M. (2000b): Bioconcentration of the xenoestrogen 4-tert-octylphenol in hepatocytes of rainbow trout. Xenobiotica., 30, 867-879
18 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
19 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   DOI   ScienceOn
20 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
21 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   DOI   ScienceOn
22 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
23 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
24 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
25 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
26 Routledge, E.J. and Sumpter, J.P. (2000): Structural features of alkylphenolic chemicals associated with estrogenic activity. J. Biol. Chem., 272, 3280-3288   DOI   ScienceOn
27 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