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4-Tert-Octylphenol의 랫드에서의 조직분포 및 독성동태에 관한 연구
강미령(Mi Kyung Kang),안미령(Mee Ryung Ahn),정혜주(Hye Joo Chung),최선옥(Sun Ok Choi),최홍석(Hong Serk Choi),양지선(Ji Sun Yang),이용복(Yong Bok Lee),유태무(Tae Moo Yoo),손수정(Soo Jung Sohn) 한국독성학회 2004 Toxicological Research Vol.20 No.3
4-Tert-octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety<br/> of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This<br/> study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male<br/> rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues<br/> samples were taken at several time intervals after administration. Analysis of samples for OP was<br/> performed by column-switching high performance liquid chromatography (HPLC). In addition, we examined<br/> tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg,<br/> single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days.<br/> After single oral administration of 200 mg/kg, Cmax of 213 ± 123 ng/ml was reached within the first 1.3 hr<br/> (Tmax) in the plasma. AUC was calculated for 1,333 ± 484 ng · hr/ml. The final elimination half-life of<br/> plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of<br/> OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion<br/> route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment<br/> and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The<br/> OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues.<br/> OP was not accumulated in the liver following single oral application but 14-day oral treatments<br/> resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the<br/> other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by<br/> OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result<br/> suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and<br/> these changes are closely related to the toxic and estrogenic effect of OP.
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