Go to the main menu
Skip to content
Go to bottom
REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Journal Basic Information
Journal DOI :
The Korean Society of Toxicology
Editor in Chief :
Volume & Issues
Volume 21, Issue 4 - Dec 2005
Volume 21, Issue 3 - Sep 2005
Volume 21, Issue 2 - Jun 2005
Volume 21, Issue 1 - Mar 2005
Selecting the target year
Anti-Androgenic Activity of Phthalate Esters (Di(2-ethylhexyl) Phthalate, Di(n-butyl) Phthalate, and Butylbenzyl Phthalate) in the Rodent 10-day Hershberger Assay using Immature Castrated Male Rats
Kang, Il-Hyun ; Kim, Hyung-Sik ; Kim, Tae-Sung ; Moon, Hyun-Ju ; Kim, In-Young ; Kang, Tae-Seok ; Park, Kui-Lea ; Choi, Kwang-Sik ; Han, Soon-Young ;
Toxicological Research, volume 21, issue 3, 2005, Pages 187~193
The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).
Determination of Insulin Signaling Pathways in Hepatocytes
Kim, Sang-Kyum ;
Toxicological Research, volume 21, issue 3, 2005, Pages 195~208
Diabetes is a major cause of morbidity and mortality, and associated with a high risk of atherosclerosis, and liver, kidney, nerve and tissue damage. Defective insulin secretion in pancreas and/or insulin resistance in peripheral tissues is a central component of diabetes. It is well established that, regardless of the degree of muscle insulin resistance, glucose levels in diabetic and non-diabetic individuals are determined by the rate of hepatic glucose production. Moreover recently studies using liver-specific insulin receptor knockout mice show the paramount role of the liver in insulin resistance and diabetes. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. The first major section of this review defines the major insulin-mediated signaling pathways including phosphatidylinositol 3-kinase and mitogen activated protein kinases. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways, including methods for determination of kinase phosphorylation, the use of pharmacological inhibitors of kinase and dominant-negative kinase constructs, and the application of new RNA interference methods.
Effects of Recombinant Human Erythropoietin Treatment in Male Cynomolgus (Macaca fascicularis) Monkeys (II): Gene Expression Profiling in Spleen
Yoon, Seok-Joo ; Hwang, Ji-Yoon ; Lim, Jung-Sun ; Jeong, Sun-Young ; Kim, Yong-Bum ; Kim, Dal-Hyun ; Kwon, Myung-Sang ; Han, Sang-Seop ; Kim, Choong-Yong ;
Toxicological Research, volume 21, issue 3, 2005, Pages 209~218
We investigated effects of recombinant human erythropoietin (rHuEPO) on profiles of mRNA transcripts in 6 male cynomolgus (M. fascicularis) monkey's spleen for 4 weeks. Six monkeys, composed of control and treatment group (Control : M1, M2, M3: Treatment : M4, M5, M6) were intravenously administered 3 times per week without or with a dose of rHuEPO 2730 IU/0.1 ml/kg. After 4 weeks rHuEPO treatment, spleen was removed for RNA isolation. Splenic gene expression was assessed using Affymetrix U133A 2.0 arrays containing 18,400 transcripts and variants, including 14,500 well-characterized human genes. Gene expression pattern was very different between individuals even in same treatment. In rHuEPO treated groups showed number of genes were up- or down-regulated (M4: 79: M5: 48; M6: 73 genes). Six genes (epidermal growth factor receptor, calgranulin A, estrogen receptor binding site associated antigen, matrix metalloproteinase 19, zinc finger and BTB domain containing 16, progestin and adipoQ receptor) were commonly expressed in rHuEPO treated group. The different individual response could be major considering factor in monkey experiment. Further study is needed to clarify the different individual response to rHuEPO in molecular level. This study will be valuable in the fundamental understanding and validation of molecular toxicology for bio-generic drugs including rHuEPO in cynomolgus monkey.
Real-Time Quantitative PCR with SYBR Green I for Living Modified Roundup Ready Soybean
Pack, In-Soon ; Jeong, Soon-Chun ; Lee, Kyu-Hwa ; Yoon, Won-Kee ; Park, Sang-Kyu ; Kim, Chang-Gi ; Kim, Hwan-Mook ;
Toxicological Research, volume 21, issue 3, 2005, Pages 219~226
Effects of Recombinant Human Erythropoietin Treatment in Male Cynomolgus Monkeys (Macaca fascicularis) (I): Hematological and Histopathological Changes
Kim, Choong-Yong ; Yoon, Seok-Joo ; Kim, Yong-Bum ; Ha, Chang-Su ; Kim, Dal-Hyun ; Kwon, Myung-Sang ; Han, Sang-Seop ;
Toxicological Research, volume 21, issue 3, 2005, Pages 227~234
Immunological Activity and Immunotoxicity of Pine Tree Pollen in Mice
Kim, Young-Ok ; Kim, Kwang-Ho ; Park, Hyun-Ji ; Park, Yeong-Chul ; Park, Sung-Wook ; Heo, Yong ;
Toxicological Research, volume 21, issue 3, 2005, Pages 235~240
Pollen has been used for prevention or treatment of certain diseases such as diabetes arthritis or cancer in traditional medicine. Among various pollens, pine tree pollen is known to relieve hypertension, suppress fatty liver progression, and facilitate the digestion, but its immunological activities are less known. To evaluate immunological reactivities and immunotoxicities of pine tree pollen, BALB/c mice were administered to the poller through oral route. Pine tree pollen suspended in distilled water or extracted with methanol has been administered at the concentration of 0, 10, or 100 mg/kg five days per week for four weeks. Polyclonal activation of splenic T cells with phytohemagglutinins did not induce a significant difference in IL-4 and
production between the pollen-administered mice groups and the control mice. Furthermore, polyclonal activation of splenic B cells with lipopolysaccharides did not result a significant difference in IgG1 and IgG2a production among the groups. These findings imply that the intake of pine tree pollen does not bring any humoral and cellular immune-dysrequlation. Whereas, viability of Listeria monocytogenes was suppressed in the mice administered with 100 mg/kg bw methanol extract, indicating the potential ability of pine tree pollen to enhance cell-mediated immunity mediated by type-1 helper T cells. In addition, aberrant upregulation of plasma IgG1 level was observed in the pollen-administered mice, which suggests a possibility of allergic response induction through the pine tree pollen uptake. Overall, pine tree pollen-mediated modulation of humoral or cellular immunity is worthy of further systematic investigation.
Antigenicity of HM10760 in Guinea Pigs
Choi, Woo-Hyuck ; Lee, Sung-Hak ; Lee, Mi-Chael ; Chung, Moon-Ku ; Kwon, Se-Chang ; Lee, Gwan-Sun ; Han, Jae-Yong ; Koh, Woo-Suk ;
Toxicological Research, volume 21, issue 3, 2005, Pages 241~247
HM10760 is a recombinant human erythropoietin that has beer developed as a drug for anemia. In this study, antigenic potential of HM10760 was examined by active systemic anaphylaxis in guinea pigs and passive cutaneous anaphylaxis in a guinea pig-guinea pig system. HM10760 was subcutaneously administered at 0, 2, and
and also as a suspension with adjuvant (
+ FCA). Ovalbumin as a suspension with adjuvant was administered to induce positive control responses. In the active systemic anaphylaxis test, no symptoms except rubbing or licking nose and urination that were considered as physiological phenomena were observed at
. Four of 5 animals at
and all the 5 animals at
showed cyanosis and lying on side. All animals in the adjuvant mixture group showed relatively mild symptoms such as rubbing or licking nose, urination, and evacuation. In the passive cutaneous anaphylaxis test, 0/5, 3/5, and 5/5 serum samples from the animals immunized with 0, 2, and
, respectively, showed positive reactions against HM10760. All 5 sera collected from the animals immunized with an adjuvant mixture contained HM10760-specific antibodies. These results suggest HM10760 have antigenicity in guinea pigs.
Primary Dermal Irritation Study of Lemon Grass (Cymbopogon citratus) Essential Oil in Rabbits
Shin, Jin-Young ; Park, Seung-Chun ; Kim, Ki-Hyun ; Shin, Dong-Ho ; Kim, Sung-Ho ; Kim, Jong-Choon ;
Toxicological Research, volume 21, issue 3, 2005, Pages 249~253
The present study was carried out to investigate the skin irritation potential of lemon grass essential oil in rabbits. A volume of 0.5 ml of test article was applied to intact and abraded skins, respectively, for 24 h in 6 healthy male New Zealand White rabbits. Parameters measured during 72 h observation period were mortality, clinical signs, body weight changes, and local irritation. All rabbits showed severe edema at both 24 h and 72 h after the application of test article. These animals also showed very slight to severe erythema and/or slight eschar formation at both 24 h and 72 h. The edema and erythema induced by lemon grass essential oil were recovered on day 7 of additional 11-day recovery period, but the eschar formation was not recovered at the end of recovery period. On the other hands, there were no treatment-related adverse effects on clinical sign, body weight and gross finding in rabbits. Based on these results, it was concluded that a single dermal application of the undiluted lemon grass essential oil caused very slight to severe edema, erythema and eschar formation in rabbits and showed a primary irritation index score of 5.63 indicating severe irritation. The results of this study strongly suggest that lemon grass essential oil should be used with care and in highly diluted forms especially when directly applied to the skin.
Acute Oral Toxicity Study of Standardized Herbal Preparations(Gami-Samhwang-San, SH-21-B) in Rats
Yu, Young-Beob ; Kim, Seon-Hyeong ; Yoon, Yoo-Sik ;
Toxicological Research, volume 21, issue 3, 2005, Pages 255~261
Gami-Samhwang-San, a herbal prescription for obesity treatment, is composed of seven crude herbs such as Rehmanniae Radix Preparata, Ephedrae Herba, Scutellariae Radix, Acori Gramineri Rhizoma, Polygalae Radix, Typhae Pollen, Armeniacae Semen, Menthae Herba. In this study, marker substances in n-butanol fraction (SH-21-B) from Gami-Samhwang-San were analyzed by high performance liquid chromatography (HPLC) and acute toxicity of standardized SH-21-B was evaluated by good laboratory practices (GLP) guideline of Korea Food and Drug Administration. Therefore we confirmed that there were baicalin of 15.92%, amygdalin of 6.57% and ephedrine of 2.49% in SH-21-B. SH-21-B was administered in rats at dose of 0 mg/kg, 2,000 mg/kg, and 5,000mg/kg. Clinical signs of both sexes of rats were observed daily for 14 days after single oral administration. Two female rats one administered at 2,000 mg/kg and the other administered at 5,000 mg/kg, died, but no dead animal was observed among male rats. Therefore
in the female rat is observed to be 8,710 mg/kg, and MLD (Minimun Lethal Dose) of the male rat is observed to be more than 5,000 mg/kg.
Four-Week Repeated Oral Toxicity Study of Clean Natural in Sprague-Dawley Rats
Kim, Eui-Kyung ; Kim, Jun-Young ; Lee, Hu-Jang ;
Toxicological Research, volume 21, issue 3, 2005, Pages 263~269
This study was performed to investigate repeated-dose toxicities of Clean natural, a new disinfectant, in Sprague-Dawley(SD) rats. In the 4-week repeated oral toxicity study, Clean Natural was orally administered once daily via gavage to male and female rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg body weight for 4-weeks. There were no deaths and clinical signs during the dosing period. In both sexes, there were no statistically significant differences between the administered and control groups in urinalysis indicators and hematological parameters. In serum biochemistry, aspartate aminotransferase(AST) was significantly decreased and sodium content was increased in the 2,000 mg/kg male group, while chlorine was significantly decreased in the 2,000 mg/kg female group. Also, albumin, total cholesterol and total bilirubin were significantly increased in the 2,000 mg/kg male and female group. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver was observed in the 2,000 mg/kg male and female groups. And pigmentation in the spleen was observed in the 2,000 mg/kg male group. In conclusion, four-week repeated oral dose of Clean Natural to rats did not cause apparent toxicological change at the dose less than 2,000 mg/kg body weight. Thus it is suggested that no-observed adverse-effect level(NOAEL) for Clean Natural in rats was considered to be 1,000 mg/kg/day.