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랫드에서 인체 재조합 적혈구 조혈인자, rHuEPO의 13주 정맥투여 아만성독성에 관한 연구
김형식,곽승준,천선아,박현선,한하수,임소영,안미영,김원배,김병문,안병옥,홍성렬,이병무 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
A recombinant human erythropoietin (rHuEPO) was administered intravenously at dosage levels of 0, 100, 500, and 2500 IU/㎏/day for a period of 13 weeks. There were no observed clinical signs and deaths related to treatment in all groups tested. Decreases in body weight gain and food consumption were observed only in males of 2,500 IU/㎏ group after 2 weeks. In hematological parameters, erythrocyte content, hematocrit values and hemoglobin concentration were dose-dependently increased in rHuEPO treated groups. The ratio between kidney weight and whole body weight was significantly increased in females of 500 and 2,500 IU/㎏ groups. The spleen weight was also increased in both sexes of 500 and 2,500 IU/㎏ groups. However, the absolute weight change of other organs was not observed. In histopathological examinations, the renal tubular basophilia was observed only in males and females of 2,500 IU/㎏ groups. From these results, it is concluded that the no-observed adverse effect level(NOAEL) of rHuEPO is 100 IU/㎏ in rats in the present study.
Kwack, Seung-Jun,Lee, Byung-Mu Korean Society of ToxicologyKorea Environmental Mu 2009 Toxicological Research Vol.26 No.2
This study was conducted to investigate the 2 week-oral toxicity of Paecilomyces sinclairii in Sprague-Dawley rats. P. sinclairii was daily administered to male and female rats for 2 weeks with different dose levels (0, 0.008, 0.04, 0.2, 1 and 5 g/kg). There were no clinical signs compared with control group, but a slight increase of white blood cell (WBC) was observed in the males rats receiving all dose levels of P. sinclairii. In biohematological analysis, the levels of glucose and cholesterol in the blood were decreased slightly in the males and females rats at doses of 0.008 or 1 g/ kg. At the all dose groups, there were no significant changes in the body weights, but autopsy findings of all organs showed reduced weights in the thymus of males in the high dose groups of 1 g/ kg and 5 g/kg. These results indicate that P. sinclairii does not induce any significant toxic effect on Sprague-Dawley rats treated for 2 weeks, but the reduced weights of thymus in males may require a further long-term investigation.
Kwack, Seung-Jun,Han, Eun-Young,Park, Jae-Seok,Bae, Jung-Yun,Ahn, Il-Young,Lim, Seong-Kwang,Kim, Dong-Hyun,Jang, Dong-Eun,Choi, Lan,Lim, Hyun-Jung,Kim, Tae-Hyung,Patra, Nabanita,Park, Kui-Lea,Kim, Hyu Korean Society of ToxicologyKorea Environmental Mu 2010 Toxicological Research Vol.27 No.1
This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2(ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP, DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day)-treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.
Risk Assessment of Soybean-Based Phytoestrogens
Kwack, Seung Jun,Kim, Kyu-Bong,Kim, Hyung Sik,Yoon, Kyung Sil,Lee, Byung Mu Informa UK (TaylorFrancis) 2009 Journal of toxicology and environmental health. Pa Vol.72 No.21
<P>Koreans generally consume high quantities of soybean-based foods that contain a variety of phytoestrogens, such as, daidzein, zenistein, and biochalin A. However, phytoestrogens are considered to be potential endocrine-disrupting chemicals (EDC), which interfere with the normal function of the hormonal and reproductive systems. Therefore, dietary exposure to soybean-based phytoestrogens is of concern for Koreans, and comparative dietary risk assessments are required between Japanese (high consumers) versus Americans (low consumers). In this study, a relative risk assessment was conducted based upon daily intake levels of soybean-based foods and phytoestrogens in a Korean cohort, and the risks of photoestrogens were compared with those posed by estradiol and other EDC. Koreans approximately 30-49 yr of age consume on average a total of 135.2 g/d of soy-based foods including soybean, soybean sauce, soybean paste, and soybean oil, and 0.51 mg/kg body weight (bw)/d of phytoestrogens such as daidzein and genistein. Using estimated daily intakes (EDI) and estrogenic potencies (EP), margins of safety (MOS) were calculated where 0.05 is for estradiol (MOS value <1, considered to exert a positive estrogenic effect); thus, MOS values of 1.89 for Japanese, 1.96 for Koreans, and 5.55 for Americans indicate that consumption of soybean-based foods exerted no apparent estrogenic effects, as all MOS values were all higher than 1. For other synthetic EDC used as reference values, MOS values were dieldrin 27, nonylphenol 250, butyl benzyl phthalate 321, bisphenol A 1000, biochanin A 2203, and coumesterol 2898. These results suggest that dietary exposure to phytoestrogens, such as daidzein and genistein, poses a relatively higher health risk for humans than synthetic EDC, although MOS values were all greater than 1.</P>
Seung Jun Kwack,Eun Young Han,Jae Seok Park,Jung Yun Bae,Il Young Ahn,Seong Kwang Lim,Dong Hyun Kim,Dong Eun Jang,Lan Choi,Hyun Jung Lim,Tae Hyung Kim,Nabanita Patra,Kui Lea Park,Hyung Sik Kim,Byung M 한국독성학회 2010 Toxicological Research Vol.26 No.1
This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2(ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP) and five phthalate monoesters including mono-(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 ㎎/㎏/day (monoesters and PA) or 500 ㎎/㎏/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP, DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 ㎎/㎏/day)-treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.
Toxicological Evaluation of an Apicidin Derivative, Histone Deacetylase Inhibitor SD-2007 in Mice
Seung Jun Kwack,김규봉,이병무 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.5
SD-2007 is a new derivative of apicidin, an anti-parasitic agent and a histone deacetylase (HDAC) inhibitor. A subacute toxicological evaluation of SD-2007 was investigated for 2 weeks in ICR mice. After oral administration of SD-2007 (0, 0.2, 1, 5 or 25 mg/mouse), the clinical signs, mortalities, body weight changes, blood biochemical parameters, absolute and relative organ weights were examined. One day after the administration of SD-2007, excretion of soft feces in 1 and 5 mg/head groups, and one male in 25 mg/mouse group developed diarrhea, but theses complications were disappeared two days after administration. No mortalities were observed in animals up to 25 mg/mouse (LD50, >25 mg/kg), but absolute and relative weights of testes were significantly lower at the highest dose group (25 mg/mouse) and serum LDH and glucose levels were elevated in male mice. In addition, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were reduced in female mice at all dosages. These data suggest that SD- 2007 may be sex specific and be toxic to the male reproductive organ, and thus our findings require further investigation and in particular chronic toxicological investigations should be investigated.
Seung Jun Kwack,Byung Mu Lee 한국독성학회 2009 Toxicological Research Vol.25 No.2
This study was conducted to investigate the 2 week-oral toxicity of Paecilomyces sinclairii in Sprague-Dawley rats. P. sinclairii was daily administered to male and female rats for 2 weeks with different dose levels (0, 0.008, 0.04, 0.2, 1 and 5 g/㎏). There were no clinical signs compared with control group, but a slight increase of white blood cell (WBC) was observed in the males rats receiving all dose levels of P. sinclairii. In biohematological analysis, the levels of glucose and cholesterol in the blood were decreased slightly in the males and females rats at doses of 0.008 or 1 g/㎏. At the all dose groups, there were no significant changes in the body weights, but autopsy findings of all organs showed reduced weights in the thymus of males in the high dose groups of 1 g/㎏ and 5 g/㎏. These results indicate that P. sinclairii does not induce any significant toxic effect on Sprague-Dawley rats treated for 2 weeks, but the reduced weights of thymus in males may require a further long-term investigation.