This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test mate...
This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.
This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.
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제안 방법
Body weight changes. Body weights were measured at the day of dosing (Day 0) immediately before treatment, 1, 2, 7, 13 and 14 days after dosing. In addition, to reduce the erratum originated from individual body weight ditferences of animals at initial dosing, body weigh gains during Day 0-Day 7, Day 7~Day 13 and Day O'Day 14 were also calculated based on measured body weight at each day.
Experimental animals. Each of thirty female and male ICR mice (6-wk old upon receipt, SLC, Japan) was used after acclimatization for 8 days. Five animals were allocated per a polycarbonate cage in a temperature (20'25℃) and humidity (40-45%) controlled room.
The objective of the present study, therefore, was to obtain the primary safety information about PGB-1, a novel polyglucosamine polymer and further clarify their safety for clinical use.
이론/모형
Changes of body weight were analyzed by Mann-Whitney U-Wilcoxon Rank Sum W test (MW test) compared to those of vehicle controls. LD50 was calculated by Probit method. Statisticalanalyses were conducted using SPSS for Windows (Release 6.
성능/효과
Changes in organ weight No meaningfulchanges on the absolute and relative organ weight of 11 principle organs were observed in all dosing groups tested compared to that of vehicle control except for signifi- cant (p < 0.01 or p< 0.05) decrease of absolute kidney weight in 500 ㎎/㎏-dosing male group, of absolute weight of testis in 125 ㎎/㎏-dosing male group and of relative weight of kidney in 125 ㎎/㎏-dosing female group, and increase of relativeweight of heart in 125 ㎎/㎏-dosing male, of absolute weight of ovary in 500 ㎎/㎏-dosing female and of relative weight of ovary in 250 ㎎/㎏-dosing female group, respectively (fable 2, 3).
From these results, oral gavage of PGB-1 caused no serious toxic effect to the male and female mice 니pto 2000 ㎎/㎏ - the highest dosage tested in this study. Therefore, PGB-1 has relatively favorable toxicologicalprofiles.
Necropsy findings. In this study, no meaningful changes on the gross findings of 12 principle organs were observed in all dosing groups tested compared to that of vehicle control except for some sporadic findings such as congestion spots of hjng, atrophy of thymus, spleen atrophy or hypertrophy, atypical white foci in liver and hypertrophy of popliteal lymph node (Table 4).
Significant (p < 0.01 or p < 0.05) decreases of body weight gains during day 7-14 of dosing of PGB-1 1000 ㎎/㎏-dosing male group, and during day 7~14 of dosing periods with whole experimental periods (Day 0-14) of PGB-1 500 and 250 ㎎/㎏-dosing mate groups were considered as not meaningful changes, because no dose dependency was observed, it was detected that no changes on the body weight gains in the same periods in the highest dosage group compared to that of vehicle control.
참고문헌 (24)
Banks, W.J. (1986). Female reproductive system in Applied veterinary histology (Banks, W.J. Ed.). Williams & Wilkins, Baltimore, pp. 506-526
Deng, S.B., Bai, R.B., Hu, X.M. and Luo, Q. (2003). Characteristics of a bioflocculant produced by Bacillus mucilaginosus and its use in starch wastewater treatment. Appl. Microbiol. Biotechnol., 60, 588-593
Dermlim, W., Prasertsan, P. and Delle, H. (1999). Screening and characterization of bioflocculant produced by isolated Klebsiella sp. Appl. Microbiol. Biorechnol., 52, 698-703
Dourish, C.T. (1987). Effects of drugs on spontaneous motor activity in experimental psychopharmacology (Greenshaw, A.J. and Dourish, C.T. Eds.). Humana Press, Clifton, pp. 325-334
Fujita, M., Ike, M., Jang, J.H., Kim, S.M. and Hirao, T. (2001). Bioflocculation production from lower-molecular fatty acids as a novel strategy for utilization of sludge digestion liquor. Water Sci. Technol., 144, 237-243
Hodge, H.C. and Sterner, J.H. (1949). Tabulation of toxicity classes. Am. Ind. Hyg. Q., 10, 93
Irwin, S. (1968). Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse, Psychopharmacology, 13, 222-257
Jang, J.H., Ike, M., Kim, S.M. and Fujita, M. (2001). Production of a novel bioflocculant by fed-batch culture of Citrobacter sp. Biotechnol. Lett., 23, 593-597
Korea Food and Drug Administration. (2005). Testing Guidelines for Safety Evaluation of Drugs (Notification No. 2005-60, issued by the Korea Food and Drug Administration on October 21, 2005)
Kurane, R., Toeda, K. and Suzuki, T. (1986). Culture conditions for production of microbial flocculant by Rhodococcus erythropolis. Agric. Biol. Chem., 50, 2309-2313
Lee, H.S., Lee, I.G. and Ku, S.K. (2006). Single oral dose toxicity study of water extracts of Picrorrhiza Rhizoma in mice. J. Toxicol. Pub. Health, 22, 117-126
Lee, H.S., Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Jung, Y.M. and Ku, S.K. (2005). Single oral dose toxicity study of Polycan, $\beta$ -glucan originated from Aureobasidium in mice. J. Toxicol. Pub. Health, 21, 361-365
Lee, Y.H., Son, M.K., Jung, Y.M., Kim, T.K., Oark, D.C., Kim, P.S. and Ku, S.K. (2007). Single oral dose toxicity studies of PGB-2, a novel polyglucosamine polymer produced from Citrobacter sp. BL-4 in mice. J. Toxicol. Pub. Health, 23, 65-72
Oh, H.M., Lee, S.J., Park, M.H., Kim, H.S., Kim, H.C., Yoon, J.H., Kwon, G.S. and Yoon, B.D. (2001). Harvesting of Chlorella vulgaris using a bioflooculant from Paenibacillus sp. AM49. Biotechnol. Lett., 23, 1229-1234
Organization for Economic Co-Operation and Development (Ed.). (2001). OECD guideline (423) for testing of chemicals - acute oral toxicity-acute toxic class method
Pineda, M.H. (1989). Female reproductive system in Veterinary endocrinology and reproduction (McDonald, L.E. and Pineda, M.H. Eds.). Lea & Febiger, Philadelphia, pp. 303- 354
Son, M.K., Shin, H.D., Huh, T.L., Jang, J.H. and Lee, Y.H. (2005). Novel cationic microbial polyglucosamine biopolymer from new Enterobacter sp. BL-2 and its bioflocculation efficacy. J. Microbol. Biotechnol., 15, 626-632
US Environmental Protection Agency. (1998). Health Effects Test Guidelines OPPTS 870.100, Acute Toxicity Testing Background, US EPA August, Washington, USA
Watanebe, M., Suzuki, Y., Sasaki, K., Nakashimada, Y. and Nishio, N. (1999). Flocculating property of extracellular polymeric substance derived from a marine photosynthetic bacterium, Rhodovulum sp. J. Biosci. Bioeng., 87, 625-629
White, S.A., Farina, P.R. and Fulton, I. (1979). Production and isolation of chitosan from Mucor ruxii. Appl. Envirin. Microbiol., 38, 323-328
Yokoi, H., Aratake, T., Hirose, J., Hayashi, S. and Takasaki, Y. (2001). Simultaneous production of hydrogen and bioflocculant by Enterobacter sp. BY-29. World J Microbiol Biotechnol., 17, 609-631
Yoon, S.H., Song, J.K., Go, S.J. and Ryu, J.C. (1998). Production of biopolymer fluocculant by Bacillus subtilis TB- 11. J. Microbiol. Biotechnol., 8, 606-612
Yu, K.W., Shin, K.S., Choi, Y.M. and Suh, H.J. (2004). Macrophage stimulating activity of exo-biopolymer from submerged culture of Lentinus edodes with rice bran. J. Microbiol. Biotechnol., 14, 658-664
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