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마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험
전태원,김지영,현선희,김남희,이상규,김춘화,우희동,양기혁,정현호,정태천,Jeon, Tae-Won,Kim, Ji-Young,Hyun, Sun-Hee,Kim, Nam-Hee,Lee, Sang-Kyu,Kim, Chun-Hwa,Woo, Hee-Dong,Yang, Gi-Hyeok,Jung, Hyun-Ho,Jeong, Tae-Cheon 대한수의학회 2003 大韓獸醫學會誌 Vol.43 No.1
Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.
연구논문 : 생명과학 ; 마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험
전태원 ( Tae Won Jeon ),김지영 ( Ji Young Kim ),현선희 ( Sun Hee Hyun ),김남희 ( Nam Hee Kim ),이상규 ( Sang Kyu Lee ),김춘화 ( Chun Hwa Kim ),우희동 ( Hee Dong Woo ),양기혁 ( Gi Hyeok Yang ),정현호 ( Hyun Ho Jung ),정태천 ( Tae C 영남대학교 약품개발연구소 2004 영남대학교 약품개발연구소 연구업적집 Vol.14 No.-