Single and Two-Week Repeated] Oral Dose Toxicity Study of DHP2, a Hydrophobic Drug Delivery Vehicle in Mice

Han, Jung-Hee,Chung, He-Sson,Lee, Jong-Hwa,Suh, Jeong-Eun,Lee, Gab-Soo,Kim, Jong-Choon,Kang, Boo-Hyon Korean Society of ToxicologyKorea Environmental Mu 2004 Toxicological Research Vol.20 No.2

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in ICR mouse

Jang, Kyung-Min,Kim, Sung-Gun,Park, Ji-Young,Choi, Won-Ho,Lee, Jae-Woo,Jegal, Hyeon-Young,Kweon, Soon-Jong,Choi, Kwang-Ho,Park, Jung-Ho 충남대학교 농업과학연구소 2016 Korean Journal of Agricultural Science Vol.41 No.2

Silk has had a reputation as a luxurious and sensuous fabric but it is not popular due to the expensive price and poor durability. To develop the silk materials that apply the various industries, the artificially synthesized gene can be introduced into the silkworm and expressed in the silk gland. Transgenic silkworms for the mass production of green fluorescent silks are generated using a fibroin H-chain expression system. For commercial use, safety assessment of the transgenic silkworms is essential. The purpose of this study was to examine the potential acute oral toxicity of EGFP protein expressed in genetically modified (GM) fluorescence silkworm and to obtain the approximative lethal dose in the male and female at 6-weeks ICR mice. EGFP protein was fed at a dose of 2,000 mg/kg body weight in five male or five female mice. Mortalities, clinical findings and body weight changes were monitored for 1, 3, 7, 14 days after dosing. At the end of 14 day observation period, all mice were sacrificed, and the postmortem necropsy were performed. The test group was not observed death case. Also the effect was not admitted by test substance administration in common symptoms, the body weight and postmortem. The results of single-dose oral toxicity test showed that approximative lethal dose of EGFP protein expressed in fluorescence silkworm was considered to exceed the 2,000 mg/kg body weight in both sexes.

Large-scale purification and single-dose oraltoxicity study of human thioredoxin and epidermal growth factor introduced into two different genetically modified soybean varieties

박정호 충남대학교 농업과학연구소 2021 Korean Journal of Agricultural Science Vol.48 No.4

Thioredoxin (TRX) protein is an antioxidant responsible for reducing other proteins by exchanging cysteine thiol-disulfide and is also known for its anti-allergic and anti-aging properties. On the other hand, epidermal growth factor (EGF) is an important material used in the cosmetics industry and an essential protein necessary for dermal wound healing facilitated by the proliferation and migration of keratinocytes. EGF also assists in the formation of granulation tissues and stimulates the motility of fibroblasts. Hence, genetically modified soybeans were developed to overexpress these industrially important proteins for mass production. A single-dose oral-toxicity-based study was conducted to evaluate the potential toxic effects of TRX and EGF proteins, as safety assessments are necessary for the commercial use of seed-specific protein-expressing transgenic soybeans. To achieve this rationale, TRX and EGF proteins were mass purified from recombinant E. coli. The single-dose oraltoxicity tests of the TRX and EGF proteins were carried out in six-week old male and female Institute of Cancer Research (ICR) mice. The initial evaluation of the single-dose TRF and EGF treatments was based on monitoring the toxicity signatures and mortality rates among the mice, and the resultant mortality rates did not show any specific clinical symptoms related to the proteins. Furthermore, no significant differences were observed in the weights between the treatment and control groups of male and female ICR mice. After 14 days of treatment, no differences were observed in the autopsy reports between the various treatment and control groups. These results suggest that the minimum lethal dose of TRX and EGF proteins is higher than the allowed 2,000 mg·kg-1 limit.

Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in ICR mouse

Kyung-Min Jang,Sung-Gun Kim,Ji-Young Park,Won-Ho Choi,Jae-Woo Lee,Hyeon-Young Jegal,Soon-Jong Kweon,Kwang-Ho Choi,Jung-Ho Park 충남대학교 농업과학연구소 2016 Korean Journal of Agricultural Science Vol.43 No.1

A Minipig can Replace a Dog in Non-rodent Toxicity Study

Sang-Koo Lee,Youn-Sang Kweon,Chester D. Solis,Shin-Joung Rho,Tae-Ho Kim 한국실험동물학회 2007 Laboratory Animal Research Vol.23 No.3

This study was conducted to compare the difference of quantitative toxicity of a compound which has different metabolic pathways in minipig and beagle dog. Coumarin which has low toxic values in human and different metabolic pathways in these two animals was chosen as a test compound. In the single dose toxicity study conducted using minipig, maximum tolerable dose (MTD) of coumarin was determined to be 200 ㎎/㎏/day and liver was confirmed as a target organ. However, MTD value of coumarin in the dog study was 60-100 ㎎/㎏/day and target organs were liver and kidneys. Minipig which has similar metabolic pathway of coumarin with human showed similar acute toxicity when compared with previously published data. Although it is difficult to conclude without further toxicity studies, it was expected from this study that animals having similar metabolic pathways with human should be chosen during the toxicity studies of new chemicals to predict the accurate toxicity and target organs in the human.

접골탕(接骨湯) 2.0의 Sprague-Dawley 랫드를 이용한단회경구투여 독성시험

최영진,김효정,김세진,김준섭,정지운,임현희,장보경,박유진,임정태,배기상,권빛나,김동욱 대한본초학회 2024 大韓本草學會誌 Vol.39 No.2

Objectives : Jeopgoltang (JGT) is a new Korean herbal medicine formulation that is used to treat bone fractures. Although JGT is frequently used in clinical practice, there is a lack of scientific evidence on its safety. This study aimed to evaluate the preclinical toxicity of JGT using a single oral dose toxicity test in Sprague-Dawley (SD) rats. Methods : Five male and female rats per group were orally administered 1,250, 2,500, or 5,000 ㎎/㎏ of JGT after fasting for 12 h. Mortality and changes in clinical signs, body weight, and necropsy findings were monitored for 14 days according to the guidelines of the Korean Ministry of Food and Drug Safety and Organisation for Economic Co-operation and Development (OECD). Results : No significant clinical signs or mortality were observed after a single administration of up to 5,000 ㎎/㎏. In addition, no significant necropsy findings related to JGT administration were observed. Conclusions: In conclusion, these results suggest that approximate Lethal Dose (ALD) of JGT on SD rats is over 5,000 ㎎/㎏.

GM 유채에 도입된 β-glucosidase 1 (AtBG1)의 단회투여독성시험

이순봉(Soonbong Lee),정광주(Kwangju Jeong),장경민(Kyung-Min Jang),김성건(Sung-Gun Kim),박정호(Jung-Ho Park),김신제(Shinje Kim) 한국생명과학회 2017 생명과학회지 Vol.27 No.2

유채는 십자화과로 분류되는 유지작물로써 전 세계적으로 재배되는 작물이다. 이전 연구결과에서 가뭄저항성을 증대시키는 것으로 보고된 애기장대의 β-glucosidase 1 (AtBG1) 유전자를 도입함으로써 가뭄저항성 형질전환 유채를 개발하였다. 새로 개발된 형질전환 작물들은 그 이용에 대한 안전성에 대하여 어떠한 정보도 제공되지 않기 때문에 작물의 안정성에 대한 증명이 필수적이다. 이러한 안정성 평가는 작물의 역사적 사용과 과학적 증거를 기초로 한다. 이번 연구에서는 AtBG1이 도입된 형질전환 유채의 급성투여독성시험을 통하여 암수 마우스 각각에서 한계투여 용량을 확인하는 것을 목적으로 하였다. 이를 위해 OECD의 급성독성의 권고안에 따라 AtBG1 단백질을 암수 각각 5마리의 ICR 마우스에 몸무게 1 kg 당 2,000 mg을 부형제에 녹여 강제구강투여 하였다. 투여일부터 14일 동안 운동성, 병리학적 이상, 몸무게를 측정하였고 마지막 14일에는 안락사 후에 부검을 통해 AtBG1 투여군과 비투여군의 차이를 확인하였다. 이상의 실험을 통하여 AtBG1 단백질이 운동성, 병리학적 이상, 몸무게 및 부검 결과에서 대조구와 실험구, 두 그룹간의 특이적인 차이를 보이지 않음을 확인하였다. 또한 AtBG1 단백질은 급성독성의 측면에서 안전한 물질로 판단되며, 한계허용치 용량이 2,000 mg을 상회함을 확인하였다. 따라서, 이는 차후 AtBG1 도입 유채의 인체위해성 평가 자료로 사용될 수 있을 것으로 사료된다. Rapeseed (Brassica napus L.) is an oil crop classified as Brassicaceae, and it is widely grown worldwide. To develop a drought-resistant rapeseed, the β-glucosidase 1 (AtBG1) gene was introduced into rapeseed because drought- and salt-resistance phenotypes were observed when the AtBG1 gene was overexpressed in arabidopsis. Newly developed genetically modified crop must be proved to be safe. Safety assessments are based on the historical usage and scientific reports of a crop. In this study, we examined the potential acute oral toxicity of AtBG1 protein expressed in genetically modified (GM) rapeseed and calculated the minimum lethal dose at 6 weeks in both male and female ICR mice. AtBG1 protein was fed at a dose of 2,000 mg/kg body weight in five male and five female mice according to the marginal capacity concentration of OECD, 2,000 mg/15 ml/kg. Mortalities, clinical findings, and body weight changes were monitored for 14 days after dosing, and postmortem necropsy was performed on day 14. This study showed that no deaths occurred in the test group, and AtBG1 protein did not result in variations in common symptoms, body weight, and postmortem findings between the two groups. This showed that the minimum lethal dose of AtBG1 protein expressed in transgenic rapeseed exceed 2,000 mg/kg body weight in both sexes.

Sprague-Dawley 랫드를 이용한 소청룡탕의 단회투여독성시험

이철원(Chul Won Lee),안원근(Won Gun An) 한의병리학회 2011 동의생리병리학회지 Vol.25 No.2