• 생명과학회지
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• 제26권2호
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• pp.204-211
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• 2016

본 실험에서는 유산균발효 독활의 마우스 단회 경구 투여 독성 자료를 얻기 위해 식품의약품안전청 고시 제 2013-121 “의약품 등의 독성시험 기준”에 의거하여, 설치류 투여 한계 용량인 2,000 mg/kg을 최고 투여군을 설정하고 공비 2로 1,000 및 500 mg/kg 투여군을 중간 및 저용량 투여군으로 설정하여 실험을 실시하였으며, 그 결과는 독활 열수 추출물 2,000 mg/kg 암수 투여군 및 암수 매체 대조군과 비교 평가 하였다. 본 실험의 결과, 설치류 투여한계 용량인 2,000 mg/kg 투여군까지, 유산균발효 독활 열수 추출물 투여와 관련된 사망례, 임상증상, 체중, 장기중량, 육안부검 및 조직병리학적 소견이 인정되지 않았다. 따라서 유산균발효 독활 열수 추출물의 마우스에 대한 단회 경구 투여 반수 치사량 및 개략적 치사량은 암수 각각 2,000 mg/kg이상으로 산출되었으며, 특정 임상증상 및 표적 장기 역시 없는 것으로 판단되어, 유산균발효 독활은 매우 안전한 물질로 판단된다. 또한 독활 열수 추출물 2,000 mg/kg 투여와 관련된 사망례, 임상 증상, 체중, 장기중량, 육안 및 조직병리학적 변화 역시 인정되지 않았다. 이러한 결과는 독활의 활용도를 증대시키는 기초 자료가 될 것으로 사료된다.

• Toxicological Research
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• 제18권1호
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• pp.23-29
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• 2002

Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

• 한국약용작물학회지
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• 제28권5호
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• pp.339-346
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• 2020

Background: Cnidium officinale Makino have been used in traditional medicine in Northeast Asia. Although gamma-ray mutagenesis has been used to develop breeding resources with novel characteristics, research on the radiation sensitivity of C. officinale Makino is limited. Hence, the optimal gamma-ray dosage for mutation breeding in C. officinale Makino was investigated. Methods and Results: Seedstocks were exposed to doses of gamma rays (5 Gy - 50 Gy), and subsequently planted in a greenhouse. After 30 days of sowing, the survival rates and growth decreased rapidly at doses above 20 Gy, while all individuals died at 50 Gy. The median lethal dose (LD₅₀) was 25.65 Gy, and the median reduction doses (RD₅₀) for plant height, number of stems, and fresh weight were 12.81, 9.32, and 23.26 Gy, respectively. Post-irradiation levels of malondialdehyde (MDA), peroxidase (POD), and chlorophyll in the aerial parts of the plant were quantified using spectrophotometry. Relative to the controls, the levels of MDA and POD increased, while the level of chlorophyll decreased at doses ≥ 10 Gy, indicating cellular damage. Conclusions: A dose of 20 Gy was found to be optimal for mutation breeding in C. officinale Makino.

• Toxicological Research
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• 제18권1호
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• 한국식품위생안전성학회지
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• 제26권4호
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• pp.377-382
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• 2011

살균소독제, 라미아-킬(benzalkonium chloride(20%), citric acid(20%))에 대하여 랫드와 토끼를 이용하여 급성경구독 성과 피부 자극성 평가를 각각 수행하였다. 랫드에 라미아-킬 2,000 mg/kg 농도를 최고농도로 하여 단회 투여 후, 14일간 관찰한 결과, 사망, 이상증상 및 체 중변화 등은 관찰되지 않아, 라미아-킬의 $LD_{50}$은 2,000 mg/kg 이상으로 추정되었다. 토끼의 등 부위의 털을 제거하고 찰과부위와 비찰과 부위에 여러 농도로 라미아-킬을 도포 한 후, 피부 자극성을 확인한 결과, 라미아-킬의 l차 자극 지수가 0.50으로 비자극성 물질로 분류되었다. 따라서, 본 연구를 통하여, 라미아-킬은 급성경구독성 시 안전한 물질이며, 피부 자극성을 야기하지 않는 물질로 평가되었다.

• Parasites, Hosts and Diseases
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• 제27권3호
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• pp.161-170
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• 1989

Toxeplasma의 추출액을 3H-casein을 기질로 반응시켰을 때, pH 6.0과 PH 8.5에서 casein을 분해하였으며, pH 6.0에서는 cysteinyl protease의 억제제 인 iodoacetamide(rAh)에 의해 억제되 었고, 활성제 인 dithiothreitol (DTT)에 의해 환성이 증가하였다. 또 pH 8.5에서는 serine protease의 억제제인 phenylmethylsulfonil fluoride (PMSF)에 의해 활성이 억제되었으며, ATP를 첨가할 때 그 활성이 증가하여 ATP 의존성 효소임을 알 수 있었다. 위의 단백질 분해 효소를 부분 정제하기 위해 여러 chromatography를 실시하였는데, 먼저 DE52 (2.Sfx40 cm)에 통과시켰을 때, 0.05M-0.IM NaCl에 의해 유출되는 분획이 pH 6.0에서 황성을 나타내었으며, 0.25V- 0.3M에서 유출되는 분획이 pH 8.5에서 황성을 나타내었다. 이 분회들을 각각 Sephadex G-200 ($2.50{\phi}{\times}40cm$) 에 통과시켜 pH 6.0에서 활성을 나타내는 분획은 exclusion limit내에서, pH 8.5의 분획은 exclusion limit 외에서 분획을 얻었다. 이들을 각각 hydroxylapatite ($2.50{\phi}{\times}10cm$과 $2.5{\phi}{\times}20cm$)를 통과시켜 각각을 0.05M Phosphate로 유출되는 분회에서 높은 환성을 얻었다. 부분 정제된 분획들의 특성을 검토하기 위하여 억제제를 농도별로 처리하였을 때, pH 0.0에서의 분해 효소는 10-3M IAA에 의해 활성이 반감되어 cysteinyl acid protease임을 알 수 있었다. pH 8.5에서의 분해 효소는 10-5M PMSF에 의해 활성이 반감되었고, ATP에 의해 활성이 증가(ATP의 농도가 2.0mM 이상에서는 억제)하여 ATP-dependent neutral serine protease임을 알 수 있었다.

• 방사선산업학회지
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• 제6권2호
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• pp.189-197
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• 2012

This study was carried out to develop the improved useful mutants for yield or composition of stevia plants using the gamma ray or chemical mutagens treatments. The seeds of stevia 'Suwon No. 11' were irradiated up to 400 Gy of gamma ray. Chemical mutagens were treated on the seeds of the 'Suwon No. 11' using 0.07% colchicine, 10 mM sodium azide, or 10 mM NMU for various durations. The germination rate, and shoot and root growth of seedling were estimated at 30 days after gamma ray irradiation or chemical mutagen treatment, and the plant height, the number of branches, and leaf length and width were examined at 3 months after mutagenesis treatments. In the case of gamma ray treatments, the germination rate and early-stage growth were decreased as the increase of radiation dose, and the 50% lethal dose was found to be 200 Gy. the plant height was decreased as the increase of radiation dose, while the number of branches per plant and leaf length were increased. Leaf shape was modified to the relatively longer one compared to the control, which was identified more apparently at the treatments of higher than 150 Gy. In the treatment of chemical mutagens, the rate of germination and survival were decreased as the increase of incubation time. The 50% lethal dose for germination rate were identified as the conditions of the 15 hours incubation in 0.07% colchicine, the 4 hrs in 10 mM sodium azide, and the 2 hrs in 10 mM NMU, in the three chemical mutagens treatments. Chemical mutagens had no influence on shoot growth, while root growth was increased, especially as the incubation time was extended. The highest root growth occurred in the NMU treatment at 6 hrs incubation time. The plant height was decreased as the increase of incubation time in the chemical mutagens treatments. Among the chemical mutagens, NMU was the most effective to induce the mutants with long-shaped or the least lobed leaves.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.27-27
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• 2021

Yacon [Samallanthus sonchifolius (Poepp. & Endl.) H. Robinson], a member of Compositae plants, has sweet taste and crisp texture. Unlike other Andean root crops such as potato and sweet potato, the cultivation area of yacon has increased recently, since it is known to have large content of fructooligosaccharides (FOS). Since there are no yacon varieties bred in Korea, we have been trying to create new genetic resources using gamma-ray. The optimal gamma-ray dosage for mutation breeding in yacon was investigated. Crown bud and green bud of yacon were exposed to doses of gamma rays from 20 Gy to 80 Gy, and subsequently planted in a greenhouse. After 50 days of sowing, the survival rates and growth decreased rapidly at doses above 40 Gy, while all of crown bud individuals died above 60 Gy. The median lethal dose (LD50) of crown bud and green bud was 22.4 and 36.6 Gy, and the median reduction doses (RD50) for plant height, fresh weights, and tuberous root weight were 20-40 Gy, respectively. A dose of 20-40 Gy was found to be optimal for mutation breeding in yacon. Considering the growth factors, the optimum doses were determined to be within the range of 20-40 Gy for the selection of useful mutant lines. M2-M3 mutant lines were obtained from 20-60 Gy gamma-ray-irradiated M1 plants through clonal propagation. These mutant lines will be used for the development of a new variety of yacon plant with high FOS and no crack tuberous root.

• Toxicological Research
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• 제6권1호
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• pp.41-49
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• 1990

Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

• 약학회지
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• 제43권2호
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.