농약 제품 및 원제의 급성경구독성과 급성경피독성 비교 평가

조유미(Youmi Jo),박수진(Soojin Park),유아선(Are-Sun You),오진아(Jin A Oh),이제봉(Je Bong Lee),박연기(Yeon-Ki Park),이주연(Ju Yeon Lee),정미혜(Mihye Jeong) 한국농약과학회 2018 농약과학회지 Vol.22 No.3

The Korean Pesticide Control Act requires acute oral and dermal toxicity tests for hazard classification and labelling of agrochemicals to protect human health. In this study, we investigated whether acute oral toxicity testing for pesticides and active ingredients could be used to determine acute dermal hazard category and acute systemic toxicity. This retrospective analysis used oral and dermal LD<SUB>50</SUB> data for 511 end-use products and 72 active ingredients submitted to RDA for registration. The concordance of oral and dermal hazard classification was 78% and 77.9% of products by RDA and GHS system, respectively. The acute oral toxicity was more potent than the acute dermal toxicity for 13.5% and 21.9% of products by RDA and GHS system. Using the oral hazard category as a predictor for dermal hazard, 91.5% and 99.7% of end-use products, by each RDA and GHS system, would have the same or more conservative dermal hazard category and therefore would have more protective hazard labelling. Also, the oral hazard category derived from oral LD<SUB>50</SUB> was the same as or over-classified the dermal hazard category from dermal LD<SUB>50</SUB> for 100% of active ingredients. However, when oral LD<SUB>50</SUB> was used for dermal toxicity category of active ingredients without acute dermal toxicity testing data, over-prediction of dermal hazard was 21.4% which indicates that oral LD<SUB>50</SUB> are sufficiently protective for acute dermal hazard classification. Taken together, dermal acute systemic toxicity data hardly provides additory value in regulatory decision making.

Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity

Dongxia Gou,Xuejing Pei,Jiao Wang,Yue Wang,Chenxing Hu,Chengcheng Song,Sisi Cui,Yifa Zhou 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.5

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca<SUP>2+</SUP>/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

WHW®의 랫드에서의 반복경구투여 독성에 관한 연구

오태우,배효상,윤철호,박용기 대한본초학회 2010 大韓本草學會誌 Vol.25 No.3

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity. Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

Acute Oral or Dermal and Repeated Dose 90-Day Oral Toxicity of Tetrasodium Pyrophosphate in Spraque Dawley (SD) Rats

서동석,권민,성하정,박철범 환경독성보건학회 2011 환경독성보건학회지 Vol.26 No.-

Objectives: Tetrasodium pyrophosphate (TSP) is used in processed meat products, as an emulsifier in cheese, and as a color preservative in soybean paste. However, little is known about its toxicity. This study was conducted to investigate the potential acute and repeated dose toxicity of TSP in Spraque Dawley (SD) rats. Methods: In the acute study, animals were administered with oral or dermal doses of 2,000 mg/kg TSP. In the repeated dose study, animals were administered doses of 0, 250, 500, and 1,000 mg/kg by oral gavage five times a week for 90 days. Results: In acute toxicity studies, no dead animals or abnormal necropsy findings were found in the control or treated group. In the repeated dose toxicity study, there were no significant changes in body weight in the 1,000 mg/kg treatment group, or food consumption, urinalysis,and hematology in any group. With regards serum biochemistry, the levels of total protein, albumin, A/G ratio, triglyceride, calcium and inorganic phosphate were altered at doses of 500 and 1,000 mg/kg. However, no changes were observed at the dose of 250 mg/kg. With regards histopathological findings, cortical tubular basophilia of the kidney increased at the dose of 1,000 mg/kg, but not at doses of 250 and 500 mg/kg. No significant changes were observed in other organs at doses of 250, 500, and 1,000 mg/kg. Conclusions: Based on the results, TSP is unclassified according to the Globally Harmonization System, with an LD50 value of over 2,000mg/kg. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) were 250 and 500 mg/kg /day respectively and the target organ appears to be the kidney.

Acute Oral Toxicity and Pathogenicity of a Potential Probiotic Bacillus sp. A9184 Isolated from Soybean Paste

Lim, Jong-Hwan,Park, Byung-Kwon,Kim, Myoung-Seok,Rhee, Man-Hee,Park, Seung-Chun,Yun, Hyo-In Korean Society of ToxicologyKorea Environmental Mu 2004 Toxicological Research Vol.20 No.4

This study provides more information about the potential toxicological risk of Bacillus sp. A9184 isolated from soybean paste. The evaluation was based on the guidelines of acute oral toxicity/pathogenicity for microbial pesticide and was to get more comprehensive understanding on the acute toxicity of the potential probiotic in Sprgue-Dawley rats. No dead animal was observed in rats after single oral administration with bacteria ($10^8$ CFU per animal). There were neither no treatment-related changes in clinical signs, nor changes in body weight and body temperature as com-pared with the untreated group. All tested animal showed the increase in body weight with time. The results obtained in this study suggest that the potential probiotic, Bacillus sp. A9184, is non-toxic for rat.

배양 노랑다발동충하초 부탄올분획의 급성경구독성

박은영,박형진,양기숙 한국생약학회 2009 생약학회지 Vol.40 No.3

Cordyceps bassiana is a parasitic fungus and used as a Chinese traditional medicine. It has been called as Dong- ChungHaCho(summer-plant, winter-worm) in China. Acute oral toxicity was examined in male and female ICR mice. Butanol fraction from Cordyceps bassiana(BuCb) was administered orally at a dose of 2,500 mg/kg, 5,000 mg/kg, 10,000 mg/kg. No death and abnormal clinical signs were observed throughout the administration period. The acute toxicity test on mouse did not show any oversign in net body weight gain, food and water consumptions, organ weights, gross pathological findings by different doses of BuCb. Also, biochemical examination revealed no evidence of specific toxicity. These findings show that BuCb has wide margin of safety on acute toxicity with single exposure.

털부처꽃 물 추출물의 Sprague-Dawley 랫드를 이용한 단회경구투여 독성시험

김희영 ( Hee-young Kim ),박예진 ( Yea-jin Park ),신수 ( Su Shin ),최민우 ( Min-woo Choi ),홍은진 ( Eun-jin Hong ),신영우 ( Young Woo Shin ),차윤엽 ( Yun-yeop Cha ),안효진 ( Hyo-jin An ) 대한본초학회 2022 大韓本草學會誌 Vol.37 No.3

Objectives : Single oral dose toxicity test of Lythri Herba water extracts (LHWE) in Sprague-Dawley (SD) rat was performed to determine approximate lethal dose (ALD) of LHWE. Methods : This test was progressed according to OECD Guidelines for the Testing of Chemicals : acute oral toxicity. After adaptation of 7 days, SD rats were divided into 2 groups : vehicle control and 5000 mg/kg LHWE-treated group. Each group consisted of 5 female rats and 5 male rats. Vehicle or 5000 mg/kg LHWE was orally administrated once a day. Survival rates, general toxicity, and changes of body weight were investigated for 14 days after administration. On the last day of examination, the weight of all animals was measured and an autopsy was performed. All internal organ abnormalities were checked macroscopically and their findings were recorded. Results : In both groups, dead animals were not observed. During 14 days of administration, abnormal clinical signs were not detected. There was also no significant difference in weight gains between each group. Autopsy analysis showed that one case of the LHWE-treated female group had retention of clear fluid in the uterus; however, it was not considered to be affected by LHWE administration. Moreover, abnormal findings were not discovered in the control male group and the LHWE-treated male group. Conclusions : These results suggest that the ALD of LHWE exceed 5000 mg/kg and single oral administration of LHWE below 5000 mg/kg is nontoxic.

Evaluation of the Oral Acute Toxicity of Black Ginseng in Rats

Lee, Mi-Ra,Oh, Chang-Jin,Li, Zheng,Li, Jing-Jie,Wang, Chun-Yan,Wang, Zhen,Gu, Li-Juan,Lee, Sang-Hwa,Lee, Jae-Il,Lim, Beong-Ou,Sung, Chang-Keun The Korean Society of Ginseng 2011 Journal of Ginseng Research Vol.35 No.1

We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/kg dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/kg did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral $LD_{50}$ of the BG extract in the rats is higher than 15 g/kg. Compared to the control group, no treatment-related biologically significant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed significant differences at 10 and 15 g/kg doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.

Development of chitosan-catechol conjugates as mucoadhesive polymer: assessment of acute oral toxicity in mice

Loveleen Kaur,Ritu Raj,Ajay Kumar Thakur,Inderbir Singh 환경독성보건학회 2020 환경독성보건학회지 Vol.35 No.3

Development of modified polymers is the focused area of research for developing stable, effective, sustainable and economical polymeric materials for developing different drug delivery systems. Modification of chitosan by catechol functionalization is useful for developing chitosan derivative with the improved mucoadhesive property. Present study was designed to perform single dose acute oral toxicity on chitosan-catechol conjugates in Swiss albino mice as per international guidelines. Oral administration of modified chitosan did not exhibit any significant change in body weight, behavioural pattern, haematology, food intake and clinical symptoms in the experimental animals. In the histopathological study, no pathological changes were observed in the vital organs of mice when administered perorally with 300 mg/kg and 2,000 mg/kg body-weight doses of chitosan-catechol polymeric conjugates. Overall, it was concluded from the acute oral toxicity study that the oral administration of chitosan-catechol conjugates in mice did not produce any toxicity. Hence, chitosan-catechol conjugates could be designated and recommended as safe polymeric material for developing different drug delivery systems.

Evaluation of the Oral Acute Toxicity of Black Ginseng in Rats

Mi-Ra Lee,Chang-Jin Oh,Zheng Li,Jing-Jie Li,Chun-Yan Wang,Zhen Wang,Li-Juan Gu,Sang-Hwa Lee,Jae-Il Lee,Beong-Ou Lim,Chang-Keun Sung 고려인삼학회 2011 Journal of Ginseng Research Vol.35 No.1

We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/㎏ dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/㎏ did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral LD?? of the BG extract in the rats is higher than 15 g/㎏. Compared to the control group, no treatment-related biologically signifi cant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed signifi cant differences at 10 and 15 g/㎏ doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.