• Title/Summary/Keyword: Toxicity Test

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Toxicity prediction of chemicals using OECD test guideline data with graph-based deep learning models (OECD TG데이터를 이용한 그래프 기반 딥러닝 모델 분자 특성 예측)

  • Daehwan Hwang;Changwon Lim
    • The Korean Journal of Applied Statistics
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    • v.37 no.3
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    • pp.355-380
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    • 2024
  • In this paper, we compare the performance of graph-based deep learning models using OECD test guideline (TG) data. OECD TG are a unique tool for assessing the potential effects of chemicals on health and environment. but many guidelines include animal testing. Animal testing is time-consuming and expensive, and has ethical issues, so methods to find or minimize alternatives are being studied. Deep learning is used in various fields using chemicals including toxicity prediciton, and research on graph-based models is particularly active. Our goal is to compare the performance of graph-based deep learning models on OECD TG data to find the best performance model on there. We collected the results of OECD TG from the website eChemportal.org operated by the OECD, and chemicals that were impossible or inappropriate to learn were removed through pre-processing. The toxicity prediction performance of five graph-based models was compared using the collected OECD TG data and MoleculeNet data, a benchmark dataset for predicting chemical properties.

Insecticidal Activity of Japanese Pine Sawyer (Monochamus alternatus) and Toxicity Test of Honeybee (Apis mellifera) using 5 Kinds of Neonicotinoids (5종의 네오니코티노이드계 약제에 대한 솔수염하늘소의 살충활성과 꿀벌독성)

  • Cho, Woo Seong;Jeong, Dae-Hoon;Lee, Jae Seon;Kim, Hyun Kyung;Seo, Sang-Tae;Kim, Gil-Hah
    • The Korean Journal of Pesticide Science
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    • v.21 no.1
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    • pp.33-41
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    • 2017
  • Susceptibility and persistence of Japanese pine sawyer, Monochamus alternatus adults, and acute contact toxicity, foliage contact toxicity, and residual toxicity to honeybee, Apis mellifera were evaluated by using 5 kinds of neonicotinoid pesticides. All neonicotinoids pesticides showed over 80% mortality 48 hour after body spray treatment. However, only 2 kinds of acetamiprid ME and acetamiprid+buprofezin showed over 80% mortality in the twig dipping treatment. All of the five neonicotinoides pesticides used in M. alternatus adults showed residual effect of 60-80% mortality, but the efficacy decreased rapidly after 1 day of treatment. Acetamiprid ME showed the lowest toxicity in the acute and foliage contact toxicity test of A. mellifera. The residual toxicity of leaves on A. mellifera was very low in acetamiprid ME and acetamiprid+buprofezin. However, the residual toxicity of all pesticides treatments decreased to 10-30% after 1 day of treatment and further decreased with time. These results indicate that acetamiprid ME among five neonicotinoid agents showed a high insecticidal activity in the M. alternatus adults, while it exhibited relatively low contact and residual toxicity in the A. mellifera. It is thought that acetamiprid ME can be effectively used for the control of the M. alternatus adults as vector of pine wilt disease.

Fundamentals of Ecotoxicity Evaluation Methods using Domestic Aquatic Organisms in Korea : (I) Fish (국내 생물종을 이용한 생태독성평가 기반연구 : (I) 어류)

  • Nam, Sun-Hwa;Yang, Chang-Yong;An, Youn-Joo;Lee, Jae-Kwan
    • Korean Journal of Ecology and Environment
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    • v.40 no.2
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    • pp.173-183
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    • 2007
  • The Ministry of Environment plans to introduce the Whole Effluent Toxicity (WET) system in Korea. The WET test is well established in developed countries with recognizing of the limitations of physicochemical analysis method and potential risk of chemicals in water medium. Therefore, it is essential to build the ecotoxicity infrastructure for the induction of WET test. In this study, we extensively collected the domestic and foreign toxicity test methods which employ native test species to Korea. And we suggested that the domestic ecotoxicity test methods with domestic test species in Korea through extracting the range of test conditions. Five domestic fish species selected were Carassiu auratus (Crucian carp), Cyprinus carpio(Common carp), Gasterosteus aculeatus (Three spine stickleback), Misgurnus anguillicaudatus (Oriental weather fish) and Oryzias latipes (Japanese medaka), The toxicity test methods with native test species to Korea were collected from the standard methods (OECD, U.S. EPA, ASTM), government reports, SCI papers and domestic papers. We collected the 32 test methods, and suggested the suitable aquatic toxicity test methods for fish. It is expected that this study could prove a useful information to establish the ecotoxicity test methods with domestic aquatic organisms in Korea henceforth.

Application of Toxicity Identification Evaluation Procedures for Toxic Effluents from the Aluminum Rolling Industry (알루미늄 가공 공장 배출 방류수의 독성 원인물질 탐색)

  • Ra, Jin-Sung;Lee, Jiho;Kim, Ki-Tae
    • Journal of Environmental Health Sciences
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    • v.41 no.5
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    • pp.305-313
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    • 2015
  • Objectives: The objective of this study is to identify toxicants causing acute toxicity in effluents from the aluminum rolling industry that violate the discharge limits in Korea. Methods: Whole effluent toxicity tests (WET) were conducted on effluent discharged from the aluminum rolling industry following the US EPA WET test methods. We collected effluent samples three times and evaluated acute toxicity by using Daphnia magna. We employed toxicity identification evaluation (TIE) procedures to identify toxicants causing toxicity in the effluent. Results: No specific chemical groups were identified in the seven different manipulations applied to the of wastewater effluent samples showing 1.3 toxic units (TU) according to the TIE phase I procedures. Water quality parameters for water hardness, electric conductivity and heavy metals (Mn) were 4,322 mg/l as $CaCO_3$, 11.39 mS/cm, and $5,551{\mu}g/l$, respectively. Considering water hardness and reference toxicity, high concentrations of Mn can be disqualified from the causative toxicants. Consequently, high ionic concentrations of $Na^+$(1,648 mg/l), $Ca^{2+}$(1,048 mg/l), $Mg^{2+}$(1,428 mg/l) and $SO_4{^{2-}}$(7,472 mg/l) were identified to be causative toxicants. Water hardness and electric conductivity exceed the $EC_{50}$ value obtained by biological toxicity tests using Daphnia magna. Conclusion: According to TIE procedures, high salt concentration is determined to be a major toxicant in the effluent of agro-industrial wastewater treatment plants receiving wastewater from the aluminum rolling industry.

Subacute Inhalation Toxicity of Cyclohexanone in B6C3F1 Mice

  • Lee, Yong-Hoon;Chung, Yong Hyun;Kim, Hyeon-Yeong;Shin, Seo Ho;Lee, Sang Bae
    • Toxicological Research
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    • v.34 no.1
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    • pp.49-53
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    • 2018
  • Cyclohexanone ($C_6H_{10}O$, CAS No. 108-94-1) is a colorless oily liquid obtained through the oxidation of cyclohexane or dehydrogenation of phenol. It is used in the manufacture of adhesives, sealant chemicals, agricultural chemicals, paint and coating additives, solvent, electrical and electronic products, paints and coatings, photographic supplies, film, photochemicals, and as an intermediate in nylon production. Owing to the lack of information on repeated inhalation toxicity of cyclohexaone, in this study, we aimed to characterize the subacute inhalation toxicity. B6C3F1 mice were exposed to 0, 50, 150, and 250 ppm of cyclohexanone for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation in accordance with the OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study). Mortality, clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weights, as well as gross and histopathological findings were evaluated between the control and exposure groups. No mortality or remarkable clinical signs were observed during the study. No adverse effects on body weight, food consumption, hematology, serum biochemistry, and organ weights, gross or histopathological lesions were observed in any male or female mice in any of the exposure groups, although some statistically significant changes were observed in organ weights. We concluded that no observable adverse effect level (NOAEL) is above 250 ppm in mice exposed to cyclohexanone for 6 hr/day for 5 days/week.

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

  • Gou, Dongxia;Pei, Xuejing;Wang, Jiao;Wang, Yue;Hu, Chenxing;Song, Chengcheng;Cui, Sisi;Zhou, Yifa
    • Journal of Ginseng Research
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    • v.44 no.5
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    • pp.717-724
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    • 2020
  • 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 Ca2+/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.

Environmental Toxicity of ACQ-Treated Wood Based on the Fish Acute Test (어류급성독성 시험에 의한 ACQ 방부목재의 환경 독성)

  • Woo, Ji-Keun;Kim, Du-Won;Kim, Sung-Kyun
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.14 no.2
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    • pp.107-115
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    • 2011
  • The purpose of the study is to analyze the environmental characteristics of fish acute toxicity that is dependent on the harmfulness of ACQ (Alkaline Copper Quat)-Treated Wood and Oryzias latipes mortality in a comprehensive way, provide objective verification method on the eco-toxicity and environment-friendliness of landscaping materials and methods, and utilize it as a basic datum for evaluation criteria. The main results are summarized as follows : 1. As a result of analysis on the harmfulness characteristics, each experimental plot showed different values respectively. In particular, it has been found that in proportion to the volume of testing materials, COD and Cu increases at a constant rate, compared to the input water. In the plot C with three testing materials, COD increased 67 times more than that of the input water, and Cu increased up to 12.36mg/L. 2. In case of fish toxicity, plot C, B, A all showed a mortality rate of 100%, indicating that fish toxicity is strong. In particular, the mortality rate of each plot within the initial time of one and a half hour showed clearly, which suggests that the fish toxicity is influenced by the increased concentration of hazardous substances depending on the volume ratio of testing materials. 3. As a result of comparison and analysis on the harmfulness and fish toxicity, the harmfulness showed different values on each experimental plot but, we found that the changing rate of values of toxicity of COD and Cu is mutually similar to that of mortality in the initial hour according to the experiment of fish toxicity, which shows that COD and Cu are major factors to increase fish toxicity.

4 Weeks Repeated Oral Dose Toxicity Studies with LMK02-Jangwonhwan in SD Rats (LMK02의 Sprague-Dawley 랫드를 이용한 4 주간 반복 경구투여 DRF 독성시험)

  • Lyu, Yeoung-Su;Kim, Ji-Hwon;Park, Hyun-Je;Yi, Kyung-Hee;Lee, Jong-Hwa;Kang, Hyung-Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.1034-1041
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    • 2010
  • The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.

A 13-Week Repeated Oral Dose Toxicity Test and a 4-Week Recovery Test of Standardized Cornus officinalis and Psoralea corylifolia L . in Sprague-Dawley Rats (산수유(山茱萸)와 보골지(補骨脂) 복합추출물의 Sprague-Dawley 랫드를 이용한 13 주 반복경구투여 독성시험 및 4 주 회복시험)

  • Sim, Seo-Ah;Kang, Sung-Chul;Jin, Bo-Ram;Kim, Min-jeong;Yeo, Sujung;Park, In-hwa;Jerng, Ui Min;Cha, Yun-yeop;Ahn, Ji-Hye;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.36 no.6
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    • pp.27-37
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    • 2021
  • Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery test of standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30 % ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

Toxicity Study of Red Ginseng Acidic Polysaccharide (RGAP) : Single and 2-week Repeated Oral Dose Toxicity Study in Rats

  • Park, Jong-Dae;Song, Yong-Bum;Kwak, Yi-Seong;Kim, Jong-Choon;Im, Doo-Hyun;Junghee Han
    • Toxicological Research
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    • v.19 no.3
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    • pp.173-180
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    • 2003
  • The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day 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 RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.