• Title/Summary/Keyword: toxicity screening

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A Systematic Review of Toxicological Studies to Identify the Association between Environmental Diseases and Environmental Factors (환경성질환과 환경유해인자의 연관성을 규명하기 위한 독성 연구 고찰)

  • Ka, Yujin;Ji, Kyunghee
    • Journal of Environmental Health Sciences
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    • v.47 no.6
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    • pp.505-512
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    • 2021
  • Background: The occurrence of environmental disease is known to be associated with chronic exposure to toxic chemicals, including waterborne contaminants, air/indoor pollutants, asbestos, ingredients in humidifier disinfectants, etc. Objectives: In this study, we reviewed toxicological studies related to environmental disease as defined by the Environmental Health Act in Korea and toxic chemicals. We also suggested a direction for future toxicological research necessary for the prevention and management of environmental disease. Methods: Trends in previous studies related to environmental disease were investigated through PubMed and Web of Science. A detailed review was provided on toxicological studies related to the humidifier disinfectants. We identified adverse outcome pathways (AOPs) that can be linked to the induction of environmental diseases, and proposed a chemical screening system that uses AOP, chemical toxicity big data, and deep learning models to select chemicals that induce environmental disease. Results: Research on chemical toxicity is increasing every year, but there is a limitation to revealing a clear causal relationship between exposure to chemicals and the occurrence of environmental disease. It is necessary to develop various exposure- and effect-biomarkers related to disease occurrence and to conduct toxicokinetic studies. A novel chemical screening system that uses AOP and chemical toxicity big data could be useful for selecting chemicals that cause environmental diseases. Conclusions: From a toxicological point of view, developing AOP related to environmental diseases and a deep learning-based chemical screening system will contribute to the prevention of environmental diseases in advance.

Screening of Biological Activity of Crude Drugs Using Brine Shrimp Bioassay (Brine Shrimp Bioassay를 이용한 수종생약의 생리 활성 검색)

  • Lee, Ji-Sook;Kim, Jin-Woong
    • Korean Journal of Pharmacognosy
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    • v.21 no.1
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    • pp.100-102
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    • 1990
  • Brine shrimp bioassay has been frequently utilized as a basic screening method for detecting a broad range of bioactive compounds from natural products. Each methanol, chloroform, and water extract of thirty-eight crude drugs were screened in the brine shrimp bioassay, and a number of crude drugs exhibited toxicity against brine shrimp nauplii.

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28-day Repeated-dose Toxicity Study of Flutamide, an Anti- androgenic Agent, in Rats: Establishment of Screening Methods for Endocrine Disruptors (내분비계 장애물질 검색법의 확립을 위한 항안드로젠성 물질 flutamide의 랫드 28일 반복투여 독성실험)

  • 정문구;김종춘;임광현;하창수
    • Toxicological Research
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    • v.16 no.2
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    • pp.163-172
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

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A Study for Testing Conditions of Microtox Toxicity Test to the Quality of Sediment in Domestic Rivers (국내 하천 퇴적물 건강성평가를 위한 Microtox 독성시험 조건확립 연구)

  • 정홍배;박정규;문성환;류태권;김소정;배철한;황인영
    • Environmental Analysis Health and Toxicology
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    • v.16 no.4
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    • pp.143-151
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    • 2001
  • Six rivers were selected as preliminary screening sites to determine the test conditions of Microtox in assessing the toxicity of the sediment. In addition, a pH range of 6.0∼6.5 was established in testing pore water, aqueous extracts and organic extracts. Each extractable fraction of sediment showed different toxicities. Therefore, in order to properly examine the toxicity in the sediment, all extractable fractions of sediment samples needed to be tested with Microtox. Thus, sediment samples were additionally collected from at least 4 secondary sites within 50∼100m area of the primary sampling site to reduce any variation or deviation in toxicity assessment. From all sediment toxicity data that was collected from this study, it was concluded that the Keumho river was the most polluted with the highest sediment toxicity of all the rivers analyzed and needed further detailed research on its pollution problem.

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The Long-Term Safety and Efficacy of Intrathecal Therapy Using Sufentanil in Chronic Intractable Non-Malignant Pain

  • Monsivais, Jose Jesus;Monsivais, Diane Burn
    • The Korean Journal of Pain
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    • v.27 no.3
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    • pp.297-300
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    • 2014
  • This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome.

Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

  • Nam, Chunja;Hwang, Jae-Sik;Han, Kyoung-Goo;Jo, Eunhye;Yoo, Sun-kyoung;Eom, Ig-Chun;Kang, Jong-Koo
    • Toxicological Research
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    • v.32 no.4
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    • pp.327-335
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    • 2016
  • This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day.

Analysis of quantitative high throughput screening data using a robust method for nonlinear mixed effects models

  • Park, Chorong;Lee, Jongga;Lim, Changwon
    • Communications for Statistical Applications and Methods
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    • v.27 no.6
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    • pp.701-714
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    • 2020
  • Quantitative high throughput screening (qHTS) assays are used to assess toxicity for many chemicals in a short period by collectively analyzing them at several concentrations. Data are routinely analyzed using nonlinear regression models; however, we propose a new method to analyze qHTS data using a nonlinear mixed effects model. qHTS data are generated by repeating the same experiment several times for each chemical; therefor, they can be viewed as if they are repeated measures data and hence analyzed using a nonlinear mixed effects model which accounts for both intra- and inter-individual variabilities. Furthermore, we apply a one-step approach incorporating robust estimation methods to estimate fixed effect parameters and the variance-covariance structure since outliers or influential observations are not uncommon in qHTS data. The toxicity of chemicals from a qHTS assay is classified based on the significance of a parameter related to the efficacy of the chemicals using the proposed method. We evaluate the performance of the proposed method in terms of power and false discovery rate using simulation studies comparing with one existing method. The proposed method is illustrated using a dataset obtained from the National Toxicology Program.

Biological Evaluation for Characteristics of Leachate Toxicity from Municipal Solid Waste Landfill (생물학적 방법에 의한 도시생활폐기물 매립지의 침출수 독성특성 평가)

  • 황인영;류경무
    • Environmental Analysis Health and Toxicology
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    • v.11 no.1_2
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    • pp.31-39
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    • 1996
  • Leachate from municipal solid waste (MSW) landfill, effluent from leachate treatment plant, and ground water sample from a monitoring well near landfill site were tested for an acute toxicity. Microtox toxicity test was used for testing the acute toxicity of leachate and other samples. EC$_{50}$ values which a concentration of pollutant for reducing 50% light output from luminescent bacteria, Photobacterium phosphoreum were determined to assess the toxicity of pollutants as well as the relative toxicity. In addition, characteristics of leachate were studied and compared to those of phenol and pentachlorophenol (PCP) which are typical aquatic toxic pollutants. For leachate, EC$_{50}$ for 30 min incubation was 10.8%, while for phenol and PCP, 46 ppm and 1.2 ppm, respectively. the relative toxicity of treated leachate by in situ aeration with activated sludge was reduced to more than 75% of toxicity of the untreated leachate. Microtox toxicity test was failed to figure out EC$_{50}$ values for groundwater from a monitoring well since the relative toxicity of the unconcentrated sample was too low to estimate EC$_{50}$. Addition of activated carbon to leachate was reduced the relative toxicity. The reduction Pattern of the relative toxicity of leachate by mechanical aeration was similar to that of PCP, but different from that of phenol. These findings suggest that the toxicity of leachate may come from PCP-like toxic compounds rather than phenol-like one. In conclusion, the process of aeration with activated sludge might be very important to reduce the environmental toxicity of leachate. And Microtox test could be a reasonable bioassay for screening and monitoring the environmental toxicity of leachate from municipal solid waste landfill as well as for determining the reduction efficiency of the leachate toxicity by various treatment processes in leachate treatment plant.

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Toxicity Assessment of PFOA and PFOS Using Freshwater Flea Hyalella azteca (담수산 물벼룩인 Moina macrocopa를 이용한 과불화화합물 PFOA와 PFOS의 독성평가)

  • Lee, Chul-Woo;Kim, Hyun-Mi;Choi, Kyung-Hee
    • Environmental Analysis Health and Toxicology
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    • v.22 no.3
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    • pp.271-277
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    • 2007
  • Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are fully flurorinated organic compounds which are highly persistent in environment and accumulated in organism. These chemicals are released to the environment at their manufacture, during their use in industrial and consumer applications and from disposal after their use. The purpose of this study was to determine the effects of PFOA and PFOS on the freshwater flea (Moina macrocopa). Acute toxicity test and chronic toxicity test were performed for 2 days and 10 days, respectively. Acute toxicity was assessed on the basis of mortality, while chronic toxicity was assessed by fecundity as well as mortality. The acute toxicity studies on PFOA and PFOS showed that the values of $LC_{50}$ were $73.9\;mg/L\;and\;27.7\;mg/L$ respectively. In the chronic toxicity test, fecundity was reduced significantly at 24.1 mg/L of PFOA and 9.3 mg/L of PFOS, respectively. Conclusively, the results of this work suggest that Moina macrocopa could be a suitable model organism for screening and assessing of environmental pollutants in water.

Toxicity Screening After Single Dose of a Newly Developed Oral Heparin Derivative in Male Cynomolgus Monkeys (게잡이 원숭이에 있어 새로운 헤파린유도체의 단회투여 독성스크리닝)

  • Kim, Choong-Yong;Kim, Sang-Kyoon;Woo, Young-Ah;Jeong, Eun-Ju;Han, Su-Cheol;Heo, Jeong-Doo;Park, Kui-Lea;Byun, Young-Ro
    • Toxicological Research
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    • v.23 no.2
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    • pp.159-164
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    • 2007
  • Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.