• Title/Summary/Keyword: BIOLOGICAL TOXICITY

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Toxicity of nanoparticles_ challenges and opportunities

  • Ramanathan, Amall
    • Applied Microscopy
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    • v.49
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    • pp.2.1-2.11
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    • 2019
  • Nanomaterials (NMs) find widespread use in different industries that range from agriculture, food, medicine, pharmaceuticals, and electronics to cosmetics. It is the exceptional properties of these materials at the nanoscale, which make them successful as growth promoters, drug carriers, catalysts, filters and fillers, but a price must be paid via the potential toxity of these materials. The harmful effects of nanoparticles (NPs) to environment, human and animal health needs to be investigated and critically examined, to find appropriate solutions and lower the risks involved in the manufacture and use of these exotic materials. The vast number and complex interaction of NM/NPs with different biological systems implies that there is no universal toxicity mechanism or assessment method. The various challenges need to be overcome and a number of research studies have been conducted during the past decade on different NMs to explore the possible mechanisms of uptake, concentrations/dosage and toxicity levels. This review article examines critically the recent reports in this field to summarize and present opportunities for safer design using case studies from published literature.

γ-Aminobutyric acid (GABA) confers chromium stress tolerance in mustard (Brassica juncea L.) seedlings by modulating the antioxidant defense and glyoxalase systems

  • Al Mahmud, Jubayer;Hasanuzzaman, Mirza;Nahar, Kamrun;Rahman, Anisur;Hossain, Md. Shahadat;Fujita, Masayuki
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.235-235
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    • 2017
  • Chromium (Cr) toxicity is hazardous to the seed germination, growth, and development of plants. ${\gamma}$-Aminobutyric acid (GABA) is a non-protein amino acid and is involved in stress tolerance in plants. To investigate the effects of GABA in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.) seedlings with Cr (0.15 mM and 0.3 mM $K_2CrO_4$, 5 days) alone and in combination with GABA ($125{\mu}M$) in a semi-hydroponic medium. The roots and shoots of the seedlings accumulated Cr in a dose-dependent manner, which led to an increase in oxidative damage [lipid peroxidation; hydrogen peroxide ($H_2O_2$) content; superoxide ($O{_2}^{{\cdot}-}$) generation; lipoxygenase (LOX) activity], MG content, and disrupted antioxidant defense and glyoxalase systems. Chromium stress also reduced growth, leaf relative water content (RWC), and chlorophyll (chl) content but increased phytochelatin (PC) and proline (Pro) content. Furthermore, supplementing the Cr-treated seedlings with GABA reduced Cr uptake and upregulated the non-enzymatic antioxidants (ascorbate, AsA; glutathione, GSH) and the activities of the enzymatic antioxidants including ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II), and finally reduced oxidative damage. Adding GABA also increased leaf RWC and chl content, decreased Pro and PC content, and restored plant growth. These findings shed light on the effect of GABA in improving the physiological mechanisms of mustard seedlings in response to Cr stress.

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Single Oral Dose-increasing Toxicity Test and Four Weeks Repeated Oral Dose Determinating Test of ACM (Added Chongmyung-tang) in Beagle Dogs (ACM의 비글견을 이용한 단회 경구투여 용량증가 독성 시험 및 4주 반복 경구투여 용량 결정 시험)

  • Lim, Jung-Hwa;Lee, Sang-Ryong;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.24 no.1
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    • pp.131-144
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    • 2013
  • Objectives : To provide information on the safety of ACM, we carried out a single oral dose-increasing toxicity and 4-weeks repeated oral dose determining test of ACM in beagle dogs. Methods : In a single oral dose-increasing toxicity test, beagles were treated with ACM orally increasing dose level (1,000, 2,000, 5,000 mg/㎏) at interval of 3 days. After administration, signs of toxicity were observed for two weeks. In 4-weeks repeated oral dose determinating test, beagles were treated with ACM with oral dose 500, 1,000, 2,000 mg/kg for 4 weeks. Mortality, clinical signs, body weight changes, food consumption, urinalysis, hematological and biochemical parameters, organ weights, necropsy findings, and histological findings were monitored during the study period. Results : In a single oral dose-increasing toxicity test, we found no mortality, abnormalities in clinical signs, body weight, and necropsy findings during the study period. In 4-weeks repeated oral dose determinating test, we found no mortality, abnormalities in clinical signs, body weight, food consumption, urinalysis, hematological and biological parameters, gross findings, organ weights, necropsy findings, and histopathological findings in any of the beagles tested. Conclusions : The results obtained in these studies suggest that maximum tolerated dose (MTD) of ACM in male and female beagle dogs was supposed to be over 5,000 mg/kg. For the future studies of toxicity, it is advisable that high dose and low dose are set at 2000 mg/kg and 500 mg/kg, respectively.

Decomposition Characteristics of 1,4-dioxane in an E-beam Process and Toxicity Assessment (전자빔 공정을 적용한 1,4-dioxane의 제거특성 및 독성평가)

  • Hwang, Haeyoung;Chang, Soonwoong
    • Journal of the Korean GEO-environmental Society
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    • v.12 no.2
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    • pp.63-68
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    • 2011
  • The aim of this study was 1,4-dioxane's degradation efficiency and toxicity test applying E-beam. The experiments were shows that the degradation efficiency in the initial concentration of 1,4-dioxane and the irradiation capacity of E-beam and the degree of mineralization based on a change of scavenger gas. The biological toxicity test by using on of green algae, Pseudokirchneriella Subcapitata was conducted to lead the reducing toxicity. Degradation efficiency of 1,4-dioxane was improved when E-beam irradiation intensity was higher and the efficiency of TOC removal using Radical scavenger gas was increased by $N_2O$, $O_2$ and $N_2$ in order. In 4 days(96hrs), toxicity test results indicated that toxicity effect was decreased by increase of E-beam irradiation intensity.

Synthesis and Biological Effects of 2, 3-Diphenyl-5-Methoxyindole and Substituted Benzophenone Derivatives

  • Hishmat, O.H.;El-Sbabrawy, O.A.;Nakkady, S.S.;Mahmoud, S.S.
    • Archives of Pharmacal Research
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    • v.12 no.3
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    • pp.149-153
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    • 1989
  • Seven 2, 3-diphenyl-5-methoxyindole derivatives were synthesized. The effect of structural variation of these molecules on biological activities was examined. None of the tested compounds was found to be toxic up 5 gm/Kg body weight. Four compounds demonstrated smooth muscle relaxant effects and one showed a persistent hypotensive effect. Only the parent compound, 2, 3-diphenyl-5-methoxyindole, showed a significant analgesic effect.

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Acute Oral Toxicity of Phlorotannins in Beagle Dogs (비글견을 이용한 phlorotannin의 단회 경구투여 독성시험)

  • Yang, Hyejin;Yoon, Minseok;Kim, Jiyoung;Cho, Suengmok
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.47 no.4
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    • pp.356-362
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    • 2014
  • Phlorotannins, the major constituent in brown algae, possess various biological activities; however, there is little information their toxicological effects. To assess the safety of phlorotannins, we investigated the acute oral toxicity of a high-purity phlorotannin preparation (PRT; total phlorotannin content 90%) in beagle dogs. Six beagle dogs (3 males, 3 females) were assigned randomly to three experimental groups. PRT was administered at oral doses of 250, 500, and 750 mg/kg by capsule. Vomiting by male and female beagles was observed with 500 and 750 mg/kg on the first day. In addition, one beagle given 750 mg/kg had soft stool and diarrhea on days 3 and 13. No deaths or abnormal clinical signs were observed during the experiment. All groups showed similar body weight gain and food consumption. Our acute toxicity study showed that PRT did not cause any toxicological effects in beagle dogs.

Viable Alternatives to in vivo Tests for Evaluating the Toxicity of Engineered Carbon Nanotubes

  • Kwon, Soon-Jo;Eo, Soo-Mi
    • Journal of Environmental Health Sciences
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    • v.38 no.1
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    • pp.1-7
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    • 2012
  • Carbon nanotubes (CNTs) stand at the frontier of nanotechnology and are destined to stimulate the next industrial revolution. Rapid increase in their production and use in the technology industry have led to concerns over the effects of CNT on human health and the environment. The prominent use of CNTs in biomedical applications also increases the possibility of human exposure, while properties such as their high aspect ratio (fiber-like shape) and large surface area raise safety concerns for human health if exposure does occur. It is crucial to develop viable alternatives to in vivo tests in order to evaluate the toxicity of engineered CNTs and develop validated experimental models capable of identifying CNTs' toxic effects and predicting their level of toxicity in the human respiratory system. Human lung epithelial cells serve as a barrier at the interface between the surrounding air and lung tissues in response to exogenous particles such as air-pollutants, including CNTs. Monolayer culture of the key individual cell types has provided abundant fundamental information on the response of these cells to external perturbations. However, such systems are limited by the absence of cell-cell interactions and their dynamic nature, which are both present in vivo. In this review, we suggested two viable alternatives to in vivo tests to evaluate the health risk of human exposure to CNTs.

Effects of Morphine and Panax ginseng on the Opioid Receptor-G protein Interactions

  • Kim, Young-Ran;Kim, Ae-young;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
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    • v.7 no.1
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    • pp.1-6
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    • 1999
  • Effects of Panax ginseng on the morphine toxicity were studied in relation to its effects on the opioid receptor-G protein interactions. Morphine treatments (3 days) reduced the body weight increment rate and the weight of the thymus and spleen. These changes were usually recovered by the concomitant administration of ginseng total saponin (GTS) but occasionally further deteriorated. This discrepancy was studied in relation to the opioid receptor coupling to G protein, that is, the effects of morphine and GTS on the opioid receptors were studied using the antagonist-agonist competitive binding studies. When GTS recovered the morphine toxicity, morphine shifted the striatal $\delta$ receptors to slightly higher affinity state, and this was partly recovered by the GTS treatment. However, morphine did not have any effect on the affinity state of $\delta$ receptor from NG108-15 cells, suggesting that additional factors were needed for the modulation of the affinity states of $\delta$ receptor. Effects of morphine and GTS on $\mu$ receptor were complicate and variable, and we could not reach a clear conclusion. The morphine toxicity might accompany complicate biological involvements, and the modulation of the affinity states of the opioid receptors might explain a part of the effects of GTS on the morphine toxicity.

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Adverse Outcome Pathways for Prediction of Chemical Toxicity at Work: Their Applications and Prospects (작업장 화학물질 독성예측을 위한 독성발현경로의 응용과 전망)

  • Rim, Kyung-Taek;Choi, Heung-Koo;Lee, In-Seop
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.29 no.2
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    • pp.141-158
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    • 2019
  • Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.

4-week dose range finding toxicity test of Magnoliae Flos extract in Sprague-Dawley rats (Sprague-Dawley 랫드를 이용한 신이 추출물의 4주 반복 용량 결정 독성시험)

  • Park, Ju-Hyoung;Ahn, Eun-Kyung;Park, Kitae;Hwang, Min Hee;Cho, Young-Rak;Lee, Dong-Ryung;Choi, Bong-Keun;Oh, Joa Sub
    • Journal of Applied Biological Chemistry
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    • v.65 no.1
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    • pp.43-48
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    • 2022
  • Medicinal herb demonstrated in many pharmacological effects and recognized to be safe has been used for a long time. However, side effects including safety of medicinal herb have not been identified yet. The aim of the study was to estimate safety evaluation of Magnoliae Flos used for the treatment of pain, rhinitis, and pneumonia in Korea, China and Japan through four-week dose range finding toxicity test in male and female Sprague-Dawley rats. Magnoliae Flos was orally administered to male and female SD rats once a day for 28 days at 1,500 and 3,000 mg/kg. The safety evaluation was determined to examine clinical signs, mortality, body weight, food intake, hematology, serum biochemistry and relative organ weights and there were no significant changes related toxicity. Consequently, these findings indicates that Magnoliae Flos did not show any side effects including toxicity in dose range finding toxicity test and the no observed adverse effect level for Magnoliae Flos was estimated as more than 3,000 mg/kg.