• Title/Summary/Keyword: Chronic toxicity studies

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Dietary Reference Intakes of sodium for Koreans: focusing on a new DRI component for chronic disease risk reduction

  • Kim, Hyun Ja;Lee, Yeon-Kyung;Koo, Hoseok;Shin, Min-Jeong
    • Nutrition Research and Practice
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    • v.16 no.sup1
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    • pp.70-88
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    • 2022
  • Sodium is a physiologically essential nutrient, but excessive intake is linked to the increased risk of various chronic diseases, particularly cardiovascular. It is, therefore, necessary to accomplish an evidence-based approach and establish the Korean Dietary Reference Intakes (KDRIs) index, to identify both the nutritional adequacy and health effects of sodium. This review presents the rationale for and the process of revising the KDRIs for sodium and, more importantly, establishing the sodium Chronic Disease Risk Reduction Intake (CDRR) level, which is a new specific set of values for chronic disease risk reduction. To establish the 2020 KDRIs for dietary sodium, the committee conducted a systematic literature review of the intake-response relationships between the selected indicators for sodium levels and human chronic diseases. In this review, 43 studies published from January 2014 to December 2018, using databases of PubMed and Web of Science, were finally included for evaluating the risk of bias and strength of evidence (SoE). We determined that SoE of the relationship between dietary sodium and cardiovascular diseases, cerebrovascular disease, and hypertension, was moderate to strong. However, due to insufficient scientific evidence, we were unable to establish the estimated average requirement and the recommended nutrient intake for dietary sodium. Therefore, the adequate intake of sodium for adults was established to be 1,500 mg/day, whereas the CDRR for dietary sodium was established at 2,300 mg/day for adults. Intake goal for dietary sodium established in the 2015 KDRIs instead of the tolerable upper intake level was not presented in the 2020 KDRIs. For the next revision of the KDRIs, there is a requirement to pursue further studies on nutritional adequacy and toxicity of dietary sodium, and their associations with chronic disease endpoint in the Korean population.

Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II-III resectable rectal cancer: a meta-analysis of randomized controlled trials

  • Song, Jin Ho;Jeong, Jae Uk;Lee, Jong Hoon;Kim, Sung Hwan;Cho, Hyeon Min;Um, Jun Won;Jang, Hong Seok;Korean Clinical Practice Guideline for Colon and Rectal Cancer Committee
    • Radiation Oncology Journal
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    • v.35 no.3
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    • pp.198-207
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    • 2017
  • Purpose: Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II-III rectal cancer. Materials and Methods: We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. Results: Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41-0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). Conclusions: As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

Pharmacological Studies on Ether Fraction of Corni Fructus (산수유 에텔분획물의 약리작용에 관한 연구)

  • 이은방;최병천;조태순
    • YAKHAK HOEJI
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    • v.29 no.1
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    • pp.1-10
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    • 1985
  • The ether fraction obtained from dry fruit of Cornus officinalis was investigated for the anti-inflammatory action, acute toxicity and central nervous system activities. From several pharmacological examinations, it was found that the ether fraction suppressed considerably carrageenin edema at the dose of 600mg/kg p.o. in rats, inhibited the granuloma formation in rats as given 100mg/kg p.o. for 7 days and decreased the swelling of both of complete adjuvant injected and noninjected (contralateral) paws of the rats at the dose of 100mg/kg p.o. given for 14 days. The $LD_{50}$ of the fraction are estimated to be more than 2,000mg/kg p. o. and 642mg/kg i. p. in mice. And the fraction did not show any sedative, stimulative, analgesic and anticonvulsant action but exhibited hypothermic action. These results might be concluded that the ether fraction of Corni fructus showed anti-inflammatory action in both of acute and chronic type models without any considerable central nervous depressant activity and exhibited very weak acute toxicity in mice.

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TOXICOLOGICAL STUDIES ON GINSENG (인삼의 독성 연구)

  • Soldati F.
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.119-126
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    • 1984
  • Several publications in scientific journals affirming that ginseng could be toxic and have harmful effects on the organism, gave us reason to undertake extensive investigations as to the toxicity of the standardized ginseng extract G115, Acute and chronic toxicity, teratogenicity, carcinogenicity, its action on the cardiovascular and the hormonal system have been studied. The data obtained, which represent five years of research, are confirmed by clinical results: The standardized ginseng extract G115 is absolutely safe, no toxic actions or side effects were observed.

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Phosphamidon-induced apoptosis in the testis of chickens and rats (Phosphamidon 을 투여한 닭 및 랫트 고환의 Apoptosis 에 대한 연구)

  • Lee, Cha-Soo;Chung, Jae-Yong;Park, Sang-Joon;Jeong, Kyu-Shik
    • Korean Journal of Veterinary Pathology
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    • v.3 no.1
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    • pp.27-33
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    • 1999
  • Phosphamidon(PMD) is orgnophosphate insecticide broadly using in agriculture. In order to study PMD toxicity in the testis, histopathological change and apoptosis were assessed following acute and chronic oral administration in rats and chickens. In acute studies, histopathological changes included necrosis and desquamation of spermatogenic cells, multinucleated giant cells in the lumen of seminiferous tubules, and necrotic cells and the giant cells in the epididymal lumen. Atrophy of seminiferous tubule was seen in the chronic exposure with low doses. The toxic effects of PMD in chronic exposure including clinical signs and histopathological changes were more pronounced in chickens than rats. Apoptosis assessment was performed by TUNEL method and Hoechst staining. TUNEL-positive apoptotic cells were found in spermatocytes of seminiferous tubules, testicular apoptosis was more prominent following acute exposure than control and chronic exposure. Above mentioned result noticed that PMD causes apoptotic death and effects directly the spermatocytogenesis.

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Anti-inflammatory activity of aqueous methanolic extract of Swietenia mahagoni (L.) Jacq. (Meliaceae) leaves

  • Roy, S;Besra, SE;Banerjee, B;Mukherjee, J;Vedasiromoni, JR
    • Advances in Traditional Medicine
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    • v.9 no.1
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    • pp.74-82
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    • 2009
  • Pharmacological investigations were carried out with aqueous methanolic extract (AME) of Swietenia mahagoni (L.) Jacq. (Meliaceae) leaves. Acute toxicity studies revealed that the $LD_{50}$ dose of AME was 600 mg/kg, i.p. AME was found to possess significant anti-inflammatory activity in acute, sub-chronic and chronic models of inflammation. AME selectively inhibited cyclooxygenase (COX)-2 activity, which is involved in arachidonic acid metabolism and biosynthesis of prostaglandins under inflammatory conditions. Treatment with AME significantly enhanced total peritoneal cell count and the number of macrophages in normal mice, which revealed that AME may also alter the immune response along with its anti-inflammatory effect. The saponins or the alkaloids present in AME may be responsible for the anti-inflammatory activity.

Single and 4-Week Repeated Dose Toxicity Studies of DA-3585, a Recombinant Human Erythropoietin, in Rabbits (사람 적혈구 조혈인자 DA-3585의 토끼에 대한 단회 및 4주 반복투여 독성시험)

  • Cho, Hyeon;Kim, Dong-Hwan;Kang, Kyung-Koo;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.171-181
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    • 1998
  • DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

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Mathematical modeling to simulate the adsorption and internalization of copper in two freshwater algae species, Pseudokirchneriella subcapitata and Chlorella vulgaris

  • Kim, Yongeun;Lee, Minyoung;Hong, Jinsol;Cho, Kijong
    • Korean Journal of Environmental Biology
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    • v.39 no.3
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    • pp.298-310
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    • 2021
  • Prediction of the behavior of heavy metals over time is important to evaluate the heavy metal toxicity in algae species. Various modeling studies have been well established, but there is a need for an improved model for predicting the chronic effects of metals on algae species to combine the metal kinetics and biological response of algal cells. In this study, a kinetic dynamics model was developed to predict the copper behavior(5 ㎍ L-1, 10 ㎍ L-1, and 15 ㎍ L-1) for two freshwater algae (Pseudokirchneriella subcapitata and Chlorella vulgaris) in the chronic exposure experiments (8 d and 21 d). In the experimental observations, the rapid change in copper mass between the solutions, extracellular and intracellular sites occurred within initial exposure periods, and then it was slower although the algal density changed with time. Our model showed a good agreement with the measured copper mass in each part for all tested conditions with an elapsed time (R2 for P. subcapitata: 0.928, R2 for C. vulgaris: 0.943). This study provides a novel kinetic dynamics model that is compromised between practical simplicity and realistic complexity, and it can be used to investigate the chronic effects of heavy metals on the algal population.

Comparative In Vitro Biological Toxicity of Four Kinds of Air Pollution Particles

  • Shin, Han-Jae;Cho, Hyun Gi;Park, Chang Kyun;Park, Ki Hong;Lim, Heung Bin
    • Toxicological Research
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    • v.33 no.4
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    • pp.305-313
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    • 2017
  • Accumulating epidemiological evidence indicates that exposure to fine air pollution particles (APPs) is associated with a variety of adverse health effects. However, the exact physiochemical properties and biological toxicities of fine APPs are still not well characterized. We collected four types of fine particle (FP) (diesel exhaust particles [DEPs], natural organic combustion [NOC] ash, synthetic organic combustion [SOC] ash, and yellow sand dust [YSD]) and investigated their physicochemical properties and in vitro biological toxicity. DEPs were almost entirely composed of ultrafine particles (UFPs), while the NOC, SOC, and YSD particles were a mixture of UFPs and FPs. The main elements in the DEPs, NOC ash, SOC ash, and YSD were black carbon, silicon, black carbon, and silicon, respectively. DEPs exhibited dose-dependent mutagenicity even at a low dose in Salmonella typhimurium TA 98 and 100 strains in an Ames test for genotoxicity. However, NOC, SOC, and YSD particles did not show any mutagenicity at high doses. The neutral red uptake assay to test cell viability revealed that DEPs showed dose-dependent potent cytotoxicity even at a low concentration. The toxicity of DEPs was relatively higher than that of NOC, SOC, and YSD particles. Therefore, these results indicate that among the four FPs, DEPs showed the highest in vitro biological toxicity. Additional comprehensive research studies such as chemical analysis and in vivo acute and chronic inhalation toxicity tests are necessary to determine and clarify the effects of this air contaminant on human health.

Effects of Methyl Ethyl Ketone and Methanol on the Survival and Reproduction of Paronychiurus kimi (Collembola: Onychiuridae) (메틸에틸케톤과 메탄올이 김어리톡토기의 사망 및 번식에 미치는 영향)

  • Wee, June;Lee, Yun-Sik;Son, Jino;Kim, Yongeun;Mo, Hyoung-ho;Cho, Kijong
    • Korean Journal of Environmental Biology
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    • v.35 no.2
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    • pp.169-174
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    • 2017
  • Acute and chronic toxicities of methyl ethyl ketone and methanol were investigated on Paronychiurus kimi (Collembola), for evaluating the potential effects of accidental exposures of these chemical substances on the terrestrial environments. This study was undertaken to establish a toxicity database for these chemical substances, which was required for the preparation of the response compensation and liability act for agricultural production and environmental damage. The 7-d acute toxicity and 28-d chronic toxicity were conducted using the OECD artificial soil spiked with varying, serially diluted concentrations of methyl ethyl ketone and methanol. Mortality was recorded after 7-d and 28-d of exposures, and the number of juveniles were determined after 28-d of exposure in the chronic toxicity test. In both assessments, methanol was more toxic than methyl ethyl ketone in terms of mortality ($LC_{50}$) and reproduction ($EC_{50}$). The 7-d $LC_{50}$ of methyl ethyl ketone and methanol were 762 and $2378mg\;kg^{-1}$ soil dry wt., respectively, and the 28-d $LC_{50}s$ were 6063 and $1857mg\;kg^{-1}$ soil dry wt., respectively. The 28-d $EC_{50}$ of methyl ethyl ketone and methanol were 265 and $602mg\;kg^{-1}$ soil dry wt., respectively. Comparison of results obtained in this study with literature data revealed that P. kimi was more sensitive to methanol than other soil invertebrates. However, given the high volatility of the chemicals tested in this study, further studies are necessary to improve the current test guideline, or to develop new test guidelines for an accurate assessment of chemicals that require toxicity databases for chemical accidents.