• Title/Summary/Keyword: Subchronic

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Process for Allowing Pesticide Use on Food

  • Chen, William L.
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.121-123
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    • 2003
  • The registration of a pesticide for use in the gardens or a farmer's field requires assessment of the potential negative effects of that pesticide on human health. To anticipate how a pesticide might impact human health, laboratory animals such as mice and rats are exposed to varying dosages in their foods -from very minimal to extremely high levels. Toxicologists then evaluate the observable effect(s) of consuming known quantities of that specific pesticide on acute, subchronic, chronic, mutational, reproduction and neurological effects. Information gained from such test is evaluated by toxicologists and medical experts to determine potential human effects

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Prioritization of Chemicals for Chronic/Carcinogenic Inhalation Testing (만성발암성 흡입독성시험 우선순위 물질 선정 연구)

  • Rim, Kyung-Taek;Lim, Cheol-Hong;Kim, Hyeon-Yeong;Cha, Shin-Woo;Heo, Yong;Yoon, Jin-Ha;Kim, Hyung-A
    • Journal of Environmental Health Sciences
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    • v.43 no.1
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    • pp.23-41
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    • 2017
  • Objectives: In this study, we seek to perform a priority selection for test substances for chronic inhalation toxicity studies, including acute and subchronic inhalation toxicity studies, which are to be performed after the construction of a chronic/carcinogenicity inhalation toxicity study facility and enactment of pertinent legislation. Methods: Through this study, qualitative and quantitative priority evaluation of test substances according to acute, subchronic and chronic categories were respectively performed and priorities were suggested by expert group review, redundancy and other methods. Meanwhile, a draft on test substance selection criteria, procedures and methods referring to the National Toxicology Program (NTP) system was proposed. Results: This study selected priorities for candidate substances for chronic inhalation toxicity studies to be conducted from 2016. Conclusions: In the future, by assessing in advance the toxicological effects of chemicals to which workers can be potentially exposed in the workplace via long-term inhalation, expected health disturbances among workers will be reduced and it is anticipated that occupational disease induced by chemicals will be effectively prevented.

Subchronic Oral Toxicity Study of Acanthopanax divaricatus var. albeofructus in Rats

  • Kim, Myoung Jun;Lee, Mi Ju;Lee, Yong-Hoon;Park, Sun Hee;Kim, Duyeol;Park, Cheol Beom;Kang, Jin Seok;Kang, Jong-Koo
    • Toxicological Research
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    • v.33 no.1
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    • pp.15-23
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    • 2017
  • Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

Antidepressant Effect of the Subchronic Administration of the Methanolic Extract of Wild-ginseng and Cultivated-ginseng in Mice Tail Suspension Test (산삼과 인삼 메탄올 추출물 아만성 복용의 Mice Tail Suspension Test에서의 항우울 효과에 대한 비교연구)

  • Kwon, Sun-Oh;Choi, Soo-Min;Kim, Myung-Hwan;Lee, Bom-Bi;Park, Moo-Won;Lee, Hye-Jung;Park, Hi-Joon;Hahm, Dae-Hyun
    • Journal of Acupuncture Research
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    • v.26 no.4
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    • pp.99-106
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    • 2009
  • Objectives : The antidepressant effect of the subchronic administration of the methanolic extract of wild ginseng(WG) was investigated compared with that of cultivated ginseng(CG, panax ginseng) extract. Methods : To assess the antidepressant effect of the ginseng extracts, tail suspension test(TST) was executed in mice after daily administration of WG or CG extract for five consecutive days. Results : The WG extract at daily dose of 600mg/kg significantly reduced the total duration of immobility in the TST, whereas there was no significant reduction at daily dose of 300mg/kg WG and 600mg/kg CG. There were no individual differences between experimental groups in open field test (OFT) to evaluate psychostimulant effects of WG or CG extract. In the high performance liquid chromatography(HPLC) analysis of the extracts, it was found that WG included four times more ginsenoside Rg1 and Re, three times more Rf, and six times more Rb1 and Rc than CG. Conclusions : It is suggested that WG extract has stronger antidepressant effect than CG extract, which means it includes more antidepressant compounds than CG.

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A Study on Subchronic Inhalation Toxicity of 2-Methylpentane (2-Methylpentane 아만성 흡입독성 연구)

  • Chung, Yong Hyun;Lim, Cheol Hong;Han, Jeong Hee
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.24 no.2
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    • pp.169-181
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    • 2014
  • Objectives: The purpose of this study was to obtain information regarding classification and health hazards that may result from a 13-week inhalation exposure to 2-methylpentane by Sprague-Dawley rats. Materials: The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The rats were divided into four groups(ten male and ten female rats in each group) and exposed to 0 ppm, 290 ppm, 1,160 ppm, 4,640 ppm 2-Methylpentane in each exposure chamber for six hours per day, five days per week, for 13 weeks. Results: No death or particular clinical presentation including weight change and change of feed rate was observed. The relationships between dose, gender and response were also not significantly changed in urinalysis, hematologic examination, or biochemical examination of blood(except for total cholesterol being up, total protein being up, and chloride ion being down in males), and blood coagulation time. For the relative weight measurement of organs, in the male group the weight change of both kidney and liver were increased in proportion to dose. In histopathological examination, nephropathy in the kidney(cystic change of renal tubules, regenerative tubule, inflammatory cell infiltration and necrosis in the interstitial tissue) was increased in a dose-dependent manner in the male group(290 ppm, 1,160 ppm, 4,640 ppm). However, other organs were not affected by the test substance. Conclusions: 2-methylpentane was estimated as a chemical causing nephropathy in the male group. NOAEL(No Observable Adverse Effect Level) in the female group is more than 4,640 ppm, while inthe male group it is less than 290 ppm.

Validation of a Rodent Nose-only Exposure System for Inhalation Toxicity Evaluation of Cigarette Smoke (담배 흡입독성 평가를 위한 설치류 담배연기노출시스템의 유효화)

  • Sohn, Hyung-Ok;Lee, Hyeong-Seok;Shin, Han-Jae;Park, Chul-Hoon;Yoo, Ji-Hye;Jang, Mi;Hyun, Hak-Chul
    • Journal of the Korean Society of Tobacco Science
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    • v.36 no.1
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    • pp.20-25
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    • 2014
  • As part of a balanced testing battery, subchronic inhalation studies on rats are performed to ensure that proposed cigarette modifications do not increase the toxicity of smoke and to demonstrate any instances where a modification may actually contribute to harm reduction. For subchronic inhalation studies with aerosols, the OECD suggests an exposure regimen of 6 hours/day (OECD Guideline 413, 1981), but alternative regimens have also been published: 1 hour/day and $2{\times}1$ hour/day. The aim of this study was to validate a rodent nose-only exposure system for the assessment of inhalation toxicity of cigarette smoke. In this study, cigarette smoke exposure system is consisted of cigarette smoke generator, smoke concentration adjusting system, and 20-port nose-only exposure system. Male SD rats were exposed for 35 days ($2{\times}1$ hour/day) to 3R4F Reference cigarette smoke and analysed major monitoring items of OECD Gudeline 413. WTPM, was measured in the test atmosphere, respiratory function (Buxco Biosystems) during exposure, postexposure urinary exposure biomarkers and alveolar neutrophiles in BAL fluid (Day 35) were evaluated. Validation demonstrated steady WTPM ($257{\pm}20ug/L$, $502{\pm}27ug/L$) and spatial uniformity (<10%). Nose port temperature ($22{\sim}26^{\circ}C$ and RH (45~75%) were acceptable over 35 days. Reductions in respiratory rate and minute volume and increase in the neutrophiles in BALF and the urinary exposure biomarkers were observed cigarette smoke dose dependently. This validation and 35-day inhalation study has shown that the rodent nose-only exposure system may be useful in the inhalation toxicity assessment of cigarette smoke.

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.

Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs

  • Li, Wei;Zhang, Xiangrong;Ding, Meng;Xin, Yanfei;Xuan, Yaoxian;Zhao, Yuqing
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.562-571
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    • 2019
  • Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

Fingernail for the Physiological Indicator of Fluoride Exposure in Korean Children

  • Kho, Young-Lim;Hwang, Jung-Hee;Kim, Sung-Yeon;Ma, Deuk-Sang;Jung, Se-Hwan
    • Proceedings of the Korean Environmental Health Society Conference
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    • 2004.06a
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    • pp.213-216
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    • 2004
  • This work was based on the hypotheses that fingernail clippings can be used as a biomarker for the subchronic exposure to fluoride. This study was conducted to prove the hypotheses and fingernail clippings were collected form 120 preschool children aged $3{\sim}6$ residing in Jumunjin(community water fluoridation area) and Kangnung(non-fluoridation area). The acid-diffusible fluoride in the fingernail clipping was isolated by the acid-diffusion technique and measured with a fluoride electrode. The mean fingernail fluoride as the children's living area were 4.49ug/g(SD 2.43) to Jumunjin and 2.68ug/g(SD 1.13) to Kangnung. As would be expected, the fluoride concentration in fingernail clippings were significantly different between the two geographical groups(p<0.001) determined by t-test.

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