• Title/Summary/Keyword: Single-dose toxicity

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Male Reproductive Toxicity of DA-125, a New Anthracycline Anticancer Agent, in Rats (수컷랫드에 있어서 새로운 안트라사이클린계 항암제 DA-125의 생식독성 연구)

  • 김종춘;김갑호;신호철;정문구
    • Toxicological Research
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    • v.14 no.2
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    • pp.193-203
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    • 1998
  • The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.

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The First Report to Evaluate Safety of Cyanobacterium Leptolyngbya sp. KIOST-1 for Use as a Food Ingredient: Oral Acute Toxicity and Genotoxicity Study

  • Lee, Youngdeuk;Kim, Taeho;Lee, Won-Kyu;Ryu, Yong-Kyun;Kim, Ji Hyung;Jeong, Younsik;Park, Areumi;Lee, Yeon-Ji;Oh, Chulhong;Kang, Do-Hyung
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.290-297
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    • 2021
  • Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

Beneficial Effects of Phyto-Extract Complex (CME) on Degenerative Arthritis (식물추출복합물(CME)의 퇴행성관절염 개선효과)

  • Seo, Hyeong-Ho;Jeong, Jong-Moon
    • The Korea Journal of Herbology
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    • v.28 no.6
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    • pp.87-93
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    • 2013
  • Objectives : Degenerative arthritis arises from several physiological factors. The purpose of this study is to investigate the beneficial effects of Phyto-extract Complex (CME) on degenerative arthritis. Methods : CME is composed of extracts of mulberry (Morus alba L.) fruit, mulberry leaves and black beans (Glycine max (L.) Merr.). To measure the toxicity of CME, we performed the single-dose toxicity study. For the evaluation of its effects on degenerative arthritis, we examined the inhibition of cyclooxygenase-2 (COX-2) activity, using in vitro enzyme activity assay, the reduction of protein expression of COX-2, 5-lipoxygenase (5-LO), and inducible nitric oxide synthase (iNOS) in RAW264.7 cells which were stimulated by lipopolysaccharide (LPS). We also examined the serum level of prostaglandins (PGs) and injury of the knee joint cartilage, using animal model of degenerative arthritis induced by mono-sodium iodoacetate (MIA). Results : CME did not have any toxicity in single-dose toxicity study. The CME inhibited the activity of COX-2 and could reduce the protein expression of COX-2, 5-LO and iNOS in RAW264.7 cells. The CME also reduced the serum level of PGs and prevented from the cartilage injury of knee joint in animal model of degenerative arthritis induced by MIA. Conclusions : Taken altogether, the CME could be useful for the improvement of degenerative arthritis through its various anti-inflammatory activities and prevention from the cartilage injury of knee joint.

Acute Testis Toxicity of Bisphenol A Diglycidyl Ether in Sprague-Dawley Rats

  • Yang, Yun-Jung;Lee, Shin-Young;Kim, Kyung-Yong;Hong, Yeon-Pyo
    • Journal of Preventive Medicine and Public Health
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    • v.43 no.2
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    • pp.131-137
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    • 2010
  • Objectives: Bisphenol A diglycidyl ether (BADGE) is a liquid compound obtained by condensation of two molecules of epichlorohydrin with one molecule of bisphenol A. General and reproductive toxicity with BADGE has been reported higher than 1000 mg/kg/day. This study was performed to show the effects of acute exposure to BADGE below 1000 mg/kg/day on the testis in adult male rats. Methods: BADGE was administered by gastric lavage in a single dose of 500, 750, 1000, and 2000 mg/kg/day in 8-week old male SPF Sprague-Dawley rats. The right testis was processed for light microscopic analysis. The left testis was homogenized and spermatids were counted to determine the daily sperm production and daily abnormal sperm production. The sperm count, sperm motility, and incidence of abnormal sperm were estimated in the epididymis. In testicular sections, the seminiferous tubules were observed for qualitative changes. The progression of spermatogenesis was arbitrarily classified as full-matured, maturing, and immature. The specimen slide was observed at 3 points and 10 seminiferous tubules were evaluated at each point. Results: The male rats exposed to single oral dose of BADGE at 750, 1000, and 2000 mg/kg/day were significantly increased the number of immature and maturing sperm on the testis. There were no significant differences with respect to sperm head count, sperm motility, and sperm abnormality in the BADGE treatment groups. Conclusions: These results suggest that single oral exposure of BADGE 750 mg/kg/day can affect adult male testis development.

Acute Toxicity Study of the Hwangryunhaedok-tang Extract in ICR Mice (황련해독탕(黃連解毒湯) 열수 추출물의 급성독성 연구)

  • Lee, Ji-Hye;Eum, Hyun-Ae;Chung, Tae-Ho;Lee, Yoon-Hee;Um, Young-Ran;Yim, Nam-Hui;Kim, Dong-Seon;Ma, Jin-Yeul
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.159-166
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    • 2010
  • Objective : The objective of this study was to evaluate the single dose oral toxicity of Hwangryundaedok-tang extract in ICR mice. Methods : 0(control group), 1250, 2500 and 5000 mg/kg of Hwangryundaedok-tang extracts were orally administered to 20 male and 20 female ICR mice. After single oral administration of Hwangryundaedok-tang extract to ICR mice, we observed number of the death, clinical signs, changes of body weights for 14 days. After 14 day of Hwangryundaedok-tang extract administration, all mice were sacrificed and major organs were observed. Results : Compared with the control group, we could not find any toxic signs in the mortalities, clinical signs, body weight changes, necropsy findings and hematological values in all treated groups(1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ value of Hwangryundaedok-tang extracts may be over 5000 mg/kg and it may have no side toxic effect to ICR mice.

Acute and Subacute Toxicity Studies of New Won-bangwoohwangchungsimwon in Beagle Dogs (비글개에서 신원방우황청심원의 급성 및 아급성독성시험)

  • 성하정;권오경;방명주;곽형일;신대희;이진영;박대규;정규혁;윤효인
    • Toxicological Research
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    • v.14 no.2
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    • pp.273-283
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    • 1998
  • Single and 4 weeks oral administration of New wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material qf musk, to beagle dogs of both sexes were per-formed to investigate both acute and subacute toxicity. Beagle dogs (3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NSCH, 160 mg/kg/day (low dosage group), 400 mg/kg/day (middle dosage group), 1,000 mg/kg/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Ad-ministration (l996. 4. 16). $LD_{50}$ value for beagle dogs was more than 2,000 mg/kg per oral for both male and females. In animals administered with NSCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NSCH in beagle dogs is considered to be safe.

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Acute and Subacute Toxicity of New Woohwangchungsimwon in Beagle Dogs (비글개에서 신우황청심원의 급성 및 아급성독성시험)

  • 권오경;성하정;곽형일;방명주;신대희;이진영;박대규;정규혁;윤효인
    • Toxicological Research
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    • v.14 no.2
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    • pp.249-260
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    • 1998
  • Single and 4 weeks oral administration of New Woohwangchungsimwon (NWCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NWCH, 160 mg/kg/day (low dosage group), 400 mg/kg/day (middle dosage group), 1,000 mg/kg/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). $LD_{50}$/ value for beagle dogs was more than 2,000 mg/kg per oral for both male and fe-males. In animals administered with NWCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NWCH in beagle dogs is considered to be safe.

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Acute Toxicity of Enrofloxacin-Colistin Combinations after a Single Oral and Intravenous Administration in ICR Mice (ICR계 마우스에서 Enrofloxacin과 Colistin 복합체의 단회 경구 및 정맥투여시 급성독성)

  • Kim, Min-Kyu;Park, Seung-Chun;Yun, Hyo-In;Oh, Tae-Kwang;Choi, Yang-Woong
    • Toxicological Research
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    • v.14 no.3
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    • pp.385-391
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    • 1998
  • The study was carried out to evaluate the acute toxicity of enrofloxacin-colistin combination via a single oral(p.o.)and intravenous(i.v.) administration in ICR mice. All procedures of the test were performed by the established regulation of Korean National Institute of Safety Research (1994. 4.14). The maximal dose of oral and intravenous routes was 5,000mg/kg and 90mg/kg, consisting with each 6 groups including control of male and female, respectively. As the results, $LD_{50}$m}'s of the combinations showed 3,075mg/kg (f)and 2,564mg/kg(m) after oral administrations, together with 48mg/kg(f) and 40mg/kg(m) after intravenous administration. These facts indicated that acute toxicitiy of enrofloxacin-colistin combination were different depending on the administration routes and sexes in ICR mice. In conclusion, the route of enrofloxacin-colistin combination must not choose as i.v. route administration in terms of acute toxicity based on $LD_{50}$.

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Study on Acute Subcutaneous Toxicity of Hydroxyapatite Sinter Produced from Tuna Bone in Sprague-Dawley Rats (참치뼈로부터 제조한 Hydroxyapatite 소결체의 랫드에 대한 급성피하독성시험)

  • 김세권;박표잠;김용태
    • Journal of Life Science
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    • v.11 no.2
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    • pp.97-102
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    • 2001
  • This study was performed to evaluate the actue sbucutaneous toxicity of hydroxyapatite sinter produced from tuna bone in Sprague-Dawley(SD) rats. Hydroxyapatite sinter was administrated at dose levels of 5000, 2500, 1250, 625, 312.5 and 0 mg/kg. After single subcutaneous adiminstration to both sexes to both sexes SD rats, we observed rats for 14 days. Hydroxyapatite sinter did not induce any toxic signs inmortalities, clinical findings, body weights and gross findings of the rats. In view of result, it was impossible to estimate LD/ sub 50/ values in SD rats. In conclusion, these results suggest that hydroxyapatite sinter produced from tuna bone has no effect on acute subcutaneous toxicity in SD rats.

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THE EFFECTS OF ALTERING THE HEPATIC DRUG METABOLIZING ENZYME ACTIVITY ON THE ACUTE TOXICITY OF DIETHYL-4-NITROPHENYL PHOSPHOROTHIOATE (PARATHION) IN FEMALE RATS1.

  • Kim, Young-Chul;Park, Jae-Hwa;Lim, Hye-Kyung
    • Toxicological Research
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    • v.4 no.2
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    • pp.107-115
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    • 1988
  • The effects of altering the hepatic mixed-function oxidase(MFO) activities on the acute toxicity of parathion were examined in female rats. Phenobarbital sodium pretreatment (50mg/kg/day, i.p.) for 4 consecutive days has resulted in significant decreases in the toxicity of parathion (2 or 4 mg/kg, i.p.) as determined by lethality and cholinesterase activities wheras the toxicity arising from a single dose of CCl4(2 mmol/kg, i.p.) 24 hr prior to parathion challenge was potentiated.

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