The international validation of a fixed-dose procedure as an alternative to the classical LD50 test

Heuvel, Marianne J. van den; Clark, David G.; Fielder, R.J.; Koundakjian, P.P.; Oliver, G.J.A.; Pelling, D.; Tomlinson, N.J.; Walker, A.P.

doi:10.1016/0278-6915(90)90117-6

Cited by 135 publications

(39 citation statements)

References 5 publications

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“…Acute toxicity was calculated as OECD guidelines 420 (Fixed dose method) [37,38]. Ten male Wistar albino rats weighing (180-200 g) were used for acute toxicity study.…”

Section: Toxicity Study (Oecd 420)mentioning

confidence: 99%

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Sayed

Fahmy

Soliman

et al. 2016

Int J Pharm Pharm Sci

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Objective: The ethanolic extract of Vitis vinifera leaves (VVE) (500 mg/kg body weight), ranitidine (50 mg/kg body weight) and both of them were tested for their gastroprotective and curative effects against the incidence of peptic ulcer. Methods:The antiulcer effects of VVE were investigated using a combination of indomethacin and cold-stress for 2h. To ascertain the mechanism of action of VVE, its protective and curative effects were studied on gastric volume, gastric juice acidity, ulcer index and malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO) activities of both stomach and duodenum of rats. Moreover, histopathological effects on stomach and duodenum were determined. Results:The antioxidant activity of VVE was demonstrated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) test. VVE was found to reduce the ulcer index, gastric volume and the level of gastric juice acidity. Also, VVE showed gastroprotective and curative activities mainly through improvement of antioxidant status and decreasing lipid peroxidation accompanied with amelioration of both stomach and duodenum architectures. Conclusion:The prophylactic and curative effects of VVE proved to be effective in preventing gastric and duodenal ulceration which may be probably due to its antioxidant and anti-acid secretory effects.

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“…Acute toxicity was calculated as OECD guidelines 420 (Fixed dose method) [37,38]. Ten male Wistar albino rats weighing (180-200 g) were used for acute toxicity study.…”

Section: Toxicity Study (Oecd 420)mentioning

confidence: 99%

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Sayed

Fahmy

Soliman

et al. 2016

Int J Pharm Pharm Sci

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“…For all the methods, the study outcome is likely to be influenced by the choice of starting dose level(s) relative to the true LD 50 value, especially in the case of shallow slopes (Gribaldo et al, 2005). Therefore, information on toxic effects seen only at dose levels close to a lethal dose will not be obtained (Van der Heuvel et al, 1990). However, the dangerous dose for humans may be 1-100% more or less of the determined LD 50 (Dreisbach & Robertson, 1987).…”

Section: Introductionmentioning

confidence: 99%

Toxicity studies of drugs and chemicals in animals: an overview

Saganuwan¹

2017

BJVM

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SummarySaganuwan, S. A., 2017. Toxicity studies of drugs and chemicals in animals: An overview. Bulg. J. Vet. Med., 20, No 4, Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD 50 ) first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety assessment of drugs and chemicals, LD 50 values are no longer used. In view of this, literature search was carried out with a view to investigating the relevance of LD 50 in development and assessment of drugs and chemicals. The findings revealed that in the past, many animals had been used for LD 50 determination. OECD has reduced the number of test animals to 5-15 and presently it is further reduced to 2-6. Acute toxicity study is being carried out in medicinal plants research and in the study of patent medicine. Although the application of LD 50 has been drastically reduced, it is still applied and accepted in some parts of the world. Moreover, animals on which LD 50 tests are conducted, should be allowed to die to see the end effect of the test drug or chemical because euthanisia of test animals may mask some toxicity signs of the test agents. Therefore, toxicity study of drugs and chemicals is a scientific process necessary for discovery and development of drugs as well as identification of potential toxicants.

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“…Bartsch et al 1976van den Heuvel et al 1990van den Heuvel et at. 1990 unclassified Smyth et al 1950unclassified Filatova et al 1982 m = male, f = female; m/f = male and female groups combined; (m/l) = sex not specified.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, another alternative test procedure -the fixed dose method -has gained acceptance from the OECD and the European Community (van den Heuvel et al 1990). In principle this method relies on signs of toxicity rather than on mortality for the evaluation of the toxicity of a test material and it uses 50% fewer animals when compared to the LDs0 test (OECD 1981).…”

Section: Introductionmentioning

confidence: 99%

A national validation study of the acute-toxic-class method—an alternative to the LD50 test

Schlede¹,

Mischke

Roll

et al. 1992

Arch Toxicol

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In a national collaborative study an alternative to the classical LD50 test--the acute-toxic-class method--was validated. With this testing procedure mortality ranges are determined between defined dose levels that are used for classification and labelling in the European Community. The results were compared with LD50 data obtained from the literature which were categorized according to the defined dose levels. The results of this collaborative study have shown that the acute-toxic-class method allows allocation to the toxicity classes of very toxic, toxic, harmful and unclassified in the same manner as on the basis of the classical LD50 tests. The acute-toxic-class method uses fewer animals and subjects fewer animals to pain and distress than the LD50 test and yields the same information on toxic signs in the treated animals. Identical classifications were obtained by the six participating laboratories in 86% of the tests. This demonstrates that the acute-toxic-class method results in excellent reproducibility in comparison to the classical LD50 test and that this new method is a reliable alternative to the LD50 test.

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The international validation of a fixed-dose procedure as an alternative to the classical LD50 test

Cited by 135 publications

References 5 publications

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Toxicity studies of drugs and chemicals in animals: an overview

A national validation study of the acute-toxic-class method—an alternative to the LD50 test

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