The international validation study of the acute toxic class method (oral)

Schlede, Eva; Mischke, U.; Diener, W; Kayser, D.

doi:10.1007/s002040050229

Cited by 46 publications

(29 citation statements)

References 11 publications

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“…Animals were fed ad libitum. Body weights of animals were measured at the beginning and at the end of the study (Schlede et al, 1995). All animals were sacrificed on the 91st day.…”

Section: Subchronic Toxicity Studiesmentioning

confidence: 99%

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae)

Asare¹,

Bugyei²,

Sittie³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Phyllanthus niruri is a medicinal plant (commonly known as stone breaker) found in the tropics and other parts of the world. It is known for its capacity to block the formation of calcium oxalate crystals and kidney stone formation in urolithiasis. This plant has been used to treat hyperglycemia, hypertension, pain, and mild cases of malaria. We examined the geno-, cyto-and overall toxicity of P. niruri whole plant ethanolic extract. The extract was administered as a single dose of 30 or 300 mg/kg to laboratory rats by gavage, accompanied by negative (0.9% saline) and positive (10 mg/mL N-ethyl-N-nitrosourea) controls that were injected intramuscularly 48 h after extract administration. The ratio of polychromatic (PCE)/normochromatic erythrocytes (NCE) from femur bone marrow was scored for genotoxicity. Cytotoxicity was determined using descending concentrations (0.2-0.0125 g/mL) of the extract incubated with peripheral blood mononuclear cells. Phyllanthus niruri geno-and cytotoxicity Lactate dehydrogenase release from damaged cells was determined and the CC 50 calculated. Subchronic administration of the extract at 30 or 300 mg/kg was done for 90 days to determine general toxicity. PCE:NCE (%) for the extract and negative control was 63, compared to 168 (positive control). The CC 50 was 26.3 mg/mL and hepato-renal toxicity after subchronic extract administration was nil. We conclude that ethanol extract of P. niruri is not cytotoxic or genotoxic, and is generally non-toxic on subchronic administration.

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“…Animals were fed ad libitum. Body weights of animals were measured at the beginning and at the end of the study (Schlede et al, 1995). All animals were sacrificed on the 91st day.…”

Section: Subchronic Toxicity Studiesmentioning

confidence: 99%

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae)

Asare¹,

Bugyei²,

Sittie³

et al. 2012

Genet. Mol. Res.

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“…The result of the acute toxicity study showed mortality at highest dose of up to 2900mg/kg indicating that the LD 50 of pirimiphos methyl is 2154mg/kg. This shows that pirimiphos methyl is not safe for oral usage and according to Organization for Economic Cooperative and Development (OECD) standard for ranking toxic substances [22], any substance whose LD 50 is greater than 500mg/kg and less than 5000mg/kg can be ranked under category 4 of the OECD guidelines for acute toxicity and can be said to be slightly toxic if swallowed [23].…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of Pirimiphos-Methyl on Wistar Rats

Nosiri¹,

Okereke²,

Arunsi³

et al. 2017

IOSR JESTFT

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“…Further hydrolysis of either intermediate results in the production of arginine, which is then further converted to ornithine and urea, following normal amino acid catabolism via the urea and citric acid cycles resulting in the formation of 14 Ccarbon dioxide and 14 C-urea, which are excreted in the expired air and in urine respectively. The ornithine could either be degraded further to citrulline and other amino acids in the urea cycle or to the metabolic intermediate α-ketoglutarate, which could then enter the citric acid cycle with subsequent metabolism to carbon dioxide (Voet and Voet 1990;Schlede et al, 1994). In another study reported by the applicant the pharmacokinetics of ethyl-Να-lauroyl-L-arginate in rats was characterised.…”

Section: Absorption Distribution Metabolism and Excretionmentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to an application on the use of ethyl lauroyl arginate as a food additive

Flavourings¹

2007

EFSA Journal

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SUMMARYThe Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food has been asked to evaluate the safety in use of ethyl lauroyl arginate as a food preservative for use in the food categories specified in the dossier.The active ingredient of ethyl lauroyl arginate, ethyl-N α -lauroyl-L-arginate HCl, is the hydrochloride salt of an N-fatty acylsubstituted amino acid ethyl ester. Ethyl lauroyl arginate is intended to be used as a preservative. The anti-microbial activity of ethyl lauroyl arginate is due to the cationic surfactant properties of its active ingredient ethyl-N α -lauroyl-L-arginate.Ethyl lauroyl arginate has been shown by in vivo and in vitro studies in rats and humans to be rapidly metabolised by hydrolysis of the ethyl ester and lauroyl amide to the intermediate products, arginine ethyl ester and N α -lauroyl-L-arginine, and then to ethanol, lauric acid and arginine. Arginine undergoes natural amino acid catabolism to urea and ornithine. Ornithine can then be further metabolised to CO 2 and urea. Lauric acid is a fatty acid that can enter normal fatty acid metabolism. Ethanol can be converted by alcohol dehydrogenase and aldehyde dehydrogenase to acetate, which can enter normal biochemical pathways. It is concluded that, on ingestion by humans, ethyl lauroyl arginate will be broken down to products of normal metabolism.The Panel considered the bacterial reverse mutation assay study could not be used for evaluation of mutagenicity due to the high toxicity of ethyl-N α -lauroyl-L-arginate towards the bacterial cells. The Panel noted that this toxicity was predictable since ethyl-N α -lauroyl-Larginate is a preservative with antimicrobial activity. Based on the results from the mouse lymphoma L5178Y cell mutation test and from the test for chromosomal aberrations in human lymphocytes it is concluded that ethyl-N α -lauroyl-L-arginate is not genotoxic in mammalian cells. It showed no evidence of a genotoxic effect in the in vivo mouse micronucleus test. Lauric arginate The EFSA Journal (2007) 511, p. 2 of 27According to the available evidence, ethyl lauroyl arginate is devoid of reproductive and developmental toxicity. Long-term carcinogenicity studies are lacking. However, the rapid metabolism of ethyl-N α -lauroyl-L-arginate to compounds endogenously present in much higher levels, the absence of preneoplastic toxic effects in the in vivo studies performed, together with the absence of genotoxic activity in the mouse lymphoma assay, the human lymphocyte assay and the micronucleus test, does not suggest a carcinogenic potential. Therefore the Panel concludes that there is no need to perform carcinogenicity studies.The Panel notes that effects on white blood cells were seen in different rat strains and in different sexes in two 90-day studies and in the 52-week study and concludes that these effects cannot be disregarded. Therefore the Panel concludes, given the fact that the effects on white blood cell counts at 26 weeks are significant for all dose groups, th...

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The international validation study of the acute toxic class method (oral)

Cited by 46 publications

References 11 publications

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae)

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae)

Hepatotoxicity of Pirimiphos-Methyl on Wistar Rats

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to an application on the use of ethyl lauroyl arginate as a food additive

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