Tumorigenicity study of disodium glycyrrhizinate administered orally to mice

Kobuke, Toshihiro; Inai, Kei; Nambu, Shigeru; Ohe, Keiji; Takemoto, Tsuyoshi; Matsuki, Kei; Nishina, H.; Huang, Isaac; Tokuoka, Shoji

doi:10.1016/0278-6915(85)90247-9

Cited by 29 publications

(11 citation statements)

References 4 publications

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“…Erythrosine B is not carcinogenic in mice and rats. 29,30 Oral administration of erythrosine B results in DNA damage in specific organs of mice, as detected by an in vivo comet assay. 31 However, at the concentrations used in the present study, erythrosine B exhibits negative responses for cell transformation, 13 UDS, 11 and chromosome aberrations (Hagiwara et al unpublished data) in SHE cells.…”

Section: Discussionmentioning

confidence: 99%

Ability of 13 chemical agents used in dental practice to induce sister-chromatid exchanges in Syrian hamster embryo cells

Miyachi

Tsutsui

2005

Odontology

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To evaluate the genotoxic potential of 13 chemical agents used in dental practice, the abilities of these agents to induce sister-chromatid exchanges (SCEs) were examined using Syrian hamster embryo (SHE) cells. Statistically significant increases in the frequencies of SCEs were observed in SHE cells treated with all seven of the chemical agents used as endodontic medicaments: p-chlorophenol, m-cresol, formaldehyde, guaiacol, hydrogen peroxide, p-phenolsulfonic acid, and sodium hypochlorite (P < 0.01; Student t test). Assessment of two chemical agents that are applied to the oral mucosa as antiseptics showed that SCEs were induced by iodine (P < 0.01), but not by chlorhexidine. Of three chemical agents that are used as dyes for disclosing dental plaque, erythrosine B had no effect on SCE induction, while acid fuchsin and basic fuchsin increased the SCE frequencies in SHE cells (P < 0.01). Glutaraldehyde, which is used as a disinfectant for dental instruments and impressions, also induced SCEs (P < 0.01). Because SCE assays are used as a sensitive indicator for evaluating genetic toxicity of chemicals, the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.

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Section: Discussionmentioning

confidence: 99%

Ability of 13 chemical agents used in dental practice to induce sister-chromatid exchanges in Syrian hamster embryo cells

Miyachi

Tsutsui

2005

Odontology

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“…For a long time, extracts of licorice and its main constituent, glycyrrhetinic acid, have been widely used in medicine and as natural sweetening additives. [6][7][8][9][10][11][12][13][14][15][16][17] Kobuke et al 28 reported that the long-term oral administration of the sodium salt of glycyrrhetinic acid in drinking water (up to 0.5%) to mice did not yield any evidence of chronic toxicity, which suggested that the extracts of licorice and glycyrrhetinic acid are devoid of systematic toxicity and, therefore, may be used as effective and practical chemopreventive agents against tumorigenicity in humans.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of 18β-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice

2005

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Glycyrrhetinic acid is an aglycone of glycyrrhizic acid, another major active component of licorice roots. Licorice root extract has been used for a long time as a medicine and a natural sweetening additive. In the present study, we found that glycyrrhetinic acid inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA) mediated oxidative stress and tumor promotion in murine skin. Topical application of TPA alone in mouse skin enhances ornithine decarboxylase activity and also increases [3H]-thymidine incorporation in DNA. Topical application of TPA also resulted in the depletion of glutathione, activities of glutathione metabolizing and antioxidant enzymes. Application of glycyrrhetinic acid prior to TPA treatment reduces this enhanced ODC activity, [3H]-thymidine incorporation in DNA and oxidative stress. Glycyrrhetinic acid was also found to inhibit DMBA/TPA-induced skin tumor formation at doses of 1.25 and 2.5 mg by reducing the number of tumors per mouse by 24% (P < 0.05) and 62% (P < 0.05), respectively. These results suggest that glycyrrhetinic acid, an antioxidant, is a potential chemopreventive agent that can inhibit DMBA/TPA-induced cutaneous oxidative stress and tumor promotion.

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“…A reduced abdominal fat content was found at all doses (Sedghi et al, 2010); because of this a NOAEL could not be derived. Kobuke et al (1985) found no effect on the incidence of any tumour when disodium glycyrrhizinate was administered to B6C3F 1 mice at concentrations of up to 0.15 % (males) or 0.3 % (females) in drinking water for 96 weeks in a carcinogenicity study.…”

Section: Repeated-dose Toxicity Studiesmentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

Högstrand¹

2015

EFSA Journal

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European Food Safety Authority (EFSA), Parma, Italy ABSTRACTGlycyrrhizic acid is extracted from the dried and ground rhizome and root portions of the perennial leguminous plant Glycyrrhiza glabra L., native to southern Europe and Central Asia, or other species of the genus Glycyrrhiza. It is currently listed in the register of flavouring substances, allowing its use in food without restriction. Glycyrrhyzic acid ammoniated is safe at the concentration of 1 mg/kg complete feed for all species, except chickens for fattening and laying hens. For these two categories, a safe concentration of 0.3 mg/kg complete feed applies. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the safety of the additive used in water for drinking. The FEEDAP Panel considers that the use of glycyrrhizic acid ammoniated in animal nutrition would not measurably increase consumer exposure. In the absence of data on user safety, the FEEDAP Panel considers it prudent to treat glycyrrhizic acid ammoniated as an irritant to skin, eyes and respiratory tract and as a skin sensitiser. The use of glycyrrhizic acid ammoniated in animal feeds would not pose a risk to the environment. As glycyrrhizic acid ammoniated is used in food as a flavouring, no further demonstration of efficacy is necessary. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30-miscellaneous substances) when used as a flavouring for all animal species.The FEEDAP Panel concludes that glycyrrhyzic acid ammoniated is safe at the concentration of 1 mg/kg complete feed for all species except chickens for fattening and laying hens. For these two categories, a safe concentration of 0.3 mg/kg complete feed applies. The FEEDAP Panel cannot conclude on the safety of the additive used in water for drinking.The FEEDAP Panel considers that the use of glycyrrhizic acid ammoniated in animal nutrition would not measurably increase consumer exposure.In the absence of data on user safety, the FEEDAP Panel considers it prudent to treat glycyrrhizic acid ammoniated as an irritant to skin, eyes and respiratory tract and as a skin sensitiser.The use of glycyrrhizic acid ammoniated in animal feeds would not pose a risk to the environment.As glycyrrhizic acid ammoniated is used in food as a flavouring, no further demonstration of efficacy is necessary.Glycyrrhizic acid ammoniated for all animal species EFSA Journal 2015;13(1):3971 3

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Tumorigenicity study of disodium glycyrrhizinate administered orally to mice

Cited by 29 publications

References 4 publications

Ability of 13 chemical agents used in dental practice to induce sister-chromatid exchanges in Syrian hamster embryo cells

Ability of 13 chemical agents used in dental practice to induce sister-chromatid exchanges in Syrian hamster embryo cells

Inhibitory effect of 18β-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

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