• Toxicological Research
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• v.29 no.4
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• pp.249-255
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• 2013

Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 ${\mu}g$/plate in bacterial reverse mutation tests, 5,000 ${\mu}g/ml$ in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y $tk^{+/-}$ cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y $tk^{+/-}$ cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo.

• Journal of Microbiology and Biotechnology
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• v.16 no.5
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• pp.817-820
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• 2006

The potential genotoxicity of methylsulfonylmethane, a crystalline organic sulfur, derived from chemically modified lignin from plants was evaluated using in vitro and in vivo assays. In the bacterial reverse mutation test using Salmonella typhimurium TA98, TA100, TA1535, and TA1538, methylsulfonylmethane did not induce any significant increase of His' revertants. In the in vitro chromosome aberration test using Chinese Hamster Lung (CHL) cells, no aberration effects were seen. In the in vivo evaluation using a micronucleus test, negative results were obtained. Accordingly, the results indicated that methylsulfonylmethane is not genotoxic and its use is unlikely to present a potential hazard.

• The Plant Pathology Journal
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• v.27 no.1
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• pp.89-92
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• 2011

Cyclic AMP receptor-like protein (Clp), is known to be a global transcriptional regulator for the expression of virulence factors in Xanthomonas campestris pv. campestris (Xcc). Sequence analysis showed that Xanthomonas oryzae pv. oryzae (Xoo) contains a gene that is strongly homologous to the Xcc clp. In order to determine the role of the Clp homolog in Xoo, a marker exchange mutant of $clp_{xoo4158}$ was generated. Virulence and virulence factors, such as the production of cellulase, xylanase, and extracellular polysaccharides (EPS) and swarming motility were significantly decreased in the $clp_{xoo4158}$ mutant. Moreover, the mutation caused the strain to be more sensitive to hydrogen peroxide and to over-produce siderophores. Complementation of the mutant restored the mutation-related phenotypes. Expression of $clp_{xoo4158}$, assessed by reverse-transcription realtime PCR and clp promoter activity, was significantly reduced in the rpfB, rpfF, rpfC, and rpfG mutants. These results suggest that the clp homolog, $clp_{xoo4158}$, is involved in the control of virulence and resistance against oxidative stress, and that expression of the gene is controlled by RpfC and RpfG through a diffusible signal factor (DSF) signal in Xanthomonas oryzae pv. oryzae KACC10859.

• Journal of Life Science
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• v.28 no.5
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• pp.605-614
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• 2018

Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

• Journal of Food Hygiene and Safety
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• v.31 no.2
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• pp.107-112
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• 2016

This study was to determine genotoxicity from the extracts of fermented Acanthopanax koreanum. The bacterial reverse mutation assay, the extracts of fermented A. koreanum did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA with or without metabolic activation of S-9 mixture. In addition, the micronucleus formation in ICR mice, the extracts of fermented A. koreanum treated with dose of 500, 1,000 and 2,000 mg/kg did not affected micronucleated polychromatic erythrocytes (MNPCE/2,000 PCE) and polychromatic erythrocytes (PCE)/200 polychromatic erythrocyte+normochromatic erythrocyte (RBC). The cytotoxicity effects using CHO-K1 cells observed no significant changes compared with negative control group (p < 0.05). Moreover, the extracts of fermented A. koreanum did not cause a significant chromosome aberration on CHO-K1 cells in the chromosome aberration assay. Therefore, these results suggest that the extracts of fermented A. koreanum did not induce any harmful genotoxic effects.

• The Korean Journal of Pesticide Science
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• v.8 no.4
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• pp.288-298
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• 2004

Benzimidazole pesticide carbendazim that is effective against a wide range of fungal plant pathogens is a protective, eradicant, and systemic fungicide. For genetic toxicity evaluation of carbendazim on DNA, genes and chromosome, were investigated with chromosome aberration, bacterial reverse mutation, micronucleus test in mouse born marrow and DNA damage assay by single cell microgel electrophoresis. Substitution and frameshift mutation were not induce at variable concentration of carbendazim on Ames test with or without rat liver microsomal activation. For the result of chromosome aberration test, numerical changes of chromosome were detected at the concentrations higher than $4.0{\mu}g/m{\ell}$, but structural aberration was not induced. Positive control, Mitomycin-C and captafol made a structural aberration, but numerical change of chromosome did not appear. In the micronucleus test for mouse born marrow, carbendazim was negative, but was weak positive in DNA damage assay by single cell microgel electrophoresis because of increased DNA moving length of 20% to control.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.10
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• pp.1406-1413
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• 2016

This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

• Toxicological Research
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• v.30 no.2
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• pp.121-130
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• 2014

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.83-87
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• 2009

In this study, we assessed the stability and toxicological safety of Angelica gigas Nakai (A. gigas Nakai) extract, which is comprised of decursin and decursinol angelate (D/DA). D/DA was tested for mutagenicity using Ames Salmonella tester strains (TA102, TA1535, and TA1537) with or without metabolic activation (S9 mix). No increase in the number of revertants was observed in response to any of the doses tested (1.25, 12.5, 125, and $1,250{\mu}/mLg$). In addition, a chromosome aberration test was conducted in the Chinese hamster lung (CHL) cell line. To accomplish this, cells were treated with D/DA (3.28, 13.12, 52.46, and $209.84{\mu}g/mL$) or with Mitomycin C ($0.1{\mu}/mLg$) as a positive control in the case of no metabolic activation or benzo(a)pyrene ($20{\mu}g/mL$) in the case of metabolic activation. No significant increase in chromosome aberrations was observed in response to treatment with any of these concentrations, regardless of activation of the metabolic system. According to these results, we concluded that D/DA did not induce bacterial reverse mutation or clastogenicity in vitro in the range of concentrations evaluated in these experiments.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.