• Fibers and Polymers
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• v.6 no.4
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• pp.297-305
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• 2005

A series of new direct dyes based on benzidine congeners, 2,2'-dimethyl-5,5'-dipropoxybenzidine and 5,5'-dipropoxybenzidine, were evaluated for mutagenicity in Salmonella typhimurium strains TA98 and TA100. All of the dyes examined were judged to be non-mutagenic with and without metabolic activation while toxicity was seen in some dyes at high doses. The study also suggested that the standard Salmonella mutagenicity plate-incorporated assay was an excellent method for evaluation of direct dyes for mutagenicity.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.251-257
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• 1996

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is subject of great concern at present. In this respect, the genetic toxicity of fenpropathrin ((RS)-.alpha.-cyano-3-phenoxybenzyl-2,2,3,3-tetramethyl cyclopropane carboxylate, CAS No.:39514-41-8), a pyrethroid insecticide, was evaluated in bacterial gene mutation system, chromosome aberration in mammalian cell system and in vivo micronucleus assay with rodents. In bacterial gene mutation assay, no mutagenicity of fenpropathrin (62-$5000\mug/plate$) was observed in Salmonella typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activaton system. In mammalian cell system using chinese hamster lung fibroblast, no clastogenicity of fenpropathrin was also observed both in the absence and in the presence of metabolic activation system in the concentration range of $7-28\mug/ml$. And also, in vivo micronucleus assay using mouse bone marrow cells, fenpropathrin also revealed no mutagenic potential in the dose range of 27-105 mg/kg body weight of fenpropathrin (i.p.). Consequently, no mutagenic potential of fenpropathrin was observed in vitro bacterial, mammalian mutagenicity systems and in vivo micronucleus assay in the dose ranges used in this experiment.

• Korean Journal of Pharmacognosy
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• v.36 no.2 s.141
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• pp.93-96
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• 2005

Mutagenicity of Gamgung-tang (GGT) was tested using in vitro S-9 mixture in vitro host-mediated assay with Salmonella typhimurium. In the previous reports, GGT was tested for the safety using Ames(-S-9), Bacillus subtilis Rec, and umu gene expression mutagenicity tests. Mutagenic activity in any assays we tested was not found. In this report, we further investigated safety of GGT after metabolic activation in vivo. Ames test with S-9 mixture and host-mediated assay with Salmonella typhimurium TA98 were used to identify metagenic property of GGT. GGT was administered 3 times with i.m. to Balb/c mice did not induced mutagenic effect in Salmonella typhimurium TA98 recovered from the liver after 3.5h with i.p. treatment. Over the entire dose range $(3{\sim}150mg/mouse)$ tested no toxicity was detected to the bacterial cells. These results suggest that there was no DNA damage and mutagenicity by GGT.

• Environmental Mutagens and Carcinogens
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• v.20 no.1
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• pp.21-25
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• 2000

Recently there is increasing interest in the use of structure activity relationships for predicting the biological activity of chemicals. The reasons for the interest include the decrease cost and time per chemical as compared with animal or cell system for identifying toxicological effects of chemicals and the reduction in the use of animals for toxicological testing. This study is to test the validity of the mutagenicity data generated from QSAR (Quantitative Structure Activity Relationship) program. Thirty chemicals, which had been evaluated by Ames test during 1997-1999, were assessed with TOPKAT QSAR mutagenicity prediction module. Among 30chemicals experimented, 28 were negative and 2 were positive for Ames test. On the contrary, 23 chemicals showed the high confidence level indicating high prediction rate in mutagenicity evaluation, and 7 chemicals showed the lsow to moderate confidence level indicating low prediction in mutagenicity evaluation. Overall mutagenicity prediction rate was 77% (23/30). The prediction rates for non-mutagenic chemicals were 79% (22/28) and mutagenic chemicals were 50% (1/2). QSAR could be a useful tool in providing toxicological data for newly introduced chemicals or in furnishing data for MSDS or in determining the dose in toxicity testing for chemicals with no known toxicological data.

• Toxicological Research
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• v.35 no.2
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• pp.119-129
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• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.179-188
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• 2005

To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

• 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.

• 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.

• Toxicological Research
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• v.29 no.4
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• pp.263-278
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• 2013

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.