• Journal of Ginseng Research
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• 제41권4호
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• pp.595-601
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• 2017

Background: Red ginseng oil (RGO) is produced by supercritical $CO_2$ extraction of secondary products derived from Korean Red Ginseng extract. As the use of RGO has increased, product safety concerns have become more important. Methods: In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of RGO were evaluated. Sprague-Dawley rats were orally administered with RGO for 28 d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500 mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation tests included five bacterial strains (Escherichia coli WP2 and Salmonella typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or absence of metabolic activation. The plated incorporation method for mutation test was used with RGO concentrations ranging from $312.5{\mu}g$ to $5,000{\mu}g$ per plate. Results: The subacute oral toxicity test results did not reveal any marked changes in clinical characteristics. There were no toxicological changes related to RGO administration in hematological and serum biochemical characteristics in either control or treatment animals. Furthermore, no gross or histopathological changes related to RGO treatment were observed. The bacterial reverse mutation test results did not reveal, at any RGO concentration level and in all bacterial strains, any increase in the number of revertant colonies in the RGO treatment group compared to that in the negative control group. Conclusion: The no-observed-adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce genotoxicity related to bacterial reverse mutations.

• Toxicological Research
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• 제35권3호
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• pp.215-224
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• 2019

As various populations are rapidly becoming an aging society worldwide and interest in health issues has increased, demand for functional foods including herbal products has increased markedly to maintain a healthy state which has led to safety issues about their intake as an inevitable result. The objective of this study was to identify the safety profile of a Korean red ginseng and Salvia plebeia R. Br. extract mixture (KGC-03-PS) which is a valuable ingredient that can be used as a functional food. In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of KGC-03-PS were evaluated. Sprague Dawley rats were administered KGC-03-PS orally for 28 days by gavage. Daily KGC-03-PS dose concentrations were 0, 500, 1,000, or 2,000 mg/kg body weight (bw) per day. Bacterial reverse mutation test with KGC-03-PS dose levels ranging from 312.5 to $5,000{\mu}g/plate$ was carried out by OECD test guideline No. 471. Five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) were tested in the presence or absence of metabolic activation by plate incorporation method. There were no toxicological effects related with test substance in the clinical evaluation of subacute oral toxicity test including clinical signs, body weight, and food consumption. Moreover, no toxicological changes related to KGC-03-PS were observed in the hematological and serum biochemical characteristics as well as in the pathological examinations, which included organ weight measurements and in the gross- or histopathological findings. KGC-03-PS did not induce an increase in the number of revertant colonies in all bacterial strains of the bacterial reverse mutation test. The no-observed-adverse-effect level of KGC-03-PS is greater than 2,000 mg/kg bw/day, and KGC-03-PS did not induce genotoxicity related to bacterial reverse mutations under the conditions used in this study.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.14.1-14.6
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• 2012

Objectives: The root barks of Periploca sepium Bge. (P. sepium) has been used in traditional Chinese medicine for healing wounds and treating rheumatoid arthritis. However, toxicity in high-doses was often diagnosed by the presence of many glycosides. The potential mutagenicity of P. sepium was investigated both in vitro and in vivo. Methods: This was examined by the bacterial reverse mutation (Ames) test using Escherichia coli WP2uvrA and Salmonella typhimurium strains, such as TA98, TA100, TA1535, and TA1537. Chromosomal aberrations were investigated using Chinese hamster lung cells, and the micronucleus test using mice. Results: P. sepium did not induce mutagenicity in the bacterial test or chromosomal aberrations in Chinese hamster lung cells, although metabolic activation and micronucleated polychromatic erythrocytes were seen in the mice bone marrow cells. Conclusions: Considering these results, it is suggested that P. sepium does not have mutagenic potential under the conditions examined in each study.

• 대한약침학회지
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• 제25권4호
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• pp.364-368
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• 2022

Objectives: Verbenalin is a compound found in herbs such as Cornus officinalis and Verbena officinalis. This study investigated whether verbenalin is safe by analyzing its mutagenicity. Methods: To examine the mutagenic potential of verbenalin, a bacterial reverse mutation test (Ames test) was conducted with Salmonella typhimurium and Escherichia coli strains. Experiments with and without metabolic activity were performed. Results: The mean colony number was less than double that of the control. Growth inhibition and precipitation of verbenalin were not apparent in all strains at different concentrations regardless of metabolic activity. Conclusion: Verbenalin did not show any signs of mutagenicity in this study. Additional toxicity studies including repeated oral toxicity, reproductive toxicity, and carcinogenicity tests are needed.

• Toxicological Research
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• 제29권3호
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• Archives of Pharmacal Research
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• 제21권3호
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• pp.305-309
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• 1998

Human cytochrome P450 1A2 is one of the major cytochrome P450s in human liver. It is known to be capable of activating a number of carcinogens such as arylamines and heterocyclic amines. In order to develop the new bacterial mutagenicity test system with human P450, a full length of human P450 1A2 cDNA inserted into pCW bacterial expression vector was introduced to Escherichia coli WP2 uvrA strain which is a well-known E. coli strain for bacterial reverse mutagenicity assay. Expressed human P450 1A2 showed typical P450 hemoprotein spectra. Maximum expression was achieved at 48 hrs after incubating at $30^{\circ}C$ in terrific broth containing ampicillin, IPTG and other supplements. High level expression of P450 1A2 in E. coli WP2 uvrA membranes was determined in SDS-PAGE. The well-known mutagens 2-aminoanthracene and MElQ increased the revertant colonies of E. coli WP2 uvrA expressing human P450 1A2 without an exogenous rat hepatic post-mitochondrial supernatant (S9 fraction) in a dose-dependent manner. The results show that the functional expression of human P450 in bacterial mutagenicity tester strain will provide a useful tool for studying the mechanism of the mutagenesis and carcinogenesis of new drugs and environmental chemicals.

• 한국산업보건학회지
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• 제24권3호
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• pp.330-335
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• 2014

Objectives: To evaluate the mutagenicity of lithium carbonate, a bacterial reverse mutation(Ames) test was carried out using four strains of S. typhimurium(TA1535; TA1537; TA98; and TA100) and one strain of E. coli(WP2uvrA). Materials: This was carried out in a dose range from 312.5 to $5,000{\mu}g/plate$ in triplicate with and without S9 activation, which is the most commonly used metabolic activation system supplemented by a post-mitochondrial fraction prepared from the livers of rodents treated with enzyme-inducing agents such as Aroclor 1254 or a combination of phenobarbitone and ${\beta}$-naphthoflavone. Results: No significant increases in the number of revertants were observed under the conditions examined in this study. Conclusions: Based on the above observations, it can be concluded that lithium carbonate has no mutagenic activity. Despite the results, it can have an effect by inducing acute oral toxicity, eye irritation and acute aquatic toxicity. Based on this study, we suggest that future studies should be directed toward chronic, carcinogenic testing and other related areas.

• Preventive Nutrition and Food Science
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• 제18권2호
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• pp.111-116
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• 2013

Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, ${\alpha}$-cadinol, camphene, pinocarvone, ${\beta}$-caryophyllene, 3-cyclohexen- 1-ol, and ${\gamma}$-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral single gavage administration of C. indicum flower oil. There were no mortality and clinical signs of toxicity at 2,000 mg/kg body weight/day of C. indicum flower oil throughout the 15 day period. Micronucleated erythrocyte cell counts for all treated groups were not significantly different between test and control groups. Levels of 15.63~500 ${\mu}g$ C. indicum flower oil/plate did not induce mutagenicity in S. Typhimurium and E. coli, with or without the introduction of a metabolic activation system. These results indicate that ingesting C. indicum flower oil produces no acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation.

• Journal of Dairy Science and Biotechnology
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• 제34권2호
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• pp.91-98
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• 2016

본 시험은 안전식품인 우유단백질에서 분리되어 영유아 식품 등에 세계적으로 사용되고 있는 GMP 내 기본적으로 7%로 결합되어 있는 지표성분인 sialic acid의 함유량이 높게 제조한 23%-GNANA를 기능성 식품 원료 개발함에 최종 연구 목표를 두었다. 시험물질은 23% sialic acid와 GMP 단백질로 구성(제품명: HELICOBACTROL-23)되어 있으며, (주)한일바이오메드사(한국)에서 공여 받아 미생물복귀돌연변이시험을 실시하였다. 미생물에 대한 돌연변이 유발성 유무를 검색하기 위해 히스티딘 요구성 균주인 Salmonella typhimurium TA98, TA100, TA1535 및 TA1537과 트립토판 요구성 균주인 Escherichia coli WP2uvrA를 이용하였다. 미생물복귀돌연변이시험은 시험물질을 5단계의 농도군(0, 61.7, 185, 556, 1,670, $5,000{\mu}g/plate$)으로 하여 평가하였다. 평가결과로서, 대사활성계 존재 유무와 관계없이 5균주 모두에서 시험물질의 각 농도에 의한 복귀돌연변이 유발원 양성기준인 콜로니 생성수치가 재현성있는 증가를 나타내지 않았으며, 용량의존성도 확인되지 않았다. 결론적으로, 시험물질인 23%-GNANA의 식품첨가물로서 등록을 위하여 수행한 미생물돌연변이시험에서 안전성이 확인되었다.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.319-323
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• 2002

In order to investigate the safety of Aralia elata extract causing the reduction in the blood glucose level and oxidative stress in diabetes animals, these genotoxicity studies in bacterial and mammalian cell assay system such as Ames bacterial reverse mutation test and chromosomal aberration assay were performed. As results, in Ames bacterial reversion assay the extract in the range of 5,000-625 ug/plate did not induce mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains with and without metabolic activation of S-9 mixture. For chromosomal aberration assay, $IC_{50}$ (50% inhibition concentration of cell growth) of the extract were determined; 792 $\mu\textrm{g}$/$m\ell$ without and 524 $\mu\textrm{g}$/$m\ell$ with S-9 mixture in Chinese hamster lung (CHL) fibroblast cell culture. Any significant chromosomal aberration was not observed in CHL cells treated with the extract at the concentrations of 792, 396 and 198 $\mu\textrm{g}$/$m\ell$ or 524, 262 and 131 $\mu\textrm{g}$/$m\ell$ in the absence or presence of S-9 metabolic activation, respectively. From these results, Aralia elata extract did not induce any harmful effects on the gene in bacteria and mammalian cell system used in these experiments.