[논문]미생물복귀돌연변이(Ames)시험을 통한 탄산리튬의 변이원성 고찰

임경택; 김수진

doi:10.15269/jksoeh.2014.24.3.330

[국내논문] 미생물복귀돌연변이(Ames)시험을 통한 탄산리튬의 변이원성 고찰
Mutagenicity of Lithium Carbonate Assessed by Bacterial Reverse Mutation(Ames) Test 원문보기

한국산업위생학회지 = Journal of Korean Society of Occupational and environmental hygiene, v.24 no.3, 2014년, pp.330 - 335

임경택 (한국산업안전보건공단 산업안전보건연구원) , 김수진 (한국산업안전보건공단 산업안전보건연구원)

Abstract ▼ AI-Helper

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.

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문제 정의

In this test, treatment of lithium carbonate at each five dose did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA with and without metabolic activation. These results indicate that the lithium carbonate do not have mutagenic potentials under the conditions examined in this study.

제안 방법

According to toxicity data in table 1, the half lethal dose is 525 mg/kg, it is ranked category 4 of the globally harmonized classification system with oral route, but the available genotoxicity data on this chemical are still nothing. Thus it was evaluated to determine the genotoxicity or mutagenicity with Ames test with GLP guideline. So it is the first trial to evaluate the mutagenicity of lithium carbonate.
The cytotoxicity test was detected by a reduction in the number of reverting colonies, a clearing or diminution of the background lawn, or the degree of survival of treated cultures.
It is the first trial to evaluate the mutagenicity of this chemical with GLP level. From this study, it was performed the reverse mutation assay both in direct method and metabolism activated method for 6 hr treatment in test with several strains. This study should help to improve testing of this chemical by generally used genotoxicity testing methods as well as investigations on the underlying mechanism and the interpretation of genotoxicity data on this chemical with hazard, and could applicative for workers’ health.
In this study, the reverse mutation test with S. typhimurium and E. coli was carried out in order to examine the mutagenicity of lithium carbonate from the data obtained in this study, this chemical in non-mutagenic since there was either a less than two-fold increase over spontaneous reversion rate(percent of control <200%) or no dose-response curve when dilutions were tested.

대상 데이터

The lithium carbonate(99.997%, Sigma-Aldrich, MO, USA) was dissolved in vehicles(sterilized distilled water, Dai Han Pharm. Co., Ltd., Seoul, Korea) and diluted if appropriate prior to treatment of the bacteria.
In this study, sodium azide(98%, WAKO, Osaka, Japan), 9-aminoacridine(9AA)(98%, Sigma-Aldrich, MO, USA), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide(AF-2)(98%, WAKO, Osaka, Japan) and 2-aminoanthracene(2AA) (98%, WAKO, Osaka, Japan) were used as positive controls. Dimethyl sulfoxide(99.5%, Sigma-Aldrich, MO, USA) was used as a solvent.
The culture containing a high titer of viable bacteria(MDF-U3086S, Sanyo, Osaka, Japan) was used in the experiment. Five strains include four strains of S.

성능/효과

In this test, treatment of lithium carbonate at each five dose did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA with and without metabolic activation. These results indicate that the lithium carbonate do not have mutagenic potentials under the conditions examined in this study.

후속연구

This study should help to improve testing of this chemical by generally used genotoxicity testing methods as well as investigations on the underlying mechanism and the interpretation of genotoxicity data on this chemical with hazard, and could applicative for workers’ health.

참고문헌 (13)

Ames BN, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 1975;31:347-364

상세보기
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European Chemicals Bureau(ECB). IUCLID Dataset, Lithium Carbonate(CAS # 554-13-2) [serial online] 2007 [cited 2014 May 30]. Available from: http://esis.jrc.ec.europa.eu/
Gatehouse D, Haworth S, Cebula T, Gocke E, Kier L, et al. Report from the working group on bacterial mutation assays: international workshop on standardization of genotoxicity test procedures. Mutat Res 1994; 312: 217-233

상세보기
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상세보기
National Institute for Occupational Safety and Health(NIOSH). International Safety Cards. Lithium carbonate.(CAS # 554-13-2) [serial online] 2007 [cited 2014 May 30]. Available from: http://www.cdc.gov/niosh/ipcs/nicstart.html
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O'Neil MJ. The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, Merck and Co. Inc., New Jersey; 2006. p. 958
Organization for Economic Cooperation and Development (OECD). Section 4 of the OECD guidelines for the testing of chemicals: bacterial reverse mutation test, guideline 471, adopted July 21st, 1997.
Ullmann. Encyclopedia of Industrial Chemistry. 6th ed. Vol 1. Wiley-VCH Verlag GmbH & Co., Germany; 2003. p. V20
Zeiger E. Identification of rodent carcinogens and noncarcinogens using genetic toxicity tests: premises, promises, and performance. Regul Toxicol Pharmacol 1998;28:85-95

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