Abstract
The widespread usage and ubiquitous distribution of triclocarban (3,4,4′-trichlorocarbanilide, TCC) have raised public concerns about its health effects. At present, there is little information about the genotoxicity of TCC. In this study, we used a battery of genotoxicity testing methods including salmonella reverse mutation test (Ames test), comet assay and micronucleus assay to detect the effects of TCC on gene mutation, DNA breakage, and chromosome damage. The results of Ames test showed that TCC at 0.1–1000 μg/plate did not significantly increase the number of revertant colonies in the four standard Salmonella typhimurium strains, i.e., TA97, TA98, TA100, and TA102, when compared to the vehicle control. The results from comet assay demonstrated that exposure to 5, 10, or 15 μM TCC for 24 h did not significantly increase the percentage of comet cells, tail length (TL), DNA in tail (T DNA%), or olive tail moment (OTM) in keratinocyte HaCaT and hepatic L02 cells. Moreover, TCC did not markedly enhance the frequency of micronucleated cells or micronuclei in HaCaT and L02 cells in the micronucleus assay. Taken together, the results indicated that TCC did not exhibit any genotoxic effects. Our study provides additional information for the safety profile of TCC.
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References
Birch CG, Hiles RA, Eichhold TH, Jeffcoat AR, Handy RW, Hill JM, Willis SL, Hess TR, Wall ME (1978) Biotransformation products of 3,4,4′-trichlorocarbanilide in rat, monkey, and man. Drug Metab Dispos 6:169–176
Chen C, Jiang X, Lai Y, Liu Y, Zhang Z (2015) Resveratrol protects against arsenic trioxide-induced oxidative damage through maintenance of glutathione homeostasis and inhibition of apoptotic progression. Environ Mol Mutagen 56:333–346. https://doi.org/10.1002/em.21919
Cimino MC (2006) Comparative overview of current international strategies and guidelines for genetic toxicology testing for regulatory purposes. Environ Mol Mutagen 47:362–390. https://doi.org/10.1002/em.20216
Clive D (1985) Mutagenicity in drug development: interpretation and significance of test results. Regul Toxicol Pharmacol 5:79–100
Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26:249–261. https://doi.org/10.1385/mb:26:3:249
De Flora S, Camoirano A, Zanacchi P, Bennicelli C (1984) Mutagenicity testing with TA97 and TA102 of 30 DNA-damaging compounds, negative with other Salmonella strains. Mutat Res 134:159–165
Enright HA, Falso MJS, Malfatti MA, Lao V, Kuhn EA, Hum N, Shi Y, Sales AP, Haack KW, Kulp KS, Buchholz BA, Loots GG, Bench G, Turteltaub KW (2017) Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model. PLoS One 12:e0181996. https://doi.org/10.1371/journal.pone.0181996
FDA (2016) Safety and effectiveness of consumer antiseptics; topical antimicrobial drug products for over-the-counter human use. Final rule. Fed Regist 81:61106–61130
Gao L, Yuan T, Cheng P, Bai Q, Zhou C, Ao J, Wang W, Zhang H (2015) Effects of triclosan and triclocarban on the growth inhibition, cell viability, genotoxicity and multixenobiotic resistance responses of Tetrahymena thermophila. Chemosphere 139:434–440. https://doi.org/10.1016/j.chemosphere.2015.07.059
Gasperi J, Geara D, Lorgeoux C, Bressy A, Zedek S, Rocher V, El Samrani A, Chebbo G, Moilleron R (2014) First assessment of triclosan, triclocarban and paraben mass loads at a very large regional scale: case of Paris conurbation (France). Sci Total Environ 493:854–861. https://doi.org/10.1016/j.scitotenv.2014.06.079
Gu S, Chen C, Jiang X, Zhang Z (2015) Resveratrol synergistically triggers apoptotic cell death with arsenic trioxide via oxidative stress in human lung adenocarcinoma A549 cells. Biol Trace Elem Res 163:112–123. https://doi.org/10.1007/s12011-014-0186-2
Halden RU (2014) On the need and speed of regulating triclosan and triclocarban in the United States. Environ Sci Technol 48:3603–3611. https://doi.org/10.1021/es500495p
Halden RU (2016) Lessons learned from probing for impacts of triclosan and triclocarban on human microbiomes. mSphere 1. doi: https://doi.org/10.1128/mSphere.00089-16
Halden RU, Lindeman AE, Aiello AE, Andrews D, Arnold WA, Fair P, Fuoco RE, Geer LA, Johnson PI, Lohmann R, McNeill K, Sacks VP, Schettler T, Weber R, Zoeller RT, Blum A (2017) The Florence Statement on triclosan and triclocarban. Environ Health Perspect 125:064501. https://doi.org/10.1289/ehp1788
Han J, Won EJ, Hwang UK, Kim IC, Yim JH, Lee JS (2016) Triclosan (TCS) and triclocarban (TCC) cause lifespan reduction and reproductive impairment through oxidative stress-mediated expression of the defensome in the monogonont rotifer (Brachionus koreanus). Comp Biochem Physiol C Toxicol Pharmacol 185-186:131–137. https://doi.org/10.1016/j.cbpc.2016.04.002
Healy MG, Fenton O, Cormican M, Peyton DP, Ordsmith N, Kimber K, Morrison L (2017) Antimicrobial compounds (triclosan and triclocarban) in sewage sludges, and their presence in runoff following land application. Ecotoxicol Environ Saf 142:448–453. https://doi.org/10.1016/j.ecoenv.2017.04.046
Huang H, Du G, Zhang W, Hu J, Wu D, Song L, Xia Y, Wang X (2014) The in vitro estrogenic activities of triclosan and triclocarban. J Appl Toxicol 34:1060–1067. https://doi.org/10.1002/jat.3012
Kersten B, Zhang J, Brendler-Schwaab SY, Kasper P, Muller L (1999) The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity. Mutat Res 445:55–71
Li X, Gu S, Sun D, Dai H, Chen H, Zhang Z (2018) The selectivity of artemisinin-based drugs on human lung normal and cancer cells. Environ Toxicol Pharmacol 57:86–94. https://doi.org/10.1016/j.etap.2017.12.004
Lozano N, Rice CP, Ramirez M, Torrents A (2018) Fate of triclocarban in agricultural soils after biosolid applications. Environ Sci Pollut Res Int 25:222–232. https://doi.org/10.1007/s11356-017-0433-0
Maron DM, Ames BN (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173–215
Miller B, Albertini S, Locher F, Thybaud V, Lorge E (1997) Comparative evaluation of the in vitro micronucleus test and the in vitro chromosome aberration test: industrial experience. Mutat Res 392(45–59):187–208
Mortelmans K, Zeiger E (2000) The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29–60
Musee N (2018) Environmental risk assessment of triclosan and triclocarban from personal care products in South Africa. Environ Pollut 242:827–838. https://doi.org/10.1016/j.envpol.2018.06.106
OECD (1997) OECD guideline for testing of chemicals: bacterial reverse mutation test. Organization for Economic Cooperation and Development http://www.oecd.org/dataoecd/18/31/1948418.pdf
Pu X, Wang Z, Klaunig JE (2015) Alkaline comet assay for assessing DNA damage in individual cells. Curr Protoc Toxicol 65:3.12.11–3.12.11. https://doi.org/10.1002/0471140856.tx0312s65
Ribado JV, Ley C, Haggerty TD, Tkachenko E, Bhatt AS (2017) Household triclosan and triclocarban effects on the infant and maternal microbiome. EMBO Mol Med 9:1732–1741. https://doi.org/10.15252/emmm.201707882
Rochester JR, Bolden AL (2017) Potential developmental and reproductive impacts of triclocarban: a scoping review. J Toxicol 2017:9679738. https://doi.org/10.1155/2017/9679738
Rodrigues S, Antunes SC, Correia AT, Nunes B (2017) Rainbow trout (Oncorhynchus mykiss) pro-oxidant and genotoxic responses following acute and chronic exposure to the antibiotic oxytetracycline. Ecotoxicology 26:104–117. https://doi.org/10.1007/s10646-016-1746-3
Satyro S, Saggioro EM, Verissimo F, Buss DF, de Paiva Magalhaes D, Oliveira A (2017) Triclocarban: UV photolysis, wastewater disinfection, and ecotoxicity assessment using molecular biomarkers. Environ Sci Pollut Res Int 24:16077–16085. https://doi.org/10.1007/s11356-017-9165-4
SCCP European Commission (2004) Opinion on triclocarban for other uses than as a preservative. Scientific Committee on Consumer Products Report No.: SCCP/0851/04
Shi Q, Zhuang Y, Hu T, Lu C, Wang X, Huang H, Du G (2019) Developmental toxicity of triclocarban in zebrafish (Danio rerio) embryos. J Biochem Mol Toxicol 33:e22289. https://doi.org/10.1002/jbt.22289
Simon A, Maletz SX, Hollert H, Schaffer A, Maes HM (2014) Effects of multiwalled carbon nanotubes and triclocarban on several eukaryotic cell lines: elucidating cytotoxicity, endocrine disruption, and reactive oxygen species generation. Nanoscale Res Lett 9:396. https://doi.org/10.1186/1556-276x-9-396
Sood S, Choudhary S, Wang HC (2013) Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin. Biochem Biophys Res Commun 438:600–606. https://doi.org/10.1016/j.bbrc.2013.08.009
Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD (2019) ROS and the DNA damage response in cancer. Redox Biol 25:101084. https://doi.org/10.1016/j.redox.2018.101084
Sun D, Zhao T, Li X, Zhang Z (2019) Evaluation of DNA and chromosomal damage in two human HaCaT and L02 cells treated with varying triclosan concentrations. J Toxic Environ Health A 82:473–482. https://doi.org/10.1080/15287394.2019.1618758
Thybaud V, Lorge E, Levy DD, van Benthem J, Douglas GR, Marchetti F, Moore MM, Schoeny R (2017) Main issues addressed in the 2014-2015 revisions to the OECD genetic toxicology test guidelines. Environ Mol Mutagen 58:284–295. https://doi.org/10.1002/em.22079
Turkez H, Arslan ME, Ozdemir O (2017) Genotoxicity testing: progress and prospects for the next decade. Expert Opin Drug Metab Toxicol 13:1089–1098. https://doi.org/10.1080/17425255.2017.1375097
Vimalkumar K, Seethappan S, Pugazhendhi A (2019) Fate of triclocarban (TCC) in aquatic and terrestrial systems and human exposure. Chemosphere 230:201–209. https://doi.org/10.1016/j.chemosphere.2019.04.145
Wang F, Xu R, Zheng F, Liu H (2018) Effects of triclosan on acute toxicity, genetic toxicity and oxidative stress in goldfish (Carassius auratus). Exp Anim 67:219–227. https://doi.org/10.1538/expanim.17-0101
Wei L, Qiao P, Shi Y, Ruan Y, Yin J, Wu Q, Shao B (2017) Triclosan/triclocarban levels in maternal and umbilical blood samples and their association with fetal malformation. Clin Chim Acta 466:133–137. https://doi.org/10.1016/j.cca.2016.12.024
Witorsch RJ, Thomas JA (2010) Personal care products and endocrine disruption: a critical review of the literature. Crit Rev Toxicol 40(Suppl 3):1–30. https://doi.org/10.3109/10408444.2010.515563
Xu X, Lu Y, Zhang D, Wang Y, Zhou X, Xu H, Mei Y (2015) Toxic assessment of triclosan and triclocarban on Artemia salina. Bull Environ Contam Toxicol 95:728–733. https://doi.org/10.1007/s00128-015-1641-2
Ye X, Wong LY, Dwivedi P, Zhou X, Jia T, Calafat AM (2016) Urinary concentrations of the antibacterial agent triclocarban in United States residents: 2013-2014 National Health and Nutrition Examination Survey. Environ Sci Technol 50:13548–13554. https://doi.org/10.1021/acs.est.6b04668
Zhao JL, Zhang QQ, Chen F, Wang L, Ying GG, Liu YS, Yang B, Zhou LJ, Liu S, Su HC, Zhang RQ (2013) Evaluation of triclosan and triclocarban at river basin scale using monitoring and modeling tools: implications for controlling of urban domestic sewage discharge. Water Res 47:395–405. https://doi.org/10.1016/j.watres.2012.10.022
Zhu Q, Jia J, Wang Y, Zhang K, Zhang H, Liao C, Jiang G (2019) Spatial distribution of parabens, triclocarban, triclosan, bisphenols, and tetrabromobisphenol A and its alternatives in municipal sewage sludges in China. Sci Total Environ 679:61–69. https://doi.org/10.1016/j.scitotenv.2019.05.059
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This work was supported by the grant from the National Science Foundation of China (No. 81773380) to Zunzhen Zhang.
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Sun, D., Zhao, T., Wang, T. et al. Genotoxicity assessment of triclocarban by comet and micronucleus assays and Ames test. Environ Sci Pollut Res 27, 7430–7438 (2020). https://doi.org/10.1007/s11356-019-07351-9
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DOI: https://doi.org/10.1007/s11356-019-07351-9