Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Assessment of the Dermal and Ocular Irritation Potential of Lomefloxacin by Using In Vitro Methods

  • Ahn, Jun-Ho (Department of Biology, College of Natural Sciences, University of Incheon) ;
  • Eum, Ki-Hwan (Department of Biology, College of Natural Sciences, University of Incheon) ;
  • Lee, Mi-Chael (Department of Biology, College of Natural Sciences, University of Incheon)
  • Published : 2010.03.04
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Abstract

The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using $KeraSkin^{TM}$ human skin model system. 3T3 neutral red uptake assay has been proposed as a potential replacement alternative for the Draize Eye irritation test. In this study, the $IC_{50}$ value obtained for lomefloxacin was 375 ${\mu}g$. According to the classification model used for determining in vitro categories, lomefloxacin was classified as moderately irritant. For evaluation of skin irritation, engineered epidermal equivalents ($KeraSkin^{TM}$) were subjected to 10 and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue viability evaluation, and by the release of a pro-inflammatory mediator, interleukin- 1${\alpha}$. Lomefloxacin increased the interleukin-1${\alpha}$ release after 15 minutes of exposure and 42 hours of post incubation, although no decrease in viability was observed. Therefore, lomefloxacin is considered to be moderately irritant to skin and eye.

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References

  1. Aaronson, S.A. and Todaro, G.J. (1968). Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J. Cell. Physiol., 72, 141-148. https://doi.org/10.1002/jcp.1040720208
  2. Alepee, N., Tornier, C., Robert, C., Amsellem, C., Roux, M.H., Doucet, O., Pachot, J., Meloni, M. and de Brugerolle de Fraissinette, A. (2010). A catch-up validation study on reconstructed human epidermis (SkinEthic RHE) for full replacement of the Draize skin irritation test. Toxicol. In Vitro, 24, 257-266 https://doi.org/10.1016/j.tiv.2009.08.024
  3. Ball, P., Mandell, L. and Toillotson, G. (1999). Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf., 21, 407-421. https://doi.org/10.2165/00002018-199921050-00005
  4. Brantom, P.G., Bruner, L.H., Chamberlain, M., de Silva, O., Dupis, J., Earl, L.K., Lovell, D.P., Pape, W.J.W., Uttley, M., Bagley, D.M., et al. (1997). A summary of the COPILA international validation study on alternatives to the Draize Rabbit Eye irritation test. Toxicol. In Vitro, 11, 141-179. https://doi.org/10.1016/S0887-2333(96)00069-0
  5. Calvin, G. (1992). New approaches to the assessment of eye and skin irritation. Toxicol. Lett., 64, 157-164. https://doi.org/10.1016/0378-4274(92)90185-M
  6. Chetlat, A.-A., Albertini, S. and Gocke, E. (1996). The photomutagenicity of fluoroquniolones in tests for gene mutation, chromosomal aberration test, gene conversion and DNA breakage (Comet assay). Mutagenesis, 11, 497-504. https://doi.org/10.1093/mutage/11.5.497
  7. Coquette, A., Berna, N., Vandenbosch, A., Rosdy, M., De Wever, B. and Poumay, Y. (2003). Analysis of interleukin-1a (IL-1a) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization. Toxicol. In Vitro, 17, 311-321. https://doi.org/10.1016/S0887-2333(03)00019-5
  8. Corsini, E., Bruccoleri, A., Marinovich, M. and L., G.C. (1996). Corsini, E., A. Bruccoleri, M. Marinovich, and C.L. Galli. Endogenous interleukin-1 alpha associated with skin irritation induced by tributyltin. Toxicol. Appl. Pharmacol., 138, 268-274. https://doi.org/10.1006/taap.1996.0125
  9. Fitzhugh, O.G., Woodard, G. and Braun, H.A. (1946). The toxicities of compounds related to 2,3-dimercaptopropanol (BAL) with a note on their relative therapeutic efficiency. J. Pharmacol. Exp. Ther., 87, 23-27.
  10. Freeberg, F.E., Nixon, G.A., Reer, P.J., Weaver, J.E., Bruce, R.D., Griffith, J.F. and Sanders, L.W.I. (1986). Human and rabbit eye responses to chemical insult. Fundam. Appl. Toxicol., 7, 626-634. https://doi.org/10.1016/0272-0590(86)90112-0
  11. Gautheron, P., Dukic, M., Alix, D. and Sina, J.F. (1992). Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam. Appl. Toxicol., 18, 442-449. https://doi.org/10.1016/0272-0590(92)90142-5
  12. Griffith, J.F., Nixon, G.A., Bruce, R.D., Reeer, P.J. and Bannan, E.A. (1980). Dose-response studies with chemical irritants in the albino rabbis eye as a basis for selecting optimum testing conditions for predicting hazard to the humane eye. Toxicol. Appl. Pharmacol., 55, 501-512. https://doi.org/10.1016/0041-008X(80)90052-6
  13. Hatao, M., Murakami, N., Sakamoto, K., Ohnuma, M., Matsushige, C., Kakishima, H., Ogawa, T., Kolima, H., Matsukawa, K., Masuda, K., Chiba, K., Yoshizawa, K., Kaneko, T., Iwabuchi, Y., Matsushima, Y., Momma, J. and Ohno, Y. (1999). Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (4) Haemoglobin denaturation test. Toxicol. In Vitro, 13, 125-137. https://doi.org/10.1016/S0887-2333(98)00067-8
  14. Hong, M.-Y., Kim, J.-Y., Lee, Y.M. and Lee, M. (2005). Assessment of sensitivity of photo-chromsomal assay in the prediction of photo-carcinogenicity. J. Toxicol. Pub. Health, 21, 99-105.
  15. Jung, K.-M., Moon, J.-Y., Lee, S.-H., Kim, C.-W., Park, C.-B. and Kim, B.H. (2008). The validation of alternative methods of reconstructed human skin equivalents for the assessment of skin irritation. J. Altern. Ani. Exp., 2, 31-38.
  16. Kim, J.-Y., Koh, W.S. and Lee, M. (2006). Validation of photocomet assay as a model for the prediction of photocarcinogenicity. J. Toxicol. Pub. Health, 22, 423-429.
  17. Lee, H.-K., Noh, K.-J., Seok, S.-H., Baek, M.-W., Lee, H.-Y., Kim, D.-J., Na, Y.-R., Park, S.-H., Kim, B.H., Park, G.-R., Lee, J.-G. and Park, J.H. (2008). Establishment of the neutral red uptake assay as alternatives to the Draize test and its validation. J. Altern. Ani. Exp., 2, 5-9.
  18. Luepke, N.P. (1985). Hen's egg chorioallantoic membrane test for irritation potential. Fd. Chem. Toxicol., 23, 287-291. https://doi.org/10.1016/0278-6915(85)90030-4
  19. Mosman, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  20. NICEATM (2003). Test Method Protocol for BALB/c 3T3 Neutral Red Uptake Cytotoxicity Assay Phase III - Validation Study (November 4, 2003).
  21. OECD (2007). OECD Guidelines for the Testing of Chemicals (December, 2007) Draft proposal for a new guideline 'In Vitro Skin Irritation: Human Skin Model Test'.
  22. Osborne, R., Perkins, M.A. and Roberts, D.A. (2000). In vitro method for eye and skin irritation testing. United States Patent 6020148 (http://www.freepatentsonline.com/6020148.html).
  23. Pape, W.J., Pfannenbeckker, U. and Hoppe, U. (1987). Validation of the red blood cell test system as in vitro assay for the rapid screening of irritation potential of surfactants. Mol. Toxicol., 1, 525-536.
  24. Prinsen, M.K. and Koeter, H.B. (1993). Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits. Fd. Chem. Toxicol., 31, 69-76. https://doi.org/10.1016/0278-6915(93)90182-X
  25. Rosdy, M. and Clauss, L.C. (1990). Terminal epidermal differentiation of human keratinocytes grown in chemically defined medium on inert filter substrates at the air-liquid interface. J. Invest. Dermatol., 95, 409-414. https://doi.org/10.1111/1523-1747.ep12555510
  26. Spielmann, H., Liebsch, M., Moldenhauer, F., Holzhutter, H.-G. and de Silva, O. (1995). Modern biostatistical methods for assessing in vitro/in vivo correlation of severely eye irritating chemicals in a validation study of in vitro alternatives to the Draize eye test Toxicol. In Vitro, 9, 549-556. https://doi.org/10.1016/0887-2333(95)00043-8
  27. Vinardell, M.P. and Mitjans, M. (2008). Alternative methods for eye and skin irritation tests: an overview. J. Pharm. Sci., 97, 45-59.
  28. Yang, X., Zhang, W., Yang, Y., Xiong, X., Xie, X. and Tan, X. (2007) Preliminary study on neutral uptake assay as an alternative method for eye irritation test. AATEX, 14, 509-514.
  29. Yang, W. and Acosta, D. (1994). Cytotoxicity potential of surfactant mixtures evaluated by primary cultures of rabbit corneal epithelial cells. Toxicol. Lett., 70, 309-318. https://doi.org/10.1016/0378-4274(94)90125-2
  30. York, M. and Steiling, W. (1998). A critical review of the assessment of eye irritation potential using the Draize rabbit eye test. J. Appl. Toxicol., 18, 233-240. https://doi.org/10.1002/(SICI)1099-1263(199807/08)18:4<233::AID-JAT496>3.0.CO;2-Y

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