Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Mixture Toxicity of Methylisothiazolinone and Propylene Glycol at a Maximum Concentration for Personal Care Products

  • Park, Juyoung (College of Pharmacy, Dongduk Women's University) ;
  • Lee, Handule (College of Pharmacy, Dongduk Women's University) ;
  • Park, Kwangsik (College of Pharmacy, Dongduk Women's University)
  • Received : 2018.02.28
  • Accepted : 2018.07.04
  • Published : 2018.10.15
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Abstract

Methylisothiazolinone (MIT) has been used in combination with methylchloroisothiazolinone (CMIT) for cosmetic products such as shampoo, body lotion, and skin care products. The mixture of CMIT/MIT has been found to cause allergic contact dermatitis and is thus no longer permitted for use as a preservative in leave-on cosmetics. However, MIT itself was approved as a stand-alone preservative at a maximum concentration of 100 ppm as the toxicity was derived from CMIT rather than MIT. However, in many countries, allergic skin irritation caused by MIT remains a social concern. In this study, skin irritation was assessed for the presence of MIT, propylene glycol, and their mixture using a 3D human skin model $EpiDerm^{TM}$. Although non-diluted MIT causes serious skin toxicity, skin irritation was not observed at a concentration of 100 ppm, the maximum permissible level for cosmetics and personal care products according to European regulations. Propylene glycol, the most widely used vehicle for MIT, did not cause skin irritation in the 3D skin model. The results are expected to provide information for regulatory policies and guidelines on the use of biocides in consumer products.

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References

  1. de Groot, A.C. and Weyland, J.W. (1988) Kathon CG: a review. J. Am. Acad. Dermatol., 18, 350-358. https://doi.org/10.1016/S0190-9622(88)70051-1
  2. Yazar, K., Johnsson, S., Lind, M.L., Boman, A. and Liden, C. (2011) Preservatives and fragrances in selected consumeravailable cosmetics and detergents. Contact Derm., 64, 265-272. https://doi.org/10.1111/j.1600-0536.2010.01828.x
  3. Concha-Garzon, M.J., Solano-Lopez, G., Montes, A., Fraga, J. and Sanchez, J. (2015) Follicular allergic contact dermatitis due to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in a rinse-off soap product. Clin. Exp. Dermatol., 40, 690-691. https://doi.org/10.1111/ced.12583
  4. Liuti, F., Hernandez, H.Z. and Borrego, H.L. (2014) Increased sensitization to Kathon CG (methylchloroisothiazolinone plus methylisothiazolinone) in the south of Gran Canaria, Spain. Actas Dermosifiliogr., 105, 882-883. https://doi.org/10.1016/j.ad.2014.03.004
  5. Hou, F., Xing, C., Li, B., Cheng, J., Chen, W. and Zhang, M. (2015) Application of BALB/c mouse in the local lymph node assay: BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals. J. Pharmacol. Toxicol. Methods, 72, 53-58. https://doi.org/10.1016/j.vascn.2015.01.001
  6. Gerberick, G.F., Ryan, C.A., Kimber, I., Dearman, R.J., Lea, L.J. and Basketter, D.A. (2000) Local lymph node assay: validation assessment for regulatory purposes. Am. J. Contact Dermat., 11, 3-18. https://doi.org/10.1016/S1046-199X(00)90027-7
  7. Mary, A.L. (1992) Final report on the safety assessment of methylisothiazolinone and methylchloroisothiazolinone. J. Am. Coll. Toxicol., 11, 75-128. https://doi.org/10.3109/10915819209141993
  8. Thomsen, A.V., Schwensen, J.F., Bossi, R., Banerjee, P., Gimenez-Arnau, E., Lepoittevin, J.P., Liden, C., Uter, W., White, I.R. and Johansen, J.D. (2017) Isothiazolinones are still widely used in paints purchased in five European countries: a follow-up study. Contact Derm., 78, 246-253.
  9. Aerts, O., Goossenc, A. and Giordano-Labadie, F. (2015) Contact allergy caused by methylisothiazolinone: the Belgian-French experience. Eur. J. Dermatol., 25, 228-233.
  10. Ali, F.R., Shephered, E.L., Yell, L.C., Buckley, D.A. and Williams, J.D. (2014) Escalating methylisothiazolinone/ methylchloroisothiazolinone allergy probably attributable to methylisothiazolinone in leave-on body cosmetics. Contact Derm., 70, 316-317. https://doi.org/10.1111/cod.12236
  11. Uter, W., Amario-Hita, J.C., Balato, A., Ballmer-Weber, B., Bauer, A., Belloni, F.A., Bircher, C.M.M.U., Cooper, S.M., Czarnecka-Operacz, M., Dugonik, A., Gallo, R., Gimenez-Arnau, A., Johansen, J.D., John, S.M., Kiec-Świerczynska, M., Kmecl, T., Kręcisz, B., Larese, F.F., Mahler, V., Pesonen, M., Rustemeyer, T., Sadowska-Przytocka, A., Sanchez-Perez, J., Schliemann, S., Schuttelaar, M.L., Simon, D., Spiewak, R., Valiukevičienė, S., Weisshaar, E., White, I.R. and Wilkinson, S.M. (2017) European Surveillance System on Contact Allergies (ESSCA): results with the European baseline series, 2013/14. J. Eur. Acad. Dermatol. Venereol., 31, 1516-1525. https://doi.org/10.1111/jdv.14423
  12. Isaksson, M., Ale, I., Andersen, K.E., Elsner, P., Goh, C.L., Goossens, A., Jerajani, H., Matsunaga, K., McFadden, J. and Bruze, M. (2017) Multicenter patch testing with methylisothiazolinone and methylchloroisothiazolinone/methylisothiazolinone within the international contact dermatitis research group. Dermatitis, 28, 210-214. https://doi.org/10.1097/DER.0000000000000272
  13. Warbrick, E.V., Dearman, R.J., Basketter, D.A. and Kimber, I. (1999) Influence of application vehicle on skin sensitization to methylchloroisothiazolinone/methylisothiazolinone: an analysis using the local lymph node assay. Contact Derm., 41, 325-329. https://doi.org/10.1111/j.1600-0536.1999.tb06181.x
  14. Devos, F.C., Pollaris, L., Van Den Broucke, S., Seys, S., Goossens, A., Nemery, B., Hoet, P.H. and Vanoirbeek, J.A. (2015) Methylisothiazolinone: dermal and respiratory immune responses in mice. Toxicol. Lett., 235, 179-188. https://doi.org/10.1016/j.toxlet.2015.04.009
  15. Miles, A., Berthet, A., Hopf, N.B., Gilliet, M., Raffoul, W., Vernez, D. and Spring, P. (2014) A new alternative method for testing skin irritation using a human skin model: a pilot study. Toxicol. In Vitro, 28, 240-247. https://doi.org/10.1016/j.tiv.2013.10.022
  16. McGowan, M.A., Scheman, A. and Jacob, S.E. (2017) Propylene glycol in contact dermatitis: a systematic review. Dermatitis, 29, 6-12.
  17. OECD (2015) OECD Guidelines for the Testing of Chemicals, Section 4. Test No. 439, In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method. doi: 10.1787/9789264242845-en/.
  18. Kim, H., Choi, J., Lee, H., Park, J., Yoon, B.I., Jin, S.M. and Park, K. (2016) Skin corrosion and irritation test of nanoparticles using reconstructed three-dimensional human skin model, EpiDermTM. Toxicol. Res., 32, 311-316. https://doi.org/10.5487/TR.2016.32.4.311
  19. Choi, J., Kim, H., Choi, J., Oh, S.M., Park, J. and Park, K. (2014) Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model. Environ. Health Toxicol., 29, e2014004. https://doi.org/10.5620/eht.2014.29.e2014004
  20. Park, D., Ryu, S., Lim, H., Kim, S., Roh, H., Cha, W. and Park, D.Y. (2016) Estimation of humidifier disinfectant amounts inhaled into the respiratory system. J. Environ. Health Sci., 42, 141-146.
  21. Yoon, J., Cho, H.J., Lee, E., Choi, Y.J., Kim, Y.H., Lee, J.L., Lee, Y.J. and Hong, S.J. (2017) Rate of humidifier and humidifier disinfectant usage in Korean children: A nationwide epidemiologic study. Environ. Res., 155, 60-63. https://doi.org/10.1016/j.envres.2017.01.030
  22. Vauhkala, A.R., Pesonen, M., Suomela, S., Kuuliala, O., Suuronen, K. and Aalto-Korte, K. (2015) Occupational contact allergy to methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone. Contact Derm., 73, 150-156. https://doi.org/10.1111/cod.12413
  23. Engfeldt, M., Bråred-Christensson, J., Isaksson, M., Matura, M., Ryberg, K., Stenberg, B., Svedman, C. and Bruze, M. (2015) Swedish experiences from patch testing methylisothiazolinone separately. Acta Derm. Venereol., 95, 717-719. https://doi.org/10.2340/00015555-2029
  24. Lee, M., Hwang, J.H. and Lim, K.M. (2017) Alternatives to in vivo draize rabbit eye and skin irritation tests with a focus on 3d reconstructed human cornea-like epithelium and epidermis models. Toxicol. Res., 33, 191-203. https://doi.org/10.5487/TR.2017.33.3.191
  25. Macfarlane, M., Jones, P., Goebel, C., Dufour, E., Rowland, J., Araki, D., Costabel-Farkas, M., Hewitt, N.J., Hibatallah, J., Kirst, A., McNamee, P., Schellauf, F. and Scheel, J. (2009) A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: skin irritation. Regul. Toxicol. Pharmacol., 54, 188-196. https://doi.org/10.1016/j.yrtph.2009.04.003