Journal of Literature Pharmacy Sciences

İlaçlar ve Kimyasal Maddelerin Oküler Toksisitesinin Belirlenmesinde Kullanılan Güncel Yöntemler
Recent Methods Used in the Determination of Ocular Toxicity of Drugs and Chemicals
Hülya TEZELa, Suna SABUNCUOĞLUa, Pınar ERKEKOĞLUa
aHacettepe Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Ankara, TÜRKİYE
J Lit Pharm Sci. 2021;10(1):65-75
doi: 10.5336/pharmsci.2020-77093
Article Language: TR
Full Text
ÖZET
 İnsan gözü, fizyolojik yapısı itibarıyla tehlikeli çevresel koşullara ve maddelere maruz kalan hassas bir organdır. Endüstriyel maddeler, çevresel kimyasallar, kozmetikler, kişisel bakım ürünleri ve yanlış uygulandığı takdirde bazı ilaçlar korneada irritasyona, inflamasyona ve hatta görme kaybına bile neden olabilir. Bu nedenle tehlikeli maddelere maruz kalma riskini azaltmak için ilaçların, kozmetiklerin ve bu ürünlerin içerisinde yer alan bileşenlerin test edilerek, göz irritasyon potansiyellerinin değerlendirilmesi gerekir. Günümüzde birçok ilaç ve kimyasal maddenin göz üzerindeki etkilerini araştırmak için birçok in vitro yöntem geliştirilmektedir. Bu yöntemlerin en sık kullanılanları 'yeniden yapılandırılmış insan korneası (RhCE)' modelleridir. RhCE modellerinde, insan kornea hücreleri veya insan derisi keratinositleri gibi hücreler kullanılabilir. RhCE epitel hücrelerinin kullanıldığı sistemlerle ilgili Ekonomik Kalkınma ve İşbirliği Örgütünün Test Kılavuzu, 492 kılavuz yayımlanmıştır. Ayrıca birçok yeni oküler toksisite doku modelinin, gelecekte kullanıma girmesi için çalışmalar devam etmektedir. Ancak ilaç ve biyomedikal sektörlerinde göz irritasyonunu değerlendirmek için hâlâ hayvan deneyleri yapılmaktadır. Diğer taraftan, Avrupa Birliği Kozmetik Komitesi tarafından onaylanan Kozmetik Direktifi (76/768/EEC) ile 2013'ten itibaren kozmetik bileşenler ve bitmiş ürünler için hayvanlar üzerinde test edilmesi tamamen yasaklanmıştır. Kozmetik sektöründe hayvan deneylerinin yasaklanmasıyla birlikte, oküler toksisiteyi değerlendirmek için ex vivo ve in vitro birçok alternatif yöntem geliştirilmiştir. Bu derlemede, oküler toksisite test yöntemlerindeki en son gelişmeler hakkındaki bilgiler özetlenecek, yöntemlerin avantajları ve dezavantajları tartışılacaktır.

Anahtar Kelimeler: Oküler irritasyon; Draize testi; alternatif yöntemler; hücre kültürü
ABSTRACT
 Human eye is exposed to dangerous environmental conditions and substances due to its physiological structure. Industrial substances, chemicals, cosmetics, personal care products and some medications when wrongly used can cause ocular irritation, inflammation, or even loss of sight. Therefore, in order to reduce the risk of exposure to hazardous substances, drugs, cosmetics and their ingredients should be tested and evaluated for their eye irritation potentials. Today, several in vitro methods are being developed for the determination of several drugs and chemical substances on eye. The most widely used methods are 'reconstructed human eye cornea (RhCE) models'. In RhCE models, cells of cornea or non-cornea origin human cornea cells or human skin keratinocytes can be used. Concerning RhCE epithelial cell systems, Organisation for Economic Co-operation and Development has published Test Guideline 492. Moreover, there is ongoing research on for the future use of several new ocular toxicity tissue models. However, animal experiments are still carried out in the pharmaceutical and biomedical industry for the evaluation of ocular irritation. On the other hand, nimal experiments for cosmetic ingredients and end products have been banned in the European Union, since 2013. With the prohibition of animal experiments in the cosmetics industry, many alternative ex vivo and in vitro methods have been developed to assess ocular toxicity. In this review, information on the latest developments in ocular toxicity test methods will be summarized and the advantages and disadvantages of these methods will be discussed.

Keywords: Ocular irritation; draize test; alternative methods; cell culture
REFERENCES:
  1. Vinardell MP, Mitjans M. Alternative methods for eye and skin irritation tests: an overview. J Pharm Sci. 2008;97(1):46-59. [Crossref] [PubMed] 
  2. Wilson SL, Ahearne M, Hopkinson A. An overview of current techniques for ocular toxicity testing. Toxicology. 2015;2;327:32-46. [Crossref]  [PubMed] 
  3. McCaa CS. The eye and visual nervous system: anatomy, physiology and toxicology. Environ Health Perspect. 1982;44:1-8. [Crossref]  [PubMed]  [PMC] 
  4. Willoughby CE, Ponzin D, Ferrari S, Lobo A, Landau K, Omidi Y. Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function-a review. Clinical & Experimental Ophthalmology. 2010;38(1):2-11. [Crossref] 
  5. Huhtala A, Salminen L, Tähti H, Uusitalo H. Corneal models for the toxicity testing of drugs and drug releasing materials. In: Ashammakhi N, eds. Vol 1. Multifunctional Biomaterials and Devices. Oulu University E-book Series. Oulu, Finland Publisher; 2008; p.1-24. [Link] 
  6. Lotz C, Schmid FF, Rossi A, Kurdyn S, Kampik D, De Wever B, et al. Alternative methods for the replacement of eye irritation testing. ALTEX. 2016;33(1):55-67. [Crossref] [PubMed] 
  7. Maurer JK, Parker RD, Jester JV. Extent of initial corneal injury as the mechanistic basis for ocular irritation: key findings and recommendations for the development of alternative assays. Regul Toxicol Pharmacol. 2002;36(1):106-17. [Crossref] [PubMed] 
  8. Eskes C, Bessou S, Bruner L, Curren R, Harbell J, Jones P, et al. Eye irritation. Altern Lab Anim. 2005;33 Suppl 1:47-81. [Crossref]  [PubMed] 
  9. OECDiLibrary [İnternet]. © 2017 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 405: Acute eye irritation/corrosion. Paris: OECD Publishing; 2017. Erişim linki:[Crossref] 
  10. EUR-Lex [İnternet]. European Union (EU). Council Directive 93/35/EEC of 14 June 1993 amending for the sixth time Directive 76/768/ EEC on the approximation of the laws of the Member States relating to cosmetic products.(Last Access Date: 14.01.2021) Erişim linki: [Link] 
  11. Türkiye İlaç ve Tıbbi Cihaz Kurumu (TİTCK) [İnternet]. [Erişim tarihi: 04-05.2020]. Kozmetik ürünler üzerinde yapılan hayvan deneylerine alternatif test metotlarına ilişkin kılavuz sürüm 1.0. Erişim linki: [Link] 
  12. Lee M, Hwang JH, Lim KM. 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. 2017;33(3):191-203. [Crossref] [PubMed] [PMC] 
  13. Luechtefeld T, Maertens A, Russo DP, Rovida C, Zhu H, Hartung T. Analysis of draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data. Altex. 2016;33(2):123-34. [Crossref] [PubMed] [PMC] 
  14. Barile FA. Validating and troubleshooting ocular in vitro toxicology tests. J Pharmacol Toxicol Methods. 2010;61(2):136-45. [Crossref] [PubMed] [PMC] 
  15. Ubels JL, Clousing DP. In vitro alternatives to the use of animals in ocular toxicology testing. Ocul Surf. 2005;3(3):126-42. [Crossref] [PubMed] 
  16. Freeberg FE, Nixon GA, Reer PJ, Weaver JE, Bruce RD, Griffith JF, et al. Human and rabbit eye responses to chemical insult. Fundam Appl Toxicol. 1986;7(4):626-34. [Crossref] [PubMed] 
  17. Organisation for Economic Co-operation and Development (OECD).Unclassified Joint Meeting of the Chemicals Committee and The Working Party on Chemicals, Pesticides and Biotechnology Cancels & Replaces. The Same Document Of 6 July 2018 Guidance Document No 263 On Integrated Approaches To Testing and Assessment Iata. 2019;263(263). (Last Access Date: 14.01.2021). [Link] 
  18. Luepke NP, Kemper FH. The HET-CAM test: an alternative to the draize eye test. Food Chem Toxicol. 1986;24(6-7):495-6. [Crossref] 
  19. OECDiLibrary [İnternet]. © 2021 OECD. Test No. 438: Isolated chicken eye test method for ıdentifying ocular corrosives and severe irritants. Paris: OECD Publishing; 2009. Erişim linki:[Crossref] 
    20. (Last Access Date: 14.01.2021)
  20. OECDiLibrary [İnternet]. © 2021 OECD. Test No. 437: Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants. Paris: OECD Publishing; 2009. Erişim linki: [Link] 
    21. (Last Access Date: 14.01.2021).
  21. Piehl M, Gilotti A, Donovan A, DeGeorge G, Cerven D. Novel cultured porcine corneal irritancy assay with reversibility endpoint. Toxicol In Vitro. 2010;24(1):231-9. [Crossref] [PubMed] 
  22. OECDiLibrary [İnternet]. © 2019 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 496: In vitro macromolecular test method for identifying chemicals inducing serious eye damage and chemicals not requiring classification for eye irritation or serious eye damage. Paris: OECD Publishing; 2019. Erişim linki: [Crossref] 
    23. (Last Access Date: 14.01.2021).
  23. Hagino S, Kinoshita S, Tani N, Nakamura T, Ono N, Konishi K, et al. IInterlaboratory validation of in vitro eye irritation tests for cosmetic ingredients. (2) Chorioallantoic membrane (CAM) test. Toxicol In Vitro. 1999;13(1):99-113. [Crossref] [PubMed] 
  24. Spielmann H. Ocular irritation. In: Castell JV, Gómez-Lechón MJ, eds. In Vitro Methods in Pharmaceutical Research. 1st ed. San Diego: Academic Press; 1999. p.265-87. [Crossref] 
  25. OECDiLibrary [İnternet]. © 2017 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 460: Fluorescein leakage test method for identifying ocular corrosives and severe irritants. Paris: OECD Publishing; 2017. Erişim linki:[Crossref] 
    26. (Last Access Date: 14.01.2021)
  26. Organisation for Economic Cooperation and Development (OECD). OECD guideline for the testing of chemicals draft proposal for a new guideline; 2010. p.1-16. [Link] 
  27. OECDiLibrary [İnternet]. © 2018 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 491: Short time exposure in vitro test method for identifying i) chemicals inducing serious eye damage and ii) chemicals not requiring classification for eye irritation or serious eye damage. Paris: OECD Publishing; 2018. Erişim linki: [Crossref] 
    28. (Last Access Date: 14.01.2021)
  28. Pape WJ, Pfannenbecker U, Hoppe U. Validation of the red blood cell test system as in vitro assay for the rapid screening of irritation potential of surfactants. Mol Toxicol. 1987-1988;1(4):525-36. [PubMed] 
  29. Lewis RW, McCall JC, Botham PA. Use of an in vitro test battery as a prescreen in the assessment of ocular irritancy. Toxicol In Vitro. 1994;8(1):75-9. [Crossref] [PubMed] 
  30. OECDiLibrary [İnternet]. © 2019 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 492: Reconstructed human cornea-like epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage. Paris: OECD Publishing; 2019. Erişim linki: [Crossref] 
    31. (Last Access Date: 14.01.2021)
  31. Katoh M, Uemura N, Hamajima F, Ogasawara T, Hata K. Morphological characterization of a reconstructed human corneal epithelial model (LabCyte CORNEA-MODEL) as an alternative to the Draize eye test for the assessment of eye irritation. Altern to Anim Test Exp. 2012;17(1):2-8. [Link] 
  32. Takezawa T, Ozaki K, Nitani A, Takabayashi C, Shimo-Oka T. Collagen vitrigel: a novel scaffold that can facilitate a three-dimensional culture for reconstructing organoids. Cell Transplant. 2004;13(4):463-73. [Crossref]  [PubMed] 
  33. OECDiLibrary [İnternet]. © 2019 OECD. OECD guidelines for the testing of chemicals, section 4. Test No. 494: Vitrigel-eye irritancy test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage. Paris: OECD Publishing; 2019. Erişim linki:[Crossref] 
    34. (Last Access Date: 14.01.2021)
  34. European Chemicals Agency (ECHA). How to use new or revised in vitro test methods to address Serious eye damage/eye irritation. 2018;1-7. [Link] 
  35. Rönkkö S, Vellonen KS, Järvinen K, Toropainen E, Urtti A. Human corneal cell culture models for drug toxicity studies. Drug Delivery and Translational Research. 2016;6(6):660-75. [Crossref]  [PubMed]  [PMC] 
  36. Köse Ö, Erkekoğlu P, Sabuncuoğlu S, Koçer-Gümüşel B. Kozmetik ürünlerin göz irritasyon potansiyellerinin değerlendirilmesinde geleneksel ve alternatif yöntemler. [Traditional and alternative methods for the evaluation of eye irritation potential of cosmetic products]. Marmara Pharm J. 2017;21(2):195-206. [Crossref] 

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