Dr. Helena Kandarova, ERT

1. Development, Evaluation, Optimization and Validation of the EpiDerm Skin Irritation protocol as replacement of the rabbit skin irritation test – the assay, as developed, was implemented into the OECD and EU Test Guidelines (B.46, OECD TG 439) in 2009. The guidelines were updated several times to accommodate some new knowledge gained after the main validation process. Papers related to this project that started in 2003 are summarized below. Dr. Kandarova served as primary investigator or co-investigator in all below mentioned studies.

 

1. Kanďárová, H., Liebsch, M., Genschow, E., Ingrid, Gerner, Traue, D., Slawik, B., Spielmann, H., (2004). Optimisation of the EpiDerm Test Protocol for the upcoming ECVAM Validation Study on In Vitro Skin Irritation Tests. ALTEX 21, 3/04, 107-114.

2. Kanďárová, H., Liebsch, M.,  Gerner, I., Schmidt, E., Genschow, E., Traue, D.,  Spielmann, H., (2005). EpiDerm Skin Irritation Test Protocol – Assessment of the performance of the optimised test. ATLA 33 (4), p. 351

3. Spielmann, H., Hoffmann, S., Liebsch, M., Botham, P., Fentem, J., Eskes, C., Rouguet, R., Cotovio, J., Cole, T., Worth, A., Heyling, J., Jones, P., Robles, C., Kandárová, H., Gamer, A., Remmele, M., Curren, R., Raabe, H., Cockshott, A., Gerner, I. and Zuang, V. (2007). The ECVAM International Validation Study on In Vitro Tests for Acute Skin Irritation: Report on the Validity of the EPISKIN and EpiDerm Assays and on the Skin Integrity Function Test. ATLA 35, 559–601

4. Jírová, D., Liebsch. M., Basketter, D., Kandárová, H., Bendová, H., Marriott, M., Kejlová, K., Spiller, E. (2008)  Comparison of human skin irritation and photo-irritation patch test data with cellular in vitro assays and animal in vivo data. Alternatives to Animal Testing and Experimentation - AATEX 14. 359–365.

5. Kandárová H., Hayden, P., Klausner, M., Kubilus, J., Sheasgreen, J. (2009). An In Vitro Skin Irritation Test (SIT) using the EpiDerm Reconstructed Human Epidermal (RHE) Model. JoVE. 29. http://www.jove.com/index/details.stp?id=1366, doi: 10.3791/1366.

6. Kandárová H., Hayden, P., Klausner, M., Kubilus, J., Kearney, P. and Sheasgreen, J. (2009): In Vitro Skin Irritation Test: Improving the Sensitivity of the EpiDerm Skin Irritation Test Protocol. ATLA  37 (6), pp. 671 – 669.

7. Jirova, D., Basketter, D., Liebsch, M., Bendova, H., Kejlova, K, Marriott, M., Kanďárová H. (2009) Comparison of Human Skin Irritation Patch Test Data with In Vitro Skin Irritation Assays and Animal Data. Contact Dermatitis 62 (2), pp. 109 -116.

8. Basketter, D., Jirova, D., Kandarova, H (2012). Review of skin irritation/corrosion Hazards on the basis of human data: A regulatory perspective. Interdisciplinary toxicology 06/2012; 5(2):98-104.

9. Kandarova H. and Liebsch M. (2017).The EpiDerm Skin Irritation Test (EpiDerm SIT) – book chapter 3 In: Alternatives for Dermal Toxicity Testing. Editors: Eskes, Ch., van Vliet, E.,  Maibach, H.,  592 pages. ISBN 978-3-319-50351-6

 

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2. Optimization of the SkinEthic skin  corrosion and skin irritation assays that aimed into the enlarged portfolio of testing methods for the topical toxicity testing - the assays ware implemented into the OECD and EU Test Guidelines (B.40, OECD TG 431). Dr. Kandarova served as the primary investigator or co-investigator in all below mentioned studies.

 

1. Kanďárová, H., Liebsch, M., Schmidt, E., Traue, D., Spielmann, H., Meyer, K., Steinhoff, C., Tornier, C., De Wever, B., Rosdy, M., (2006). Assessment of the skin irritation potential of chemicals using the SkinEthic RHE and the “common skin irritation protocol” evaluated in the ECVAM Skin irritation validation study. ATLA 34, 393–406.

2. Kanďárová, H., Liebsch, M., Spielmann, H., Genschow, E., Schmidt, E., Guest, R., Whittingham, A., Warren, N., Gamer, A., Remmele, M., Kaufmann, T., Wittmer, E., De Wever, B., Rosdy, M., (2006). Assessment of the SkinEthic Reconstituted Human Epidermis for skin corrosion testing according to OECD guideline 431. Toxicology in Vitro 20, 547–559.

 

3. Co-development of in vitro test protocol using reconstructed tissue model EpiOcular replacing the Draize eye irritation test in vivo. Active and long lasting involvement in the CosEU/ECVAM validation project on in vitro eye irritation methods that resulted into acceptance of the EpiOcular eye irritation test as OECD TG 492 for identification of substances that do not require labeling. Consultant and co-investigator.

 

1. Kaluzhny, Y., Kandárová, H., Hayden, P. Kubilus, J., d'Argembeau-Thornton, L., Klausner, M. (2011). Development of the EpiOcular(TM) eye irritation test for hazard identification and labelling of eye irritating chemicals in response to the requirements of the EU cosmetics directive and REACH legislation. ATLA, 39 (4), 339-364.

2. Kolle, S.N., Kandárová, H., Wareing, B., van Ravenzwaay, B.,  Landsiedel, R. (2011). In-house validation of the EpiOcular(TM) eye irritation test and its combination with the bovine corneal opacity and permeability test for the assessment of ocular irritation. ATLA, 39 (4), 365-387.

3. Kaluzhny, Y., Kandárová, H., Handa, Y., DeLuca, J., Truong, T., Hunter, A., Kearney, P., d'Argembeau-Thornton, L., Klausner, M. (2015). The EpiOcular Eye Irritation Test (EIT) for hazard identification and labelling of eye irritating chemicals: protocol optimisation for solid materials and the results after extended shipment.  Alternatives to Laboratory Animals : ATLA [2015, 43(2):101-127]

4. Kaluzhny, Y., Kandárová, H., d'Argembeau-Thornton, L., Kearney, P., Klausner, M. (2015). Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model. JoVE (Journal of Visualized Experiments), 102, 2015

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4. Expanding the applicability domain of the EpiDerm Skin Corrosion test protocol for subcategorization of the Corrosive materials into the cat 1A, Cat 1/BC and no cat. The project led to the major update of the OECD TG 431. Dr. Kandarova served as investigator and consultant in the project.

 

1. Desprez B., Barroso J., Griesinger C., Kandárová H., Alépée N., Fuchs H.W (2015). Two novel prediction models improve predictions of skin corrosive sub-categories by test methods of OECD Test Guideline No. 431, Toxicology in Vitro, Volume 29, Issue 8, December 2015, Pages 2055-2080

2. Kandarova H. and Liebsch M. (2017).The EpiDerm Skin Corrosion Test – book chapter 9 In: Alternatives for Dermal Toxicity Testing. Editors: Eskes, Ch., van Vliet, E.,  Maibach, H.,  592 pages. ISBN 978-3-319-50351-6

 

5. Optimization, Pre-Validation and Validation of the EpiDerm Skin Irritation protocol for Mediclal Device Testing as replacement of the rabbit skin irritation tests. Dr. Kandarova served as the primary investigator or co-investigator in below mentioned studies. Papers published in a special issue of Toxicology in Vitro in 2018.

           

1. Kandárová H., Bendová H., Letasiova S., de Jong W., Coleman K.P., and Jírova D. (2018). Evaluation of the Benchmark Materials in the Controlled Human Patch Testing and in the EpiDerm Skin Irritation Protocol for testing of Medical Devices.  Toxicology In Vitro. Available online 31 January 2018, In Press.

2. Kandarova, H., Willoughby, J.; de Jong, W.; Letasiova, S., Milasova T., Bachelor, M.; Breyfogle, B.;  Handa Y., de la Fonteyne, L.; Coleman, K. (2018). Pre-validation of an in vitro Skin Irritation Test for Medical Devices Using the Reconstructed Human Tissue Model EpiDerm. Submitted into Toxicology In Vitro in 2017. Available online 10 February 2018. In Press,

3. De Jong WH, Hoffmann S, Lee M, Kandárová H, Pellevoisin C, Haishima Y, Rollins B, Zdawczyk A, Willoughby J, Bachelor M, Schatz T, Skoog S, Parker S, Sawyer A, Pescio P, Fant K, Kim KM, Kwon JS, Gehrke H, Hofman-Hüther H, Meloni M, Julius C, Briotet D, Letasiova S, Kato R, Miyajima A, De La Fonteyne LJJ, Videau C, Tornier C, Turley AP, Christiano N, Rollins TS, Coleman KP., Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts. Toxicol In Vitro. 2018. Available online 8 January 2018, In Press

4.  Coleman KP, Grailer TP, McNamara LR, Rollins BL, Christiano NJ, Kandárová H, De Jong WH. Preparation of Irritant Polymer Samples for an In Vitro Round Robin Study.  Toxicol In Vitro Available online 2 February 2018, In Press, Corrected Proof

 

6. Development, Evaluation, Optimization and Validation of the Phototoxicity protocols for the assessment of the phototoxicity of topical photo-toxins and implementation of the methods into the regulatory guidelines. Dr. Kandarova was responsible for generating EpiDerm phototoxicity data for topical phototoxins and retrospective analysis of all tissue models regarding their predictive ability and readiness to cover the photo-irritation endpoint. Based on the data produced with several reconstructed tissue models, the use of in vitro RHT was implemented into the ICH guideline S10 for the topical phototoxins. 

 

1. Kandarova, H. (2006). Evaluation and Validation of Reconstructed Human Skin Models as Alternatives to Animal Tests in Regulatory Toxicology - PhD Thesis. http://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000002248

2. Kejlová, K., Jírová, D., Bendová, H., Kandárová, H., Weidenhoffer Z., Kolářová, H. and Liebsch M (2007). Phototoxicity of Bergamot oil assessed by in vitro techniques in combination with human patch tests. Toxicology in Vitro 21, p. 1298–1303.

3. Ceridono, M., Tellner,P., Bauer, D., Barroso,J., Alépée,N., Corvi, R., De Smedt,A., Fellows,M.D., Gibbs,N.K. Heisler, E., Kandarova, H. [......] and Wilcox, J. (2012). The 3T3 neutral red uptake phototoxicity test: practical experience and implications for phototoxicity testing--the report of an ECVAM-EFPIA workshop. Regulatory Toxicology and Pharmacology; 63(3):480-8.

4. Liskova A., Milasova T., Janotva S., Brezova V., Letasiova S., Kandarova H (2016). Assessment of the phototoxicity of three different TiO2 nano-forms using reconstructed human tissue model EpiDerm. Toxicology Letters. Volume 258, Supplement, 16 September 2016, Page S66 – Manuscript in Preparation.

5. Kandarova H. and Liebsch M. (2017).The EpiDerm Phototoxicity Test (EpiDerm H3D-PT) – book chapter 35 In: Alternatives for Dermal Toxicity Testing. Editors: Eskes, Ch., van Vliet, E.,  Maibach, H.,  592 pages. ISBN 978-3-319-50351-6

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7. Expanding the applicability domain of the EpiOcular protocol and other methods for subcategorization of the irritating materials into the cat 1, cat 2 and no cat. Implementation of the EpiOcular assays into the testing strategies – CON4 EI Project supported by Cefic.  Dr. Kandarova served as or co-investigator and consultant in the projects for the EpiOcular method. Papers were published in a special issue of Toxicology in Vitro. Volume 49, Pages 1-116 (June 2018)

 

1. Adriaens E, Alépée N, Kandarova H, Drzewiecka A, Gruszka K, Guest R, Willoughby JA Sr, Verstraelen S, Van Rompay AR.(2017). CON4EI: Selection of the reference chemicals for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 44, October 2017, Pages 44-48. Reprint in Toxicology in Vitro. Volume 49, Pages 1-116 (June 2018).

2. Adriaens E, Verstraelen S, Alépée N, Kandarova H, Drzewiecka A, Gruszka K, Guest R, Willoughby JA Sr, Van Rompay AR. (2018). CON4EI: Development of testing strategies for hazard identification and labelling for serious eye damage and eye irritation of chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 99-115

3. Kandarova H., Letasiova S., Adriaens E., Guest R., Willoughby Sr J.A., Drzewiecka A., Gruszkae K., Alépée N,, Verstraelen S., Van Rompay A.R. (2018). CON4EI: CONsortium for in vitro Eye Irritation testing strategy - EpiOcular™ time-to-toxicity (EpiOcular ET-50) protocols for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 21-33

4. Kandarova H., Letasiova S., Adriaens E., Guest R., Willoughby Sr J.A. Drzewiecka A., Gruszka K., Alépée N., Verstraelen S., Van Rompay A.R. (2018). CON4EI: EpiOcular™ Eye Irritation Test (EpiOcular™ EIT) for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 34-52

5. Verstraelen S., Maglennon G., Hollanders K.,  Boonen F., Adriaens E., Alépée N., Drzewiecka A.,  Gruszka K., Kandarova H., Willoughby Sr, J.A, Guest R., Schofield J., Van Rompay  A.R. (2017). CON4EI: Bovine Corneal Opacity and Permeability (BCOP) test for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro 44, 122-133. Reprint in Toxicology in Vitro. Volume 49, Pages 1-116 (June 2018).  

6. E.Adriaens, R.Guest, J.A.Willoughby Sr, P.Fochtman, H.Kandarova, S.Verstraelen, A.R.Van Rompay, (2018). CON4EI: Slug Mucosal Irritation (SMI) test method for hazard identification and labelling of serious eye damaging and eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 77-89. 

7. Adriaens E, Willoughby J.A. Sr, Meyer B.R., Blakeman L.C., Alépée N, Fochtman P., Guest R., Kandarova H., Verstraelen S., Van Rompay A.R. (2018). CON4EI: Short Time Exposure (STE) test method for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 65-76 

8. Geerts L., Adriaens E., Alépée N., Guest R.,Willoughby Sr J.A., Kandarova, H., Drzewiecka A., Fochtman P., Verstraelen S., Van Rompay A.R. (2018). CON4EI: Evaluation of QSAR models for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 90-98. 

9. Van Rompay A.R., Alépée N., Nardelli L., Hollanders K., Leblanc V., Drzewiecka A., Gruszka K., Guest R., Kandarova H., Willoughby Sr. J.A., Verstraelen S., Adriaens E. (2018). CON4EI: SkinEthic™ Human Corneal Epithelial Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals. Toxicology in Vitro, Volume 49, June 2018, Pages 11-20

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8. Enhancing the knowledge about the alternative methods and reconstructed human tissue models and their use in the toxicology. Ongoing Dissemination of the technology and methods towards the toxicologists, teachers and students. Improving performance of the methods by retrospective analysis of available data.

 

1.  Červinka, M., Kandarova, H., Forgacs, Z., Śladowski, D.: Chapter 2.6 - The Three Rs and Alternatives in the Visegrád (V4) Countries (2019). In:  The History of Alternative Test Methods in Toxicology. Edited by Michael Balls, Robert Combes and Andrew Worth. 2019, Pages 59-70 

2. Kandarova, H. and Iscan, M. (2017) 53rd EUROTOX Congress: Connecting for a Safer Future. EUROTOX 2017 Supplement, Foreword. Toxicol Lett. 2017 Oct 20; 280 Suppl 1:S1. doi: 10.1016/j.toxlet.2017.08.001. Epub 2017 Aug 8.

3. Sarah Gordon, Mardas Daneshian, Joke Bouwstra, Francesca Caloni, Samuel Constant, Donna E Davies, Gudrun Dandekar, Carlos A Guzman, E Fabian, Eleonore Haltner, Thomas Hartung, Nina Hasiwa, P Hayden, H Kandarova, S Khare, HF Krug, C Kneuer, Marcel Leist, G Lian, U Marx, Marco Metzger, K Ott, P Prieto, MS Roberts, EL Roggen, T Tralau, C van den Braak, Heike Walles, Claus-Michael Lehr (2015). Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.Altex,32,4,327-378.

4. Hayden, P. J., Bachelor, M., Klausner, M. and Kandárová, H. (2016) Predicting Organ Toxicity In Vitro, in Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers (eds Y. Will, J. E. McDuffie, A. J. Olaharski and B. D. Jeffy), John Wiley & Sons, Inc, Hoboken, NJ. doi: 10.1002/9781119053248.ch12

5. Hayden, Patrick J; Bachelor, Michael; Ayehunie, Seyoum; Letasiova, Silvia; Kaluzhny, Yulia; Klausner, Mitchell; Kandárová, Helena (2015). Application of MatTek In Vitro Reconstructed Human Skin Models for Safety, Efficacy Screening, and Basic Preclinical Research".  Applied In Vitro Toxicology,1,3,226-233,2015,"Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA"

6. Kandárová, H., Letasiová, S. (2011). Alternative methods in toxicology: pre-validated and validated methods. Interdiscip Toxicol, 4 (3), 107-113.                     

7. Kandárová, H., Richter, H. Liebsch, M. and Lademann J. (2007): Stratum corneum architecture of reconstructed human skin models monitored by fluorescent confocal laser scanning microscopy. Laser Phys. Lett. Volume 4/4, Pages 308 – 311.

8. Schreiber, S., Mahmoud, A., Vuia, A., Rübbelke, M.K., Schmidt, E., Schaller, M., Kandárová, H., Haberland, A., Schäfer, U.F., Bock, U., Korting, H.C., Liebsch, M. and Schäfer-Korting, M., (2005). Reconstructed Epidermis versus Human and Animal Skin in Skin Absorption Studies Toxicology in Vitro, 19 (6), p.813-822.

9. Kandárová, H., Jantová, S., Hojerová, J., (2004). New approaches to safety evaluation of cosmetic products and ingredients. Review. Česko - Slovenská dermatologie 79 (2), p. 75-83 (Indexed/Excerpted in: Bibliographia Medica Čechoslovaca, EMBASE/Excerpta Medica, Biological Abstracts, Chemical Abstracts).

10. Kandárová, H., Hojerová, J., Jantová, S., (2002): Safety of Cosmetic products - In vitro methods. Derma 4, p.15-17