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VOLUME 3 , ISSUE 3 ( July-September, 2020 ) > List of Articles

REVIEW ARTICLE

Overview of Safety Assessment and Toxicological Screening of Dermal Formulations

Subramani Parasuraman, Subramani Balamurugan, Raipan Vanishya

Keywords : Draize\'s criteria, Globally harmonized system, Organisation for Economic Co-operation and Development, Toxicity

Citation Information : Parasuraman S, Balamurugan S, Vanishya R. Overview of Safety Assessment and Toxicological Screening of Dermal Formulations. 2020; 3 (3):96-103.

DOI: 10.5005/jp-journals-10082-02258

License: CC BY-NC 4.0

Published Online: 01-09-2020

Copyright Statement:  Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

The skin is one of our largest organs and the delivery of drugs via the skin is gorgeous and also challenging vicinity in research. The dermal formulations are used for cosmetic and therapeutic purposes by various age groups. Hence, the safety data are essential for these preparations and required long-term toxicity testing is essential to prevent delayed effects on users/consumers. In recent years, use of dermal preparations including cosmetic products has ever increased globally which exhibiting potential health risks including mild hypersensitivity and lethal intoxication. Hence, testing any formulation including dermal preparations for its toxicity is the basic requirement in most toxicological frameworks. Moreover, many of the dermal preparations are available over-the-counter. Hence, the data on the safety of these preparations are very essential, which can be studied using preclinical models, preferably using cell lines or animals. The purpose of the current review is to summarize the toxicity testing methods for dermal preparations.


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  1. Riebeling C, Luch A, Tralau T. Skin toxicology and 3Rs-current challenges for public health protection. Exp Dermatol 2018;27(5): 526–536. DOI: 10.1111/exd.13536.
  2. Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv 2010;1(1):109–131. DOI: 10.4155/tde.10.16.
  3. Arunachalam A, Karthikeyan M, Kumar DV, Prathap M, Sethuraman S, Ashutoshkumar S, et al. Transdermal drug delivery system: a review. Cur Pharma Res 2010;1(1):70. DOI: 10.33786/JCPR.2010.v01i01.015.
  4. List of Pharmaceutical dosage forms. Available in https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fother%2Flist-pharmaceutical-dosage-forms_en.xls. Last assessed on 24-05-2020.
  5. Sachan R, Bajpai M. Transdermal drug delivery system: a review. IJRDPL 2013;3:748–765.
  6. Dermal Fillers Market Size, Growth & Revenue Analysis 2026. https://www.fortunebusinessinsights.com/industry-reports/dermal-fillers-market-100939. Last assessed on 24-05-2020.
  7. Dermal Fillers Market Value to Hit US $10.4B by 2026: Global Market Insights, Inc. Available in https://www.prnewswire.com/news-releases/dermal-fillers-market-value-to-hit-us-10-4b-by-2026-global-market-insights-inc-300999555.html. Last assessed on 24-05-2020.
  8. Bilal M, Iqbal HM. An insight into toxicity and human-health-related adverse consequences of cosmeceuticals-a review. Sci Total Environ 2019;670:555–568. DOI: 10.1016/j.scitotenv.2019.03.261.
  9. Lohani A, Verma A, Joshi H, Yadav N, Karki N. Nanotechnology-based cosmeceuticals. ISRN Dermatol 2014;2014:843687. DOI: 10.1155/2014/843687.
  10. Parasuraman S. Toxicological screening. J Pharmacol Pharmacother 2011;2(2):74–79. DOI: 10.4103/0976-500X.81895.
  11. Acute Dermal Toxicity. Available in https://www.schc.org/assets/docs/ghs_info_sheets/Acute%20Dermal%20Toxicity%20(Final%202018-03).pdf. Last assessed on 25-05-2020.
  12. Wakure BS, Bhatia NM. Acute dermal toxicity and irritability studies of Ag2Ga nanoneedle mediated silver formulation as per OECD 402 and 404 protocols. Int J Pharm Sci Res 2018;9(9):4015–4020.
  13. OECD Test No. 402: Acute Dermal Toxicity, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing. DOI: 10.1787/9789264070585-en.
  14. GHS Classification Criteria for Acute Toxicity. Available in https://www.chemsafetypro.com/Topics/GHS/GHS_classification_criteria_acute_toxicity_category.html. Last assessed on 25-05-2020; Acute Dermal Toxicity. Available in https://www.schc.org/assets/docs/ghs_info_sheets/Acute%20Dermal%20Toxicity%20(Final%202018-03).pdf. Last assessed on 25-05-2020.
  15. Combes RD. Alternatives to Animal Testing. In Comprehensive Medicinal Chemistry II Taylor JB, Triggle DJ, ed. Elsevier; 2007. p. 473. ISBN: 978-0-08-045044-5.
  16. OECD Test No. 411: Subchronic Dermal Toxicity: 90-day Study, OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris 1981. DOI: https://doi.org/10.1787/9789264070769-en.
  17. Health Effects Test Guidelines: OPPTS 870.3250 90-Day Dermal Toxicity [EPA 712–C–98–202]. Available in https://www.regulations.gov/contentStreamer?documentId=EPA-HQ-OPPT-2009-0156-0013&contentType=pdf. Last assessed on 25-05-2020.
  18. Deshpande PO, Mohan V, Thakurdesai P. Preclinical safety assessment of standardized extract of Centella asiatica (L.) urban leaves. Toxicol Int 2015;22(1):10–20. DOI: 10.4103/0971-6580.172251.
  19. Zuang V, Alonso M, Botham PA, Eskes C, Fentem J, Liebsch M, et al., Skin Irritation/Corrosion. Skin Irritation/Corrosion - European Commission. Available in ec.europa.eu. Last assessed on 25-05-2020.
  20. OECD Test No. 404: Acute Dermal Irritation/Corrosion, OECD Guidelines for the Testing of Chemicals. 2002, Available in https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecdtg404.pdf. Last assessed on 25-05-2020.
  21. Wang J, Li Z, Sun F, Tang S, Zhang S, Lv P, et al. Evaluation of dermal irritation and skin sensitization due to vitacoxib. Toxicol Rep 2017;4:287–290. DOI: 10.1016/j.toxrep.2017.06.003.
  22. Globally Harmonized System of Classification and Labelling of Chemicals (GHS) (Rev.5) (2013). Available in http://www.unece.org/trans/danger/publi/ghs/ghs_rev05/05files_e.html. Last assessed on 26-05-2020.
  23. OECD Test No. 442B: Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA or –FCM, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2018. DOI: https://doi.org/10.1787/9789264090996-en.
  24. OECD (1092) Test No. 406. Skin Sensitisation. OECD Guidelines for the Testing of Chemicals. Available in https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecdtg406.pdf. Last assessed on 26-05-2020.
  25. ICCVAM-Recommended Test Method ProtocolUpdated Protocol for the Murine Local Lymph Node Assay. Available in https://ntp.niehs.nih.gov/iccvam/docs/protocols/llnaupdated.pdf. Last assessed on 27-05-2020.
  26. Kim K, Park H, Lim KM. Phototoxicity: its mechanism and animal alternative test methods. [published correction appears in Toxicol Res. 2015;31(3):321] Toxicol Res 2015;31(2):97–104. DOI: 10.5487/TR.2015.31.2.097.
  27. Rittié L, Fisher GJ. Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med 2015;5(1):a015370. DOI: 10.1101/cshperspect.a015370.
  28. Kornhauser A, Wamer WG, Giles AL. Psoralen Phototoxicity: correlation with serum and epidermal 8-methoxypsoralen and 5-methoxypsoralen in the guinea pig. Science 1982;217(4561): 733–735. DOI: 10.1126/science.7100920.
  29. Horio T, Miyauchi H, Asada Y, Aoki Y, Harada M. Phototoxicity and photoallergenicity of quinolones in guinea pigs. J Dermatol Sci 1994;7(2):130–135. DOI: 10.1016/0923-1811(94)90086-8.
  30. Yonezawa Y, Katou H, Kuga K. Multi-site study of an in vivo phototoxicity evaluation in Sprague-Dawley (SD) rats aimed at incorporating the phototoxicity assessments: effects of repeated administration and toxicokinetic blood collection on drug-induced phototoxicity. Fundam Toxicol Sci 2019;6(6):197–206. DOI: 10.2131/fts.6.197.
  31. OECD Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2019. DOI: https://doi.org/10.1787/9789264242845-en.
  32. do Nascimento Pedrosa T, Catarino CM, Pennacchi PC, de Assis SR, Gimenes F, Consolaro ME, et al. A new reconstructed human epidermis for in vitro skin irritation testing. Toxicol In Vitro 2017;42: 31–37. DOI: 10.1016/j.tiv.2017.03.010.
  33. Schmidt FF, Nowakowski S, Kluger PJ. Improvement of a three-layered in vitro skin model for topical application of irritating substances. Front Bioeng Biotechnol 2020;8:388. DOI: 10.3389/fbioe.2020.00388.
  34. OECD Test No. 431: In Vitro Skin Corrosion: Human Skin Model Test. OECD Publishing, Paris 2004. DOI: https://doi.org/10.1787/9789264071148-en.
  35. Reconstructed human epidermis: An efficient prediction tool. Life Sci 2011;40(6):1–2.
  36. Kim H, Choi J, Lee H, Park J, Yoon B, Jin SM, et al. Skin corrosion and irritation test of nanoparticles using reconstructed three-dimensional human skin model, EpiDerm™. Toxicol Res 2016;32(4):311–316. DOI: 10.5487/TR.2016.32.4.311.
  37. Choi J, Kim H, Choi J, Oh SM, Park J, Park K. Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model. Environ Health Toxicol 2014;29:e2014004. DOI: 10.5620/eht.2014.29.e2014004.
  38. OECD, Test No. 442E: In Vitro Skin Sensitisation: In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome Pathway for Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2018. DOI: 10.1787/9789264264359-en.
  39. OECD, Test No. 442D: In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2018. DOI: https://doi.org/10.1787/9789264229822-en.
  40. OECD, Test No. 442C: In Chemico Skin Sensitisation: Assays addressing the Adverse Outcome Pathway key event on covalent binding to proteins, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2019. DOI: https://doi.org/10.1787/9789264229709-en.
  41. Bauch C, Kolle SN, Ramirez T, Eltze T, Fabian E, Mehling A, et al. Putting the parts together: combining in vitro methods to test for skin sensitizing potentials. Regul Toxicol Pharmacol 2012;63(3):489–504. DOI: 10.1016/j.yrtph.2012.05.013.
  42. Motahari P, Sadeghizadeh M, Behmanesh M, Sabri S, Zolghadr F. Generation of stable ARE- driven reporter system for monitoring oxidative stress. Daru 2015;23(1):38. DOI: 10.1186/s40199-015- 0122-9.
  43. Zagoura D, Canovas-Jorda D, Pistollato F, Bremer-Hoffmann S, Bal-Price A. Evaluation of the rotenone-induced activation of the Nrf2 pathway in a neuronal model derived from human induced pluripotent stem cells. Neurochem Int 2017;106:62–73. DOI: 10.1016/j.neuint.2016.09.004.
  44. Takenouchi O, Miyazawa M, Saito K, Ashikaga T, Sakaguchi H. Predictive performance of the human cell line activation test (h-CLAT) for lipophilic chemicals with high octanol-water partition coefficients. J Toxicol Sci 2013;38(4):599–609. DOI: 10.2131/jts.38.599.
  45. OECD, Test No. 432: In Vitro 3T3 NRU Phototoxicity Test, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2019. DOI: https://doi.org/10.1787/9789264071162-en.
  46. Toyoda A, Sugiyama M, Furihata S, Nishizumi K, Omori T, Itagaki H. Development of a modified 3T3 neutral red uptake phototoxicity test protocol for evaluation of poorly water-soluble substances. J Toxicol Sci 2017;42(5):569–577. DOI: 10.2131/jts.42.569.
  47. Ates G, Vanhaecke T, Rogiers V, Rodrigues RM. Assaying cellular viability using the neutral red uptake assay. In Cell Viability Assays. New York, NY: Humana Press; 2017. pp. 19–26.
  48. ROS (Reactive Oxygen Species) assay for photosafety in OECD guideline for the testing of chemicals. Available in http://www.oecd.org/env/ehs/testing/Draft%20TG%20ROS%20161012.pdf. Last assessed on 27-05-2020.
  49. Onoue S, Suzuki G, Kato M, Hirota M, Nishida H, Kitagaki M, et al. Non-animal photosafety assessment approaches for cosmetics based on the photochemical and photobiochemical properties. Toxicol In Vitro 2013;27(8):2316–2324. DOI: 10.1016/j.tiv.2013.10.003.
  50. Onoue S, Hosoi K, Wakuri S, Iwase Y, Yamamoto T, Matsuoka N, et al. Establishment and intra-/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation. J Appl Toxicol 2013;33(11):1241–1250. DOI: 10.1002/jat.2776.
  51. Lee YS, Yi JS, Lim HR, Kim TS, Ahn IY, Ko K, et al. Phototoxicity evaluation of pharmaceutical substances with a reactive oxygen species assay using ultraviolet A. Toxicol Res 2017;33(1):43–48. DOI: 10.5487/TR.2017.33.1.043.
  52. Pellevoisin C, Bouez C, Cotovio J. Cosmetic industry requirements regarding skin models for cosmetic testing. In Skin Tissue Models. Academic Press; 2018. pp. 3–37.
  53. Genotoxicity. Available in http://alttox.org/mapp/toxicity-endpoints-tests/genotoxicity/. Last assessed on 27-05-2020.
  54. Barabadi H, Najafi M, Samadian H, Azarnezhad A, Vahidi H, Mahjoub MA, et al. A systematic review of the genotoxicity and antigenotoxicity of biologically synthesized metallic nanomaterials: are green nanoparticles safe enough for clinical marketing? Medicina (Kaunas) 2019;55(8):439. DOI: 10.3390/medicina55080439.
  55. Chave J. Advances in genotoxicity testing: a keystone of our work on alternatives. Cosmet Eur Res Newslet 2017(2): Available in https://www.cosmeticseurope.eu/files/9314/9675/8761/Research_Newsletter_issue_2.pdf. Last assessed on 27-05-2020.
  56. Auletta CS. Current in vivo assays for cutaneous toxicity: local and systemic toxicity testing. Basic Clin Pharmacol Toxicol 2004;95(5): 201–208. DOI: 10.1111/j.1742-7843.2004.pto950501.x.
  57. Bridging or waiving data requirements. Available in https://www.epa.gov/pesticide-registration/bridging-or-waiving-data-requirements. Last assessed on 27-05-2020.
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