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Identification of Skin Irritants and Allergens by In Vivo and In Vitro Methods

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Book cover Kanerva’s Occupational Dermatology

Abstract

Skin is prone to developing allergic, irritant, and urticarial reactions in response to contact with a number of drugs and chemicals on a daily basis. Hence, a variety of assays (in vivo and in vitro) have been developed to determine absorption through the skin and their ability to cause skin reactions.

Absorption of substances through skin is influenced by a number of factors such as concentration/pH of the chemical at the skin surface, type of vehicle, integrity of the skin, subject’s age, and the surface area exposed.

In vivo percutaneous absorption assays have been conducted in a number of animal models and involve the measurement of radiolabeled chemicals containing 14C or 3H in urine and/or feces after applying a known quantity of the chemical on the skin. In vitro percutaneous penetration assays are conducted in excised human or animal skin using radioactively tagged chemicals.

Understanding the structure and biological activity of any agent (quantitative structure-activity relationship (QSAR)) helps in determining the potential allergenicity of chemicals with similar structures.

A great deal of advancement has taken place with regard to testing the irritant potential of a substance, and many new in vitro skin models have been developed for the same.

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References

  • Ale IS, Maibach HI (2007) Mechanisms in irritant and allergic contact dermatitis. In: Zhai H, Maibach HI, Wilhelm K-P (eds) Marzulli and Maibach’s Dermatotoxicology, 7th edn. CRC Press, Boca Raton

    Google Scholar 

  • Alepee N, Carine T, Robert C, Amsellem C, Roux M, Doucet O, Pachot J, Melont M, 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

    Article  CAS  PubMed  Google Scholar 

  • Andersen KE, Maibach HI (1984) Multiple-application delayed-onset contact urticaria: possible relation to certain unusual formalin and textile reactions. Contact Dermatitis 10:227–234

    Article  CAS  PubMed  Google Scholar 

  • Anderson K, Maibach H (1985) Contact allergy predictive tests in Guinea pigs. Karger, Basel

    Google Scholar 

  • Anderson C, Sundberg K, Groth O (1986) Animal model for assessment of skin irritancy. Contact Dermatitis 15:143–151

    Article  CAS  PubMed  Google Scholar 

  • Ball N, Cagen S, Carrillo JC, Certa H, Eigler D, Emter R, Faulhammer F, Garcia C, Graham C, Haux C, Kolle S, Kreiling R, Natsch A, Mehling A (2011) Evaluating the sensitization potential of surfactants: integrating data from the local lymph node assay, guinea pig maximization test, and in vitro methods in a weight-of-evidence approach. Regul Toxicol Pharmacol 60: 289–400

    Article  CAS  Google Scholar 

  • Baran R, Maibach H (eds) (1998) Textbook of cosmetic dermatology. Martin Dunitz, London

    Google Scholar 

  • Bartek MJ, LaBudde JA (1975) Percutaneous absorption in vitro. In: Maibach HI (ed) Animal models in dermatology. Churchill Livingstone, New York, pp 103–120

    Google Scholar 

  • Bartek MJ, LaBudde JA, Maibach HI (1972) Skin permeability in vivo: comparison in rat, rabbit, pig and man. J Invest Dermatol 58:114–123

    Article  CAS  PubMed  Google Scholar 

  • Bloch B, Steiner-Wourlisch A (1930) Die Sensibilisierung des Meerschweinchens gegen Prirneln. Arch Dermatol Syphilol 162:349–378

    Article  Google Scholar 

  • Bronaugh RL, Collier S (1991) Protocol for in vitro percutaneous absorption studies. In: Bronaugh RL, Maibach HI (eds) In vitro percutaneous absorption: principles, fundamentals and applications. CRC Press, Boca Raton, pp 237–242

    Google Scholar 

  • Bronaugh RL, Maibach HI (eds) (1985) Percutaneous absorption: mechanisms methodology-drug delivery. Marcel Dekker, New York

    Google Scholar 

  • Bronaugh RL, Maibach HI (eds) (1991) In vitro percutaneous absorption: principles, fundamentals and applications. CRC Press, Boca Raton

    Google Scholar 

  • Bronaugh RL, Kraeling MEK, Yourick JJ (2005) Determination of percutaneous absorption by in vitro techniques. In: Bronaugh RL, Maibach HI (eds) Percutaneous absorption: drugs-cosmetics-mechanisms-methodology. Taylor & Francis Informa, New York, pp 265–268

    Chapter  Google Scholar 

  • Buehler EV (1964) A new method for detecting potential sensitizers using the guinea pig. Toxicol Appl Pharmacol 6:341

    Article  Google Scholar 

  • Cagen SZ, Malley LA, Parker CM, Gardiner TH, Van Gelder GA, Jud VA (1984) Pyrethroid-mediated skin sensory stimulation characterized by a new behavioral paradigm. Toxicol Appl Pharmacol 76:270–279

    Article  CAS  PubMed  Google Scholar 

  • Draize JH (1955) Procedures for the appraisal of the toxicity of chemicals in foods, drugs, and cosmetics. VIII. Dermal toxicity. Food Drug Cosmetic Law J 10: 722–731

    Google Scholar 

  • Draize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membrane. J Pharmacol Exp Ther 82:377–390

    CAS  Google Scholar 

  • Dugard PH (1986) Absorption through the skin: theory, in vitro techniques and their applications. Food Chem Toxicol 24:749–753

    Article  CAS  PubMed  Google Scholar 

  • Emery BE, Edwards LD (1940) The pharmacology of soaps. II. The irritant action of soaps on human skin. J Am Pharm Assoc (Wash) 29:251–254

    Article  CAS  Google Scholar 

  • EPA (U.S. Environmental Protective Agency) (1984) Pesticide assessment guidelines. Subdivison F: Hazard evaluation – human and domestic animals, Revised Ed. PB 86-108958, Series 81–6

    Google Scholar 

  • Eskes C, van Vliet E, Maibach H (2017) Alternatives for dermal toxicity testing. Springer, Cham

    Book  Google Scholar 

  • Feldman RJ, Maibach HI (1967) Regional variations in percutaneous penetration of [14C] cortisone in man. J Invest Dermatol 48:181–183

    Article  Google Scholar 

  • Franz TI (1975) Percutaneous absorption on the relevance of in vitro data. J Invest Dermatol 64:190–195

    Article  CAS  PubMed  Google Scholar 

  • Frosch PJ (1982) Irritancy of soap and detergent bars. In: Frost P, Horwitz SN (eds) Principles of cosmetics for the dermatologist. CV Mosby, St. Louis, pp 5–12

    Google Scholar 

  • Frosch PJ, Kligman AM (1977) A method for appraising the stinging capacity of topically applied substances. J Soc Cosmet Chem 28:197–207

    Google Scholar 

  • Frosch PJ, Kligman AM (1979) The Duhring chamber: an improved technique for epicutaneous testing of irritant and allergic reactions. Contact Dermatitis 5:73–81

    Article  CAS  PubMed  Google Scholar 

  • Galbiati V, Papale A, Marinovich M, Gibbs S, Roggen E, Corsini E (2017) Development of an in vitro method to estimate the sensitization induction level of contact allergens. Toxicol Lett 271:1–11

    Article  CAS  PubMed  Google Scholar 

  • Gibbs S, Corsini E, Spiekstra S, Galbiati V, Fuchs H, DeGeorge G, Troese M, Hayden P, Deng W, Roggen E (2013) An epidermal equivalent assay for identification and ranking potency of contact sensitizers. Toxicol Appl Pharmacol 272:529–541

    Article  CAS  PubMed  Google Scholar 

  • Gimenez-Arnau A, Maibach H (2015) Contact urticaria syndrome. CRS Press, Boca Raton

    Google Scholar 

  • Guillot JP, Gonnnet JF, Clement C, Caillard L, Truhaut R (1982) Evaluation of the cutaneous-irritation potential of 56 compounds. Food Chem Toxicol 20:563–572

    Article  CAS  PubMed  Google Scholar 

  • Hayes BB, Patrick E, Maibach HI (2007) Dermatotoxicology. In: Hayes AW (ed) Principles and methods of toxicology, 5th edn. Informa Healthcare, New York, pp 1359–1405

    Google Scholar 

  • Henderson CR, Riley EC (1945) Certain statistical considerations in patch testing. J Invest Dermatol 6:227–230

    Article  Google Scholar 

  • Hostynek JJ, Magee PS (1997) Fragrance allergens: classification and ranking by QSAR. Toxicol In Vitro 11:377–384

    Article  CAS  PubMed  Google Scholar 

  • Hostynek JJ, Lauerma AI, Magee PS, Bloom E, Maibach HI (1995) A local lymph-node assay validation study of a structure-activity relationship model for contact allergens. Arch Dermatol Res 287:567–571

    Article  CAS  PubMed  Google Scholar 

  • Hostynek JJ, Magee PS, Maibach HI (1996) QSAR predictive of contact allergy: scope and limitations. In: Elsner P, LaChapelle JM, Wahlberg JE (eds) Prevention of contact dermatitis. Karger, Basel, pp 18–27

    Google Scholar 

  • Hotchkiss SAM (1992) Skin as a xenobiotic metabolising organ. In: Gibson GG (ed) Progress in drug metabolism, vol 13. Taylor and Francis, London, pp 217–262

    Google Scholar 

  • Jadassohn J (1895) Zur kenntniss der medicamentosen dermatosen. Verhdlg Deutsch Derm Gesellsch 5:103

    Google Scholar 

  • Jung K, Lee S, Jang W, Jung H, Heo Y, Park Y, Bae S, Lim K, Seok S (2014) KeraSkin-VM: a novel reconstructed human epidermis model for skin irritation tests. Toxicol In Vitro 28:742–750

    Article  CAS  PubMed  Google Scholar 

  • Kaminsky M, Szivos MM, Brown KR (1986) Application of the hill top patch test chamber to dermal irritancy testing in the albino rabbit. J Toxicol Cutan Ocul Toxicol 5:81–87

    Article  CAS  Google Scholar 

  • Kero M, Hannuksela M (1980) Guinea pig maximization test, open epicutaneous test and chamber test in induction of delayed contact hypersensitivity. Contact Dermatitis 6:341–344

    Article  CAS  PubMed  Google Scholar 

  • Klecak G (1983) Identification of contact allergens: predictive tests in animals. In: Marzulli FN, Maibach HI (eds) Dermatotoxicology. Hemisphere, New York, pp 193–236

    Google Scholar 

  • Klecak G (1985) The Freund’s complete adjuvant test and the open epicutaneous test. In: Andersen KE, Maibach HI (eds) Contact allergy predictive tests in guinea pigs. Karger, Basel, pp 152–171

    Google Scholar 

  • Kligman AM (1983) A biological brief on percutaneous absorption. Drug Dev Ind Pharm 19:521–560

    Article  Google Scholar 

  • Kligman AM, Wooding WM (1967) A method for the measurement and evaluation of irritants on human skin. J Invest Dermatol 49:78–94

    Article  CAS  PubMed  Google Scholar 

  • Kreiling R, Hollnagel HM, Hareng L, Eigler D, Lee MS, Griem P, Dreeben B, Kleber M, Albrecht A, Garcia C, Wendel A (2008) Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT). Food Chem Toxicol 46:1896–1904

    Article  CAS  PubMed  Google Scholar 

  • Lahti A (1980) Nonimmunologic contact urticaria. Acta Derm Venereol Suppl (Stockh) 60:1–49

    Google Scholar 

  • Lahti A, Maibach HI (1984) An animal model for nonimmunologic contact urticaria. Toxicol Appl Pharmacol 76:219–224

    Article  CAS  PubMed  Google Scholar 

  • Lahti A, Maibach HI (1985) Species specificity of nonimmunologic contact urticaria: guinea pig, rat and mouse. J Am Acad Dermatol 13:66–69

    Article  CAS  PubMed  Google Scholar 

  • Landsteiner K, Chase MW (1937) Studies on the sensitization of animals with simple chemical compounds. IV. Anaphylaxis induced by picryl chloride and 2:4 dinitrochlorobenzene. J Exp Med 66:337–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landsteiner K, Jacobs J (1935) Studies on the sensitization of animals with simple chemical compounds. J Exp Med 61:643–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landsteiner K, Jacobs J (1936) Studies on the sensitization of animals with simple chemical compounds. II. J Exp Med 64:625–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanman B, Elvers WB, Howard CS (1968) The role of human patch testing in a product development program. In: Proceedings of the joint conference of cosmetic sciences. The Toilet Goods Association, Washington, DC, pp 135–145

    Google Scholar 

  • Magee PS, Hostynek JJ, Maibach HI (1994) A classification model for allergic contact dermatitis. Quant Struct-Act Relat 13:22–33

    CAS  Google Scholar 

  • Magnusson B, Hersle K (1965) Patch test methods. I. A comparative study of six different types of patch tests. Acta Derm Venereol 45:123–128

    CAS  PubMed  Google Scholar 

  • Maibach H, Honari G (2014) Applied dermatotoxicology: clinical aspects. Elsevier, Amsterdam

    Google Scholar 

  • Maibach HI, Johnson HL (1975) Contact urticaria syndrome. Contact urticaria to diethyltoluamide (immediate-type hypersensitivity). Arch Dermatol 111:726–730

    Article  CAS  Google Scholar 

  • Marzulli FN, Maibach HI (1973) Antimicrobials: experimental contact sensitization in man. J Soc Cosmet Chem 24:399–421

    CAS  Google Scholar 

  • Marzulli FN, Maibach HI (eds) (1997) Handbook of dermatology. Taylor and Francis, Washington, DC

    Google Scholar 

  • Mathias CG, Maibach HI (1978) Dermatoxicology monographs I. Cutaneous irritation: factors influencing the response to irritants. Clin Toxicol 13:333–346

    Article  CAS  PubMed  Google Scholar 

  • Maurer T, Thomann P, Weirich EG, Hess R (1975) The optimization test in the guinea pig. A method for the predictive evaluation of the contact allergenicity of chemicals. Agents Actions 5:174–179

    Article  CAS  PubMed  Google Scholar 

  • Modjtahedi B, Fortenbach C, Marsano J, Gandhi A, Staab R, Maibach HI (2011) Guinea pig sensitization assays: an experimental comparison of three methods. Cutan Ocul Toxicol 30:129–137

    Article  CAS  PubMed  Google Scholar 

  • Motoyoshi K, Toyoshima Y, Sato M, Yoshimura M (1979) Comparative studies on the irritancy of oils and synthetic perfumes to the skin of rabbit, guinea pig, rat, miniature swine, and man. Cosmet Toiletries 94:41–48

    CAS  Google Scholar 

  • Office of the Federal Registrar, National Archives of Records Service (1985) Code of Federal Regulations. General services administration title 16, parts 1500.50-1500.41

    Google Scholar 

  • Ostrenga J, Steinmetz C, Poulsen B, Yett S (1971) Significance of vehicle composition. II. Prediction of optimal vehicle composition. J Pharm Sci 60:1180–1183

    Article  CAS  PubMed  Google Scholar 

  • Phillips L, Steinberg M, Maibach HI, Akers WA (1972) A comparison of rabbit and human skin response to certain irritants. Toxicol Appl Pharmacol 21:369–382

    Article  CAS  PubMed  Google Scholar 

  • Prottey C (1978) The molecular basis of skin irritation. In: Breuer MM (ed) Cosmetic science. Academic, London, pp 275–349

    Google Scholar 

  • Rapaport M, Anderson D, Pierce V (1978) Performance of the 21-day patch test in civilian populations. Cosmet Toiletries 93:29–31

    Google Scholar 

  • Rougier A, Goldberg L, Maibach H (1994) Irritation: in vitro approaches. In: Rougier A, Goldberg L, Maibach H (eds) In vitro toxicology. Academic, London, pp 23–185

    Google Scholar 

  • Scheuplein RJ (1978) Permeability of skin: a review of major concepts. Curr Probl Dermatol 7:172–186

    Article  CAS  PubMed  Google Scholar 

  • Scheuplein RJ, Bronaugh RL (1983) Percutaneous absorption. In: Goldsmith LA (ed) Biochemistry and physiology of the skin. Oxford University Press, New York, pp 1255–1295

    Google Scholar 

  • Shelanski HA (1951) Experience with and considerations of the human patch test method. J Soc Cosmet Chem 2:324–331

    CAS  Google Scholar 

  • Simpson WL, Cramer W (1943) Fluorescence studies of carcinogens in skin. Cancer Res 3:362–369

    CAS  Google Scholar 

  • Trottet L, Maibach H (2017) Dermal drug selection and development. Springer, Cham

    Book  Google Scholar 

  • Vijverberg HP, van den Bercken J (1979) Frequency-dependent effects of the pyrethroid insecticide decamethrin in frog myelinated nerve fibers. Eur J Pharmacol 58:501–504

    Article  CAS  PubMed  Google Scholar 

  • von Krogh C, Maibach HI (1982) The contact urticaria syndrome. Semin Dermatol 1:59–66

    Google Scholar 

  • Weigand DA, Gaylor JR (1974) Irritant reaction in Negro and Caucasian skin. South Med J 67:548–551

    Article  CAS  PubMed  Google Scholar 

  • Wester RC, Maibach HI (1983) Cutaneous pharmacokinetics: 10 steps to percutaneous absorption. Drug Metab Rev 14:169–205

    Article  CAS  PubMed  Google Scholar 

  • Zhai H, Maibach HI, Wilhelm K-P (eds) (2007) Marzulli and Maibach’s Dermatotoxicology, 7th edn. CRC Press, Boca Raton

    Google Scholar 

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Reddy, R., Maibach, H.I., Belum, V.R., Sethi, G., Hewitt, P. (2020). Identification of Skin Irritants and Allergens by In Vivo and In Vitro Methods. In: John, S., Johansen, J., Rustemeyer, T., Elsner, P., Maibach, H. (eds) Kanerva’s Occupational Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-68617-2_104

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  • DOI: https://doi.org/10.1007/978-3-319-68617-2_104

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