A Review of Methods for Evaluating Adverse Skin Reactions

Mengyao Bing; Yao Pei; Chang'ou Wang; Gaocai Han; Qunfang Zhou; Guibin Jiang

doi:10.7536/PC240902

PDF(1416 KB)

Prog Chem ›› 2025, Vol. 37 ›› Issue (7) : 1002-1010. DOI: 10.7536/PC240902

Review

A Review of Methods for Evaluating Adverse Skin Reactions

Mengyao Bing ¹^,² ,
Yao Pei ¹^,³ ,
Chang'ou Wang ⁴ ,
Gaocai Han ⁴ ,
Qunfang Zhou ¹^,²^,³^,^* ,
Guibin Jiang ¹^,²^,³

Author information +

History +

Abstract

With the rapid development of the economy and society， various types of new chemicals are constantly emerging， and have been widely applied in daily life and work， including medical devices， metal jewelry， beauty and personal care products， and smart wearable products. However， the adverse skin reactions caused by contact with these daily products seriously threaten human health and reduce the quality of life of patients. Therefore， it is of great significance to evaluate the adverse skin reactions of daily necessities and their ingredients. These evaluations aid in identifying potentially hazardous chemicals， and guiding the effective management of the product manufacturing. Traditional methods for evaluating adverse skin reactions have relied heavily on animal experiments. But in light of concerns regarding animal welfare and the need for improving test throughput and prediction efficacy of methods， great efforts have been made to develop various in vivo and in vitro alternative methods. Against this backdrop， the mechanisms of adverse skin reactions， especially for skin irritation/corrosion， atopic dermatitis and allergic contact dermatitis， and their evaluation methods were summarized in this review， based on a large number of studies published in recent years. Finally， the shortcomings and perspectives of research in this field are prospected.

Contents

1 Introduction

2 Adverse skin reactions and evaluating methods

2.1 Non-allergic skin reactions

2.2 Allergic skin reactions

3 Evaluating methods for ACD

3.1 Animal experiments

3.2 In vivo alternative assays

3.3 In vitro alternative assays

4 Conclusion and outlook

Key words

adverse skin reactions / evaluating methods / skin irritation/corrosion / atopic dermatitis / allergic contact dermatitis

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Mengyao Bing , Yao Pei , Chang'ou Wang , et al . A Review of Methods for Evaluating Adverse Skin Reactions[J]. Progress in Chemistry. 2025, 37(7): 1002-1010 https://doi.org/10.7536/PC240902

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	Boguniewicz M, Leung D Y M. J. Allergy Clin. Immunol., 2006, 117(2): S475. Cited in this article [1]

[2]	Mockenhaupt M. Chem. Immunol Allergy, 2012, 97: 1. Cited in this article [1]

[3]	Karavaizoglu C, Suleyman A, Yavuz Alıc R, Dolu K O, Yucel E, Demirkale Z H, Cimen S S, Ozdemir C, Tamay Z U. Int. Arch. Allergy Immunol., 2024, 185(1): 56. Cited in this article [1]

[4]	Huang L N, Zhong Y P, Liu D, Wang X H, Gong C Y, Wen S, Elias P M, Yang B, Man M Q. Contact Dermat., 2018, 79(6): 365. Cited in this article [1]

[5]	Khatsenko K, Khin Y, Maibach H. Dermatitis, 2020, 31(5): 283. Cited in this article [2]

[6]	Symanzik C, Johansen J D, Weinert P, Babić Ž, Hallmann S, Havmose M S, Kezic S, Macan M, Macan J, Strahwald J, Turk R, van der Molen H F, John S M, Uter W. Contact Dermat., 2022, 86(5): 333. Cited in this article [1]

[7]	Bains S N, Nash P, Fonacier L. Clin. Rev. Allergy Immunol., 2019, 56(1): 99. Cited in this article [3]

[8]	Leung D Y, Bieber T. Lancet, 2003, 361(9352): 151. Cited in this article [2]

[9]	Kaplan D H, Igyártó B Z, Gaspari A A. Nat. Rev. Immunol., 2012, 12(2): 114. Cited in this article [3]

[10]	Smylie A, Gill N, Oosterhuis R, Mathura P, Elliott J, Straube S, Dytoc M. J. Cutan. Med. Surg., 2021, 25(2): 216. Cited in this article [1]

[11]	European Union. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products. Office J. Europ Union, 2009, Vol 342. Cited in this article [1]

[12]	European Union. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Office J. Europ Union, 2010, Vol 276. Cited in this article [1]

[13]	Welss T, Basketter D A, Schröder K R. Toxicol. Vitro, 2004, 18(3): 231. Cited in this article [1]

[14]	OECD. Test No. 404: Acute Dermal Irritation/Corrosion. Paris: Organisation for Economic Cooperation and Development, 2015. Cited in this article [2]

[15]	Jírová D, Basketter D, Liebsch M, Bendová H, Kejlová K, Marriott M, Kandárová H. Contact Dermat., 2010, 62(2): 109. Cited in this article [2]

[16]	OECD. Test No. 430: In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER). Paris: Organisation for Economic Cooperation and Development, 2015. Cited in this article [2]

[17]	OECD. Test No. 435: In Vitro Membrane Barrier Test Method for Skin Corrosion. Paris: Organisation for Economic Cooperation and Development, 2015. Cited in this article [2]

[18]	OECD. Test No. 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method. Paris: Organisation for Economic Cooperation and Development, 2019. Cited in this article [2]

[19]	OECD. Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method. Paris: Organisation for Economic Cooperation and Development, 2021. Cited in this article [2]

[20]	Bieber T. N. Engl. J. Med., 2008, 358(14): 1483. Cited in this article [1]

[21]	David Boothe W, Tarbox J A, Tarbox M B. Management of Atopic Dermatitis. Cham: Springer International Publishing, 2017, 21. Cited in this article [1]

[22]	Hassan S, Hamideh N, Poulos C, Cheema S, Rangwani S, Lio P A. Dermatitis, 2021, 32(1S): S8. Cited in this article [1]

[23]	Hanifin J M, Rajka G. Acta Derm. Venereol., 1980, 60: 44. Cited in this article [1]

[24]	Reynolds M, Gorelick J, Bruno M. J. Drugs Dermatol., 2020, 19(3): 244. Cited in this article [1]

[25]	Williams H C, Jburney P G, Pembroke A C, Hay R J. Br. J. Dermatol., 1994, 131(3): 406. Cited in this article [2]

[26]

Eichenfield

L F

, Tom

W L

, Chamlin

S L

, Feldman

S R

, Hanifin

J M

, Simpson

E L

, Berger

T G

, Bergman

J N

, Cohen

D E

, Cooper

K D

, Cordoro

K M

, Davis

D M

, Krol

, Margolis

D J

, Paller

A S

, Schwarzenberger

, Silverman

R A

, Williams

H C

, Elmets

C A

, Block

, Harrod

C G

, Smith

Begolka W

, Sidbury

. J. Am. Acad. Dermatol., 2014, 70(2): 338.

Cited in this article [1]

[27]	Liu P, Zhao Y, Mu Z L, Lu Q J, Zhang L, Yao X, Zheng M, Tang Y W, Lu X X, Xia X J, Lin Y K, Li Y Z, Tu C X, Yao Z R, Xu J H, Li W, Lai W, Yang H M, Xie H F, Han X P, Xie Z Q, Nong X, Guo Z P, Deng D Q, Shi T X, Zhang J Z. Chin. Med. J., 2016, 129(7): 757. Cited in this article [1]

[28]	Inagaki N, Nagai H. J. Pharmacol. Sci., 2009, 110(3): 251. Cited in this article [1]

[29]	Yang L, Fu J R, Han X, Zhang C Y, Xia L, Zhu R H, Huang S H, Xiao W F, Yu H M, Gao Y J, Liang Q Y, Li W, Zhou Y F. J. Allergy Clin. Immunol., 2022, 149(6): 2021. Cited in this article [1]

[30]	Karlberg A T, Baron J, Merk H. Advances in Molecular Toxicology. Amsterdam: Elsevier, 2008, 87. Cited in this article [2]

[31]	Karlberg A T, Börje A, Duus Johansen J, Lidén C, Rastogi S, Roberts D, Uter W, White I R. Contact Dermat., 2013, 69(6): 323. Cited in this article [1]

[32]	Buehler E V. Arch. Dermatol., 1965, 91(2): 171. Cited in this article [3]

[33]	Magnusson B, Kligman A M. J. Investig. Dermatol., 1969, 52(3): 268. Cited in this article [4]

[34]	Gad S C, Dunn B J, Dobbs D W, Reilly C, Walsh R D. Toxicol. Appl. Pharmacol., 1986, 84(1): 93. Cited in this article [4]

[35]	Kimber I, Mitchell J A, Griffin A C. Food Chem. Toxicol., 1986, 24(6/7): 585. Cited in this article [4]

[36]	OECD. The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins. Paris: Organisation for Economic Cooperation and Development, 2014. Cited in this article [1]

[37]	Gerberick G F. Toxicol. Sci., 2004, 81(2): 332. Cited in this article [3]

[38]	Emter R, Ellis G, Natsch A. Toxicol. Appl. Pharmacol., 2010, 245(3): 281. Cited in this article [3]

[39]	Ashikaga T, Yoshida Y, Hirota M, Yoneyama K, Itagaki H, Sakaguchi H, Miyazawa M, Ito Y, Suzuki H, Toyoda H. Toxicol. Vitro, 2006, 20(5): 767. Cited in this article [3]

[40]	Maurer T. Methods, 2007, 41(1): 48. Cited in this article [2]

[41]	OECD. Test No. 442C: In Chemico Skin Sensitisation: Assays Addressing the Adverse Outcome Pathway Key Event on Covalent Binding to Proteins. Paris: Organisation for Economic Cooperation and Development, 2024. Cited in this article [2]

[42]	Ramirez T, Mehling A, Kolle S N, Wruck C J, Teubner W, Eltze T, Aumann A, Urbisch D, van Ravenzwaay B, Landsiedel R. Toxicol. Vitro, 2014, 28(8): 1482. Cited in this article [2]

[43]	OECD. Test No. 442D: In Vitro Skin Sensitisation: Assays Addressing the Adverse Outcome Pathway Key Event on Keratinocyte Activation. Paris: Organisation for Economic Cooperation and Development, 2024. Cited in this article [2]

[44]	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. Paris: Organisation for Economic Cooperation and Development, 2024. Cited in this article [3]

[45]	Fabian E, Vogel D, Blatz V, Ramirez T, Kolle S, Eltze T, van Ravenzwaay B, Oesch F, Landsiedel R. Arch. Toxicol., 2013, 87(9): 1683. Cited in this article [4]

[46]	Ashikaga T, Sakaguchi H, Sono S, Kosaka N, Ishikawa M, Nukada Y, Miyazawa M, Ito Y, Nishiyama N, Itagaki H. Altern. Lab. Anim., 2010, 38(4): 275. Cited in this article [2]

[47]	Piroird C, Ovigne J M, Rousset F, Martinozzi-Teissier S, Gomes C, Cotovio J, Alépée N. Toxicol. Vitro, 2015, 29(5): 901. Cited in this article [3]

[48]	OECD. Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to Be Used within Integrated Approaches to Testing and Assessment (IATA) for Skin Sensitisation. Paris: Organisation for Economic Cooperation and Development, 2017.

[49]	Otsubo Y, Nishijo T, Miyazawa M, Saito K, Mizumachi H, Sakaguchi H. Regul. Toxicol. Pharmacol., 2017, 88: 118.

[50]	Hennen J, Aeby P, Goebel C, Schettgen T, Oberli A, Kalmes M, Blömeke B. Toxicol. Sci., 2011, 123(2): 501. Cited in this article [2]

[51]	Hennen J, Bloemeke B. ALTEX-Altern. Anim. Exp., 2017, 34(2): 279. Cited in this article [2]

[52]	Cao Y P, Ma P C, Liu W D, Zhou W Q, Tao Y, Zhang M L, Li L J, Chen Z Y. Immunopharmacol. Immunotoxicol., 2012, 34(2): 196. Cited in this article [2]

[53]	Galbiati V, Maddalon A, Iulini M, Marinovich M, Corsini E. Toxicol. Vitro, 2020, 68: 104929. Cited in this article [2]

[54]	Van Den Bogaard E H, Tjabringa G S, Joosten I, Vonk-Bergers M, Van Rijssen E, Tijssen H J, Erkens M, Schalkwijk J, Koenen H J P M. J. Investig. Dermatol., 2014, 134(3): 719. Cited in this article [2]

[55]	Huppert C, Paris C, Langonné I, Muller S, Mathiot J, Abdessadeq H, Gagnaire F, Battais F, Sponne I. Contact Dermat., 2018, 79(2): 67. Cited in this article [2]

[56]	Sonnenburg A, Stahlmann R, Kreutz R, Peiser M. Arch. Toxicol., 2023, 97(6): 1677. Cited in this article [2]

[57]	De Ávila R I, Lindstedt M, Valadares M C. Regul. Toxicol. Pharmacol., 2019, 108: 104445. Cited in this article [1]

[58]	Johansson H, Albrekt A S, Borrebaeck C A K, Lindstedt M. Toxicol. Vitro, 2013, 27(3): 1163. Cited in this article [1]

[59]	Parise C B, Sá-Rocha V M, Moraes J Z. Toxicol. Vitro, 2015, 30(1): 318. Cited in this article [1]

[60]	Hong Z X, Zhu S T, Li H, Luo J Z, Yang Y, An Y, Wang X, Wang K. Mil. Med. Res., 2023, 10: 40. Cited in this article [1]

We would like to thank Xiao Dan and Ding Qian from Beijing Xiaomi Mobile Software Co., Ltd. for their guidance on the content related to skin adverse reactions in this article.