In vitro skin irritation:: facts and future.: State of the art review of mechanisms and models

被引:195
作者
Welss, T
Basketter, DA
Schröder, KR
机构
[1] Henkel KGaA, VTB Skin Biochem, D-40191 Dusseldorf, Germany
[2] SEAC, Unilever Colworth, Sharnbrook, Beds, England
关键词
apligraf; calcium; differential gene expression; emulsifier; epidermis; EpiDerm; episkin; IL-1; alpha; IL-1ra; IL-6; IL-8; IL-10; prostaglandin; proteases; protease-inhibitors; reactive oxygen species; skin equivalent; skin irritation; skinethic; solvents; Surfactants; TNF-alpha;
D O I
10.1016/j.tiv.2003.09.009
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The skin is the main target tissue for exogenous noxes, protecting us from harmful environmental hazards, UV-irradiation and endogenous water loss. It is composed of three layers, whereas the outermost epidermis is a squamous epithelium that mainly consists of keratinocytes. These cells execute a terminal differentiation, which finally results in the assembly of the stratum corneum. This layer, consisting of cornified keratinocytes, is an effective barrier against a vast number of substances. Apart of this, keratinocytes play crucial roles in the immune surveillance and the initiation, modulation and regulation of inflammation in the epidermis. Regarding cutaneous inflammatory reactions, skin irritation is one of the most common adverse effect in humans. For reasons of human safety assessment new chemicals are still evaluated for irritant potentials by application to animals followed by visible changes such as erythema and oedema. Testing for skin irritation in animals potentially cause them pain and discomfort. Furthermore, the results are not always predictive for those found in humans. In order to replace animal testing and to improve the prediction of irritants, the cosmetic and toiletry industry, in Europe represented by Colipa, develops and uses several alternative in vitro test systems. In this respect, the use of in vitro reconstructed organotypic skin equivalents are mostly favored, because of their increasingly close resemblance to human skin. Due to ethical and scientific questions and on account of the 7th amendment of the European Council Directive 76/768/EEC, the authors see the requirement to drive the development of alternative tests for irritants. Therefore, this article centres on cosmetic ingredients and provides the readership an overview of the state of art of cellular mechanisms of skin irritation and summarizes the results of the commonly used skin equivalents to evaluate irritation in vitro. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:231 / 243
页数:13
相关论文
共 115 条
  • [31] Skin2® -: an in vitro human skin model:: the correlation between in vivo and in vitro testing of surfactants
    Demetrulias, J
    Donnelly, T
    Morhenn, V
    Jessee, B
    Hainsworth, S
    Casterton, P
    Bernhofer, L
    Martin, K
    Decker, D
    [J]. EXPERIMENTAL DERMATOLOGY, 1998, 7 (01) : 18 - 26
  • [32] Some magnesium salts and a mixture of magnesium and calcium salts accelerate skin barrier recovery
    Denda, M
    Katagiri, C
    Hirao, T
    Maruyama, N
    Takahashi, M
    [J]. ARCHIVES OF DERMATOLOGICAL RESEARCH, 1999, 291 (10) : 560 - 563
  • [33] Visual imaging of ion distribution in human epidermis
    Denda, M
    Hosoi, J
    Asida, Y
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 272 (01) : 134 - 137
  • [34] Negative electric potential induces alteration of ion gradient and lamellar body secretion in the epidermis, and accelerates skin barrier recovery after barrier disruption
    Denda, M
    Kumazawa, N
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (01) : 65 - 72
  • [35] Dinarello C A, 1998, Int Rev Immunol, V16, P457, DOI 10.3109/08830189809043005
  • [36] Draize JH, 1944, J PHARMACOL EXP THER, V82, P377
  • [37] INVITRO RECONSTRUCTION OF HUMAN SKIN - THE USE OF SKIN EQUIVALENTS AS POTENTIAL INDICATORS OF CUTANEOUS TOXICITY
    DYKES, PJ
    EDWARDS, MJ
    ODONOVAN, MR
    MERRETT, V
    MORGAN, HE
    MARKS, R
    [J]. TOXICOLOGY IN VITRO, 1991, 5 (01) : 1 - &
  • [38] SURFACTANTS AND EXPERIMENTAL IRRITANT CONTACT-DERMATITIS
    EFFENDY, I
    MAIBACH, HI
    [J]. CONTACT DERMATITIS, 1995, 33 (04) : 217 - 225
  • [39] ENK AH, 1992, J IMMUNOL, V149, P92
  • [40] EARLY MOLECULAR EVENTS IN THE INDUCTION-PHASE OF CONTACT SENSITIVITY
    ENK, AH
    KATZ, SI
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (04) : 1398 - 1402