322
Views
19
CrossRef citations to date
0
Altmetric
Research Article

In Vitro Approaches to the Identification and Characterization of Skin Sensitizers

&
Pages 359-373 | Published online: 10 Oct 2008

REFERENCES

  • Rustemeyer T, Hoogstraten IMW, von Blomberg BME, Scheper RJ. Mechanisms in allergic contact dermatitis. In: Frosch PJ, Menné T, Lepoittevin J-P, eds. Contact Dermatitis, 4th edition. Heidelberg: Springer Verlag, 2006:11–44.
  • Dupuis G, Benezra C. Allergic Contact Dermatitis to Simple Chemicals: a Molecular Approach. New York and Basel: Marcel Dekker Inc., 1982.
  • Lepoittevin, J-P, Basketter, DA, Dooms-Goossens A, Karlberg A-T. Allergic Contact Dermatitis; The Molecular Basis. Heidelberg: Springer-Verlag, 1997.
  • Karlberg A-T, Basketter DA, Goossens A, Lepoittevin J-P. Regulatory classification of substances oxidized to skin sensitizers by exposure to the air. Contact Derm 1999; 40: 183–188.
  • Matura M, Skold M, Borje A, Andersen KE, Bruze M, Frosch P, Goossens A, Johansen JD, Svedman C, White IR, Karlberg AT. Selected oxidized fragrance terpenes are common contact allergens. Contact Derm 2005; 52: 320–328.
  • Pease Smith CK, Basketter DA, Patlewicz GY. Contact allergy: the role of skin chemistry and metabolism. Clin Exp Dermatol 2003; 28: 177–183.
  • Elahi EM, Wright Z, Hinselwood D, Hotchkiss SA, Basketter DA, Pease CK. Protein binding and metabolism influence the relative skin sensitisation potency of cinnamic compounds. Chem Res Toxicol 2004; 17: 301–310.
  • Smith CK, Hotchkiss SAM. Allergic Contact Dermatitis: Chemical and Metabolic Mechanisms. London, UK: Taylor & Francis Ltd., 2001.
  • Divkovic M, Pease CM, Gerberick GF, Basketter DA. Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitisation. Contact Derm 2005; 53: 189–200.
  • Proksch E, Folster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci 2006; 43: 159–169.
  • Matzinger P. Friendly and dangerous signals. Is the tissue in control? Nat Immunol 2007; 8: 11–13.
  • Welss T, Basketter DA, Schroder KR. In vitro skin irritation: facts and future. State of the art review of mechanisms and models. Toxicol in Vitro 2004; 18: 231–243.
  • Cumberbatch M, Clelland K, Dearman RJ, Kimber I. Impact of cutaneous IL-10 on resident epidermal Langerhans' cells and the development of polarized immune responses. J Immunol 2005; 175: 43–50.
  • Griffiths, CE, Dearman RJ, Cumberbatch M, Kimber I. Cytokines and langerhans cell mobilisation in mouse and man. Cytokine 2005; 32: 67–70.
  • Kupper, TS, Fuhlbrigge RC. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004; 4: 211–222.
  • Steinhoff M, Brzoska T, Luger TA. Keratinocytes in epidermal immune responses. Curr Opin Allergy Clin Immunol 2001; 1: 469–476.
  • Van Och FMM, Vandebriel RJ, De Jong WH, Van Loveren H. Effect of prolonged exposure to low antigen concentration for sensitization. Toxicol 2003; 184: 23–30.
  • Smith HR, Basketter DA, McFadden JP. Irritant dermatitis, irritancy and its role in allergic contact dermatitis. Clin Exp Dermatol 2002; 27: 138–146.
  • Kimber I, Cumberbatch M, Dearman RJ, Bhushan M, Griffiths CE. Cytokines and chemokines in the initiation and regulation of epidermal Langerhans cell mobilization. Br J Dermatol 2000; 142: 401–412.
  • Kissenpfennig A, Malissen B. Langerhans cells-revisiting the paradigm using genetically engineered mice. Trends Immunol 2006; 27: 132–139.
  • Cumberbatch, M, Dearman RJ, Kimber I. Langerhans cells require signals from both tumour necrosis factor-alpha and interleukin-1 beta for migration. Immunol 1997; 92: 388–395.
  • Cumberbatch M, Dearman RJ, Griffiths CE, Kimber I. Epidermal Langerhans cell migration and sensitisation to chemical allergens. APMIS 2003; 797–804.
  • Macatonia SE, Knight SC, Edwards AJ, Griffiths S, Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med 1987; 166: 1654–1667.
  • Henri S, Vremec D, Kamath, A, Waithman J, Williams S, Benoist C, Burnham K, Saeland S, Handman E, Shortman K. The dendritic cell populations of mouse lymph nodes. J Immunol 2001; 167: 741–748.
  • Sallusto F, Lanzavecchia A. Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev 2000; 177: 134–140.
  • Martin-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F. Regulation of dendritic cell migration to the draining lymph node: Impact on T lymphocyte traffic and priming. J Exp Med 2003; 198: 615–621.
  • Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol 2006; 6: 476–4.
  • Vocanson M, Anca Hennino A, Cluzel-Tailhardat M, Saint-Mezard P, Benetiere J, Chavagnac C, Berard F, Kaiserlian D, Nicolas JF. CD8 + T cells are effector cells of contact dermatitis to common skin allergens in mice. J of Invest Dermatol 2006; 126: 815–820.
  • Basketter DA, Evans P, Fielder RJ, Gerberick GF, Dearman RJ, Kimber I. Local lymph node assay—validation, conduct and use in practice. Food Chem Toxicol 2002; 40: 593–598.
  • Lepoittevin J-P, Basketter DA, Goosssens A, Karlberg A-T. Eds. Allergic Contact Dermatitis. The Molecular Basis. Heidelberg: Springer, 1997.
  • Lepoittevin J-P. Molecular aspects of allergic contact dermatitis. In: Frosch PJ, Menné T, Lepoittevin J-P, eds. Contact Dermatitis, 4th edition. Heidelberg: Springer-Verlag, 2006: 45–68.
  • Aptula AO, Patlewicz G, Roberts DW. Skin sensitization: reaction mechanistic applicability domains for structure-activity relationships. Chem Res Toxicol 2005; 18(9): 1420–1426.
  • Roberts DW, Patlewicz G, Kern PS, Gerberick GF, Kimber I, Dearman RJ, Ryan CA, Basketter DA, Aptula AO. Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitisation. Chemical Research in Toxicology 2007; 16: 1019–1030.
  • Divkovic M, Pease CM, Gerberick G, Basketter DA. Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitisation. Contact Derm 2005; 53: 189–200.
  • Barratt MD, Langowski JJ. Validation and subsequent development of the Derek skin sensitization rulebase by analysis of the BgVV list of contact allergens. J Chem Inf Comput Sci 1999; 39: 294–298.
  • Langton K, Patlewicz GY, Long A, Marchant CA, Basketter DA. Structure activity-relationships for skin sensitisation: recent improvements to DEREK for windows. Contact Derm 2006; 55: 342–347.
  • Patlewicz G, Aptula AO, Roberts DW, Kern PS, Gerberick GF, Kimber I, Dearman RJ, Ryan CA, Basketter DA. An Evaluation of selected global (Q) SARs/expert systems for the prediction of skin sensitisation potential. SAR and QSAR in Environmental Research, 2007; 18: 515–541.
  • Roberts DW, Williams DL. The derivation of quantitative correlations between skin sensitization and physico–chemical parameters for alkylating agents and their application to experimental data for sultones. J Theor Biol 1982; 99: 807–825.
  • Roberts DW, Basketter DA. Quantitative structure-activity relationships: sulfonate esters in the local lymph node assay. Contact Derm 2000; 42(3): 154–161.
  • Aptula AO, Roberts DW, Patlewicz G. Mechanistic applicability domains for non-animal based toxicological endpoints. QSAR analysis of the Schiff Base applicability domain for skin sensitization. Chem Res Toxicol 2006; 19(9): 1228–1233.
  • Patlewicz G, Basketter DA, Pease CK, Wilson K, Wright ZM, Roberts DW, Bernard G, Arnau EG, Lepoittevin JP. Further evaluation of quantitative structure–activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens. Contact Derm 2004; 50: 91–97.
  • Roberts DW, Aptula AO, Cronin MTD, Hulzebos E, Patlewicz G. Global (Q)SARs for skin sensitization–assessment against OECD principles, SAR QSAR Environ. Res., in press (2007).
  • Aptula AO, Roberts DW, Pease CK. Haptens, prohaptens and prehaptens, or electrophiles and proelectrophiles. Contact Derm 2007; 56: 54–56.
  • Karlberg A-T, Basketter DA, Goossens A, Lepoittevin J-P. Regulatory classification of substances oxidized to skin sensitizers by exposure to the air. Contact Derm 1999; 40: 183–188.
  • Nohynek GJ, Duche D, Garrigues A, Meunier PA, Toutain H, Leclaire J. Under the skin: Biotransformation of para-aminophenol and para-phenylenediamine in reconstructed human epidermis and human hepatocytes. Toxicol Lett 2005; 158: 196–212.
  • Eilstein J, Gimenez-Arnau E, Duche D, Rousset F, Lepoittevin JP. Synthesis and reactivity toward nucleophilic amino acids of 2,5-[13C]-dimethyl-p-benzoquinonediimine. Chem Res Toxicol 2006; 19: 1248–1256.
  • Pease Smith CK, Basketter DA, Patlewicz GY. Contact allergy: The role of skin chemistry and metabolism. Clin Exp Dermatol 2003; 28: 177–183.
  • Mekenyan O, Dimitrov S, Dimitrova N, Dimitrova G, Pavlov T, Chankov G, Kotov S, Vasilev K, Vasilev R. Metabolic activation of chemicals: in-silico simulation. SAR QSAR Environ Res 2006; 17: 107–120.
  • Gerberick GF, Vassallo JD, Bailey RE, Chaney JG, Morrall SW, Lepoittevin JP. Development of a peptide reactivity assay for screening contact allergens. Toxicol Sci. 2004; 81(2): 332–343.
  • Alvarez-Sanchez R, Basketter DA, Pease CK, Lepoittevin J-P. Covalent binding of the 13C-labeled skin sensitizers 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI) to a model peptide and glutathione. Biorg Med Chem Lett 2004; 14: 365–368.
  • Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittevin JP. Quantification of chemical peptide reactivity for screening contact allergens: a classification tree model approach. Toxicol Sci 2007; 97: 417–427.
  • Aleksic M, Pease CK, Basketter DA, Panico M, Morris HR, Dell A. Investigating protein haptenation mechanisms of skin sensitisers using human serum albumin as a model protein. Toxiol in Vitro, in press (2007).
  • Aleksic M, Thain E, Gutsell SJ, Pease CK, Basketter DA. Investigating non-covalent serum albumin binding of skin sensitising chemicals. J Cut Ocular Toxicol accepted (2007).
  • Elahi EM, Wright Z, Hinselwood D, Hotchkiss SAM, Basketter DA, Smith Pease CK. Protein binding and metabolism influence the relative skin sensitisation potency of cinnamic compounds. Chem Res Toxicol 2004; 17: 301–310.
  • Alvarez-Sanchez R, Divkovic M, Basketter D, Pease C, Panico M, Dell A, Morris H, Lepoittevin JP. Effect of glutathione on the covalent binding of the 13C labeled skin sensitizer 5-chloro-2-methylisothiazol-3-one (MCI) to human serum albumin: Identification of adducts by nuclear magnetic resonance, matrix-assisted laser desorption/ionization mass spectrometry and nanoelectrospray tandem mass spectrometry. Chem Res Toxicol 2004; 17: 1280–1288.
  • Martin S, Lappin MB, Kohler J, Delattre V, Leicht C, Preckel T, Simon JC, Weltzien HU. Peptide immunization indicates that CD8 + T cells are the dominant effector cells in trinitrophenyl-specific contact hypersensitivity. J Invest Dermatol 2000; 115: 260–266.
  • Thierse HJ, Gamerdinger K, Junkes C, Guerreiro N, Weltzien HU. T cell receptor (TCR) interaction with haptens: Metal ions as non-classical haptens. Toxicol 2005; 209: 101–107.
  • Basketter D, Pease C, Kasting G, Kimber I, Casati S, Cronin M, Diembeck W, Gerberick F, Hadgraft J, Hartuang T, Marty JP, Nikolaidis E, Patlewicz G, Roberts D, Roggen E, Rovida C, van de Sandt J. Skin sensitisation and epidermal disposition. Alternatives to Laboratory Animals 2007; 35: 137–154.
  • Kretsos K, Kasting GB, Nitsche JM. Distributed diffusion-clearance model for transient drug distribution within the skin. J Pharm Sci 2004; 93: 2820–2835.
  • Smith CK, Hotchkiss SAM. Allergic Contact Dermatitis: chemical and metabolic mechanisms. London: Taylor and Francis, 2002.
  • Bergstrom MA, Luthman K, Nilsson JL, Karlberg AT. Conjugated dienes as prohaptens in contact allergy: In vivo and in vitro studies of structure-activity relationships, sensitizing capacity, and metabolic activation. Chem Res Toxicol 2006; 19(6): 760–769.
  • Kandarova H, Liebsch M, Gerner I, Schmidt E, Genschow E, Traue D, Spielmann H. The EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests—An assessment of the performance of the optimised test. Alternatives to Laboratory Animals 2005; 33: 351–367.
  • Cotovio J, Grandidier MH, Portes P, Roguet R, Rubinstenn G. The in vitro acute skin irritation of chemicals: optimisation of the EPISKIN prediction model within the framework of the ECVAM validation process. Alternatives to Laboratory Animals 2005; 33: 329–349.
  • Perkins NC, Heard CM. In vitro dermal and transdermal delivery of doxycycline from ethanol/migliol 840 vehicles. Int J Pharm 1999; 190: 155–164.
  • Welss T, Basketter DA, Schroder KR. In vitro skin irritation: Facts and future. State of the art review of mechanisms and models. Toxicol in Vitro 2004; 18: 231–243.
  • Frosch PJ, John SM. Clinical aspects of irritant contact dermatitis. In: Frosch PJ, Menné T, Lepoittevin J-P, eds. Contact Dermatitis, 4th edition. Heidelberg: Springer-Verlag, 2006; 255–294.
  • Fentem JH, Briggs D, Chesne C, Elliott GR, Harbell JW, Heylings JR, Portes P, Roguet R, van de Sandt JJ, Botham, PA. A prevalidation study on in vitro tests for acute skin irritation. results and evaluation by the Management Team. Toxicol in Vitro 2001; 15: 57–93.
  • Casati S, Aeby P, Basketter DA, Cavani A, Gennari A, Gerberick GF, Griem P, Hartuang T, Kimber I, Lepoittevin JP, Meade BJ, Pallardy M, Rougier N, Rousset F, Rubinstenn G, Sallusto F, Verheyen GR, Zuang, V. Dendritic cells as a tool for the predictive identification of skin sensitisation hazard. Alternatives to Laboratory Animals 2005; 33: 47–62.
  • Ryan CA, Gerberick GF, Gildea LA, Hulette BC, Betts CJ, Cumberbatch M, Dearman RJ, Kimber I. Interactions of contact allergens with dendritic cells: opportunities and challenges for the development of novel approaches to hazard assessment. Toxicol Sci 2005; 88: 4–11.
  • Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z, Zwirner J, Blankenstein T, Henning G, Forster R. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 2004; 21: 279–288.
  • Ratzinger G, Stoitzner P, Ebner S, Lutz MB, Layton GT, Rainer C, Senior RM, Shipley JM, Fritsch P, Schuler G, Romani N. Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin. J Immunol 2002; 168: 4361–4371.
  • Caux C, it-Yahia S, Chemin K, de Bouteiller O, Dieu-Nosjean MC, Homey B, Massacrier C, Vanbervliet B, Zlotnik A, Vicari A. Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Semin Immunopathol 2000; 22: 345–369.
  • Kimber I, Cumberbatch M, Betts CJ, Dearman RJ. Dendritic cells and skin sensitisation hazard assessment. Toxicol in Vitro 2004; 18: 195–202.
  • Antonopoulos H, Cumberbatch M, Dearman RJ, Daniel RJ, Kimber I, Groves RW. Functional caspase-1 is required for langerhans cell migration and optimal contact sensitization in mice. J Immunol 2001; 166: 3672–3677.
  • Cumberbatch M, Dearman RJ, Antonopoulos C, Groves RW, Kimber I. Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor-alpha- and IL-1 beta-dependent mechanism. Immunol 2001; 102: 323–330.
  • Wang B, Zhuang LH, Fujisawa H, Shinder GA, Feliciani C, Shivji GM, Suzuki H, Amerio P, Toto P, Sauder DN. Enhanced epidermal Langerhans cell migration in IL-10 knockout mice. J Immunol 1999; 16: 277–283.
  • Pichowski JS, Cumberbatch M, Dearman RJ, Kimber I, Basketter DA. Investigation of induced changes in interleukin 1β mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. Toxicol in Vitro 2000; 14(4): 351–360.
  • Pichowski JS, Cumberbatch M, Dearman RJ, Basketter DA, Kimber I. Allergen-induced changes in interleukin 1 beta (IL-1 beta) mRNA expression by human blood-derived dendritic cells: Inter-individual differences and relevance for sensitization testing. J Appl Toxicol 2001; 21: 115–121.
  • Krasteva M, Moulon C, Peguet-Navarro J, Courtellemont P, Redziniak G, Schmitt D. In vitro sensitization of human T cells with hapten-treated Langerhans cells: a screening test for the identification of contact allergens. Curr Probl Dermatol 1996; 25: 28–36.
  • Sakaguchi H, Ashikaga T, Miyazawa M, Yoshida Y, Ito Y, Yoneyama K, Hirota M, Itagaki, H, Toyoda H, Suzuki H. Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT). II. An inter-laboratory study of the h-CLAT. Toxicol in Vitro 2006; 20(5): 774–784.
  • Lutz MB, Kukutsch N, Ogilvie LJ, Ogilvie AL, Rossner S, Koch F, Romani N, Schuler G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Meth 1999; 223: 77–92.
  • EU. Directive 2003/15/EC of the European Parliament and the Council of 27 February 2003 amending Council Directive 76/768/EEC on the approximations of laws of the Member States relating to cosmetic products. Off J Eur Union 2003; L66: 26–35.
  • Ryan, C, Gildea LA, Hulette BC, Dearman RJ, Kimber I, Gerberick GF. Gene expression changes in peripheral blood-derived dendritic cells following exposure to a contact allergen. 6. Toxicol Lett 2004; 150: 301–316.
  • Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers. J Immunol 2001; 166: 3837–3845.
  • Aiba S, Manome H, Yoshino Y, Tagami H. In vitro treatment of human transforming growth factor-beta(1)-treated monocyte-derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction. Immunol 2000; 101: 68–75.
  • Aiba S, Manome H, Nakagawa S, Mollah ZU, Mizuashi M, Ohtani T, Yoshino Y, Tagami H. p38 Mitogen-activated protein kinase and extracellular signal-regulated kinases play distinct roles in the activation of dendritic cells by two representative haptens, NiCl2 and 2,4-dinitrochlorobenzene. J Invest Dermatol 2003; 120: 390–399.
  • Tuschl H, Kovac R, Weber E. The expression of surface markers on dendritic cells asindicators for the sensitizing potential of chemicals. Toxicol In Vitro 2000; 14: 541–549.
  • De Smedt T, Butz E, Smith J, Maldonado-Lopez R, Pajak B, Moser M, Maliszewski C. CD8alpha(−) and CD8alpha(+) subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo. J Leukoc Biol 2001; 69: 951–958.
  • Ashikaga T, Hoya M, Itagaki H, Katsumura Y, Aiba S. Evaluation of CD86 expression and MHC class II molecule internalization in THP-1 human monocyte cells as predictive endpoints for contact sensitizers. Toxicol In Vitro 2002; 16: 711–716.
  • Yoshida Y, Sakaguchi H, Ito Y, Okuda M, Suzuki M. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line. Toxicol in Vitro 2003; 17: 221–228.
  • Python F, Goebel C, Aeby P. Modulation of human myeloid cell lines phenotype and function by chemicals. J Toxicol Appl Pharmacol. In press (2007).
  • Hulette BC, Ryan CA, Gerberick GF. Elucidating changes in surface marker expression of dendritic cells following chemical allergen treatment. Toxicol Appl Pharmacol 2002; 182: 226–233.
  • Azam P, Peiffer JL, Chamousset D, Tissier MH, Bonnet PA, Vian L, Fabre I, Ourlin JC. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers. Toxicol Appl Pharmacol 2006; 212(1): 14–23.
  • Ashikaga T, Yoshida Y, Hirota M, Yoneyama K, Itagaki H, Sakaguchi H, Miyazawa M, Ito Y, Suzuki H, Toyoda H. Development of an in vitro skin sensitization test using human cell lines: The human Cell Line Activation Test (h-CLAT) I. Optimization of the h-CLAT protocol. Toxicol In Vitro 2006; 20(5): 767–773.
  • Sakaguchi H, Miyazawa M, Yoshida Y, Ito Y, Suzuki H. Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1. Arch Derm Res 2007; 298: 427–437.
  • Dearman RJ, Cumberbatch M, Clelland K, Portsmouth C, Maxwell G, Westmoreland C, Basketter DA, Kimber I. Syngeristic effects of chemical insult and toll-like receptor ligands in dendritic cell (DC) activation.
  • Hauser C, Katz SI. Generation and characterization of T-helper cells by primary in vitro sensitization using Langerhans cells. Immunol Rev 1990; 117: 67–84.
  • Moulon C, Peguet-Navarro J, Courtellemont P, Redziniak G, Schmitt D. In vitro primary sensitization and restimulation of hapten-specific T cells by fresh and cultured human epidermal Langerhans' cells. Immunol 1993; 80: 373–379.
  • Guironnet G, Biez-Gauthier C, Rousset F, Schmitt D, Peguet-Navarro J. In vitro human T cell sensitization to haptens by monocyte-derived dendritic cells. Toxicol in Vitro 2000; 14: 517–522.
  • Kimber I, Dearman RJ, Betts, Gerberick GF, Ryan CA, Kern PS, Patlewicz GY, Basketter DA. The local lymph node assay and skin sensitisation: a cut-down screen to reduce animal requirements. Contact Derm 2006; 54: 181–185.
  • Jowsey IR, Basektter DA, Westmoreland C, Kimber I. A future approach to measuring relative skin sensitization potency: A proposal. J Appl Toxicol 2006; 26: 341–350.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.