Development of an in vitro method to estimate the sensitization induction level of contact allergens.

No standardized in vitro methods to assess potency of skin sensitizers are available. Recently, we standardized a procedure which combines the epidermal equivalent potency assay with assessment of IL-18 to provide a single test for identification and classification of skin sensitizers. This current study aimed to extend tested chemicals, and to provide a simple in vitro method for estimation of the expected sensitization induction level interpolating in vitro EC50 and IL-18 SI2 values to predict LLNA EC3 and/or human NOEL from standards curves generated using reference contact allergens. Reconstituted human epidermis was challenged with 14 chemicals not previously tested benzoquinone, chlorpromazine, chloramine T, benzyl salicylate, diethyl maleate, dihydroeugenol, 2,4-dichloronitrobenzene, benzyl cinnamate, imidazolidinyl urea, and limonene as contact sensitizers while benzyl alcohol, isopropanol, dimethyl isophthalate and 4-aminobenzoic acid as non-sensitizers in the LLNA. Where for benzyl salicylate and benzyl cinnamate no sensitization was observed in human predictive studies, positive responses to benzyl alcohol and dimethyl isophthalate were reported. The proposed method correlates better with human data, correctly predicting substances incorrectly classified by LLNA. With the exception of benzoquinone (interference with both MTT and IL-18 ELISA), and chloramine T (underestimated in the interpolation), a good estimation of LLNA EC3 and in vivo available human NOEL values was obtained.

[1]  D. Basketter,et al.  Dichloronitrobenzene: a reappraisal of its skin sensitization potential , 1996, Contact dermatitis.

[2]  Marina Marinovich,et al.  Use of IL-18 production in a human keratinocyte cell line to discriminate contact sensitizers from irritants and low molecular weight respiratory allergens. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[3]  Carl Westmoreland,et al.  A future approach to measuring relative skin sensitising potency: a proposal , 2006, Journal of applied toxicology : JAT.

[4]  E. Corsini,et al.  Alternative Approach for Potency Assessment: In Vitro Methods , 2016 .

[5]  Gavin Maxwell,et al.  Allergic contact dermatitis: a commentary on the relationship between T lymphocytes and skin sensitising potency. , 2012, Toxicology.

[6]  R. Pieters,et al.  International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive-capacity. , 2014, ALTEX.

[7]  Janine Ezendam,et al.  Anchoring molecular mechanisms to the adverse outcome pathway for skin sensitization: Analysis of existing data , 2014, Critical reviews in toxicology.

[8]  Frank Gerberick,et al.  Predictive identification of human skin sensitization thresholds , 2005, Contact dermatitis.

[9]  James M McKim,et al.  A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells , 2010, Cutaneous and ocular toxicology.

[10]  João Barroso,et al.  Categorization of Chemicals According to Their Relative Human Skin Sensitizing Potency , 2014, Dermatitis : contact, atopic, occupational, drug.

[11]  Aynur Aptula,et al.  Local Lymph Node Data for the Evaluation of Skin Sensitization Alternatives: A Second Compilation , 2010, Dermatitis : contact, atopic, occupational, drug.

[12]  Petra Kern,et al.  A dataset on 145 chemicals tested in alternative assays for skin sensitization undergoing prevalidation , 2013, Journal of applied toxicology : JAT.

[13]  Ian Kimber,et al.  IL‐18 is a key proximal mediator of contact hypersensitivity and allergen‐induced Langerhans cell migration in murine epidermis , 2008, Journal of leukocyte biology.

[14]  I Kimber,et al.  Contact allergenic potency: correlation of human and local lymph node assay data. , 2001, American journal of contact dermatitis : official journal of the American Contact Dermatitis Society.

[15]  G Frank Gerberick,et al.  Chemical allergy: translating biology into hazard characterization. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  F. Capon,et al.  Occupational contact dermatitis caused by computer mice , 1996, Contact dermatitis.

[17]  M. Boeniger,et al.  Federal government regulation of occupational skin exposure in the USA , 2003, International archives of occupational and environmental health.

[18]  T. Estlander,et al.  Occupational allergic contact urticaria from chloramine‐T solution , 1997, Contact dermatitis.

[19]  L. Belin,et al.  Immunological specificity of chloramine‐T‐induced IgE antibodies in serum from a sensitized worker , 1989, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[20]  Andre Boorsma,et al.  The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat. , 2008, Toxicology.

[21]  Emanuela Corsini,et al.  Transfer of a two-tiered keratinocyte assay: IL-18 production by NCTC2544 to determine the skin sensitizing capacity and epidermal equivalent assay to determine sensitizer potency. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[22]  K Schneider,et al.  Quantitative relationship between the local lymph node assay and human skin sensitization assays. , 2004, Regulatory toxicology and pharmacology : RTP.

[23]  E. Corsini,et al.  Safety Evaluation of Cosmetic Ingredients: In Vitro Opportunities for the Identification of Contact Allergens , 2014 .

[24]  A. M. Api,et al.  Fragrance material review on benzyl salicylate. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[25]  A. Api,et al.  Fragrance material review on butyl salicylate. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  M. Gola,et al.  Unusual occupational allergic contact dermatitis in a nurse , 1989, Contact dermatitis.

[27]  Anton C. de Groot,et al.  Patch testing : test concentrations and vehicles for 3700 chemicals , 1994 .

[28]  A O Aptula,et al.  Electrophilic reactivity and skin sensitization potency of SNAr electrophiles. , 2014, Chemical research in toxicology.

[29]  H. Okamura,et al.  Cloning of a new cytokine that induces IFN-gamma production by T cells. , 1995, Nature.

[30]  Petra S Kern,et al.  Assessing skin sensitization hazard in mice and men using non-animal test methods. , 2015, Regulatory toxicology and pharmacology : RTP.

[31]  H. Okamura,et al.  Cloning of a new cytokine that induces IFN-γ production by T cells , 1995, Nature.

[32]  A. Pérez Montero,et al.  Allergic contact urticaria to oatmeal , 2002, Allergy.

[33]  J. Geier,et al.  Sensitization to 26 fragrances to be labelled according to current European regulation , 2007, Contact dermatitis.

[34]  D. Basketter,et al.  Investigating protein haptenation mechanisms of skin sensitisers using human serum albumin as a model protein. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[35]  G Frank Gerberick,et al.  Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients. , 2008, Regulatory toxicology and pharmacology : RTP.

[36]  A. Api,et al.  Fragrance material review on 2-methyl-5-phenylpentanol. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[37]  A. M. Api,et al.  Fragrance material review on benzyl alcohol. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[38]  Allan Linneberg,et al.  The epidemiology of contact allergy in the general population – prevalence and main findings , 2007, Contact dermatitis.

[39]  S. Ohkawara,et al.  Activation of the human transient receptor potential vanilloid subtype 1 by essential oils. , 2010, Biological & pharmaceutical bulletin.

[40]  C L Galli,et al.  Further development of the NCTC 2544 IL-18 assay to identify in vitro contact allergens. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[41]  Thomas Rustemeyer,et al.  Mechanisms of Allergic Contact Dermatitis , 2018, Kanerva’s Occupational Dermatology.

[42]  S. Gibbs,et al.  Preliminary performance data of the RHE/IL‐18 assay performed on SkinEthic™ RHE for the identification of contact sensitizers , 2017, International journal of cosmetic science.

[43]  Marina Marinovich,et al.  NCTC 2544 and IL-18 production: a tool for the identification of contact allergens. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[44]  Emanuela Corsini,et al.  An epidermal equivalent assay for identification and ranking potency of contact sensitizers. , 2013, Toxicology and applied pharmacology.

[45]  A. W. Toorenenbergen,et al.  Occupational Asthma Due to Inhalation of Chloramine-T , 1981 .

[46]  I Kimber,et al.  Threshold for classification as a skin sensitizer in the local lymph node assay: a statistical evaluation. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[47]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[48]  J. Saurat,et al.  A toxicological and dermatological assessment of aryl alkyl alcohols when used as fragrance ingredients. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[49]  Carsten Goebel,et al.  Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data. , 2003, Regulatory toxicology and pharmacology : RTP.

[50]  A. Dooms‐goossens,et al.  Allergic contact urticaria due to chloramine , 1983, Contact dermatitis.

[51]  C. Duarte,et al.  Effect of Skin Sensitizers on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Skin Dendritic Cells: Role of Different Immunosuppressive Drugs , 2007, Immunopharmacology and immunotoxicology.

[52]  A. Api,et al.  Fragrance material review on benzyl cinnamate. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[53]  A. Draper,et al.  Occupational Asthma , 2002, The Journal of asthma : official journal of the Association for the Care of Asthma.

[54]  A. M. Api,et al.  Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects , 2011, Cellular and Molecular Life Sciences.

[55]  Ian Kimber,et al.  Compilation of Historical Local Lymph Node Data for Evaluation of Skin Sensitization Alternative Methods , 2005, Dermatitis : contact, atopic, occupational, drug.