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Key Event Title
Key Event Components
Key Event Overview
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Key Event Description
Skin sensitisation is an immunological process that is described in two phases: the induction of sensitisation and the subsequent elicitation of the immune reaction. A sensitised subject has the capacity to mount a more accelerated secondary response to the same chemical. Upon reaching an unknown threshold number of hapten-specific T cells an individual will be said to be sensitised and will elicit a T cell-mediated eczematous skin reaction (termed allergic contact dermatitis, ACD) at the site of sensitiser re-exposure. Above the threshold, the severity of the adverse effect is assumed to increase proportionally to the dose, so the total dose per area of skin (e.g. μg/cm2) is the critical exposure determinant. In this regard, animal data is consistent with human clinical data. The allergic reaction causes inflammation of the skin manifested by varying degrees of erythema, oedema, and vesiculation. It takes up to one week or more for individuals to develop specific sensitivity to a new allergen following exposure. An individual who never has been sensitised to a substance may develop only a mild dermatitis 2 weeks following the initial exposure but typically develops severe dermatitis within 1-2 days of the second and subsequent exposures.
How It Is Measured or Detected
Human sensitisation testing is conducted with the Human Repeat Insult Patch Test (HRIPT), as described by McNamee et al.;. Skin biopsy may help to confirm the diagnosis and exclude other disorders.
Animal models have been developed to assess the sensitisation potential of chemicals. Adler et al. (2011) have reviewed animal test methods for skin sensitisation. Briefly, among these in vivo assays are the guinea-pig occluded patch test;, the Magnusson-Kligman guinea pig maximization test;;, and the murine Local Lymph Node Assay;;. Using LLNA data, sensitisers can be grouped into potency groups (e.g. extreme, strong, moderate, weak and non-sensitisers). However, as noted by Basketter et al. , the LLNA is not without limitations.
Domain of Applicability
In vivo studies remain the basis of assessing the sensitisation potential of chemicals (see ). As previously noted, human sensitisation testing is conducted with the HRIPT. Other in vivo methods include the guinea-pig occluded patch test;, the Magnusson- Kligman guinea-pig maximization test  and the mouse LLNA;;.
Regulatory Significance of the Adverse Outcome
Skin sensitisation is an endpoint that needs to be assessed within:
- CLP Regulation (EC) No1272/2008 for "Classification, Labelling and Packaging of substances and Mixtures",
- REACH Regulation (EC) No1907/2006 concerning the Registration, Evaluation, Authorization and Restriction of Chemicals,
- PPP Regulation (EC) No1107/2009 concerning the placing of plant protection products on the market,
- Biocidal Products Regulation (BPR) (EU) No528/2012 concerning the making available on the market and use of biocidal products,
- Cosmetics Regulation (EC) No1223/2009.
- Api AM, Basketter DA, Cadby PA, Cano MF, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford B. 2008. Dermal sensitisation quantitative risk assessment (QRA) for fragrance ingredients. Regul Toxicol Pharmacol. 52(1):3-23.
- Hogan DJ and James WD.2015. Allergic Contact Dermatitis Workup Updated: Apr 22, 2015. Available on: http://emedicine.medscape.com/article/1049216-overview accessed 17.9.2015
- Bernstein IL, Li JT, Bernstein DI et al.2008. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 100(3 Suppl 3):S1-148.
- McNamee PM, Api AM, Basketter DA, Frank Gerberick G, Gilpin DA, Hall BM, Jowsey I, Robinson MK.2008. A review of critical factors in the conduct and interpretation of the human repeat insult patch test. Regul Toxicol Pharmacol. 52(1):24-34.
- Larkin A and Rietschel RL.1998. The utility of patch tests using larger screening series of allergens. Am. J. Contact Dermat. 9(3):142-5.
- Adler S, Basketter D, Creton S, Pelkonen O, van Benthem J, Zuang V, Ejner-Andersen K, Angers- Loustau A, Aptula A, Bal-Price A, Benfenati E, Bernauer U, Bessems J, Bois FY, Boobis A, Brandon E, Bremer S, Broschard T, Casati S, Coecke S, Corvi R, Cronin M, Daston G, Dekant W, Felter S, Grignard E, Gundert-Remy U, Heinonen T, Kimber I, Kleinjans J, Komulainen H, Kreiling R, Kreysa J, Batista Leite S, Loizou G, Maxwell G, Mazzatorta P, Munn S, Pfuhler S, Phrakonkham P, Piersma A, Poth A, Prieto P, Repetto G, Rogiers V, Schoeters G, Schwarz M, Serafimova R, Tahti H, Testai E, van Delft J, van Loveren H, Vinken M, Worth A, Zaldivar JM. 2011. Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Arch. Toxicol. 85: 367-485.
- OECD 1992. Test No. 406: Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing. doi: 10.1787/9789264070660-en.
- Buehler EV. 1965. Delayed hypersensitivity in the guinea pig. Arch. Dermatol. 91: 171-177.
- Magnusson B and Kligman AM. 1970. Allergic Contact Dermatitis in the Guinea Pig. Identification of Contact Allergens. Charles C Thomas; Springfield, IL USA.
- Maurer T, Arthur A and Bentley P. 1994. Guinea-pig contact sensitisation assays. Toxicology 93: 47-54.
- OECD 2010. Test No429: Skin Sensitisation: Local Lymph Node Assay, OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing. doi: 10.1787/9789264071100-en
- OECD 2010b. Test No442A: Skin Sensitisation: Local Lymph Node Assay: DA, OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing. doi: 10.1787/9789264090972- en.
- OECD 2010c. Test No442B: Skin Sensitisation: Local Lymph Node Assay: BrdU-ELISA, OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing. doi: 10.1787/9789264090996-en
- Basketter DA, McFadden JF, Gerberick F, Cochshott A and Kimber I. 2009. Nothing is perfect, not even the local lymph node assay: a commentary and the implications for REACH. Contact Dermat. 60: 65-69.
- OECD 1992. Test No 406: Skin Sensitisation, OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing. doi: 10.1787/9789264070660-en
- Magnusson B, Kligman AM. The identification of contact allergens by animal assay.1969. The guinea pig maximization test. J. Invest. Dermatol. 52(3):268-76.