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Event: 827

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

sensitisation, skin

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
sensitisation, skin
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Skin Sensitisation AOP AdverseOutcome Sharon Munn (send email) Open for citation & comment WPHA/WNT Endorsed

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
mouse Mus musculus High NCBI
guinea pig Cavia porcellus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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[1]. 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[2].

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

[3]Human sensitisation testing is conducted with the Human Repeat Insult Patch Test (HRIPT), as described by McNamee et al.[4];[5]. 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[6]. Briefly, among these in vivo assays are the guinea-pig occluded patch test[7];[8], the Magnusson-Kligman guinea pig maximization test[7];[9];[10], and the murine Local Lymph Node Assay[11];[12];[13]. 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. [14], the LLNA is not without limitations.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

In vivo studies remain the basis of assessing the sensitisation potential of chemicals (see [6]). As previously noted, human sensitisation testing is conducted with the HRIPT[4]. Other in vivo methods include the guinea-pig occluded patch test[6];[15], the Magnusson- Kligman guinea-pig maximization test [16] and the mouse LLNA[11];[12];[13].

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

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.

References

List of the literature that was cited for this KE description. More help
  1. 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.
  2. 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
  3. 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.
  4. 4.0 4.1 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.
  5. 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.
  6. 6.0 6.1 6.2 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.
  7. 7.0 7.1 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.
  8. Buehler EV. 1965. Delayed hypersensitivity in the guinea pig. Arch. Dermatol. 91: 171-177.
  9. Magnusson B and Kligman AM. 1970. Allergic Contact Dermatitis in the Guinea Pig. Identification of Contact Allergens. Charles C Thomas; Springfield, IL USA.
  10. Maurer T, Arthur A and Bentley P. 1994. Guinea-pig contact sensitisation assays. Toxicology 93: 47-54.
  11. 11.0 11.1 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
  12. 12.0 12.1 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.
  13. 13.0 13.1 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
  14. 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.
  15. 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
  16. 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.