Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

To identify the skin sensitisation potential of the test substance a comprehensive testing strategy conducting three in chemico / in vitro studies (DPRA, LuSens, and h-CLAT) was performed.

According to Basketter et al. (2005) & ECHA guidance R.7a (2014), due to the complexity of the mechanisms of skin sensitisation, a single test is not be able to replace the currently required animal procedures. However, a combination of several in chemico / in vitro tests, covering all the relevant mechanistic steps of skin sensitisation (i.e., (i) the ability to penetrate into the skin, (ii) to react with protein, and (iii) to be recognised as antigenic by cells of the immunological system) into a test battery could lead to replacement of the in vivo tests.

Hence, the following in chemico / in vitro studies (addressed to a specific mechanistic step of skin sensitisation) were conducted with the test item under consideration:

(i) In chemico skin sensitisation: Direct Peptide Reactivity Assay (DPRA) in accordance with draft proposal (July 2014)

(ii) In vitro skin sensitisation: ARE Reporter Assay (LuSens) in accordance with Bauch et al. (2012), Maxwell et al. (2011) and Bauch et al. (2011)

(iii) In vitro skin sensitisation: Human Cell Line Activation Test (h-CLAT) in accordance with Bauch et al. (2012), Bauch et al. (2011), Maxwell et al. (2011), Ashikaga et al. (2010) and Sakaguchi et al. (2010).

Two of these tests (i.e., DPRA and LuSens) result in a positive outcome, whereas one study (i.e., h-CLAT) gives a negative result.

However, in case of conflicting results a pragmatic weight of evidence approach may be used in according to Bauch et al. 2012. The authors approach is to classify the respective substance as sensitiser if two of these three tests performed, resulting in a positive outcome (any two of three tests rule the overall result). Using this approach, 47 out of 50 or 44 out of 53 test substances were predicted correctly if compared to human or LLNA, respectively.

References:

- ECHA (2014): Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a: Endpoint specific guidance, v 3.0

- Bauch et al. (2012): Putting the parts together: Combining in vitro methods to test for skin sensitizing potentials, Regul Toxicol Pharmacol, 63(3):489-504.

- Bauch et al. (2011): Intralaboratory validation of four in vitro assays for the prediction of the skin sensitizing potential of chemicals. Toxicology in Vitro 25, 1162-1168, 2011.

- Maxwell et al. (2011): Skin sensitisation: the Colipa strategy for developing and evaluating nonanimal test methods for risk assessment.ALTEX 28(1): 50-5, 2011.

- Ashikaga et al. (2010): A comparative evaluation of in vitro skin sensitisation tests: the human cell-line activation test (h-CLAT) versus the local lymph node assay (LLNA). Altern Lab Anim. 38(4):275-84.

- Sakaguchi et al. (2010): Predicting skin sensitization potential and inter-laboratory reproducibility of a human Cell Line Activation Test (h-CLAT) in the European Cosmetics Association (COLIPA) ring trials. Toxicol In Vitro. 24(6):1810-20.

- Basketter et al. (2005): 3.4. Skin Sensitisation, ATLA 33, Suppl. 1, 83–103, 2005


Migrated from Short description of key information:
Skin sensitisation: sensitising (test battery of in chemico / in vitro methods: DPRA, LuSens, and h-CLAT)

Justification for selection of skin sensitisation endpoint:
three reliable in chemico / in vitro skin sensitisation studies (DPRA, LuSens, and h-CLAT) conducted with the test item

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In conclusion, based on a weight of evidence approach, the test substance under assessment is sensitising to the skin. Hence, test item does require classification as skin sensitiser according to Directive 67/548/EEC and its subsequent amendments (Xi; R43 May cause sensitisation by skin contact) and according to Regulation (EC) No 1272/2008 and subsequent regulations (Skin Sens. Cat. 1; H317: May cause an allergic skin reaction).