Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data on in vitro skin irritation / corrosion are available for the substance under assessment, and results indicate that the substance is corrosive to skin (Skin Corr. 1B) and thus, based on worst case consideration (pH 2 for a saturated test item solution) the substance causes serious eye damage (Eye Damage 1).

The classification for eye damaging based on Regulation (EC) No 1272/2008: “… if a substance or mixture is classified as Skin corrosive Category 1 then serious damage to eyes is implicit and there is no need to proceed with classification for eye effects.

In accordance with Regulation (EC) No 1907/2006 Annex VII point 8.3 column 2 the study on skin sensitisation does not need to be conducted for animal welfare reasons, if the substance is a strong acid with a pH ≤ 2 or should be classified for corrosivity, which is the case for the substance under consideration.

However, 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 vitrostudies (addressed to a specific mechanistic step of skin sensitization) 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 negative outcome, whereas one study (i.e., h-CLAT) gives a positive 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 non-sensitiser if two of these three tests performed, resulting in a negative outcome. 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: not 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 does not need to be classified as skin sensitiser.