Benzoic acid, 2-hydroxy-, reaction products with formaldehyde, coupled with diazotized 5-amino-8-[[4-[(4-nitro-2-sulfophenyl)amino]phenyl]azo]-2-naphthalenesulfonic acid disodium salt

Endpoint summary

Description of key information

h-CLAT test: Positive

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Under the experimental conditions of the available study, the test item, was positive in the h-CLAT and is therefore considered to have the potential to activate dendritic cells and therefore, to up-regulate the cell surface marker (CD86 and CD54) expression of THP- 1 cells.

Justification for classification or non-classification

Skin sensitisation

In the CLP Regulation (EC) no. 1272/2008 a skin sensitizer is defined as a substance that will lead to an allergic response following skin contact. Validated in vitro/in chemico methods exist with the aim to identify a sensitising potential of a chemical. The subject of in vitro testing for skin sensitisation is discussed in the Guidance on IR&CSA, Section R.7.3.4. There are several validated test methods for the assessment of skin sensitisation potential in vitro and, for some of them, EU/OECD- adopted test guidelines are available. These test methods have been developed with the purpose of using several in chemico/in vitro methods together, as described in section 8.3.1 of Annex VII to the REACH Regulation. Annex VII to the REACH Regulation specifies that when new data need to be generated to fulfil the standard information requirement for skin sensitisation, as a first stepin chemico/in vitrostudies assessing three key events of skin sensitisation should be performed, unless data from fewer key events already allows classification and risk assessment, as specified in Annex VII, section 8.3, column 2. Indicators of potency such as the level of peptide depletion and concentration-responses can be obtained from the existing in chemico and in vitro tests, respectively. Data from the tests:

(i) Direct Peptide Reactivity Assay (DPRA) for Key Event 1 Peptide/protein binding

(ii) ARE-Nrf2 Luciferase Test Method (KeratinoSensTM) for Key Event 2 Keratinocyte response

(iii) Human Cell Line Activation Test (h-CLAT) for Key Event 3 Monocytic /Dendritic cell response.

may be accepted to fulfil Annex VII requirement when used in combination with each other. These test methods were developed to address specific events of the skin sensitisation AOP (OECD, 2012). The AOP for skin sensitisation describes the current understanding of key events linked to skin sensitisation. As each of the test methods only addresses a specific key event of skin sensitisation, currently they should not be used in isolation to identify a skin sensitizer or a non-sensitizer. In particular for the test substance the following results were obtained:

(iii)  potential to activate dendritic cells under the conditions of the h-CLAT test.

Therefore, based on the results of skin sensitisation, a classification for skin sensitization is warranted under the CLP Regulation (EC) no. 1272/2008 as UN GHS category 1.