Registration Dossier

Administrative data

Description of key information

Not a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

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

Three in vitro experimental studies were available which assessed the sensitising potential of the test item. Specifically, these three studies examine the ability of the test item to induce peptide/protein bonding (Adverse Outcome Pathway (AOP) Key Event 1, in a DPRA), a keratinocyte response (AOP Key Event 2, in an ARE Nrf2 LuSens assay) and a monocytic/dendritic cell response (AOP Key Event 3, in a h-CLAT). The following experimental findings are reported:

(1) Potential to induce peptide/protein bonding was evaluated in a Cysteine 1:10/Lysine 1:50 prediction model of the Direct Peptide Reactivity Assay (DPRA), according to the OECD Guideline 442C (2015). The cysteine depletion value was 1.89%, the lysine depletion value was 0.99% and the mean of the cysteine and lysine depletion values was 1.44%. The test item was considered to be negative with no or minimal reactivity in the Direct Peptide Reactivity Assay, indicating that it induces no or low molecular interaction via skin proteins, via peptide/protein bonding.

(2) The test item's potential to activate the Nrf2 transcription factor was assessed in the genetically modified keratinocyte cell-line ARE Nrf2 Luciferase “LuSens” Assay (Bauch et al. 2012), according to the OECD Guideline 442D (2015). No substantial, reproducible, dose-dependent increase in luciferase induction above 1.5-fold was observed up to the maximal test item concentration of 200 mM in two experiments. Therefore, the assay was negative and the test item is not considered to have the potential to activate Nrf2 transcription factor and does not induce a keratinocyte response.

(3) A Human Cell Line Activation Test (h-CLAT) was performed on the human monocytic leukaemia cell line (THP-1 cells), according to a method equivalent to the OECD Guideline 442E. 10 µg/mL test item resulted in RQ values of less than two among both CD86 and CD54 gene expression, therefore it can be considered negative in this h-CLAT and does not have the potential to activate a dendritic cell response under the conditions of the assay.

Additionally, a QSAR evaluation of the sensitisation potential of the substance was performed using QSAR Toolbox 4.2. By analysing the general reactivity of the molecule, no alerts were generated that may trigger concern for sensitisation potential. An analogous substance (SC02) was registered as a mild sensitiser as it had a positive result from a GPMT. However, this result is questionable as it records also a high positive rate among control animals. Therefore, the QSAR prediction supports the three negative in vitro test results. Further, according to producers of the substance, no incidences of sensitisation have been recorded among exposed workers have been reported at the manufacturing site.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the CLP Regulation (EC) no. 1272/2008, a skin sensitiser is an agent that will lead to an allergic response in susceptible individuals following skin contact. As a consequence of a secondary - usually organ-specific - subsequent re-exposure, adverse health effects occur on the skin (allergic contact dermatitis). Skin sensitisers are classified in Category 1 with the signal word “warning” and the Hazard statement H317 “May cause an allergic skin reaction”. Where data are sufficient, skin sensitisers can be divided into sub-categories. If data are not sufficient for sub-categorisation, Category 1 must be chosen. The CLP (and UN GHS) criteria for classifying sensitisers are based on standard animal data and human data; data obtained from non-standard methods such as read-across or in vitro/in chemico test methods may be used in combination in a Weight of Evidence approach.

Indicators of potency of a substance can be obtained fromin chemico/in vitrotesting; specifically, the following tests may be accepted to fulfill the requirements of Annex VII:

(i) Direct Peptide Reactivity Assay (DPRA) addresses AOP Key Event 1: Peptide/protein binding

(ii) ARE-Nrf2 Luciferase Test Method (KeratinoSensTM) addresses AOP Key Event 2: Keratinocyte response

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

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 potential skin sensitiser but rather in combination in a Weight of Evidence approach.

Based on the negative DPRA (molecular interaction with skin proteins), negative LuSens assay (inflammatory response in keratinocytes) and negative h-CLAT (dendritic cell activataion), the data is sufficient for a Weight of Evidence approach as all three key event requirements for Article 13(3) are fulfilled. Using a Weight of Evidence approach, the test item can be considered not a potential skin sensitiser. Data is not sufficient for classification, therefore, the test item is not classified as a skin sensitiser according to the CLP Regulation (EC) no. 1272/2008. This is supported by the absense of alerts for sensitisation potential using QSAR Toolbox 4.0.