Sulphophthalic acid derivatives reaction products of fatty alcohol C12-C14 and sodium hydroxide

Endpoint summary

Description of key information

Skin sensitizer

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

ARE-Nrf2 Luciferase Test (KeratinoSens™)

The purpose of this study was to support a predictive, adverse-outcome-pathway evaluation of whether the test item is likely to be a skin sensitizer using the ARE-Nrf2 Luciferase Test (KeratinoSens™).

The I_maxfor the test item was 6.94 in test 1 and 5.51 in test 2. The I_maxfor both tests was >1.5 fold and statistically significant compared to the DMSO control. The EC_1.5for the test item was 12.40 µg/ml in test 1 and 43.55 µg/ml in test 2. The cellular viability fell below 70 % in both tests. The IC₃₀value was 116.07 µM in test 1 and 135.81 µM in test 2 and the IC₅₀values were 124.23 µM and 155.94 µM in tests 1 and 2, respectively. 

All acceptance criteria for the positive control,cinnamic aldehyde,were met.

It was concluded that the test item gave a positive response in the ARE-Nrf2 Luciferase Test (KeratinoSens™), supporting the prediction that the test item is a skin sensitizer.

in vitro Human Cell Line Activation Test (h-CLAT)

This in vitro Human Cell Line Activation Test (h-CLAT) was performed to assess the dendritic cell activation potential (third key event of a skin sensitization AOP) of the test item.

The test item with an unknown log Pow was tested in 2 independent runs. The cell viability was additionally detected by setting an R1-gate (dead cells are gated-out by staining with 7-AAD) in both h-CLAT runs that was used for the evaluation of the cell viability in this study instead of the calculated cell viabilities.

In the DMSO control, RFI values compared to the medium control of both CD54 and CD86 did not exceed the positive criteria (CD54 ≥ 200 % and CD86 ≥ 150 %). The RFI values of the positive controls (DNCB) for CD54 and CD86 exceeded the positive criteria (CD54 ≥ 200 % and CD86 ≥ 150 %) and the cell viability was >50 %. Except the CD54 RFI value of the positive control (2.0 µg/ml DNCB) in the second h-CLAT run did not exceed the positive criterion (CD54 ≥ 200 %). However, this is considered to be acceptable since the CD54 RFI value of the positive control (3.0 µg/ml DNCB) in the second h-CLAT run exceeded the positive criteria.

In conclusion, the test item with an unknown log Pow activated THP-1 cells under the test conditions of this study. Therefore the test item is considered positive for the third key event of the skin sensitisation Adverse Outcome Pathway (AOP).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the OECD442D and OECD442E results, the substance activates the dendritic cells, have the potential to bind to peptides/protein and can activate the Nrf2 transcription factor and thus satisfies the key event 2 and key event 3. No experimental data is available for the evaluation of the key event 1 (Peptide/protein binding capacity), however, based on the QSAR Toolbox v.4.0 for Protein binding potency Lys and Cys, the substance is reactive. According to the Guidance on the CLP criteria (ECHA, version 5.0, July 2017) validated in vitro/in chemico methods exist with the aim to identify a sensitising potential of a chemical. These include OECD TG442C (Peptide/protein binding), TG442D (keratinocyte response) and TG 442E (monocytic/dendritic cell response). The in vitro/in chemico tests are not regarded as stand alone tests and the result from such a test should be used together with other data in an overall WoE assessment. Further, at present there is no agreed strategy on how to use in vitro/in chemico methods for direct estimation of sensitising potency, but data from such tests can be used in a WoE assessment together with other data in order to assess skin sensitisation potency. According to Chapter R7a-Endpoint specific guidance (ECHA, version 16, July 2017) if information from test method(s) addressing one or two of the key events in column 1 already allows classification and risk assessment according to point 8.3, studies addressing the other key event(s) need not be conducted.

Two out of three in vitro tests result positive.

Based on the above considerations, the substance is considered to be sensitiser and thus a classification as Skin Sensitizer Cat. 1 was attributed according to the CLP Regulation (EC) No.1272/2008.