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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Skin sensitisation (in vitro):

1. Direct Peptide Reactivity Assay (DPRA): Negative (OECD 442C/GLP)

2.ARE-Nrf2 luciferase test assay: Inconclusive (OECD 442D/GLP)

3. Human Cell Line Activation Test (h-CLAT) assay: Positive (OECD442E/GLP)

The combined results of the 3 in vitro tests were not conclusive so read-across was performed to a LLNA test from Phenethyl alcohol (CAS No. 60 -12 -8).

Read-across from Phenethyl alcohol - Skin sensitisation (in vivo): Not sensitisting (OECD429, LLNA/GLP)

Key value for chemical safety assessment

Skin sensitisation

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

Skin sensitisation (in vitro):

Three in vitro skin sensitisation assays are available: Direct Peptide Reactivity Assay (DPRA), ARE-Nrf2 luciferase test assay and Human Cell Line Activation Test (h-CLAT) assay.

Direct Peptide Reactivity Assay (DPRA)

In an in chemico skin sensitization: direct peptide reactivity assay (DPRA; OECD 442C/GLP), DMPEC (99.7%) in acetonitrile was evaluated by monitoring peptide depletion following a 24-hour contact between the test item and synthetic cysteine and lysine peptides. At the end of the incubation, the concentrations of residual peptides were evaluated by HPLC with Ultra-Violet detection at 220 nm. Peptide reactivity was reported as percent depletion based on the peptide peak area of the replicate injection and the mean peptide peak area in the three relevant reference control sample C in acetonitrile. The positive control was cinnamaldehyde.

The acceptance criteria for the calibration curve samples, the reference and positive controls as well as for the study samples were satisfied. The study was therefore considered to be valid. Analysis of the chromatograms of the co-elution samples indicated that the test item did not co-elute with either the lysine or the cysteine peptides. As a result, the mean percent depletion values calculated for each peptide were 0.75% for the cysteine peptide and 0.01% for the lysine peptide. The mean of the percent cysteine and percent lysine depletions was equal to 0.38%. However, since precipitate was observed at the end of the incubation with the peptides, the peptides depletion may be underestimated.  Since the mean of the percent cysteine and percent lysine depletions was < 6.38%, the test item was considered to have no or minimal reactivity. Therefore, the DPRA prediction for DMPEC is considered as negative, though with limitations as the test item precipitates with the peptides at the end of the incubation.

ARE-Nrf2 luciferase test assay

In an in vitro skin sensitisation: ARE-Nrf2 luciferase test method assay; (OECD 442D/GLP), DMPEC (99.7%) was evaluated for its potential to activate the Nrf2 transcription factor in KeratinoSens cells. DMPEC (in 1% DMSO in DMEM culture medium) was applied to KeratinoSens cells at concentrations from 0.98 to 2000 µM for 48 hrs. Luciferase production was measured by flash luminescence. Cytotoxicity was measured using an MTT assay. The positive control was 2 trans-Cinnamaldehyde.

In the first run, no precipitate/emulsion was observed in any test item-treated wells at the end of the 48-hour treatment period. No noteworthy decrease in cell viability was noted at any tested concentrations (i.e. cell viability > 70%), thus no IC30 or IC50 was calculated. No statistically significant gene-fold induction above the threshold of 1.5 was noted in comparison to the negative control at any tested concentrations. Moreover, the Imax value was < 1.5 (i.e. 1.33). Thus, the evaluation criteria for a negative response were met in this first run. In the second run, no precipitate/emulsion was observed in any test item-treated wells at the end of the 48-hour treatment period. No noteworthy decrease in cell viability was noted at any tested concentrations (i.e. cell viability > 70%), thus no IC30 or IC50 was calculated. Statistically significant gene-fold inductions above the threshold of 1.5 were noted in comparison to the negative control at concentrations ≥ 500 µM with an apparent dose-response relationship; the Imax was 1.87 and the calculated EC1.5 was 390.40 µM. Thus, the evaluation criteria for a positive response were fully met in this second run. The evaluation criteria for a negative response were met in the first run and those for a positive response were fully met in the second run. Since the results of the two runs were not concordant, a third run should have been performed to conclude definitively on the profile of test item. At the request of the Sponsor, no third run was performed, and the final outcome is therefore inconclusive.

Human Cell Line Activation Test (h-CLAT) assay

In an in vitro skin sensitisation: human Cell Line Activation Test (h-CLAT; 45135TIH), DMPEC (99.7%) was evaluated by the ability to induce an increase in cell surface marker expression (CD54, CD86) in THP-1 cells. DMPEC (in 0.2% DMSO in cRPMI culture medium) was applied to THP-1 cells at concentrations from 92.95 to 333.05 μg/mL for 24 hrs. Flow cytometry analysis was carried out on IgG1-FITC, CD86-FITC and CD54-FITC antibody labelled cells. The % Relative Fluorescence Index (%RFI) for CD86 and CD54 expression for each tested concentration was then calculated. Propidium Iodide was used for viability discrimination. The positive controls were 2,4-Dinitrochlorobenzene and Nickel Sulfate.

All acceptance criteria for controls and test item were reached in each run. The study was therefore considered to be valid. The results from run A were (i) Post-treatment observations: no precipitate/emulsion was noted in treated wells (ii) Cytotoxicity was noted at the concentration of 333.05 µg/mL, (iii) RFI CD86 did not exceed the positivity threshold at any concentrations and (iv) RFI CD54 exceeded the positivity threshold at all concentrations except the highest one due to cytotoxicity. The results from run B were (i) Post-treatment observations: no precipitate/emulsion was noted in treated wells (ii) No cytotoxic effect (i.e. cell viability < 50%) was noted at any tested concentration (iii) RFI CD86 did not exceed the positivity threshold at any concentrations and (iv) RFI CD54 exceeded the positivity threshold at concentrations ≥ 111.54 µg/mL. Both runs A and B were therefore considered positive for CD54.

As the results of the 3 in vitro tests were not conclusive for the skin sensitisation endpoint and to avoid any animal testing, read-across was performed to a LLNA test from Phenethyl alcohol (CAS No. 60 -12 -8).

Read-across from Phenethyl alcohol - Skin sensitisation (in vivo):

In a dermal sensitization study (OECD 429/GLP) with Phenylethyl Alcohol (99.9%; in 25% ethanol/75% diethylphthalate), young adult CBA/Ca/Ola/Hsd mice (4 females) were tested in the Local Lymph Node Assay. The reliability of the test system was confirmed by the most recent positive control assay (Hexylcinnamaldehyde in acetone; April 2003). The positive control, Hexylcinnamaldehyde, gave the appropriate response. Treatment with Phenylethyl Alcohol at 2.5, 5, 10, 25 and 50% w/v in 25% ethanol/75% diethylphthalate resulted in stimulation indices of 1.06, 1.01, 0.87, 0.95 and 0.84  respectively. The estimated concentration giving rise to a 3 fold increase in lymphocyte proliferation (EC3) was greater than 50% w/v (greater than 12500µg/cm2). There was no effect on body weights during the study. In this study, Phenylethyl Alcohol is not a dermal sensitizer. DMPEC is also predicted not to be a dermal sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information in the dossier, the substance DMPEC (CAS No. 103-05-9) does not need to classified  for skin sensitisation when the criteria outlined in Annex I of 1272/2008/EC and Annex I of 286/2011/EC are applied, based on the results of the read-across study from PEA (CAS No. 60 -12 -8).