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EC number: 217-316-1
CAS number: 1809-19-4
Not a skin sensitiser.
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
(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.
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.
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:
Peptide Reactivity Assay (DPRA) addresses AOP Key Event 1:
Luciferase Test Method (KeratinoSensTM) addresses AOP Key Event 2:
Human Cell Line Activation Test (h-CLAT) addresses AOP Key Event 3:
Monocytic /Dendritic cell response.
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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