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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in chemico
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
GLP compliance:
yes (incl. QA statement)
Type of study:
other: Direct Peptide Reactivity Assay (DPRA)

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(4-methoxyphenyl)-2-methyl -2-morpholinopropan-1-one
EC Number:
849-913-3
Cas Number:
93216-90-1
Molecular formula:
C15H21NO3
IUPAC Name:
1-(4-methoxyphenyl)-2-methyl -2-morpholinopropan-1-one
Test material form:
solid

In chemico test system

Details on the study design:
The OECD AOP (The adverse outcome pathway for skin sensitisation) is initiated by key event 1 (Covalent interaction with skin proteins), which is followed sequentially by three key events (KE): (KE2) keratinocyte activation, (KE3) dendritic cell activation, and (KE4) proliferation of antigen-specific T cells. However, none of the assays addressing the different KEs is currently accepted as stand-alone test method and may not be sufficient to conclude on the presence or absence of skin sensitisation potential of chemicals. But supports the discrimination between skin sensitisers and non sensitisers in combination with other complementary data.
The direct peptide reactivity assay (DPRA) addresses the molecular initiating event (KE1) of the AOP. It is an in chemico assay to quantify the depletion of synthetic model peptides caused by known amounts of the test item measured by HPLC.
This study is performed in order to evaluate the reactivity of 1-(4-methoxyphenyl)-2-methyl-2-(morpholin-4-yl)propan-1-one towards cysteine and lysine containing peptides. The peptide depletion compared to the solvent controls is calculated and leads to a DPRA prediction (reactive/positive or non-reactive/negative) that could be used to support the discrimination between skin sensitisers and non-sensitisers. Additionally, an assignment to one of four reactivity classes could be made in order to possibly support a potency assessment.
The DPRA is part of a tiered strategy for the evaluation of the skin sensitization potential. Thus, all data generated with the present Test Guideline OECD 442C and EU-Method B.59 should be used in the context of an integrated approach to testing and assessment (IATA).

Results and discussion

In vitro / in chemico

Resultsopen allclose all
Key result
Run / experiment:
other: Calculated peptide depletion values for the Cys-Peptide
Parameter:
other: Depletion [%]
Value:
1.51
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Key result
Run / experiment:
other: Calculated peptide depletion values for the Lys-Peptide
Parameter:
other: Depletion [%]
Value:
1.51
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
The DPRA prediction is “negative” according to the Cysteine 1:10/Lysine 1:50 pre-diction model. Thus, under the experimental conditions reported, the test item 1-(4-methoxyphenyl)-2-methyl-2-(morpholin-4-yl)propan-1-one shows no or minimal to-wards the two model synthetic peptides.
This assignment supports the discrimination between skin sensitisers and non-sensitisers in the framework of an integrated approach (IATA).
For sensitising potency assessment within an IATA, the test item 1-(4-methoxyphenyl)-2-methyl-2-(morpholin-4-yl)propan-1-one could be assigned to the reactivity class that covers no or minimal reactivity under the conditions of this study.

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