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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:
weight of evidence
Study period:
The laboratory phase of the study was conducted from 18 December 2014 to 25 June 2015 at the Institute for In Vitro Sciences, Inc.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
Deviations:
no
GLP compliance:
yes
Type of study:
direct peptide reactivity assay (DPRA)
Justification for non-LLNA method:
Non animal test method - OECD approved. The Direct Peptide Reactivity assay provides an in vitro procedure used for supporting the discrimination between skin sensitizers and non sensitizers in accordance with the UN GHS. According to REACH, In vivo methods can only be used if the in chemico or in vitro test methods are not adequate for the substance or cannot be used for classification and risk assessment.

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(2-methylpropyl)benzyl propyl ether
EC Number:
826-704-5
Cas Number:
1631962-93-0
Molecular formula:
C14H22O
IUPAC Name:
4-(2-methylpropyl)benzyl propyl ether
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
-Source and lot/batch No of test material: Sponsor Lot No. RB272-88
-Expiration date of the lot/batch: 31 December 2015
-Purity: >99%
-Appearance: clear colorless liquid
-Storage condition of test material: Ambient temperature, dark

In chemico test system

Details on the study design:
The DPRA is an in chemico method which quantifies the remaining concentration of cysteine- or lysine-containing peptide following 24 hours incubation with the test chemical at 25+/- 2.5ºC. The synthetic peptides contain phenylalanine to aid in the detection. Relative peptide concentration is measured by high performance liquid chromatography (HPLC) with gradient elution and UV detection at 220 nm. Cysteine and lysine peptide percent depletion values are then calculated and used in a prediction model which allows assigning the test chemical to one of four reactivity classes used to support the discrimination between sensitisers and non-sensitisers.

Results and discussion

Positive control results:
Cinnamic aldehyde % peptide depletion for cysteine and lysine were 81.8% and 63.0%, respectively.

In vitro / in chemico

Results
Key result
Run / experiment:
other: Single run
Parameter:
other: % mean peptide depletion of cysteine and lysine
Value:
10.5
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Prediction Model:

Mean Peptide Depletion of Cysteine and Lysine (%)

DPRA Prediction

Peptide Depletion of Cysteine (%)

0 - 6.38

Minimal Reactivity

Negative

0 - 13.89

Minimal Reactivity

6.39 - 22.62

Low Reactivity

Positive

13.90 - 23.09

Low Reactivity

22.63- 42.47

Moderate Reactivity

23.10- 98.24

Moderate Reactivity

42.48 - 100

High Reactivity

98.25 - 100

High Reactivity

DPRA Results:

IIVS Test Article Number

Sponsor’s Designation

% Mean Peptide Depletion

% Mean Peptide Depletion of Cysteine and Lysine

Reactivity (Cysteine and Lysine)

Potential Sensitizer?

Cysteine

Lysine

14AQ07

FRET 11-0539

17.0

4.1

10.5

Low

Yes

Positive Control

Cinnamic Aldehyde

81.8

63.0

 

 

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
Based on the results of the Direct Peptide Reactivity Assay for the test article, FRET 11-0539 (Lot# RB272-88), was predicted to be a potential skin sensitizer.
Executive summary:

The Direct Peptide Reactivity Assay was used to assess the skin sensitization potenetial of the test substance, FRET 11-0539 (Lot# RB272 -88). The skin sensitization potential of the test substance was evaluated by measuring the depletion of synthetic peptides containing either cysteine or lysine amino acids following incubation with the test substance, using the protocol that is consistent with the OECD Test Guideline 442C “In ChemicoSkin Sensitization: Direct Peptide Reactivity Assay (DPRA)”[1]. Based upon the results of this study, the test substance, FRET 11-0539, was classified as a skin sensitizer.


[1]           OECD Test Guideline 442C “In ChemicoSkin Sensitization: Direct Peptide Reactivity Assay (DPRA)”, Adopted 4 February 2015.