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Diss Factsheets

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
Study period:
13 Jun 2017 - 27 Jun 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
Version / remarks:
4 February 2015
Deviations:
no
GLP compliance:
yes
Type of study:
direct peptide reactivity assay (DPRA)

Test material

Constituent 1
Chemical structure
Reference substance name:
4-phenylbenzophenone
EC Number:
218-345-2
EC Name:
4-phenylbenzophenone
Cas Number:
2128-93-0
Molecular formula:
C19H14O
IUPAC Name:
{[1,1'-biphenyl]-4-yl}(phenyl)methanone
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Sponsor; 20161118
- Expiration date of the batch: 17 November 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature protected from light
- Solubility and stability of the test substance in the solvent/vehicle: Yes, maximum temperature: 90°C; Solubility of the test item in an appropriate solvent was assessed before performing the DPRA.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No reactivity with the vehicle.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
-Preparation of test item: No correction for the purity/composition of the test item was performed.
- Final preparation of a solid: For the cysteine and lysine reactivity assay, respectively, 42.67 mg of and 26.05 mg Omnirad 4 PBZ were pre-weighed into a clean amber glass vial and dissolved, just before use, in 1652 µL and 1009 µL ACN to obtain 100 mM solutions.

FORM AS APPLIED IN THE TEST (if different from that of starting material)
Liquid

Results and discussion

Positive control results:
Cinnamic aldehyde - The mean Percent SPCC Depletion for the positive control cinnamic aldehyde was 78.1% ± 1.8%. This was within the acceptance range of 60.8% to 100% with a SD that was below the maximum (SD <14.9%).

In vitro / in chemico

Resultsopen allclose all
Key result
Parameter:
other: SPCC depletion
Value:
0.6
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of skin sensitisation
Key result
Parameter:
other: SPCL depletion
Value:
2.5
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
not determinable
Other effects / acceptance of results:
Acceptability of the Cysteine Reactivity Assay:
The correlation coefficient (r2) of the SPCC standard calibration curve was 0.996. Since the r2 was >0.99, the SPCC standard calibration curve was accepted.
The means of Reference Control samples A and C were both within the acceptance criteria of 0.50±0.05 mM. This confirms the suitability of the HPLC system and indicates that the solvent (ACN) used to dissolve the test item did not impact the Percent SPCC Depletion.
The Coefficient of Variation (CV) of the peptide areas for the nine Reference Controls B and C was 2.3%. This was within the acceptance criteria (CV <15.0%) and confirms the stability of the HPLC run over time.
The mean area ratio (A220/A258) of the Reference Control samples was 18.78. The mean A220/A258 ratio ± 10% range was 16.90-20.65. Each sample showing an A220/A258 ratio within this range gives an indication that co-elution has not occurred.
The mean Percent SPCC Depletion for the positive control cinnamic aldehyde was 78.1% ± 1.8%. This was within the acceptance range of 60.8% to 100% with a SD that was below the maximum (SD <14.9%).

Acceptability of the Lysine Reactivity Assay:
The correlation coefficient (r2) of the SPCL standard calibration curve was 0.991. Since the r2 was >0.99, the SPCL standard calibration curve was accepted.
The means of Reference Control samples A and C were both within the acceptance criteria of 0.50±0.05 mM. This confirms the suitability of the HPLC system and indicates that the solvent (ACN) used to dissolve the test item did not impact the Percent SPCL Depletion.
The CV of the peptide areas for the nine Reference Controls B and C was 2.2%. This was within the acceptance criteria (CV <15.0%) and confirms the stability of the HPLC run over time.
The mean area ratio (A220/A258) of the Reference Control samples was 14.32. The mean A220/A258 ratio ± 10% range was 12.89-15.75. Each sample showing an A220/A258 ratio within this range gives an indication that co-elution has not occurred.
The mean Percent SPCL Depletion for the positive control cinnamic aldehyde was 60.9% ± 1.9%. This was within the acceptance range of 40.2% to 69.0% with a SD that was below the maximum (SD <11.6%).

Any other information on results incl. tables

 Test item  SPCC depletion   SPCL depletion    DPRA prediction and reactivity classification
   Mean  ± SD  Mean   ± SD Mean of SPCC and SPCL depletion        Cysteine 1:10 / Lysine 1:50 prediction model
  Omnirad 4 -PBZ  0.6%  1.1%  2.5%  2.7%  1.5%  Negative: No or minimal reactivity

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
In conclusion, this DPRA test is valid. The substance was negative in the DPRA and was classified in the “no or minimal reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since precipitation was observed upon addition of the test item to the SPCL peptide solution,it is not certain how much test item remained in the solution to react with the SPCL peptide. Consequently, this SPCL result is uncertain and should be interpreted with due care.
Executive summary:

An In Chemico Skin Sensitization: Direct Peptide Reactivity Assay (DPRA) was employed to evaluate the skin sensitisation potential of the substance by determining the reactivity of the substance towards model synthetic peptides containing either cysteine or lysine, and to categorize the test item in one of four classes of reactivity for supporting the discrimination between skin sensitizers and non-sensitizers. The substance was used neat as provided and the study met the acceptance criteria. In the cysteine reactivity assay the test item showed 0.6% SPCC depletion while in the lysine reactivity assay the test item showed 2.5% SPCL depletion. The mean of the SPCC and SPCL depletion was 1.5% and as a result Omnirad 4-PBZ was classified in the “no or minimal reactivityclass” when using the Cysteine 1:10 / Lysine 1:50 prediction model. However, since precipitate formation was observed in the lysine incubation samples after incubation, the % SPCL depletion might be underestimated. Consequently, this SPCL result is uncertain and should be interpreted with due care.