4-(2-acryloyloxy-ethoxy) benzophenone

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in chemico

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))

Deviations:

no

Remarks:

No deviations that negatively impacted the results of the study ocurred.

GLP compliance:

yes

Type of study:

direct peptide reactivity assay (DPRA)

Test material

Test material information

Constituent 1

Reference substance name:

4-(2-acryloyloxy-ethoxy) benzophenone

EC Number:

836-681-3

Cas Number:

22421-66-5

Molecular formula:

C18H16O4

IUPAC Name:

4-(2-acryloyloxy-ethoxy) benzophenone

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
3M Company, Lot 30029
- Expiration date of the lot/batch:
25 July, 2020
- Purity test date:
25 July, 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
At room temperature, protected from light.
- Stability under storage conditions:
No data
- Stability under test conditions:
No data
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium:
Soluble and stable in acetonitrile.
- Reactivity of the test substance with the solvent/vehicle /test medium (if applicable):
No reaction observed.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The test article was dissolved in acetonitirile.

FORM AS APPLIED IN THE TEST (if different from that of starting material)
: Dissolved in acetonitirile.

In chemico test system

Details on the study design:

Skin sensitisation (In chemico test system) - Details on study design:
The Direct Peptide Reactivity Assay was used to assess the skin sensitization potential of the test article. Synthetic peptides containing cysteine or lysine were reacted with each test article for 24 ± 2 hours. After the incubation period, the extent of peptide depletion was analyzed using High Performance liquid Chromatography {HPLC) coupled with ultra-violet {UV) spectrometric detection.

Results and discussion

Positive control results:

The positive control (Cinnamic Aldehyde) performed as expected and depleted cysteine by 71.49% and lysine by 64.02%.

In vitro / in chemico

Results

Results 1

Key result

Group:

test chemical

Run / experiment:

mean

Parameter:

mean cystein depletion

Value:

99.01 %

At concentration:

100 mM

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

positive indication of skin sensitisation

Results 2

Key result

Group:

test chemical

Run / experiment:

mean

Parameter:

lysine depletion

Value:

61.72 %

At concentration:

100 mM

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

positive indication of skin sensitisation

Results 3

Key result

Group:

test chemical

Run / experiment:

mean

Parameter:

other: Mean Peptide Depletion (%) of Cysteine and Lysine

Value:

80.37

At concentration:

100 mM

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

positive indication of skin sensitisation

Outcome of the prediction model:

high reactivity [in chemico]

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: None observed.

DEMONSTRATION OF TECHNICAL PROFICIENCY: IIVS is technically proficient in running the OECD 442C.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for solvent control: The peak area CV for the solvent controls was less than 15%.
- Acceptance criteria met for positive control: The positive control met the following criteria: The percent peptide depletion for the cysteine peptide exposed to the positive control (cinnamic aldehyde) must be> 60.8% and the SD for the replicates must be< 14.9%. For the lysine peptide, the percent depletion by the positive control must be > 40.2% and < 69.4% and the SD for the replicates must be< 11.6%.
- Acceptance criteria met for variability between replicate measurements: The SD for the test article replicates was < 14.9% for the cysteine depletion and < 11.6% for the lysine depletion.

Applicant's summary and conclusion

Interpretation of results:

Category 1A (indication of significant skin sensitising potential) based on GHS criteria

Conclusions:

Based on the results of the study, MTDID 32918 is predicted to be a sensitizer with high reactivity (99.01% cysteine depletion, 61.72% lysine depletion and 80.37% combined cysteine and lysine depletion) within this stage of the skin sensitization adverse outcome pathway (AOP).

Executive summary:

The sensitization potential of the test article was examined using the Direct Peptide Reactivity Assay (DPRA). The test was performed under GLP conditions and followed the guidance in OECD 442C (2015). The test article was solubilized in acetonitrile to yield a final concentration of 100 mM. The cysteine peptide was prepared at 0.667 mM in cysteine Reaction buffer and the lysine peptide was prepared at 0.667 mM in Lysine Reaction buffer as outlined in OECD 442C. The reaction mix for cysteine peptide had a 1:10 test peptide to reference article ratio (0.5 mM cysteine to 5 mM reference article). The reaction mix for lysine peptide had a 1:50 peptide to reference article ratio (0.5 mM lysine to 25 mM reference article). Reactions for test and reference articles were run in triplicate. Vehicle control reactions were also made with acetonitrile containing no reference or test articles. After 24 ± 2 hours incubation DPRA samples were assayed for peptide depletion via HPLC/UV. The separations module used in this assay was a Waters 2695 HPLC system. This system consisted of a solvent management system for the mobile phases and a sample management system for the test article and controls. The HPLC system was coupled to a photodiode array detector set at 220 nm. The dimensions of the column used were 2.1 mm x 100 mm x 3.5 micron. The test article depleted 99.01% cysteine and 61.72% lysine for a combined depletion (cysteine and lysine) of 80.37%. Per the DPRA prediction models, MTDID 32918 was predicted to have high reactivity in both the combined depletion model (42.48-100%) as well as the cysteine depletion model (98.25-100%). Based on the results of the study, MTDID 32918 is predicted to be a sensitizer with high reactivity (99.01% cysteine depletion, 61.72% lysine depletion and 80.37% combined cysteine and lysine depletion) within this stage of the skin sensitization adverse outcome pathway (AOP).