4-(2-acryloyloxy-ethoxy) benzophenone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

2017

Deviations:

no

Remarks:

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

GLP compliance:

yes

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 II
- Expiration date of the lot/batch:
25 July, 2020
- Purity test date:
03 May, 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
At room temperature protected from light
- Stability under storage conditions:
Stable
- Stability under test conditions:
Stable

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

FORM AS APPLIED IN THE TEST: Neat

Test animals / tissue source

Species:

cattle

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: Bovine eyes from young cattle were obtained from the slaughterhouse (Vitelco, 's Hertogenbosch, The Netherlands), where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter.
- Number of animals: No data
- Characteristics of donor animals (e.g. age, sex, weight): No data
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): Eyes were collected and transported in physiological saline in a suitable container under cooled conditions.
- Time interval prior to initiating testing: No data
- indication of any existing defects or lesions in ocular tissue samples: Only eyes with no detectable defects were utilized.
- Indication of any antibiotics used: No data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 uL

Duration of treatment / exposure:

10 minutes at 32 C

Duration of post- treatment incubation (in vitro):

120 minutes at 32 C

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION AND PREPARATION OF CORNEAS
Bovine eyes from young cattle were obtained from the slaughterhouse (Vitelco, 's Hertogenbosch, The Netherlands), where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter. The eyes were checked for unacceptable defects, such as opacity, scratches, pigmentation and neovascularization by removing them from the physiological saline and holding them in the light. Those exhibiting defects were discarded. The isolated corneas were stored in a petri dish with cMEM (Earle’s Minimum Essential Medium (Life Technologies, Bleiswijk, The Netherlands) containing 1% (v/v) L-glutamine (Life Technologies) and 1% (v/v) Foetal Bovine Serum (Life Technologies)). The isolated corneas were mounted in a corneal holder (one cornea per holder) of BASF (Ludwigshafen, Germany) with the endothelial side against the O-ring of the posterior half of the holder. The anterior half of the holder was positioned on top of the cornea and tightened with screws. The compartments of the corneal holder were filled with cMEM of 32 C. The corneas were incubated for the minimum of 1 hour at 32 C. After the incubation period, the medium was removed from both compartments and replaced with fresh cMEM. Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany). The opacity of each cornea was read against a cMEM filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used. Three corneas were selected at random for each treatment group.

QUALITY CHECK OF THE ISOLATED CORNEAS
Only eyes with no detectable defects were utilized.

NUMBER OF REPLICATES
3

NEGATIVE CONTROL USED
Yes, physiological saline

POSITIVE CONTROL USED
Yes, ethanol

APPLICATION DOSE AND EXPOSURE TIME
750 uL, 10 minutes

TREATMENT METHOD
Open chamber

POST-INCUBATION PERIOD:
Yes, 120 minutes

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period:
- POST-EXPOSURE INCUBATION:

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany).
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

in vitro irritation score

Run / experiment:

1

Value:

-1.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

in vitro irritation score

Run / experiment:

2

Value:

-0.7

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

in vitro irritation score

Run / experiment:

3

Value:

-0.1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: None

DEMONSTRATION OF TECHNICAL PROFICIENCY: The laboratory that conducted the study is technically proficient in conducting the OECD 437 BCOP assay.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Met
- Acceptance criteria met for positive control: Met

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean In Vitro Irritancy Score (IVIS) of MTDID 32918 was -0.8. In conclusion, since MTDID 32918 induced an IVIS of <=3, no classification is required for eye irritation or serious eye damage. MTDID 32918 is not irritating to the eye.

Executive summary:

The ocular irritation potential of MTDID 32918 was evaluated in the Bovine Corneal Opacity and Permeability Test. The study was conducted according to OECD 437 in compliance with OECD GLP. Corneas (n=3) were exposed to 0.75mL of MTDID 32918 undiluted, negative control (physiological saline), or positive control (ethanol) for 10 minutes at 32 C. Following the exposure period the corneas were washed and incubated for 120 minutes at 32 C. Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany). Corneal permeability was evaluated by passage of sodium fluorescein dye through the corneas measured with the aid of microtiter plate reader (OD490). Individual In Vitro Irritancy Scores (IVIS) were -1.5, -0.7, and -0.1. The mean In Vitro Irritancy Score (IVIS) of MTDID 32918 was -0.8. Based on a mean IVIS of -0.8, no classification is required for eye irritation or serious eye damage. MTDID 32918 is not irritating to the eye.