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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 Nov 2021
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2022
Report date:
2022

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:
adopted 26 June 2020
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethoxydimethylsilane
EC Number:
214-189-4
EC Name:
Dimethoxydimethylsilane
Cas Number:
1112-39-6
Molecular formula:
C4H12O2Si
IUPAC Name:
dimethoxydimethylsilane
Test material form:
liquid

Test animals / tissue source

Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: slaughterhouse (Vitelco, 's Hertogenbosch, The Netherlands)
- Storage, temperature and transport conditions of ocular tissue: Eyes were collected and transported in physiological saline in a suitable container under cooled conditions.
- Time interval prior to initiating testing: Eyes were tested the day of arrival in the laboratory.
- Indication of any existing defects or lesions in ocular tissue samples: no
- Indication of any antibiotics used: no
- Quality check of the isolated corneas: 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.
- Selection and preparation of corneas: The isolated corneas were stored in a petri dish with cMEM (Eagle’s Minimum Essential Medium containing 1% (v/v) L-glutamine and 1% (v/v) Foetal Bovine Serum).
The isolated corneas were mounted in a corneal holder (one cornea per holder) 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 ± 1°C. The corneas were incubated for the minimum of 1 hour at 32 ± 1°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. 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.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 750 µL
- Concentration: neat

Negative and positive control
- Amount(s) applied: 750 µL
Duration of treatment / exposure:
10 ± 1 min at 32 ± 1°C
Duration of post- treatment incubation (in vitro):
120 ± 10 minutes at 32 ± 1°C
Number of animals or in vitro replicates:
triplicates for each treatment and control groups
Details on study design:
TREATMENT METHOD:
The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control or test item was introduced onto the epithelium of the cornea. The holders were slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the control or the test item over the entire cornea. Corneas were incubated in a horizontal position for 10 ± 1 minutes at 32 ± 1°C.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After the incubation the solutions were removed and the epithelium was washed with MEM with phenol red (Eagle’s Minimum Essential Medium, Life Technologies) and thereafter with cMEM. Possible pH effects of the test item on the corneas were recorded. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM. Subsequently the corneas were incubated for 120 ± 10 minutes at 32 ± 1°C.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: The opacity of a cornea was measured by the diminution of light passing through the cornea.
The light was measured as illuminance (I = luminous flux per area, unit: lux) by a light meter.
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of a microtiter plate reader (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS) = mean opacity value + (15 x mean OD490 value)

DECISION CRITERIA:
Test substance with an IVIS > 55 was regarded as serious eye damage and labelled Category 1 according to CLP/EPS/GHS.
Test substance with an IVIS ≤ 3 was regarded as non-irritant and labelled in no category.
Test substance with an IVIS > 3; ≤ 55 no prediction can be made.

Results and discussion

In vitro

Results
Irritation parameter:
in vitro irritation score
Remarks:
mean value of 3 corneas
Run / experiment:
10 min exposure
Value:
16
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
no definite prediction on ocular irritation can be made
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: The corneas treated with the positive control and test item were observed to be turbid after the 10 min treatment.
- pH effects: No pH effects of the negative and positive controls as well as of the test item were observed on the rinsing of the corneas with MEM (with phenol red).


ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes for two negative controls: the negative control responses resulted in opacity and permeability values that were less than the upper limits of the laboratory historical range. One of the negative control eyes was excluded from the analysis since the permeability was increased. This resulted in an IVIS above the cut-off value of 3.0. This had no impact on the study validity.
- Acceptance criteria met for positive control: yes: the positive control gave an in vitro irritancy score that fell within two standard deviations of the current historical mean.

Any other information on results incl. tables

Table 1: Summary of Opacity, Permeability and In Vitro Scores

Treatment

Mean

Opacity1

Mean

Permeability1

Mean In vitro Irritation Score1, 2

Negative control

-0.3

-0.018

-0.6

Positive control

(Ethanol)

19

1.110

36

Test item

8.7

0.474

16

1  Calculated using the negative control corrected mean opacity and mean permeability values for the positive control and test item.

2  In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).

 

Table 2: Opacity Score

Treatment

Opacity before treatment

Opacity after treatment

Final Opacity1

Negative control corrected Final Opacity2

Mean Final Opacity

Negative control

3.7*

2.5*

-1.2*

 

 

-0.3

 

1.9

2.1

0.2

1.9

1.0

-0.9

Positive control

3.4

22.5

19.1

19

 

19

 

1.5

17.5

15.9

16

3.5

25.8

22.3

22

Test item

2.7

10.5

7.8

7.8

 

8.7

2.2

11.2

9.0

9.0

0.9

10.0

9.1

9.1

Calculations are made without rounding off.

1   Final Opacity = Opacity after treatment – Opacity before treatment.

2   Negative control corrected Final Opacity = Final opacity – Mean final opacity negative control.

3  In case the mean final opacity of the negative control is below zero, no correction will be made.

* Excluded from analysis.

 

Table 3: Permeability Score Individual Values (Uncorrected)

Treatment

Dilution factor

OD490

OD490

OD490

Average OD

Final OD

Mean final negative control

1

2

3

Negative control

1

0.583*

0.589*

0.587*

0.586*

0.586*1

-0.018

1

-0.011

-0.020

-0.018

-0.016

-0.016

1

-0.022

-0.019

-0.020

-0.020

-0.020

Positive control

1

1.381

1.378

1.380

1.380

1.380

 

1

1.051

1.042

1.040

1.044

1.044

 

1

0.853

0.852

0.852

0.852

0.852

 

Test item

1

0.400

0.395

0.394

0.396

0.396

 

1

0.477

0.477

0.481

0.478

0.478

 

1

0.496

0.493

0.486

0.492

0.492

 

*  Excluded from analysis.

Calculations are made without rounding off.

 

Table 4: Permeability Score Individual Values (Corrected)

Treatment

Dilution factor

Negative control corrected OD490 1#

Negative control corrected OD490 2#

Negative control corrected OD490 3#

Negative control corrected OD490

Average

Negative control corrected final

OD490

Average OD

Positive control

1

1.399

1.396

1.398

1.398

1.398

1.110

1

1.069

1.060

1.058

1.063

1.063

1

0.871

0.870

0.870

0.871

0.871

Test item

1

0.418

0.413

0.412

0.415

0.415

0.474

1

0.495

0.495

0.499

0.497

0.497

1

0.514

0.511

0.504

0.510

0.510

Calculations are made without rounding off.

OD490 values corrected for the mean final negative control permeability (-0.018).

 

Table 5: In Vitro Irritancy Score

Treatment

Final Opacity2

Final OD4902

In vitro Irritancy Score1

Negative control

-1.2*

0.586*

7.6*

0.2

-0.016

0.0

-0.9

-0.020

-1.2

Positive control

19

1.398

40

16

1.063

32

22

0.871

35

Test item

7.8

0.415

14.1

9.0

0.497

16.5

9.1

0.510

16.7

1  In vitro irritancy score (IVIS) = opacity value + (15 x OD490 value).

2  Positive control and test item are corrected for the negative control.

* Excluded from analysis.

 

 

Table 6: Historical Control Data for the BCOP Studies

 

Negative control

Positive control

 

Opacity

Permeability

In vitro Irritancy Score

In vitro Irritancy Score

Min

-2.50

-0.017

-2.50

26

Max

3.70

0.065

4.00

86

Mean

0.86

0.002

0.89

50

SD

1.26

0.009

1.28

14

n

143

143

143

143

SD = Standard deviation

n = Number of observations

The above mentioned historical control data range of the controls were obtained by collecting all data over the period of May 2018 to May 2021.

 

Applicant's summary and conclusion

Interpretation of results:
other: non-corrosive
Conclusions:
In a BCOP test according to OECD TG 437 and in compliance with GLP, dimethoxy(dimethyl)silane induced ocular irritation as assessed for both endpoints (corneal opacity and
permeability), resulting in a mean in vitro irritancy score (IVIS) of 16 after 10 minutes of treatment. Since the test substance induced an IVIS > 3 ≤ 55, no definitive prediction on ocular irritation can be made.