Oxybis(2,1-ethanediyloxy-2,1-ethanediyl)diacrylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

One old rabbit study report was available to evaluate the eye irritation/corrosion potential of tetraethyleneglycol diacrylate (TNO 1978). In this study, only one rabbit was exposed to the test substance and the observation period was of 7 days after exposure. The scores (mean 24-48-72hr) showed irritating effects. The cornea opacity score increased between 72h and 7th day after exposure (score 2 > 3) showing a corrosive effect. As the study was finished 7 days after exposure instead of 21 days as required by the test guideline OECD 405, it is not possible to conclude if the substance is eye irritating or eye corrosive. The other limitation of this study is the absence of information on substance purity.
An in vitro eye corrosion test was performed in order to determine the correct classification for human hazard assessment. The results of this OECD 437 (BCOP) test were negative with an IVIS score of 1.2%. With this result, no GHS classification is required.
The registrants are surprised of the non-classification for eye irritation and decided to perform a new in vivo study according to the OECD TG 405 in order to be sure that no classification of the substance is needed for eye irritation.

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oxybis(2,1-ethanediyloxy-2,1-ethanediyl)diacrylate

EC Number:

241-789-3

EC Name:

Oxybis(2,1-ethanediyloxy-2,1-ethanediyl)diacrylate

Cas Number:

17831-71-9

Molecular formula:

C14H22O7

IUPAC Name:

2-(2-{2-[2-(prop-2-enoyloxy)ethoxy]ethoxy}ethoxy)ethyl prop-2-enoate

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle, France
- Age at study initiation: approximately 16 weeks old
- Weight at study initiation: 3197 g
- Housing: individually in labeled cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 70-98 %
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation)
- Photoperiod (hrs dark / hrs light): A 12-hour light/12-hour dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Number of animals or in vitro replicates:

1 rabbit

Details on study design:

The animal was treated by instillation of 0.1 mL of the test item, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then
gently held together for about one second to prevent loss of the test item. The other eye remained untreated and served as the reference control.
Throughout the study, the animal was observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed
from the cage during observation, unless necessary for identification or confirmation of possible findings. The animal, showing pain, distress or discomfort, which was considered not
transient in nature or is likely to become more severe, was sacrificed for humane reasons based on OECD guidance document on the recognition, assessment, and use of clinical signs
as humane endpoints for experimental animals used in safety evaluation.
Observations for toxicity were performed once daily throughout the study.
The animal was weighed individually on Day 1 (pre-dose).
The eyes of the animal were examined approximately 1 after instillation of the test item. The irritation scores and a description of all other (local) effects were recorded.

The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) .................................................................. .0
Scattered or diffuse areas of opacity, details of iris clearly visible ......................................................................... .1
Easily discernible translucent area, details of iris slightly obscured ....................................................................... .2
Nacreous area, no details of iris visible, size of pupil barely discernible ............................................................... .3
Opaque cornea, iris not discernible through the opacity ........................................................................................ .4
Area of cornea involved:
No ulceration or opacity ......................................................................................................................................... .0
One quarter or less but not zero ............................................................................................................................. .1
Greater than one quarter, but less than half ............................................................................................................ .2
Greater than half, but less than three quarters......................................................................................................... .3
Greater than three quarters, up to whole area ......................................................................................................... .4

IRIS
Normal ................................................................................................................................................................... .0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of
these or combination thereof, iris still reacting to light (sluggish reaction is positive) .......................................... .1
No reaction to light, hemorrhage, gross destruction (any or all of these) ............................................................... .2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal ............................................................................................................................................. .0
Some blood vessels definitely hyperaemic (injected) ............................................................................................. .1
Diffuse, crimson color, individual vessels not easily discernible ........................................................................... .2
Diffuse beefy red .................................................................................................................................................... .3
Chemosis (refers to lids and/or nictitating membranes):
No swelling ………………………………………… ........................................................................................... .0
Any swelling above normal (includes nictitating membranes) .............................................................................. .1
Obvious swelling with partial eversion of lids ....................................................................................................... .2
Swelling with lids about half closed ...................................................................................................................... .3
Swelling with lids more than half closed ................................................................................................................ .4
Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) ..................................... 0
Any amount different from normal and/or lacrimation ........................................................................................... 1
Discharge with moistening of the lids and hairs just adjacent to lids ...................................................................... 2
Discharge with moistening of the lids and hairs (considerable area around the eye) ............................................. 3
Where standard lighting was considered inadequate for observing minor effects, eye examinations were
performed using an ophthalmic examination lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

observation time : 1h

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

observation time : 1h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritant / corrosive response data:

Instillation of a volume of 0.1 mL into one eye of the rabbit resulted in severe irritation of the conjunctivae, which consisted of redness, chemosis and discharge. Scoring of the cornea and iris was not possible due to the extreme swelling. The animal was sacrificed for humane reasons one hour after dosing. At necropsy, dissection of the eye did not reveal iridial
irritation or corneal epithelial damage.
Based on the severity of the effects, the two other animals assigned to the study were not dosed.

Other effects:

No staining of (peri) ocular tissues by the test item was observed and no test item remnants were seen.
Head tilt was noted in the animal, which indicates severe pain.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the initial rabbit dosed, SR268 should be classified as: having irreversible effects on the eyes (Category 1).

Executive summary:

The objective of this acute eye irritation study was to assess the possible irritation or corrosion potential when a single dose of SR268 was placed in the conjunctival sac of the rabbit eye.

A single sample of 0.1 mL was instilled into one eye of the rabbit. Observations were made 1 hour after instillation.

Instillation of the test item resulted in severe irritation of the conjunctivae, which consisted of redness, chemosis and discharge. Scoring of the cornea and iris was not possible due to the extreme swelling. Furthermore, head tilt was noted in the animal indicating severe pain. The animal was sacrificed for humane reasons one hour after dosing. At necropsy, dissection of the eye did not reveal iridial irritation or corneal epithelial damage.

Based on the severity of the effects, the two other animals assigned to the study were not dosed.

Based on the initial rabbit dosed, SR268 should be classified as: having irreversible effects on the eyes (Category 1).