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

Endpoint summary

Description of key information

Based on the reliable in vivo studies, Tetraethylene Glycol Diacrylate is considered to be irritating on skin and corrosive to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Three old rabbit study reports were available to evaluate the skin irritation/corrosion potential of tetraethyleneglycol diacrylate: two reliable studies with some restrictions (Hundingdon 1976, BASF 1978) and a not reliable study (IndBioTest 1977).
Industrial Biotest Laboratory was found to use fraudulent practices in some of their studies and reports. Since these studies were performed before the implementation of Good Laboratory Practices, it is not possible to verify the scientific credibility of most of these studies.
The two reliable studies (Hundingdon 1976, BASF 1978) were performed with 24-hours of exposure and showed contradictory results. The study of 1976 was performed on 3 rabbits and concluded that the substance is skin corrosive based on high individual erythema score (mean 24-72h). The study of 1978 was performed on 6 rabbits and concluded that the substance is slightly skin irritating but not classified into category 2 according to the GHS criteria (all the individual 24-72h scores for erythema and oedema below than 1.3 for 4/6 animals). The limitations of both studies are the longer exposure duration (24-hr instead of 4-h required to determine the skin irritation classification according to GHS) and the absence of information on substance purity.
Based on these contradictory conclusion, an in vitro skin irritation test was performed in order to determine the correct classification for human hazard assessment. The results of this OECD 439 test were negative with a viability score of 111%. With this result, no GHS classification is required.
The registrants are surprised of the non-classification for skin irritation and decided to perform a new in vivo study according to the OECD TG 404 in order to be sure that no classification of the substance is needed for skin irritation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo Global Services Inc., Denver, PA.
- Age at study initiation: Young adult (at least 12
- Weight at study initiation: 2.6 - 3.3 kg.
- Housing: individually housed in suspended wire-bottom cages.
- Diet (e.g. ad libitum): Fresh, Certified Rabbit LabDiet® (No. 5322) was provided daily
- Water (e.g. ad libitum): water was available ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): continuously recorded
- Humidity (%): continuously recorded
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

3 min, 1h and 4h

Observation period:

Exposure Site 1 of the initial animal was scored for dermal irritation immediately post-exposure and at one hour post-exposure.
Sites 2 (one-hour exposure) and 3 (four-hour exposure) were scored for dermal irritation at 1, 24, 48 and 72 hours and on Day 7 for all three animals and on Day 14 for two animals post-patch removal.

Number of animals:

one male - two females

Details on study design:

TEST SITE
Approximately 24 hours prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair.
The prepared site was approximately 10% of the body surface and remained intact.

Initially, one rabbit was dosed on Site 1. The test article was dosed by volume, 0.5 ml per site and placed onto a 2 x 3 cm gauze patch which was placed on the dose site. Gentle pressure was applied to aid in the distribution of the test article over the prepared site. The dose patch was secured with non-irritating tape and the rabbit was gently held in place. The dose patch was removed at 3 minutes post-exposure and the test site was gently washed with gauze saturated with corn oil and blotted dry with gauze following patch removal. The outline of the dose site was marked using an indelible marker.
Due to no observed corrosive or severely irritating effects in the initial animal, two additional animals were added to the study and dosed in the same manner. All three animals were dosed at Site 2 for an exposure period of one hour and Site 3 for an exposure period of four hours. The clipped area of the torso was covered with a piece of porous dressing large enough to cover all dose sites with at least 5 cm2 to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. After the exposure period, the wrappings and patches were removed and the sites gently washed with gauze saturated with corn oil and blotted dry with gauze. The outline of the dose site was marked using an indelible marker.

REMOVAL OF TEST SUBSTANCE
- Washing : no

SCORING SYSTEM:
- Method of calculation:
Erythema and edema were scored according to the numerical Draize1 scale. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional
signs were described.

ERYTHEMA
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

EDEMA
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised > 1 mm & extending beyond the area of exposure) 4

Body weights were recorded pre-test and at study termination.
Animals were observed for mortality, toxicological and pharmacological effects at least once daily.
All animals were humanely euthanized with a 1 ml intravenous injection (via the marginal ear vein) of Fatal-Plus® following study termination

Irritation parameter:

erythema score

Remarks:

1-hour exposure

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Mean Individual data = 2 - 1.67 - 2

Irritation parameter:

edema score

Remarks:

1-h exposure

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Mean individual data : 1 - 1 - 1,67

Irritation parameter:

erythema score

Remarks:

4-h exposure

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

2.4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Mean individual score = 2 - 2.3 - 3

Irritation parameter:

edema score

Remarks:

4-h exposure

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Mean individual scores = 2 - 1.3 - 2.3

Irritant / corrosive response data:

3-minute exposure : no edema observed after 1 hour. Erythema of 2 observed after 1 hour. Based on these results, the test item is not considered as corrosive.
1-hour exposure : moderate erythema and slight edema were observed in the 3 rabbits exposed. Based on these results, the test item is not considered as corrosive.
4-hour exposure : moderate erythema and edema observed in the 3 rabbits exposed. Based on these results, the test item is considered as irritating to the skin.

Other effects:

Abnormal physical signs including diminished food consumption, wetness, soiling and yellow staining of the anogenital area were observed.
Body weight : Two animals gained weight and one animal’s weight remained the same by study termination.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the experimental conditions of this study, the test item was considered as irritating to skin when applied topically to rabbits after 4 -hour exposure according to the Regulation EC 1272/2008 (CLP) and GHS criteria.

Executive summary:

The purpose of this study was to determine the irritant or corrosive effects, if any, of a test article when applied to the skin of a rabbit.

Initially, one healthy male New Zealand White rabbit was dosed dermally with 2-Propenoic acid, oxybis(2,1-ethanediyloxy-2,1-ethanediyl) ester.The test article (0.5 ml) was applied dermally to Site 1 for an exposure period of 3 minutes. Erythema and edema were scored immediately post-exposure and at one hour post-exposure. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Due to no observed corrosive or severely irritating effects in the initial animal, two additional animals (females) were added to the study.

All three animals were dosed at Site 2 for an exposure period of one hour and Site 3 for an exposure period of four hours. Erythema and edema were scored at 1, 24, 48 and 72 hours and on Day 7 for all three animals and on Day 14 for two animals for the one and four-hour exposures. Animals were observed for mortality, toxicological and pharmacological effects at least once daily. Body weights were recorded pre-test and at termination.

 

No unscheduled deaths occurred during the study. and no clinical signs were noted in any animals.

Abnormal physical signs including diminished food consumption, wetness, soiling and yellow staining of the anogenital area were observed.

Two animals gained weight and one animal’s weight remained the same by study termination.

After 3 -minute exposure (one animal), erthema score was of 2, and edema score of 0 : no sign of corrosion.

After a 1-hour exposure (three animals), mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.            erythema: 2 - 1.67 - 2

.            edema: 1 - 1 - 1,67

 

After a 4-hour exposure (three animals), mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.            erythema: 2 - 2.3 - 3

.            edema: 2 - 1.3 - 2.3

 

Under the experimental conditions of this study, the test item was considered as irritating to skin when applied topically to rabbits after 4 -hour exposure according to the Regulation EC 1272/2008 (CLP) and GHS criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

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

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.

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

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not determinable

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.

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN IRRITATION

Four old rabbit study reports were available to evaluate the skin irritation/corrosion potential of tetraethyleneglycol diacrylate: three reliable studies with some restrictions (Sugar 1981, TNO 1978, Kynoch 1976) and a not reliable study (IndBioTest 1977).

Industrial Biotest Laboratory was found to use fraudulent practices in some of their studies and reports. Since these studies were performed before the implementation of Good Laboratory Practices, it is not possible to verify the scientific credibility of most of these studies.

The three reliable studies (Sugar 1981, TNO 1978, Kynoch 1976) were performed with 24-hours of exposure and showed contradictory results. The study of 1976 was performed on 3 rabbits and concluded that the substance is skin corrosive based on high individual erythema score (mean 24-72h). The studies of 1978 and 1981 was performed on 6 rabbits (on intact skin) and concluded that the substance is slightly skin irritating but not classified into category 2 according to the GHS criteria (all the individual 24-72h scores for erythema and oedema below than 2.3 for 3 or 4/6 animals).

The limitations of the reliable studies are the longer exposure duration (24-hr instead of 4-h required to determine the skin irritation classification according to GHS), the absence of information on substance purity and the short observation period (72h or 7 days instead of 14 days required in the OECD test guideline n°404).

Based on these contradictory conclusion, an in vitro skin irritation test was performed in order to determine the correct classification for human hazard assessment. The results of this OECD 439 test were negative with a viability score of 111%. With this result, no GHS classification is required.

The registrants are surprised of the non-classification for skin irritation and decided to perform a new in vivo study according to the OECD TG 404 in order to be sure that no classification of the substance is needed for skin irritation.

In vitro skin irritation study (Eurling 2017a):

The objective of this study was to evaluate Tetraethylene glycol diacrylate for its ability to induce skin irritation on a human three dimensional epidermal model (EPISKIN Small model (EPISKIN-SMTM)). The possible skin irritation potential of Tetraethylene glycol diacrylate was tested through topical application for

15 minutes. The study procedures described in this report were based on the most recent OECD and EC guidelines.

The test item was applied undiluted (25 µl), directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42 hour postincubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. The test item did interact with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). In addition to the normal procedure, three killed tissues treated with test item and three killed untreated tissues were used for the cytotoxicity evaluation with MTT. The non specific reduction of MTT by the test item was 2.96% of the negative control tissues. The net OD of the treated killed tissues was subtracted from the ODs of the test item treated viable tissues. Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 111%. Since the mean relative tissue viability for the test item was above 50% after 15 ± 0.5 minutes treatment the test item is considered to be non-irritant.

The positive control had a mean cell viability of 22% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was = 11%, indicating that the test system functioned properly.

In conclusion, Tetraethylene glycol diacrylate is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report.

In vivo skin irritation study (CRL 2020):

The purpose of this study was to determine the irritant or corrosive effects, if any, of a test article when applied to the skin of a rabbit.

Initially, one healthy male New Zealand White rabbit was dosed dermally with 2-Propenoic acid, oxybis(2,1-ethanediyloxy-2,1-ethanediyl) ester.The test article (0.5 ml) was applied dermally to Site 1 for an exposure period of 3 minutes. Erythema and edema were scored immediately post-exposure and at one hour post-exposure. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Due to no observed corrosive or severely irritating effects in the initial animal, two additional animals (females) were added to the study.

All three animals were dosed at Site 2 for an exposure period of one hour and Site 3 for an exposure period of four hours. Erythema and edema were scored at 1, 24, 48 and 72 hours and on Day 7 for all three animals and on Day 14 for two animals for the one and four-hour exposures. Animals were observed for mortality, toxicological and pharmacological effects at least once daily. Body weights were recorded pre-test and at termination.

 No unscheduled deaths occurred during the study. and no clinical signs were noted in any animals.

Abnormal physical signs including diminished food consumption, wetness, soiling and yellow staining of the anogenital area were observed.

Two animals gained weight and one animal’s weight remained the same by study termination.

After 3 -minute exposure (one animal), erthema score was of 2, and edema score of 0 : no sign of corrosion. After a 1-hour exposure (three animals), mean scores calculated for each animal over 24, 48 and 72 hours were as follows: erythema: 2 - 1.67 - 2 ; edema: 1 - 1 - 1,67.  After a 4-hour exposure (three animals), mean scores calculated for each animal over 24, 48 and 72 hours were as follows:erythema: 2 - 2.3 - 3 ; edema: 2 - 1.3 - 2.3.

Under the experimental conditions of this study, the test item was considered as irritating to skin when applied topically to rabbits after 4 -hour exposure according to the Regulation EC 1272/2008 (CLP) and GHS criteria.

EYE IRRITATION

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.

In vitro eye irritation study (Eurling 2017b) :

The objective of this study was to evaluate the eye hazard potential of Tetraethylene Glycol Diacrylate as measured by its ability to induce opacity and increase permeability in an isolated bovine cornea using the Bovine Corneal Opacity and Permeability test (BCOP test).

The eye damage of the test item was tested through topical application for 10 minutes. The test item was applied as it is (750 µl) directly on top of the corneas.

Tetraethylene Glycol Diacrylate did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 1.2 after 10 minutes of treatment.

In conclusion, since the test item induced an IVIS = 3, no classification is required for eye irritation or serious eye damage.

In vivo eye irritation study (CRL 2020):

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).

Justification for classification or non-classification

Based on the available data, Tetraethylene Glycol Diacrylate should be classified as skin irritating (Skin irrit. 2, H315) and eye corrosive (Eye irrit.1, H318) according to the Regulation EC no.1272/2008.