Registration Dossier

Administrative data

Description of key information

DGEBA diacrylate showed no signs of skin irritation. 
DGEBA diacrylate showed only slight and transient signs of eye irritation for conjunctivae score that were fully reversed within several days.

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:
From May 27 to June 13, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis; animals exposed occasionally to humidity higher than 70%
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 6 weeks (at least)
- Weight at study initiation: 1.0 kg (at least)
- Housing: Housed individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Pelleted diet (K-H from SSNIFF® Spezialdiaten GmbH, Soest, Germany), 100 g/day; hay (TecniLab-BMI BV, Someren, The Netherlands) provided at least three times a week
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 °C
- Humidity (%): 32-74%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours fluorescent light
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Flank skin (150 cm2 )
- Type of wrap if used: Test material was applied to the skin using a metalline patch (2x3 cm) and then covered with Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed using tap water and/or watery ethanol (50% v/v)
- Time after start of exposure: 4 hours

SCORING SYSTEM: Scoring system same as recommended by OECD Guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Mean individual scores at 24, 48 and 72 hours after exposure for the 3 animals were 0, 0, 0 for erythema score and 0, 0, 0 for oedema score
Other effects:
No
Interpretation of results:
GHS criteria not met
Remarks:
not skin irritating
Conclusions:
Under the test conditions, Bisphenol A epoxy diacrylate is not classified as irritating to the skin.
Executive summary:

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP, three New-Zealand White male rabbits were dermally exposed to 0.5 mL of Bisphenol A epoxy diacrylate, under a semi-occlusive bandage for 4 hours to clipped skin of the flank (150 cm2). Animals were then observed for 7 days. Irritation was scored by the method of OECD Guideline 404 at 1, 24, 48 and 72 hours after exposure.

There was no irritant effect at any observation time point. In this study, Bisphenol A epoxy diacrylate is not a dermal irritant on male rabbits. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
From June 02 to 12, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no certificate of analysis
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 6 weeks (at least)
- Weight at study initiation: 1.0 kg (at least)
- Housing: Housed individually in labelled cages with perforated floors
- Diet (e.g. ad libitum): Pelleted diet (K-H from SSNIFF® Spezialdiaten GmbH, Soest, Germany), 100 g/day; hay (TecniLab-BMI BV, Someren, The Netherlands) provided at least three times a week
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 5 days (at least)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2-21.5 °C
- Humidity (%): 45-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours fluorescent light
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 0.1 mL
Duration of treatment / exposure:
Not aplicable ( eye not rinsed)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Not applicable

SCORING SYSTEM: Scoring system same as recommended by OECD Guideline 405

CORNEAL IRRlTATlON
- 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 circumcorneaI 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 IRRlTATlON
- 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 sweIling 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

TOOL USED TO ASSESS SCORE: Eye examinations were performed using fluorescein (2%) and/or an ophthalmic examination lamp (if standard lighting was inadequate)
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
for each animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: Individual mean score: 0.7-0.7-0.7
Irritant / corrosive response data:
- Irritation of the conjunctivae which consisted of redness, chemosis and discharge, completely resolved within 72 hours
- Traces of the test substance were present and on the outside of the eyelids throughout the observation period
- See table 1 and 2 for further details
Other effects:
- No mortality or symptoms of systemic toxicity
- Slight bodyweight loss observed in one animal but considered of no toxicological relevance, based on the absence of corroborative findings

Table 1: Individual eye irritation scores

Animal

Time after dosing (hours)

Cornea

Iris

Conjunctivae

Comments

Opacity

Area

Fluor area (%)2

Redness

Chemosis

Discharge

8471

1

0

0

0

0

2

2

1

c

24

0

0

0

1

0

1

c

48

0

0

0

1

0

0

c

72

0

0

0

0

0

0

c

859

1

0

0

0

0

2

2

1

c

24

0

0

0

1

0

1

c

48

0

0

0

1

0

0

c

72

0

0

0

0

0

0

c

861

1

0

0

0

0

2

1

1

c

24

0

0

0

1

0

1

c

48

0

0

0

1

0

0

c

72

0

0

0

0

0

0

c

1Sentinel

2Green staining after fluorescein treatment (percentage of total corneal area)

c: Remnants of the test substance on the outside of the eyelids

Table 2: Mean (24, 48 and 72 hours) value eye irritation scores

Animal

 

 

Corneal opacity

 

 

Iris

 

 

Conjunctivae

Redness

Chemosis

847

0

0

0.7

0

859

0

0

0.7

0

861

0

0

0.7

0

Interpretation of results:
GHS criteria not met
Remarks:
not eye irritating
Conclusions:
Under the test conditions, Bisphenol A epoxy diacrylate is not classified as irritating to the eye.
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Bisphenol A epoxy diacrylatein one of the eyes while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded according to the method of OECD Guideline 405.

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.7, 0.7 for conjunctivae score and 0, 0, 0 for chemosis score.

Under the test conditions, Bisphenol A epoxy diacrylate is not classified as irritating to the eye according to the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP (key study, 2008), three New-Zealand White male rabbits were dermally exposed to 0.5 mL of Bisphenol A epoxy diacrylate, under a semi-occlusive bandage for 4 hours to clipped skin of the flank (150 cm2). Animals were then observed for 7 days. Irritation was scored by the method of OECD Guideline 404 at 1, 24, 48 and 72 hours after exposure. There was no irritant effect at any observation time point. In this study, Bisphenol A epoxy diacrylate is not a dermal irritant on male rabbits. 

In the OECD 404 supporting study (1994), three New-Zealand White female rabbits were dermally exposed to 0.5 mL of DGEBA diacrylate to clipped skin, under semi-occlusive conditionsfor 4 hours. Animals were then observed for 3 days. There was no irritant effect at any observation time point. In this study, DGEBA diacrylate is not a dermal irritant on female rabbits. 

Eye irritation

In the key study (2008) conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Bisphenol A epoxy diacrylate in one of the eyes while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded according to the method of OECD Guideline 405. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.7, 0.7 for conjunctivae score and 0, 0, 0 for chemosis score. Under the test conditions, Bisphenol A epoxy diacrylate is not considered to be irritating to the eyes.

In the first supporting study (OECD 405, 1994), 3 healthy female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted DGEBA acrylate in one of the eyes while the other eye corresponded to the control. Instillation of the test substance resulted in slight irritation of the conjunctivae, which consisted of slight redness and discharge. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 1, 1, 0.3 for conjunctivae score and 0.3, 0, 0 for chemosis score. All irritating effects were reversed after 7 days. Under the test conditions, DGEBA diacrylate is slightly irritating to the eyes.

In the second supporting study (B5 method, 1992), three rabbits were each administered a single ocular dose of 0.1 ml of the test substance and observed for a maximum of seven days after instillation. A single instillation of test substance into the eye of the rabbit elicited mild conjunctival irritation. All reactions had resilved four days after instillation. Based on this study, DGEBA diacrylate is slightly irritating to the eyes.

Justification for classification or non-classification

As DGEBA diacrylate showed no severe signs of eyes and no skin irritation, no classification for irritation is required according to the CLP Regulation (EC) N° (1272-2008).