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Administrative data

Description of key information

Several studies are available to evaluate the irritating potential of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate.

Based on these studies, the substance is considered to be not skin irritating but eye corrosive.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
May 12, 198 1
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
September 19, 1984
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler ; D-W6050 Offenbach, FRG
- Age at study initiation: young adult
- Weight at study initiation: 2.43 - 2.60 kg
- Housing: single, in stainless steel cages (40 cm x 51 cm)
- Diet (e.g. ad libitum): KLIBA diet 341 ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: > 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

Duration of treatment / exposure:
4h
Observation period:
72h (study terminated after 72h since no irritation was observed)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 X 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): polyethylenglycol and polyethylenglycol / water (1:1)
- Time after start of exposure: 4h

SCORING SYSTEM:
according to Draize (and as documented in OECD Guideline 404)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48h
Remarks on result:
other: Mean individual scores : 0 - 0.33 - 0.33
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Mean individual scores = 0 - 0 - 0
Interpretation of results:
GHS criteria not met
Remarks:
not skin irritating
Conclusions:
Based on the conditions of this study, the substance is not classified as irritating to the skin according to CLP classification criteria.
Executive summary:

The potential of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 rabbits for 4 hours under semiocclusive dressing. The average score (24-48-72h) for irritation was calculated to be 0.2 for erythema and 0 for edema. The skin reactions were reversible within 48 hours, thus the study was terminated 72h after application. Under the test conditions chosen and considering the described findings, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate does not give indication of an irritant property to the skin.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Feb. 1987
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ace Animals
- Age at study initiation:8-12 weeks
- Weight at study initiation: 2.3 -2.5kg
- Housing: single in suspended cages
- Diet (e.g. ad libitum): Purina rabbit chow (diet #5321) ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h / 12h
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
Duration of treatment / exposure:
substance not washed out
Observation period (in vivo):
28days
Observations after 1h, 24h, 48h, 72h, 7days, 14days, 21days, 28days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize + scoring of ocular discharge
0: No discharge
1: Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs, and considerable area around the eye.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: pannus observed on days 7 (2 animals) and 14 (1 animal). Mean individual scores = 2 - 2 - 2
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days (2 animals), 21 days (1 animal)
Remarks on result:
other: Mean individual scores = 2 - 2 - 2.7
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 28 days (1 animal)
Remarks on result:
other: Mean individual scores = 3 - 4 - 2
Irritant / corrosive response data:
Corneal opacity, noted in 3 of 3 eyes, persisted to day 28 in one eye. Iritis, noted in 3 out of 3 eyes, cleared by day 7. Conjunctival irritation, noted in 3 out of 3 eyes, persisted to day 28 in one eye.
Other effects:
There were no abnormal physical signs noted during the study.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Due to the irreversible effects in 1 animal, the test substance is considered corrosive to the eye.
Executive summary:

Three rabbits were doses with 0.1 ml of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate placed into the left conjunctival sac of each rabbit. The eyes remained unwashed. The eyes were examined and scored by the Draize technique at 1 hour post dose and on days 1, 2, 3, 7, 14, 21 and 28. Body weight were recorded pretest. Corneal opacity, noted in 3 of 3 eyes, persisted to day 28 in one eye. Iritis, noted in 3 out of 3 eyes, cleared by day 7. Conjunctival irritation, noted in 3 out of 3 eyes, persisted to day 28 in one eye. There were no abnormal physical signs noted during the study. Under the conditions of this study, the test article is corrosive based on persistant corneal opacity noted through day 28.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

 SKIN IRRITATION

Key study (1993): The potential of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 rabbits for 4 hours under semiocclusive dressing. The average score (24-48-72h) for irritation was calculated to be 0.2 for erythema and 0 for edema. The skin reactions were reversible within 48 hours, thus the study was terminated 72h after application. Under the test conditions chosen and considering the described findings, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate does not give indication of an irritant property to the skin.

Supporting study n°1 (1997): A single occlusive application of the test substance was done to intact and abraded rabbit skin for 24 hours. The skin application elicited very slight dermal irritation. For intact skin, the mean erythema and oedema scores (24-72h) were : 0 – 0,5 – 1 – 1- 0 – 0, and 0 – 0,5 – 0,5 -0,5 – 0 – 0, respectively. The irritating effects were completely resolved within 72 h.

Supporting study n°2 (1994): Six rabbits were dosed with 0.5 ml of the test substance on intact skin. The test substance was kept in contact with the skin for 24 hours at which time the wrappings were removed and dermal reactions were scored (at 24h, 48h, 72h and 96h after dermal application). Erythema, absent to well defined at 24h and 48 hours after dermal application, was absent to slight at 72h and 96h. Edema, absent to moderate at 24h after dermal application, was absent to well defined at 28, 72h and 96h. No abnormal physical signs were noted during the study. The mean erythema and oedema scores (24-72h) were : 0.67 – 1.67 – 0 – 1 – 1.67 – 0, and 0 – 1.67 – 0 -0 – 2 – 0, respectively. The irritating effects were not completely resolved within 96 h.

 

EYE IRRITATION

Key study (1994): Three rabbits were doses with 0.1 ml of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate placed into the left conjunctival sac of each rabbit. The eyes remained unwashed. The eyes were examined and scored by the Draize technique at 1 hour post dose and on days 1, 2, 3, 7, 14, 21 and 28. Body weight were recorded pretest. Corneal opacity, noted in 3 of 3 eyes, persisted to day 28 in one eye. Iritis, noted in 3 out of 3 eyes, cleared by day 7. Conjunctival irritation, noted in 3 out of 3 eyes, persisted to day 28 in one eye. There were no abnormal physical signs noted during the study. Under the conditions of this study, the test article is corrosive based on persistant corneal opacity noted through day 28.

Supporting study (1993): The potential of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate to cause damage to the conjunctiva, iris or cornea was assessed in 3 rabbits, subjected to a single ocular application of 0.1 mf of the test substance on day 0. The average score (24h-48h-72h) for irritation was calculated to be 2.0 for conjunctivae redness and 3.2 for chemosis. No mean for 3 animals was calculated for corneal opacity and iris because in one animal showed a severe edema. The findings were not considered to be reversible, this the study was terminated on day 15. Symptoms observed (pannus) indicates that the test substance may be severely irritant to the eyes. Under the test conditions chosen and considering the described findings, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate gives indication of a severe irritant property to the eyes.

Justification for classification or non-classification

Based on available data, no classification for skin irritation is required for butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate according to the Regulation EC n°1272/2008

Based on the available data and due to the severe symptoms and irreversible effects after application to the eye, butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate should be classified as Eye Dam 1 (H318).