Registration Dossier

Administrative data

Description of key information

Skin 
In-vitro:
- EpiDerm Corrosivity test: not corrosive (BASF AG 2004, Val. 2)
In vivo:
- Rabbit, 4 h, semiocclusive: not irritating to skin (acc. OECD 404; BASF AG 2004)
- Rabbit, 4 h, semiocclusive: mildly irritating to skin (Huntingdon 2002, Val. 1)
- Rabbit, 4 h, occlusive: not irritating to skin (BASF AG 1982, Val. 2)
Eye
In-vitro:
HET-CAM corrosion test: non corrosive (BASF AG 2004, Val. 2)
In vivo:
- Rabbit, 24 h, substance was not washed out: irritating (BASF AG 2004, acc. OECD 405)
- Rabbit, 24 h, substance was not washed out: severely irritating (BASF AG 1982, comp. OECD 405)
Respiratory system
No data available

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:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., Vonnas, France
- Weight at study initiation: 3.80 - 4.63 kg
- Housing: individually in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet: Kliba-Labordiaet, about 130 g/animal per day
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml, undiluted
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull
stretch (adhesive fleece), Beiersdorf AG, semiocclusive

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was removed at the end of the exposure period with Lutrol and Lutrol / water (1:1).
- Time after start of exposure: after the 4 hours of exposure


SCORING SYSTEM: accodring to OECD guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24/48/72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: the first 24 hours before the reading
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24/48/72 hours
Score:
0
Max. score:
4
Reversibility:
other: always zero
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24/48/72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24/48/72 hours
Score:
0
Max. score:
4
Reversibility:
other: always zero
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24748/72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24/48/72 hours
Score:
0
Max. score:
4
Reversibility:
other: always zero
Other effects:
Slight eryrthema (grade 1) was observed in two animals immediately and 1 hour after removal of the patch and persisted in one animal up to 24 hours. Moderate erythema (grade 2), noted in one animal immediately and 1 hour after removal of the patch, decreased to slight erythema after 24 hours.
No other cutaneous reactions were observed during the study.
The cutaneous reactions were reversible in one animal within 24 hours and in two animals within 48 hours after removal of the patch.
The mean values (24, 48 and 72 h) of the scores of either erythema or 
edema formation in this test was calculated over all animals tested or for 
each animal individually. The value for edema formation was zero over all 
animals tested and zero for individual animals. The value for erythema 
formation was 0.22 over all animals tested and 0.33 in 2/3 animals.
Therefore, under the conditions of the study, the substance was considered to 
be not irritating to the skin of rabbits both under EU and GHS criteria.

The substance is classified in Annex I as irritating to eyes, respiratory system 
and skin.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Although the substance was considered to be not irritating to the skin of rabbits both under EU and GHS criteria, the substance is classified in Annex I as irritating to eyes, respiratory system and 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:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., Vonnas, France
- Weight at study initiation: 3.12 - 3.22 kg
- Housing: individually in stainless steel wire mesh cages with grating, floor acrea: 3000 cm2
- Diet: Kliba-Labordiaet, about 130 g/animal per day
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: with 3 to 6 ml of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 24 hours after application


SCORING SYSTEM: according to OECD guideline 405


TOOL USED TO ASSESS SCORE: daylight tubes "Lumilux" (L 58/860 Plus Eco 25x1, Osram, Germany)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean value 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean value 24/48/72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean value 24/48/72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean value 24/48/72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean value 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean value 24/48/72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean value 24/48/72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean value 24/48/72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean value 24/48/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean value 24/48/72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean value 24/48/72 hours
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean value 24/48/72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Suppuration, contracted pupil, discharge of blood and  injected scleral vessels
in a circumscribed area or circular were noted during the observation period 
within the first 72 hours. All findings were fully reversible within 7 days at the
latest.

The average score (24 to 72 hours) for irritation was calculated to be 1.0 for corneal opacity, 0.44 for iris, 2.33 for conjunctival redness and 1.67 for chemosis.
EU-classification: The mean scores calculated over all animals tested were below 2 for corneal opacity, below 1 for iris lesions, below 2.5 for redness of the conjunctivae and below 2 for edema formation. There was only one animal with a mean score of 2.67 for redness, the other two animals were at 2 and 2.33. Therefore the substance is considered to be not irritating to the eye of rabbits according to EU-criteria under the conditions of the study. GHS-classification (UN): As the mean score of corneal opacity was 1 in 3/3 animals and the mean score for redness was 2, 2.33 and 2.67 in the animals respectively and all readings were reversed to 0 at the 7 day reading, the substance has to be classified as mildy irritating to eyes (Category 2B) according to GHS-criteria. The substance is classified in Annex I as irritating to eyes, respiratory system and skin.
Interpretation of results:
moderately irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are valid in-vitro and in-vivo data available for the assessment of the skin and eye irritation potential of tripropylene glycol diacrylate.

Skin

In an in-vitro EpiDerm test, tripropylene glycol diacrylate was investigated for possible corrosive properties (BASF AG 2004, Val. 2). The undiluted test material was exposed to the EpiDerm model for 3 minutes and for 1 hour. The evaluation of the results led to the conclusion, that the substance is non corrosive.

In-vivo, a skin irritation test was performed with three New Zealand White rabbits, according to OECD guideline 404 (BASF AG 2004, Val. 1). A 4-hour semiocclusive exposure to ca. 0.5 ml of the undiluted test substance produced the following effects: slight eryrthema (grade 1) was observed in two animals immediately and 1 hour after removal of the patch and persisted in one animal up to 24 hours. Moderate erythema (grade 2), noted in one animal immediately and 1 hour after removal of the patch, decreased to slight erythema after 24 hours. No other cutaneous reactions were observed during the study. The cutaneous reactions were reversible in one animal within 24 hours and in two animals within 48 hours after removal of the patch.

Also in a further in-vivo study, according to OECD guideline 404 the test material caused only slight irritating effects on the skin of New Zealand White rabbits, as the mean value for erythema formation was 0.78 and 0.67 for edema formation over all animals and the effects observed were fully reversible within at least 14 days.

Mild effects were seen in another study, which was conducted with rabbits according to OECD guideline 404 (Huntingdon 2002, Val. 1). Very-slight or well-defined erythema with or without very-slight or slight edema was apparent throughout the first 72 hours after bandage removal. On day 8 exfoliation was apparent in two animals, one of which showed very-slight erythema; the animals were overtly normal a week later.

Mild effects were also seen in another study, when rabbits were treated with the test material under occlusive conditions for 4 hours (BASF AG 1982, Val. 2). The value for edema formation was 1 over all animals tested and 1 for individual animals. The value for erythema formation was 1.5 over all animals tested and 2 in the first animals and 1 in the second animal. In one animal erythema was not fullyreversible at the end of the observation period on day 8.

Additionaly studies are available where rabbits are exposured to the test substance for 24 hours under occlusive conditions. In these studies a skin irritation potential was observed. Due to the harsh test conditions, compared to actual guideline recommendations, the results obtained are considered to be overpredictive and where not included.

Eye

In an in-vitro HET-CAM test, tripropylene glycol diacrylate was investigated for possible corrosive properties (BASF AG 2004, Val. 2). The test substance was applied to 3 eggs undiluted and to another 3 eggs as a 10 % solution in olive oil. The time (seconds) until appearance of haemorrhagia and coagulation was noted for each. No effects within the observation period of 300 seconds were noted. Neither haemorrhagia nor coagulation occured in any of the eggs tested. The test substance did not produce changes indicative for severe eye irritation.

An eye irritation test was performed with 3 New Zealand White rabbits, according to OECD guideline 405 (BASF AG 2004, Val. 1). Eyes were left unwashed after application of 0.1 ml tripropylene glycol diacrylate and the animals were observed for 7 days. Suppuration, contracted pupil, discharge of blood and injected scleral vessels in a circumscribed area or circular were noted during the observation period within the first 72 hours. All findings were fully reversible within 7 days at the latest. The average score (24 to 72 hours) for irritation was calculated to be 1.0 for corneal opacity, 0.44 for iris, 2.33 for conjunctival redness and 1.67 for chemosis.

In another study, a Draize test was conducted with 6 New Zealand White rabbits, the eyes were also left unwashed after application of 0.1 ml tripropylene glycol diacrylate and the animals were observed for 8 days (BASF AG 1982, Val. 2). Symptoms included ulceration, loss of hair at the border of the eye lids, scars on the eyelid and narrowed pupils. The mean scores were 1.17 for corneal opacity (1.0 for 3/6 rabbits and 1.33 for the other 3/6 animals), 1 for iris lesions (1 for 6/6 animals), 1.94 for redness of the conjunctivae (2.0 for 5/6 and 1.67 for the 6th animal) and 1.39 for edema formation (0.67, 1, 1, 1.67, 2 and 2 for the individual rabbits). The lesions were still present at the end of the observation period in most of the animals. This result, however, should be considered as overpredictive due to the harsh test conditions if compared to actual guideline recommendations (substance was not washed out after 24 hours, observation period was completed after 8 days). Additionally, no information was available in terms of the amount and definition of impurities within the test material.

 

Respiratory system

No data available

Data from Read across substance Hexamethylene Diacrylate (HDDA)

HDDA also causes skin and eye irritation in vivo.


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin

The available data did not clearly indicate a skin irritation potential of the test material: The scores obtained from studies which were conducted according to the current OECD guideline 404 (4h, semiocclusive conditions) do not justify a classification regarding this endpoint.

Skin irritation effects were observed when test was conducted according to the method of Draize (24 h, occlusive conditions), but due to the harsh test conditions, compared to actual guideline recommendations, the results obtained are considered to be overpredictive.

Nevertheless, tripropylene glycol diacrylate is legally classified as a skin irritant category 2 (Annex I, 67/548/EEC).

 

Eye

Eye irritation effects were observed on corneal opacity, iritis, conjunctival redness and chemosis in several studies. The results obtained for the test material in the key study (with a test material purity > 95 %), which was conducted acc. to OECD guideline, fulfill the requirements to be classified as Category 2 acc. to GHS criteria. Additionally, tripropylene glycol diacrylate is legally classified as an eye irritant (Annex I 67/548/EEC).

 

Respiratory system

Actually, there are no data available for a classification according to this endpoint, but tripropylene glycol diacrylate is legally classified to cause irritation of the respiratory tract (STOT SE 3).