Registration Dossier

Administrative data

Description of key information

2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-: a stereoisomer of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- is considered to be irritating to the skin, but not corrosive or irritating to the eye determined in an OECD 404 and OECD 405 guideline study, respectively.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG
- Weight at study initiation: 3.05, 2.87, and 2.91kg
- Housing: 1 animal per cage, stainless steel cages with wire mesh walk floors; floor area: 40 cm x 51 cm, no bedding in the cages
- Diet: 130 g per day Kliba 341, 4 MM (Firma Klingenmuehle AG, CH-4303 Kaiseraugst, Switzerland)
- Water: 250 mL per day tap water
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air: room were fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
0.5 mL to the test patch (2.5 cm x 2.5 cm)
Duration of treatment / exposure:
4 h
Observation period:
15 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: upper third of the back of flanks, 2.5 cm x 2.5 cm
- Type of wrap if used: test patch was secured in position with porous dressing (four layers of absorbent gauze + porous bandage)

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

SCORING SYSTEM:
- Skin irritation/corrosion scoring according to 83/467/EEC criteria of July 29th, 1983
- Readings 30-60 minutes after removal of the test patches and 24h, 48h, 72h, 8d, and 15d after beginning of application
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
In animal 1 and 3 scaling was observed at day 8, for animal 1 also at day 15.
Interpretation of results:
irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, the substance is considered to be irritating to the skin.
Executive summary:

The potential to cause acute dermal irritation or corrosion was assessed, in a OECD 404 guideline study, by a single topical application of an amount of 0.5 mL of the test substance for 4 hours to the intact skin of three White New Zealand rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing. After removal of the patch, the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch and approximately 24, 48, 72 hours, and 8, 15 days after removal. The mean score (24 to 72 hours) for erythema was calculated to be 2.7, 1.3 and 3.0 for animal 1, 2 and 3 respectively. The mean score for edema was calculated to be 2.0, 0 and 1.3 for animal 1, 2 and 3 respectively. It was concluded that the test substance was irritating to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG
- Weight at study initiation: 2.93, 3.30, 3.08 kg
- Housing: 1 animal per cage, stainless steel cages with wire mesh walk floors; floor area: 40 cm x 51 cm, no bedding in the cages
- Diet: 130 g per day, Kliba 341, 4 MM (Firma Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland)
- Water: 250 mL per day tap water
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1 mL to the conjunctival sac of the right eye
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- No removal

SCORING SYSTEM:
- calculation of the mean scores according to 83/467/EEC criteria of July 29th, 1983
- readings performed 1h, 24h, 48h, 72h and 8 days after application
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 - 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 - 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 - 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
In animal 1 and 2 pupil contraction was observed 1 h after exposure. In animal 3 pupil contraction and loss of corneal tissue were observed 24 to 72 h after exposure, which was fully reversible within 8 days. In the same animal small retractions in the eyelids was observed 48 h to 8 days after exposure.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, the substance is considered not to be irritating to the eye.
Executive summary:

The potential to cause damage to the conjunctiva, iris of cornea was assessed, in an OECD 405 guideline study, in 3 white Vienna rabbits subjected to a single ocular application of 0.1 mL of the test substance on day 0. The mean score (24 to 72 hours) for irritation was calculated to be 0, 0, and 1 for corneal opacity, 0,0, and 0 for iritis, 0, 0.3, and 0.7 for chemosis, and 0.7, 1.7, and 1.7 for conjunctivae redness, for animal 1, 2, and 3 respectively. Findings were reversible within 8 days after application. It was concluded that the test substance was not irritating to the eye. 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No studies on the skin and eye irritating properties of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- were available. However, Article 13 of REACH states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. A skin and an eye irritation study of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl- (MBDA) a stereoisomer of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- are available.

Skin irritation / corrosion

MBDA was tested for its potential to cause acute dermal irritation or corrosion, in a OECD 404 guideline study, by a single topical application of an amount of 0.5 mL of the test substance for 4 hours to the intact skin of three White New Zealand rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing (BASF 1989). After removal of the patch, the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch and approximately 24, 48, 72 hours, and 8, 15 days after removal. The mean score (24 to 72 hours) for erythema was calculated to be 2.7, 1.3 and 3.0 for animal 1, 2 and 3 respectively. The mean score for edema was calculated to be 2.0, 0 and 1.3 for animal 1, 2 and 3 respectively. It was concluded that the test substance was irritating to the skin.

Eye irritation

MBDA was tested for its potential to cause damage to the conjunctiva, iris of cornea, in an OECD 405 guideline study, in 3 white Vienna rabbits subjected to a single ocular application of 0.1 mL of the test substance on day 0 (BASF 1989). The mean score (24 to 72 hours) for irritation was calculated to be 0, 0, and 1 for corneal opacity, 0,0, and 0 for iritis, 0, 0.3, and 0.7 for chemosis, and 0.7, 1.7, and 1.7 for conjunctivae redness, for animal 1, 2, and 3 respectively. Findings were reversible within 8 days after application. It was concluded that the test substance was not irritating to the eye. 


Justification for selection of skin irritation / corrosion endpoint:
One skin irritation study performed with a steroisomer of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- is available. This study is adequate for covering this endpoint.

Justification for selection of eye irritation endpoint:
One eye irritation study performed with a steroisomer of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- is available. This study is adequate for covering this endpoint.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the positive results of the available skin irritation study of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, a steroisomer of 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- and in accordance with Directive 67/548/EEC (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, 2-Propenal, 3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-methyl-, (E)- has to be classified Xi:R38: Irritating to skin and Cat 2:H315: Causes skin irritation, respectively.

Based on the available data of the stereoisomer and in accordance with Directive 67/548/EEC (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for eye irritation.