Registration Dossier

Administrative data

Description of key information

Skin
Rabbit, 4h, semiocclusive: irritating (CrayValley 1999, according to OECD 404 and GLP)
Rabbit, 4h, semiocclusive: mildly irritating (BASF SE 1998, according to OECD 404 and GLP)
Eye
Rabbit: not irritating (Cray Valley 1993, according to EU Method B5 and GLP)

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:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
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: Charles River, UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 1.289 - 1.487 kg
- Housing: individually
- Diet (e.g. ad libitum): standard lab rabbit diet (Charles River Breeding and Maintenance diet for rabbits) app. 100g / day and animal,
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50%
- Air changes (per hr): 15
- 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 animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

Duration of treatment / exposure:
4h
Observation period:
14 days
1, 24, 48, 72h, 7, 14 days after exposure
Number of animals:
3m
Details on study design:
TEST SITE
- Area of exposure: 2 x 3cm
- Type of wrap if used: micropore tape, secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removal of the dressing with water
- Time after start of exposure: 4h
Dry or sticky remnants were present on the skin up to 72h

SCORING SYSTEM: Draize
ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) 4

In cases where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) 4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72h (mean)
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72h (mean)
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72h (mean)
Score:
3.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72h (mean)
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72h (mean)
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72h (mean)
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Other effects:
No mortality occured. Lethargy, pale skin, diarrhoea, loss of appetite, piloerection, emaciation and/or swelling of the abdomen were noted in animal 570 and 572 and the animals felt cold from 72 hours or 7 days after treatment onwards until 7 or 13 days respectively after treatment. These signs were evaluated by the veterinarian and study director and were considered signs of a general decline in health and not test substance related signs. This event was evaluated by the study director and considered not to have affected the study integrity.

Time after exposure Animal #1 Animal #2 Animal #3
Erythema Edema Erythema Edema Erythema Edema
1h 2 3 2 3 2 3
24h 3 2 3 2 3 2
48h 3 3 4 3 3 4
72h 3 2 4 2 3 3
7 days 1 0 2 2 2 1
14 days 0 0 0 0 0 0

Bald skin was observed on day 14 (animal #2, 3)

Scaliness was observed after 7 days in all animals and on day 14 in animal no. 1

Interpretation of results:
irritating
Remarks:
Migrated information
Conclusions:
Dermal application of the test substance resulted in a primary irritation index of 5.78 (severely irritating) when applied to the intact rabbit skin.

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:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield (UK)
- Age at study initiation: 10-13 weeks
- Weight at study initiation: 2.3 - 3.1kg
- Housing: individually in metal cages
- Diet (e.g. ad libitum): SDS Stanrab (P) ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: all rabbits were acclimatised

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light):12h/12h
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
substance was not washed out
Observation period (in vivo):
7 days
1h, 1, 2, 3, 4, 7 days after instillation
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Day 1-7
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Day1-7
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Day 1-7
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Day 1-7
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: #2,3
Time point:
other: 1h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 1day
Irritation parameter:
chemosis score
Basis:
animal: #2,3
Time point:
other: 1h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 1 day
Other effects:
No signs of toxicity were observed.
Interpretation of results:
not irritating
Remarks:
Migrated information
Conclusions:
The test substance was not irritating to the eyes of three rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are valid in-vivo data available for the assessment of the skin and eye irritation potential of (5-ethyl-1,3-dioxan-5-yl)methyl acrylate.

Skin

In an acute dermal irritation or corrosion study according to OECD 404 and GLP, 0.5 ml of the test substance were topically applied to the intact skin of three New Zealand White rabbits for 4 hours under semiocclusive dressing (Cray Valley, 1999). Moderate to severe or severe erythema and moderate or severe oedema were observed in the treated skin-areas of the three rabbits. The skin irritation had resolved in all animals at termination (after 14 days). Scaliness was observed among the animals after 7 days and/or 14 days. Bald skin was noted in two animals at termination (after 14 days).

In a second in vivo study according to OECD 404 and GLP, 0.5ml of the test substance were applied to the intact skin of 6 New Zealand White rabbits for 4h under semi-occlusive conditions (BASF, 1998). Moderate to severe erythema with moderate oedema and desquamation (characterised by dryness and sloughing) was noted in one rabbit. Reactions were persistent in this animal until study termination on day 14. Well-defined erythema with or without very slight oedema was seen in three animals, that were fully reversible either after 7 or 8 days. Transient very slight erythema only was observed in one further animal up to 24h after removal of the dressing. No dermal reactions were seen in the sixth animal.

Eye:

3 New Zealand White rabbits were subjected to a single ocular application of 0.1ml of the test substance on day 0 in a GLP study according to EU Method B.5 (Cray Valley 1993) . Slight irritation was observed 1h after installation, which was reversible within the first day. Thus, the average scores (24 to 72h) for all rabbit were calculated to be 0.0 for corneal opacity, 0.0 for iris, 0.0 for conjunctivae redness, and 0.0 for chemosis.


Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

In two studies, skin irritation was observed. Though severity of these reactions in the second study just miss the classification criteria according to CLP/EU-GHS, reactions in one rabbit persisted until the end of the study and more severe skin reactions were observed in the first study. No corrosion was observed in both studies Thus (5-ethyl-1,3-dioxan-5-yl)methyl acrylate is classified as R38 according to 67/548/EEC and as skin irritant Category 2 according CLP/EU-GHS.

Since no eye irritation was observed 24 h to 72 h after instillation, classification according to 67/548/EEC or CLP/EU-GHS is not justified.