Registration Dossier

Administrative data

Description of key information

Based on several studies the test substance is not regarded as irritating to eyes and skin.

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:
1997-07-15 to 1997-07-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study report
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna Ltd., Huntingdon, Cambridgeshire. England, UK
- Age at study initiation: 10 - 12 wks
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: individually in metal cages
- Diet: ad libitum, standard diet (SDS Stanrab /P) SQC Rabbit Diet)
- Water: ad libitum, tap water
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.5 - 21.5
- Humidity (%): 60 - 74
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
4 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorso lumbar region (6.25 mm²)
- Type of wrap if used: elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize et al. (1959)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No dermal reaction to treatment was observed in any animal throughout the study period.
Other effects:
There were no signs of toxicity observed in any rabbit during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information
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:
1997-07-21 to 1997-07-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study report
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Interfauna Ltd., Huntingdon, Cambridgeshire. England, UK
- Age at study initiation: 11 - 13 wks
- Weight at study initiation: 2.5 - 3.0 kg
- Housing: individually in metal cages
- Diet: ad libitum, standard diet (SDS Stanrab /P) SQC Rabbit Diet)
- Water: ad libitum, tap water
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 - 21.5
- Humidity (%): 50 - 74
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: adjacent eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
Single exposure. Eyes of the animals were not washed.
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: according to Draize et al (1959)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritant / corrosive response data:
No corneal damage or iridial inflammation was observed. A diffuse, crimson colouration of die conjunctivae with slight swelling and above normal discharge to discharge with moistening of the lids and hairs just adjacent to the lids was observed in all animals. These reactions had resolved in all instances by one or two days after instillation.
Interpretation of results:
not irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

key study

Following the experimental design according to EPA OPP 81-5, 0.5 mL of the test substance was administered to six New Zealand White rabbits for four hours (Hoechst-Celanese, 434/973184/SE, 1997). The sample was applied to about six square centimeters of clipped skin, which was then covered with a gauss pad and a semi-occlusive bandage. The cover was removed after the four hour exposure period and the skin washed free of excess test material using saline and blotted dry. Evaluation of skin condition was conducted, using the Draize scoring system, approximately 60 minutes after removal of the cover and at 1, 2, and 3 days after removal. The maximum-mean dermal irritation score at any observation was 0.0 (maximum possible score is 8.0). No animal showed any indication of dermal irritation. The test substance was found to be non-irritant to rabbit skin.

supporting studies

The skin irritation potential of the test substance was also assessed (BASF, 80/199, 1980), by applying 0.5 mL of the test substance to the intact skin of two Vienna White rabbits under an occlusive dressing for 3 min and 2 hours. The test substance was washed off with lutrol and lutrol/water (1:1) after the exposure time. Evaluation of skin was conducted, using the Draize scoring system.

No irritating effects were observed after 3 minutes of application. After 2 hours of application both animals showed slight erythema and edema at the 24-hour reading. Slight erythema persisted until study day 8 with scaling.

Following the experimental design according to Federal Register 38, No. 187, § 1500.41, S. 27019, 27. Sept. 1973, 0.5 mL of the test substance was applied to the intact and abraded skin of six Vienna White rabbits under an occlusive dressing for 24 hours (BASF, 80/199, 1980). Evaluation of skin was conducted, using the Draize scoring system.

All animals showed questionable to slight redness and edema of the skin during the first 72 hours after application period. After 8 days, questionable erythema was still observed on 4 animals. Scaling was observed on all animals at the end of the observation period. Edema were all fully reversible within 8 days.

In the third supporting skin irritation study, 4 rabbits were exposed to 0.5 mL of the neat substance and covered with an abraded patch (Celanese Corp. C-802, 1985). No details on duration of exposure were given. Scoring of skin results was conducted, using the Draize scoring system. Animals were then observed for 72 hours. The only dermal irritation seen was very slight (barely perceptible) erythema in two of the four animals. No edema were observed. The substance is regarded as non-irritant to the intact skin of rabbits.

Conclusion

The test substance is regarded as non-irritant to the intact rabbit skin as shown in the key study and the supporting study of Celanese Corp. Both BASF studies can be regarded as worst case as both were conducted with an occlusive dressing. Furthermore animals were only observed for 8 days. Normally a 14 day observation period should be conducted after exposure in order to address the reversibility of findings.

Eye irritation

key study

Following the experimental design according to EPA OPP 81-4, the right eye of one healthy New Zealand White rabbit was treated with 0.1 mL undiluted liquid test material (Hoechst-Celanese, 435/973246/SE, 1997). Eyes were not washed. As only mild irritation was observed, five additional animals were treated in a similar manner. Ocular lesions were scored approximately 1 hour, 1, 2, and 3 days after treatment by the Draize method. All six treated eyes showed signs of slight to moderate redness one hour after treatment and slight chemosis. On day one, only 2/6 animals showed irritation (slight) and all irritation was resolved by day 2.

The test substance is regarded as non-irritant to the eyes.

supporting studies

Following the experimental design according to Federal Register 38, No. 187, § 1500.42, S. 27019, 27. Sept. 1973, 0.1 mL of the test substance was instilled in the conjunctival sac of six Vienna White rabbits (BASF, 80/199, 1981). The eyes were not washed. Animals were observed for 8 days. Irritation was scored by the method of Draize et al..

The application to the intact eye resulted in slight cornea opacity up to 72 hours after treatment in three rabbits. In one animal, opacity persisted until study day 8. Iritis was only observed in one animal until study day 8. All animals showed slight to moderate conjunctival redness at the 24 h reading. In one animal, redness persisted until study day 8. Redness was fully reversible in the other animals. Slight to moderate chemosis was observed in all but one animal at the 24 h reading. Chemosis only persisted in one animal until study day 8. The test substance is regarded as non-irritant to the eyes.

In the second supporting eye irritation study, 4 rabbits were singly exposed to 0.1 mL of the neat substance (Celanese Corp. C-802, 1985). Eyes were not washed and scoring was conducted according to Draize et al. Animals were then observed for 72 hours. The four animals did not show any significant irritation during the course of the test. The test substance was therefore regarded as non-irritant to the rabbit eye.


Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study report

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study report

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled as eye or skin irritating under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EU) No 2015/1221.