Registration Dossier

Administrative data

Description of key information

skin irritation
key study, in vivo, rabbit: not irritant (non-GLP, similar to OECD 404, BASF SE, 1981)
eye irritation
key study, in vivo, rabbit: not irritant (non-GLP, guideline Fed. Reg. 38, No. 187, BASF SE, 1981)

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline with acceptable restrictions (occlusive conditions, 72 h reading missing, 8-day observation period)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive conditions, 72 h reading missing, limited documentation
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler Offenbach/Main, Germany
- Weight at study initiation: male 2.98 kg, female 3.72 kg
- Housing: one animal per cage of stainless steel with wire mesh walk floors, floor area: 40 cm x 51 cm,
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke, Duesseldorf , Germany (about 130 g per animal per day)
- Water (e.g. ad libitum): About 250 ml per animal per day: demineralized water (Monday-Friday), tap water (Saturday/Sunday)
- Acclimation period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): Conventional (about 30 - 70%)
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Type of coverage:
occlusive
Preparation of test site:
other: clipping of the fur at least 15 hours before beginning of the study
Vehicle:
water
Controls:
other: Untreated skin sites of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance is applied
- Concentration (if solution): 50 % aqueous formulation
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
1 male, 1 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm, Upper third of the back or flank

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period with Lutrol and Lutrol/water (1:1)

SCORING SYSTEM: According to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health

READINGS: 30 - 60 minutes after removal of the test patches and 24 h, 48 h and 8 d after the beginning of application

ADDITIONAL EXAMINATIONS: After sacrifice the animals are examined by gross pathology. If there are clinical signs of necroses, these are confirmed by gross-pathological examination after incision of the skin.


Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 - 48 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 - 48 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
No effects were observed 8 days after the treatment.
Other effects:
No other effects.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study: Draize test with an observation period of 8 days
Qualifier:
according to
Guideline:
other: Fed. Reg. 38, No. 187, § 1500.42, p. 27019, Sept. 27, 1973
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Mean Weight at study initiation: males: 2.90 kg; females: 2.87 kg
- Housing: one animal per cage, stainless steel with wire mesh walk floors, floor area: 40 cm x 51 cm,
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke, Duesseldorf, Germany (about 130 g per animal per day)
- Water (e.g. ad libitum): About 250 ml per animal per day: demineralized water (Monday - Friday), tap water (Saturday/Sunday)
- Acclimation period: About 8 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): Conventional (about 30 - 70)
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml bulk volume (about 75 mg of the triturated test substance)/undiluted

Duration of treatment / exposure:
unspecified; the substance was not washed out
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h and 8 d after application
Number of animals or in vitro replicates:
6 (3 males, 3 females)
Details on study design:
APPLICATION SITE
- Single application to the conjunctival sac of the eyelid

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the substance is not washed out

SCORING SYSTEM: According to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Remarks on result:
other: No effects at in any animal
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Remarks on result:
other: No effects in any animal
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72h (mean)
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72h (mean)
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72h (mean)
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 24, 48 and 72h (mean)
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24, 48 and 72h (mean)
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: 24, 48 and 72h (mean)
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72h (mean)
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
other: animals # 1,2,4,5,6
Time point:
other: 24, 48 and 72h (mean)
Score:
0
Max. score:
4
Other effects:
Discharge was observed in one animal at readings 24-48h (score 2) and 72h (score 1). This was reversible within 8 days.

Table 1: Irritation results

Animal

Reading

Cornea

Iritis

Conjunctiva

 

Opacity

Area

Redness

Chemosis

Symptoms

1

24 h

0

0

0

0

0

 

2

24 h

0

0

0

0

0

 

3

24 h

0

0

0

2

2

RE

4

24 h

0

0

0

1

0

 

5

24 h

0

0

0

1

0

 

6

24 h

0

0

0

1

0

 

1

48 h

0

0

0

0

0

 

2

48 h

0

0

0

1

0

 

3

48 h

0

0

0

2

1

RE

4

48 h

0

0

0

0

0

 

5

48 h

0

0

0

0

0

 

6

48 h

0

0

0

0

0

 

1

72 h

0

0

0

0

0

 

2

72 h

0

0

0

1

0

 

3

72 h

0

0

0

1

0

RE

4

72 h

0

0

0

0

0

 

5

72 h

0

0

0

0

0

 

6

72 h

0

0

0

0

0

 

1

8 d

0

0

0

0

0

 

2

8 d

0

0

0

0

0

 

3

8 d

0

0

0

0

0

RE

4

8 d

0

0

0

0

0

 

5

8 d

0

0

0

0

0

 

6

8 d

0

0

0

0

0

 

Mean animal 1

24 - 72 h

0

0

0

0

0

 

Mean animal 2

24 - 72 h

0

0

0

0.67

0

 

Mean animal 3

24 - 72 h

0

0

0

1.67

1

 

Mean animal 4

24 - 72 h

0

0

0

0.3

0

 

Mean animal 5

24 - 72 h

0

0

0

0.3

0

 

Mean animal 6

24 - 72 h

0

0

0

0.3

0

 

Mean animal 1 - 6

24 - 72 h

0

0

0

0.7

0.2

 

RE =small retractions in the eyelids

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

There are reliable studies available to assess the potential of the test substance for skin and eye irritation.

Skin irritation

To assess the acute skin irritation or corrosion potential of the test substance in vivo a skin irritation test in Vienna White rabbits similar to OECD guideline 404 was performed (BASF SE, 1981). The test item was applied by topical occlusive application of 0.5 g of the 50% test substance solution to the upper third of the back or flank of each of two rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 24 and 48 hours, as well as 8 days after removal of the dressing.

The test item did not elicit any skin reactions at the application site at any of the observation times (all scores 0). No clinical signs were observed.

Under the conditions of the present experiment, the test material does not give indication of an irritant property to rabbit skin.

Eye irritation

In a primary eye irritation test the acute eye irritation or corrosion potential of the test substance was assessed by a single ocular application of 0.1 mL bulk volume (about 75 mg) of the unchanged test substance to each one eye of three Vienna White rabbits according to Fed. Reg. 38, No. 187 (BASF SE, 1981). The test item was not washed out. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours as well as 8 after application.

Slight or moderate conjunctival redness was observed in some animals during the course of the study, while slight to moderate conjunctival chemosis and slight to moderate discharge only were observed in one animal.

The ocular reactions were reversible in all animals within 8 days after application at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity and for iris, 0.55 for conjunctival redness and 0.16 for chemosis. Discharge was observed in one animal at readings 24 - 48h (score 2) and 72h (score 1). This was reversible within 8 days

Considering the described ocular reactions as well as the average score for irritation, the test item is not irritating according to the CLP/GHS evaluation criteria.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin or eye irritation under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the third time in Directive EC 618/2012.