Registration Dossier

Administrative data

Description of key information

Skin irritation:

rabbit, 4h, semiocclusive: not irritating (BASF 1986, OECD 404): key

rabbit, 24h, occlusive: slightly irritating (BASF 1994, USA/EPA/FIFRA: Subdivision F, Series 81, GLP)

rabbit, 24h, occlusive: not irritating (BASF 1997, Federal Register 38, No 187, Paragraph 1500.41, GLP)

rabbit, 24h, occlusive: slightly irritating (BASF 1984, Federal Register 38, No 187, Paragraph 1500.41)

 

Eye irritation:

rabbit: not irritating (BASF 1986, OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
- Lot/batch No.: Batch no. 7/85, 8.7.85
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main
- Age at study initiation: not mentioned
- Weight at study initiation: male: 3.02 kg; females: 3.13 kg (mean of two animals)
- Housing: single housing
- Diet: Kliba 341, 4 mm, Klingentalmuehle AG, Switzerland (about 130 g per animal per day)
- Water: about 250 ml tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted


Duration of treatment / exposure:
4 hrs
Observation period:
72 hrs
Number of animals:
3 (one male, two females)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap: test patches with a 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 hrs

OBSERVATION TIME POINTS
30-60 minutes after removal of the test patches and 24 hrs, 48 hrs, 72 hrs after the beginning of application.

SCORING SYSTEM: according to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
At the 4 hrs reading, erythema could be detected (score 1) on the skin of all three tested animals, but it was reversible within 24 hrs.
Other effects:
No other effects were detected.
Interpretation of results:
GHS criteria not met
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
10 May 1995 to 13 May 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, §16, Section 1500.41.
Version / remarks:
27 September 1973
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Lot number: 667-8674
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: approximately 10 to 12 weeks of age
- Weight at study initiation: 2.3-2.7 kg
- Housing: individual housing
- Diet: standard laboratory diet SDS Stanrab (P) Rabbit Diet, ad libitum
- Water: ad libitum
- Acclimation period: there was an acclimation period, but the duration was not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: undiluted
Duration of treatment / exposure:
24 hrs
Observation period:
3 days
Number of animals:
6 (4 males and 2 females)
Details on study design:
TEST SITE
- Area of exposure: 25 mm x 25 mm (dorso-lumbar region of each rabbit)
- Type of wrap: gauze pads, covered with "Elastoplast" elastic adhesive dressing backed with "Sleek" waterproof strapping

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water (30-40°C)
- Time after start of exposure: 24 hrs

OBSERVATION TIME POINTS
Clinical signs were observed daily. Examination of the treated skin was made 24 and 72 hrs after exposure.

SCORING SYSTEM: scoring system according to Code of Federal Regulations, Title 16, Section 1500.41 (Draize test).
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritant / corrosive response data:
At the 24 hrs reading: very slight erythema was seen in two of the six animals; additionally. The described reactions had resolved completely by the 72 hrs reading. The Primary Irritation Index was calculated to be 0.2.
Other effects:
There were no clinical signs of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
study cannot be used for classification
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
other: Code of Federal Regulations, §16, Section 1500.41.
Version / remarks:
27 September 1973
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
Lot/batch No.: 17 622/10
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: 2.34 - 2.49 kg
- Housing: single in stainless steel cages (40X51cm)
- Diet: Ovator Solikanin 4 mm; Muskator-Werke Düsseldorf, Germany: app. 130g per day and animal, ad libitum
- Water: app. 250ml tap water per day and animal, ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact (shaved) skin
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: app. 0.5 mL
- Concentration: unchanged
Duration of treatment / exposure:
24h
Observation period:
Observations: day 1 (30-60min after removal of dressing), day 2, day 3, and day 8
Number of animals:
5 males, 7 females (6 each with intact of abraded skin)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing: remaining substance was wiped off
- Time after start of exposure: 24h (after removal of dressing)

SCORING SYSTEM: according to Draize
Erythema and Edema
0: no effect
1: weak effect
2: defined effect
3. medium to strong effect
4: strong to very strong effect
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Interpretation of results:
study cannot be used for classification
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
17 August 1994 to 20 August 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Version / remarks:
November 1984
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch number: T 104
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, Prouzel, France
- Age at study initiation: no data available
- Weight at study initiation: mean body weight of the 6 used animals: 2.5 kg
- Housing: individually
- Diet: free access to 112 C pelleted diet; each batch of food was analysed (composition and contaminants) by the supplier
- Water: filtered by a F.G. Millipore membrane (0.22 micron) and contained in bottles, ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
occlusive
Preparation of test site:
other: scarified and non-scarified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted
Duration of treatment / exposure:
24 hrs
Observation period:
24 and 72 hrs
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap: hypoallergenic occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
Erythema and eschar formation:
- no erythema: 0
- slight erythema (barely perceptible): 1
- well-defined erythema: 2
- pronounced erythema: 3
- severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Edema formation
no edema. 0
- very slight oedema (barely pereeptible): 1
- slight oedema (edges of area well-defined by definite raising): 2
- moderate oedema (raised approximately 1 millimetre): 3
- severe oedema (raised more than 1 millimetre and extending beyond area of exposure): 4

Any other lesions were noted.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/72 hrs
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24/72 hrs
Score:
0
Max. score:
4
Irritant / corrosive response data:
Non-scarified flank: Slight to marked erythema (scores 1 to 3) was observed on all animals 24 hrs after application of the test substance. Erythema (scores 1 to 3) persisted on 5 animals at the 72 hrs reading. Severe edema (score 4) was noted on 1 animal (animal 1) 24 hrs after application of the test substance. Dryness of the skin was observed on 2 animals (animal 1 and 4) at the 72 hrs reading. The Cutanous Primary Irritation Index was calculated to be 2.0.
Interpretation of results:
study cannot be used for classification
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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
Batch no. 7/85, 8.7.85
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler; Offenbach/Main
- Age at study initiation: not mentioned
- Weight at study initiation: male: 3.08 kg (mean of two animals); female: 2.94
- Housing: single housing
- Diet: Kliba 341, 4 mm, Klingentalmuehle AG, Switzerland (about 130 g per animal per day)
- Water: about 250 ml tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
No washing performed.
Observation period (in vivo):
72 hrs
Number of animals or in vitro replicates:
3 (two males, one female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing performed

OBSERVATIONS: Examination and scoring were performed after 1 hr, 24 hrs, 48 hrs, 72 hrs after instillation of the eye with the test substance.

SCORING SYSTEM: according to OECD Guideline 405; Calculation of the mean according to 83/467/EEC Criteria of July 29th, 1983, only the readings of 24, 48 and 72 hrs were used.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After 1 hr conjunctivae redness and chemosis could be detected. But the conjunctivae redness was reversible within 24 hrs (animal 1 and animal 3) or 48 hrs (animal 2), and the chemosis was reversible within 24 hrs.
Other effects:
No other effects observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Several in vivo guideline studies exist, that evaluate the skin irritating potential of the test substance. Only one was performed according to current OECD guideline 404 (BASF, 1986) and was therefore chosen as key study. Intact skin of 1 male and 2 female White Vienna rabbits was exposed to 0.5 mL of the test substance for four hours under semi-occlusive conditions. No erythema or edema were observed in any animal within the first 72 hours, and the study was terminated after 3 days.

 

In a study according to the USA/EPA/FIFRA guideline, subdivision F, Series 81 and GLP (BASF, 1994), 6 New Zealand White rabbits were treated with 0.5 mL of the test substance under occlusive conditions for 24 hours. Edema grade 1 was observed in one rabbit only. Erythema scores ranged from 0.5 to 3 (individual grades: 0.5, 1, 2.5, 2.5, 1.5, 3), half of which were not fully reversible within 72 hours.

 

In a similar study performed according to Federal Register 38, No 187, Paragraph 1500.41 and GLP (BASF 1997), also 6 New Zealand White rabbits were treated with 0.5 mL of the test substance for 24 hours under occlusive conditions. In this case, no edema were observed, and only 2 out of 6 rabbits showed erythema grade 0.5 (mean value from 24h, 48h, and 72h reading).

 

6 White Vienna rabbits were exposed to 0.5 mL of the test substance for 24 hours using occlusive conditions in an additional study according to Federal Register 38, No 187, Paragraph 1500.41 and GLP (BASF, 1984). All animals showed erythema between grade 1 and 2.6 (mean values from 24h, 48h, and 72h readings), and edema grade 0.3 (3 animals) or grade 2 (3 animals).

 

No eye irritation was observed in an in vivo study according to OECD 405 (BASF, 1986). 0.1 mL of the test substance was applied to the eyes of 2 male and 1 female White Vienna rabbit. All scores for iris, cornea, chemosis and conjunctival redness were 0, except for one rabbit which showed a mean value (24 - 72h) of 0.3 for conjunctival redness.

Justification for classification or non-classification

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

Two out of four skin irritation studies, which were performed under harsh occlusive conditions, showed a slight irritating potential, which was just not sufficient for classification according to Regulation (EC) No 1272/2008. The other two studies, of which one was performed according to current OECD recommended conditions, while the other also used long-term occlusive exposure, showed no skin irritation. In addition, no eye irritating potential was observed. Based on these data, the substance is considered to be classified neither for skin nor for eye irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.