Registration Dossier

Administrative data

Description of key information

Skin irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to rabbit skin.
Eye irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to the eye.

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:
1996
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D - 88397 Biberach / Riss, Germany
- Age at study initiation: 15-17 weeks
- Weight at study initiation: 2.8-3.1 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-08-07 To: 1996-08-15
Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
water
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72h
Number of animals:
1 male, 2 female animals
Details on study design:
TEST SITE
- Area of exposure: back
- coverage: approx. 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water
- Time after start of exposure: 4h

SCORING SYSTEM:

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) to slight eschar formation (injuries in depth) 4
Maximum possible score 4

EDEMA FORMATION
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Maximum possible score 4

Maximum cumulative score: 8
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 1h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritant / corrosive response data:
The substance showed a primary irritation score of 0.00, when applied to healthy intact rabbit skin.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
No clinical signs of systemic toxicity were observed.
Light orange staining by the test article of the treated skin was observed.
The body weight gain of all rabbits was within the normal range of variability.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is classified as "not irritating" to rabbit skin.
Executive summary:

The primary skin irritation potential of the test article was investigated by Directive 92/69 EEC, B.4. "Acute Toxicity - Skin Irritation", July 31, 1992, U.S. Environmental Protection Agency, Code of Federal Regulations 40, Part 798, Health Effects Testing Guidelines, Subpart E, Specific organ/tissue toxicity, Paragraph 798.4470 "Primary dermal irritation", revised as of July 1, 1993, and OECD Guidelines for Testing of Chemicals, Section 4, number 404, "Acute Dermal Irritation / Corrosion", adopted July 17, 1992 (reported Paris April 29, 1993).

500 mg of the test item were topically applied onto 6 cm² intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of

figures. Under the conditions of this experiment, the substance was found to cause a primary irritation score of 0.00 (max. 8.0) when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused light orange staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based upon the referred classification criteria , the substance is classified as "not irritating" to rabbit skin.

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:
1996
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4500 (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: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D - 88397 Biberach / Riss, Germany
- Age at study initiation: 15-17 weeks
- Weight at study initiation: 2.8-3.1 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-08-14 To: 1996-08-22
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
Single treatment with the test item.
Observation period (in vivo):
Observation at 1, 24, 48, and 72h after instillation of the test item into the eye.
Number of animals or in vitro replicates:
Three animals (1 male, 2 females)
Details on study design:
SCORING SYSTEM: Standard Draize system
Corneal irritation: 0-4
Iris irritation: 0-2
Conjunctival redness: 0-3
Chemosis: 0-4

REMOVAL OF TEST SUBSTANCE
- Washing: not performed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean values 24 - 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean values 24 - 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean values 24 - 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Remarks on result:
other: conjunctiae redness (score = 2) was observed only at hour 1, but was zero after 24 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean values 24 - 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Remarks on result:
other: chemosis observed (max. score = 1) was observed only at hour 1, but was zero after 24 hours
Irritant / corrosive response data:
The substance showed a primary irritation score of 0.00, when applied to the conjunctival sac of the rabbit eye.
After one hour, moderate reddening of the conjunctivae and slight watery discharge were noted in all animals, and slight swelling was noted in two of three animals. All signs of irritation were reversible after 24 hours.
No corrosion of the cornea was observed at any of the reading times.
Other effects:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
- Light orange staining of the sclera was seen in all animals after one hour. Light orange staining of the conjunctivae was noted after one and 24 hours in two of three animals.
- The body weight of the animals was within the normal range of variability.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria, the substance is classified as "not irritating" to the eye.
Executive summary:

The primary irritation potential of the substance was investigated according to Directive 92/69 EEC, B.5. "Acute Toxicity - Eye Irritation", July 31, 1992, U. S. Environmental Protection Agency, Code of Federal Regulations 40, Part 798, Health Effects Testing Guidelines, Subpart E, Specific organ/tissue toxicity, Paragraph 798.4500 "Primary eye irritation", revised as of July 1, 1993, and OECD Guidelines for Testing of Chemicals, Section 4, number 405 "Acute Eye Irritation / Corrosion", adopted February 24, 1987.

0.1 g of the test item was instilled undiluted into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of figures.

The primary irritation score was 0.00 (max. 13). After one hour, reddening of the conjunctivae and watery discharge were noted in all animals, and swelling was noted in two of three animals. All signs of irritation were reversible after 24 hours. Light orange staining of the sclera was seen in all animals after one hour. Light orange staining of the conjunctivae was noted after one and 24 hours in two of three animals.

No corrosion was observed at any of the measuring intervals.

Based upon the referred classification criteria, the substance is classified as "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

Two valid in-vivo studies on skin and eye iritation have been conducted with the registration substance. In order to assess the skin irritating potential of the test substance, 500 mg of the test item were topically applied onto 6 cm² intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test article caused light orange staining of the treated skin. Under the conditions of this experiment, the substance was found to cause a primary irritation score of 0.00 when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

In order to assess the primary eye irritating potential of the test substance, 0.1 g of the test item was instilled undiluted into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The primary irritation score was 0.00. After one hour, reddening of the conjunctivae and watery discharge were noted in all animals, and swelling was noted in two of three animals. All signs of irritation were reversible after 24 hours. Light orange staining of the sclera was seen in all animals after one hour. Light orange staining of the conjunctivae was noted after one and 24 hours in two of three animals. No corrosion was observed at any of the measuring intervals.


Justification for selection of skin irritation / corrosion endpoint:
The selected study was performed under GLP and in accordance with OECD TG 404. No other studies are available.

Justification for selection of eye irritation endpoint:
The selected study was performed under GLP and in accordance with OECD TG 405. No other studies are available.

Justification for classification or non-classification

Skin irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to rabbit skin.

Eye irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to the eye.