Registration Dossier

Administrative data

Description of key information

The substance is not irritating to skin and eyes.

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:
1986
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
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Remarks:
Research & Consulting Company AG
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 15 to 16 weeks
- Weight at study initiation: 2.5 to 2.6 kg
- Housing: Housed individually in stainless steel cages
- Diet (e.g. ad libitum): Pelleted standard Kliba 341
- Water (e.g. ad libitum): Community tap mater
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Jun 6, 1986 To: Jun 13, 1986
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: Tap water and 2 to 3 drops of Tween 80
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- The test article was applied moistened with tap water and 2 to 3 drops of Tween 80
Duration of treatment / exposure:
4 hours
Observation period:
Up to 72 hours after the removal of the dressing
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- % coverage: Coverage was 3.0 cm x 3.0 cm
- Type of wrap if used: Test article was applied to the intact skin of the shaved area and was covered with a patch of surgical gauze. The gauze was covered with aluminum foil and then covered with an occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Four hours after the application, the dressing was removed and the skin was flushed with luke warm tap water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The same scoring system as the one provided in the OECD guideline 404.
To classify the irritating property of the test article, the mean values of erythema / eschar as well as of edema formation were calculated for each individual, using the scores between 24 and 72 hours (EEC Council Directive 83/467/EEC, July 1983, Brussels/Belgium). The dermal irritation scores were evaluated in conjunction with the nature and reversibility or otherwise of the responses observed.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
Erythema and edema scores of 0 were reported in all animals tested at 1, 24, 48, and 72 hours. No staining of the treated skin by pigment or coloring of the test article was observed. No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.
Other effects:
No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. No macroscopic organ examination was performed. The body weight gain of all rabbits was similar.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this experiment, the test article is considered to be not irritating to the rabbit skin.
Executive summary:

The primary skin irritation potential of the test substance was investigated in a GLP compliant study according to OECD test guideline 404. The test item (0.5 g) was moistened with tap water and 2 to 3 drops of Tween 80 and applied by topical occlusive application to the intact dorsal area of three young adult New Zealand White rabbits. The duration of treatment was four hours after which the test article was removed by washing with lukewarm water. The skin reaction was assessed at 1, 24, 48 and 72 hours intervals after the removal of the dressing, gauze patch and test article. The corrosive properties of the test article to and the color of the treated skin area were described and recorded. The observation was terminated 72 hours after application of the test article. To classify the irritating property of the test article, the mean values of erythema / eschar as well as of edema formation were calculated for each individual, using the scores between 24 and 72 hours. Erythema and edema scores of 0 were reported in all animals tested at 1, 24, 48, and 72 hours. No staining of the treated skin by pigment or coloring of the test article was observed. No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin. No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. No macroscopic organ examination was performed. The body weight gain of all rabbits was similar. Thus, the test item did not induce significant irreversible damage to the skin and is therefore not regarded as a skin irritant.

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:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Remarks:
Research & Consulting Company AG (CH 4452 Itingen/Switzerland)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG (CH 4414 Fuellinsdorf/Switzerland)
- Age at study initiation: 15 to 16 weeks
- Weight at study initiation: 2.6 to 2.7 kg
- Housing: Individually housed in stainless steel cages
- Diet: ad libitum pelleted standard Kliba 341, Batch 15/86 rabbit maintenance diet
- Water: Community tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Jun 6, 1986 To: Jun 13, 1986
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Single dose administration, eyes were kept unwashed
Observation period (in vivo):
Up to 72 hours
Number of animals or in vitro replicates:
2 males and 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
Not rinsed.

SCORING SYSTEM: Same as the scale provided in the OECD guideline 405.

TOOL USED TO ASSESS SCORE: slit lamp and a Varta Cliptrix diagnostic lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Conjunctivae score of 1 after 1 hour in all three animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
The test article showed a primary irritation score of 0.3, when applied to the rabbit eye mucosa. In all three animals, minimal redness of the conjunctivae was observed at the 1 hour time point, but this effect was reversible within 24 hours. No corrosion of the cornea was observed at any of the measuring intervals. In the area of application, staining of the cornea and conjunctivae by pigment or coloring of the test article was observed.
Other effects:
No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. The observation was terminated 72 hours after administration of the test article. The body weight gain of all rabbits was similar. Due to the results obtained, no macroscopic organ examination was indicated.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance caused only minimal conjunctival redness revesible within 24 hours and is therefore classified as not irritating to the rabbit eye.
Executive summary:

In a GLP-compliant eye irritation study performed according to OECD guideline 405, three New Zealand White rabbits were treated with 0.1 g of the undiluted test article. The test material was placed into the conjunctival sac of the left eye of each animal; the lids were then held together for about one second in order to prevent loss of the test material. The ocular reactions were evaluated 1, 24, 48 and 72 hours after instillation and animals were checked daily for signs of systemic toxicity. The ocular reactions were graded according to the scoring scale presented in the OECD guideline 405. Under the experimental conditions employed the test article induced minimal conjunctival redness at the 1 hour time point (score of 1). All signs of irritation disappeared within 24 hours. In the area of application staining of the cornea and conjunctivae by coloring of the test article was observed. No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred. In conclusion, based on the results of this study, the test article is regarded as not irritating to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation

In a GLP-compliant dermal irritation study performed according to OECD guideline 404, the test substance (0.5 g) in tap water supplemented with 2 to 3 drops of Tween 80 was applied under occlusive conditions to the intact skin of three New Zealand White rabbits. Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed according to the OECD Guidelines for Testing of Chemicals at 1, 24, 48 and 72 hours after removal of the dressing. No skin reactions could be observed in any animal at any point of time.

In a second dermal irritation study performed according to OECD 404, the skin of three female New Zealand white rabbits were treated with 0.5 g of the test substance in water under occlusive conditions for four hours. The skin reactions were evaluated 1, 24, 48 and 72 hours after removing the gauze patches according to the OECD scoring system. Minimal to mild erythema formation in all animals and minimal edema formation in one animal was observed. All findings were reversible within 72 hours. The mean values of the recordings 24 to 72 hours after application were under the threshold of significance.

In conclusion, the test substance does not need to be classified for skin irritation.

Eye irritation

In an eye irritation study performed according to OECD guideline 405, 0.1 g of the test substance was placed in the conjunctival sac of the left eyes of three New Zealand White rabbits. The eyes of each animal were examined 1, 24, 48 and 72 hours after administration. The irritation was assessed according to the OECD Guidelines for testing of Chemicals. All mean values after 24, 48 and 72 hours were zero. Only minimal redness of the conjunctivae was observed in all animals after 1 hour, but this finding was reversed to normal after 24 hours.

In two supporting studies the test item's potential to cause eye irritation was investigated in New Zealand White rabbits. The mean scores after 24, 48 and 72 hours in the first study were zero except for conjunctival redness, which scored 0.33 in one animal and 0.66 in two animals. In the second study, all mean scores were zero in all animals for all parameters. Only minimal redness of the conjunctivae was observed in all animals after 1 hour, but this finding was reversed to normal after 24 hours.

In conclusion, the test substance does not need to be classified for eye irritation.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, the test substance is not classified as skin or eye irritant