Registration Dossier

Administrative data

Description of key information

There was no evidence for a skin and eye irritation potential of the test item.

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:
06-Nov-1996 to 14-Nov-1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD test guideline 404)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted on 17-Jul-1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, 88397 Biberach/Riss, Germany
- Age at study initiation: 15 weeks
- Weight at study initiation: 3.0 kg (male), 3.0-3.1 kg (females)
- Housing: individually, in stainless steel cages
- Diet: pelleted standard rabbit maintenance diet (Kliba 341, Kliba Mühlen AG, 4303 Kaiseraugst, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 40-70 %
- Air changes: 10-15 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: 06-Nov-1996 to 14-Nov-1996
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: moistened with bi-distilled water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
at least 72 hours
Number of animals:
1 male, 2 female rabbits
Details on study design:
TEST SITE
- Area of exposure: dorsal
- Area of exposure: 6 cm²
- Type of wrap if used: surgical gauze patch with semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in Directive 93/21/EEC (according to Draize, 1959) at approximately 1, 24, 48 and 72 hour(s) after the removal of the dressing, gauze patch and test item.
Minimal score: 0, maximal score: 4 (erythema and eschar formation, oedema formation)
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
overall irritation score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
8
Remarks on result:
other: calculated value
Irritant / corrosive response data:
The test item showed no irritant or corrosive potential.
Other effects:
No clinical signs of systemic toxicity were observed during the test and observation period, and no mortality occurred. No staining of the treated skin by the test item was observed. The body weight gain of all rabbits was within the normal range of variability.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the test article is regarded as not irritating to the rabbit skin.
Executive summary:

The primary skin irritation potential of the test article was investigated by semiocclusive, topical application of 0.5 g onto 6 cm2 intact dorsal skin of each of three young adult New Zealand rabbits. After 4 hours, the test item was removed with lukewarm water. 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 totaling 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 test 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. No clinical signs of systemic toxicity were observed during the test and observation period, and no mortality occurred. No staining of the treated skin by the test item was observed. The body weight gain of all rabbits was within the normal range of variability. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Based on the results of this study, the test article is regarded as not irritating to the 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:
13-Nov-1996 to 21-Nov-1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD test guideline 405)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted on 24-Feb-1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
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, 88397 Biberach/Riss, Germany
- Age at study initiation: 15 weeks old
- Weight at study initiation: 2.8 kg (male), 2.9-3.0 kg (females)
- Housing: individually, in stainless steel cages
- Diet: pelleted standard rabbit maintenance diet (Kliba 341, Kliba Mühlen AG, 4303 Kaiseraugst, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 40-70 %
- Air changes: 10-15 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: 13-Nov-1996 to 21-Nov-1996
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
single treatment, no washout performed
Observation period (in vivo):
at least 72 hours after the single treatment
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in Directive 92/69/EEC (according to Draize, 1959) at approximately 1, 24, 48 and 72 hour(s) after administration. Minimal score: 0, maximal score: 4 (corneal opacity, conjunctival chemosis), 3 (conjunctival redness) or 2 (iris lesions)

In addition, 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. Minimal score: 0, maximal score: 13

TOOL USED TO ASSESS SCORE:
Varta Cliptrix diagnostic lamp
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: individual mean score
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: individual mean score
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: individual mean score
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
3
Remarks on result:
other: individual mean score
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Remarks on result:
other: individual mean score
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
3
Remarks on result:
other: individual mean score
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(male)
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(female)
Time point:
other: 24, 48, 72 hours
Score:
0.33
Max. score:
4
Remarks on result:
other: individual mean score
Irritation parameter:
overall irritation score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0.44
Max. score:
13
Remarks on result:
other: calculated value
Irritant / corrosive response data:
Treatment with the test item resulted in a primary irritation score of 0.44. Slight redness and slight swelling of the conjunctivae as well as a slight watery discharge were noted in all animals after 1 hour. Hyperaemia of the scleral blood vessels was seen in one animal only at the 1 hour reading. The remaining 2 animals had slight reddening and slight swelling of the conjunctivae combined with slight watery discharge after 24 hours. All findings were reversible in these animals after 48 hours.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. No staining of the cornea, sclera or conjunctivae by the test item was observed. The body weight of the animals was within the normal range of variability.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the test material is considered to be not irritating to the rabbit eye.
Executive summary:

The primary irritation potential of the test article was investigated by an eye irritation study following OECD guideline 405 in compliance with GLP. 0.1g of the test article was instilled 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 totaling 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 0.44 (max. 13). Redness and swelling of the conjunctivae, as well as watery discharge were noted in all animals after one hour. Hyperemia of the scleral blood vessels was seen in one animal only after one hour. The remaining two animals had reddening and swelling of the conjunctivae combined with watery discharge after 24 hours. All findings were reversible after 48 hours. No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals. Based on the results of this study, the test material is considered to be not irritating to the rabbit eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The primary skin irritation potential of the test article was investigated in a dermal irritation study according to OECD guideline 404 in compliance with GLP (RTC, 1997). 0.5 g of the test item was applied topically to an area of 6 cm2 intact dorsal skin of each of three young adult New Zealand rabbits for 4 hours under semiocclusive conditions. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. Under the conditions of this experiment, the test 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. No clinical signs of systemic toxicity were observed during the test and observation period, and no mortality occurred. No staining of the treated skin by the test item was observed. The test article did not cause staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Based on the results of this study, the test article is regarded as not irritating to the rabbit skin.

This result is supported by the findings of a second in vivo irritation study (MB Research, 1984). In this study, only minimal dermal reactions were observed in 2/6 rabbits reversible within 72 hours. The test article was regarded as not irritating.

Eye irritation

The primary irritation potential of the test article was investigated by an eye irritation study following OECD guideline 405 in compliance with GLP (RTC, 1997). 0.1g of the test article was instilled 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. Redness and swelling of the conjunctivae, as well as watery discharge were noted in all animals after one hour. Hyperemia of the scleral blood vessels was seen in one animal only after one hour. The remaining two animals had reddening and swelling of the conjunctivae combined with watery discharge after 24 hours. All findings were reversible after 48 hours. No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals. Based on the results of this study, the test material is considered to be not irritating to the rabbit eye.

This result is supported by the findings of a second in vivo irritation study (MB Research, 1984). In this study, treatment with the test article caused minimal to mild ocular reactions below the threshold of regulatory significance. Therefore, based on the results of this study, the test article is considered to be not irritating to the rabbit eye.

Justification for classification or non-classification

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. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant OECD 405 study is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. 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 seventh time in Regulation (EC) No 2015/1221.