Registration Dossier

Administrative data

Description of key information

Skin irritation: No adverse effect observed (not irritating)
Eye irritation: No adverse effect observed (not irritating)

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:
29 September to 2 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.56 to 2.61 kg
- Housing: animals were housed individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 20 °C
- Humidity (%): 58 to 78 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/ 12
- on 2 occasions the relative humidity was above the limit specified in the study protocol (70 %). This deviation was considered not to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: moistened with water
Controls:
no
Amount / concentration applied:
0.5 g of the test material, moistened with 0.5 mL of distilled water
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape
- Type of wrap if used: the trunk of each animal was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scheme
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 2 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 1 at 1 hour observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 27 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No erythema/eschar observed at any observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 167 - female)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 1 at 1 hour observation
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 2 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No edema observed at any observation
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 27 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No edema observed at any observation
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 167 - female)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No edema observed at any observation
Irritant / corrosive response data:
The individual scores for erythemaleschar and oedema, are given in Table 1 (see attached background material)
Mean values required for EU labelling regulations are given in Table 2 (see attached background material).

Very slight erythema was noted in 2 treated skin sites 1 hour after patch removal. All treated skin sites appeared normal at the 24-hour observation.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The skin irritancy potential of the test material was assessed according to OECD guideline 404. The test material produced a primary irriation of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion) and Method B4 of Commission Directive 92/69/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of 3 rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation.

The test material produced a primary irritation of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

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 October 1997 to 19 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.54 to 2.75 kg
- Housing: animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 19 °C
- Humidity (%): 55- 74 %
- Air changes (per hr): 15 changes per hr
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): volume 0.1 mL , which was found to weigh approximately 41 mg
Duration of treatment / exposure:
Single application lasting 72 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
One rabbit was initially treated. A volume of 0.1 mL of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about 1 s immediately after application, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, 2 additional animals were treated.

Assessment of ocular damage/irritation was made approximately 1 h and 24, 48 and 72 h following treatment, according to the Draize scale for scoring ocular irritation.

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No corneal effects at any observation in any animal
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: No iridial effects at any observation in any animal
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
(Animal 1 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
(Animal 14 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
(Animal 15 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 14 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 1 at 1 hour observation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 15 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 1 at 1 hour observation
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Tables 1 and 2 (attached background material). The individual means scores are presented in Table 3 (attached background material).

Residual test material was noted around 1 treated eye at the 1-hour observation but did not prevent an evaluation of the ocular responses.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes 1 h after treatment with minimal conjunctival irritation at the 24-hour observation. Minimal conjunctival persisted in 1 treated eye at the 48-hour observation.

Treated eyes appeared normal at the 48 or 72-hour observations.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The eye irritancy potential of the test material was assessed according to OECD guideline 405.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce postive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion) and Method B4 of Commission Directive 92/69/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of 3 rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation.

The test material produced a primary irritation of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material does not meet the criteria for classification as irritant or corrosive according to Regulation (EC) No. 1272/2008 (CLP).

Eye irritation:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Treated eyes appeared normal at the 48 or 72-hour observations.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to Regulation (EC) No. 1272/2008 (CLP).


Justification for selection of skin irritation / corrosion endpoint:
The study has been conducted according to OECD guideline 404 and GLP and is adequately reported. Therefore, the study has been assigned a reliability 1 and is considered suitable for classification and labelling purposes.

Justification for selection of eye irritation endpoint:
The study has been conducted according to OECD guideline 405 and GLP and is adequately reported. Therefore, the study has been assigned a reliability 1 and is considered suitable for classification and labelling purposes.

Justification for classification or non-classification

Skin irritation: The test material did not meet the criteria for classification as a skin irritant according to Regulation 1272/2008 based on the mean scores obtained for each animal for erthema/eschar and oedema. The slight erythema noted at the 1 hour observation was fully reversible. Therefore the substance is not classified as a skin irritant.

Eye irritation: The test material did not meet the criteria for classification as an eye irritant according to Regulation 1272/2008 based on the mean scores obtained for each animal for corneal opacitiy, iritis, conjunctival redness and chemosis. The conjunctival irritation observed was fully reversible. Therefore the substance is not classified as an eye irritant.