Registration Dossier

Administrative data

Description of key information

Skin: not irritating; Evonik, 1571/0017, 2008; OECD Guideline 404
Eye: not irritating; Evonik, 1571/0018, 2009; OECD Guideline 405

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
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)
Version / remarks:
(adopted 24 April 2002)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Safepharm Laboratories Limited, Shardlow, Derbyshire, UK
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: twelve to twenty weeks
- Weight at study initiation: 2 - 3.5 kg
- Housing: individually
- Diet: Free access to food (Certified Rabbit Diet)
- Water: Free access to drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
3 min, 1 h and 4 h
Observation period:
one hour following the removal of the patches, 24, 48 and 72 hours later; additional observations were made on Days 7 and 14;
Number of animals:
- 3 min and 1 h: 1 rabbit;
- 4 h: 3 rabbits
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area (one animal), back (two animals)
- Type of wrap if used: The test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 3 minutes, 1 hour and 4 hours after application

SCORING SYSTEM: according to OECD 404 / Draize J. H. (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.46-59
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(animal 1 - 3)
Time point:
other: 24 - 48 - 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: see table below for details
Irritation parameter:
edema score
Basis:
mean
Remarks:
(animal 1-3)
Time point:
other: 24 - 48 - 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: edema (score 1) only detected in one animal; see table below for details
Irritant / corrosive response data:
- 3-Minute Exposure Period:
Very slight erythema was noted at the treated skin site at the 24-hour observation, with well defined erythema and very slight oedema at the 48-hour observation. Very slight erythema, very slight oedema and loss of skin elasticity were noted at the 72-hour observation

- 1-Hour Exposure Period:
Very slight erythema was noted at the treated skin site one hour after patch removal and at the 24-hour observation, with well defined erythema and very slight oedema at the 48-hour observation. Very slight erythema, very slight oedema and loss of skin elasticity were noted at the 72-hour observation. Slight desquamation was noted at the 7-day observation.

- 4-Hour Exposure Period:
Very slight erythema was noted at one treated skin site one hour after dressing removal. Very slight to well defined erythema was noted at all treated test sites at the 24-hour, 48-hour and 72-hour observations. Very slight oedema was noted at one treated skin site one hour after dressing removal and at the 24-hour, 48-hour and 72-hour observations. Loss of skin elasticity was noted at two treated skin sites at the 48-hour observation and at all
treated skin sites at the 72-hour observation, with loss of flexibility at one treated skin site. Crust formation was noted at one treated skin site, with slight desquamation at one other treated skin site at the 7-day observation. One treated skin site appeared normal at the 7-day observation, and one treated skin site appeared normal at the 14-day observation.

Exposition:  3 min
Animal  Reading  Erythema Edema Symptoms
1 1 h 0 0  
1 24 h 1 0  
1 48 h 2 1  
1 72 h 1 1 loss of skin elasticity
1 7 d 0 0  
1 14 d 0 0  
mean 24 - 72 h 1.30 0.70  
Exposition:  1 h
Animal  Reading  Erythema Edema Symptoms
1 1 h 1 0  
1 24 h 1 0  
1 48 h 2 1  
1 72 h 1 1 loss of skin elasticity
1 7 d 0 0 slight desquamation
1 14 d 0 0  
mean 24 - 72 h 1.30 0.70  

Exposition:  4 h 
Animal  Reading  Erythema Edema
1 1 h 1 1
2 1 h 0 0
3 1 h 0 0
1 24 h 2 1
2 24 h 1 0
3 24 h 1 0
1 48 h 2 1
2 48 h 1 0
3 48 h 1 0
1 72 h 2 1
2 72 h 1 0
3 72 h 1 0
1 7 d 0 0
2 7 d 0 0
3 7 d 0 0
1 14 d 0 0
2 14 d not required not required
3 14 d not required not required
mean animal 1 24 - 72 h 2 1
mean animal 2 24 - 72 h 1 0
mean animal 3 24 - 72 h 1 0
mean animal 1-3 24 - 72 h 1.30 0.30

Primary irritation index = 1.7

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
other: GLP Guedeline study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
SafePharm Laboratories Limited, Shardlow, Derbyshire, UK
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: RarIan UK Limited, Bicester, Oxon, UK
- Age at study initiation: the animals were twelve to twenty weeks old
- Weight at study initiation: mean: 2.82 kg
- Housing: individually
- Diet: Certified Rabbit Diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): at least fifteen changes per hour
- 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): 0.1 ml


Duration of treatment / exposure:
72 h (no washing out conducted)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 male animals
Details on study design:
SCORING SYSTEM: OECD 405 / Assessment of ocular damage/irritation was made according to Draize J. H. (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49. Using the numerical data obtained a modified version of the system described by Kay J. H. and Calandra J. C. (1962), J. Soc. Cosmet. Chem. 13, 281-289 was used to classify the ocular irritancy potential of the test material.

TOOL USED TO ASSESS SCORE: 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:
(animal 1-3)
Time point:
other: 24 - 48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
(animal 1 - 3)
Time point:
other: 24 - 48 - 72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(animal 1- 3)
Time point:
other: 24 - 48 - 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(animal 1 - 3)
Time point:
other: 24 - 48 - 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: chemosis (score 1) 1 h after substance instillation in all animals
Irritant / corrosive response data:
No corneal or iridial effects were noted. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in two treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.
Other effects:
All animals showed expected gain in bodyweight during the study.

    Cornea Iris Conjunctiva
Animal  Reading  Opacity Area involved Redness Chemosis Discharge
1 1 h 0 0 0 2 1 1
2 1 h 0 0 0 1 1 1
3 1 h 0 0 0 1 0 1
1 24 hrs 0 0 0 1 0 0
2 24 hrs 0 0 0 1 0 0
3 24 hrs 0 0 0 1 0 0
1 48 hrs 0 0 0 0 0 0
2 48 hrs 0 0 0 0 0 0
3 48 hrs 0 0 0 0 0 0
1 72 hrs 0 0 0 0 0 0
2 72 hrs 0 0 0 0 0 0
3 72 hrs 0 0 0 0 0 0
mean animal 1 24/48/72 hrs 0.0   0.0 0.3 0.0  
mean animal 2 24/48/72 hrs 0.0   0.0 0.3 0.0  
mean animal 3 24/48/72 hrs 0.0   0.0 0.3 0.0  
mean animal 1-3 24/48/72 hrs 0.0   0.0 0.3 0.0  
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin:

In a primary dermal irritation study (OECD 404, Evonik, 1571/0017, 2008), 3 New Zealand White rabbits were dermally exposed to 0.5 mL of the test substance for 4 hours under semiocclusive conditions. Animals then were observed for 14 days. Irritation was scored by the method of Draize as described in the OECD guideline 404. The mean score for the 24, 48 and 72 h reading for erythema was 1.3 and for edema was 0.3. The skin reactions observed were fully reversible until day 7. In this study, the test substance is not a dermal irritant. This result is supported by another study which shows similar results.

 

 

Eye:

An eye irritation test was performed with three male New Zealand White rabbits acc. to OECD 405 (Evonik, 1571/0018, 2009). Eyes were left unwashed after application of 0.1 mL test substance and the animals were observed 72 h. The mean scores for the 24, 48 and 72 h reading for iritis, cornea opacity and conjunctivae chemosis were 0 at any reading time point. For conjunctivae redness the mean score was found to be 0.66 which was fully reversible within 48 hours. This result is supported by another study which shows similar results.

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. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No. 1272/2008.