Registration Dossier

Administrative data

Description of key information

Skin irritation (rabbit, OECD 404): non-irritant
Eye irritation (rabbit, OECD 405): non-irritant
Respiratory irritation: not tested

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 study in compliance with international guidelines
Reference:
Composition 0
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)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three New Zealand White rabbits were supplied by an accredited supplier. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to twenty weeks old. After an aeclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (Certified Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve horns darkness.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: not applicable
Amount / concentration applied:
At each test site a quantity of 0.5ml of 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.
Duration of treatment / exposure:
4 hours
Observation period:
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.
Number of animals:
3 rabbits
Details on study design:
On the day before the test each rabbit was clipped free of fir from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5ml of 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 1 and 4 hour exposure periods.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 ml of test material. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.
Irritation parameter:
other: erythema/eschar formation
Basis:
other: sum of 24 abd 72 h readings for 3 rabbits
Time point:
other: 1 h
Score:
2
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
other: erythema/eschar formation
Basis:
other: sum of 24 abd 72 h readings for 3 rabbits
Time point:
other: 24 h
Score:
2
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
other: erythema/eschar formation
Basis:
other: sum of 24 abd 72 h readings for 3 rabbits
Time point:
other: 48 h
Score:
2
Max. score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
other: erythema/eschar formation
Basis:
other: sum of 24 abd 72 h readings for 3 rabbits
Time point:
other: 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
other: sum of 24 abd 72 h readings for 3 rabbits
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by 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.47:
Primary Irritation Index Classification of Irritancy
0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant
Interpretation of results:
not irritating
Remarks:
Migrated information mild irritant Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 0.3 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. However, the substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.
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 study in compliance with international guidelines
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White rabbits were supplied by an accredited supplier. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (Certified Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
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.
Duration of treatment / exposure:
72 h
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately I hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from 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).
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
Initially, a single rabbit was 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 one second immediately after treatment, 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 according to the six point scale shown in the field "attached background material"
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Irritation parameter:
overall irritation score
Basis:
other: animal #1, #2, #3
Time point:
other: 1 h
Score:
6
Max. score:
6
Reversibility:
fully reversible within: 48 h
Irritation parameter:
overall irritation score
Basis:
animal: #1, #2, #3
Time point:
other: 24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
overall irritation score
Basis:
animal: #1, #2, #3
Time point:
other: 48 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
overall irritation score
Basis:
animal: #1, #2, #3
Time point:
other: 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:
Score for conjunetivae = (A + B + C) x 2
Score for iris = D x 5
Seoreforcomea = (ExF)x5
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra 3 C (1962), 3. Soc. Cosmet. Chem. 13, 28 1-289 (see Appendix 3) was used to classi& the ocular irritaney potential of the test material. This was achieved by adding together the scores for the cornea, iris and eonjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.
Interpretation of results:
not irritating
Remarks:
Migrated information minimal irritant Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 6.0 and was classified as a minimal irritant (class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.However, according to the Official Journal of the European Union 1272/2008 (CLP) dated December 16th2008 the test item shall not be classified as eye irritating.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation/Corrosion:

in vivo Skin irritation / corrosion - rabbit - 2007 - key: Klimisch 1 – GLP-compliant guideline (OECD guideline 404) study without deviation. Sponsored by Daikin Industries, Ltd and conducted by Safepharm Laboratories Limited At each test site a quantity of 0.5ml of 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. One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored. The test material produced a primary irritation index of 0.3 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. However, the substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.

Eye Irritation:

in vivo Eye irritation / corrosion - rabbit - 2007 - key: Klimisch 1 – GLP-compliant guideline (OECD guideline 405) study without deviation. Sponsored by Daikin Industries, Ltd and conducted by Safepharm Laboratories Limited. 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. Assessment of ocular damage/irritation was made approximately I hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977). The test material produced a maximum group mean score of 6.0 and was classified as a minimal irritant (class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.However, according to the Official Journal of the European Union 1272/2008 (CLP) dated December 16th2008 the test item shall not be classified as eye irritating.


Justification for selection of skin irritation / corrosion endpoint:
GLP study in compliance with international guidelines

Justification for selection of eye irritation endpoint:
GLP study in compliance with international guidelines

Justification for classification or non-classification

The attached Key studies, both of Klimish 1 reliability, bring to the conclusion that the substance should not be classified as irritant for eyes and skin.