Registration Dossier

Administrative data

Description of key information

Skin irritation: The test substance is not a dermal irritant. The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Eye irritation: The test substance produced moderate conjunctival irritation in all treated eyes one hour after treatment. All treated eyes appeared normal at the 48‑Hour observation. The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

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:
guideline study
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.
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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White rabbits were supplied by David Percival ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.61 to 2.90 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (Stanrab SQC Rabbit diet supplied by Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur
Vehicle:
other: Test material moistened with 0.5ml dried arachis oil
Controls:
other: Dried arachis oil applied to a separate skin site of animal also treated with test material
Amount / concentration applied:
TEST MATERIAL
For the purpose of the study the test item was ground to a powder before use.

At each test site a quantity of 0.5 g of the test item, moistened with 0.5 ml of dried arachis oil was introduced under a 2.5 cm x 2.5cm gauze patch.
Duration of treatment / exposure:
4 hours (all animals)
Observation period:
1 hour, 24 hours, 48 hours, 72 hours and on Day 7.
Number of animals:
2 males and 1 female
Details on study design:
PROCEDURE:
On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 g of the test item, moistened with 0.5 ml of dried arachis oil, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the left shorn flank. Similarly a quantity 0.5ml of dried arachs oil was applied to a separate skin silte on the shorn right flank. The patches were secured in position with a strips of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

4 hours after application the corset and patches were removed from each animal and any residual test item and control material removed by gentle swabbing with cotton wool soaked in dried arachis oil followed by 74% industrial methylated spirits..

SCORING SYSTEM:
Approximately 1 hour following removal of the patches and 24, 48 and 72 hours later, the test and control sites were examined for evidence of primary irritation and scored according to the Draize scale (see evaluation of skin reactions below).

Any other skin reactions if present, were also recorded.

An additional observation was made on Day 7 to assess the reversibility of skin reactions.

Individual bodyweights were recorded on Day 0 (the day of treatment.









Irritation parameter:
erythema score
Basis:
mean
Remarks:
(animal #1 - 22)
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Test material
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 1 - 22
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Test material
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2 - 23
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Test material
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 2 - 23
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Test material
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 3 - 30
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Test material
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 3 - 30
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Test material
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 1 - 22
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Control arachis oil
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # - 22
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Control arachis oil
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 2 - 23
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Control arachis oil
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # - 23
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Control arachis oil
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 3 - 30
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Control arachis oil
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 3 - 30
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Control arachis oil
Irritant / corrosive response data:
For individual skin reacions see attached background information.
Test material
Very slight erythema was noted at two treated skin sites at the 24, 48 and 72 hour observations.

Control material - dried arachis oil
Very slight erythema was noted at two treated skin sites at the 24 and 48 hour observations and persisted at one treated skin site at the 72 hour observation.
Other effects:
Test material
Loss of skin elasticity was noted at two treated skin sites at t he 72 hour observation. Slight desquamation. was noted in one treated skin site at the 7 day observation. Two treated skin sites appeared normal at the 7 day observation

Control material - dried arachis oil
Loss of skin elasticity was noted at one treated skin site at the 72 hour observation. Slight desquamation was noted in one treated skin site at the 7 day observation. Two treated skin sites appeared normal at the 7 day observation.

Results summary

 Treatment  Primary irritation index  Classifcation
 Test material  0.7  Mild irrtant
 Control arachis oil  0.5  Mild irriatnt

 

The test material does not meet the criteria for classifciation as irritant or corrosive according to CLP regulations.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No corrosive effects were noted.The test item produced a primary irritation index of 0.7 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.
Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 92/69/EEC

Results. 

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight erythema. Other skin reactions noted were loss of skin elasticity and slight desquamation.

A single 4-hour, semi-occluded application of the vehicle control dried arachis oil to the intact skin of three rabbits produced very slight erythema. Other skin reactions noted were loss of skin elasticity and slight desquamation.

Conclusion. 

The test item did not present any significantly greater risk than the control material..

The test item produced a maximum individual mean score of 1.0 and therefore did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

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:
guideline study
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
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 (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White rabbits were supplied by David Percival ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.52 to 2.88 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (Stanrab SQC Rabbit diet supplied by Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Vehicle:
unchanged (no vehicle)
Remarks:
Test material ground to a powder
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test material was ground to a powder before use. A volume of 0.1ml weighing approximately 60mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.
Duration of treatment / exposure:
SIngle application without irrigation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
PROCEDURE:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced

Initially, a single rabbit was treated. A volume of 0.1 ml of the test item, which was found to weigh approximately 60 mg (as measured by gently compacting the required volume into an adapted syringe) 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 item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made.

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


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 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 Priciples and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p48 to 49. See attached background information

Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Other:
Individual bodyweights were recorded on the Day of treatment.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1 (201)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1 (201)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
animal #1 (201)
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1 (201)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2 (205)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2 (205)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
animal #2 (205)
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2 (205)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3 (210)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3 (210)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
animal #3 (210)
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3 (210)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Ocular Reactions:
Individual and group mean scores for ocular irritation are given in the attached background information.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24 hour observations.

All treated eyes appeared normal at the 48-Hour observation.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48 Hour observation.
The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.
Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 February 1987)

- Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 92/69/EEC

Result. 

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48‑Hour observation.

Conclusion. 

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 92/69/EEC

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight erythema. Other skin reactions noted were loss of skin elasticity and slight desquamation.

A single 4-hour, semi-occluded application of the vehicle control dried arachis oil to the intact skin of three rabbits produced very slight erythema. Other skin reactions noted were loss of skin elasticity and slight desquamation.

The test item produced a maximum individual mean score of 1.0 and therefore did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Eye Irritation

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 February 1987)

- Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 92/69/EEC

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48‑Hour observation.

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Justification for classification or non-classification

The results from skin irritation and eye irritation studies were evaluated according to the Classification, Labelling and Packaging Regulation (CLP).

Skin irritation:

The test item produced a maximum individual mean score of 1 for erythema (based on scores at 24, 48 and 72) in two animals only and therefore does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP).

Eye irritation:

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP), as although some moderate conjunctival irritation was observed, all treated eyes appeared normal at the 48 hour observation The effects were insufficient to meet the criteria for classification according to the Classification, Labelling and Packaging Regulation.