Registration Dossier

Administrative data

Description of key information

Skin irritation = Not irritating, rabbit, OECD 404, EU method B.4, de Jouffrey 1995c
Eye irritation = Not irritating, rabbit, OECD 405, EU method B.5, de Jouffrey 1995b

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:
21 June 1995 to 3 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed to valid guidelines and the study was conducted under GLP conditions.
Reason / purpose:
reference to other study
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:
TEST ANIMALS
- Sex: male
- Weight at study initiation: 2.4 ± 0.1 kg (mean)
- Housing: individually in polystyrene cages
- Diet: pelleted diet, ad libitum
- Water: filtered drinking water (0.22 µm), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 21 June 1995 to 3 July 1995
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
3 days post administration
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: On the day prior to application, the flanks of each animal were clipped using electric clippers. A dose of 500 mg of test material was applied to a 6 cm² hydrophilic gauze pad moistened with 0.5 mL of distilled water and this was then applied to the right flank of the animals for 4 hours. The left flank did not receive any test material and served as an untreated control.
- Type of wrap if used: The test material and gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the dressing was removed and any residual test material was wiped off with a gauze pad moistened with water.
- Time after start of exposure: approximately 4 hours

SCORING SYSTEM:
The Draize scale, presented as table 1 in the field "Any other information on material and methods incl. tables" was used to assess the degree of erythema and oedema at the application sites approximately 1 hour and 1, 2 and 3 days after the removal of the dressings. Any other lesions were recorded.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable since no skin reaction was noted in any of the animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Max. score:
4
Reversibility:
no data
Remarks on result:
other: Scores for erythema could not be determined due to the skin colouration caused by the test material
Irritant / corrosive response data:
No oedema was noted at any time point.
Other effects:
Moderate to very slight purple colouration of the test site was noted on all animals which masked any observations of erythema of grades 1 to 3. The colouration persisted for 10 to 12 days post test material application.

Table 2: Results

Rabbit number

Dermal irritation

Scores

Mean irritation score

1 h

24 h

48 h

72 h

1

Erythema

C2

C2

C2

C2

(2)

Oedema

0

0

0

0

0

2

Erythema

C2

C2

C2

C2

(2)

Oedema

0

0

0

0

0

3

Erythema

C3

C3

C3

C2

(2)

Oedema

0

0

0

0

0

C2 = purple colouration of the skin would mask an erythema score of grades 1 or 2

C3 = purple colouration of the skin would mask an erythema score of grades 1 or 3

(2) = not calculated

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material did not elicit any reaction in any of the animals during the course of the study that meant the test material required classification as a skin irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The skin irritation potential of the test material was determined in accordance with standardised guidelines OECD 404 and EU Method B.4. Three rabbits received a single four hour application of 500 mg of the test material and were assessed for the following 3 days for any signs of skin irritation. The mean score over 24, 48 and 72 hours for each individual animal was 0.0 for oedema. Scores for erythema could not be calculated due to skin colouration. Due to skin colouration, evaluation of skin irritation could not be made. However, the absence of oedema in this study, the very weak ocular reactions observed in the acute eye irritation study (rabbits; de Jouffrey 1995b) and the absence of local effects observed in an acute dermal study (rat; de Jouffery 1996a) allows us to conclude that the test material is not a skin irritant based on expert judgment.

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:
29 June 1995 to 2 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, performed to valid guidelines and the study was conducted under GLP conditions.
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute 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:
TEST ANIMALS
- Sex: males
- Weight at study initiation: 2.6 ± 0.2 kg (mean)
- Housing: individually in polystyrene cages
- Diet: pelleted diet, ad libitum
- Water: filtered drinking water (0.22 µm), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 29 June 1995 to 2 July 1995
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
A single application was performed
Observation period (in vivo):
72 hours following dose administration
Number of animals or in vitro replicates:
3 males
Details on study design:
ADMINISTRATION
- Dose administration: Approximately 100 mg of the test material was applied into the conjunctival sac of the left eye of each rabbit by gently pulling the lower lid away from the eyeball. The lower and upper eyelids were then gently held together for about 1 second to avoid any loss of test material. The right eye was untreated (control eye).

REMOVAL OF TEST SUBSTANCE
- The eyes were not rinsed after administration of the test material.

SCORING SYSTEM
- The reactions observed were scored in accordance with the criteria of Draize (see field "Any other information on materials and methods incl. tables" for further information), at 1, 24, 48 and 72 hours after administration of the test material.

TOOL USED TO ASSESS SCORE: Direct corneal examination was performed, if necessary with an Ultra Violet lamp. 1 or 2 drops of 0.5 % sodium fluorescein solution was used to determine the presence or absence of corneal opacification.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no effects observed
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: no iridial effects noted throughout study
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no corneal effects noted throughout study
Irritant / corrosive response data:
Very slight or slight conjunctival redness (grade 1 or 2) was observed at the 24 hour reading in all animals. Conjunctival redness was masked by a garnet colouration of the conjunctiva one hour after treatment only; in addition, a moderate clear discharge (grade 2) was noted in one animal only. No effects on the iris or cornea were noted. No ocular reactions were observed after the 24 hour reading.

Table 2: Results

Rabbit number

Region of eye

Ocular reaction

Score

Mean irritation score**

1 hour

24 hours

48 hours

72 hours

1

Conjunctivae

Chemosis

0

0

0

0

0.0

Redness

C

1

0

0

0.3

Discharge

0

0

0

0

0.0

Iris

0

0

0

0

0.0

Corneal opacity

Intensity

0

0

0

0

0.0

Area

0

0

0

0

0.0

Other

*

*

*

*

Fluorescein

/

U

/

/

2

Conjunctivae

Chemosis

0

0

0

0

0.0

Redness

C

2

0

0

0.7

Discharge

0

0

0

0

0.0

Iris

0

0

0

0

0.0

Corneal opacity

Intensity

0

0

0

0

0.0

Area

0

0

0

0

0.0

Other

*

*

*

*

Fluorescein

/

U

/

/

3

Conjunctivae

Chemosis

0

0

0

0

0.0

Redness

C

1

0

0

0.3

Discharge

2

0

0

0

0.0

Iris

0

0

0

0

0.0

Corneal opacity

Intensity

0

0

0

0

0.0

Area

0

0

0

0

0.0

Other

*

*

*

*

Fluorescein

/

U

/

/

** = Mean of readings taken at 24, 48 and 72 hours only

C = scoring obscured by garnet colouration

* = None

/ = fluorescein not used

U = fluorescein used

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The eye irritation potential of the test material was determined in accordance with standardised guidelines OECD 405 and EU Method B.5. Approximately 100 mg of test material was applied into one eye of each of three rabbits; the animals were assessed for up to 72 hours to determine the grade of ocular reaction. Very slight or slight conjunctival redness (grade 1 or 2) was observed at the 24 hour reading in all animals. Conjunctival redness was masked by a garnet colouration of the conjunctiva one hour after treatment only; in addition, a moderate clear discharge (grade 2) was noted in one animal only. No effects on the iris or cornea were noted. No ocular reactions were observed after the 24 hour reading. Based on these observation it was determined that the test material in not classified for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

The skin irritation potential of the test material was determined in accordance with standardised guidelines OECD 404 and EU Method B.4. Three rabbits received a single four hour application of 500 mg of the test material and were assessed for the following 3 days for any signs of skin irritation. The mean score over 24, 48 and 72 hours for each individual animal was 0.0 for oedema. Scores for erythema could not be calculated due to skin colouration. Due to skin colouration, evaluation of skin irritation could not be made. However, the absence of oedema in this study, the very weak ocular reactions observed in the acute eye irritation study (rabbits; de Jouffrey 1995b) and the absence of local effects observed in an acute dermal study (rat; de Jouffery 1996a) allows us to conclude that the test material is not a skin irritant based on expert judgment.

Eye

The eye irritation potential of the test material was determined in accordance with standardised guidelines OECD 405 and EU Method B.5. Approximately 100 mg of test material was applied into one eye of each of three rabbits and were assessed for up to 72 hours to determine the grade of ocular reaction. Very slight or slight conjunctival redness (grade 1 or 2) was observed at the 24 hour reading in all animals. Conjunctival redness was masked by a garnet colouration of the conjunctiva one hour after treatment only; in addition, a moderate clear discharge (grade 2) was noted in one animal only. No effects on the iris or cornea were noted. No ocular reactions were observed after the 24 hour reading. Based on these observation it was determined that the test material in not classified for eye irritation.

Both studies presented to assess the irritation and corrosion potential of the test material were performed in line with GLP and accepted standardised guidelines with a high standard of reporting. Both studies were assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material.

The available data are considered to be complete and the conclusion for both skin irritation and corrosion and eye irritation, not irritating, was taken forward for risk assessment.


Justification for selection of skin irritation / corrosion endpoint:
Only one study is available.

Justification for selection of eye irritation endpoint:
Only one study is available.

Justification for classification or non-classification

Skin

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for skin irritation.

Eye

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for eye irritation.