Registration Dossier

Administrative data

Description of key information

OECD 404 study skin irritation

OECD 405 eye irritation

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:
2008.07.15. - 2008.07.30.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: From sponsor; CIBA Inc.
- Batch No.of test material: 512051
- Expiration date of the lot/batch: December 2008
- Purity test date: certificate of analysis dated June 16, 2008
- pH: 7.15
- Colour: colourless
- Form: liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

The test item was considered as 100% for the study
Species:
rabbit
Strain:
New Zealand White
Remarks:
Albinos
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste - F40260 Linxe)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: 2.56-3.20 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 43-63%
- Air changes (per hr): at least 10 per h; 22 volumes per hour measured
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Controls:
not specified
Amount / concentration applied:
0,5 mg/L
Duration of treatment / exposure:
4 hours
Observation period:
4 hours; one animal was initially, after consideration of responses, two additional animals were treated
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: on one flanck of each animal
- Coverage area: 6 cm2
- Type of wrap if used: Patch secured in position with surgical tape

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of patch and on days until day 14

SCORING SYSTEM:
Grading scale: Erythema and Eschar/oedema formations
Scales 0-4
0: No erythema/oedema
1: Very slight erythema/oedema
2: Well defined erythema/ slight oedema
3: Moderate to severe erythema/ moderate oedema
4: Severe erythema/odema
Irritation parameter:
erythema score
Basis:
animal: All treated
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: day 5 - day 6
Remarks:
5 - 6 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal: All treated
Time point:
24/48/72 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
fully reversible within: day 4 - day 7
Remarks on result:
positive indication of irritation
Other effects:
On the cutaneous structure, a dryness was noted on the treated area from day 3 in two animal and from day 4 in the last one. The skin recovered a normal aspect between day 7 and day 8 in two animals, but a slight dryness was still noted at the end of the observation time (day 14) in the last animal.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The results obtained under these experimental conditions (OECD 404) enable to conclude that the test item Dermosoft DGMC is irritant according to the scales of interpretation retained.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must be classified in category 2 “irritant”. The signal word “Warning” and hazard statement H315 “Causes skin irritation” are required.
Executive summary:

The skin irritating properties of test item Dermosoft DGMC was tested in accordance with OECD guideline 404. The test item was applied at the dose og 0.5 ml. under semi-occlusive dressing during 4 hours on undamaged skin area of 3 rabbits.

No clinical signs related to the test item was observed. A well defined erythema associated with a moderate oedema was noted on the treated area of all treated animals 24 hours after the test item application. The oedematous reactions were totally reversible between day 4 and day 7 and the erythematous reactions were totally reversible between day 5 and day 6.

On the cutaneous structure, a dryness was noted on the treated area from day 3 in two animal and from day 4 in the last one. The skin recovered a normal aspect between day 7 and day 8 in two animals, but a slight dryness was still noted at the end of the observation time (day 14) in the last animal.

The mean scoring in relation to erythema for all three animals was 2 based on the 24; 48 and 72 h readings.

The mean scorings in relation to oedema were based on the 24;48 and 72 h readings 2.7; 2.3 and 2.7 for the indiviudal animals i.e. within the criteria range for classification as an irritant: at least two of three animals with a mean scoring >2.3 - <4.

The results obtained under these experimental conditions (OECD 404) enable to conlcude that the test item Dermosoft DGMC) is an irritant according to the scales of interpretattion retained. In accordance with the Globally Harmonized System (COM(2007)355 final) the test item must be classified in category 2 “irritant”. The signal word “Warning” and hazard statement H315 “Causes skin irritation” are required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
21st of July to 6th of August 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: From sponsor; CIBA Inc.
- Batch No.of test material:
512051
- Expiration date of the lot/batch: December 2008
- Purity test date: certificate of analysis dated June 16, 2008

- pH: 7.15
- Colour: colourless
- Form: liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room temperature

The test item was considered as 100% for the study
Species:
rabbit
Strain:
New Zealand White
Remarks:
Albino females
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste - F40260 Linxe)
- Sex: Females
- Age at study initiation: 11-14 weeks
- Weight at study initiation: 2.13-3.35 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 43-63%
- Air changes (per hr): at least 10 per h; 20-24 volumes per hour measured on July 7, 2008
- Photoperiod (hrs dark / hrs light): 12 h/12 h
Vehicle:
unchanged (no vehicle)
Controls:
other: The other untreated eye served as control
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
One time
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
The grades of ocular reaction (conjunctivae, cornea and iris) were recorded at each examination. Any lesions in the eye (e.g. pannus, staining) or adverse systemic effects were als reported.

EXAMINATIONS:
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment and then on further days until day 14.

TOOL USED TO ASSESS SCORE:
Fluorescein - After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein at 2%. Furthermore, examination of reactions was facilitated by use of an opthalamoscope (Heine Optotechnik, Gemany)
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: between day 3 an day 9
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: day 9
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: between day 9 and day 14
Remarks on result:
positive indication of irritation
Other effects:
A corneal neo-vascularisation at day 2 in one animal and at day 2 and 3 in one a second animal was noted

The ocular reactions observed during the study have been moderate and totally revesible in all three animals.

- at the conjunctivae level: a moderate redness, noted one hour after the test item instillation and totally reversible at day 9, associated with a moderate chemosis, noted one hour after the test item instillation and totally reversible between day 3 and 9;

- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation and totally reversible between day 9 and day 14

- at the iris level: a congestion noted at day 1 and day 2 in one animal and at day 3 and 4 in a second animal

The mean scorings for the 24.48 and 72 readings for the indivudal animals were (chemosis -redness - iris - cornea)

Animal 1: 2.0 - 2.0 - 0.3 - 2.0

Animal 2: 1.0 - 2.0 - 0.0 - 2.0

Animal 3: 1.3 - 2.0 - 0.7 - 1.7

As all animals had a mean scoring > 1 for corneal opacity and a mean scoring of 2 for redness these two parameters according to the classification criteria waarant a classification as Eye Irrit 2 H319

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The results obtained under these experimental conditions (OECD 405) enable to conlcude that the test item Dermosoft DGMC) is irritating to the eye according to the scales of interpretattion retained. In accordance with the Globally Harmonized System (COM(2007)355 final) the test item must be classified in category 2 “irritating to eyes”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.
Executive summary:

The eye irritating properties of test item Dermosoft DGMC was tested in accordance with OECD guideline 405. The test item was instilled as supplied into the eye of three New Zealand rabbits at the dose og 0.1 ml.

No clinical signs related to the test item was observed.

The ocular reactions observed during the study have been moderate and totally revesible in all three animals.

- at the conjunctivae level: a moderate redness, noted one hour after the test item instillation and totally reversible at day 9, associated with a moderate chemosis, noted one hour after the test item instillation and totally reversible between day 3 and 9;

- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation and totally reversible between day 9 and day 14

- at the iris level: a congestion noted at day 1 and day 2 in one animal and at day 3 and 4 in a second animal

A corneal neo-vascularisation at day 2 in one animal and at day 2 and 3 in one a second animal was noted.

The mean scorings for the 24.48 and 72 readings for the indivudal animals were (chemosis -redness - iris - cornea)

Animal 1: 2.0 - 2.0 - 0.3 - 2.0

Animal 2: 1.0 - 2.0 - 0.0 - 2.0

Animal 3: 1.3 - 2.0 - 0.7 - 1.7

As all animals had a mean scoring>1 for corneal opacity and a mean scoring of 2 for redness these two parameters according to the classification criteria warrant a classification as Eye Irrit 2 H319

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Based on the scoring for oedema of the skin the substance is to be classified as Skin Irrit.2 H315.

Based on the individual scoring for corneal opacity and conjunctival redness the substance is to be classified as Eye Irrit.2 H319.