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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-05-16 to 2006-05-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study reliable without restrictions Minor deviations with no effects on the study: - According to the guideline, for the initial test in one animal, the test site is also examined immediately after the patch has been removed. In this study report there was no statement indicating if this was done. - According to the guideline a rationale for in vivo testing should be stated in the study report. This is missing in this study report. - According to the guideline, the individual animal weights at the start and at the conclusion of the test should be stated. In this study report only a mean body weight with standard deviation was stated, which only indicated the mean body weight at the beginning of the study.. - According to the guideline, in the test report the volume of vehicle used should be stated. This was missing in this study report.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Deviations:
yes
Remarks:
Minor deviations with no effect on the study (see rationale for reliability)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: On the day of treatment, the animals were 2 to 4 months old
- Weight at study initiation: On the day of treatment, the animals had a mean body weight +/- standard deviation of 2.5 +/- 0.1 kg
- Housing: The animals were housed individually in Pajon (50 cm X 57 cm X 75 cm) cages. Each cage was equipped with a food container and a water bottle.
- Diet: During the study, the animals had free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (ad libitum): Drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 3 °C
- Relative humidity: 30 to 70 %
- Ventilation: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg of the test item
No further information on amount/concentration applied was stated.
Duration of treatment / exposure:
One animal : 3 minutes, 1 hour and 4 hours
Other animals: 4 hours
Observation period:
Observation period was 1 hour, 24, 48 and 72 hours after removal of the dressing. The study was ended on day 4.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
The day before treatment, both flanks of each animal were clipped using electric clippers. Doses of 500 mg of the test item in its original form were placed on a gauze pad moistened with purified water, which was then applied to an area of approximately 6 cm^2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad.

SCORING SYSTEM:
Draize scoring system
No further information on details on study design was stated.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24,48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No erythema was observed.
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 1
Time point:
other: 24,48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No oedema was observed.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 2
Time point:
other: 24,48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24,48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No oedema was observed.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal # 3
Time point:
other: 24, 48, and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No erythema was observed.
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal # 3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No oedema was observed.
Irritant / corrosive response data:
After a 3 minute exposure (one animal):
No cutaneous reactions were observed.
After 1 hour exposure (one animal)
An orange colouration of the skin was noted at 1 hour and at 24 hours.
After a 4 -hour exposure (three animals):
A very slight erythema (grade 1 ) was noted in 2/3 animals at one hour; it persisted in one of them at 24 hours.
An orange colouration of the skin was observed in 2/3 animals at 1 hour.

Raw data for 3 -minute exposure:

Rabbit No.

Dermal irritation

1 hour

24 hours

48 hours

72 hours

Mean irritation score

(24 h, 48 h, 72h)

1

Erythema

0

0

0

0

0.0

Oedema

0

0

0

0

0.0

Raw data for 1 hour-exposure:

Rabbit No.

Dermal irritation

1 hour

24 hours

48 hours

72 hours

Mean irritation score

(24 h, 48 h, 72h)

1

Erythema

0

0

0

0

0.0

Oedema

0

0

0

0

0.0

Raw data for 4 hour-exposure:

Rabbit No.

Dermal irritation

1 hour

24 hours

48 hours

72 hours

Mean irritation score

(24 h, 48 h, 72h)

1

Erythema

0

0

0

0

0.0

Oedema

0

0

0

0

0.0

2

Erythema

1

1

0

0

0.3

Oedema

0

0

0

0

0.0

3

Erythema

1

0

0

0

0.0

Oedema

0

0

0

0

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the test item Peconal H was very slightly irritant when applied topically to rabbits.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances, the test item Peconal H should not be classified as irritating to the skin.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not irritating.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-05-23 to 2006-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study reliable without restrictions Minor deviations without an effect on the study: - According to the guideline a rationale for in vivo testing should be stated in the study report. This is missing in this study report. - According to the guideline, the individual body weight at start and conclusion of the the test should be stated. The body weight at the conclusion of the test is missing. - In the Draize scoring system referes conjunctival redness to palpebral and bulbar conjunctivae and excludes cornea and iris. In this study cornea and iris are included in the scoring system.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
, adopted 2002-04-24
Deviations:
yes
Remarks:
Minor deviations with no effect on the study (see rationale for reliability)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: On the day of treatment, the animal was 2 to 4 months old
- Weight at study initiation: 2.7 kg
- Housing: The animal was housed in Pajon cage (50 cm X 57 cm X 75 cm) equipped with a food container and a water bottle.
- Diet: During the study, the animal had free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (ad libitum): Drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 3 °C
- Relative humidity: 30 to 70 %
- Ventilation: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item in its original form
No further information on amount/concentration applied was stated.
Duration of treatment / exposure:
not stated
Observation period (in vivo):
The eyes were examined approximately 1 hour and 24 hours after administration of the test item. As severe irritant effects were observed, the animal was scarificed on day 2 (after scoring) for ethical reasons.
Number of animals or in vitro replicates:
1 male rabbit
Details on study design:
REMOVAL OF TEST SUBSTANCE
The eyes were not rinsed after administration of the test item.
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: Conjucntival reactions, iritis and corneal opacification were evaluated daily for each animal. For evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5 % sodium fluorescein solution ( a clear fluorscence is visible in the area of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.
No further information in details on study design was stated.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 hour
Score:
3
Max. score:
3
Remarks on result:
other: Due to the severe ocular reactions observed, the animal was sacrificed for ethical reasons on day 2 (after scoring).
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 hours
Score:
3
Max. score:
3
Remarks on result:
other: Due to the severe ocular reactions observed, the animal was sacrificed for ethical reasons at 24 hours (after scoring).
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Max. score:
4
Remarks on result:
other: Due to the severe ocular reactions observed, the animal was sacrificed for ethical reasons at 24 hours (after scoring).
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 hours
Score:
4
Max. score:
4
Remarks on result:
other: Due to the severe ocular reactions observed, the animal was sacrificed for ethical reasons at 24 hours (after scoring).
Irritant / corrosive response data:
A severe chemosis (maximal grade of 4), a severe redness of the conjunctiva (maximal grade of 3) and a clear discharge were observed on days 1 and 2.
The evaluation of iris and corneal lesions was masked by severe chemosis.
A brownish area on the conjunctivae, similar to a burn, was noted on day 2.
Due to the severe ocular reactions observed, the animal was sacrificed for ethical reasons at 24 hours (after scoring).

Raw data of one animal examined at 1 hour and 24 hours.

Rabbit No.

Region of eye

Eye irritation

1 hour

Day 1

24 hours

Day 2

1

Conjunctivae

Chemosis

4

4

Redness

3

3

Discharge

2

3

Iris

 

Scoring masked by marked chemosis

Scoring masked by marked chemosis

Corneal opacity

Intensity

Scoring masked by marked chemosis

Scoring masked by marked chemosis

Area

Scoring masked by marked chemosis

Scoring masked by marked chemosis

 

Other

 

Residual test item

Brownish area on conjunctiva

 

Fluorescein

 

Fluorescein not used

Fluorescein not used

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the test item Peconal H was severly irritant when administered by ocular route to rabbits.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances, the test item Peconal H should be classified as irritating to the eyes abd assigned the symbol Xi, the indication of danger "Irritant" and the risk phrase R 41: "Risk of serious damage to eyes".
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Key study

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation

The reference Pelcot (2007) is considered as the key study for skin irritation and will be used for classification.Cobalt(II) 4-oxopent-2-en-2-olatewas very slightly irritant when applied topically to rabbits. The classification criteria according to regulation (EC) 1272/2008 as irritant to skin are not met, hence no classification required.

 

Eye irritation

The reference Pelcot (2007) is considered as the key study for severe eye irritation and will be used for classification. The overall irritation results 1 and 24 hours after application for the animal are as follows:

- severe chemosis (maximal grade of 4)

- severe redness of the conjunctiva (maximal grade of 3)

- clear discharge were observed on days 1 and 2

- evaluation of iris and corneal lesions was masked by severe chemosis

- brownish area on the conjunctivae, similar to a burn, was noted on day 2

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to eyes are met, since in the animal severe ocular reactions were not reversible (the animal was sacrificed for ethical reasons at 24 hours). Cobalt(II) 4-oxopent-2-en-2-olate will be classified eye damage category 1 (H318: Causes serious eye damage).