Registration Dossier

Administrative data

Description of key information

The substance is not irritating to the skin of rabbits but is irritating to the eye of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-07-08 to 2014-07-15
Reliability:
1 (reliable without restriction)
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: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.45 and 2.49 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2014-07-08 to 2014-07-15
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Test item was used as supplied (undiluted)
- pH of the undiluted test item: 7.0
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4h
Observation period:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, the sites were examined for evidence of primary irritation.
An additional observation was made on Day 7 to assess the reversibility of skin reactions.
Number of animals:
2 females
Details on study design:
TEST SITE
- Area of exposure: On the day of the test a suitable site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch.
- Type of wrap if used: Treatment site was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: Four hours after application the corset and patches were removed from animals and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize method
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Very slight erythema was noted at one treated skin site 1 hour after patch removal and at both treated sites at the 24, 48 and 72 hour observations.
Both treated skin sites appeared normal at the 7 day observations.
No corrosive effects were noted.

The test item produced a primary irritation index of 1.0.
Other effects:
Both animals showed expected gain in body weight during the study.

Individual skin reactions

Skin reaction

Observation Time (following patch removal)

Individual score – Rabbit number and sex

Total

74481 Female

74482 Female

Erythema/Eschar Formation

Immediately

0

0

(0)

1 hour

0

1

(1)

24 hours

1

1

2

48 hours

1

1

(2)

72 hours

1

1

2

7 days

0

0

(0)

Edema formation

Immediately

0

0

(0)

1 hour

0

0

(0)

24 hours

0

0

0

48 hours

0

0

(0)

72 hours

0

0

0

7 days

0

0

(0)

Sum of 24 and 72-hour readings (S):        4

Primary Irritation Index (S/4):                     4/4 = 1.0

Classification:                                                MILD IRRITANT

 

( ) = Total values not used for calculation of primary irritation index

Individual body weights and body weight change

Rabbit number and sex

Individual body weight (kg)

Body weight change (kg)

Day 0

Day 7

74481 Female

2.45

2.60

0.15

74482 Female

2.49

2.66

0.17

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions the substance is not classified as irritating to skin according to the criteria of CLP Regulation (EC) No. 1272/2008.
Executive summary:

Test Guidance

OECD guideline 404 and EC Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion).

 

Method and materials

Two New Zealand White female rabbits were dermally exposed to 0.5 mL of the test material for 4 h under a semi-occlusive dressing. After removal of the residual test item, irritation was scored immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, according to Draize method.

 

Results

Very slight erythema was noted at one treated skin site 1 hour after patch removal and at both treated sites at the 24, 48 and 72 hour observations.

Both treated skin sites appeared normal at the 7 day observations.

No corrosive effects were noted.

Both animals showed expected gain in body weight during the study.

The test item produced a primary irritation index of 1.0.

 

Conclusion

Under the test conditions the substance is not classified as irritating to skin according to CLP Regulation (EC) No. 1272/2008.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
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:
2014-07-14 to 2014-08-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
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: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.48 and 2.68 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 2014-07-14 to 2014-08-04
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Test item was used as supplied (undiluted)
- pH of undiluted test item: 7.0
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Eyes were not rinsed throughout study
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 h following treatment.
An additional observation on Day 7 was made to assess reversibility of effects.
Number of animals or in vitro replicates:
2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
No corneal effects were noted during the study.
Iridial inflammation was noted in both treated eyes 1 hour after treatment.
Moderate conjunctival irritation was noted in both treated eyes 1 and 24 hours after treatment. Moderate conjunctival irritation persisted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 48 hour observation. Minimal conjunctival irritation was noted in both treated eyes at the 72 hour observation.
Both treated eyes appeared normal at the 7-day observation.
Other effects:
One animal showed a body weight loss and the other animal showed an expected gain in body weight during the study.

See attached document.

Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is irritating to the eye of rabbits. Classification as Eye Irrit. 2 in accordance with the CLP Regulation (EC) No. 1272/2008 is required.
Executive summary:

Test Guidance

OECD guideline 405 and EC Method B.5 (Acute Toxicity: Eye Irritation / Corrosion).

Method and materials

Two New Zealand White female rabbits were exposed to 0.1 mL of test item in the right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for one second before releasing. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

Results

No corneal effects were noted during the study. Iridial inflammation was noted in both treated eyes 1 hour after treatment. Moderate conjunctival irritation was noted in both treated eyes 1 and 24 hours after treatment. Moderate conjunctival irritation persisted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 48 hour observation. Minimal conjunctival irritation was noted in both treated eyes at the 72 hour observation. Both treated eyes appeared normal at the 7-day observation.

One animal showed a body weight loss and the other animal showed an expected gain in body weight during the study.

Conclusion

The substance is irritating to the eye of rabbits. Under the test conditions, the substance is classified as irritating to eyes according to CLP Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

In a key study to OECD guideline 404 and EC Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion), two New Zealand White female rabbits were dermally exposed to 0.5 mL of the test material for 4 h under a semi-occlusive dressing. After removal of the residual test item, irritation was scored immediately following removal of the patches and approximately 1, 24, 48 and 72 h later, according to Draize method.

Very slight erythema was noted at one treated skin site 1 hour after patch removal and at both treated sites at the 24, 48 and 72 hour observations. Both treated skin sites appeared normal at the 7 day observations. No corrosive effects were noted.

Both animals showed expected gain in body weight during the study.

The test item produced a primary irritation index of 1.0.

Under the test conditions the substance is not classified as irritating to skin according to CLP Regulation (EC) No. 1272/2008.

Eye

In a key study to OECD guideline 405 and EC Method B.5 (Acute Toxicity: Eye Irritation / Corrosion), two New Zealand White female rabbits were exposed to 0.1 mL of test item in the right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for one second before releasing. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

No corneal effects were noted during the study. Iridial inflammation was noted in both treated eyes 1 hour after treatment. Moderate conjunctival irritation was noted in both treated eyes 1 and 24 hours after treatment. Moderate conjunctival irritation persisted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 48 hour observation. Minimal conjunctival irritation was noted in both treated eyes at the 72 hour observation. Both treated eyes appeared normal at the 7-day observation.

One animal showed a body weight loss and the other animal showed an expected gain in body weight during the study.

The substance is irritating to the eye of rabbits. Under the test conditions, the substance is classified as irritating to eyes according to CLP Regulation (EC) No. 1272/2008.

Effects on eye irritation: irritating

Justification for classification or non-classification

According to the CLP criteria for classification and labelling of dangerous substances the substance is not classified as a skin irritant but is irritating to the eye and classification as Eye Irrit. 2 is required.