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Administrative data

Description of key information

A guideline skin irritation study in rabbits showed the test substance to be irritating to skin. An eye irritation test performed similar to OECD 405 showed that the substance is corrosive to eyes.

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:
June 16, 1992 - June 30, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD 404 and GLP (no deviations). Batch number and purity not given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, United Kingdom
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.70 - 2.78 kg
- Housing: the animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit diet, Dalgety Agriculture Ltd., Almondsbury, Bristol, United Kingdom)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 50 - 69%
- Air changes (per hr): approximately 15 changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark
Type of coverage:
semiocclusive
Preparation of test site:
other: on the day before the substance was applied, the animals were clipped free of fur from the dorsal flank area using veterinary clippers.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE: not applicable
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
2 males and 1 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm (6.25 cm^2)
- Type of wrap if used: gauze patch, secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 x 4.0 cm) to prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD 404 (2002)
Irritation parameter:
erythema score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days (in all 3 animals)
Remarks on result:
other: Individual mean scores: 2-2-2
Irritation parameter:
edema score
Basis:
other: mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days (in 2 of the 3 animals)
Remarks on result:
other: Individual mean scores: 4-4-4

- At all treated skin sites well-defined (score 2) to severe erythema (score 3) was noted at the 7 day observation (average of the 3 animals: 2.67)

- Well-defined and very slight oedema were noted at 2 treated skin sites at the 14 day observation (averages of the 3 animals: 1.33 (erythema) and 0.67 (oedema)).

- The oedema extended ventrally below all treated skin sites at the 1 hr to 72 hrs observations

- Fissuring was noted at 1 treated skin site at the 7 day observation.

- Adverse reactions prevented accurate evaluation of oedema at all treated skin sites at the 7 day observation

- Crust formation, glossy skin and/or reduced re-growth of fur were noted at all treated skin sites at the 14 day observation. Reactions extended up to 5 cm beyond all treatment sites.

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on an in vivo skin irritation study (OECD 404), the substance is classified as irritating to the skin (Category 2).
Executive summary:

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 and GLP, 2 male and 1 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the undiluted substance. Well-defined erythema and severe oedema were noted at all treated skin sites 1 hr after patch removal and at the 24, 48 and 72 hour observations with well-defined to severe erythema at the 7 day observation. Erythema was not fully reversible within 14 days in all 3 animals and oedema in 2 of the 3 animals. In accordance with the CLP Regulation the substance is classified as irritating to the skin (Category 2) as the mean value for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal is ≥ 2.3.

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:
February 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted before the adoption of OECD 405, but similar (no deviations). Batch number and purity not given.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Test for Eye irritants, prescribed by The Consumer Product Safety Commission of the USA in The Code of Federal Regulations, Title 16, Section 1500.42
Deviations:
not applicable
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: no data
ENVIRONMENTAL CONDITIONS: no data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not applicable

VEHICLE: not applicable
Duration of treatment / exposure:
No data
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 albino rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE: no data
SCORING SYSTEM: according to OECD 405
TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
other: conjunctivae score: redness
Basis:
other: mean for animals #1, #2, #3, #4, #5 and #6
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
2.05
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Individual mean scores: 2-2-2-2-2.3-2
Irritation parameter:
other: conjunctivae score: chemosis
Basis:
other: mean for animals #1, #2, #3, #4, #5 and #6
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
3.78
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Individual mean scores: 3.7-4-3.7-3.7-3.7-4

- Corneal opacities and iritis were observed in all 6 animals

- A diffuse, crimson or beefy-red colouration of the conjunctivae accompanied by considerable swelling with the eye almost completely closed was observed in all 6 animals

- The scored ocular reactions were as follows: 

Animal No.

Ocular lesions

DAY after installation

1

2

3

4

7

1

Cornea

1

3

3

*

**

Iris

*

*

1

*

Conjunctivae

Redness

2

2

2

2

Chemosis

3

4

4

4

2

Cornea

1

2

2

3

Iris

*

0

1

1

Conjunctivae

Redness

2

2

2

2

Chemosis

4

4

4

4

3

Cornea

*

1

2

2

Iris

*

0

0

1

Conjunctivae

Redness

2

2

2

2

Chemosis

4

4

3

3

4

Cornea

*

2

2

2

Iris

*

0

1

1

Conjunctivae

Redness

2

2

2

2

Chemosis

4

4

3

3

5

Cornea

1

*

3

3

Iris

*

*

1

1

Conjunctivae

Redness

2

2

3

3

Chemosis

3

4

4

4

6

Cornea

*

*

3

3

Iris

*

*

1

1

Conjunctivae

Redness

2

2

2

2

Chemosis

4

4

4

4

* Due to the severity of the conjunctival reactions, the scoring could not be assessed

** Due to the severity of the conjunctival reactions, the animals were killed on day 7

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
As the effects on conjunctiva were not fully reversible within the observation period of 7 days, the substance is classified as Causing serious damage to eyes (Category 1)
Executive summary:

In a test similar to OECD 405 eye irritation of the test substance was tested in rabbits. Corneal opacity, iritis, and a diffuse, crimson or beefy-red colouration of the conjunctivae accompanied by considerable swelling with the eye almost completely closed were observed in all 6 animals. Animals were killed for humane reasons on day 7. As reversibility could not be observed, the substance should be classified according to Regulation EC 1272/2008 with category 1, H318 "Causes serious eye damage".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 and GLP, 2 male and 1 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the undiluted substance. Well-defined erythema and severe oedema were noted at all treated skin sites 1 hr after patch removal and at the 24, 48 and 72 hour observations with well-defined to severe erythema at the 7 day observation. Erythema was not fully reversible within 14 days in all 3 animals and oedema in 2 of the 3 animals. Fissuring (a corrosive effect) was noted in 1 animal on day 7.

In a test similar to OECD 405 eye irritation of the test substance was tested in rabbits. Corneal opacity, iritis, and a diffuse, crimson or beefy-red colouration of the conjunctivae accompanied by considerable swelling with the eye almost completely closed were observed in all 6 animals. Animals were killed for humane reasons on day 7. Reversibility was not observed.


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

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

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

In accordance with the CLP Regulation the substance is classified as irritating to the skin (Category 2, H315 "causes skin irritation") as the mean value for oedema from gradings at 24, 48 and 72 hours after patch removal in at least 2 of 3 tested animals is ≥ 2.3 and as a corrosive effect (fissuring) was only noted in 1 animal (on day 7).

As reversibility could not be observed in the eye irritation test, the substance should be classified according to Regulation EC 1272/2008 with category 1, H318 "Causes serious eye damage".