Registration Dossier

Administrative data

Description of key information

The substance is corrosive to the skin (Cat. 1B) and causes serious eye damage (Cat. 1).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to guideline study
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
1) 4 hours and
2) 3 minutes
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: gauze patch with impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess material is removed after the 4-hr or 3-min contact period

SCORING SYSTEM: Table of Draize (as in OECD 404)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 5 hr after skin contact
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Remarks:
Skin necroses were seen at the 5-hr reading in 3 rabbits. Irreversible skin alterations were seen in all animals at 14 after 14 days post treatment.
Remarks on result:
other: 3-minute skin contact
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 5 hr after skin contact
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 3-minute skin contact
Irritant / corrosive response data:
At the 5-hr skin examination and thereafter, skin necrosis was seen in most rabbits exposed for 3 minutes and all animals exposed for 4 hours. Full thickness necrosis was confirmed at termination. No reading was made within 1 hour after skin contact.

Skin reactions after 4-hr contact period (means of 6 animals); 0.5 mL dosed

Time post
skin contact

Erythema
(mean score)

Edema
(mean score)

Specific effects(selected effects))
N=necrosis
U = ulceration

5 hours

2.0

4.0

N (all animals)

1 day

2.5

4.0

N (all animals)

2 days

3.0

4.0

N (all animals)
U (1 animal)

3 days

2.8

4.0

N (all animals)
U (5 animals)

7 days

1.0

-

N (all animals)
U (5 animals)

10 days

0.3

-

N (all animals)
U (5 animals)

14 days

0.0

-

N (all animals)
U (5 animals)

 

Skin reactions after a 3-minute contact period (means of 6 animals); 0.5 mL dosed

 

Time post
skin contact

Erythema
(mean score)

Edema
(mean score)

Specific effects(selected effects)
N=necrosis
U = ulceration
D = desquamation

5 hours

1.3

2.5

N (3 animals)

1 day

2.3

3.8

N (3 animals)

2 days

2.2

3.0

N (4 animals)

3 days

0.0

2.3

N (4 animals)

7 days

0.0

0.0

N (5 animals)
D (5 animals)

10 days

0.0

0.0

N (5 animals)
D (5 animals)

14 days

0.0

0.0


D (5 animals)

 

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
2-methylbuytric acid caused full thickness skin necrosis in 5 animals after a 3-minute contact to the intact rabbit skin. Necrosis was already seen in 3 animals at the first reading at 5 hours after skin contact. The substance is at least a CAT1B skin corrosive; classification as a CAT 1A corrosive is also possible but cannot be judged because this would require a reading within one hour after the skin contact (Regulation (EC) No. 1272/2008).
Executive summary:

Skin irritating/corrosive properties of the test item were investigated in New Zealand rabbits in a study similar to OECD TG 404. Rabbits were exposed for 3 minutes or 4 hours toward 0.5 mL of the undiluted test item and observed for up to 14 days. Full thickness skin corrosion was observed in animal after 3 minutes or 4 hour exposure and was evident already at the first reading at 5 hours after the start of the exposure.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritating/corrosive properties of the test item were investigated in a valid study similar to OECD TG 404 in New Zealand rabbits. Rabbits were exposed for 3 minutes or 4 hours toward 0.5 mL of the undiluted test item and observed for up to 14 days. Full thickness skin corrosion was observed in animal after 3 minutes or 4 hour exposure and was evident already at the first reading at 5 hours after the start of the exposure, indicating that the substance is corrosive. The results of the key study indicate that the substance should at least be classified as skin corrosive Cat. 1B. Due to the experimental design (first reading after 5 hours but not after 1 hour after the end of the exposure) it remains unclear if the substance falls under Cat. 1A. Corrosive properties were also reported in two other references of insufficient reliability (RL 4) due to insufficient documentation.

There is no reliable study available which investigated effects on the eyes. However, in a study which was not sufficiently documented for assessment (BASF, 1980) irreversible effects on the rabbit eye were described which indicate that the substance causes severe eye damage (e.g. mean cornea score of 3, scar formation). This finding is supported by the results of two other studies of low reliability and is in line with the observation that the substance is skin corrosive.

Justification for classification or non-classification

Based on the available data a classification as skin corrosive Cat. 1B (H314) and causing serious eye damage (Cat. 1; H318) is suggested according to the criteria of Regulation (EC) No. 1272/2008.