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Administrative data

Description of key information

DMD is corrosive to the skin and leads to severe damage of the eyes of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
BASF test
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.79 - 3.5 kg


Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye was left untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
24 h, eyes were not washed out
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:



SCORING SYSTEM: according to Draize

Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
55.8
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
3.2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0.75
Max. score:
2
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
3.6
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritant / corrosive response data:
The application of the test substance caused severe damage of ophthalmic tissue including corneal opacity. Due to severe edema, eyeball was not assessable at all readings. After 8 days, the study was terminated since reversibility of the findings was not expected.

Eye irritation scores:

24 h  48 h   72 h  8 days        
Cornea 4/3/3  */3/*   */3/* */*/*        
Iris */1/0  */1/*   */1/*  */*/*        
Conjunctiva 2/2/2  */2/*   */2/*  */*/*        
Chemosis  3/4/3 4/4/3  4/4/3  3/3/3         

* severe edema, eyeball not assessable,

The application of the test substance caused severe damage of ophthalmic tissue including corneal opacity. Due to severe edema, eyeball was not assessable at all readings. After 8 days, the study was terminated since reversibility of the findings was not expected.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

For the assessment of the skin irritation/corrosion potential of the test substance a weight of evidence approach was applied, using the Corrositex in vitro skin corrosion test (BASF SE, 2011) and an in vivo study in rabbits (BASF AG, 1979d).

In the skin irritation study, Vienna white rabbits were exposed to the undiluted test substance for 3 minutes (4 animals) and 1 hour (2 animals) under occlusive conditions. Readings were performed directly after exposure and after 1, 2, and 8 days post exposure. After exposure for 3 minutes, necrotic changes (irreversible full thickness necrosis) were observed in 3/4 rabbits 8 days after application (BASG AG, 1979d). The in vivo study revealed a corrosive potential of the test substance, but due to a lacking reading point 1 hour after the 3 minutes exposure, an accurate classification (Cat 1A or 1B) was not possible. Therefore the in-vitro Corrositex-skin corrosion test was performed according OECD TG 435 and GLP, confirming the corrosive potential of the test substance and providing more information for the classification of the test substance (BASF SE, 2011). The break through time in this membrane barrier test was 6:41 min, indicating that the test substance has an intermediate corrosive potential and should be assigned to the skin corrosivity subcategory 1B as specified in OECD TG 435 (adopted 19 July 2006) and the test system manufacturer. The results of the negative, positive, and historical control data confirmed the validity of the test performance.

 

Two in vivo studies in rabbits were available for the assessment of the eye irritating potential of the test substance (BASF AG, 1979e; BASF AG, 1956), which were performed using methods comparable to relevant guidelines.

In the eye irritation key study, 100 µl of the undiluted test substance was applied to the right conjuntival sac of three rabbits. The left eye was left untreated and served as a control. The substance was not washed out. The application of the test substance caused severe damage of ophthalmic tissue including corneal opacity. Due to severe edema, the eyeball was not assessable at all readings. After 8 days, the study was terminated since reversibility of the findings was not expected (BASG AG, 1979e).

The supporting study (BASF AG, 1956) tested undiluted DMD using two rabbits. The test substance produced strong redness, corneal opacity, purulent lacrimation and scabbing. Depilation was observed at the area around the treated eye. The observed severe corneal opacity was considered to be an irreversible effect to ophthalmic tissue.


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the classification is Cat. 1B (H314) for skin damaging properties and Cat. 1 for eye damaging properties.