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Toxicological information

Eye irritation

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Administrative data

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: Basic data given, comparable to standards (deviations from test guideline: only 2 animals tested, dose applicated 0.05 mL)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Principles of method if other than guideline:
Primary eye irritation study using an internal BASF method
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-methylbutanal, isovaleraldehyde

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.83 kg (female), 2.73 kg (male)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: NaCl-treated other eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 50 µl
- Concentration (if solution): 100%
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 d
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
The original BASF grading was converted into the numerical grading according to the OECD Draize system.

TOOL USED TO ASSESS SCORE: fluorescein at day 8

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: no effect
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
1.8
Max. score:
3
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48, 72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
1.78
Max. score:
3
Reversibility:
fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 d

Any other information on results incl. tables

Readings Animal Corneal opacity Iris conjunctiva  
Erythema Chemosis Additional findings
24 h 1 1 0 2 1  
2 1 0 2 0 l
48 h 1 1 0 2 0  
2 0 0 2 0  
72 h 1 1 0 1 0 s
2 0 0 2 0 bn
6 d 1 1 0 1 0 s
2 0 0 1 0  
8 d 1 0* 0 0 0 s
  2 0* 0 0 0  
Mean 24 - 72 h    1 1.0 0.0 1.7 0.3  
2 0.3 0.0 2.0 0.0  
Mean   0.7 0.0 1.8 0.2  

l: lacrimation

s: scar

bn: bloody nictitating membrane

*coneal opacity has been described after addition of fluorescein.

Transient myosis has been observed within the first 10 minutes after test substance administration.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After application of 0.05 mL of test substance to 2 rabbit eyes, mean (24, 48, and 72 h) cornea scores of 1 and 0.33 and conjunctivae scores of 1.78 and 2 were observed for the two test animals respectively. All eye irritating effects were fully reversible within 8 day at the maximum. EU criteria for reversible effects on the eye (Regulation (EC) No 1271/2008) are reached.
According to recent test guidelines, the amount of test substance to be applied in a primary eye irritation test in vivo has to be 0.1 mL. Taking into account the data available and the time course of eye irritating effects, it is estimated that with the higher dose, the reversibility of effects still will be maintained but the scores will be elevated. Thus isovaleraldehyde is assessed to be irritating to the eye according to EU regulations.
Executive summary:

In a primary eye irritation/corrosion test, 2 rabbits were exposed to 0.05 mL isovaleraldehyde each. Irritation reactions of cornea and conjunctivae were recorded starting at 24 hour after application. Effects persisted up to a maximum of 8 days. At the end of the observation period (8 days) all irritation effects had subsided.

 

For rabbit 1, the mean (24, 48, 72 h) cornea and conjunctivae scores were 1 and 1.78 respectively. For rabbit 2, the mean cornea and conjunctivae scores were 0.33 and 2 thus reaching the EU criteria (CLP regulation) for classification (irritating to eyes - Category 2) (BASF 1974).

 

For recent primary eye irritation tests in vivo, test guidelines require the application of 0.1 mL test substance. Considering the data available and the time course of the eye irritating effects, it is estimated that with the higher dose, scores will be elevated but still remain below the criteria for irreversible effects and the reversibility of effects within 21 days will be maintained. Based on the data available, isovaleraldehyde will be classified as irritating to eyes (Category 2).

 

This study bears some deviations from actual test guidelines. Nevertheless, the data are assessed to be sufficiently valid to evaluate the eye irritation potential of isovaleraldehyde. Using available results conforms to the tiered testing and evaluation strategy for eye irritation/corrosion and further testing can be avoided.