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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 (deviations from test guideline: only 2 animals tested, dose applicated 0.05 mL, no grading of eye reaction at 72 h)
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Principles of method if other than guideline:
Internal BASF method was used (deviations from OECD test guideline: only 2 animals tested, dose applicated 0.05 mL, no grading of eye reaction at 72 h)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Valeraldehyde
EC Number:
203-784-4
EC Name:
Valeraldehyde
Cas Number:
110-62-3
Molecular formula:
C5H10O
IUPAC Name:
valeraldehyde
Details on test material:
- Name of test material (as cited in study report): n-Valeraldehyd
- Physical state: fluid
- Substance No.: XXVI 30

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 2.78, 3.06 kg

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: NaCl-treated eye of same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 ml
- Concentration (if solution): 100%
Duration of treatment / exposure:
one application
Observation period (in vivo):
8 days
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:
Cornea
(A) Opacity-degree of density (area most dense taken for reading)
0 = No opacity
1 = Scattered or diffuse area, details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Opalescent areas, no details of iris visible, size of pupil barely discernible
4 = Opaque, iris invisible

(B) Area of cornea involved
1 = One quarter (or less) but not zero
2 = Greater than one quarter, but less than half
3 = Greater than half, but less than three quarters
4 = Greater than three quarters, up to whole area

Iris
(A) Values
0 = Normal
1 = Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination af any thereof) iris still reacting to light (sluggish reactions is positive)
2 = No reaction to light, hemorrhage, gross destruction (any or all of these)

(3) Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
0 = Vessels normal
1 = Vessels definitely injected above normal
2 = More diffuse, deeper crimson red, individual vessels not easily discernible
3 = Diffuse beefy red

(B) Chemosis
0 = No swelling
1 = Any swelling above normal (includes nictitatinq membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids about half closed to completely closed

(C) Discharge
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye



TOOL USED TO ASSESS SCORE: fluorescein at day 8

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 h
Score:
1.5
Max. score:
3
Reversibility:
fully reversible within: 5 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 h
Score:
1.8
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 d

Any other information on results incl. tables

Readings Animal Corneal opacity Iris conjunctiva  
Erythema Chemosis Additional findings
1h 1 1 0 1 2
2 1 0 1 2 o
3 h 1 1 0 1 2 o
2 1 0 1 2 o
24 h 1 1 0 2 1 o, s
2 1 0 2 1 o
48 h 1 0 0 1 1 o, s
2 2 0 2 1 o
5 d 1 0 0 0 0  
2 1 0 1 0 o
7 d 1 0 0 0 0  
2 1 0 0 0  
8 d 1 0 0 0 0  
2 0 0 0 0  
Mean 24 - 48 h 1 0.5 0.0 1.5 1.0  
2 1.5 0.0 2.0 1.0  
Mean   1.0 0.0 1.8 1.0  

o: smudgy overlay

s: scar

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes)
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 and 48 h, no reading at 72 h) cornea scores of 0.5 and 1.5 and conjunctivae scores of 1.5 and 2 were observed for the two test animals respectively. All effects were fully reversible within 8 d at the maximum. For one rabbit, classification criteria of regulation (EC) No 1272/2008 for reversible effects on the eye (Category 2) are reached or exceeded. Considering the time course of cornea scores for rabbit 2, mean cornea score will be > 1 even if a 72h reading were available. In addition, the amount of the dose applied (0.05 mL instead of 0.1 mL according to EU test guideline) has to be allowed for. It is estimated that with the higher dose, the reversibility of effects still will be maintained but the scores will be elevated. Thus, valeraldehyde is assessed to be irritating to the eye according to EU regulations.
Executive summary:

In an acute eye irritation/corrosion test, 2 rabbits were exposed to 0.05 mL valeraldehyde each. Irritation reactions of cornea and conjunctivae developed within 1 hour after application and 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 and 48 h, no reading at 72 h) cornea and conjunctivae scores were 0.5 and 1.5 respectively. For rabbit 2, the mean cornea and conjunctivae scores were 1.5 and 2 thus exceeded or reaching the EU criteria for classification (reversible effect on the eye - Category 2) (BASF 1977). Considering the dose applied and the time course of the development of irritating effects, valeraldehyde requires classification as irritating to eyes (Category 2).

 

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, valeraldehyde 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 valeraldehyde. Using available results conforms to the tiered testing and evaluation strategy for eye irritation/corrosion and further testing can be avoided.