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Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981-08-03 to 1981-08-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, national standard study, without GLP
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
Not relevant
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyraldehyde
EC Number:
204-646-6
EC Name:
Butyraldehyde
Cas Number:
123-72-8
Molecular formula:
C4H8O
IUPAC Name:
butanal
Details on test material:
- Name of test material (as cited in study report): Butyraldehyde
- Molecular formula (if other than submission substance): Not documented
- Molecular weight (if other than submission substance): Not documented
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Not documented
- Physical state: Thin, clear liquid
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: Not documented
- Expiration date of the lot/batch: Not documented
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Not documented
- Storage condition of test material: Room temperature
- Other: Not documented

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratories, Inc., Denver, Pennsylvania.
- Age at study initiation: Young adults
- Weight at study initiation: 2.2 - 3.0 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum Municipal water supply.
- Acclimation period: 21 day (equilibration period)


ENVIRONMENTAL CONDITIONS
- Temperature: 17.2 - 20.5 °C (monitored twice daily)
- Humidity (%): not specified (monitored daily)
- Air changes (per hr): not documented
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.

IN-LIFE DATES: From: July 13th 1981 To: August 17th 1981

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
The test material was administered as received.

Duration of treatment / exposure:
single dose
Observation period (in vivo):
Approximately 24, 48, and 72 hours and 4 and 7 days after treatment.
Up to 14 days if signs of irritation were evident on Day 7.
If no signs of irritation at Day 7, no additional observations were made.
Number of animals or in vitro replicates:
9
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 additional animals
- Time after start of exposure: 20 sec

SCORING SYSTEM
Draize scale according to Draize 1959 (Report Appendix A, p. 11)

Evaluation of scores:
according to 16 CFR 1500.42 (see Report, Chapter III, p. 4, and footnote Table I)

Effects such as pannus formation, blistering of the conjunctiva, ulceration were interpreted in terms of corrosivity.
"Necrosis" is obviously used in a broader sense, as it is also applied to tissue-destructive effects that are fully reversible.

TOOL USED TO ASSESS SCORE: fluorescein dye was used to confirm the presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 8292F
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.43
Irritation parameter:
iris score
Basis:
animal: 8292F
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0
Irritation parameter:
chemosis score
Basis:
animal: 8292F
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.86
Irritation parameter:
conjunctivae score
Basis:
animal: 8292F
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2
Irritation parameter:
cornea opacity score
Basis:
animal: 8293M
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.67
Irritation parameter:
iris score
Basis:
animal: 8293M
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.33
Irritation parameter:
chemosis score
Basis:
animal: 8293M
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2
Irritation parameter:
conjunctivae score
Basis:
animal: 8293M
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2
Irritation parameter:
cornea opacity score
Basis:
animal: 8290F
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0
Irritation parameter:
iris score
Basis:
animal: 8290F
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0
Irritation parameter:
chemosis score
Basis:
animal: 8290F
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.83
Irritation parameter:
conjunctivae score
Basis:
animal: 8290F
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2.33
Irritation parameter:
cornea opacity score
Basis:
animal: 8291M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1
Irritation parameter:
iris score
Basis:
animal: 8291M
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.29
Irritation parameter:
chemosis score
Basis:
animal: 8291M
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.71
Irritation parameter:
conjunctivae score
Basis:
animal: 8291M
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2.33
Irritation parameter:
cornea opacity score
Basis:
animal: 8288F
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1
Irritation parameter:
iris score
Basis:
animal: 8288F
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.29
Irritation parameter:
chemosis score
Basis:
animal: 8288F
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.57
Irritation parameter:
conjunctivae score
Basis:
animal: 8288F
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2
Irritation parameter:
cornea opacity score
Basis:
animal: 8287M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1
Irritation parameter:
iris score
Basis:
animal: 8287M
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 0.25
Irritation parameter:
chemosis score
Basis:
animal: 8287M
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1.625
Irritation parameter:
conjunctivae score
Basis:
animal: 8287M
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1.875
Irritation parameter:
cornea opacity score
Basis:
animal: 8286F
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.86
Irritation parameter:
iris score
Basis:
animal: 8286F
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.17
Irritation parameter:
chemosis score
Basis:
animal: 8286F
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.57
Irritation parameter:
conjunctivae score
Basis:
animal: 8286F
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2.143
Irritation parameter:
cornea opacity score
Basis:
animal: 8285M
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17
Irritation parameter:
iris score
Basis:
animal: 8285M
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17
Irritation parameter:
chemosis score
Basis:
animal: 8285M
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 1.5
Irritation parameter:
conjunctivae score
Basis:
animal: 8285M
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2.17
Irritation parameter:
cornea opacity score
Basis:
animal: 8284F
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.67
Irritation parameter:
iris score
Basis:
animal: 8284F
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17
Irritation parameter:
chemosis score
Basis:
animal: 8284F
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 1.33
Irritation parameter:
conjunctivae score
Basis:
animal: 8284F
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2
Irritant / corrosive response data:
In 4/6 animals, necrotic effects on the conjunctivae are stated, also in 2/3 animals whose eyes had been washed showed necrosis.
Individual effect scores were 3 for erythema in all animals at 24, 48, and 72 h, including washed eyes. Positive scores (in the sense of the Hazard Regulation 16 CFT 1500.42) were exhibited by all animals for conjunctival redness, chemosis, and necrosis as well as corneal ulceration, by 8 animals for corneal opacity, and 7 animals for iridal irritation. All animals were free of signs of ocular irritation by the end of the study (14 days).
Other effects:
Responses were slightly, but not substantially less severe in animals with washed eyes than in those with unwashed eyes.

Any other information on results incl. tables

 Results of eye irritation study (24-h exposure): Mean effects scores over all animals and time (Individual data were taken from Report Table I)

 

Cornea (opacity)

Iris

Conjunctiva

Redness

Chemosis

Score (average of animals investigated)

0 to 4

0 to 2

0 to 3

0 to 4

1 h

24 h

1.67

1.00

3.00

3.00

48 h

1.75

0.42                          

3.00

2.33

72 h

1.50

0.67

3.00

2.17

Average 24 h, 48 h, 72 h

1.64

0.70

3.00

2.50

Reversibility*

c

c

c

c

Average time for reversion

7 d

7 d

9 d

9 d

*             c :           completely reversible
               n c :        not completely reversible
               n :           not reversible

 

 

 

 

Note: The average scores are not documented in the report but were calculated from the individual effects data.

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:

Based on CLP, butyraldehyde has to be allocated to the Category 2 (irritating to eyes).
Executive summary:

In a valid standard guideline study (described under 40 CFR Part 163.81 -4), undiluted butyraldehyde (0.1 ml) produced severe irritation and injury to all eye parts observed in all treated animals. The recovery period for conjunctival tissue lesions was greater than 7 d for most rabbeits. Eye washing after 20 sec after dosing failed to reduce irritating effects or responses to a significant extent. The detailed documentation of the observations and individual grading allows to evaluate the data in terms of current criteria.