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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: Non-GLP, near guideline study, published in peer reviewed literature. No restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
An objective method for the evaluation of eye irritation in vivo
Author:
Jacobs GA and Martens MA
Year:
1989
Bibliographic source:
Fd Chem Toxic. Vol 27. No. 4 pp 255-258

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
ultrasonic pachometry included, 6 rabbits used
Principles of method if other than guideline:
Phase 1 - 3 animals tested and scored clinically; Phase 2 - 3 animals tested, scored and corneal swelling measured using ultrasconic pachometer.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Acetic acid
EC Number:
200-580-7
EC Name:
Acetic acid
Cas Number:
64-19-7
Molecular formula:
C2H4O2
IUPAC Name:
acetic acid
Details on test material:
- Name of test material (as cited in study report): Acetic acid
- Physical state: liquid
- Analytical purity: 99.5%
- Other: obtained from Merck, Darmstadt, FRG

Test animals / tissue source

Species:
rabbit
Strain:
other: Rsk:NZW
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Six healthy rabbits used in two phases, each phase separated by about 6 months (3 rabbits per phase)
- No further details reported

ENVIRONMENTAL CONDITIONS
- No details reported.

IN-LIFE DATES: No dates reported

Test system

Vehicle:
other: 10% acetic acid in water tested
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 uL
- Concentration (if solution): 10%


Duration of treatment / exposure:
4 h
Observation period (in vivo):
4, 24, 48, 72, 96 and 168 h
Number of animals or in vitro replicates:
3 / phase
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were not washed following instillation

SCORING SYSTEM:
- Erythema, chemosis, iritis and corneal opacity were scored according to Draize scores

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein - none reported
Ultrasonic pachometry used to assess corneal thickness in Phase 2 rabbits

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: erythema score
Basis:
mean
Time point:
other: 24, 48 & 72 h
Score:
2.67
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: erythema score, 10% acetic acid
Irritation parameter:
other: % corneal swelling
Basis:
mean
Remarks:
based on three rabbits
Time point:
other: 24, 48 & 72 h
Score:
87
Reversibility:
not specified
Remarks on result:
other: % corneal swelling, 10% acetic acid
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
based on six rabbits
Time point:
24/48/72 h
Score:
1.72
Reversibility:
not specified
Remarks on result:
other: 10 % acetic acid
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
based on six rabbits
Time point:
24/48/72 h
Score:
1.67
Reversibility:
not specified
Remarks on result:
other: 10% acetic acid
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
other: Not reported
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
other: Not reported
Irritant / corrosive response data:
Instillation of 10% acetic acid resulted in a mean erythema score of 2.67, which is considered to justify the classification "irritant" according to EEC classification, and a mean % corneal swelling of 87%.
There was shown to be a good correlation between corneal opacity and corneal swelling in this study and from this it was deduced that 80% mean corneal swelling corresponds to a corneal opacity value of 2, the EEC threshold for classification as an irritant.
was irritant to the rabbit eye
Other effects:
None reported

Any other information on results incl. tables

Table 1 - Eye irritation scores for 10% acetic acid

Mean erythema score

Mean chemosis score

Mean corneal opacity score

Mean % corneal swelling

2.67 *

1.67

1.72

87 *

Means are for 6 rabbits, except for mean % corneal swelling which is for 3 rabbits.

* these values justify the term irritant

The mean erythema, chemosis and corneal opacity scores were calculated for all six rabbits and the scores at the three observation times, 24, 48 and 72 h, were pooled. In this study mean erythema was calculated by reading the erythema of the upper eyelid, the lower eyelid and the nictitating membrane. The mean of thee readings was considered to be the erythema of the palpebral conjunctiva of a rabbit at a given time.

Corneal swelling was expressed as a percentage and calculated according to the formula:

%CS=        [(corneal thickness at time t  / corneal thickness at time 0) - 1] x 100.

The mean % swelling is calculated over 3 rabbits for each observation time.

Applicant's summary and conclusion

Conclusions:
10% acetic acid was shown to be irritating to the rabbit eye using the mean erythema score and % corneal swelling as measured using ultrasonic pachometry.
Executive summary:

To eliminate the difficulties of subjective judgement in assessing eye irritants, the relationship between corneal swelling, measured objectively using ultrasonic pachometry, and the reading of other symptoms was investigated in this study, using 34 substances. Erythema, oedema and corneal opacity were evaluated according to EEC directive 83/467/EEC. Good correlations were found between the mean percentage corneal swelling after 24, 48 and 72 h and mean corneal opacity (r=0.94) and erythema scores (r=0.93) after the same observation times.

10% acetic acid was shown to be irritating to the rabbit eye using the mean erythema score and % corneal swelling as measured using ultrasonic pachometry.