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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test item 4-nitrophenyl-acetic acid
Batch No. 0046D93
Physical state solid, crystalline powder
Colour yellowish to yellow-brownish
Storage cool, dry place, protected from light

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species and strain: New Zealand white rabbit
Source: S&K LAP Kft.
Hygienic level during the study: good conventional
Number of animal: 3 males
Age of animals: adult rabbits, 11 weeks old
Body weight range at the beginning of the study: 2338 - 2950 g
Body weight range at the end of the study: 3364 - 3780 g
Acclimatisation time: 5 days in first animal, 6 days in second animal and 7 days in third animal
Animal health: Only animals in acceptable health condition were used for the test.

Housing: Animals were housed individually in metal cage.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20 ± 3 °C
Relative humidity: 30-70 %
Ventilation: 10-15 air exchanges/hour by central air-condition system

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye served as control.
Amount / concentration applied:
0.1 g of the finely grounded test item was used for the study, as a single dose.
Duration of treatment / exposure:
The eyes of the test animals were not washed out 24 hour after test item application, because the test item had been removed from the eye of test animal by physiological mechanisms.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours, then 1, 2 and 3 weeks after the application.
Number of animals or in vitro replicates:
3 male
Details on study design:
In the first step an initial test was performed using one animal. The test item was placed into the conjunctival sac of the left eye. The eyelids were held closed gently for about one second to prevent any loss of the test item. The contralateral eye served as control.
In the initial test slight to moderate irritant effect was observed 24 hours after treatment. The confirmatory test was conducted using a second animal. Slight to moderate irritant effects were observed 24 hour after treatment. Following treatment of the second animal, the third confirmatory test was conducted using a third animal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: in one animal
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Irritation parameter:
other: redness (conjunctival)
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
1 - 1.33
Max. score:
1.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: in one animal
Irritation parameter:
chemosis score
Remarks:
(conjunctival)
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
0.66 - 1
Max. score:
1
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: in one animal
Irritation parameter:
other: conjunctival discharge
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
0.33 - 1.33
Max. score:
1.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: in one animal
Irritant / corrosive response data:
Treated and control eyes were examined at 1, 24, 48 and 72 hours, then 1, 2 and 3 weeks after the application.
1 hour after the single application of test item into the eye of the rabbits, slight redness, slight to moderate chemosis, moderate to severe discharge of the conjunctivae and slight cornea opacity occurred, as well.
1 week after treatment slight redness, chemosis and discharge of the conjunctivae and slight cornea opacity occurred in one animal, as well. The area of cornea involved was greater than one quarter, but less than half in two animals and the area of cornea involved was greater than one quarter, but not zero (score 1) in one animal, as well. The area of cornea involved was greater than half, but less than three quarters (score 3). Two animals became free of symptoms by this observation time.
2 weeks after treatment two animals were free of symptoms. Moderate redness, moderate to severe chemosis, severe discharge of the conjunctivae and moderate to severe cornea opacity occurred in one animal. The area of cornea involved was greater than three quarters, up to the whole area (score 4).
3 weeks after treatment two animals were free of symptoms. Severe redness, moderate to severe chemosis, severe discharge of the conjunctivae and severe cornea opacity occurred in one animal. The area of cornea involved was greater than three quarters, up to the whole area (score 4).
Three weeks after the treatment the study was finished, because the cornea opacity and symptoms of conjunctivae have not fully reversed within an observation period of 21 days in one animal.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
In conclusion, test item 4-NITROPHENYL-ACETIC ACID (CAS 104-03-0) applied to the rabbits' eye mucosa caused conjunctival and cornea irritant effects which were fully reversible within 1 week in two animals, but the conjunctival effects and effect on the cornea did not reverse within an observation period of 21 days in one animal. The test item should be classified into “Category 1 (irreversible effects on the eye/serious damage to eyes)”.