Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start: 08 January 2002 End : 11 January 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: There are no deviations from the recommended guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Phenyloxindole
- Physical state: Light beige powder
- Analytical purity: 99.80%
- Lot/batch No.: CHAD 9902K
- Expiration date of the lot/batch: 14 November 2002 (allocated by NOTOX, 1 year after receipt of the test substance)
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: Animals used within the study were at least 6 weeks old.
- Weight at study initiation: 2247-2834 g
- Housing: Individually in labelled cages with perforated floors (Scanbur Denmark, dimensions 53.5x63x38.5 cm).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day.
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 3ºC
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: Start: 08 January 2002; End : 11 January 2002

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 42.5 (42.1 - 42.9) mg of the test substance (a volume of approximately 0.1 ml).


Duration of treatment / exposure:
The substance was not removed.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.


Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:


SCORING SYSTEM: Included in the Study Report.


TOOL USED TO ASSESS SCORE: lmmediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
other: redness
Basis:
mean
Time point:
other: 24-72 h
Score:
0.67
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
other: discharge
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Irritant / corrosive response data:
lnstillation of approximately 42.5 mg of the test substance (a volume of approximately 0.1 ml) into one eye of each of three rabbits resulted in irritation of the conjunctivae which was seen as redness, chemosis and discharge. The irritation had completely resolved within 48 hours in one animal and within 72 hours in the other two animals.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

There was no evidence of ocular corrosion.

No staining of (peri) ocular tissues by the test substance was observed.
Remnants of the test substance were present in the eyes of all animals on day 1
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 7.3.2: Mean eye irritation scores

Redness

Chemosis

Discharge

Opacity

Iris

1 hour

1.67

1

1

0

0

24 hours

1.33

0

0

0

0

48 hours

0.67

0

0

0

0

72 hours

0

0

0

0

0

Mean score

24-72 h

0.67

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Phenyloxindole is considered as non-irritating.
Executive summary:

Single samples of approximately 42.5 mg of Phenyloxindole (a volume of approximately 0.1 ml) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. lnstillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness, chemosis and discharge. The irritation had completely resolved within 48 hours in one animal and within 72 hours in the other two animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any af the animals. Phenyloxindole is considered as non-irritating.