4-(4-chlorophenyl)-2-phenyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butanenitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24-March-1987 to 31-March-1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-chlorophenyl)-2-phenyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butanenitrile

EC Number:

406-140-2

EC Name:

4-(4-chlorophenyl)-2-phenyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butanenitrile

Cas Number:

114369-43-6

Molecular formula:

C19H17ClN4

IUPAC Name:

4-(4-chlorophenyl)-2-phenyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butanenitrile

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Received from Hazleton Research Animals, Denver, PA.
- Age at study initiation: Approximately 12 weeks old
- Weight at study initiation: From 2.5 to 3.1 kg
- Housing: The animals were individually housed in stainless steel cages (18" x 24" x 15") suspended above absorbant paper pan liners which were changed 3 times a week.
- Diet: Approximately 225 g/day of Purina Laboratory Rabbit Chow High Fiber Diet
- Water: Filtered tap water (via automatic watering)
- Acclimation period: Approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C
- Humidity (%): Between 40 and 60%.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test item was ground in a mortar and pestle, and 0.1 g of the test material was applied to the corneal surface of the left eye of each rabbit.

Duration of treatment / exposure:

The treated and control eyes of three of the nine rabbits were irrigated with distilled water for approximately 60 seconds, beginning 20 to 30 seconds after dosing. The treated and control eyes of the remaining six animals were rinsed with water after the 24 hour observation for 30 to 60 seconds.

Observation period (in vivo):

24, 48 and 72 hr and 7 days after dosing

Number of animals or in vitro replicates:

9 male rabbits

Details on study design:

PREPARATION AND SELECTION OF ANIMALS: Upon arrival, all animals were examined for physical abnormalities, identified by uniquely numbered ear tags, and quarantined for approximately 2 weeks. One day prior to being dosed, nine healthy rabbits were selected from a stock population. All eyes were examined grossly and with an aqueous 2.0% sodium fluorescein solution. Rabbits with ocular abnormalities were excluded from the study.

SCORING SYSTEM: The degree of eye irritation was scored according to the procedure of Draize et al (J. Pharmacol. Exp. Therap., 82, 377-390, 1944).

TOOL USED TO ASSESS SCORE: When no gross lesions were evident on the cornea, the eyes were examined by using a 2.0% aqueous sodium fluorescein solution.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals (unwashed eyes) and 3 animals (washed eyes)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals (unwashed eyes) and 3 animals (washed eyes)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals (unwashed eyes) and 3 animals (washed eyes)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals (unwashed eyes) and 3 animals (washed eyes)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritant / corrosive response data:

No ocular effects were observed in the washed and unwashed treated eyes at any observation time. The eye irritation scores are detailed below (Table 1).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an in vivo eye irritation study performed according to OECD guideline, the test item was concluded not to be irritant and/or corrosive to the eye.