Benzeneacetic acid, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-.alpha.,.alpha.-dimethyl-, ethyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sample reception: 31-10-1997 / Study completion date: 12-03-1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethyl-ethyl ester benzeneacetic acid

EC Number:

616-391-1

Cas Number:

76812-02-7

Molecular formula:

C34 H41 N O4

IUPAC Name:

4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethyl-ethyl ester benzeneacetic acid

Constituent 2

Reference substance name:

4-(4-(4-Hydroxydiphenylmethyl)-1-piperidinyl)-1-oxobutyl- alpha,alphadimethylbenzeneacetic acid ethyl ester

IUPAC Name:

4-(4-(4-Hydroxydiphenylmethyl)-1-piperidinyl)-1-oxobutyl- alpha,alphadimethylbenzeneacetic acid ethyl ester

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FEXOFENDONETHYLESTER
- Lot/batch No.: TAM 40/96/13
- Phycal state: white powder
- Container: one plastic flask
- Date of receipt: 31 October 1997
- Storage condition of test material: at +4°C and protected from light
- The pH of the test substance at the concentration of 10% in purified water, measured at C.I.T., was approximately 6 to 7.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Breeder: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Housing: polystyrene cages (35 cm x 55 cm x 32 cm or 48.2 cm x 58 cm x 36.5 cm).
- Weight on the day of treatment: 3.0 ± 0.3 kg.
- Food: free access to 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France).
- Water: filtered by a F.G. Millipore membrane (0.22 µ)
- Acclimatization: at least 5 days before the beginning of the study.

Environmental conditions:
- temperature: 18 ± 3°C
- relative humidity: 30 to 70%
- light/dark cycle: 12 h/12 h
- ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye, which remained untreated, served as control.

Amount / concentration applied:

A single dose of 100 mg of the test substance was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

The lower and upper eyelids were held together for about one second to avoid any loss of test substance.
Both eyes were rinsed 24 hours after treatment, using 0.5 ml of sterile isotonic saline solution (0.9% NaCl).

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test substance.

Number of animals or in vitro replicates:

3 animals were used, as recommended by the International Regulations and taking into account that a good correlation of results can be obtained with either three or six animals. The animals were identified individually with a metal tag in the ear.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

3

Results 3

Irritation parameter:

iris score

Remarks:

lesions

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

cornea opacity score

Remarks:

intensity

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

cornea opacity score

Remarks:

Area

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Only ocular discharge was noted in one animal on day 1.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under our experimental conditions, the test substance FEXOFENDONETHYLESTER is non-irritant when administered by ocular route in rabbits.