2-[(2S,3S)-3-[[(1,1dimethylethoxy)carbonyl]amino]-2-hydroxy-4-phenylbutyl]-2-[[4-(2pyridinyl)phenyl]methyl]-,1,1-dimethylethyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Study was conducted prior to changes in Annex VI requirements

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl 2-{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-2-[4-(pyridin-2-yl)benzyl]hydrazinecarboxylate

EC Number:

606-396-7

Cas Number:

198904-86-8

Molecular formula:

C32H42N4O5

IUPAC Name:

tert-butyl 2-{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-2-[4-(pyridin-2-yl)benzyl]hydrazinecarboxylate

Test material form:

solid

Details on test material:

- Appearance: Off-white powder
- Storage condition of test material: At room temperature protected from light

Specific details on test material used for the study:

BMS233101, purity 99.95%, off white solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits, supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK, were used. At the start of the study the animals weighed 2.79 to 3.15 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food {STANRAB SQC Rabbit Diet, Special Diets
Services Ltd, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 17 to 21 'C and relative humidity of 48 to 65%. The rate of air exchange was approximately fifteen
changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml of the test material, which was found to weigh approximately 49 mg

Observation period (in vivo):

1 hour and 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

3 animals

Details on study design:

One rabbit was initially treated. A volume of 0.1 ml of the test material, which was found to weigh approximately 49 mg {as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctiva! sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs.

Irritant / corrosive response data:

No corneal effects were noted during the study.
Iridial inflammation was noted in one treated eye at the 1-hour observation. No other iridial effects were noted.
Moderate conjunctival irritation was noted at the 1-hour observation with minimal conjunctival irritation apparent at the 24-hour observation. All treated eyes appeared normal at the 48-hour observati

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, BMS 233101-01, produced a maximum group mean score of 11.7 and was classified as a MINIMAL IRRITANT (CLASS 3 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system.
The test material did not produce positive criteria in any rabbit according to the EU labelling regulations. No symbol and risk phrase are therefore required.