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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-11-24 to 1998-12-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

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:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor and 002

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dissolved in arachis BP oil to the appropiate concentration

FORM AS APPLIED IN THE TEST (if different from that of starting material)
Dose concentration was 200 mg test substance/ml for both males and females, with an amount equal to 10 ml test solution/kg bodyweight

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 8-12 weeks
- Weight at study initiation: males were 226-242 g, females 202-217 g
- Fasting period before study: Overnight fast immediately before dosing.
- Housing: 3 by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum (Rat and Mouse Expanded Diet No.1, Specia! Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum drinking water
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 44-66%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg test substance/ml
- Amount of vehicle (if gavage): 10 ml/kg bodyweight
- Justification for choice of vehicle: Dissolves the test substance well and is known to be non-toxic orally

MAXIMUM DOSE VOLUME APPLIED:
2.71 ml

Doses:

2000 mg test substance/kg bodyweight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations 0.5, 1, 2, and 4 hours after dosing, then once daily. Weighing was conducted on Day 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made as shown in the schematic diagram

Results and discussion

Preliminary study:

No preliminary study was conducted.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

This study validly found that the test substance is not classified under GHS criteria for oral toxicity.