tert-butyl {(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}carbamate

Endpoint summary

Description of key information

BMS 217947 -01 was tested for acute oral toxicity on Sprague-Dawley male and female rats, according to EU Test Method B.1 bis (fixed dose procedure) and OECD Test Guideline 423. No deaths were observed on 3 male and 3 female rats at the 200 mg/kg bw dose, while all 3 female rats died at the dose level of 2000 mg/kg bw. Based on this, the oral LD50 for the substance was estimated to be 300 - 500 mg/kg bw. This is sufficient to classify the substance as acute toxic, categorty 4, according to CLP. No clinical signs or adverse effects were observed at the 200 mg/kg bw dose level.

A study was carried out on male and female Sprague-Dawley rats to determine the acute dermal (systemic) toxicity potential for substance BMS 217947 -01, according to EU Test Method B3, Part 3 of Directive 92/69/EEC and OECD Test Guideline No 402. None of the 5 male and 5 female rats died when exposed to doses of 200 mg/kg bw and 2000 mg/kg bw. Therefore, the LD50 value for dermal exposure is greater than 2000 mg/kg bw. As a result, the substance is not classified as acute dermal toxic.

A method devlopment trial was conducted on BMS 217947 -01 to determine the perforance of a OECD Guidelines for Testing of Chemicals, Section 4, Health Effects. No.436, "Acute Inhalation Toxicity - Acute Toxic Class Method. This study was conducted in order to develop and method for the generation of a suitable test atmosphere. Limitiations to generate a suitable test atmosphere were found and it was concluded that becasue of the intrinsic properties of substance it was not technically possible to determine the inhalation toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Nov. 1998 to 15 Dec. 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD method and GLP

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Vehicle:

other: Arachis oil BP.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 500 mg/kg bw

Based on:

test mat.

Mortality:

Male: 200 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 3
Female: 200 mg/kg bw; Number of animals: 3; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: Deaths were noted at a dose level of 2000mg/kg. There were no deaths at a dose level of 200mg/kg. Signs of toxicity noted at a dose level of 2000mg/kg were hunched posture, lethargy, ataxia decreased respira

Gross pathology:

Effects on organs:
Dose level 2000mg/kg = haemorrhagic lungs, dark liver, pale spleen, dark kidneys, pale appearance of the gastric mucosa and haemorrhage of the small intestine.

Dose level 200mg/kg = No abnormalities were detected.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD 50 is estimated to be 300-500 mg/kg and classified as acute toxic class 4.

Executive summary:

BMS 217947 -01 was tested for acute oral toxicity on Sprague-Dawley male and female rats, according to EU Test Method B.1 bis (fixed dose procedure) and OECD Test Guideline 423. No deaths were observed on 3 male and 3 female rats at the 200 mg/kg bw dose, while all 3 female rats died at the dose level of 2000 mg/kg bw. Based on this, the oral LD50 for the substance was estimated to be 300 - 500 mg/kg bw. This is sufficient to classify the substance as acute toxic, categorty 4, according to CLP.

No clinical signs or adverse effects were observed at the 200 mg/kg bw dose level.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Study period:

05 June 2015

Data waiving:

study technically not feasible

Justification for data waiving:

other:

GLP compliance:

no

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 July - 26 August 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: done under GLP and OECD method

Qualifier:

according to guideline

Guideline:

other: Directive 92/69/EEC, Method B3 Part 3;OECD Guideline No.402

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Type of coverage:

semiocclusive

Vehicle:

other: 1% methylcellulose.

Duration of exposure:

24 h

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No deaths occurred in any of the animals. A slight bodyweight loss was noted in two females on day 8 and day 15. One female gained no weight on day 8. No other systemic responses were observed in any animals.

Gross pathology:

Effects on organs:
No macroscopic abnormalities were observed for animals
killed at study termination on Day 15.

Other findings:

Signs of toxicity (local):
Transient slight to well-defined irritation (erythema/oedema
Grade 1 or 2) was notable in four males and four females
following removal of dressings, resolving in all instances
by Day 5. No dermal response was evident in the remaining
two rats throughout the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose to rats was demonstrated to be greater than 2000mg/kg bodyweight

Executive summary:

A study was carried out on male and female Sprague-Dawley rats to determine the acute dermal (systemic) toxicity potential for substance BMS 217947 -01, according to EU Test Method B3, Part 3 of Directive 92/69/EEC and OECD Test Guideline No 402. None of the 5 male and 5 female rats died when exposed to doses of 200 mg/kg bw and 2000 mg/kg bw. Therefore, the LD50 value for dermal exposure is greater than 2000 mg/kg bw. As a result, the substance is not classified as acute dermal toxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The oral LD50 for the substance was estimated to be 300 - 500 mg/kg bw. This is sufficient to classify the substance as acute toxic, categorty 4, according to CLP.

The LD50 value for dermal exposure is greater than 2000 mg/kg bw. As a result, the substance is not classified as acute dermal toxic.