Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July to December 2002
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Appearance: light tan solid
Storage conditions: at room temp, protected by light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals chosen for this study were selected from a stock supply of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England.

They were in the weight range of 93 to 123 g and approximately five to seven weeks of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a minimum period of five days prior to the start of the study.

Rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of three rats of the same sex in metal cages with wire mesh floors in Building F21, Room 28.

A standard laboratory rodent diet (Special Diet Services RMI (E) SQC expanded pellet) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approximately four hours after dosing. The batch(es) of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organisms. Results of routine physical and chemical examination of drinking water, as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd. at regular intervals throughout the year.

Animal room environmental controls were set to maintain temperature within the range 22 ± 3°C and relative humidity 40 - 70%. Any minor deviations from these ranges would not have had an adverse effect on the animals and would not affect the integrity or validity of the study. These environmental parameters were recorded daily and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to provide 12 hours of artificial light (0600 - 1800 hours GMT) in each 24-hour period.

Each animal was identified by tail marking. Each cage was identified by a coloured label displaying the dose level, study number, animal mark and the initials of the Study Director and Home Office licensee.


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The appropriate dose volume of the test substance was administered to each rat by oral gavage using a plastic syringe and catheter (8 ch).

The day of dosing was designated Day 1.

Doses:
Dose: 2000mg/kg at a concentration fo 200 mg/ml.
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
A group of three fasted female rats received a single oral gavage dose of the test substance, formulated in water for inigation, at a dose level of 2000 mg/kg. As results at this dosage indicated the acute lethal oral dose of the test material to be greater than 2000 mg/kg bodyweight, in compliance with the study guidelines, a group of three fasted males was dosed at 2000 mg/kg to confirm results at this dosage and complete the study

Results and discussion

Preliminary study:
There was no preliminary study
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single oral gavage dose of BMS 482204-03 (MSA Salt) to a group of six rats (three males and three females) at a dose level of 2000 mg/kg bodyweight.
Clinical signs:
Clinical signs of reaction to treatment were confined to salivation, which was observed approximately 5 minutes after dosing in one male and one female only. Recovery of rats, as judged by external appearance and behaviour, was complete in both animals approximately 30 minutes after dosing ..


Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute lethal oral dose to rats of BMS 482204-03 (MSA Salt) was demonstrated to be greater than 2000 mg/kg bodyweight.

BMS 482204-03 (MSA Salt) will not require labelling with the risk phrase R22 "Harmful if swallowed", in accordance with Commission Directive 93/21/EEC.
Executive summary:

This study was performed to assess the acute oral toxicity of BMS482204 -03 (MSASalt) to the rat. The method followed was that described in : EEC Methods for the determination of toxicity, Annex to Directive  96/54/EEC  (Official Journal No.L248, 30.9.96), PartB, Method B.l tris -  Acute toxicity (oral) -acute toxic class method.

  OECD Guideline for Testing of Chemicals No.423 'Acute OralToxicity -AcuteToxic Class Method' Adopted 22 March 1996.

 

A group of three fasted female rats received a single oral gavage dose of the test substance, formulated in water for irrigation, at a dose level of 2000mg/kg. As results at this dosage indicated the acute lethal oral dose of the test material to be greater than 2000mg/kg body weight, in compliance with the study guidelines, a group of three fasted males was dosed at 2000mg/kg to confirm results at this dosage and complete the study.

 

All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period.

 

Clinical signs of reaction to treatment were confined to salivation which was observed approximately 5 minutes after dosing in one maleand one female only.   Recovery of rats, as judged by external appearance and behaviour, was complete in both animals approximately 30 minutes after dosing.

 

All animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

The acute lethal oral dose to rats of BMS482204 -03 (MSASalt) wasdemonstrated to be greater than

2000mg/kg body weight.

 

BMS 482204-03 (MSA Salt) will not require labelling with the risk phrase R22 "Harmful  if swallowed", in accordance with Commission Directive 93/21/EEC.