Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 24 november and 10 December 1998
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(adopted 22 March 1996)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Commission Directive 96/54/EC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Batch Number: 004 (Vendor Lot# 4-9126-7-01-01)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals were supplied by Charles River (UK) Ltd, Margate, Kent, UK. At the start of the study the males weighed 220 to 227 g and the females 200 to 216 g and were eight to twelve weeks old. After an acclimatisation period of at least fice days, the animals were selected at random and given a number unique within the cage by tail marking.

The animals were housed in groups of up to three by sex in solid-floor PP cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19 to 21 C and relative humidity of 44 to 66%. 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.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Arachis oil BP
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the dime of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confirm the survival of the previously dosed animals.
Doses:
Dose level: 2000 mg/kg
Concentration: 200 mg/ml
Dose volume: 10 mg/kg
No. of animals per sex per dose:
3 animals per sex per dose
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual body weights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the animals were killed by overexposure to carbon dioxide. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

The number of animals dying during the study or killed for humane reasons was determined. The nature, severity, time of onset and duration of toxic effects were also determined. Effects on bodyweights and abnormalities noted at necropsy were identified. Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Statistics:
Not mentioned

Results and discussion

Preliminary study:
The animals were exposed on a single dose of 2000 mg/kg bw, selected according to the available information.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No signs of systemic toxicity were noted during the study period.
All animals showed expected gains in bodyweight over the study period.
Body weight:
Bodyweight gain during Week 1 / Week 2
Female 1-0: 23 / 15
Female 1-1: 31 / 17
Female 1-2: 36 / 2
Male 2-0: 50 / 43
Male 2-1: 56 / 34
Male 2-2: 64 / 45
Gross pathology:
Effects on organs:
No abnormalities were noted at necropsy of animals killed at the end of the study period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test material, BMS 214702-01, in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg.
No symbol and risk phrase are required according to EU labelling regulations.
Executive summary:

Methods

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

Procedures

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level. Dosing was performed sequentially.

The test material was administered orally as a suspension in arachis oil BP. The animals were observed 0.5, 1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14. At the end of the observation period all animals were killed by overexposure to carbon dioxide and were subjected to gross necropsy.

Results

The following results were obtained:

  • There were no deaths.
  • There were no signs of systemic toxicity.
  • All animals showed expected gains in bodyweight over the study period.
  • No abnormalities were noted at necropsy.
  • The acute median lethal dose, LD50, of the test material was estimated as being greater than 2000 mg/kg.

Conclusion

No symbol and risk phrase are required according to EU labelling regulations.