Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04-NOV-2003 to 13-JAN-2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted February 2nd, 2000 [RS 813.016.5]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26Ih, 1997 by decision of the OECD Council [C(97)186/Final].

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 2,3-O-(1-methylethylidene)-5-O-[(4-methylphenyl)sulfonyl]-ß-D-ribofuranoside
EC Number:
609-920-2
Cas Number:
4137-56-8
Molecular formula:
C16H22O7S
IUPAC Name:
Methyl 2,3-O-(1-methylethylidene)-5-O-[(4-methylphenyl)sulfonyl]-ß-D-ribofuranoside
Details on test material:
Identification TOSYLFURANOSID
Description Solid
Expiry date August 2004
Stability of test item dilution Unknown in PEG 300; is excluded from the statement of compliance.
Storage conditions At room temperature (range of 20 ± 3 °C), light protected.

Test animals

Species:
rat
Strain:
other: Rat, HanBrl: Wist (SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST SYSTEM
Test system Rat, HanBrl: Wist (SPF)
Rationale Recognized by the international guidelines as a recom-mended test system.
Source RCC Ltd, Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
Number of animals per group 3 females
Total number of animals 6 females
Age when treated 12 weeks
Identification Unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
HUSBANDRY
Room no. 104 / RCC Ltd, Füllinsdorf
Conditions Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environ-ment with target ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70 % (values above 70 % during cleaning process possible), automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
Accommodation In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
Diet Pelleted standard Provimi Kliba 3433 rat/mouse mainte-nance diet, batch no. 54/03 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
Water Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are ar-chived at RCC Ltd, Itingen.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
VEHICLE The following information was provided by RCC Ltd: Identification Polyethylene glycol 300 (PEG 300) Description Colorless viscous liquid Lot number 448174/1 21203148 Source FLUKA Chemie GmbH, CH-9471 Buchs Stability of vehicle Stable under storage
Details on oral exposure:
Two groups, each of three female HanBrl: WIST (SPF) rats, were treated with TOSYLFURANOSID by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and adminis-tered at a volume dosage of 10 mL/kg.
Doses:
2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.
No. of animals per sex per dose:
Two groups, each of three female HanBrl: WIST (SPF) rats, were treated with TOSYLFURANOSID by oral gavage administration at a dosage of 2000 mg/kg body weight
Details on study design:
The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were re-corded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
Statistics:
No statistical analysis was used.

Results and discussion

Preliminary study:
Two groups, each of three female HanBrl: WIST (SPF) rats, were treated with TOSYLFURANOSID by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and adminis-tered at a volume dosage of 10 mL/kg.
The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were re-corded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
All animals survived until the end of the study period.
No clinical signs were observed during the course of the study.
The body weight of the animals was within the range commonly recorded for this strain and age.
No macroscopic findings were recorded at necropsy.
The median lethal dose of TOSYLFURANOSID after single oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the end of the study period.
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The median lethal dose of TOSYLFURANOSID after single oral administration to female rats, observed over a period of 14 days is:
LD50 (female rat): greater than 2000 mg/kg body weight
Executive summary:

Two groups, each of three female HanBrl: WIST (SPF) rats, were treated with TOSYLFURANOSID by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and adminis-tered at a volume dosage of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were re-corded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No clinical signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose of TOSYLFURANOSID after single oral administration to female rats, observed over a period of 14 days is:

LD50 (female rat): greater than 2000 mg/kg body weight