Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1994-04-27 to 1994-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 401 and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Program (inspection date: 1992-10-27 / signed on: 1992-012-04)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: clear colourless liquid
- Storage condition of test material: in the dark at approximately 4°C

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Remarks:
Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: approximately 100 g
- Fasting period before study: overnight before dosing
- Housing: in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays.
- Diet: pelleted diet ad libitum (SQC rat and mouse maintenance No. 1 Expanded, produced by Special Diets Services, Witham, Essex).
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 36-62 %
- Air changes (per hr): no data, air conditioned room
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: delivered on 1994-05-22 for the range-finding study and 1994-04-29 from the main study

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
Range-finding test: 25, 50 and 100 mg/mL
main test: 100 mg/mL

DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
Range-finding test: 500, 1000 and 2000 mg/kg bw
Main test: 2000 mg/kg bw
No. of animals per sex per dose:
Range-finding test: 2 animals/sex/dose
Main test: 5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: approximately 30 minutes, 1, 2 and 4 hours afters dosing and thereafter for a further 7 days in the range finding study and 14 days in the main study.
Weighing: on the day of dosing, on days 8 and 15.
- Necropsy of survivors performed: yes, including opening of the thoracic and visceral cavities, opening and examination of the stomach and representative sections of the gastro-intestinal tract and examination of the major organs. Abnormal tissues and organs were preserved in buffered formol saline. Necropsy was not performed on range-finding animals.
Statistics:
none

Results and discussion

Preliminary study:
No deaths occurred and no signs of toxicity were exhibited by any animal in any dose group in the range-finding study
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred.
Clinical signs:
All animals maintained a healthy appearance throughout the 15 day observation period.
Body weight:
There was no adverse effect on bodyweight gain in animals of either sex.
Gross pathology:
At necropsy, the submandibular lymph nodes were enlarged and the urinary bladder was distended with fluid in one male. The thymus was red and swollen in one female. No abnormalities were detected in the remaining animals.
Other findings:
none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 Combined > 2000 mg/kg bw
Executive summary:

In a limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, groups of fasted, 4 -6 weeks old, Crl:CD(SD) rats (5/sex) were administered a single oral dose of ST 06 C 93 diluted in water at 2000 mg/kg bw by gavage. This limit dose was selected based on the absence of mortality and clinical signs in 2 animals/sex/dose (500, 1000 or 2000 mg/kg bw) in the range-finding study.

The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. At necropsy, the submandibular lymph nodes were enlarged and the urinary bladder was distended with fluid in one male. The thymus was red and swollen in one female. No abnormalities were detected in the remaining animals.

 

Oral LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, ST 06 C 93 is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.