[Name confidential or not available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1981

Deviations:

yes

Remarks:

Dose volumes could not be kept constant but increased with increasing dose up to the double volume of that recommended by OECD401 for aqueous dose formulations. Numbers of animals used were confined to 3 males and 3 females per dose group.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA, 1959

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Certified by BAM according to DIN EN 45001.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Winkelmann, Paderborn (SPF-Quality) with appropriate range of bodyweight at study start.
- Bodyweight at study start (day of dosing): Males: minimum 210 g, maximum 225 g,
Females: minimum 190 g, maximum 206 g.
- Housing: Group housing with up to 3 animals by sex in cages.
- Fasting period: From 16 hours before test start
- Diet (except for fasting period): Commercially available standard laboratory animal diet:
"Rat/Mouse Maintenance" from Altromin, Lage, Germany
- Water was provided ad libitum

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 22.5 ± 2°C
- Relative Humidity (%): 50 to 60%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Dose formulation: Suspension: 20% test material in vehicle (water) and warmed to body temperature (40°C).
Administration of the dose formulation to the animals at body temperature.
- Dose volume: 1.0, 2.0 and 4.0 mL / 100 g bw attaining test material doses of 2000, 4000 and 8000 mg/kg bw, respectively.
Individual dose volume was calculated based on individual bodyweight.
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.

Doses:

WS400506: 2000, 4000 and 8000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
It has not been clearly specified in the report at what time points clinical signs and mortality were recorded, but the following records have been
reported:
Clinidal signs: At least shortly after dosing (Day 0) and occasionally over 24 hours after dosing and at 7 and 14 days post dosing.
Mortality: At least at 24 hours and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume, and on Days 7 and 14 (end of observation period).
- Necropsy: All animals were necropsied at termination of the study.
- Control animals were untreated. As animals from a stock culture served as controls, apparently these were not necropsied concurrent with dosed animals.

Statistics:

LD50 was estimated for 24 hours and 14 days post dosing. Determination of a slope function was inappropriate as there were no deaths in the present study.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 000 mg/kg bw

Based on:

test mat.

Remarks:

WS400506

Remarks on result:

other: No deaths at 2000, 4000 or 8000 mg/kg bw

Mortality:

There were no deaths during the 14-day observation period post dosing:
Single Dose of WS400506 at: Mortality
2000 mg/kg bw 0/3 (m); 0/3 (f)
4000 mg/kg bw 0/3 (m); 0/3 (f)
8000 mg/kg bw 0/3 (m); 0/3 (f)

Clinical signs:

Shortly after dosing and 7 and 14 days afterwards clinical signs attributable to the treatment with the test material were not evident. There was a subjective impression that animals in the top dose group behaved a little more apathic within 24 hours post dosing than control animals from a stock culture. This was attributed to the high administration volume in this dose group, rather than to the test substance itself.

Body weight:

There were no adverse effects on body weight gain.

Gross pathology:

Macroscopic pathology findings attributable to the treatment with the test material were not evident.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Remarks:

according to Regulation (EC) 1272/2008

Conclusions:

In view of the attained absence of mortality at doses of WS400506 up to 8000 mg/kg bodyweight, the outcome of the present study does not necessitate any classification and labelling regarding acute oral toxicity according to Regulation (EC) 1272/2008. In addition, sex-related differences in toxicity of the test material after single oral administration were not evident.