Registration Dossier

Administrative data

Description of key information

No death in the acute oral toxicity study in rats at the limit dose of 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
of 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
of 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
of 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries. Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD(SD) with appropriate range of bodyweight at study start.
- Source: Charles River (UK) Ltd.
- Age at study start (day of dosing): 8 to 12 weeks.
- Weight at start (day of dosing): Females: minimum 232 g, maximum 255 g.
- Fasting period: Overnight immediately prior to dosing until ca. 4 hours post administration.
- Housing: In groups of 3 by sex in solid bottomed polycarbonate cages inside a barriered rodent facility.
- Bedding material: Autoclaved wood flake bedding
- Cage enrichment: Soft white chew block and plastic shelter (chew block removed during fasting).
- Diet: Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
containing no added antibiotic, chemotherapeutic or prophylactic agent.
- Drinking water (ad libitum): Pottable drinking water from the public supply
- Acclimation period: At least 6 days before dosing.

Routine analysis of the batch of diet used, water and chew blocks did not provide evidence of contamination that might have prejudiced the study.

ENVIRONMENTAL CONDITIONS

Air conditioned room kept at positve pressure without re-circulation of the filtered fresh air supplied to the room.
Controlled environment, environmental conditions were set at:
- Temperature (°C): 21 ± 2°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
- Rate of air exchange: Ca. 15 changes/h

There were no deviations from these ranges, which compromised the quality, integrity or outcome of the study.



Route of administration:
oral: gavage
Vehicle:
other: aqueous methylcellulose
Details on oral exposure:
DOSE FORMULATION AND DOSE VOLUME:

- Concentration of test material in vehicle: 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw

Preparation of the test material formulation was on the day of dosing. Formulations were stirred before and throughout the dosing procedure.

ACUTE TOXIC CLASS METHOD - Rationale for the selection of the starting dose:

The starting dose of 2000 mg/kg was chosen based on information provided by the Sponsor.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (females only)
Control animals:
no
Details on study design:
- Duration of observation period following administration on Day 1: 14 days (Days 1 to 15)
- Frequency of observations and weighing:
Mortality checks: At least twice daily.
Observation of clinical signs: Ca. 3 minutes post dosing and at frequent intervals thereafter on Day 1; subsequently twice daily and on Day 15 in the morning
Weighing of each animal: Day 1 prior to dosing and on Days 8 and 15.
- Necropsy performed: Yes, of all animals.




Statistics:
Not applicable, as there were no deaths and only one dose group. In addition, the acute toxic class method is not intended for the calculation of a precise LD50 value.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at 2000 mg/kg bw
Mortality:
Dose level Mortality
2000 mg/kg 0/3 (f)
2000 mg/kg 0/3 (f)
Clinical signs:
Clinical signs were not evident.
Body weight:
No adverse effects on body weight.
Gross pathology:
Necropsy of each animal at the end of the 14-day post treatment observation period (Day 15) did not reveal any macroscopic pathology abnormalities.
Conclusions:
In view of the oral LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any labelling regarding acute oral toxicity according to EU regulations (REGULATION (EC) 1272/2008).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived a single limit dose of 2000 mg WS405777 per kg body weight. Therefore, classification of WS405777 for acute oral toxicity is not required [REGULATION (EC) 1272/2008].

Non-classification of WS405777 by the dermal route was reasonable, because of the absence of effects indicative of relevant systemic toxicity and/or local irritation and the absence of any relevant adverse effects in all available in toxicity studies with WS405777.

 

Non-classification of WS405777 by the inhalation route was justified by its low vapour pressure making inhalation exposure of humans to any vapour phase unlikely.