Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: CRL:(WI) rats
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 188 – 207 g
- Fasting period before study: overnight prior administration
- Housing: 3 animals/cage (Type II polypropylene/polycarbonate)
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg b.w.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As the chemical type of test material tested in the present study was not expected to cause any mortality, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 and 300 mg/kg b.w.
No. of animals per sex per dose:
3 female rats/2000 mg/kg b.w. and 2 x 3 female rats/300mg/kg b.w. (incl. the confirmatory group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Frequency of observations (clinical signs, see below): at 15 and/or 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
Frequency of weighing: on the day before treatment (Day -1), on the day of treatment (Day 0, prior to dosing) and weekly thereafter.
- Necropsy of survivors performed: yes

Clinical signs observed: skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 2/3 animals died at 2000 mg/kg. 0/6 animals died at 300 mg/kg.
Mortality:
WS400402 caused mortality at a single dose of 2000 mg/kg bw in two of three animals (2/3), but did not cause mortality at the dose of 300 mg/kg bw (0/6).
Clinical signs:
Treatment with WS400402 at the dose of 2000 mg/kg bw caused decreased activity (3/3), hunched back (3/3), incoordination (3/3), continuous tremors (3/3), tonic convulsion (1/3) and death (2/3).
Treatment with 300 mg/kg bw did not cause any clinical signs during the 14 days observation period.
Body weight:
Body weight gains of surviving WS400402 treated animals during the study showed no indication of a test material-related effect.
Gross pathology:
Found dead animals:
Dark/red discoloration/focus of the non-collapsed lungs was found at necropsy.
Terminal animals:
There were no macroscopic findings noted in the surviving animals

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test material WS400402 was found to be between 300 and 2000 mg/kg bw in female CRL:(WI) rats.
According to Regulation (EC) No 1272/2008 WS400402 should be classified as "harmful" and “Category 4” for acute oral exposure, respectively.