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)
Version / remarks:
(17th Dec. 2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(30th May 2008)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

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: adult rats, 8 weeks old
- Weight at study initiation: 192 – 207 g
- Fasting period before study: the night before treatment (water ad libitum)
- 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
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg b.w.

MAXIMUM DOSE VOLUME APPLIED: ca. 2 ml

DOSAGE PREPARATION: The test material mixed with the vehicle was warmed up on a water bath to 50 ºC for approximately 10 minutes thus facilitating preparation of a suitable dose formulation. Pending administration to the animals, the dose formulation was stirred on a magnetic stirrer at room temperature and was protected from light.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
2 x 3 female rats /2000 mg/kg b.w. (incl. the confirmatory group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: 30 min., 1, 2, 3, 4, 6 h after administration, daily for 14 days
weighing: day before treatment (day -1), day of treatment prior to dosing (day 0) and than weekly
- Necropsy of all animals performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths
Mortality:
no mortality
Clinical signs:
Treatment with WS400104 at the dose of 2000 mg/kg bw caused transient decreased activity, hunched back and incoordination in all of six animals on the day of treatment. All animals recovered on Day 1.
Body weight:
Body weight gains showed no indication of a test material-related effect.
Gross pathology:
No macroscopic observed effects

Any other information on results incl. tables

Table 1: CLINICAL OBSERVATIONS:DOSE: 2000mg/kg b.w., Treatment on Day 0

 

 

CageNo.

 

Animal

Number

 

 

Observations

Observationdays

 

0

 

 

1

 

 

2

 

 

3

 

 

4

 

 

5

 

 

6-14

30'

1h

2h

3h

4h

6h

 

 

 

 

 

 

 

 

1

 

 

1176

SymptomFree

-

-

-

-

-

-

+

+

+

+

+

+

 

Activitydecreased

1

1

1

1

1

1

-

-

-

-

-

-

 

Hunchedback

-

+

+

+

-

-

-

-

-

-

-

-

 

Incoordination

1

1

1

1

1

-

-

-

-

-

-

-

 

 

 

1177

SymptomFree

-

-

-

-

-

-

+

+

+

+

+

+

 

Activitydecreased

1

1

1

1

1

1

-

-

-

-

-

-

 

Hunchedback

-

+

+

+

-

-

-

-

-

-

-

-

 

Incoordination

1

1

1

1

1

-

-

-

-

-

-

-

 

 

 

1178

SymptomFree

-

-

-

-

-

-

+

+

+

+

+

+

 

Activitydecreased

1

1

1

1

1

1

-

-

-

-

-

-

 

Hunchedback

-

+

+

+

+

+

-

-

-

-

-

-

 

Incoordination

1

1

1

1

1

-

-

-

-

-

-

-

 

 

 

 

 

 

 

 

 

2

 

 

1179

SymptomFree

+

-

-

-

-

-

+

+

+

+

+

+

 

Activitydecreased

-

-

1

1

1

1

-

-

-

-

-

-

 

Hunchedback

-

-

+

+

-

-

-

-

-

-

-

-

 

Incoordination

-

1

1

1

1

-

-

-

-

-

-

-

 

 

 

1180

SymptomFree

+

-

-

-

-

+

+

+

+

+

+

+

 

Activitydecreased

-

-

1

1

1

-

-

-

-

-

-

-

 

Hunchedback

-

-

+

+

-

-

-

-

-

-

-

-

 

Incoordination

-

1

1

1

1

-

-

-

-

-

-

-

 

 

 

1181

SymptomFree

+

-

-

-

-

+

+

+

+

+

+

+

 

Activitydecreased

-

-

1

1

1

-

-

-

-

-

-

-

 

Hunchedback

-

-

+

+

-

-

-

-

-

-

-

-

 

Incoordination

-

1

1

1

1

-

-

-

-

-

-

-

 

Applicant's summary and conclusion

Interpretation of results:
other: not acutely toxic
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test item WS400104 was found to be above 2000 mg/kg bw in female CRL:(WI) rats.
According to the Globally Harmonised System (GHS) (UNITED NATIONS 2005 and more recent revisions) and according to Regulation (EC) No 1272/2008 WS400104 should be ranked as "Unclassified" for acute oral exposure.