Registration Dossier

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:
other: see 'Remark'
Remarks:
The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
of 1987
Deviations:
no
Qualifier:
according to
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. certificate)
Remarks:
Certified by BAM according to DIN EN 45001.
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 214 g, maximum 231 g,
Females: minimum 194 g, maximum 210 g.
- Housing: Group housing with up to 5 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 ± 2.5°C
- Relative Humidity (%): 40 to 60%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
- Dose formulation: 20% and 50% of the test material emulsified in the vehicle by warming it to 50°C and using an ultraturrax.
Administration of the dose formulation to the animals at body temperature.
- Dose volume: 1 mL / 100 g bw at each dose.
Individual dose volume was calculated based on individual bodyweight.
- For different doses and dose volumes, see Table 1 in "Any other information on materials and methods incl. tables"
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.
Doses:
see Table 1 in "Any other information on materials and methods incl. tables"
No. of animals per sex per dose:
5
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 and over 8 hours after dosing (Day 0), 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 both dose groups.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 515 mg/kg bw
Based on:
test mat.
Remarks:
WS400517
Remarks on result:
other: No deaths at 1006 or 2515 mg/kg.
Mortality:
There were no deaths during the 14-day observation period post dosing:
Single Dose of WS400517 at: Mortality
1006 mg/kg bw 0/5 (m); 0/5 (f)
2515 mg/kg bw 0/5 (m); 0/5 (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. Apathic behaviour, minimal in degree, was seen in the high dose group within 8 hours post dosing. This was not considered to represent a clear indication of toxicity of the test material.
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:
GHS criteria not met
Conclusions:
In view of the attained oral LD50 > 5000 mg/kg bodyweight for the test material equivalent to > 2515 mg/kg bodyweight for WS400517, the outcome of the present study does not necessitate any classification and labelling regarding acute oral toxicity according to EU regulations [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008]. In addition, sex-related differences in toxicity of the test material after single oral administration were not evident.