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 in a contract research organization. The study is scientifically valid and adequate for assessment with acceptable restrictions (e.g. due to limited reporting). Purity and stability of the test material were not reported for the batch of test material used.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
of 1981
Deviations:
yes
Remarks:
Doses of test material were quite high. Therefore, this was dosed undiluted and dose volumes could not be kept constant but increased with increasing dose.
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
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.
- Weight at study initiation (day of dosing): Males: 210 to 221 g; Females: 200 to 208 g
- Housing: Group housing with 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 from Altromin, Lage, Germany
- Water was provided ad libitum

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 22 ± 1°C
- Relative Humidity (%): 45 to 55%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Dose volume: The administered volume of test material, increased with increasing dose thus achieving quite high target doses.
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:
no
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 at 7 and 14 days post dosing.
Mortality: At least at 24 hours, 48 hours, 7 days and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume and on Day 14 (end of observation period).
- Necropsy: All animals were necropsied at termination of the study.
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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 385 mg/kg bw
Based on:
act. ingr.
Remarks:
WS400123
Remarks on result:
other: No deaths at 2692 or 5385 mg/kg bw
Mortality:
There were no deaths during the 14-day observation period post dosing:
Dose of Test Material: Equivalent Dose of WS400123: Mortality
5.0 mL/kg bw 2692 mg/kg bw 0/5 (m); 0/5 (f)
10.0 mL/kg bw 5385 mg/kg bw 0/5 (m); 0/5 (f)

m = male, f = female
Clinical signs:
Group 1
Shortly after dosing and 7 and 14 days afterwards remarkable clinical signs or any findings attributable to the treatment with the test material were not evident.
Group 2
Reflexes slightly decreased; shortly after dosing, increased frequency of respiration (due to dose volume). Differences in appearance and behaviour from "normal" were no longer evident at 7 and 14 days post dosing.
Body weight:
There were no adverse effects on body weight.
Gross pathology:
Necropsy of each animal at the end of the 14-day post treatment observation period did not reveal any macroscopic pathology findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In view of the attained oral LD50 of test material > 10.0 mL/kg bodyweight corresponding to an LD50 > 5385 mg/kg bw for neat WS400123, the outcome of the present study does not necessitate any labelling regarding acute oral toxicity according to EU regulations (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008). In addition, relevant sex-related differences in toxicity of the test material after single oral administration were not evident.