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:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
of 1981
Deviations:
yes
Remarks:
Due to physicochemical properties of the test material and to achieve the high target doses dose volumes could not be kept constant but increased with increasing dose up to the double volume of that recommended by OECD401 for non-aqueous dose formulations
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: minimum 200 g, maximum 216 g,
Females: minimum 195 g, maximum 206 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 ± 1°C
- Relative Humidity (%): 45 to 55%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Emulsion in mixture of CMC (carboxymethyl cellulose) and Tween 20 containing 50% of the test substance
Details on oral exposure:
- Dose formulation: 50% of the test substance in vehicle, i.e. emulsion at the maximum practical concentration
- Dose volume: The administered volume of test material formulation 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, 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
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at 5000 or 10000 mg/kg.
Mortality:
There were no deaths during the 14-day observation period post dosing:
Single Dose at: Mortality
5000 mg/kg bw 0/5 (m); 0/5 (f)
10000 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.
Body weight:
There were no adverse effects on body weight.
Gross pathology:
Macroscopic pathology findings attributable to the treatment with the test material were not evident.

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to EU regulation