Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 Apr 2005 - 12 Jul 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

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:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar HsdCpb:Wu
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan/Winkelmann GmbH, Borchen, Germany
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 161 - 176 g
- Housing: The animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding (J. Rettenmaier & Sohne, Rosenberg, Germany). The cages of the animals were placed on racks, in ascending group number order. The wood granulate was randomly checked for contaminants at regular intervals and the results have been stored at the Department for Laboratory Animal Services, Bayer HealthCare AG, Wuppertal, Germany. The cages were changed at least once a week. Feed racks and water bottles were not changed. All cage material was washed with hot water which did not contain any detergent or disinfectant.
- Diet: Provimi Kliba 3883.0.15 Maus/Ratte Haltung (Kaiseraugst, Switzerland), ad libitum. Food was withheld prior to dosing.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): 55 ±5
- Air changes (per hr): approx. 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hrs

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
with the aid of 2% Cremophor EL
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1%, 20% concentrations were tested to ensure the formulations are stable at room temperature. The exact concentration in the vehicle used in the study is not reported.
- Amount of vehicle (if gavage): not reported.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose was selected based on the stepwise procedure described in the flow charts of Annex 2, OECD guideline 423, with each step using three animals of a single sex (normally females), and evaluating the effect. As the substance was expected to have low toxicity, the highest limit dose of 2000 mg/kg bw was selected as the initial dose. As there was no mortality during the first step, 3 additional rats were treated with the same dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Step 1: 3 females
Step 2: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of administration and subsequently at least once daily for an observation period of at least 14 days. Mortality and in the event of symptoms occurring, nature, duration and intensity were recorded individually.The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality
Mortality:
During the 14-day observation period, no mortality occurred among females after treatment with 2000 mg/kg bw.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no toxicological effects on body weight or body weight gain.
Gross pathology:
The necropsies performed at the end of the study revealed no treatment-related findings.

Any other information on results incl. tables

Dose response table:

 dose mg/kg bw.        toxicological results*  occurrence of signs  time of death  mortality (%)
(1st)  2000  0  0  3  -  -  0
(2nd) 2000  0  0  3  -  -  0

* number of animals which died spontaneously and/or were sacrificed in moribund state / number of animals with signs of toxicity / total number of animals used per group

Applicant's summary and conclusion