Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 26, 2000 - September 28, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
March 22, 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
September 30, 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: about 6 to 8 weeks
- Weight at study initiation: 172 (range from 159 to 181) g
- Fasting period before study: Diet was withheld from about 17 hours before dosing up to 4 hours after treatment.
- Housing: separately in Makrolon cages type HI with a shelter
- Diet: ad libitum, LONG LIFE for mice and rats 9439, Eberle Nafag)
- Water: ad libitum, tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 28
- Humidity (%): 50 to 66
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Methocef K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1.25, 10, 100 g/L

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:
25, 200, 2000 mg/kg bw
No. of animals per sex per dose:
3 (see table1)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 200 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals of the highest dose died within a few minutes after administration.
Clinical signs:
Signs of toxicity were seen from 1 to 15 minutes up to day 3 after administration.
2000 mg/kg bw (f): lateral position, motor excitation, and dyspnea.
200 mg/kg bw (m + f): abdominal and dorsal position, lococmotor disturbance, and dyspnea.
25 mg/kg bw(m): locomotor disturbance was the only symptom.
Body weight:
Body weight development of the surviving rats was inconspicuous.
Gross pathology:
At pathology all rats which died showed mild local changes in the gastro intestinal tract. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to the results of this study the LD50 value is expected between 200 - 2000 mg/kg bw.
Executive summary:

A study according OECD TG 423 (Acute Class Method) was performed to determine the acute oral toxicity of the test item. The test material was administered by oral gavage using doses of 25, 200, and 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel® K4M Premium solution as vehicle.

Signs of toxicity were seen from 1 to 15 minutes up to day 3 after administration. In females of the 2000 mg/kg be dose group lateral position, motor excitation, and dyspnea was reported.

In all animals of the 200 mg/kg bw dose group abdominal and dorsal position, locomotor disturbance, and dyspnea was detected. In the 25 mg/kg bw dose group males showed locomotor disturbance.

All animals of the highest dose died within a few minutes after administration. Body weight development of the surviving rats was inconspicuous.

At pathology all rats which died showed mild local changes in the gastro intestinal tract. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.

According to the results of this study the LD50 value is expected between 200 - 2000 mg/kg bw.