Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-10-30 to 1997-11-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Stone Ridge (Kingston), NY
- Age at study initiation: 7- 10 weeks
- Weight at study initiation: males: 187 - 203 g; females: 150 -189 g
- Housing: singly, in stainless-steel, wire mesh cages
- Diet: Certified Rodent Diet (PMI #5002, pelleted) was available ad libitum.
- Water: municipal drinking water, regularly assayed
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): 48 - 55 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Initially, a Iimit dose of 2000 mg/kg bw of the test substance was selected as the dose Ievel for the oral toxicity study. Based on results of this dose Ievel, additional dose Ievels of 1000 and 500 mg/kg bw of the test substance were selected for female rats.
Doses:
2000 mg/kg bw for male and female rats, 1000 and 500 mg/kg for female rats only
No. of animals per sex per dose:
2000 mg/kg bw dose group: 5 males and females
1000 mg/kg bw dose group: 5 females
500 mg/kg bw dose group: 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: three times on the day of administration, at least once each workday
- Observations included, but were not limited to examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory systern, circulatory system, autonomic nervous system, central nervous system, and behavior patterns.
- Necropsy of survivors performed: yes, any animal that died during the study was necropsied as soon as possible. All surviving animals were euthanatized and necropsied at the completion of the 14-day observation period.
Statistics:
not required

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 414 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed for the male animals.
Four of five female animals died following the administration of 2000 mg/kg bw.
No animal died follwing the administration of 1000 and 500 mg/kg bw.
Clinical signs:
Abnormal clinical signs were limited to reduced feces on the day following dosing from the male and female rats in the 2000 mg/kg bwdose group which survived to Day 1
Body weight:
One female rate of the dose group 500 mg/kg lost weight between Days 7 and 14, all other animals which survived to termination of the 14-day observation period gained weight during both weeks of the study
Gross pathology:
Treatment-related changes observed at necropsy for the 2000 mg/kg bw female rats that died within 24 hours of test substance administration consisted of distention of the stomach with mucus, and necrosis and hemorrhage of the glandular gastric mucosa. No treatment-related changes were observed at necropsy for animals that survived the 14-day observation period. Incidental findings consisted of uterine hydrometra for single female rats from the 1000 and 500 mg/kg bw dose groups.
Other findings:
none

Applicant's summary and conclusion