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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study was performed according to OECD guideline but prior to GLP requirements, but follows principles thereof. Study was selected as key study because the dose range was tested in a closer range than the supporting study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
GLP not implemented at that time.
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
- Source: F. Winkelmann, Borchen, Germany
- Weight at study initiation: males 115 g, females 106 g
- Housing: 1-5 animals per cage (Makrolon type III)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 1°C
- Humidity (%): 60% +/- 5%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21.10.1985 To: 05.11.1985

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUMES APPLIED: 1.08-1.706 mg/kg
Doses:
1000, 1250, 1580 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation up to 6 hours after application and daily thereafter, weighing before application and 1, 7 and 14 days thereafter
- Necropsy of survivors performed: yes
Statistics:
LD50 value was determined according to Litchfield and Wilcoxon (J. Pharmacol. Exp. Ther. 96, 1949, 99).

Results and discussion

Preliminary study:
A preliminary study for dose finding purposes was performed but not reported.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 330 mg/kg bw
Mortality:
Mortality was seen in all dose groups:
1000 mg/kg bw: 0/5 males, 1/5 females (within 3.5 h)
1250 mg/kg bw: 1/5 males, 4/5 females (within 24 h)
1580 mg/kg bw: 4/5 males, 3/5 females (within 120 h)
Clinical signs:
Piloerection, tremors and dizziness occured approx. 30 min after application. Slight sedation, ataxia, impaired respiration, hypothermia, temporarily abdominal posture, convulsions and halfclosed or closed eyes were observed. Animals dosed with 1000 and 1250 mg/kg were symptom free after 48 h. One animal dosed with 1580 mg/kg bw showed slightly piloerection and hunched posture up to 6 d.
Body weight:
No changes in body weight gain.
Gross pathology:
Post mortem hyperemia of gastric and intestinal mucosa, extended liver and spleen were observed. One animal showed a decoloured kidney and pancreas.
Some of the necropsied animals showed hyperemia of gastric and intestinal mucosa und dark spots on the kidneys.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the study an acute oral LD50 of 1330 mg/kg bw in rats was found.