Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline 401 (1981) under GLP-like quality surveillance (QAU statement included)

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)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid
- purity: commercial grade

Test animals

Species:
rat
Strain:
other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif x RII 2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 166-221 g
- Fasting period before study: overnight
- Housing: in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: January 7, 1985 - January 29, 1985

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
100, 500, and 1000 mg/kg body weight
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 and weighing: Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days; Signs and Symptoms: daily; Body weight: on days 1, 7, 14 and at death
- Necropsy: Spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.
Statistics:
- From the body weights, the group means and their standard deviations were calculated.
- The LD50 values (including their 95% confidence limits) were computed by the logit model (J. Berkson, J. Am. Stat. Ass. iS (1944), 357-365).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
515 mg/kg bw
Based on:
test mat.
95% CL:
236 - 2 577
Sex:
female
Dose descriptor:
LD50
Effect level:
365 mg/kg bw
Based on:
test mat.
95% CL:
149 - 765
Sex:
male/female
Dose descriptor:
LD50
Effect level:
461 mg/kg bw
Based on:
test mat.
95% CL:
296 - 779
Mortality:
1000 mg/kg: all animal died within 3 hours after treatment
500 mg/kg: 1 male died 1/5 day after treatment and 3/5 females died within 3 hours after treatment.
100 mg/kg: all animals survived the treatment.
Clinical signs:
Dyspnea, exophthalmos, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Tremor was seen in all dose groups within 24 hours after application. The animals of the two higher dose groups showed sedation on the application day, with a dose-releated increase in severity. In the same groups, clonicotonic convulsions were observed on the application day. Hemorrhagic discharge in the mouth was seen in the animals of the highest dose group on the application day. The surviving animals recovered within 11-12 days.
Body weight:
All surviving animals gained weight.
Gross pathology:
Enlargement of the liver was observed in one male of the 100 mg/kg bw dose group. Hemorrhagic lungs were seen in one male of the 500 mg/kg bw dose group. In one male of the 1000 mg/kg bw dose group, dilatation of the small intestine was observed.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Upon an acute oral administration and 14 day post-treatment observation period, the following LD50 were determined: 515 mg/kg bodyweight (males), 365 mg/kg bodyweight (female), 461 mg/kg bodyweight (both sexes).