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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
Study period:
1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
prior to GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

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: 159 - 215 g
- Fasting period before study: overnight
- Housing: groups of 5
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), provided ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 55+/- 15
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight
Doses:
1000, 2000, 4000 mg/kg bw
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- 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, 28 and at death
- Necropsy of survivors performed: yes, 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.
Where feasable, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 756 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 340 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 984 mg/kg bw
Based on:
test mat.
Remarks on result:
other: average value of both sexes
Mortality:
males:
1000 mg/kg/bw: 0/5 animals died
2000 mg/kg/bw: 1/5 animals died
4000 mg/kg/bw: 4/5 animals died

females:
1000 mg/kg/bw: 2/5 animals died
2000 mg/kg/bw: 3/5 animals died
4000 mg/kg/bw: 5/5 animals died
Clinical signs:
Dyspnoea, exophthalmus, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition sedation, lateral and ventral body position, chromodacryorrhea, diarrhea, tonic clonic convulsions and bilateral paresis of the hindlimbs were observed. Extended skin erythema and reversible alopecia was noted in several animals.
From day 6 onward some animals in the 1000 and 2000 mg/kg groups showed skin erythema for several days and alopecia in either the dorsal or ventral body area. After 3 weeks the fur started to grow again and by the end of the observation period the fur appeared to be normal.
In the 2000 mg/kg group one female showed bilateral ocular opacity which did not reverse until the end of the experiment.
The surviving animals recovered within 28 days.
Body weight:
Body weights were in the normal range
Gross pathology:
Besides two cases of spotted lung in the high dose group no findings were made at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test material to male and female rats was determined to be 1984 mg/kg bw.