Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 24, 1982 (date of test substance administration) to December 9, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
None

Test animals

Species:
rat
Strain:
other: Tif: RAI (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tiertarm, 4334, Sisseln, Switzerland
- Age at study initiation: 7 to 8 weeks old
- Initial body weight range: 180-217 g
- Fasting period before study: overnight
- Housing: in groups of 5 in macrolon cages type 3 individually marked with picric acid
- Diet: rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland); ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3 °C,
- Humidity: 55±15 %
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light
- Air changes: approximately 15 air changes/h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
DOSAGE PREPARATION:
FAT 31016/C was suspended in polyethylene glycol to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Fasting details:
Animals fasted overnight were treated by single oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.
Doses:
1000, 2500 and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- Other examinations performed: clinical signs, mortality check and autopsies
- Mortality: daily, a.m. and p.m. on working days
- Signs and symptoms: daily
- Body weights: on days 1, 7, 14 and at death
- Necropsies: 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

Preliminary study:
None
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 289 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 384 - <= 3 788
Mortality:
One male was found dead in animals treated at 1000 mg/kg bw. 1 male and 2 females at the dose of 2500 mg/kg bw, while 5 males and 5 females at the dose of 5000 mg/kg bw were found dead during the observation period.
Clinical signs:
No specific symptoms were seen. The treated rats from all dosages showed sedation (except 1000 mg/kg bw), dyspnoea, exophthalmus, curved body position and ruffled fur. Further, rats treated at 5000 mg/kg bw also exhibited ventral and lateral body position within 1 hour of dosing. The surviving animals recovered within 13 days.
Body weight:
No adverse effect on body weight changes were seen in surviving animals.
Gross pathology:
No compound related gross organ changes were seen.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of FAT 31016/I in rats was determined to be 2289 mg/kg bw.
Executive summary:

The acute oral LD50 of FAT 31016/I was determined in a study conducted according to OECD Guideline 401. Groups of 5 males and 5 females each, were administered the test substance at the doses of 1000, 2500 and 5000 mg/kg bw. Clinical signs and mortality check were recorded during an observation period of 14 days. Body weights were recorded immediately prior to dosing (control weights) and at 7 and 14 days. The treated rats were submitted to necropsy whenever they died, survivors at the end of the observation period. One male was found dead in animals treated at 1000 mg/kg bw. 1 male and 2 females at the dose of 2500 mg/kg bw, while 5 males and 5 females at the dose of 5000 mg/kg bw were found dead during the observation period. No specific symptoms were seen. The treated rats from all dosages showed sedation (except 1000 mg/kg bw), dyspnoea, exophthalmus, curved body position and ruffled fur. Further, rats treated at 5000 mg/kg bw also exhibited ventral and lateral body position within 1 hour of dosing. The surviving animals recovered within 13 days. No substance related gross organ changes were seen. Hence based on the above findings, the acute oral LD50 of FAT 31016/I was determined to be 2289 mg/kg bw, with 95 % confidence limits being 1384 – 3788 mg/kg bw.