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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:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

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:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
None

Test animals

Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 185 to 245 g
- Fasting period before study: overnight
- Housing: Macrolon cages type 4, with standardized soft wood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least for 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hour/day light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled water
Details on oral exposure:
None
Doses:
2000 mg/kg (males and females)
Volume applied: 10 ml/kg bw
No. of animals per sex per dose:
10 animals in total: 5 males and 5 females
Control animals:
no
Details on study design:
- Mortality: daily; a.m. and p.m. on working, days, a.m. on weekend days.
- Signs and symptoms: daily for 14 days
- Body weight: immediately before administration and on days 7 and 14
- Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.
- Other examinations performed: clinical signs, body weight.
Statistics:
No data

Results and discussion

Preliminary study:
None
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred in this study.
Clinical signs:
Piloerection, hunched posture and dyspnoea were seen, being common symptoms in acute tests. Additionaly, reduced locomotor activity was observed in the females. The animals recovered within 6 days.
Body weight:
None
Gross pathology:
At necropsy, no deviations from normal morphology were found in all animals.
Other findings:
None

Any other information on results incl. tables

In-life observations:

         Administartion day              Day after administration         
  Animal N° observations  1 hrs  3 hrs  5 hrs  1  2  3  4  5  6  7  8
 2000 mg/kg, males                                
 1 -5 piloerection  +  +  ++  ++  +  +  +  +      
 1 -5 hunched posture  ++  ++  ++  +            
 1 -5 dyspnea  +  +  +  +              
  2000 mg/kg, females                                
 1 -5 piloerection  +  ++  ++  +  +  +  +  +      
 1 -5 hunched post  +  +  +  +  +  +          
 1 -5 dyspnea  +  +  +  +              
 1 -5 red. locom. act.    +  +                

+ = slight, ++ = moderate, +++ = severe

hunched post = hunched posture

red.locom.act= reduced locomotor activity

Body weight and necropsy findings:

Animal number  Body weight (g) d0   Body weight (g) d7   Body weight (g) d14   *  Gross necropsy findings
 2000 mg/kg, males               
 1  239 302  335  TS  NOA 
 2  245 317  367    TS   NOA 
 3  240 301 336    TS   NOA 
 4  241 303  345    TS   NOA 
 5  243 299  333    TS   NOA 
 Mean  242 304  343     
 SD  2.4 7.2  14.1     
 2000 mg/kg, females                     
 1  205 227  241   TS   NOA 
 2  203 240  243   TS   NOA 
 3  185 210  222   TS   NOA 
 4 200  222  229   TS   NOA 
 5  189 213  225   TS   NOA 
 Mean  196 222  232     
 SD  8.9 12.0  9.5     

* TS: terminal sacrifice

NOA: no observable abnormalities

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for FAT 36038/F was found to be greater than 2000 mg/kg bw.
Executive summary:

A key study was conducted to determine the acute oral toxicity of FAT 36038/F in albino rats according to the test guidelines OECD 401, 92/69/EEC, B.l and the study protocol.

Ten rats (5 males and 5 females) were treated by oral gavage at dose level of 2000 mg/kg. FAT 36038/F was dissolved in distilled water. Prior to dosing by gastric intubation, the animals were fasted overnight. After administration, the animals were observed daily for clinical signs and mortality. Body weight was recorded immediately before administration, on day 7 and day 14. At the end of the observation period, the animals were observed for a gross necropsy at the end of the study period.

Results:

Mortality: No deaths occurred during the test.

Signs of toxicity: Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. Additionally, reduced locomotor activity was observed in the females. The animals recovered within 6 days.

Effects in organs: At necropsy, no deviations from normal morphology were found in all animals.

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 (with 95 % confidence limits calculated, where possible) was determined for FAT 36038/F:

LD50 in male rats: greater than 2000 mg/kg bw

LD50 in female rats: greater than 2000 mg/kg bw

LD50 in rats of both sexes: greater than 2000 mg/kg bw