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Description of key information

- LD50 in male rats: greater than 2000 mg/kg body weight.
- LD50 in female rats: greater than 2000 mg/kg body weight.
- LD50 in rats of both sexes: greater than 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Date of administration: July 4, 1990 and July 12, 1990 ; Date of completion: July 26, 1990.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
other: Limit test.
Limit test:
yes
Species:
rat
Strain:
other: Albino rats Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Choice of species: The rat has been selected for this test as being a standard species for the determination of the acute oral toxicity.
Young adult albino rats of both sexes (Tif: RAI f (SPF)), initial age 6 to 8 weeks, bred and raised on the premises, were used in the experiment.
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein/Switzerland
- Initial body weight range: 171 to 218 grams.

Hunsbandry and diet:
The rats were kept in an animal room under conventional laboratory conditions, on a 12 hour/day light cycle. The air conditioning system (approximately 15 air changes per hour) maintened a temperature of 22 +/-2°C and relative humidity of 55 +/- 10%.
The animals were housed in Macrlon cages type 4, with standardized soft wood beddling (Societe Parisienne des Sciures, Pantin, France). They were acclimatized at least for 5 days before administration. Rat diet (NAFAG 890 Tox, NAFAG Gossau/SG, Switzerland) and waterwere provided ad libitum. Prior to dosing, the animals were fasted overnight.

Group size and identification:
The animals, segregated by sex, were group-housed (5 animals per cage). Within the groups the animals were identified with numbers from 1 to 5 using picric acid stain on the fur. After dosing, the animals were placed in their cages, which were marked with a cage card containing the date of administration and the characteristics of the experiment and dose group.
Route of administration:
other: Gastric intubation (GAVAGE), one single oral dose.
Vehicle:
other: 0.5 % (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80 (Prepared by Pharmaceuticals Division, Ciba-Geigy Ltd.,Basel)
Details on oral exposure:
- VEHICLE: 0.5 % (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80 (Prepared by Pharmaceuticals Division, Ciba-Geigy Ltd.,Basel).

- DOSE VOLUME APPLIED: 10 ml/kg body weight



Doses:
2000 mg/kg (males and females)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes. The animals were submitted to a gross necropsy at the ned of the observation period.
- Other examinations performed: clinical signs, body weight, rate of death, necropsy.

Observations and records:
- 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.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured in the study.
Clinical signs:
Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests.
Additionally, reduced locomotor activity was observed in one female one hour after administration.
The animals recovered within 4 to 6 days.
Body weight:
Normal body weight gain expected.
Gross pathology:
At autopsy, no deviations from normal morphology were found.

Mean body weight and standard deviation (g).

   Administration day  Day 7  Day 14
 Males 2000 mg/kg  209 +/- 7.6  265 +/- 10.7  299 +/- 8.8
 Females 2000 mg/kg  181 +/- 10.3 209 +/- 8.9   235 +/- 17.8

Observation of symptoms.

         hrs after adm.                         Days after administration 
 Observations  1  3 1 9 -14 
     2000 mg/kg, males                                
 piloerection  + ++  ++             
 hunched post  +                
 dyspnea  +                  
   2000 mg/kg, females                                  
 piloerection  ++ ++  ++   +  +        
 hunched post.  +  +  +  +          
 dyspnea  +  +            
 red. loc. act.  +                      

+ = slight

++ = moderate

+++ = severe

hunched post=hunched posture

red.loc.act. = reduced locomotor activity

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 in male rats: greater than 2000 mg/kg body weight.
LD50 in female rats: greater than 2000 mg/kg body weight.
LD50 in rats of both sexes: greater than 2000 mg/kg body weight.
Executive summary:

The study was conducted to determine the acute oral toxicity of test item in albinos rats.

The study design followed the OECD Guideline 401, "Acute Oral Toxicity", adopted February 24, 1987 and the study protocol from June 18, 1990.

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 the test substance.

- LD50 in male rats: greater than 2000 mg/kg body weight.

- LD50 in female rats: greater than 2000 mg/kg body weight.

- LD50 in rats of both sexes: greater than 2000 mg/kg body weight.

Observations:

Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute test. Additionally, reduced locomotor activity was observed in one female one hour after administration.

The animals recovered within 4 to 6 days.

At autopsy, no deviations from normal morphology were found.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study is Klimisch 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The study was conducted to determine the acute oral toxicity of test item in albinos rats according to the OECD Guideline 401, "Acute Oral Toxicity", adopted February 24, 1987 and the study protocol from June 18, 1990.

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 the test substance.

Observations:

Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute test. Additionally, reduced locomotor activity was observed in one female one hour after administration.

The animals recovered within 4 to 6 days.

At autopsy, no deviations from normal morphology were found.

In conclusion, LD50 in rats of both sexes: greater than 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
Only this study is available.

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).