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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:
Started on April 2, 1979.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Old study, but well documented and scientifically acceptable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The acute oral LD50 of the test item in rats of both sexes was assessed administering three doses at 5000, 6500, 8000 and 10000 mg/kg bw. Animals were observed over a period of 14 days.
GLP compliance:
no
Remarks:
Pre GLP
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Tif RAIf (SPF) strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: animals were raised on the premises were used for these experiments.
- Age at study initiation: 7 to 8 weeks old.
- Weight at study initiation: males in the range of 168-199 g; females in the range of 159-177 g.
- Housing: during the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3).
- Diet: ad libitum rat food - NAFAG, Gossau SG.
- Water: ad libitum.
- Acclimation period: for a minimum of 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 10 hours light cycle day.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2 %
Details on oral exposure:
- Volume: 20 ml/kg
Doses:
5000, 6500, 8000 and 10000 mg/kg bw
No. of animals per sex per dose:
5 x sex x group.
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes; animals were at random to a necropsy at the end of the observation period.
- Examinations performed: bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.
Statistics:
LD50 including 95 % confidence limits were calculated by the logit model.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No dead occurred at all the doses tested.
Clinical signs:
The rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur.
The animals recovered within 6 to 7 days.
Gross pathology:
No substance related gross organ changes were seen.

Any other information on results incl. tables

Rate of deaths

Dose mg/kg Sex No. of animals No. of animals dead Death rate %
5000 M 5 0 0
6500 M 5 0 0
8000 M 5 0 0
10000 M 5 0 0
5000 F 5 0 0
6500 F 5 0 0
8000 F 5 0 0
10000 F 5 0 0

Signs and symptoms

5000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ + + + +
Salivation
Ruffled fur + + + + + +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

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

6500 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  +
Salivation
Ruffled fur + + + + + +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

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

8000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  
Salivation
Ruffled fur + + + + + +  +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

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

10000 mg/kg bw

Signs and symptoms Hours Days
1 2 3 5 24 2 3 4 5 6 7 8 9 10 11 12 13 14
Sedation + + + + +  +  +
Dyspnoea + + + + + + + + +  +
Dacryorrhoea
Chromodacryorrhoea
Rinorrhoea
Epistaxis
Exophthalmos ++ ++ ++ ++ + +  +  
Salivation
Ruffled fur + + + + + +  +  +
Pallor
Cyanosis
Diarrhoea
Body position (ventral)
Body position (lateral)
Body position (curved) + + + + + + + +
Ataxia
Trismus
Tremor
Tonic clonic muscle spasms
Convulsions

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

Bodyweight changes

Dose 5000 6500 8000 10000
Day 1 M Mean BW/SD (g) 168/4.8 184/12.9 199/12.1 190/7.4
Day 1 F 177/3.7 159/7.1 177/3.4 172/5.9
Day 7 M 268/5.9 240/10.7 244/22.4 247/11.4
Day 7 F 209/9.5 185/5.5 203/6.0 198/7.9
Day 14 M 272/15.3 282/17.4 292/11.5 280/17.4
Day 14 F 266/9.2 198/6.4 221/10.4 210/11.3

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information According to the CLP Regulation. Criteria used for interpretation of results: EU
Conclusions:
LD50 > 10000 mg/kg bw
Executive summary:

Method

The acute oral LD50 of the test item in rats of both sexes was assessed administering three doses at 5000, 6500, 8000 and 10000 mg/kg bw. Animals were observed over a period of 14 days.

Results

No dead occurred at all the doses tested. The rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position, diarrhoea and ruffled fur; the animals recovered within 7 to 10 days.

LD50 > 10000 mg/kg bw