Registration Dossier

Administrative data

Description of key information

The following LD50 was determined for CA 1139 A:

LD50 in male rats: > 2000 mg/kg body weight

LD50 in female rats: > 1000, approx. 2000 mg/kg body weight

LD50 in rats of both sexes: > 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:
June - September 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Remarks:
This study has been performed in compliance with GLP in Switzerland, Procedures and Principles, March 1986, issued by the Swiss federal Department of the Interior and the Intercantonal Office for the Control of Medicaments.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80
Doses:
1000 mg/kg, males and females
2000 mg/kg, males and females
No. of animals per sex per dose:
5 animals per sex per dose (total number of animals: 20)
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Remarks on result:
other: approx. 2000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

In-life observations

 

Animal No.

Observations

Admin. day

Days after administration

1h

3h

5h

1

2

3

4

5

6

7

8

1000 mg/kg, males

1-5

Piloerection

+

+

+

+

+

+

 

 

 

 

 

1-5

Hunched post

+

++

++

+

+

 

 

 

 

 

 

1-5

Dyspnea

++

++

++

+

 

 

 

 

 

 

 

1-5

red. locom. act

 

+

+

 

 

 

 

 

 

 

 

1000 mg/kg, females

1, 3-5

Piloerection

+

+

+

+

++

+

+

+

 

 

 

2

Piloerection

+

+

+

 

 

 

 

 

 

 

 

1, 3-5

Hunched post

++

++

++

++

++

+

+

 

 

 

 

2

Hunched post

++

++

++

 

 

 

 

 

 

 

 

1, 3-5

Dyspnea

++

++

++

++

+

+

 

 

 

 

 

2

Dyspnea

++

++

++

 

 

 

 

 

 

 

 

1, 3-5

red. locom. act

+

++

++

+

+

 

 

 

 

 

 

2

red. locom. act

+

++

++

 

 

 

 

 

 

 

 

1, 3-5

tremor

 

 

+

+

 

 

 

 

 

 

 

2

tremor

 

 

+

 

 

 

 

 

 

 

 

1-5

ataxia

 

 

+

 

 

 

 

 

 

 

 

2000 mg/kg, males

1-4

Piloerection

+

+

++

++

++

++

+

+

 

 

 

5

Piloerection

+

+

++

 

 

 

 

 

 

 

 

1-4

Hunched post

+

++

++

++

+

+

+

 

 

 

 

5

Hunched post

+

++

++

 

 

 

 

 

 

 

 

1-4

Dyspnea

++

++

++

++

+

+

 

 

 

 

 

5

Dyspnea

++

++

++

 

 

 

 

 

 

 

 

1-5

red. locom. act

+

+

+

 

 

 

 

 

 

 

 

2000 mg/kg, females

1,2,5

Piloerection

+

+

+

+

+

+

+

+

+

 

 

3

Piloerection

+

+

+

 

 

 

 

 

 

 

 

4

Piloerection

+

+

+

+

 

 

 

 

 

 

 

1,2,5

Hunched post

+

++

++

++

++

+

+

+

 

 

 

3

Hunched post

+

++

++

 

 

 

 

 

 

 

 

4

Hunched post

+

++

++

++

 

 

 

 

 

 

 

1,2,5

Dyspnea

++

++

++

++

+

+

+

 

 

 

 

3

Dyspnea

++

++

++

 

 

 

 

 

 

 

 

4

Dyspnea

++

++

++

++

 

 

 

 

 

 

 

1-5

red. locom. act

+

+

+

 

 

 

 

 

 

 

 

3

Tonic spasm

 

 

+

 

 

 

 

 

 

 

 


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

hunched post = hunched posture

red. locom. act. = reduced locomotor activity

 

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 in male rats: > 2000 mg/kg body weight
LD50 in female rats: > 1000, approx. 2000 mg/kg body weight
LD50 in rats of both sexes: > 2000 mg/kg body weight
Executive summary:

In an acute oral toxicity study (performed according to the OECD guideline 401), groups of young adult albino rats (Tif: RAI f (SPF)) of both sexes were given a single oral dose by gastric intubation of CA 1139 A in 0.5% (w/v) carboxymethylcellulose (in 0.1% (w/v) aqueous polysorbate 80) at doses of 1000 and 2000 mg/kg bw and observed for 14 days.

The following LD50 was determined for CA 1139 A:

LD50 in male rats: > 2000 mg/kg body weight

LD50 in female rats: > 1000, approx. 2000 mg/kg body weight

LD50 in rats of both sexes: > 2000 mg/kg body weight

Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Additionally, reduced locomotor activity was observed in all animals. In the females dosed 1000 mg/kg tremor, ataxia and respiratory sounds were noticed. In one female dosed with 2000 mg/kg tonic spasms were observed.

One female dosed with 1000 and one male and two females dosed with 2000 mg/kg died spontaneously within two days after administration.

The animals recovered within 4 to 7 days.

At necropsy, a spotted thymus was found in one female dosed with 2000 mg/kg. No deviations from normal morphology were found in the remaining animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

In a Guideline study according to OECD 401 no death animals were found with:

The following LD50 was determined for CA 1139 A:

LD50 in male rats: > 2000 mg/kg body weight

LD50 in female rats: > 1000, approx. 2000 mg/kg body weight

LD50 in rats of both sexes: > 2000 mg/kg body weight

Therefore no classification for acute toxicity is necessary.