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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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
- Principle of test: To evaluate the oral acute toxicity of a substance.
- Short description of test conditions: The test substance is administered orally by gavage in graduated doses to several groups of experimental animals, one dose being used per group. After administration, observations of effects and deaths are made for 7 days.
- Parameters analysed / observed: Mortality and adverse effects produced after the administration of the substance.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Citicoline
EC Number:
213-580-7
EC Name:
Citicoline
Cas Number:
987-78-0
Molecular formula:
C14H26N4O11P2
IUPAC Name:
(2-{[({[(2R, 3S, 4R, 5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl] methyl phosphonato}oxy)(hydroxy)phosphoryl]oxy}ethyl)trimethylazanium
Details on test material:
Synonym: CDP-Choline

Test animals

Species:
rat
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
11520, 14400, 18000 and 22500 mg/kg.
No. of animals per sex per dose:
10
Control animals:
yes

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
18 501 mg/kg bw
Based on:
test mat.
95% CL:
> 16 590 - < 21 213
Mortality:
After 7 days, deaths were observed at doses 14400 (1), 18000 (5) and 22500 (8) mg/kg bw. In most animals, death occurred between 2 and 48 hours after administration.
Clinical signs:
Toxicological signs were sedation, convulsion, dyspnea, lacrimation, and collapse. This signs were severer in the dead animals and some of them continued until the death.

Any other information on results incl. tables

Table 1. Acute toxicity of citicoline at day 7 after single administration on male rats.

Dosage (mg/kg) p.o.

Distribution of dead animals

Mortality

LD50 Values (mg/kg) (95% confidence limits)

30 min.

1

2

3

4

5

6

7 days

22500

0

8

0

0

0

0

0

0

8/10

18501

(16590 – 21213)

18000

0

4

1

0

0

0

0

0

5/10

14400

0

0

1

0

0

0

0

0

1/10

11520

0

0

0

0

0

0

0

0

0/10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of Citicoline is 18501 mg/kg body weight by oral route in male rats.
Executive summary:

An acute toxicity study of Citicoline has been published. Following a method similar to OECD Guideline 401, 10 male rats were administered orally with 11520, 14400, 18000 and 22500 mg/kg bw of citicoline. After 7 days, mortality was observed at all doses except for the lowest. In most animals, death occurred between 2 and 48 hours after administration. Toxicological signs were sedation, convulsion, dyspnea, lacrimation, and collapse, which were severer in the dead animals and some of them continued until the death. According to the results, the LD50 of Citicoline is 18501 mg/kg body weight by oral route in male rats.

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