Cytidine 3'-(dihydrogen phosphate)

Acute Toxicity: oral

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

Test material information

Constituent 1

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:

other: 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.