Choline hydrogen carbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only abstract available

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Abstracts Thirty-Third Annual Meeting American College of Clinical Pharmacology October 3-5, 2004, Litchfield Park (Phoenix), Arizona - Prolonged sympathic stimulation with oral choline and urinar yexcretion of histamine and catecholamines in the rat

Author:

Salazar-Rodriguez M, Sosa A, Campos HA

Year:

2004

Bibliographic source:

J Clin Pharmacol 2004 44: 1185/1203

Reference 2

Reference Type:

publication

Title:

Abstracts Thirty-Third Annual Meeting American College of Clinical Pharmacology October 3-5, 2004, Litchfield Park (Phoenix), Arizona -Sympathic stimulation with oral choline fails to increase urinary histamine excretion in spontaneously hypertensive rats

Author:

Sosa A, Salazar-Rodriguez M, Losada M, Campos HA

Year:

2004

Bibliographic source:

J Clin Pharmacol 2004 44: 1185/1203

Materials and methods

Principles of method if other than guideline:

The study originally aimes to examine urinary excretion, determination of toxic effects of the compounds were side-observations. Rats were administered orally by gavage the test compound on three consecutive days.

GLP compliance:

not specified

Test type:

other: 3 d intermittend gavage

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Choline

EC Number:

200-535-1

EC Name:

Choline

Cas Number:

62-49-7

IUPAC Name:

2-hydroxy-N,N,N-trimethylethanaminium

Constituent 2

Reference substance name:

choline chloryde

IUPAC Name:

choline chloryde

Constituent 3

Reference substance name:

Choline chloride

EC Number:

200-655-4

EC Name:

Choline chloride

Cas Number:

67-48-1

IUPAC Name:

2-hydroxy-N,N,N-trimethylethanaminium chloride

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): choline / choline chloryde

Test animals

Species:

rat

Strain:

other: Sprague-Dawley / spontaneously hypertensive rats (SHR), Sprague-Dawley and Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS

Sprague-Dawley rats
- Sex: male
- Weight at study initiation: 300-400 g
- Housing: individually in metabolic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Sprague-Dawley / spontaneously hypertensive rats (SHR), Sprague-Dawley and Wistar
- Sex: unknown
- Weight at study initiation: 250-300 g
- Housing: individually in metabolic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Rats were administered orally with destilled water, 4 mL/kg, for 3 days. Days 4, 5 and 6 choline (20 mmole each) in the same volume was administered daily by the same route. Days 7, 8 and 9, water was again administered orally.

Doses:

20 mmole/kg (i.e. 2.79 g/kg bw) each on three consecutive days, resulting in an total amount of 8.37 g/kg bw.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: at least 3 days
- Other examinations performed: urinary analysis

Results and discussion

Effect levels

Effect levels 1

Sex:

not specified

Dose descriptor:

LD0

Effect level:

>= 2 790 mg/kg bw

Based on:

test mat.

Remarks on result:

other: given on three consecutive days, hence LD0 can be calculated as intermittent total dose to 8.37 g/kg bw

Effect levels 2

Sex:

not specified

Dose descriptor:

LD0

Effect level:

>= 3 300 mg/kg bw

Based on:

other: Choline bicarbonate

Remarks on result:

other: re-calculated from LD0 of pure Choline chloride; given on three consecutive days, hence LD0 can be calculated as intermittent total dose to 9.90 g/kg bw

Mortality:

none

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although only abstracts are available and hence the reliability is not assessable, the results are consistent with the data provided in the key study, so the LD0 ≥ 3.30 g/kg bw resp. LD0 ≥ 9.90 g/kg (three consecutive days, intermittent gavage) obtained in this study can be used to support the classification of being practically nontoxic as stated in the key study.

Executive summary:

Male Sprague-Dawley rats resp. spontaneously hypertensive rats (SHR), Sprague-Dawley and Wistar rats were administered orally on each three consecutive days 20 mmole (i.e. 2.79 g/kg bw) of of the read-across substance choline chloride, which results in a total, intermittent dose of 8.37 g/kg bw. This dosage corresponds to 3.30 g/kg bw/d and 9.90 g/kg bw choline bicarboante, respectively. No mortalities were observed, so the LD0 was found to be LD0 ≥ 3.30 g/kg bw resp. LD0 ≥ 9.90 g/kg (three consecutive days, intermittent gavage), and hence Choline hydrogen carbonate can be considered to be practically nontoxic.