Choline hydroxide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1969-06-19 to 1969-10-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not all details are given in test report and test was performed on the read-across substance choline chloride; however, the available data indicate that the study was well-performed.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1969-06-19 to 1969-10-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not all details are given in test report and it was performed on the read-across substance Choline chloride; however, the available data indicate that the study was well-performed.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline available

Principles of method if other than guideline:

A relevant guideline was not yet developed at the time the study was conducted.
An aqueous suspension of the test item choline chloride was administered once orally by gavage to rats with a post-observation period of 7 days.

GLP compliance:

no

Remarks:

Conduction of the study prior to GLP

Test type:

other: no data

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 %
- Justification for choice of vehicle: insoluble in oil
- with Tragacanth

Doses:

no data

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 11 000 mg/kg bw

Based on:

test mat.

Remarks:

Choline chloride 50 %

Remarks on result:

other: applied as 30 % aqueous suspension in water with tragacanth

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 5 500 mg/kg bw

Based on:

other: pure choline chloride

Remarks on result:

other: re-calculated from LD50 of Choline chloride 50 %

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 4 770 mg/kg bw

Based on:

other: choline hydroxide

Remarks on result:

other: re-calculated from LD50 of pure Choline chloride

Mortality:

Observed but not quantitatively denoted; at least 5 animals in whole trial.

Clinical signs:

other: Apathy, Dyspnoe, Calm behavior, accelerated respiration, individually chewing constraint, huddled posture and wet, dirty and shaggy fur

Gross pathology:

Dead Animals: 5 x more or less serous smeared snout, particularly ani, diarrhea, elsewise sepsis
Killed animals: 2 x pneumonia in the right upper half of lungs, 1x reduced bodyweight, bronchopneumonia, elsewise organs with negative results

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The present study was assessed as reliable with restrictions (Klimisch 2), because not all details are given in test report and it was performed on the read-across substance choline chloride. However, the available data indicate that the study was well-performed and consequently the obtained results are sufficiently reliable to assess the acute toxicity of choline chloride, and hence choline base, in rats.
Since the absorption after oral application is very likely to have remained unchanged, information gained from choline chloride for this endpoint can be used as supporting information without modification. This is due to the fact that, if ingested orally, the contact time of the basic solution to the oesophagus is rather short for causing severe chemical burns which will be necessary to enlarge the oral uptake. Once reaching the stomach, the basic pH of the choline base solution will be immediately neutralized by the gastric acid. Only when ingesting large amounts of choline base, the neutralization capacity of the stomach acid will be used up. However, this scenario is unlikely due to expected pain in the oral cavity and pharynx caused by hydroxide.
The LD50 was determined to be ca. 11000 mg/kg of the test item, applied as an 30 % aqueous solution with Tragacanth, which corresponds to ca. 5500 mg/kg of the pure choline chloride or 4770 mg/kg bw choline hydroxide, respectively. Consequently, choline hydroxide does not need to be classified as hazardous according to Regulation 1272/2008/EC.

Executive summary:

In an acute oral toxicity study with a 7 d post-observation period, rats were given 11000 mg/kg bw of the read-across substance Choline chloride 50%, applied as a 30 % aqueous suspension with tragacanth. The oral LD50 was determined to be ca. 11000 mg/kg of the test item, which corresponds to ca. 5500 mg/kg of pure choline chloride or 4770 mg/kg bw choline hydroxide, respectively. Clinical signs were apathy, dyspnoe, calm behavior, accelerated respiration, individually chewing constraint, huddled posture and wet, dirty and shaggy fur, necropsy findings were more or less serous smeared snout (5 x), particularly ani, diarrhoea, elsewise sepsis (dead animals) and pneumonia in the right upper half of lungs (2 x), reduced body weight (1 x), bronchopneumonia, elsewise organs with negative results (killed animals), respectively.

In summary, choline hydroxide is of very low acute oral toxicity based on the LD50 of 4770 mg/kg in rats and does therefore not need to be classified as hazardous according to Regulation 1272/2008/EC.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Principles of method if other than guideline:

A solution of the test item (4 % in aqua dest.) was administered to mice via intraperitoneal injection.

GLP compliance:

no

Remarks:

Conduction of the study prior to GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Choline chloride

EC Number:

200-655-4

EC Name:

Choline chloride

Cas Number:

67-48-1

Molecular formula:

C5H14NO.Cl

IUPAC Name:

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

Test material form:

other: solid, but applied as suspension

Details on test material:

- Name of test material (as cited in study report): Cholinchlorid Pulver 50 %
- Structural formula attached as image file (if other than submission substance): see illustration
- Substance type: formulation, solid

Test animals

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: Water with tragacanth

Details on exposure:

The substance was administered via intraperitoneal (i. p.) injection to mice.

Doses:

ca. 550 mg/kg applied as a 4 % (w/v) solution in aqua dest. with water

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Effect levels 1

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 550 mg/kg bw

Based on:

test mat.

Remarks:

Choline chloride 50 %

Remarks on result:

other: applied as 4 % (w/v) solution

Effect levels 2

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 275 mg/kg bw

Based on:

act. ingr.

Remarks:

Choline chloride

Remarks on result:

other: re-calculated for pure substance

Effect levels 3

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 240 mg/kg bw

Based on:

other: choline hydroxide

Remarks on result:

other: re-calculated from LD50 of pure choline chloride

Mortality:

Observed but not quantitatively denoted.

Clinical signs:

Ventral position, myoclonus and tremor, exophthalmos, dispnoea or accelerated and precussive respiration, cyanosis, huddled posture, sunken flanks, clotted eyes and fluffed fur

Gross pathology:

Dead Animals: sepsis
Killed animals: 4x bracket-formed adhesions on the liver, elsewise organs with negative results

Applicant's summary and conclusion

Conclusions:

The present study was assessed as reliable with restriction (Klimisch 2), because not all details are given in test report. However, the available data indicate that the study was well-performed and consequently the obtained results are sufficiently reliable to assess the acute toxicity of Choline chloride after intraperitoneal injection in mice. The LD50 i.p. was determined to be ca. 550 mg/kg of the test item in a 4 % aqueous solution of the test item, which corresponds to ca. 275 mg/kg of the pure Choline chloride and recalculated for choline hydroxide to 240 mg/kg bw, assuming, that choline base would have been applied as pH-neutralized solution.

Executive summary:

In an acute toxicity study with i.p. injection and a 7 d post-observation period, mice were given a 4 % aqueous solution of the read-across substance choline chloride (50 %) with tragacanth. The i.p. LD50 was determined to be ca. 550 mg/kg of the test item applied in a 4 % solution, which corresponds to ca. 275 mg/kg of the pure Choline chloride and hence 240 mg/kg bw of choline hydroxide. Clinical signs were ventral position, myoclonus and tremor, exophthalmos, dispnoea or accelerated and precussive respiration, cyanosis, huddled posture, sunken flanks, clotted eyes and fluffed fur, necropsy findings were sepsis (dead animals) and bracket-formed adhesions on the liver (4x), elsewise organs with negative results (killed animals), respectively.