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Administrative data

Description of key information

1) BASF, 1969 - acute oral toxicity, rats, LD50 ca. 5500 mg/kg bw
2) BASF, 1963 - acute oral toxicity, rats, LD50 ca. 3500 mg/kg bw
3) Salazar-Rodriguez/Sosa, 2004 - acute oral toxicity, rats, LD0 >= 2.79 g/kg bw, intermittent total dose LD0 >= 8.37 g/kg bw (3 consecutive days)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1963
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study result, which meets basic scientific principles
Qualifier:
no guideline followed
Principles of method if other than guideline:
A Choline chloride solution (30 % in aqua dest.) was adminstered to rats via the oral route.
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data available
Route of administration:
oral: unspecified
Vehicle:
other: aqua dest.
Details on oral exposure:
The substance was administered orally to rats
Doses:
5 mL of a 70% solution of Choline chloride, applied as a 30 % solution in aqua dest.
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no specific information available
Sex:
not specified
Dose descriptor:
approximate LD50
Effect level:
ca. 5 450 mg/kg bw
Based on:
test mat.
Remarks:
70% Choline chloride
Remarks on result:
other: refering to a 70 % Choline chloride solution
Sex:
not specified
Dose descriptor:
approximate LD50
Effect level:
ca. 3 500 mg/kg bw
Based on:
act. ingr.
Remarks:
pure Choline chloride
Remarks on result:
other: converted that corresponding to Choline chloride 100 %
Mortality:
none reported
Clinical signs:
restlessness, staggering, cramps and laboured breathing
Body weight:
not reported
Gross pathology:
no significant findings
Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
The study was considered to be of high quality (reliability Klimisch 2). The substance did not show a high toxicity after a single oral application to rats. The LD50 was identified to be ca. 3500 mg/kg bw (corresponding to a 100 % Choline chloride).
Executive summary:

The acute oral toxicity of Choline chloride was investigated in rats (BASF, 1963). The rats received doses of ca. 5 mL of a 70 % Choline chloride solution (applied as a 30 % solution in water). No mortality was reported. The main clinical symptoms of intoxications were restlessness, staggering, cramps and laboured respiration. Therefore the oral toxicity can be characterised by a approximative LD50 of ca. 5450 mg/kg bw (referring to a 70 % Choline chloride solution). This corresponds to approximatelly 3500 mg/kg bw of 100 % Choline chloride.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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; however, the available data indicate that the study was well-performed.
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 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: unsoluble in oil
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% acqueous 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%
Mortality:
Observed but not quantitatively denoted; at least 5 animals in whole trial.
Clinical signs:
Apathy, Dyspnoe
Calm behavior, accelerated respiration, individually chewing constraint, huddled posture and wet, dirty and shaggy fur
Body weight:
no data
Gross pathology:
Dead Animals: 5x more or less serous smeared snout, particularly ani, diarrhoea, elsewise sepsis
Killed animals: 2x pneumonia in the right upper half of lungs, 1x reduced bodyweight, bronchopneumonia, elsewise organs with negative results
Interpretation of results:
GHS criteria not met
Conclusions:
The present study was assessed as reliable with restrictions (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 in rats. The LD50 was determined to be ca. 11000 mg/kg of the test item, applied as an 30% aqueous solution, which corresponds to ca. 5500 mg/kg of the pure Choline chloride. Consequently, Choline chloride does not need to be classified as hazardous, neither according to Regulation 1272/2008/EC nor Directive 67/548/EEC.
Executive summary:

In an acute oral toxicity study with a 7 d post-observation period, rats were given 11000 mg/kg bw of 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. Clinical signs were apathy, dyspnoe, calm behaviour, accelerated respiration, individually chewing constraint, huddled posture and wet, dirty and shaggy fur, necropsy findings were more or less serous smeared snout (5x), particularly ani, diarrhoea, elsewise sepsis (dead animals) and pneunomia in the right upper half of lungs (2x), reduced body weight (1x), bronchopneumonia, elsewise organs with negative results (killed animals), respectively.

In summary, Choline chlroide is of very low acute oral toxicity based in the LD50 of 5500 mg/kg in rats and does therefore not need to be classified as hazardous, neither according to Regulation 1272/2008/EC nor Directive 67/548/EEC.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 500 mg/kg bw
Quality of whole database:
Two equivalent studies assessed with Klimisch 2 and one supporting study (Klimisch 4 because only abstracts could be retrieved) are available to cover the endpoint "Acute Toxicity: oral", hence, the available information meets fully the tonnage-driven data requirements of REACH. Additionally, all available studies revealed equivalent result, i.e. are all above the boundary value of 2000 mg/kg bw for classification, and so the outcomes of the studies are consistent.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity - oral:

In an acute oral toxicity study with a 7 d post-observation period (BASF, 1969), rats were given 11000 mg/kg bw of Choline chloride 50%. 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. 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 (5x), particularly ani, diarrhoea, elsewise sepsis (dead animals) and pneumonia in the right upper half of lungs (2x), reduced body weight (1x), bronchopneumonia, elsewise organs with negative results (killed animals), respectively.

The acute oral toxicity of Choline chloride was investigated in rats (BASF, 1963). The rats received doses of ca. 5 mL of a 30 % Choline chloride solution (30 % in water). No mortality was reported. The main clinical symptoms of intoxications were restlessness, staggering, cramps and laboured respiration. Therefore, the oral toxicity can be characterised by a approximative LD50 of ca. 5450 mg/kg bw (refering to a 70 % Choline chloride solution). This corresponds to approximatelly 3500 mg/kg bw of the pure Choline chloride.

These results are obtained from two studies which were classified as reliable with restrictions, and can therefore be justifiedly used to assess the hazard of Choline chloride. With an LD50 of 3500 mg/kg bw and 5500 mg/kg bw, respectively, Choline chloride is practically nontoxic and does therefore not need to be classified as hazardous, neither according Regulation 1272/2008/EC nor Directive 67/548/EEC. Although only abstracts are available and hence the reliability is not assessable, the results of the supporting study (Salazar-Rodriguez/Sosa) are consistent with the data provided in both the WoE-studies, so the LD0 ≥ 2.79 mg/kg bw resp. LD0 ≥ 8.37 mg/kg (three consecutive days, intermittent gavage) obtained in this study can be used to support the classification of being practically nontoxic / non- hazardous as stated in the WoE studies.

Acute toxicity - other routes:

In an acute toxicity study with i.p. injection and a 7 d post-observation period (BASF, 1969), mice were given a 4% aqueous solution of 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. 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.

The acute toxicity of choline chloride after intraperitoneal injection was investigated in mice (BASF, 1963). The mice received doses of ca. 0.35 mL of a 70 % choline chloride solution (applied as a 8 % solution in water). No mortality was reported. The main clinical symptoms of intoxications were restlessness, staggering, cramps and laboured respiration. The intraperitoneal toxicity with an approximative LD50 of ca. 266 mg/kg bw of 100 % choline chloride was found.

Since this route of application (intraperitoneal) is not relevant for human risk assessment, the results are not used to assess the need for classification and represent with consistent LD50(i.p.) values of 275 mg/kg bw and 266 mg/kg bw, resp., nevertheless relatively high values, the classification of Choline chloride as non-hazardous is still justified.


Justification for selection of acute toxicity – oral endpoint
One of two equally well-documented acute toxicity studies, assessed with Klimisch 2. The LD50 values of both oral studies can be considered as equivalently reliable and both above the boundary value of 2000 mg/kg bw for classification. However, the lower LD50 (3500 instead of 5500 mg/kg bw) was chosen out of precautionary principles.

Justification for selection of acute toxicity – inhalation endpoint
The test substance has a very low vapour pressure and a high melting point, so the potential for the generation of inhalable forms is low. Furthermore, the substance is distributed as an aqueous solution, so no dust with inhalable particles will be formed and therefore no acute inhalation test was performed.

Justification for selection of acute toxicity – dermal endpoint
Data waiving: According to REACH Annex VIII column 2 Testing by the dermal route is appropriate if (1) inhalation of the substance is unlikely and (2) skin contact in production and/or use is likely and (3) the physicochemical and toxicological properties suggest the potential for a significant rate of absorption through the skin. Although inhalation of Choline chloride is unlikely and skin contact may possibly occur when using Choline chloride, the latter condition does not apply. Skin absorption is influenced by several factors, i.a.:
- Molecular weight: With a molecular weight of 139.6 g/mole, absorption is possible, but not highly favoured
- LogPow: Since Choline chloride, due to its ionic structure, has a logPow of -3.77 at 25°C, dermal absorption may practically not occur because poor lipophilicity will limit penetration into the stratum corneum.
- Water solubility: Water solubility was found to be 650 g/L, i.e. over 10g/L. Also here, dermal absorption may practically not occur due to the high hydrophilicity of the compound.
- Skin irritation / corrosion: If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. Choline chloride was not classified as irritant to the skin, therefore, no additional penetration enhancement must be considered.
Hence, based on the physico-chemical properties of Choline chloride, a dermal absorption is very hindered and so unlikely. Consequently, no additional testing is required and the testing for acute toxicity via dermal route for Choline chloride can be waived.

Justification for classification or non-classification

For choline chloride, an LD50 of 3500 mg/kg bw was obtained in the most relevant key study, and therefore the substance does not need to be classified as hazardous, neither according Regulation 1272/2008/EC nor Directive 67/548/EEC.

The LD0 ≥ 2.79 g/kg bw resp. LD0 ≥ 8.37 g/kg (three consecutive days, intermittent gavage) obtained in the study by Salazar-Rodriguez/Sosa can be used to support the classification of being practically nontoxic as stated in the key study.