Registration Dossier

Administrative data

Description of key information

Triethyl citrate is of very low acute toxicity if administered to animals via all exposure routes. The substance therefore does need to be classified for acute toxicity.
Acute toxicity: oral
1) RTECS: LD50 (rat) = 5900 mg/kg bw
2) Finkelstein (1959): LD50 (rat) = ca. 7 mL/kg bw
3) Finkelstein (1959): LD50 (cat) = ca. 3.5 mL/kg bw
4) BIBRA (1998): LD50 (rat) >3.2 g/kg bw
5) BIBRA (1998): LD50 (guinea pig) > 25mL/kg bw
Acute toxicity: inhalation
1) RTECS: LC50 (rat) = 1300 ppm/6h (= 14927.34 mg/m3)
2) BIBRA (1998): LC50 (6 hours, rat) = 1300-3500 ppm (= 14927- 40189 mg/m3)
3) BIBRA (1998): A group of six guinea-pigs survived a 6 hour exposure to 1700 ppm (= 19520.37 mg/m3) vapour.
Acute toxicity: dermal
1) RTECS: LD50 (rabbit) >5000 mg/kg
2) BIBRA (1998): LD50 (rabbit) >5 g/kg bw
3) BIBRA (1998): LD50 (guinea-pig) >11.4 g/kg bw
4) Patty (1982): LD50 (Guinea-Pig) > 10 mL/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
The information does not come from a test report, and only minimum fields required can be filled in.
Qualifier:
according to
Guideline:
other: no data
Deviations:
not specified
GLP compliance:
not specified
Test type:
other: no data
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 25 mL/kg bw
Based on:
not specified
Remarks on result:
other: >28 g/kg bw, it is unclear how such a large amount was administered.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
LD50 (guinea pig) > 25mL/kg bw (>28 g/kg bw, it is unclear how such a large amount was administered)
Executive summary:

In the "toxicity profile of triethyl citrate" (TNO BIBRA, 1998) for the acute oral toxicity of triethyl citrate a LD 50 (guinea pig) of > 25 mL/kg bw ( which is about 28 g/kg bw, it is unclear how such a large amount was administered) is stated (German OS, undated). No further details are available.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 200 mg/kg bw
Quality of whole database:
As the information from each single source alone might be regarded insufficient to come to a conclusion regarding the classification of the substance, a weight of evidence approach was taken to pool all available data together, leading to the conclusion that the substance is of very low acute toxicity.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
The information does not come from a test report, and only minimum fields required can be filled in.
Qualifier:
no guideline required
Principles of method if other than guideline:
peer-reviewed database
GLP compliance:
not specified
Remarks:
Peer-reviewed database, with no information on GLP status
Test type:
other: no data
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
1 300 ppm
Based on:
not specified
Exp. duration:
6 h
Other findings:
Lungs, thorax or respiration:
- acute pulmonary oedema
- pleural effusion
- dyspnoea
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
LC50 (rat) = 1300 ppm/6h
Executive summary:

In the Registry of Toxic Effects of Chemical Substances (RTECS) database a LC50 (rat, inhalation) of 1300 ppm/6h is reported for triethyl citrate. No further details are available.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
14 927.34 mg/m³
Quality of whole database:
As the information from each single source alone might be regarded insufficient to come to a conclusion regarding the classification of the substance, a weight of evidence approach was taken to pool all available data together, leading to the conclusion that the substance is of very low acute toxicity.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
The information does not come from a test report, and only minimum fields required can be filled in.
Qualifier:
no guideline required
Principles of method if other than guideline:
Handbook data
GLP compliance:
not specified
Remarks:
Handbook data, with no information on GLP status
Test type:
other: no data
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
not specified
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
LD50 (rabbit) >5000 mg/kg
Executive summary:

In the Registry of Toxic Effects of Chemical Substances (RTECS) database and the GESTIS substance database a LD50 (rabbit) of 5000 mg/kg bw is reported for triethyl citrate. No further details are available.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
As the information from each single source alone might be regarded insufficient to come to a conclusion regarding the classification of the substance, a weight of evidence approach was taken to pool all available data together, leading to the conclusion that the substance is of very low acute toxicity.

Additional information

Acute toxicity: oral

The acute oral toxicity of triethyl citrate was investigated in several studies, reported in literature: In the RTECS and the GESTIS database a LD50 (rat, oral) of 5900 mg/kg bw is reported for triethyl citrate.

Further, the acute oral toxicity of triethyl citrate was studied in 102 rats in the range of doses from 5 to 15 mL/kg administered by stomach tube (Finkelstein & Gold, 1959). The clinical signs observed included weakness, depression, ataxia, hyperexcitability, unrest, urinary dribbling, irregular and laboured respiration, and in the advanced phase of poisoning convulsions in some animals. Their absorption was fairly rapid; signs - depending on the dose - appeared within a few minutes. The course of their poisoning was also fairly rapid, progressing to advanced stages within about an hour and terminating either in death - approximately 2 hours to 3 days after administration - or in apparent recovery after 5 hours to 4 days. The approximate LD50 in rats is 7 mL/kg, which would correspond to about 500 mL in a man of 70 kg.

The acute oral toxicity of triethyl citrate was also studied in 30 cats by single dosing via gavage with 1-9 mL/kg bw. An additional test was made in one cat: it received 5 mL/kg bw of the test substance by stomach tube. The signs observed, consisted of nausea, vomiting, ataxia, weakness, muscle twitching, tremors, reflex hyperexcitability, lowering of body temperature, gasping and shallow respiration, prostration, convulsions, respiratory failure and death. The absorption was fairly rapid, signs usually appearing within a few minutes. The course of the poisoning, as judged by the manifest signs in the intact animals, was also fairly rapid, progressing to advanced stages within about one hour and terminating in death - about 2 hours to 2 days after administration - , or apparent recovery about 4 hours to 3 days after dosage. In the additional test with only one cat the dose of 5 mL/kg bw produced severe poisoning, but the cat recovered and the test continued. The approximate LD50 in cats has been determined to be 3.5 mL/kg.

In the "toxicity profile of triethyl citrate" (TNO BIBRA, 1998) for the acute oral toxicity of triethyl citrate a LD 50 (rat) of > 3.2 g/kg bw is stated (Fassett, undated; Ohtaki et al., 1985; Sheftel, 1990).

In the same document another LD50 value for the acute oral toxicity of triethyl citrate is reported: LD 50 (guinea pig) > 25 mL/kg bw, which is about 28 g/kg bw - it is unclear how such a large amount was administered (German OS, undated). No further details are available.

Acute toxicity: inhalation

In the RTECS database a LC50 (rat, inhalation) of 1300 ppm/6h is reported for triethyl citrate.

In the "toxicity profile of triethyl citrate" (TNO BIBRA, 1998) for the acute inhalation toxicity of triethyl citrate a LC 50 (rat, 6 hours) of 1300 - 3500 ppm is stated (Fassett, undated). Further, regarding the acute inhalation toxicity of triethyl citrate, it is reported that a group of six guinea pigs survived a 6 h exposure to 1700 ppm vapour (Fassett, undated). No further details are available.

Acute toxicity: dermal

The acute dermal toxicity of triethyl citrate was investigated in several studies, reported in literature:

In the RTECS and the GESTIS database a LD50 (rabbit) of 5000 mg/kg bw is reported for triethyl citrate.

In the "toxicity profile of triethyl citrate" (TNO BIBRA, 1998) for the acute dermal toxicity of triethyl citrate a LD 50 (rabbit) of > 5 g/kg bw is stated (Levenstein I., 1975). Further, another LD 50 (guinea pig) of > 11.4 g/kg bw is stated (Fassett, undated). No further details are available.

According to "Patty's Industrial Hygiene and Toxicology" (Clayton & Clayton, 1982) the LD50 (guinea pig) of triethyl citrate is > 10 mL/kg. No further details are available in this document.

Taking all these result into account, it can be concluded that triethyl citrate is of very low acute toxicity if administered to animals via all exposure routes.


Justification for selection of acute toxicity – oral endpoint
The acute oral toxicity of triethyl citrate was investigated in several studies reported in literature, the lowest result was taken as key value.

Justification for selection of acute toxicity – inhalation endpoint
peer-reviewed database

Justification for selection of acute toxicity – dermal endpoint
peer-reviewed database

Justification for classification or non-classification

Acute oral toxicity:

The test material does not meet the criteria for classification and will not require labelling for oral toxicity in accordance with European Regulation (EC) No. 1272/2008, amending Regulation EC No. 1907/2006 (REACH).

Acute inhalation toxicity:

The test material does not meet the criteria for classification and will not require labelling for inhalation toxicity in accordance with European Regulation (EC) No. 1272/2008, amending Regulation EC No. 1907/2006 (REACH).

Acute dermal toxicity:

The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with European Regulation (EC) No. 1272/2008, amending Regulation EC No. 1907/2006 (REACH).