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EC number: 222-394-5 | CAS number: 3458-72-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
There are no acute oral toxicity data available for Triammonium citrate. However, data for the constituents of Triammonium citrate, namely citric acid and ammonium (other ammonium salts, e.g. ammonium sulfate) are available.
Citric acid:
Published data, several studies conducted according to OECD 401, species used were rats, mice and rabbits, LD50 determined: mice 5400 mg/kg bw, rats either 3000 mg/kg bw or 12000 mg/kg bw, rabbits < 7000 mg/kg bw.
Published data from database: Toxicological Data, compiled by the National Institute of Health (NIH), USA, selected and distributed by Technical Database Services (TDS), New York, 2009, rats applied citric acid via gavage, LD50 = 3000 mg/kg bw
Published data (Weiss et al., 1923): Study not performed according to OECD Guidelines because study was conducted prior to implementation of OECD and GLP Guidelines. Study in rabbits LG50 not determined but estimated fatal dose = 7000 mg/kg bw.
Ammonium sulfate:
Published results from Yamanaka et al., 1990, study similar to acute toxic class method, conducted to rats, no mortality at the highest dose of 2000 mg/kg bw, LD50 > 2000 mg/kg bw.
Results obtained from OECD SIDS report, method similar to acute toxic class method, doses applied: 2500, 3200, 4000, 5000, 6400 mg/kg bw applied by oral gavage to rats, LD50 = 4250 mg/kg bw.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Female rabbits were administered citric acid in doses of 3800, 4600, 5100, 6500 and 7000 mg/kg bw via gavage. Clinical signs and mortality were recorded once an hour for 24h.After determination of the initial fatal dose animals were fed 2.5 g/kg bw on 5 consecutive days. After this administration regimen the rabitts were administered 7 or 9 g/kg bw to determined the fatal dose.
- GLP compliance:
- no
- Test type:
- other: Test was conducted prior to implementation of OECD and GLP Guidelines
- Limit test:
- no
- Species:
- rabbit
- Strain:
- other: Belgian hare or Flamish giant
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) The rabbit, which is easily handled and retains whatever dose is administered, was selected for experimentation.
- Weight at study initiation: 1.36 to 2.27 kg.
- Diet (e.g. ad libitum): The animals were fed hay and oats, supplemented by green vegetables. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): 30-35 cc
MAXIMUM DOSE VOLUME APPLIED: 7000 mg/kg bw
- Doses:
- 3.8, 4.6, 5.1, 6.5, 7.0 g/kg bw
- No. of animals per sex per dose:
- one
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: single dose application and observation for 24h hours, thereafter administration of test item once daily for 5 consecutive days.
- Frequency of observations: once hourly for 24h
- Necropsy of survivors performed: no
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: - Key result
- Sex:
- female
- Dose descriptor:
- other: predicted fatal dose
- Effect level:
- 7 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- One female rabbit administered 7000 mg/kg bw citric acid died 2h after application
- Clinical signs:
- In the animal that was administered 7000 mg/kg bw unfavourable symptoms occurred 15 min after application, like nervous tremors violent twitching, convulsions which ended in death of the animal after 2h.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In this publication five female rabbits were administered citric acid in doses of 3800, 4600, 5100, 6500 and 7000 g/kg bw, one dose per rabbit. Up to 6500 mg/kg bw no clinical signs were observed. The animal treated with 7000 mg/kg bw showed clinical signs like convulsions, tremor or violent twitching and died two hours after application. Based on this result the estimated fatal dose for rabbits is 7000 mg/kg bw.
Since the other animals were treated with lower doses applied once for 5 consecutive days no acute LD50 value can be obtained. - Executive summary:
In the present study 5 rabbits were administered single doses of citric acid each (3800, 4600, 5100, 6500 and 7000 mg/kg bw). The animals were observed until a lethal dose was determined, at least one day. The estimated fatal doses was determined to be 7000 mg/kg bw. The treated animal died within 2h post-application and showed the following clinical signs 15 min after dosing: convulsions, tremor or violent twitching. Based on these results the LD50 is considered to be below 7000 mg/kg bw which is in line with the results of other oral toxicity studies with citric acid. Thus, citric acid is not classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Endpoint:
- acute toxicity: oral
- 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
- Guideline:
- other: no Guidline reported
- GLP compliance:
- not specified
- Test type:
- other: Test type not reported
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Doses:
- Dose range tested was not reported
- No. of animals per sex per dose:
- No. of animals were not reported
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- not specified
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- According to the National Institute of Health (NIH), USA, the oral LD50 in rats was published in Oyo Yakuri. Pharmacometrics. Vol. 43, Pg. 561, 1992. The source is generally accepted and also cited in several databases.
- Executive summary:
According to the National Institute of Health (NIH), USA, the oral LD50 in rats was published in Oyo Yakuri. Pharmacometrics. Vol. 43, Pg. 561, 1992. The source is generally accepted and also cited in several databases.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2001
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Reason / purpose for cross-reference:
- reference to other study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- according to guideline
- Guideline:
- other: Guideline not stated
- Version / remarks:
- performed 1981
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- not reported
- GLP compliance:
- not specified
- Test type:
- other: similar to standard acute method, conducted before imlementation of Guidelines
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not reported in review
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Doses:
- between 3000 mg/kg bw and 12000 mg/kg bw
- No. of animals per sex per dose:
- 10 in one study, numer of animals used not reported for the other studies
- Control animals:
- not specified
- Details on study design:
- Not reported
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 5 400 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with mice
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD100
- Effect level:
- 7 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rabbits
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rats
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 12 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for test with rats
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 5 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for test with rats
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- According to the OECD SIDS report 2001, the acute oral toxicity was tested in several species like mice, rats and rabbits. While in rabbits the lethal dose was found to be 7000 mg/kg bw in tests with rats, the recommended specises for acute toxicity testing, none of the mentioned tests revealed a LD50 value < 2000 mg/kg bw, thus, citric acid is not classified as acutely toxic via oral route according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Executive summary:
According to the OECD SIDS report 2001, the acute oral toxicity was tested in several species like mice, rats and rabbits. While in rabbits the lethal dose was found to be 7000 mg/kg bw in tests with rats, the recommended specises for acute toxicity testing, none of the mentioned tests revealed a LD50 value < 2000 mg/kg bw, thus, citric acid is not classified as acutely toxic via oral route according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- 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:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to the endpoint summary for acute Toxicity for more detailed information. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 5 400 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with mice
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD100
- Effect level:
- 7 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rabbits
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rats
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 12 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rats
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 5 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: results reported for tests with rats
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 000 mg/kg bw
- Based on:
- not specified
- Remarks on result:
- other: tests were conducted with rats
- Remarks:
- Results were listed in database entry
- Key result
- Sex:
- female
- Dose descriptor:
- other: predicted fatal dose
- Effect level:
- 7 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: Study conducted with rabbits
- Mortality:
- In the sudy of Weiss et al., the rabbit that were administered the highest dose died 2h after application.
- Clinical signs:
- In the sudy of Weiss et al., the rabbit that were administered the highest dose showed convulsions, tremors and violent twitching before death.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- According to the OECD SIDS report 2001, the acute oral toxicity was tested in several species like mice, rats and rabbits. While in rabbits the lethal dose was found to be 7000 mg/kg bw in tests with rats, the recommended specises for acute toxicity testing, none of the mentioned tests revealed a LD50 value < 2000 mg/kg bw, thus, citric acid is not classified as acutely toxic via oral route according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- according to guideline
- Guideline:
- other: Description of methods used in BASF acute toxicity and skin/eye irritation studies before pertinent OECD/EU test guidelines were in place (BASF AG, 2002)
- Version / remarks:
- 2002
- Deviations:
- no
- Principles of method if other than guideline:
- - Principle of test:
Description of methods used in BASF acute toxicity and skin/eye irritation studies before pertinent OECD/EU test guidelines were in place; similar to standard acute method
- Short description of test conditions: The test substance was given by single gavage to groups of rats at various dose levels as a 30% aqueous solution. 10 male and 10 female rats were used per dose level. The LD50 was calculated according to the method described by Litchfield-Wilcoxon.
- Parameters analysed / observed: not reported - GLP compliance:
- not specified
- Test type:
- other: similar to standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Gassner Strain
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- not reported
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- Test substance was applied as 30% solution
- Doses:
- 2500, 3200, 4000, 5000, 6400 mg/kg bw
- No. of animals per sex per dose:
- 10
- Control animals:
- not specified
- Statistics:
- The LD50 was calculated according to the method described by Litchfield-Wilcoxon.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 4 250 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 3 788 - <= 4 769
- Mortality:
- Group 6400 mg/kg bw: 12 died within the first hour, 2 within 24 hours, 4 within 48 hours; in total, 18/20 died within 7 days.
Group 5000 mg/kg bw: 8 died within the first hour, 1 within 24 hours, 1 within 48 hours; in total 11/20 died within 7 days.
Group: 4000 mg/kg bw: 7 died within 24 hours, and 2 within 48 hours; in total, 9/20 died within 7 days.
Group 3200 mg/kg bw: 1 animal died within the first hour, 1 within 24 hours, 2 within 48 hours; in total, 4/20 died within 7 days.
Group 2500 mg/kg bw: no deaths occurred. - Clinical signs:
- 4000-6400 mg/kg bw: immediately after application staggering, abdominal and lateral position, partly dorsal position, apathy, laboured and irregular breathing. On the next day, secretion out of eyes and mouth, reddened eyes and nose. In the post-exposure observation days the animals were without clinical symptoms.
3200 mg/kg bw: No symptoms on the application day. The next day, reddened eyes and nose, and irregular breathing were noted. Later without clinical signs.
2500 mg/kg bw: No clinical signs noted. - Gross pathology:
- At necropsy, fluid in the thoracic cavity was observed in a few animals. In three animals, the stomach was filled with liquid, and bloody mouth and forelegs were noted. No pathological findings were noted with regard to the inner organs.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- According to the study which was reported in the OECD SIDS report (2004) the LD50 value of 4250 mg/kg bw was determined using the Litchfield-Wilcoxon Method, thus the substance does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Executive summary:
According to the study which was reported in the OECD SIDS report (2004) the LD50 value of 4250 mg/kg bw was determined using the Litchfield-Wilcoxon Method, thus the substance does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to the endpoint summary for acute Toxicity for more detailed information. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 4 250 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: Results from the first test descibed in the report
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: Results from Yamanaka et al., 1990
- Mortality:
- Group 6400 mg/kg bw: 12 died within the first hour, 2 within 24 hours, 4 within 48 hours; in total, 18/20 died within 7 days.
Group 5000 mg/kg bw: 8 died within the first hour, 1 within 24 hours, 1 within 48 hours; in total 11/20 died within 7 days.
Group: 4000 mg/kg bw: 7 died within 24 hours, and 2 within 48 hours; in total, 9/20 died within 7 days.
Group 3200 mg/kg bw: 1 animal died within the first hour, 1 within 24 hours, 2 within 48 hours; in total, 4/20 died within 7 days.
Group 2500 mg/kg bw: no deaths occurred.
In the study of Yamanaka none of the animals died. - Clinical signs:
- 4000-6400 mg/kg bw: immediately after application staggering, abdominal and lateral position, partly dorsal position, apathy, laboured and irregular breathing. On the next day, secretion out of eyes and mouth, reddened eyes and nose. In the post-exposure observation days the animals were without clinical symptoms.
3200 mg/kg bw: No symptoms on the application day. The next day, reddened eyes and nose, and irregular breathing were noted. Later without clinical signs.
2500 mg/kg bw: No clinical signs noted.
In the study of Yamanaka no clinical signs were reported up to the highest dose. - Body weight:
- In the study of Yamanaka no significant alterations in body weight were reported
- Gross pathology:
- At necropsy, fluid in the thoracic cavity was observed in a few animals. In three animals, the stomach was filled with liquid, and bloody mouth and forelegs were noted. No pathological findings were noted with regard to the inner organs.
In the study of Yamanaka no abnormalties were found during necropsy. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- According to the study which was reported in the OECD SIDS report (2004) the LD50 value of 4250 mg/kg bw was determined using the Litchfield-Wilcoxon Method, thus the substance does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS). In the publication of Yamanaka et al.(1990) at the highest dose tested in rats (2000 mg/kg bw) no mortality, clinical signs or abnormal changes during necropsy were reported. The LD50 for Ammonium sulfate was therefore considered to be > 2000 mg/kg bw. According to Regulation (EC) No. 1272/2008 (CLP) Ammonium sulfate does not need to be classified with regard to acute oral toxicity.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Principles of method if other than guideline:
- Three rats and mice of both sexes were used at each dose level. The step 1 test was performed at a dose of 2000 mg/kg. If none of the animals died, the following toxicity test was suspended and the chemical was regarded as having an LD50 of greater than 2000 mg/kg. If some of the animals died, the step 2 test was performed at the level of 200 mg/kg and the exact LDs0 could be determined by the classical full LD50 test after the step 1 test if "valid" LD50 values were necessary. If all animals survived in the step 2 test, the chemical was considered to have an LD50 greater than 200 mg/kg. When some of the animals died, the step 3 test with the 20 mg/kg dose was performed. If all the animals died at this dose level, it meant that the chemical bad an LD50 of less than 20 mg/kg. If one or two animals died at the fixed dose level, the chemical was regarded as having an LD50 near that dose level, and the approximate LD50 of the chemical was indicated as ca. 20, 200 or 2000 mg/kg.
- GLP compliance:
- not specified
- Test type:
- other: similar to acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals were treated with the substances after at least 5 days of adaptation. In the oral toxicity test, the substances dissolved in water, olive oil or 5% arabic gum were administered orally in a single dose after fasting for 16 h.
- Route of administration:
- oral: gavage
- Vehicle:
- other: water, olive oil or 5% arabic gum
- Doses:
- 20, 200 and 2000 mg/kg bw
- No. of animals per sex per dose:
- not reported
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation of animals, including body weight changes, mortality, gross lesion and behavioural and clinical abnormality, were performed for 14 days after exposure, and necropsy was carried out at the end of the test.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on the results from a study performed similar to OECD guideline 423, in which no mortality was reported up to 2000 mg/kg bw, Ammonium sulphate does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Executive summary:
Based on the results from a study performed similar to OECD guideline 423, in which no mortality was reported up to 2000 mg/kg bw, Ammonium sulphate does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
Referenceopen allclose all
There were no descriptions of the observed parameters in the publication of Yamanaka et al., 1990.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 000 mg/kg bw
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
There are no acute oral toxicity data available for Triammonium citrate. However, data for the constituents of Triammonium citrate, namely citric acid and ammonium (other ammonium salts, e.g. ammonium sulfate) are available. Based on the ionic structure of Triammonium citrate, the salt is considered to dissociate in aqueous solutions as well as in the stomach. Thus, the animals are supposed to be exposed to the free ions of Triammonium citrate.
Triammonium citrate is a salt of citric acid in which all carboxy groups are protonated with ammonium cations. It is highly soluble in water and has a distinct buffer capacity. Thus, it is used as food additive. Beside, it exhibits an emulsifier function in food and beverages.
In an aqueous solution it dissociates into its two ionic components, namely ammonium ions and citric acid. Both constituents are ubiquitously occurring electrolytes which are an essential part of the intermediary metabolism in every eukaryotic organism. It is therefore considered to be of low acute toxicity. However, there are no toxicological relevant data available for Triammonium citrate regarding acute oral toxicity but there is information about the constituents of this salt.
Citric acid is a naturally occurring carbon acid. It can be found in citrus fruits but is also a part of the tricarboxylic acid cycle during aerobic metabolism in every cell. It is also used as food additive, as preservative, and as active substance in certain biocides (disinfectants and algaecides)(EFSA[1][2], WHO[3],citric acid assessment report PT:2).
Several international scientific commitees evaluated citric acid and it was jointly considered to be safe, e.g. because Citric acid ingested by target animals is normally rapidly metabolised to carbon dioxide and water (EFSA 2015[4]). The metabolic pathways involved in degradation of citric acid are well developed and capable of processing very high amounts of citric acid and the concentrations evaluated in these reports are not assumed to raise citric acid concentrations to a toxic level.
It was shown in several studies citric acid exhibits only a low acute oral toxicity (OECD SIDS, 2001[5]). The determined LD50 values for acute oral toxicity ranged from 3000 mg/kg bw to 12000 mg/kg bw in rats to 5400 mg/kg bw in mice (OECD SIDS, 2001). Even after s.c. administration in rats and mice the LD50 values were between 2700 and 5500 mg/kg bw.
However, there were some adverse effect reported which were correlated to the acidic nature of citric acid. Among these effects the most predominat were damage to stomach mucosa and hypocalcaemia. These effects are also dependent on the route of administration and the administered form, i.e. free acid form or salt. Administration of citrates (salt-form) did not cause any symptoms when administered orally to human Volunteers in doses that correspond to 4.7g citric acid.
Ammonia is a naturally occurring compound and an important source of nitrogen for mammals. Its ionized form Ammonium is like citrates an integral part of the intermediary metabolism. It occurs mainly during degradation of proteins and is renal eliminated after urea synthesis. Ammonia forms an equilibrium with Ammonium ions in water. In this equilibrium the generation of Ammonium ions is usually preferred at pH5-8. At high pH values the equilibrium changes to Ammonia. While Ammonia exhibits rather low LD50 values the acute toxicity of Ammonium is considered to be low.
It was shown in several studies and evaluated by the OECD panel that the LD50 for Ammonium (administered as Ammonium salts) is in the range 640 mg/kg bw to > 4000 mg/kg bw. The reasons for the rather wide range of LD50 values are the different species used and quality of the studies cited (OECD SIDS, 2004[6]). However, all studies that were performed with the recommended species, i.e. rat, showed a LD50 value of > 2000 mg/kg bw, thus Ammonium that occurs from dissociation of the respective Ammonium salt is considered to exhibit only a low toxicity.
In summary, both constituents of Triammonium citrate, namely Ammonium ions and citrate were shown to be of low toxicity, i.e. both constituents were not classified according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS). Based on the available data and for reasons of animal welfare testing of acute oral toxicity of Triammonium sulfate is scientifically not justified. Furthermore, Triammonium citrate is no considered to increase the toxicity already determined for the constituents and thus does not need to be classified with respect to acute oral toxicity.
[1]EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). "Scientific Opinion on the safety and efficacy of citric acid when used as a technological additive (acidity regulator) for all animal species."EFSA Journal 13.2 (2015): 4010.
[2]EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF). "Safety assessment of the active substances citric acid and sodium hydrogen carbonate for use in active food contact materials."EFSA Journal 14.7 (2016): e04529.
[3]Joint, F. A. O., WHO Expert Committee on Food Additives, and World Health Organization. "Toxicological evaluation of certain food additives with a review of general principles and of specifications: seventeenth report of the Joint FAO/WHO Expert Committee on Food Additives, Geneva, 25 June-4 July 1973."(1974).
[4]EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). "Scientific Opinion on the safety and efficacy of citric acid when used as a technological additive (acidity regulator) for all animal species."EFSA Journal 13.2 (2015): 4010.
[5]SIDS, OECD. "Citric Acid CAS No: 77-92-9."(2001).
[6]SIDS, OECD. "Ammonium Sulfate CAS No: 7783-20-2."(2004)
Justification for classification or non-classification
In summary, both constituents of Triammonium citrate, namely Ammonium ions and citrate were shown to be of low toxicity, i.e. both constituents were not classified according to Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS). Based on the available data and for reasons of animal welfare testing of acute oral toxicity of Triammonium sulfate is scientifically not justified. Furthermore, Triammonium citrate is no considered to increase the toxicity already determined for the constituents and thus does not need to be classified with respect to acute oral toxicity.
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