Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 211-162-9 | CAS number: 631-61-8
- 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
Acute oral toxicity: Weight of evidence: The LD50 was higher than 2000 mg/kg bw (2333.28-3546.59 mg/kg bw). Read-across approach from experimental results obtained with analogues Potassium Acetate and Ammonium Sulphate. The read-across approach acute toxicity effect is lower than the subacute toxicity data obtained from an experimental study. The difference can be explained as an estimation error of the read across (the choosen value is the lowest one). Both results are higher than 2000 mg/kg/bw and shows no oral toxicity of ammonium acetate.
Acute dermal toxicity: Weight of evidence: The LD50 was greater than 2000 mg/kg bw (> 2333.28-26556.42 mg/kg bw). Read-across approach from experimental results obtained with analogues Fumaric Acid and Ammonium Sulphate.
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:
- other: No specific test guideline was reported; however, a scientifically defensible approach was used to conduct the study.
- Principles of method if other than guideline:
- Single oral toxicity is estimated by the gastric intubation of groups of five non-fasted, Carworth-Wistar rats, four to five weeks of age and 90 to 120 grams in weight, which have been reared in the laboratory own colony and mantained from time of weaning on Rockland rat diet, complete. Dose: 3.25g/kg (2.48-4.26). The observation period was 14 days.
- GLP compliance:
- no
- Test type:
- other: method described
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Carworth-Wistar
- Sex:
- male
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Doses:
- 3.25 g/kg bw (2.48-4.26)
- No. of animals per sex per dose:
- Five male rats per group
- Control animals:
- not specified
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 3.25 other: g/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Potassium acetate LD50 is 3.25 g/kg bw (2.48-4.26).
- Executive summary:
Potassium acetate LD50is 3.25 g/kg bw (2.48-4.26).
- Endpoint:
- acute toxicity: oral
- Type of information:
- not specified
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Peer reviewed handbook: Sax's Dangerous Properties of Industrial Materials.
- Principles of method if other than guideline:
- No data provided on the method.
- GLP compliance:
- not specified
- Test type:
- other: No data
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- other: oral
- Vehicle:
- not specified
- Doses:
- 3250 mg/kg bw
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 250 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Potassium acetate oral, LD50 = 3250 mg/kg bw.
- Executive summary:
Potassium acetate oral, LD50 = 3250 mg/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the acute oral toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE CATEGORY APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (non-standard method) on the analogue Potassium Acetate.
- GLP compliance:
- no
- Test type:
- other: read-across from a non-standard study with an analogue
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2.55 other: g/kg bw
- Based on:
- test mat.
- 95% CL:
- 1.95 - 3.35
- Other findings:
- Based on the experimental results obtained with the analogue Potassium Acetate (LD 50 for male rats = 3.25 (2.48-4.26) g/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for substance Ammonium Acetate is calculated to be 2.55 (1.95-3.35) g/kg bw.
The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is -3.72 for Potassium Acetate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 2.5 g/mL at 20 ºC for Potassium Acetate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 98.14 for Potassium Acetate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for substance Ammonium Acetate is calculated to be 2.55 (1.95-3.35) g/kg bw.
- Executive summary:
Based on the experimental results obtained (reported under the endpoint record 07.02.01_01 KAc) with the analogue Potassium Acetate (LD 50 for male rats = 3.25 (2.48-4.26) g/kg) and the molecular weights, the read-across approach is applied and the LD50 for substance Ammonium Acetate is calculated to be 2.55 (1.95 -3.35) g/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the acute oral toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE CATEGORY APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published data (no information on test method) on the analogue Potassium Acetate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from study with an analogue
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 2 552.58 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Potassium Acetate (LD 50 for rats = 3250 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for substance Ammonium Acetate is calculated to be 2552.58 mg/kg bw.
The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is -3.72 for Potassium Acetate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 2.5 g/mL at 20 ºC for Potassium Acetate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 98.14 for Potassium Acetate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for substance Ammonium Acetate is calculated to be 2552.58 mg/kg bw.
- Executive summary:
Based on the experimental results obtained (reported under the endpoint record 07.02.01_02 KAc) with the analogue Potassium Acetate (LD 50 for rats = 3250 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for substance Ammonium Acetate is calculated to be 2552.58 mg/kg bw.
- 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:
- other: Test method was similar to OECD guideline 423. No data on GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- not specified
- Remarks:
- (No data on control)
- GLP compliance:
- not specified
- Test type:
- acute toxic class method
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5-6 weeks old
- Fasting period before study: 16 hours
- Acclimation period: At least, 5 days. - Route of administration:
- oral: unspecified
- Vehicle:
- water
- Doses:
- 20, 200, and 2000 mg/kg bw
- No. of animals per sex per dose:
- Three animals of each sex per dose.
- Control animals:
- not specified
- Details on study design:
- Careful observations of animals, including body weight changes, mortality figures, gross lesion and behavioural and clinical abnormality, were performed for 14 days.
Necropsy of all animals was carried out at the end of the test.
Animal experiments were performed simultaneously in two different laboratories. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 2 000 mg/kg bw
- Based on:
- test mat.
- Clinical signs:
- other: No clinical symptoms are reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium sulfate was equal or greater than 2000 mg/kg bw in male and female rats.
- Executive summary:
In a study similar to OECD guideline 423, a LD50 value of about 2000 mg/kg bw is reported for male and female rats.
- 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:
- other: Test method was similar to OECD guideline 423. No data on GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- not specified
- Remarks:
- (No data on control)
- GLP compliance:
- not specified
- Test type:
- acute toxic class method
- Species:
- mouse
- Strain:
- other: ddy
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5-6 weeks old
- Fasting period before study: 16 hours
- Acclimation period: At least, 5 days. - Route of administration:
- oral: unspecified
- Vehicle:
- water
- Doses:
- 20, 200, and 2000 mg/kg bw
- No. of animals per sex per dose:
- Three animals of each sex per dose.
- Control animals:
- not specified
- Details on study design:
- Careful observations of animals, including body weight changes, mortality figures, gross lesion and behavioural and clinical abnormality, were performed for 14 days.
Necropsy of all animals was carried out at the end of the test.
Animal experiments were performed simultaneously in two different laboratories. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Clinical signs:
- other: No clinical symptoms are reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium sulfate was greater than 2000 mg/kg bw in male and female mice.
- Executive summary:
In a study similar to OECD guideline 423, a LD50 value greater than 2000 mg/kg bw is reported for male and female mice.
- 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:
- other: Test method was similar to OECD guideline 401. No data on GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- not specified
- Remarks:
- (No data on control)
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Species:
- mouse
- Strain:
- other: ddy
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5-6 weeks old
- Fasting period before study: 16 hours
- Acclimation period: At least, 5 days. - Route of administration:
- oral: unspecified
- Vehicle:
- water
- Doses:
- 20, 200, and 2000 mg/kg bw
- No. of animals per sex per dose:
- Three animals of each sex per dose.
- Control animals:
- not specified
- Details on study design:
- Careful observations of animals, including body weight changes, mortality figures, gross lesion and behavioural and clinical abnormality, were performed for 14 days.
Necropsy of all animals was carried out at the end of the test. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 3 040 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 2 670 - 3 440
- Clinical signs:
- other: No clinical symptoms are reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium sulfate was 3040 (2670 -3440) mg/kg bw in male and female mice.
- Executive summary:
In a full LD50 test according to the Toxicity Guidelines of Japan (1984) an oral LD50 for mice of 3040 (2670 -3440) mg/kg bw was obtained. Details on clinical signs and necropsy findings were not given.
- 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:
- other: The analogue Ammonium Sulfate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the acute oral toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (test method similar to OECD 423) on the analogue Ammonium sulfate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from an acute toxic class method with an analogue
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 2 333.28 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Ammonium sulfate (LD 50 for rats >= 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be >= 2333.28 mg/kg bw.
The analogue Ammonium Sulfate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the aquatic toxicity endpoint. These properties are:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium Acetate is calculated to be >= 2333.28 mg/kg bw.
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.01_05 Ammonium sulfate) obtained with the analogue Ammonium sulfate (LD 50 for rats >= 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be >= 2333.28 mg/kg bw.
- 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:
- other: The analogue Ammonium Sulfate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the acute oral toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (test method similar to OECD 423) on the analogue Ammonium sulfate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from an acute toxic class method with an analogue
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 333.28 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Ammonium sulfate (LD 50 for mice > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
The analogue Ammonium Sulfate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the aquatic toxicity endpoint. These properties are:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.01_06 Ammonium sulfate) obtained with the analogue Ammonium sulfate (LD 50 for mice > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
- 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:
- other: The analogue Ammonium Sulfate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the acute oral toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (test method similar to OECD 401) on the analogue Ammonium sulfate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from a standard acute method with an analogue
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 3 546.59 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 3 114.93 - 4 013.25
- Other findings:
- Based on the experimental results obtained with the analogue Ammonium sulfate (LD 50 for mice = 3040 (2670-3440) mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be 3546.59 (3114.93-4013.25) mg/kg bw.
The analogue Ammonium Sulfate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the aquatic toxicity endpoint. These properties are:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium Acetate is calculated to be 3546.59 (3114.93-4013.25) mg/kg bw.
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.01_07 Ammonium sulfate) obtained with the analogue Ammonium sulfate (LD 50 for mice = 3040 (2670-3440) mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be 3546.59 (3114.93-4013.25) mg/kg bw.
Referenceopen allclose all
Potassium acetate LD50 is 3.25 g/kg bw (2.48-4.26).
Potassium acetate oral, LD50 = 3250 mg/kg bw.
The LD50 for substance Ammonium Acetate is calculated to be 2.55 (1.95-3.35) g/kg bw.
The LD50 for substance Ammonium Acetate is calculated to be 2552.58 mg/kg bw.
The LD50 for Ammonium sulfate was equal or greater than 2000 mg/kg bw in male and female rats.
The LD50 for Ammonium sulfate was greater than 2000 mg/kg bw in male and female mice.
The LD50 for Ammonium sulfate was 3040 (2670 -3440) mg/kg bw in male and female mice.
The LD50 for Ammonium Acetate is calculated to be >= 2333.28 mg/kg bw.
The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue Approach.
CAS Number
|
Source chemical 7783-20-2 |
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Ammonium sulphate |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental data: Decomposes above 280 ºC |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental data: Decomposes above 280 ºC |
Estimated data: 312.76 ºC
|
|
Density |
Experimental data: 1.769 at 50 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Experimental data: –5.1 at 25 ºC |
Estimated data: -2.79
|
|
Water solubility
|
Experimental data: 764 g/L at 20 ºC |
Experimental data: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)
|
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)
|
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)
|
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits) |
No data |
|
Acute Toxicity: Dermal |
Experimental data:
LC50 > 2000 mg/kg bw (rats, mice) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits. - Single exposure for 20 hours, intact skin: no skin effects observed. - Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin Sensitization
|
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.
The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day). |
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
- Chromosomal aberration |
Experimental data:
Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data |
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.
|
No data |
|
Reproductive Toxicity |
TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data. |
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
The LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue Approach.
CAS Number
|
Source chemical 7783-20-2 |
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Ammonium sulphate |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental data: Decomposes above 280 ºC |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental data: Decomposes above 280 ºC |
Estimated data: 312.76 ºC
|
|
Density |
Experimental data: 1.769 at 50 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Experimental data: –5.1 at 25 ºC |
Estimated data: -2.79
|
|
Water solubility
|
Experimental data: 764 g/L at 20 ºC |
Experimental data: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)
|
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)
|
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)
|
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits) |
No data |
|
Acute Toxicity: Dermal |
Experimental data:
LC50 > 2000 mg/kg bw (rats, mice) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits. - Single exposure for 20 hours, intact skin: no skin effects observed. - Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin Sensitization
|
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.
The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day). |
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
- Chromosomal aberration |
Experimental data:
Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data |
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.
|
No data |
|
Reproductive Toxicity |
TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data. |
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
The LD50 for Ammonium Acetate is calculated to be 3546.59 (3114.93-4013.25) mg/kg bw.
The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue Approach.
CAS Number
|
Source chemical 7783-20-2 |
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Ammonium sulphate |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental data: Decomposes above 280 ºC |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental data: Decomposes above 280 ºC |
Estimated data: 312.76 ºC
|
|
Density |
Experimental data: 1.769 at 50 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Experimental data: –5.1 at 25 ºC |
Estimated data: -2.79
|
|
Water solubility
|
Experimental data: 764 g/L at 20 ºC |
Experimental data: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)
|
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)
|
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)
|
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits) |
No data |
|
Acute Toxicity: Dermal |
Experimental data:
LC50 > 2000 mg/kg bw (rats, mice) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits. - Single exposure for 20 hours, intact skin: no skin effects observed. - Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin Sensitization
|
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.
The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day). |
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
- Chromosomal aberration |
Experimental data:
Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data |
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.
|
No data |
|
Reproductive Toxicity |
TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data. |
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 2 338.28 mg/kg bw
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Justification for type of information:
- JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII, column 2: In addition to the oral route (Annex VII, 8.5.1.), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information is provided for dermal route.
Reference
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- 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:
- other: The analogue Fumaric acid which shares the same functional group with Ammonium acetate, also has comparable values for the relevant molecular properties for acute dermal toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (study with a test method similar to OECD 402) on the analogue Fumaric Acid.
- GLP compliance:
- no
- Test type:
- other: read-across from a standard acute method with an analogue
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 26 556.42 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Fumaric Acid (4h-LD 50 for New Zealand rabbits > 20000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD 50 for substance Ammonium Acetate is calculated to be greater than 26556.42 mg/kg bw under test conditions.
The analogue Fumaric Acid, which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is 0.25 for Fumaric Acid and - 2.79 for Ammonium Acetate,
- water solubility which is 0.0063 g/mL at 25 ºC for Fumaric Acid and 1480 g/L at 4 ºC for Ammonium acetate, and
- molecular weights which are 116.07 for Fumaric Acid and 77.08 for Ammonium acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The (4h) LD 50 for substance Ammonium Acetate is calculated to be greater than 26556.42 mg/kg bw for rabbits.
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.03_02 Fumaric Acid) obtained with the analogue Fumaric Acid (4h-LD 50 for New Zealand rabbits > 20000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD 50 for substance Ammonium acetate is calculated to be higher than 26556.42 mg/kg bw under test conditions.
- 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:
- other: Test method was similar to OECD 402 guideline, but only three animals per dose were used. No GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- (Only 3 female rabbits were used per dose)
- GLP compliance:
- no
- Test type:
- standard acute method
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 3-4 kg bw
- Diet (e.g. ad libitum): Purina Rabbit Chow - Type of coverage:
- semiocclusive
- Vehicle:
- water
- Details on dermal exposure:
- TEST SITE
- Type of wrap if used: Test substance was kept in place by gauze patches under a latex rubber film.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of exposure:
- 4 hours
- Doses:
- No data on doses (the highest one was 20000 mg/kg bw)
- No. of animals per sex per dose:
- 3 female New Zealand rabbits were used per dose.
- Control animals:
- not specified
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 20 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality was observed at the highest dose of 20000 mg/kg bw
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Fumaric Acid is higher than 20000 mg/kg bw for rabbits.
- Executive summary:
The acute dermal toxicity of Fumaric Acid has been studied on Rabbits were clipped of all possible hair on back and flanks 24 hours before exposure. A 0.5 mL dose of Fumaric Acid was administered via a single skin penetration to three female albino New Zealand rabbits and kept in place by gauze patches under a latex rubber film. The patches remained in place for 4 hours. During that time the rabbits were fitted with leather restraining collars to prevent disturbance of the patch test. After 4 hours, the wrap and patches were removed and the test area was observed for visible tissue destruction.
No mortality was observed at the high dose of 20000 mg/kg b.w, so the LD50 is higher than 20000 mg/kg bw.
- 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:
- other: Test method according to the Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984). No data on GLP.
- Qualifier:
- according to guideline
- Guideline:
- other: Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984).
- Deviations:
- not specified
- GLP compliance:
- not specified
- Test type:
- fixed dose procedure
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5-6 weeks old
- Housing: All animals were individually housed in stainless-steel cages.
- Acclimation period: At least, 5 days. - Type of coverage:
- open
- Vehicle:
- other: water-acetone solution
- Details on dermal exposure:
- In the dermal toxicity test, hair was first removed from an area of 3 x 4 cm2 on the back of animals with an electric hair clipper, and then the chemical substance was dissolved in acetone and water and applied in a single dose to the skin surface of the clipped backs of the animals. The application sites were not covered but the treated areas were prevented from being licked by using a plastic collar or by fixing the animals on a plastic plate, and all animals were individually housed in stainless-steel cages.
- Duration of exposure:
- A single administration, but no data on removing.
- Doses:
- 20, 200, and 2000 mg/kg bw.
- No. of animals per sex per dose:
- Three animals of each sex per dose.
- Control animals:
- not specified
- Details on study design:
- Careful observations of animals, including body weight changes, mortality figures, gross lesion and behavioural and clinical abnormality, were performed for 14 days.
Necropsy of all animals was carried out at the end of the test.
Animal experiments were performed simultaneously in two different laboratories. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Clinical signs:
- other: No treatment-related clinical signs and necropsy findings were observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 was greater than 2000 mg/kg bw for rats after dermal application of ammonium sulfate.
- Executive summary:
In the dermal toxicity test, hair was first removed from an area of 3 x 4 cm2 on the back of rats with an electric hair clipper, and then the chemical substance was dissolved in acetone and water and applied in a single dose to the skin surface of the clipped backs of the animals. The application sites were not covered but the treated areas were prevented from being licked by using a plastic collar or by fixing the animals on a plastic plate, and all animals were individually housed in stainless-steel cages.
The LD50 values higher than 2000 mg/kg bw are reported for rats after dermal application of ammonium sulfate. No treatment-related clinical signs and necropsy findings were observed.
- 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:
- other: Test method according to the Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984). No data on GLP.
- Qualifier:
- according to guideline
- Guideline:
- other: Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984).
- Deviations:
- not specified
- GLP compliance:
- not specified
- Test type:
- fixed dose procedure
- Species:
- mouse
- Strain:
- other: ddy
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5-6 weeks old
- Housing: All animals were individually housed in stainless-steel cages.
- Acclimation period: At least, 5 days. - Type of coverage:
- open
- Vehicle:
- other: water-acetone solution
- Details on dermal exposure:
- In the dermal toxicity test, hair was first removed from an area of 1 x 2 cm2 on the back of animals with an electric hair clipper, and then the chemical substance was dissolved in acetone and water and applied in a single dose to the skin surface of the clipped backs of the animals. The application sites were not covered but the treated areas were prevented from being licked by using a plastic collar or by fixing the animals on a plastic plate, and all animals were individually housed in stainless-steel cages.
- Duration of exposure:
- A single administration, but no data on removing.
- Doses:
- 20, 200, and 2000 mg/kg bw.
- No. of animals per sex per dose:
- Three animals of each sex per dose.
- Control animals:
- not specified
- Details on study design:
- Careful observations of animals, including body weight changes, mortality figures, gross lesion and behavioural and clinical abnormality, were performed for 14 days.
Necropsy of all animals was carried out at the end of the test.
Animal experiments were performed simultaneously in two different laboratories. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Clinical signs:
- other: No treatment-related clinical signs and necropsy findings were observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 was greater than 2000 mg/kg bw for mice after dermal application of ammonium sulfate.
- Executive summary:
In the dermal toxicity test, hair was first removed from an area of 1 x 2 cm2 on the back of mice with an electric hair clipper, and then the chemical substance was dissolved in acetone and water and applied in a single dose to the skin surface of the clipped backs of the animals. The application sites were not covered but the treated areas were prevented from being licked by using a plastic collar or by fixing the animals on a plastic plate, and all animals were individually housed in stainless-steel cages.
The LD50 values higher than 2000 mg/kg bw are reported for mice after dermal application of ammonium sulfate. No treatment-related clinical signs and necropsy findings were observed.
- Endpoint:
- acute toxicity: dermal
- 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:
- other: The analogue Ammonium Sulfate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for acute dermal toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (study with a test method according to the Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984)) on the analogue Ammoniun sulphate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from a fixed dose procedure with an analogue
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 333.28 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Ammonium sulfate (LD 50 for rats > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
The analogue Ammonium Sulfate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the aquatic toxicity endpoint. These properties are:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw..
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.03_03 Ammonium sulfate) obtained with the analogue Ammonium sulfate (LD 50 for rats > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
- Endpoint:
- acute toxicity: dermal
- 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:
- other: The analogue Ammonium Sulfate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for acute dermal toxicity endpoint.
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format. - Reason / purpose for cross-reference:
- reference to other study
- Principles of method if other than guideline:
- Read-across approach from published experimental data (study with a test method according to the Toxicity Guidelines of Japan (Ministry of Health and Welfare in Japan, 1984)) on the analogue Ammoniun sulphate.
- GLP compliance:
- not specified
- Test type:
- other: read-across from a fixed dose procedure with an analogue
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 333.28 mg/kg bw
- Based on:
- test mat.
- Other findings:
- Based on the experimental results obtained with the analogue Ammonium sulfate (LD 50 for mice > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
The analogue Ammonium Sulfate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the aquatic toxicity endpoint. These properties are:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw..
- Executive summary:
Based on the experimental results (reported under the endpoint record 07.02.03_04 Ammonium sulfate) obtained with the analogue Ammonium sulfate (LD 50 for mice > 2000 mg/kg bw) and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
Referenceopen allclose all
The analogue Fumaric Acid which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is 0.25 for Fumaric Acid and -2.79 for Ammonium Acetate,
- similar molecular weights which are 116.07 for Fumaric Acid and 77.08 for Ammonium Acetate.
Both chemicals are grouped together by US EPA category group Carboxylic Food Acids and Salts Category.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0.Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue Approach.
CAS Number
|
Source chemical 110-17-8
|
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Fumaric acid |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental results: 290°C (sublimes) |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental results: 290 °C (sublimes) |
Estimated data: 312.76 ºC
|
|
Density |
Experimental results: 1.64 at 20 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Measured data: 1.5×10-4 mm Hg at 25°C
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Estimated data: 0.25
|
Estimated data: -2.79
|
|
Water solubility
|
Measured data: 0.0063 g/mL at 25 ºC
|
Experimental results: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental results: Readily biodegradable
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
No data |
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: 48-h EC50 = 212 mg/L (Daphnia magna) |
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data:
72-h EC50 (growth) = 41 mg/L(Scenedesmus subcapitata) |
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LD 50 = 9300 - 10700 mg/kg bw (rats) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
No data |
No data |
|
Acute Toxicity: Dermal |
Key study: LD50 (4 h) > 20000 mg/kg bw (female New Zealand White rabbits) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
No data |
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data:
Fumaric Acid has been tested by application of a drop of 10% solution to the eyes of rabbits after mechanical removal of corneal epithelium to facilitate penetration, but it appeared to do no damage, & healing was similar to that in control eyes without test chemical. |
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin sensitisation |
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Repeated dose toxicity: oral: Experimental data: Repeated dose toxicity: oral: 2-year study in male and female rats which were treated by diet. The LOAEL = 750 mg/kg bw/day (based on slight increases in mortality and increased incidence of testes degeneration at the highest dose tested). The NOAEL = 600 mg/kg bw/day.
|
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day . Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
In a bacterial reverse mutation assay usingS. typhimurium(TA98, TA100, TA1535, TA97 and TA1537) in the absence of metabolic activation and concentrations up to 1000μg/plate, fumaric acid was not mutagenic. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
Chromosomal aberration |
Fumaric acid was assayed in anin vitroassay using Chinese hamster fibroblast cells in the absence of metabolic activation at doses up to 1 mg/mL; however, insufficient information was provided in the robust summary to adequately evaluate this study. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data
|
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
No data
|
No data |
|
Reproductive Toxicity |
No data
|
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
The LD50 for Fumaric Acid is higher than 20000 mg/kg bw for rabbits.
The LD50 was higher than 2000 mg/kg bw for rats after dermal application of ammonium sulfate.
The LD50 was greater than 2000 mg/kg bw for mice after dermal application of ammonium sulfate.
The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue approach.
CAS Number
|
Source chemical 7783-20-2 |
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Ammonium sulphate |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental data: Decomposes above 280 ºC |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental data: Decomposes above 280 ºC |
Estimated data: 312.76 ºC
|
|
Density |
Experimental data: 1.769 at 50 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Experimental data: –5.1 at 25 ºC |
Estimated data: -2.79
|
|
Water solubility
|
Experimental data: 764 g/L at 20 ºC |
Experimental data: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)
|
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)
|
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)
|
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits) |
No data |
|
Acute Toxicity: Dermal |
Experimental data:
LC50 > 2000 mg/kg bw (rats, mice) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits. - Single exposure for 20 hours, intact skin: no skin effects observed. - Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin Sensitization
|
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.
The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day). |
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
- Chromosomal aberration |
Experimental data:
Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data |
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.
|
No data |
|
Reproductive Toxicity |
TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data. |
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:
- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,
- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).
Table 1. Data Matrix, Analogue Approach.
CAS Number
|
Source chemical 7783-20-2 |
Target chemical 631-61-8
|
|
CHEMICAL NAME
|
Ammonium sulphate |
Ammonium acetate |
|
PHYSICO-CHEMICAL DATA
|
|||
Melting Point |
Experimental data: Decomposes above 280 ºC |
Experimental data: 114 ºC
|
|
Boiling Point |
Experimental data: Decomposes above 280 ºC |
Estimated data: 312.76 ºC
|
|
Density |
Experimental data: 1.769 at 50 ºC |
Experimental results: 1.07-1.17 g/cm3 at 20 ºC
|
|
Vapour Pressure |
Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)
|
Estimated data: 0.02 Pa at 25 ºC |
|
Partition Coefficient (log Kow) |
Experimental data: –5.1 at 25 ºC |
Estimated data: -2.79
|
|
Water solubility
|
Experimental data: 764 g/L at 20 ºC |
Experimental data: 1480 g/L at 4 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY
|
|||
Aerobic Biodegradation
|
Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes
|
Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:
Readily biodegradable
|
|
ENVIRONMENTAL TOXICITY
|
|||
Acute Toxicity to Fish |
Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)
|
Experimental data and read-across from Potassium Acetate, based on molecular weights:
LC50 = 392.70 mg/L.
|
|
Acute Toxicity to Aquatic Invertebrates |
Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)
|
Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:
EC50 = 108.81 - 939.66 mg/L
|
|
Toxicity to Aquatic Plants
|
Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)
|
Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
|
|
MAMMALIAN TOXICITY
|
|||
Acute Toxicity: Oral |
Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse) |
Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
|
|
Acute Toxicity: Inhalation |
Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits) |
No data |
|
Acute Toxicity: Dermal |
Experimental data:
LC50 > 2000 mg/kg bw (rats, mice) |
Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
|
|
Skin Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits. - Single exposure for 20 hours, intact skin: no skin effects observed. - Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin. |
|
Eye Irritation/Corrosion |
Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).
|
Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes. |
|
Skin Sensitization
|
No data |
Weight of evidence:
Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:
All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
|
|
Repeated Dose Toxicity |
Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.
The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day). |
Repeated dose toxicity: oral: Weight of evidence: Experimental results:
Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:
The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.
Read-across from the analogue Citric acid, sodium salt, based on molecular weights:
The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
|
|
Genetic Toxicity in vitro
|
- Gene mutation in bacteria
|
Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems. |
Weight of evidence:
Read-across from Sodium Acetate (category analogue) based on functional group:
Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.
Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
|
- Mammalian gene mutation |
No data |
Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.
Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
|
|
- Chromosomal aberration |
Experimental data:
Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures. |
Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:
In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:
Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system. |
|
Genetic Toxicity in vivo
|
No data |
Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:
The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
|
|
Carcinogenicity
|
Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.
|
No data |
|
Reproductive Toxicity |
TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data. |
TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.
DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.
|
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 2 338.28 mg/kg bw
Additional information
Acute oral toxicity:
Weight of evidence: Read-across approach from experimental results obtained with analogues Potassium Acetate and Ammonium Sulphate. All results were higher than 2000 mg/kg bw.
Read-across approach from Potassium Acetate data:
LD 50 for male rats = 3.25 (2.48-4.26) g/kg bw. Based on molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be 2.55 (1.95 -3.35) g/kg bw.
LD 50 for rats = 3250 mg/kg bw. Based on molecular weights, the read-across approach is applied and the LD50 for substance Ammonium Acetate is calculated to be 2552.58 mg/kg bw.
Read-across approach from Ammonium Sulphate data:
LD 50 for rats >= 2000 mg/kg bw. Based on molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be >= 2333.28 mg/kg bw.
LD 50 for mice > 2000 mg/kg bw. Based on molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw.
LD 50 for mice = 3040 (2670-3440) mg/kg bw. Based on molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be 3546.59 (3114.93-4013.25) mg/kg bw.
Acute dermal toxicity:
Weight of evidence: Read-across approach from experimental results obtained with analogues Fumaric Acid and Ammonium Sulphate. All results were higher than 2000 mg/kg bw.
Read-across approach from Fumaric Acid:
4h-LD 50 for New Zealand rabbits was higher than 20000 mg/kg bw. Based on these results and the molecular weights, the read-across approach is applied and the LD 50 for Ammonium acetate is calculated to be higher than 26556.42 mg/kg bw.
Read-across approach from Ammonium Sulphate:
The LD 50 for rats and mice was higher than 2000 mg/kg bw. Based on these results and the molecular weights, the read-across approach is applied and the LD50 for Ammonium Acetate is calculated to be > 2333.28 mg/kg bw for rats and mice.
Justification for classification or non-classification
Acute toxicity:
Oral: LD50 > 2000 mg/kg bw: non- classification
Dermal: LD50 > 2000 mg/kg bw: non- classification
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.