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EC number: 231-984-1 | CAS number: 7783-20-2
- 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
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
In vitro
Ammonium sulfate was not mutagenic in bacteria (Ames test), yeasts, and mammalian cells (HPRT) with and without metabolic activation systems. It did not induce chromosomal aberrations in mammalian or human cell cultures.
In some cases, detailed data on purity are lacking. However, the terms "food grade" and "analytical grade" imply high purity.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Test with Salmonella typhimurium TA 102 or Escherichia coli WP2 strains not included.
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver S-9
- Test concentrations with justification for top dose:
- 20, 100, 500, 2500, 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: distilled water
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-o-phenylendiamine, 9-aminoacridine chloride monohydrate
- Remarks:
- positive control substance depending on the tester strain and activation condition; positive control substances were dissolved in dimethylsulfoxide (DMSO)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
NUMBER OF REPLICATIONS: 3 test plates per dose or per control
DETERMINATION OF CYTOTOXICITY
- Method: reduced his- background growth - Evaluation criteria:
- In general, a substance to be characterized as positive in the Ames test has to fulfill the following requirements:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results. - Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- adopted July 21, 1997
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Harlan Cytotest Cell Research GmbH, In Leppsteinswiesen 19, 64380 Rossdorf, Germany
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- hypoxanthine-guanine phosphoribosyl transferase (HPRT)
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/b-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 82.5, 165.0, 330.0, 660.0 and 1320.0 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: The solvent was chosen according to its solubility properties and its relative nontoxicity to the cells. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 7,12-dimethylbenzanthracene
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hour with and without metabolic activation, or 24 hours without metabolic activation
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 days
- Fixation time (start of exposure up to fixation or harvest of cells): 7 to 8 days
SELECTION AGENT (mutation assays): 6-thioguanine
NUMBER OF CELLS EVALUATED: 50 colonies
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- A test item is classified as positive if it induces either a concentration-related increase of the mutant frequency or a reproducible and positive response at one of the test points.
A test item producing neither a concentration-related increase of the mutant frequency nor a reproducible positive response at any of the test points is considered non-mutagenic in this system.
A positive response is described as follows:
A test item is classified as mutagenic if it reproducibly induces a mutation frequency that is three times above the spontaneous mutation frequency at least at one of the concentrations in the experiment.
The test item is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed.
However, in a case by case evaluation this decision depends on the level of the corresponding solvent control data. If there is by chance a low spontaneous mutation rate in the range normally found (3.0 – 33.2 mutants per 1000000 cells) a concentration-related increase of the mutations within this range has to be discussed. The variability of the mutation rates of solvent controls within all experiments of this study was also taken into consideration. - Statistics:
- A linear regression (least squares) was performed to assess a possible dose dependent increase of mutant frequencies using SYSTAT11 (SYSTAT Software, Inc., 501, Canal Boulevard, Suite C, Richmond, CA 94804, USA) statistics software. The number of mutant colonies obtained for the groups treated with the test item were compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05. However, both, biological and statistical significance were considered together.
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
The test medium was checked for precipitation or phase separation at the end of each treatment period (4 or 24 hours) before the test item was removed. No precipitation was observed up to the maximum concentration with and without metabolic activation.
There was no relevant change of the pH value and the osmolarity even at the maximum concentration of the test item.
RANGE-FINDING/SCREENING STUDIES: The highest concentration in the pre-experiment was 1320 µg/mL equal to approximately 10 mM.
COMPARISON WITH HISTORICAL CONTROL DATA:
ADDITIONAL INFORMATION ON CYTOTOXICITY: - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Limited documentation; only one dose level, no standard test system for chromosomal aberrations.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- 2 prepatation times and one concentration only
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- - Type and identity of media: McCoy's 5A medium supplemented with 20% fetal calf serum, 0.06 mL phytohemagglutinin M, 100 U/mL penicillin and 0.1 mg/mL dihydrostreptomycin sulfate.
- Metabolic activation:
- without
- Test concentrations with justification for top dose:
- ca. 423 mg/ml (3.2 M)
- Vehicle / solvent:
- water, medium or Alu I shipping buffer (KPO4 = 20 mM ; KC1= 50 mM; EDTA = 0 .1 mM ; dithioerythritol = 10 mM; glycerin = 50% (v/v); pH = 7.5)
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- no
- Details on test system and experimental conditions:
- Lymphocytes were isolated from whole blood in a Ficoll gradient. 1x10E6 lymphocytes were incubated in 5 mL plastic tubes in 2.5 mL McCoy's 5A medium.
METHOD OF APPLICATION: in medium
DURATION
The cultures were incubated for 50 h, including a treatment with colcemid (0.08 µg/ml) for 3 h. Treatment with Alu I, (NH4)2S04 or Alu I shipping buffer was done at culture times of 20 and 46 h.
SPINDLE INHIBITOR (cytogenetic assays): colcemid, 0.08 µg/ml
NUMBER OF REPLICATIONS: up to 7
NUMBER OF CELLS EVALUATED: 200 metaphases - Key result
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
Referenceopen allclose all
No increase in the number of his+ revertants was observed. No bacteriotoxic effect (reduced his- background growth) was observed. The test substance was completely soluble; no precipitation was observed at any concentration tested.
Under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, Ammonium sulphate is considered to be non-mutagenic in this HPRT assay.
Effects of the restriction endonuclease Alu I on chromosomes were more pronounced when the cells were treated additionally
with the test substance. The chromosomal aberrations rates in cells treated with ammonium sulfate alone were not increased. In control cells, 5.5% of aberrant metaphases in 200 analysed cells were observed. In cells treated with ammonium sulfate (20h), 6 % of aberrant metaphases were observed. The treatment with ammonnium sulfate induced no clastogenic effect in human lymphocytes.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
In vivo:
No in vivo genotoxicity tests are available. Based on the negative results from in vitro studies and the negative results in the bone marrow micronucleus test in vivo with ammonium chloride a mutagenic activity of ammonium sulfate in vivo is unlikely.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Limited documentation
- Principles of method if other than guideline:
- The maximum doses of the test compounds were determined by pilot experiments using the multisampling at multi-dose levels method according to Hayashi M et al (1984). A pilot experiment for the micronucleus test. The multi-sampling at multi-dose levels method. Mutat Res 141:, 165.
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- other: ddY
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
male ddY mice
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals, Shizuoka
- Age at study initiation: 8 weeks
- Diet (ad libitum): food pellets CE-2 (Japan Clea, Tokyo)
- Water: ad libitum
No further data.
ENVIRONMENTAL CONDITIONS: no data - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: physiol. saline
- Duration of treatment / exposure:
- single dose (pilot study) or 4 doses, divided by 24 hour intervals (see table below, Remarks on results)
- Post exposure period:
- 24 hours after dosing
- Dose / conc.:
- 62.5 mg/kg bw/day
- Remarks:
- single dosing
- Dose / conc.:
- 125 mg/kg bw/day
- Remarks:
- single dosing
- Dose / conc.:
- 250 mg/kg bw/day
- Remarks:
- single dosing
- Dose / conc.:
- 500 mg/kg bw/day
- Remarks:
- single dosing
- Dose / conc.:
- 31.3 mg/kg bw/day
- Remarks:
- multiple dosing
- Dose / conc.:
- 62.5 mg/kg bw/day
- Remarks:
- multiple dosing
- Dose / conc.:
- 125 mg/kg bw/day
- Remarks:
- multiple dosing
- Dose / conc.:
- 250 mg/kg bw/day
- Remarks:
- multiple dosing
- No. of animals per sex per dose:
- 6 mice per group
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- mitomycin C, 2.0 mg/kg bw
- Tissues and cell types examined:
- bone marrow (femur)
- Details of tissue and slide preparation:
- Mice were killed by cervical dislocation at the appropriate time after an administration. Femoral marrow cells were flushed out with fetal bovine serum and smeared on clean glass slides. Cells were fixed with methanol for 5 min, and stained with Acridine Orange for the pilot experiment and with Giemsa for the full-scale test.
The preparations were coded and analysed without any knowledge of the treatment. One thousand polychromatic erythrocytes per mouse were scored using a light microscope, with a high power objective (x 100), and the number of micronucleated polychromatic erythrocytes (MNPCEs) was recorded. The proportion of polychromatic erythrocytes (PCEs) among the total erythrocytes was also evaluated by observing 1000 erythrocytes on the same slide. - Statistics:
- The dose-response relationships were tested using the Cochran-Armitage trend test. A positive dose-response was considered significant at P < 0.05.
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Reference
There was no statistically significant increase in the frequency of micronucleated polychromatic erythrocytes.
Compound |
Route |
No. of doses |
Time between doses (hr) |
Sampling Time (hr) |
Dose level (mg/kg) |
NMPCE (%) |
PCE (%) |
Mortality |
Single dosing |
||||||||
Ammonium chloride |
ip |
1 |
24 |
0 62.5 125 250 500 |
0.18 +/- 0.18 0.12 +/- 0.12 0.15 +/- 0.14 0.13 +/- 0.05 0.12 + -/ 0.08 |
56.8 +/- 4.7 60.9 +/- 4.2 91.7 +/- 3.8 64.3 +/- 2.5 64.3 +/- 2.5 |
0/6 0/6 0/6 0/6 0/6 |
|
Mitomycin (positive control) |
ip |
1 |
24 |
2.0 |
4.18 +/- 1.30 * |
52.3 +/- 4.6 |
0/6 |
|
Repeated dosing |
||||||||
Ammonium chloride |
ip |
4 |
24 |
24 |
0 31.3 62.5 125 250 |
0.20 +/- 0.09 0.25 +/- 0.19 0.19 +/- 0.10 0.20 +/- 0.08 0.17 +/- 0.08 |
59.9 +/- 8.3 67.2 +/- 13.5 63.7 +/- 4.5 64.0 +/- 9.2 61.6 +/- 6.9 |
0/6 0/6 0/6 0/6 0/6 |
Mitomycin (positive control) |
ip |
1 |
24 |
2.0 |
7.15 +/- 3.92 * |
32.2 +/- 11.0 |
0/6 |
(*) p<0.01
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In vitro Studies
Ammonium sulfate (purity 99.5%) was not mutagenic in the standard plate and pre-incubation Ames test performed in 4 strains of Salmonella typhimurium (TA1535, TA100, TA1537, TA98) with and without a metabolic activation system up to and including the maximum tested concentration of 5000 µg/plate. No cytotoxic effects were observed (BASF, 1989).
Ammonium sulfate (food grade; no further data on purity) was also not mutagenic in Salmonella typhimurium strains TA1535, TA1537 and TA1538, and in Saccharomyces cerevisiae D4 with and without metabolic activation systems. Again, no cytotoxic effects were observed up to the highest tested concentration of 50000 ppm (Litton Bionetics, 1975).
Treatment of Chinese Hamster Ovary (CHO) (Tuschy and Obe, 1988) cells and treatment of human lymphocytes (Obe et al., 1986) with 3.2 M (423 mg/ml) ammonium sulfate (analytical grade; no further data on purity) in the absence of a metabolic activation system, did not result in chromosomal aberrations. However, ammonium sulfate enhanced the frequency of chromosome type aberrations, which had been induced by the restriction endonuclease Alu 1. A similar effect was observed with other salts (magnesium chloride, calcium chloride and sodium chloride), and is not indicative of a mutagenic effect of ammonium sulfate (Obe et al., 1986; Tuschy and Obe, 1988).
A study was performed to investigate the potential of Ammonium sulphate to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster (BASF, 2010). The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The highest concentration of 1320 µg/mL was equal to a molar concentration of about 10 mM. No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments. Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.
In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
In vivo Studies
There are no in vivo studies available with ammonium sulfate. Ammonium chloride (99.7% pure) gave negative results in a micronucleus test in mice (Hayashi et al., 1988). This micronucleus test was conducted with bone marrow in ddY mice. Animals had received a single and 4 times i.p. injection. A single dose test and 4 times dose test were dosed with 62.5 - 500 mg/kg and 31.3 - 250 mg/kg as MTD (maximum tolerated dose), respectively, with mitomycin C as positive control. No increase of erythrocytes with micronuclei was observed at any group. The potential of ammonium sulfate to induce mutagenic effects in vivo is considered to be negligible, because there is no evidence of a mutagenic effect from in vitro studies.
Justification for classification or non-classification
Classification,
Labelling, and Packaging Regulation (EC) No 1272/2008
The
available experimental test data are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. Based on the
available data, the substance is not considered to be classified for
genetic toxicity under Regulation (EC) No 1272/2008, as amended for the
ninth time in Regulation (EU) No 2016/1179.
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