Ammonium acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated 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.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2010

Materials and methods

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

Test material

Test material information

Constituent 1

Reference substance name:

Fumaric acid

EC Number:

203-743-0

EC Name:

Fumaric acid

Cas Number:

110-17-8

IUPAC Name:

but-2-enedioic acid

Details on test material:

- Name of test material (as cited in study report): Fumaric Acid
- Molecular formula (if other than submission substance): C4H4O4
- Molecular weight (if other than submission substance): 116.07
- Smiles notation (if other than submission substance): O=C(O)/C=C/C(=O)O
- InChl (if other than submission substance): InChI=1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+
- Structural formula attached as image file (if other than submission substance): see Fig. in attached report

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

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.