Ammonium acetate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

05.01.93 - 07.01.93

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: EU Method C.2 and GLP. There is no evidence that the concentration of the substance was maintained during the test. However, high concentrations up to 1000 mg/L were used and no immobilisation was observed.

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

yes

Remarks:

(there is no evidence that the concentration of the substance was maintained during the test).

GLP compliance:

yes

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna Straus
- Strain: Clone 5
- Source: own breeding
- Feeding during test: no

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Test temperature:

20 ± 1 ºC

pH:

7.4-7.5

Dissolved oxygen:

7.3-8.3 mg/L

Nominal and measured concentrations:

Nominal concentrations: 0, 20, 40, 60, 100, 200, 300, 600 and 1000 mg/L

Details on test conditions:

TEST SYSTEM
- Aeration: no
- No. of organisms per vessel: 5 organism per vessel
- No. of vessels per concentration (replicates): 4 replicates per concentration
- No. of vessels per control (replicates): 4 replicates with 5 organism per vessel

EFFECT PARAMETERS MEASURED (with observation intervals if applicable): immobilisation

Reference substance (positive control):

yes

Remarks:

(Kalium dichromat)

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

> 1 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 1 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Results with reference substance (positive control):

- Duration of exposure: 24 h
- At the concentration of 0.9 mg/l the percentage of immobilisation observed was 5%.
- At the concentration of 1.9 mg/l the percentage of immobilisation observed was 95%.

Table 6.1.3-01: Daphnia magna: immobilisation

 

Concentration (mg/l)	24 h			48 h
	Number		%	Number		%
	Mobile	Immobile	Immobile	Mobile	Immobile	Immobile
Control	20	0	0	20	0	0
20	20	0	0	20	0	0
40	19	1	5	19	1	5
60	20	0	0	20	0	0
100	19	1	5	19	1	5
200	21	0	0	21	0	0
300	21	0	0	21	0	0
600	20	0	0	20	0	0
1000	20	0	0	20	0	0

 

Validity criteria fulfilled:

no

Remarks:

(no immobilization was observed in the controls, the conditions were constant during the test, the dissolved oxygen concentration was in the acceptable range. However, there is no evidence that the substance concentration was maintained during the test).

Conclusions:

The 24h-EC50 for Daphnia magna was greater than 1000 mg/L. The 48-h EC50 for Daphnia magna was greater than 1000 mg/L.

Executive summary:

An acute toxicity test was performed with Daphnia magna in a static system. Twenty animals were exposed per concentration. The nominal concentrations used in the test were : 0, 20, 40, 60, 100, 200, 300, 600 and 1000 mg/L. The 24h-EC50 was greater than 1000 mg/L. The 48-h EC50 was greater than 1000 mg/L.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method was according to OECD 202 and GLP compliance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

Measured concentrations:
560: 564 mg/L (afetr 24h) and 564 mg/L (after 48h)
1000: 823 mg/L (after 24h) and 919 mg/L (after48h)

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The substance was directly weighed into the test vessels, with diluted water, mixed and homogenized with the Ultra-Turrax and ultrasonic bath.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna STRAUS
- Source: Department of Toxicology (Hoechst AG)

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

Test: GH: 2.7- 2.8 mmol/L

Test temperature:

Test: 20.0 ºC - 21.5 ºC, control: 20.8 ºC - 21.4 ºC.

pH:

Test: 8.0-8.3, control: 8.2-8.4.

Dissolved oxygen:

Test: 8.8-9.7, control: 8.6-9.5

Nominal and measured concentrations:

Nominal concentrations: 0, 560, 1000 mg/L of test substance LP 1848.
Measured concentrations:
560: 564 mg/L (afetr 24h) and 564 mg/L (after 48h)
1000: 823 mg/L (after 24h) and 919 mg/L (after48h)

Details on test conditions:

TEST SYSTEM
- Test vessel:
- Material, size, headspace, fill volume: test containers were 300 mL crystall (height 55 mm, diameter 95 mm, high water levels ca, 32 mm) filled with 200 ml of test water, the temperature in the test room was 20.0 - 22.0 ° C.
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates):2
- No. of vessels per control (replicates):4=2+2
- No. of vessels per vehicle control (replicates):1

OTHER TEST CONDITIONS
- Photoperiod: The illumination was carried out on fluorescent tubes in a day / night rhythm of 12 hours.

Reference substance (positive control):

no

Duration:

24 h

Dose descriptor:

EC0

Effect conc.:

564 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

dissolved

Basis for effect:

mobility

Remarks on result:

other: (Results for test substance LP1848)

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

> 919 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

dissolved

Basis for effect:

mobility

Remarks on result:

other: (Results for test substance LP1848)

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

564 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

dissolved

Basis for effect:

mobility

Remarks on result:

other: (Results for test substance LP1848)

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 919 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

dissolved

Basis for effect:

mobility

Remarks on result:

other: (Results for test substance LP1848)

Details on results:

- Other biological observations: mobility; Daphnia is considered to be one to swim, it should show after slight touch of the experimental vessel within 15 seconds swimming movements
- Mortality of control: 0

In examining the acute toxicity of the test substance LP1848 (50 % water solution of Potassium Acetate) in Daphnia magna for a total of 48 hours, results were as follows:

EC0 (24h) = 564 mg/L and EC0 (48h) = 564 mg/L (282 mg/L of Potassium acetate).

EC50 (24h) > 919 mg/L and EC50 (48h) > 919 mg/L (459.5 mg/L of Potassium acetate).

Validity criteria fulfilled:

yes

Conclusions:

In examining the acute toxicity of the test substance LP1848 (50 % water solution of Potassium Acetate) in Daphnia magna , results were as follows:
EC0 (24h) = 564 mg/L and EC0 (48h) = 564 mg/L (282 mg/L of Potassium acetate).
EC50 (24h) > 919 mg/L and EC50 (48h) > 919 mg/L (> 459.5 mg/L of Potassium acetate).

Executive summary:

In examining the acute toxicity of the test substance LP1848 (50 % water solution of Potassium Acetate) in Daphnia magna , results were as follows:

Nominal EC0 (24h) = 564 mg/L and measured EC0 (48h) = 564 mg/L (282 mg/L of Potassium acetate).

Nominal EC50 (24h) > 919 mg/L and measured EC50 (48h) > 919 mg/L (> 459.5mg/L of Potassium acetate).

The 560 mg/L group showed no changes compared to the control group.
In the groups with 1000 mg /L, immobility occurred in only one of 20 animals.

To determine the matter content were taken after 0 and 48 hours water samples. The analysis values were averaged over 80% of target concentration.

In the test, all control parameters were within the recommended range.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

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 Sodium acetate which shares the same functional group with Ammonium acetate, also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

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 Letter of Access experimental data (EU Method C.2 and GLP) on the analogue Sodium acetate.

GLP compliance:

yes

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: 324 ºC
- Boiling point: Decomposes above 400 °C
- Vapour pressure: 0.00000000537 mm Hg at 25 ºC
- Henry's law constant (for volatie substances): 5.5 E -07 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 1.25 g/mL at 25 ºC
- Solubility in organic solvents: In ethanol: 0.053 g/cm3 at 25 ºC
- log Pow: -3.72
- pKa: At 20 ºC, it ranged from 1.26 to 1.45. At 25 ºC, it ranged from 0.18 to 0.20.

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

> 939.66 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 939.66 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

Based on the experimental results obtained with the analogue Sodium acetate (48-h EC 50 > 1000 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the EC 50 for the substance Ammonium acetate is calculated to be > 939.66 mg/L under test conditions.

The analogue Sodium 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 Sodium Acetate and -2.79 for Ammonium acetate,
- a high water solubility, which is 1.25 g/mL at 25 ºC for Sodium acetate and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 82.0 for Sodium acetate and 77.08 for Ammonium acetate.

The (48 h) EC 50 for the substance Ammonium acetate is calculated to be > 939.66 mg/L (basis for effect: mobility).

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) EC 50 for the substance Ammonium acetate is calculated to be > 939.66 mg/L (basis for effect: mobility).

Executive summary:

Based on the experimental results (reported under the endpoint record 06.01.03_01 NaAc) obtained with the analogue Sodium acetate (48-h EC 50 > 1000 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the EC 50 for the substance Ammonium acetate is calculated to be > 939.66 mg/L under test conditions (basis for effect: mobility).

Reference 4

Endpoint:

short-term toxicity to aquatic invertebrates

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 aquatic toxicity endpoints.

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 Letter of Access experimental data (OECD 202 and GLP) on the analogue Potassium acetate.

GLP compliance:

yes

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: ca. 292 ºC
- Boiling point: 392.35 ºC
- Vapour pressure: 1.37 E -08 mmHg at 25 ºC
- Water solubility (under test conditions): 2.5 g/mL at 20 ºC
- Henry's law constant: 1.76 E -15 atm.m3/mole
- log Pow: -3.72
- pKa: 0.27 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable.

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 360.89 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

221.49 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

> 360.89 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

24 h

Dose descriptor:

EC0

Effect conc.:

221.49 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

Based on the experimental results obtained with the analogue Potassium acetate (48-h EC 50 > 459.5 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the EC 50 for the substance Ammonium acetate is calculated to be > 360.89 mg/L under test conditions.

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 high 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.

The (48 h) EC 50 for the substance Ammonium acetate is calculated to be > 360.89 mg/L (basis for effect: mobility).

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) EC 50 for the substance Ammonium acetate is calculated to be > 360.89 mg/L (basis for effect: mobility).

Executive summary:

Based on the experimental results (reported under the endpoint record 06.01.03_02 KAc) obtained with the analogue Potassium acetate (48-h EC 50 > 459.5 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the EC 50 for the substance Ammonium acetate is calculated to be > 360.89 mg/L under test conditions.

Reference 5

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data on test method.

Principles of method if other than guideline:

No data on test method.

GLP compliance:

not specified

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

No data

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

189 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

In a static bioassay, the (48 h) LC50 for Daphnia magna was 189 mg/L.

Validity criteria fulfilled:

not applicable

Conclusions:

In a static bioassay, the (48 h) LC50 for Daphnia magna was 189 mg/L.

Executive summary:

In a static bioassay, the (48 h) LC50 for Daphnia magna was 189 mg/L.

Reference 6

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

No data on test method.

GLP compliance:

not specified

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

not specified

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

No data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

24 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

The (48 h) LC50 for Daphnia magna was 24 mg/L.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC50 for Daphnia magna was 24 mg/L.

Executive summary:

The (48 h) LC50 for Daphnia magna was 24 mg/L.

Reference 7

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data on test method.

Principles of method if other than guideline:

No data on test method.

GLP compliance:

not specified

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia pulex

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

No data

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

187 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

In a static bioassay, the (48 h) LC50 for Daphnia pulex was 187 mg/L.

Validity criteria fulfilled:

not applicable

Conclusions:

In a static bioassay, the (48 h) LC50 for Daphnia pulex was 187 mg/L.

Executive summary:

In a static bioassay, the (48 h) LC50 for Daphnia pulex was 187 mg/L.

Reference 8

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data on test method.

Principles of method if other than guideline:

No data on test method.

GLP compliance:

not specified

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

other aquatic crustacea: Ceriodaphnia reticulata

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

No data

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

131 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

In a static bioassay, the (48 h) LC50 for Ceriodaphnia reticulata was 131 mg/L.

Validity criteria fulfilled:

not applicable

Conclusions:

In a static bioassay, the (48 h) LC50 for Ceriodaphnia reticulata was 131 mg/L.

Executive summary:

In a static bioassay, the (48 h) LC50 for Ceriodaphnia reticulata was 131 mg/L.

Reference 9

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data on test method.

Principles of method if other than guideline:

No data on test method.

GLP compliance:

not specified

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

other aquatic crustacea: Simocephalus vetulus

Test type:

not specified

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

No data

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

123 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

The (48 h) LC50 for Simocephalus vetulus was 123 mg/L.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC50 for Simocephalus vetulus was 123 mg/L.

Executive summary:

The (48 h) LC50 for Simocephalus vetulus was 123 mg/L.

Reference 10

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across approach from published experimental data on the analogue Ammonia.

GLP compliance:

not specified

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: - 77.7 ºC
- Boiling point: - 33.35 ºC
- Vapour pressure: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)
- Henry's law constant (for volatie substances): 1.61E -05 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 531 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 ºC.
- Solubility in organic solvents: In ethanol: 15 % in 95% alcohol at 20 ºC
- log Pow: - 1.14 at 25 ºC
- pKa: 9.25 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

856.95 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

Based on the experimental results obtained with the analogue Ammonia (48-h LC 50 = 189 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 856.95 mg/L under test conditions.

The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,
- a high water solubility, which is 531 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

The analogue Ammonia shares the functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:

- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,

- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and

- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

Table 1. Data matrix, Analogue approach.

CAS Number		Source chemical 7664-41-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonia	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Measured data: -77.7 ºC	Experimental data: 114 ºC
Boiling Point		Measured data: -33.35 ºC	Estimated data: 312.76 ºC
Density		Measured data: 0.7710 g/L at 760 mm Hg	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Measured data: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Measured data: - 1.14 at 25 ºC	Estimated data: -2.79
Water solubility		Measured data: 531 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 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		Experimental data:   (96 h) LC50 for Fathead minnows = 8.2 mg/L (hard water, conditions of bioassay not specified) (24-96 h) LC50 for Goldfish = 2 - 2.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Coho salmon = 0.45 mg/L (Flow-through bioassay) (72 h) LC50 for Guppy fry = 74 mg/L (Static bioassay) (72 h) LC50 Guppy fry = 1.26 mg/L (Static bioassay) (96 h) LC50 for Cutthroat trout (Salmo clarki) fry = 0.5-0.8 mg/L (Flow-through bioassay) (24 h) LC50 for Rainbow trout fertilized egg > 3.58 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout alevins (0-50 days old) > 3.58 mg/L (Static bioassay) LC50 for Rainbow trout fry (85 days old) = 0.068 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout adult = 0.097 mg/L (Static bioassay) (48 h) LC50 for Walking catfish = 0.28 mg/L (Static bioassay) (96 h) LC50 for Salmo aguabonita = 0.76 mg/L (Conditions of bioassay not specified) (18 h) LC50 for Salmo trutta > 0.15 mg/L (Conditions of bioassay not specified) LC50 for Oncorhynchus tschawytscha = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salvelinus fontinalis = 0.96-1.05 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Proposium williamsoni = 0.47 mg/L (Conditions of bioassay not specified) LC50 for Catostomus platyrhynchos = 0.67-0.82 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo trutta = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (late alevins) = 0.083 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (eyed embryos) > 1.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus kisutch = 0.55 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo salar = 0.28 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Lepomis macrochirus = 0.26-4.6 mg/L (Conditions of bioassay not specified)	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) LC50 for Daphnia magna = 189 mg/L (Static bioassay) (48 h) LC50 for Daphnia magna = 24 mg/L (Conditions of bioassay not specified) (48 h) LC50 for Daphnia pulex = 187 mg/L (Static bioassay) (48 h) LC50 for Ceriodaphnia reticulate = 131 mg/L (Static bioassay) (48 h) LC50 for Simocephalus vetulus = 123 mg/L (Conditions of bioassay not specified)	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		No data	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: LD50 = 350 mg/kg bw (rat)	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: (1 h) LC50 = 7,050 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (cat) (1 h) LC50 = 746 mg/m3 (Cat, dynamic air flow) (Cat) (1 h) LC50 = 7,050 mg/m3 (Cat, static conditions) (2 h) LC50 = 7,600 mg/m3 (rat) (1 h) LC50 = 5,100 mg/m3 (rat) (1 h) LCLo = 1,400 mg/m3 (rat) (10 min) LC50 = 7,105 mg/m3 (mouse) (1 h) LC50 = 3,360 mg/m3 (mouse) (2 h) LC50 = 3,310 mg/m3 (mouse)	No data
Acute Toxicity: Dermal		No data	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: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant.	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: Ammonia in the form of a gas or an aqueous solution is a recognized eye irritant.	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		Repeated dose toxicity: Inhalation   Experimental data:   Rats exposed to 470 mg/m3 continuously found focal or diffuse interstitial pneumonitis in all with epithelial calcification in renal tubules & bronchi, epithelial proliferation of renal tubules, myocardial fibrosis & fatty liver.   49 and 51 rats were exposed continuously for 90 days at 262 mg/m3 and for 65 days at 455 mg/m3 respectively. 262 mg/m3 produced mild nasal discharge in about 25%. All 51 rats exposed at 455mg/m3 showed mild dyspnea & nasal irritation. There were 32 deaths by day 25 and 50by day 65.   One pig exposed to 280 ppm of ammonia showed immediate irritation of the nose and mouth and abnormal respiratory patterns, and by the 36th hour of exposure had convulsions and extremely shallow and irregular breathing. Convulsions continued for 3 hours after exposure ended but the animal appeared normal several hours later. In each of 2 trials, 4 exposure groups of 9 pigs each were continuously exposed to ammonia for 5 weeks. Data from both trials were combined for analysis. Concentrations of ammonia were measured daily, and the average exposures of the groups were 12, 61, 103, and 145 ppm. Feed consumption and average daily weight gain were adversely affected by increasing ammonia concentrations. Pigs exposed to the 3 higher concentrations had excessive nasal, lacrymal, and oral secretions, but these were less pronounced in those exposed to 61 ppm. Pigs exposed to 61 ppm appeared to adjust within 3-4 days, so that their secretory rate was only slightly higher than that of animals exposed to 12 ppm. Pigs in the 2 higher concentrations coughed approximately 3 times as much as those in the lower, and coughing at 61 ppm was slightly more frequent than at 12 ppm. Five animals from each exposure group were autopsied and all gross and microscopic findings were normal.   12 guinea pigs were exposed to about 170 ppm ammonia for 6 hours a day, 5 days a week for up to 18 weeks. Chamber concentrations were monitored and ranged from 140-200 ppm. The exposed animals and 6 controls were weighed weekly. No adverse effects were observed by autopsy of the 4 exposed and 2 control animals killed after 6 weeks or after 12 weeks. In 4 animals exposed for 18 weeks, there was congestion of spleens, livers, and kidneys with early degenerative changes in suprarenal glands. Increased blood destruction was suggested by higher quantities of hemosiderin in the spleens. In the upper tubules of the kidneys there was cloudy swelling with precipitated albumin in the lumen and some casts. These changes were also seen in the lower tubules of 2 animals. The cells of the suprarenal glands were swollen and the cytoplasm in some areas had lost its normal granular structure.   Results of an unstated number of rabbits and cats for 1 hour to initial concentrations of 3.5-8.7 mg/L (approximately 5,200-12,800 ppm) of ammonia with an average concentration of 7.0 mg/L (approximately 10,360 ppm) was reported to be the "approximate LC50." The static method of gassing used probably resulted in an average concentration of half the initial concentrations or less. Also evaluated was the gas absorption of the nasobuccopharyngeal section of the respiratory tract. Rabbits which inhaled directly through a tracheal cannula, and a second group inhaled normally through nose, mouth, and throat. The mean survival time in the second group was reported to be almost twice that of the first group, 33 hr versus 18 hr. On microscopic examination, the trachea was congested and edematous. The mucosa was necrotic and sloughed off in 80-90% of the animals in which the upper respiratory tract had been bypassed, while the trachea was normal in appearance in the second group of test animals. Similar differential findings, but to a lesser degree, were shown in the bronchial mucosa. The damage to the bronchioles and alveoli surprisingly appeared to be identical in both groups. It was described as congestion, edema, hemorrhage, and atelectasis with emphysema. The upper respiratory tract acted as a protection only to the trachea and bronchi, and that small airways and alveoli were less resistant to ammonia injury in many cases within 10 minutes. Between the 6th and 10th postexposure days, 7 of the 80 died, compared with no deaths in controls.Autopsies were not performed.   Pullets exposed to 200 ppm atmospheric ammonia for 17 days had reduced feed intake & reduced growth rate when compared to controls. After the ammonia exposure period at point of lay, percent egg production was less & mortality was greater for exposed group than controls.	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/). Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/. 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:   Negative in all strains (Salmonella typhimuriumTA98, TA100, TA1535, TA1537, TA1538 andEscherichia coliWP2uvrA) with and without S9 metabolic activation.	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	No data	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:   Life-long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain.   Male Sprague Dawley rats were exposed for 24 weeks to drinking water containing 83 mg/L N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Subsequently, half of the males were exposed to water containing 0.01% ammonia solution and the other half to tap water for a period of 24 weeks. Chronic oral exposure to a 0.01% ammonia solution via the drinking water exerts a promoting effect on gastric cancer in the rat induced by MNNG. Gross pathology: In the treatment group, 3 out of 37 and in the control group 0 out of 39 rats had metastasis in the liver. The number of rats with gastric tumors was 12 out of 39 in the control group and 26 out of 37 in the treatment group. The number of gastric cancers per tumor bearing rat was significantly higher in ammonia treated rats when compared to control rats, 2.1 and 1.3 respectively. Histopathology: All animals showed signs of gastritis.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: From 2-4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low (mean 7 ppm) or moderate (mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain (MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain (MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetus-to-corpus luteum ratio were all similar between the two groups.   DEVELPMENTAL 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.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC 50 for the substance Ammonium acetate is calculated to be 856.95 mg/L under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint report 06.01.03_05 Ammonia) obtained with the analogue Ammonia (48-h LC 50 = 189 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 856.95 mg/L under test conditions.

Reference 11

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across approach from published experimental data on the analogue Ammonia.

GLP compliance:

not specified

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: - 77.7 ºC
- Boiling point: - 33.35 ºC
- Vapour pressure: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)
- Henry's law constant (for volatie substances): 1.61E -05 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 ºC.
- Solubility in organic solvents: In ethanol: 15 % in 95% alcohol at 20 ºC
- log Pow: - 1.14 at 25 ºC
- pKa: 9.25 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

108.81 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

Based on the experimental results obtained with the analogue Ammonia (48-h LC 50 = 24 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 108.81 mg/L under test conditions.

The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,
- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

The analogue Ammonia shares the functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:

- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,

- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and

- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

Table 1. Data matrix, Analogue approach.

CAS Number		Source chemical 7664-41-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonia	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Measured data: -77.7 ºC	Experimental data: 114 ºC
Boiling Point		Measured data: -33.35 ºC	Estimated data: 312.76 ºC
Density		Measured data: 0.7710 g/L at 760 mm Hg	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Measured data: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Measured data: - 1.14 at 25 ºC	Estimated data: -2.79
Water solubility		Measured data: 531 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 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		Experimental data:   (96 h) LC50 for Fathead minnows = 8.2 mg/L (hard water, conditions of bioassay not specified) (24-96 h) LC50 for Goldfish = 2 - 2.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Coho salmon = 0.45 mg/L (Flow-through bioassay) (72 h) LC50 for Guppy fry = 74 mg/L (Static bioassay) (72 h) LC50 Guppy fry = 1.26 mg/L (Static bioassay) (96 h) LC50 for Cutthroat trout (Salmo clarki) fry = 0.5-0.8 mg/L (Flow-through bioassay) (24 h) LC50 for Rainbow trout fertilized egg > 3.58 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout alevins (0-50 days old) > 3.58 mg/L (Static bioassay) LC50 for Rainbow trout fry (85 days old) = 0.068 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout adult = 0.097 mg/L (Static bioassay) (48 h) LC50 for Walking catfish = 0.28 mg/L (Static bioassay) (96 h) LC50 for Salmo aguabonita = 0.76 mg/L (Conditions of bioassay not specified) (18 h) LC50 for Salmo trutta > 0.15 mg/L (Conditions of bioassay not specified) LC50 for Oncorhynchus tschawytscha = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salvelinus fontinalis = 0.96-1.05 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Proposium williamsoni = 0.47 mg/L (Conditions of bioassay not specified) LC50 for Catostomus platyrhynchos = 0.67-0.82 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo trutta = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (late alevins) = 0.083 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (eyed embryos) > 1.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus kisutch = 0.55 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo salar = 0.28 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Lepomis macrochirus = 0.26-4.6 mg/L (Conditions of bioassay not specified)	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) LC50 for Daphnia magna = 189 mg/L (Static bioassay) (48 h) LC50 for Daphnia magna = 24 mg/L (Conditions of bioassay not specified) (48 h) LC50 for Daphnia pulex = 187 mg/L (Static bioassay) (48 h) LC50 for Ceriodaphnia reticulate = 131 mg/L (Static bioassay) (48 h) LC50 for Simocephalus vetulus = 123 mg/L (Conditions of bioassay not specified)	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		No data	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: LD50 = 350 mg/kg bw (rat)	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: (1 h) LC50 = 7,050 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (cat) (1 h) LC50 = 746 mg/m3 (Cat, dynamic air flow) (Cat) (1 h) LC50 = 7,050 mg/m3 (Cat, static conditions) (2 h) LC50 = 7,600 mg/m3 (rat) (1 h) LC50 = 5,100 mg/m3 (rat) (1 h) LCLo = 1,400 mg/m3 (rat) (10 min) LC50 = 7,105 mg/m3 (mouse) (1 h) LC50 = 3,360 mg/m3 (mouse) (2 h) LC50 = 3,310 mg/m3 (mouse)	No data
Acute Toxicity: Dermal		No data	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: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant.	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: Ammonia in the form of a gas or an aqueous solution is a recognized eye irritant.	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		Repeated dose toxicity: Inhalation   Experimental data:   Rats exposed to 470 mg/m3 continuously found focal or diffuse interstitial pneumonitis in all with epithelial calcification in renal tubules & bronchi, epithelial proliferation of renal tubules, myocardial fibrosis & fatty liver.   49 and 51 rats were exposed continuously for 90 days at 262 mg/m3 and for 65 days at 455 mg/m3 respectively. 262 mg/m3 produced mild nasal discharge in about 25%. All 51 rats exposed at 455mg/m3 showed mild dyspnea & nasal irritation. There were 32 deaths by day 25 and 50by day 65.   One pig exposed to 280 ppm of ammonia showed immediate irritation of the nose and mouth and abnormal respiratory patterns, and by the 36th hour of exposure had convulsions and extremely shallow and irregular breathing. Convulsions continued for 3 hours after exposure ended but the animal appeared normal several hours later. In each of 2 trials, 4 exposure groups of 9 pigs each were continuously exposed to ammonia for 5 weeks. Data from both trials were combined for analysis. Concentrations of ammonia were measured daily, and the average exposures of the groups were 12, 61, 103, and 145 ppm. Feed consumption and average daily weight gain were adversely affected by increasing ammonia concentrations. Pigs exposed to the 3 higher concentrations had excessive nasal, lacrymal, and oral secretions, but these were less pronounced in those exposed to 61 ppm. Pigs exposed to 61 ppm appeared to adjust within 3-4 days, so that their secretory rate was only slightly higher than that of animals exposed to 12 ppm. Pigs in the 2 higher concentrations coughed approximately 3 times as much as those in the lower, and coughing at 61 ppm was slightly more frequent than at 12 ppm. Five animals from each exposure group were autopsied and all gross and microscopic findings were normal.   12 guinea pigs were exposed to about 170 ppm ammonia for 6 hours a day, 5 days a week for up to 18 weeks. Chamber concentrations were monitored and ranged from 140-200 ppm. The exposed animals and 6 controls were weighed weekly. No adverse effects were observed by autopsy of the 4 exposed and 2 control animals killed after 6 weeks or after 12 weeks. In 4 animals exposed for 18 weeks, there was congestion of spleens, livers, and kidneys with early degenerative changes in suprarenal glands. Increased blood destruction was suggested by higher quantities of hemosiderin in the spleens. In the upper tubules of the kidneys there was cloudy swelling with precipitated albumin in the lumen and some casts. These changes were also seen in the lower tubules of 2 animals. The cells of the suprarenal glands were swollen and the cytoplasm in some areas had lost its normal granular structure.   Results of an unstated number of rabbits and cats for 1 hour to initial concentrations of 3.5-8.7 mg/L (approximately 5,200-12,800 ppm) of ammonia with an average concentration of 7.0 mg/L (approximately 10,360 ppm) was reported to be the "approximate LC50." The static method of gassing used probably resulted in an average concentration of half the initial concentrations or less. Also evaluated was the gas absorption of the nasobuccopharyngeal section of the respiratory tract. Rabbits which inhaled directly through a tracheal cannula, and a second group inhaled normally through nose, mouth, and throat. The mean survival time in the second group was reported to be almost twice that of the first group, 33 hr versus 18 hr. On microscopic examination, the trachea was congested and edematous. The mucosa was necrotic and sloughed off in 80-90% of the animals in which the upper respiratory tract had been bypassed, while the trachea was normal in appearance in the second group of test animals. Similar differential findings, but to a lesser degree, were shown in the bronchial mucosa. The damage to the bronchioles and alveoli surprisingly appeared to be identical in both groups. It was described as congestion, edema, hemorrhage, and atelectasis with emphysema. The upper respiratory tract acted as a protection only to the trachea and bronchi, and that small airways and alveoli were less resistant to ammonia injury in many cases within 10 minutes. Between the 6th and 10th postexposure days, 7 of the 80 died, compared with no deaths in controls.Autopsies were not performed.   Pullets exposed to 200 ppm atmospheric ammonia for 17 days had reduced feed intake & reduced growth rate when compared to controls. After the ammonia exposure period at point of lay, percent egg production was less & mortality was greater for exposed group than controls.	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/). Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/. 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:   Negative in all strains (Salmonella typhimuriumTA98, TA100, TA1535, TA1537, TA1538 andEscherichia coliWP2uvrA) with and without S9 metabolic activation.	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	No data	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:   Life-long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain.   Male Sprague Dawley rats were exposed for 24 weeks to drinking water containing 83 mg/L N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Subsequently, half of the males were exposed to water containing 0.01% ammonia solution and the other half to tap water for a period of 24 weeks. Chronic oral exposure to a 0.01% ammonia solution via the drinking water exerts a promoting effect on gastric cancer in the rat induced by MNNG. Gross pathology: In the treatment group, 3 out of 37 and in the control group 0 out of 39 rats had metastasis in the liver. The number of rats with gastric tumors was 12 out of 39 in the control group and 26 out of 37 in the treatment group. The number of gastric cancers per tumor bearing rat was significantly higher in ammonia treated rats when compared to control rats, 2.1 and 1.3 respectively. Histopathology: All animals showed signs of gastritis.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: From 2-4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low (mean 7 ppm) or moderate (mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain (MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain (MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetus-to-corpus luteum ratio were all similar between the two groups.   DEVELPMENTAL 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.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC 50 for the substance Ammonium acetate is calculated to be 108.81 mg/L under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint report 06.01.03_06 Ammonia) obtained with the analogue Ammonia (48-h LC 50 = 24 mg/L for Daphnia magna in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 108.81 mg/L under test conditions.

Reference 12

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

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 on the analogue Ammonia.

GLP compliance:

not specified

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: - 77.7 ºC
- Boiling point: - 33.35 ºC
- Vapour pressure: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)
- Henry's law constant (for volatie substances): 1.61E -05 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 ºC.
- Solubility in organic solvents: In ethanol: 15 % in 95% alcohol at 20 ºC
- log Pow: - 1.14 at 25 ºC
- pKa: 9.25 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

847.88 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

Based on the experimental results obtained with the analogue Ammonia (48-h LC 50 = 187 mg/L for Daphnia pulex in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 847.88 mg/L under test conditions.

The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,
- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

The analogue Ammonia shares the functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:

- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,

- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and

- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

Table 1. Data Matrix, Analogue Approach.

CAS Number		Source chemical 7664-41-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonia	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Measured data: -77.7 ºC	Experimental data: 114 ºC
Boiling Point		Measured data: -33.35 ºC	Estimated data: 312.76 ºC
Density		Measured data: 0.7710 g/L at 760 mm Hg	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Measured data: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Measured data: - 1.14 at 25 ºC	Estimated data: -2.79
Water solubility		Measured data: 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 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		Experimental data:   (96 h) LC50 for Fathead minnows = 8.2 mg/L (hard water, conditions of bioassay not specified) (24-96 h) LC50 for Goldfish = 2 - 2.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Coho salmon = 0.45 mg/L (Flow-through bioassay) (72 h) LC50 for Guppy fry = 74 mg/L (Static bioassay) (72 h) LC50 Guppy fry = 1.26 mg/L (Static bioassay) (96 h) LC50 for Cutthroat trout (Salmo clarki) fry = 0.5-0.8 mg/L (Flow-through bioassay) (24 h) LC50 for Rainbow trout fertilized egg > 3.58 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout alevins (0-50 days old) > 3.58 mg/L (Static bioassay) LC50 for Rainbow trout fry (85 days old) = 0.068 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout adult = 0.097 mg/L (Static bioassay) (48 h) LC50 for Walking catfish = 0.28 mg/L (Static bioassay) (96 h) LC50 for Salmo aguabonita = 0.76 mg/L (Conditions of bioassay not specified) (18 h) LC50 for Salmo trutta > 0.15 mg/L (Conditions of bioassay not specified) LC50 for Oncorhynchus tschawytscha = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salvelinus fontinalis = 0.96-1.05 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Proposium williamsoni = 0.47 mg/L (Conditions of bioassay not specified) LC50 for Catostomus platyrhynchos = 0.67-0.82 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo trutta = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (late alevins) = 0.083 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (eyed embryos) > 1.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus kisutch = 0.55 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo salar = 0.28 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Lepomis macrochirus = 0.26-4.6 mg/L (Conditions of bioassay not specified)	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) LC50 for Daphnia magna = 189 mg/L (Static bioassay) (48 h) LC50 for Daphnia magna = 24 mg/L (Conditions of bioassay not specified) (48 h) LC50 for Daphnia pulex = 187 mg/L (Static bioassay) (48 h) LC50 for Ceriodaphnia reticulate = 131 mg/L (Static bioassay) (48 h) LC50 for Simocephalus vetulus = 123 mg/L (Conditions of bioassay not specified)	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		No data	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: LD50 = 350 mg/kg bw (rat)	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: (1 h) LC50 = 7,050 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (cat) (1 h) LC50 = 746 mg/m3 (Cat, dynamic air flow) (Cat) (1 h) LC50 = 7,050 mg/m3 (Cat, static conditions) (2 h) LC50 = 7,600 mg/m3 (rat) (1 h) LC50 = 5,100 mg/m3 (rat) (1 h) LCLo = 1,400 mg/m3 (rat) (10 min) LC50 = 7,105 mg/m3 (mouse) (1 h) LC50 = 3,360 mg/m3 (mouse) (2 h) LC50 = 3,310 mg/m3 (mouse)	No data
Acute Toxicity: Dermal		No data	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: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant.	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: Ammonia in the form of a gas or an aqueous solution is a recognized eye irritant.	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		Repeated dose toxicity: Inhalation   Experimental data:   Rats exposed to 470 mg/m3 continuously found focal or diffuse interstitial pneumonitis in all with epithelial calcification in renal tubules & bronchi, epithelial proliferation of renal tubules, myocardial fibrosis & fatty liver.   49 and 51 rats were exposed continuously for 90 days at 262 mg/m3 and for 65 days at 455 mg/m3 respectively. 262 mg/m3 produced mild nasal discharge in about 25%. All 51 rats exposed at 455mg/m3 showed mild dyspnea & nasal irritation. There were 32 deaths by day 25 and 50by day 65.   One pig exposed to 280 ppm of ammonia showed immediate irritation of the nose and mouth and abnormal respiratory patterns, and by the 36th hour of exposure had convulsions and extremely shallow and irregular breathing. Convulsions continued for 3 hours after exposure ended but the animal appeared normal several hours later. In each of 2 trials, 4 exposure groups of 9 pigs each were continuously exposed to ammonia for 5 weeks. Data from both trials were combined for analysis. Concentrations of ammonia were measured daily, and the average exposures of the groups were 12, 61, 103, and 145 ppm. Feed consumption and average daily weight gain were adversely affected by increasing ammonia concentrations. Pigs exposed to the 3 higher concentrations had excessive nasal, lacrymal, and oral secretions, but these were less pronounced in those exposed to 61 ppm. Pigs exposed to 61 ppm appeared to adjust within 3-4 days, so that their secretory rate was only slightly higher than that of animals exposed to 12 ppm. Pigs in the 2 higher concentrations coughed approximately 3 times as much as those in the lower, and coughing at 61 ppm was slightly more frequent than at 12 ppm. Five animals from each exposure group were autopsied and all gross and microscopic findings were normal.   12 guinea pigs were exposed to about 170 ppm ammonia for 6 hours a day, 5 days a week for up to 18 weeks. Chamber concentrations were monitored and ranged from 140-200 ppm. The exposed animals and 6 controls were weighed weekly. No adverse effects were observed by autopsy of the 4 exposed and 2 control animals killed after 6 weeks or after 12 weeks. In 4 animals exposed for 18 weeks, there was congestion of spleens, livers, and kidneys with early degenerative changes in suprarenal glands. Increased blood destruction was suggested by higher quantities of hemosiderin in the spleens. In the upper tubules of the kidneys there was cloudy swelling with precipitated albumin in the lumen and some casts. These changes were also seen in the lower tubules of 2 animals. The cells of the suprarenal glands were swollen and the cytoplasm in some areas had lost its normal granular structure.   Results of an unstated number of rabbits and cats for 1 hour to initial concentrations of 3.5-8.7 mg/L (approximately 5,200-12,800 ppm) of ammonia with an average concentration of 7.0 mg/L (approximately 10,360 ppm) was reported to be the "approximate LC50." The static method of gassing used probably resulted in an average concentration of half the initial concentrations or less. Also evaluated was the gas absorption of the nasobuccopharyngeal section of the respiratory tract. Rabbits which inhaled directly through a tracheal cannula, and a second group inhaled normally through nose, mouth, and throat. The mean survival time in the second group was reported to be almost twice that of the first group, 33 hr versus 18 hr. On microscopic examination, the trachea was congested and edematous. The mucosa was necrotic and sloughed off in 80-90% of the animals in which the upper respiratory tract had been bypassed, while the trachea was normal in appearance in the second group of test animals. Similar differential findings, but to a lesser degree, were shown in the bronchial mucosa. The damage to the bronchioles and alveoli surprisingly appeared to be identical in both groups. It was described as congestion, edema, hemorrhage, and atelectasis with emphysema. The upper respiratory tract acted as a protection only to the trachea and bronchi, and that small airways and alveoli were less resistant to ammonia injury in many cases within 10 minutes. Between the 6th and 10th postexposure days, 7 of the 80 died, compared with no deaths in controls.Autopsies were not performed.   Pullets exposed to 200 ppm atmospheric ammonia for 17 days had reduced feed intake & reduced growth rate when compared to controls. After the ammonia exposure period at point of lay, percent egg production was less & mortality was greater for exposed group than controls.	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/). Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/. 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:   Negative in all strains (Salmonella typhimuriumTA98, TA100, TA1535, TA1537, TA1538 andEscherichia coliWP2uvrA) with and without S9 metabolic activation.	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	No data	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:   Life-long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain.   Male Sprague Dawley rats were exposed for 24 weeks to drinking water containing 83 mg/L N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Subsequently, half of the males were exposed to water containing 0.01% ammonia solution and the other half to tap water for a period of 24 weeks. Chronic oral exposure to a 0.01% ammonia solution via the drinking water exerts a promoting effect on gastric cancer in the rat induced by MNNG. Gross pathology: In the treatment group, 3 out of 37 and in the control group 0 out of 39 rats had metastasis in the liver. The number of rats with gastric tumors was 12 out of 39 in the control group and 26 out of 37 in the treatment group. The number of gastric cancers per tumor bearing rat was significantly higher in ammonia treated rats when compared to control rats, 2.1 and 1.3 respectively. Histopathology: All animals showed signs of gastritis.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: From 2-4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low (mean 7 ppm) or moderate (mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain (MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain (MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetus-to-corpus luteum ratio were all similar between the two groups.   DEVELPMENTAL 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.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC 50 for the substance Ammonium acetate is calculated to be 847.88 mg/L under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint report 06.01.03_07 Ammonia) obtained with the analogue Ammonia (48-h LC 50 = 187 mg/L for Daphnia pulex in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 847.88 mg/L under test conditions.

Reference 13

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

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 on the analogue Ammonia.

GLP compliance:

not specified

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: - 77.7 ºC
- Boiling point: - 33.35 ºC
- Vapour pressure: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)
- Henry's law constant (for volatie substances): 1.61E -05 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 531 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 ºC.
- Solubility in organic solvents: In ethanol: 15 % in 95% alcohol at 20 ºC
- log Pow: - 1.14 at 25 ºC
- pKa: 9.25 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

593.97 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

Based on the experimental results obtained with the analogue Ammonia (48-h LC 50 = 131 mg/L for Ceriodaphnia reticulata in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 593.97 mg/L under test conditions.

The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,
- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

The analogue Ammonia shares the functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:

- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,

- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and

- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

Table 1. Data Matrix, Analogue Approach.

CAS Number		Source chemical 7664-41-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonia	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Measured data: -77.7 ºC	Experimental data: 114 ºC
Boiling Point		Measured data: -33.35 ºC	Estimated data: 312.76 ºC
Density		Measured data: 0.7710 g/L at 760 mm Hg	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Measured data: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Measured data: - 1.14 at 25 ºC	Estimated data: -2.79
Water solubility		Measured data: 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 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		Experimental data:   (96 h) LC50 for Fathead minnows = 8.2 mg/L (hard water, conditions of bioassay not specified) (24-96 h) LC50 for Goldfish = 2 - 2.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Coho salmon = 0.45 mg/L (Flow-through bioassay) (72 h) LC50 for Guppy fry = 74 mg/L (Static bioassay) (72 h) LC50 Guppy fry = 1.26 mg/L (Static bioassay) (96 h) LC50 for Cutthroat trout (Salmo clarki) fry = 0.5-0.8 mg/L (Flow-through bioassay) (24 h) LC50 for Rainbow trout fertilized egg > 3.58 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout alevins (0-50 days old) > 3.58 mg/L (Static bioassay) LC50 for Rainbow trout fry (85 days old) = 0.068 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout adult = 0.097 mg/L (Static bioassay) (48 h) LC50 for Walking catfish = 0.28 mg/L (Static bioassay) (96 h) LC50 for Salmo aguabonita = 0.76 mg/L (Conditions of bioassay not specified) (18 h) LC50 for Salmo trutta > 0.15 mg/L (Conditions of bioassay not specified) LC50 for Oncorhynchus tschawytscha = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salvelinus fontinalis = 0.96-1.05 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Proposium williamsoni = 0.47 mg/L (Conditions of bioassay not specified) LC50 for Catostomus platyrhynchos = 0.67-0.82 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo trutta = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (late alevins) = 0.083 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (eyed embryos) > 1.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus kisutch = 0.55 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo salar = 0.28 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Lepomis macrochirus = 0.26-4.6 mg/L (Conditions of bioassay not specified)	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) LC50 for Daphnia magna = 189 mg/L (Static bioassay) (48 h) LC50 for Daphnia magna = 24 mg/L (Conditions of bioassay not specified) (48 h) LC50 for Daphnia pulex = 187 mg/L (Static bioassay) (48 h) LC50 for Ceriodaphnia reticulate = 131 mg/L (Static bioassay) (48 h) LC50 for Simocephalus vetulus = 123 mg/L (Conditions of bioassay not specified)	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		No data	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: LD50 = 350 mg/kg bw (rat)	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: (1 h) LC50 = 7,050 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (cat) (1 h) LC50 = 746 mg/m3 (Cat, dynamic air flow) (Cat) (1 h) LC50 = 7,050 mg/m3 (Cat, static conditions) (2 h) LC50 = 7,600 mg/m3 (rat) (1 h) LC50 = 5,100 mg/m3 (rat) (1 h) LCLo = 1,400 mg/m3 (rat) (10 min) LC50 = 7,105 mg/m3 (mouse) (1 h) LC50 = 3,360 mg/m3 (mouse) (2 h) LC50 = 3,310 mg/m3 (mouse)	No data
Acute Toxicity: Dermal		No data	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: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant.	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: Ammonia in the form of a gas or an aqueous solution is a recognized eye irritant.	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		Repeated dose toxicity: Inhalation   Experimental data:   Rats exposed to 470 mg/m3 continuously found focal or diffuse interstitial pneumonitis in all with epithelial calcification in renal tubules & bronchi, epithelial proliferation of renal tubules, myocardial fibrosis & fatty liver.   49 and 51 rats were exposed continuously for 90 days at 262 mg/m3 and for 65 days at 455 mg/m3 respectively. 262 mg/m3 produced mild nasal discharge in about 25%. All 51 rats exposed at 455mg/m3 showed mild dyspnea & nasal irritation. There were 32 deaths by day 25 and 50by day 65.   One pig exposed to 280 ppm of ammonia showed immediate irritation of the nose and mouth and abnormal respiratory patterns, and by the 36th hour of exposure had convulsions and extremely shallow and irregular breathing. Convulsions continued for 3 hours after exposure ended but the animal appeared normal several hours later. In each of 2 trials, 4 exposure groups of 9 pigs each were continuously exposed to ammonia for 5 weeks. Data from both trials were combined for analysis. Concentrations of ammonia were measured daily, and the average exposures of the groups were 12, 61, 103, and 145 ppm. Feed consumption and average daily weight gain were adversely affected by increasing ammonia concentrations. Pigs exposed to the 3 higher concentrations had excessive nasal, lacrymal, and oral secretions, but these were less pronounced in those exposed to 61 ppm. Pigs exposed to 61 ppm appeared to adjust within 3-4 days, so that their secretory rate was only slightly higher than that of animals exposed to 12 ppm. Pigs in the 2 higher concentrations coughed approximately 3 times as much as those in the lower, and coughing at 61 ppm was slightly more frequent than at 12 ppm. Five animals from each exposure group were autopsied and all gross and microscopic findings were normal.   12 guinea pigs were exposed to about 170 ppm ammonia for 6 hours a day, 5 days a week for up to 18 weeks. Chamber concentrations were monitored and ranged from 140-200 ppm. The exposed animals and 6 controls were weighed weekly. No adverse effects were observed by autopsy of the 4 exposed and 2 control animals killed after 6 weeks or after 12 weeks. In 4 animals exposed for 18 weeks, there was congestion of spleens, livers, and kidneys with early degenerative changes in suprarenal glands. Increased blood destruction was suggested by higher quantities of hemosiderin in the spleens. In the upper tubules of the kidneys there was cloudy swelling with precipitated albumin in the lumen and some casts. These changes were also seen in the lower tubules of 2 animals. The cells of the suprarenal glands were swollen and the cytoplasm in some areas had lost its normal granular structure.   Results of an unstated number of rabbits and cats for 1 hour to initial concentrations of 3.5-8.7 mg/L (approximately 5,200-12,800 ppm) of ammonia with an average concentration of 7.0 mg/L (approximately 10,360 ppm) was reported to be the "approximate LC50." The static method of gassing used probably resulted in an average concentration of half the initial concentrations or less. Also evaluated was the gas absorption of the nasobuccopharyngeal section of the respiratory tract. Rabbits which inhaled directly through a tracheal cannula, and a second group inhaled normally through nose, mouth, and throat. The mean survival time in the second group was reported to be almost twice that of the first group, 33 hr versus 18 hr. On microscopic examination, the trachea was congested and edematous. The mucosa was necrotic and sloughed off in 80-90% of the animals in which the upper respiratory tract had been bypassed, while the trachea was normal in appearance in the second group of test animals. Similar differential findings, but to a lesser degree, were shown in the bronchial mucosa. The damage to the bronchioles and alveoli surprisingly appeared to be identical in both groups. It was described as congestion, edema, hemorrhage, and atelectasis with emphysema. The upper respiratory tract acted as a protection only to the trachea and bronchi, and that small airways and alveoli were less resistant to ammonia injury in many cases within 10 minutes. Between the 6th and 10th postexposure days, 7 of the 80 died, compared with no deaths in controls.Autopsies were not performed.   Pullets exposed to 200 ppm atmospheric ammonia for 17 days had reduced feed intake & reduced growth rate when compared to controls. After the ammonia exposure period at point of lay, percent egg production was less & mortality was greater for exposed group than controls.	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/). Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/. 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:   Negative in all strains (Salmonella typhimuriumTA98, TA100, TA1535, TA1537, TA1538 andEscherichia coliWP2uvrA) with and without S9 metabolic activation.	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	No data	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:   Life-long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain.   Male Sprague Dawley rats were exposed for 24 weeks to drinking water containing 83 mg/L N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Subsequently, half of the males were exposed to water containing 0.01% ammonia solution and the other half to tap water for a period of 24 weeks. Chronic oral exposure to a 0.01% ammonia solution via the drinking water exerts a promoting effect on gastric cancer in the rat induced by MNNG. Gross pathology: In the treatment group, 3 out of 37 and in the control group 0 out of 39 rats had metastasis in the liver. The number of rats with gastric tumors was 12 out of 39 in the control group and 26 out of 37 in the treatment group. The number of gastric cancers per tumor bearing rat was significantly higher in ammonia treated rats when compared to control rats, 2.1 and 1.3 respectively. Histopathology: All animals showed signs of gastritis.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: From 2-4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low (mean 7 ppm) or moderate (mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain (MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain (MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetus-to-corpus luteum ratio were all similar between the two groups.   DEVELPMENTAL 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.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC 50 for the substance Ammonium acetate is calculated to be 593.97 mg/L under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint report 06.01.03_08 Ammonia) obtained with the analogue Ammonia (48-h LC 50 = 131 mg/L for Ceriodaphnia reticulata in a static test) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 593.97 mg/L under test conditions.

Reference 14

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties for aquatic toxicity endpoints.

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 on the analogue Ammonia.

GLP compliance:

not specified

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material:
PHYSICO-CHEMICAL PROPERTIES
- Melting point: - 77.7 ºC
- Boiling point: - 33.35 ºC
- Vapour pressure: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)
- Henry's law constant (for volatie substances): 1.61E -05 atm.m3/mole at 25 ºC
- Water solubility (under test conditions): 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 ºC.
- Solubility in organic solvents: In ethanol: 15 % in 95% alcohol at 20 ºC
- log Pow: - 1.14 at 25 ºC
- pKa: 9.25 at 25 ºC

OTHER PROPERTIES (if relevant for this endpoint)
- Results of test for ready biodegradability: Readily biodegradable

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

557.7 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

not specified

Details on results:

Based on the experimental results obtained with the analogue Ammonia (48-h LC 50 = 123 mg/L for Simocephalus vetulus) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 557.70 mg/L under test conditions.

The analogue Ammonia shares the same functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,
- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

The analogue Ammonia shares the functional group with Ammonium acetate, and also has comparable values for the relevant molecular properties. These properties are:

- a low log Pow value, which is -1.14 at 25 ºC for Ammonia and -2.79 for Ammonium acetate,

- a high water solubility, which is 541 mg/L at 20 ºC for Ammonia and 1480 g/L at 4 ºC for Ammonium acetate, and

- similar molecular weights, which are 17.03 for Ammonia and 77.08 for Ammonium acetate.

Table 1. Data Matrix, Analogue Approach.

CAS Number		Source chemical 7664-41-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonia	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Measured data: -77.7 ºC	Experimental data: 114 ºC
Boiling Point		Measured data: -33.35 ºC	Estimated data: 312.76 ºC
Density		Measured data: 0.7710 g/L at 760 mm Hg	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Measured data: 7,510 mm Hg at 25 ºC (from experimentally derived coefficients)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Measured data: - 1.14 at 25 ºC	Estimated data: -2.79
Water solubility		Measured data: 541 mg/L at 20 ºC; 895 mg/L at 0 ºC; 444 mg/L at 28 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		Experimental data:   (96 h) LC50 for Fathead minnows = 8.2 mg/L (hard water, conditions of bioassay not specified) (24-96 h) LC50 for Goldfish = 2 - 2.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Coho salmon = 0.45 mg/L (Flow-through bioassay) (72 h) LC50 for Guppy fry = 74 mg/L (Static bioassay) (72 h) LC50 Guppy fry = 1.26 mg/L (Static bioassay) (96 h) LC50 for Cutthroat trout (Salmo clarki) fry = 0.5-0.8 mg/L (Flow-through bioassay) (24 h) LC50 for Rainbow trout fertilized egg > 3.58 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout alevins (0-50 days old) > 3.58 mg/L (Static bioassay) LC50 for Rainbow trout fry (85 days old) = 0.068 mg/L (Static bioassay) (24 h) LC50 for Rainbow trout adult = 0.097 mg/L (Static bioassay) (48 h) LC50 for Walking catfish = 0.28 mg/L (Static bioassay) (96 h) LC50 for Salmo aguabonita = 0.76 mg/L (Conditions of bioassay not specified) (18 h) LC50 for Salmo trutta > 0.15 mg/L (Conditions of bioassay not specified) LC50 for Oncorhynchus tschawytscha = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salvelinus fontinalis = 0.96-1.05 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Proposium williamsoni = 0.47 mg/L (Conditions of bioassay not specified) LC50 for Catostomus platyrhynchos = 0.67-0.82 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo trutta = 0.47 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (late alevins) = 0.083 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus gorbuscha (eyed embryos) > 1.5 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Oncorhynchus kisutch = 0.55 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Salmo salar = 0.28 mg/L (Conditions of bioassay not specified) (96 h) LC50 for Lepomis macrochirus = 0.26-4.6 mg/L (Conditions of bioassay not specified)	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) LC50 for Daphnia magna = 189 mg/L (Static bioassay) (48 h) LC50 for Daphnia magna = 24 mg/L (Conditions of bioassay not specified) (48 h) LC50 for Daphnia pulex = 187 mg/L (Static bioassay) (48 h) LC50 for Ceriodaphnia reticulate = 131 mg/L (Static bioassay) (48 h) LC50 for Simocephalus vetulus = 123 mg/L (Conditions of bioassay not specified)	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		No data	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: LD50 = 350 mg/kg bw (rat)	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: (1 h) LC50 = 7,050 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (rabbit) (1 h) LCLo = 4,900 mg/m3 (cat) (1 h) LC50 = 746 mg/m3 (Cat, dynamic air flow) (Cat) (1 h) LC50 = 7,050 mg/m3 (Cat, static conditions) (2 h) LC50 = 7,600 mg/m3 (rat) (1 h) LC50 = 5,100 mg/m3 (rat) (1 h) LCLo = 1,400 mg/m3 (rat) (10 min) LC50 = 7,105 mg/m3 (mouse) (1 h) LC50 = 3,360 mg/m3 (mouse) (2 h) LC50 = 3,310 mg/m3 (mouse)	No data
Acute Toxicity: Dermal		No data	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: Ammonia in the form of a gas or an aqueous solution is a recognized skin irritant.	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: Ammonia in the form of a gas or an aqueous solution is a recognized eye irritant.	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		Repeated dose toxicity: Inhalation   Experimental data:   Rats exposed to 470 mg/m3 continuously found focal or diffuse interstitial pneumonitis in all with epithelial calcification in renal tubules & bronchi, epithelial proliferation of renal tubules, myocardial fibrosis & fatty liver.   49 and 51 rats were exposed continuously for 90 days at 262 mg/m3 and for 65 days at 455 mg/m3 respectively. 262 mg/m3 produced mild nasal discharge in about 25%. All 51 rats exposed at 455mg/m3 showed mild dyspnea & nasal irritation. There were 32 deaths by day 25 and 50by day 65.   One pig exposed to 280 ppm of ammonia showed immediate irritation of the nose and mouth and abnormal respiratory patterns, and by the 36th hour of exposure had convulsions and extremely shallow and irregular breathing. Convulsions continued for 3 hours after exposure ended but the animal appeared normal several hours later. In each of 2 trials, 4 exposure groups of 9 pigs each were continuously exposed to ammonia for 5 weeks. Data from both trials were combined for analysis. Concentrations of ammonia were measured daily, and the average exposures of the groups were 12, 61, 103, and 145 ppm. Feed consumption and average daily weight gain were adversely affected by increasing ammonia concentrations. Pigs exposed to the 3 higher concentrations had excessive nasal, lacrymal, and oral secretions, but these were less pronounced in those exposed to 61 ppm. Pigs exposed to 61 ppm appeared to adjust within 3-4 days, so that their secretory rate was only slightly higher than that of animals exposed to 12 ppm. Pigs in the 2 higher concentrations coughed approximately 3 times as much as those in the lower, and coughing at 61 ppm was slightly more frequent than at 12 ppm. Five animals from each exposure group were autopsied and all gross and microscopic findings were normal.   12 guinea pigs were exposed to about 170 ppm ammonia for 6 hours a day, 5 days a week for up to 18 weeks. Chamber concentrations were monitored and ranged from 140-200 ppm. The exposed animals and 6 controls were weighed weekly. No adverse effects were observed by autopsy of the 4 exposed and 2 control animals killed after 6 weeks or after 12 weeks. In 4 animals exposed for 18 weeks, there was congestion of spleens, livers, and kidneys with early degenerative changes in suprarenal glands. Increased blood destruction was suggested by higher quantities of hemosiderin in the spleens. In the upper tubules of the kidneys there was cloudy swelling with precipitated albumin in the lumen and some casts. These changes were also seen in the lower tubules of 2 animals. The cells of the suprarenal glands were swollen and the cytoplasm in some areas had lost its normal granular structure.   Results of an unstated number of rabbits and cats for 1 hour to initial concentrations of 3.5-8.7 mg/L (approximately 5,200-12,800 ppm) of ammonia with an average concentration of 7.0 mg/L (approximately 10,360 ppm) was reported to be the "approximate LC50." The static method of gassing used probably resulted in an average concentration of half the initial concentrations or less. Also evaluated was the gas absorption of the nasobuccopharyngeal section of the respiratory tract. Rabbits which inhaled directly through a tracheal cannula, and a second group inhaled normally through nose, mouth, and throat. The mean survival time in the second group was reported to be almost twice that of the first group, 33 hr versus 18 hr. On microscopic examination, the trachea was congested and edematous. The mucosa was necrotic and sloughed off in 80-90% of the animals in which the upper respiratory tract had been bypassed, while the trachea was normal in appearance in the second group of test animals. Similar differential findings, but to a lesser degree, were shown in the bronchial mucosa. The damage to the bronchioles and alveoli surprisingly appeared to be identical in both groups. It was described as congestion, edema, hemorrhage, and atelectasis with emphysema. The upper respiratory tract acted as a protection only to the trachea and bronchi, and that small airways and alveoli were less resistant to ammonia injury in many cases within 10 minutes. Between the 6th and 10th postexposure days, 7 of the 80 died, compared with no deaths in controls.Autopsies were not performed.   Pullets exposed to 200 ppm atmospheric ammonia for 17 days had reduced feed intake & reduced growth rate when compared to controls. After the ammonia exposure period at point of lay, percent egg production was less & mortality was greater for exposed group than controls.	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/). Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/. 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:   Negative in all strains (Salmonella typhimuriumTA98, TA100, TA1535, TA1537, TA1538 andEscherichia coliWP2uvrA) with and without S9 metabolic activation.	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	No data	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:   Life-long ingestion in drinking water did not produce any carcinogenic effects, and had no effect on the spontaneous development of aderiocarcinoma of the breast in C3H females, a characteristic of this strain.   Male Sprague Dawley rats were exposed for 24 weeks to drinking water containing 83 mg/L N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Subsequently, half of the males were exposed to water containing 0.01% ammonia solution and the other half to tap water for a period of 24 weeks. Chronic oral exposure to a 0.01% ammonia solution via the drinking water exerts a promoting effect on gastric cancer in the rat induced by MNNG. Gross pathology: In the treatment group, 3 out of 37 and in the control group 0 out of 39 rats had metastasis in the liver. The number of rats with gastric tumors was 12 out of 39 in the control group and 26 out of 37 in the treatment group. The number of gastric cancers per tumor bearing rat was significantly higher in ammonia treated rats when compared to control rats, 2.1 and 1.3 respectively. Histopathology: All animals showed signs of gastritis.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: From 2-4.5 months of age, gilts were exposed naturally to Mycoplasma hyponeumoniae and Pasteurella multocida, which cause enzootic pneumonia and atrophic rhinitis, respectively. At 4.5 months of age, the gilts were moved to one of two rooms and exposed to either low (mean 7 ppm) or moderate (mean 36 ppm) aerial concentrations of ammonia. Each exposure group consisted of 40 individuals. In the room with low ammonia concentration, manure was flushed weekly to maintain a 0.3 m depth. In the room with moderate ammonia concentration, manure accumulated to 0.48 m depth. Moderate aerial ammonia concentration was obtained initially and maintained by adding anhydrous ammonia from a steel tank. Mean Daily Gain (MDG) was determined by weighing the gilts biweekly. Half the gilts from each exposure concentration were sacrificed after 6 weeks. The remaining gilts were maintained in their respective environments, exposed daily to mature boars, bred at first estrus, and sacrificed at day 30 of gestation. At the end of two weeks, gilts in the moderate exposure group weighed less than those in the low exposure. After 2 weeks gilts acclimated and the Mean Daily Gain (MDG) was similar for the rest of the experiment. The gilts sacrificed at 6 weeks showed that the animals in the low exposure were heavier. At day 30 of gestation, number of fetuses, fetal length, and fetus-to-corpus luteum ratio were all similar between the two groups.   DEVELPMENTAL 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.

Validity criteria fulfilled:

not applicable

Conclusions:

The (48 h) LC 50 for the substance Ammonium acetate is calculated to be 557.70 mg/L under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint report 06.01.03_09 Ammonia) obtained with the analogue Ammonia (48-h LC 50 = 123 mg/L for Simocephalus vetulus) and the molecular weights, the read-across approach is applied and the LC 50 for the substance Ammonium acetate is calculated to be 557.70 mg/L under test conditions.

Description of key information

Short-term toxicity to aquatic invertebrates:

Weight of evidence: The (48 h) EC50 was greater than 100 mg/L (108.81-939.66 mg/L). Read-across from experimental results on analogues Sodium Acetate, Potassium Acetate and Ammonia.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

108 mg/L

Additional information

Weight of evidence: Read-across approach from experimental results obtained with analogues Sodium Acetate, Potassium Acetate and Ammonia.

In the first study report, a toxicity test was performed with Sodium Acetate. The 48 -h EC 50 was greater than 1000 mg/L for Daphnia magna in a static test. Based on these results and the molecular weights, the read-across approach is applied and the EC 50 for Ammonium acetate is calculated to be > 939.66 mg/L under test conditions (basis for effect: mobility).

In the second study report, Potassium Acetate was tested. The 48 -h EC 50 was greater than 459.5 mg/L for Daphnia magna in a static test. Based on theses results and the molecular weights, the read-across approach is applied and the EC 50 for Ammonium acetate is calculated to be > 360.89 mg/L under test conditions.

In the last publication, many experimental results are reported on Ammonia, anhydrous:

For Daphnia magna, the 48-h LC 50 were 24 and 189 mg/L in static tests. Based on these results and the molecular weights, the read-across approach is applied and the LC 50 for Ammonium acetate is calculated to be 108.81 and 856.95 mg/L, respectively, under test conditions.

For Daphnia pulex, the 48-h LC 50 was 187 mg/L in a static test. Based on these results and the molecular weights, the read-across approach is applied and the LC 50 for Ammonium acetate is calculated to be 847.88 mg/L under test conditions.

For Ceriodaphnia reticulata, the 48-h LC 50 was 131 mg/L in a static test. Based on these results and the molecular weights, the read-across approach is applied and the LC 50 for Ammonium acetate is calculated to be 593.97 mg/L under test conditions.

For Simocephalus vetulus, the 48-h LC 50 was 123 mg/L. Based on these results and the molecular weights, the read-across approach is applied and the LC 50 for Ammonium acetate is calculated to be 557.70 mg/L under test conditions.

Based on above described results can be concluded that Ammonium Acetate toxicity values, EC50 for aquatic invertebrates is over the 100mg/l treshold.