Ammonium acetate

Endpoint summary

Description of key information

Skin irritation/corrosion: Weight of evidence: The substance Ammonium Acetate is considered as not irritating for skin. Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the skin irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
See attached reporting format

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from Letter of Access experimental data (test method similar to OECD 404) on the analogue Potassium Acetate.

GLP compliance:

no

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Other effects:

Based on the experimental results obtained with the analogue Potassium Acetate, which is considered to be not irritating for New Zealand White rabbits skin, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating 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 similar water solubility which is 2.5 g/mL at 20 ºC for Potassium Acetate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 98.14 for Potassium Acetate and 77.08 for Ammonium Acetate.

The substance Ammonium Acetate is considered as not irritating under test conditions.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0.Presented results show that both substances have common (eco)toxicological behavior (attachment).

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results obtained (reported under the endpoint record 07.03.01_02 KAc) with the analogue Potassium Acetate, which is considered to be not irritating for New Zealand White rabbits skin, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1990-06-03 to 1990-06-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD guideline, with GLP compliance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG,
- Age at study initiation: 3-5 months
- Weight at study initiation: 3.4 - 4.5 kg
- Water (e.g. ad libitum): deionized chlorinated water from automatic watering, ad libitum
- Housing:in fully air-condition, spaces in single cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 ºC
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12 hours

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of test substance Safeway KA

Duration of treatment / exposure:

Approximately 24 hours prior to the experiment start, 3 rabbits in the dorsal area of the fuselage, were depilated with an electric hair clipper with an area of approximately 25 cm2.
The exposure time: 4 hours.

Observation period:

Observations were made: were made 30 - 60 minutes and 24, 48 and 72 hours after.

Number of animals:

Three (female).

Details on study design:

TEST SITE
- Area of exposure: 25 cm2
- Type of wrap if used: wound plaster ( Beiersdorf AG, Hamburg)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erytrema:
0. No erythema
1. Very slight erythema (barely perceptible)
2. Clearly circumscribed erythema
3. Medium to severe erythema,
4. Severe erythema (intense redness to slight eschar) (deep
Injuries)
* Can not be assessed.

Edema:
0. No edema
1. Very slight edema (hardly noticeable)
2. Slight edema (edges of the body are characterized by a distinct swelling clearly defined)
3. Edema (swelling of about 1 mm }....
4. Severe edema (swelling of more than 1 mm and the exposure area)
* Can not be assessed.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Throughout the trial period there were no symptoms of skin irritation.

Interpretation of results:

GHS criteria not met

Conclusions:

Throughout the trial period there were no symptoms of skin irritation.

Executive summary:

An dermal irritation test (72 hours) using 3 rabbits has been performed on the test substance LP 1848 (50 % water solution of Potassium acetate) in accordance with guideline OECD Guideline 404 (Acute Dermal Irritation / Corrosion).

Throughout the trial period there were no symptoms of skin irritation.

In this test, the control parameters were within the recommended ranges.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Scientific Review Article. No data on GLP.

Principles of method if other than guideline:

Two studies were performed using four and three restrained guinea pigs, respectively, with four dipped sites per animal, in which the animals received topical applications of 0.1 mL of 12% Ammonium Lactate lotion, pH 5.0-5.5, and 0.05 mL of Oxsoralen (as a positive control) on two contralateral sites.
The right side of each animal was shielded with cardboard and the left side was uncovered. The animals were exposed to UVA light 15-20 min after dosing; the animals were examined after 24 h.

GLP compliance:

not specified

Species:

guinea pig

Strain:

not specified

Type of coverage:

open

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

0.1 mL of 12% Ammonium Lactate lotion, pH 5.0-5.5, and 0.05 mL of Oxsoralen (as a positive control) on two contralateral sites.

Duration of treatment / exposure:

24 hours

Observation period:

24 hours

Number of animals:

Seven animals.

Details on study design:

The right side of each animal was shielded with cardboard and the left side was uncovered. The animals were exposed to UVA light 15-20 min after dosing; the animals were examined after 24 h.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

animals were examined after 24 h.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

animals were examined after 24 h.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Ammonium Lactate lotion did not produce erythema at either the irradiated or nonirradiated sites.
Numerical results are not provided.

Ammonium Lactate lotion did not produce erythema at either the irradiated or nonirradiated sites.

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Ammonium Lactate lotion did not produce erythema at either the irradiated or nonirradiated sites.

Executive summary:

Two studies were performed using four and three restrained guinea pigs, respectively, with four dipped sites per animal, in which the animals received topical applications of 0.1 mL of 12% Ammonium Lactate lotion, pH 5.0-5.5, and 0.05 mL of Oxsoralen (as a positive control) on two contralateral sites.

The right side of each animal was shielded with cardboard and the left side was uncovered. The animals were exposed to UVA light 15-20 min after dosing; the animals were examined after 24 h.

In both studies, Ammonium Lactate lotion did not produce erythema at either the irradiated or nonirradiated sites.

The positive control produced severe erythema at the irradiated site, but no reactions were observed at the non-irradiated sites.

Reference 4

Endpoint:

skin irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonium Lactate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the skin irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

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

GLP compliance:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

animals were examined after 24 h.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Remarks:

animals were examined after 24 h.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Other effects:

Based on the experimental results obtained with the analogue Ammonium Lactate, which is considered to be not irritating for guinea pigs, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

The analogue Ammonium lactate which has a very similar functional group to Ammonium acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is -3.84 for Ammonium lactate, and -2.79 for Ammonium acetate,
- a high water solubility which is 2247 g/L for Ammonium lactate, and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights which are 107.06 for Ammonium lactate, and 77.08 for Ammonium acetate.

The substance Ammonium Acetate is considered as not irritating under test conditions.

Table 1. Data Matrix, Analogue Approach.

CAS Number		Source chemical 515-98-0	Target chemical 631-61-8
CHEMICAL NAME		Ammonium lactate	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental data: 16.8 ºC	Experimental data: 114 ºC
Boiling Point		Calculated data: 204.2ºC	Estimated data: 312.76 ºC
Density		Measured data: 1.26 g/mL	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Experimental data: 0.0813 mm Hg at 25 ºC	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Experimental data: -0.72	Estimated data: -2.79
Water solubility		Estimated data: 1000 g/L	Experimental results: 1480 g/L at 4 ºC
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Easily biodegradable	Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:   Readily biodegradable
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		No data	Experimental data and read-across from Potassium Acetate, based on molecular weights:   LC50 = 392.70 mg/L.
Acute Toxicity to Aquatic Invertebrates		No data	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= 180mg/kg bw (rat/mouse)	Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
Acute Toxicity: Inhalation		No data	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 results:   Ammonium lactate (12 %) was not irritating for guinea pigs.	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 results:   Ammonium lactate (12 %) was irritating for eyes.	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		Experimental results: The sensitization potential of a 12% Ammonium Lactate lotion, pH 5.0-5.5, was examined using 10 guinea pigs. The first induction application consisted of 0.5 mL applications of undiluted material as well as 25 and 50% dilutions. The remaining two induction applications (one per week), as well as the two subsequent challenge applications (applied 2 and 3 weeks after the last induction dose), of 0.5 mL were undiluted lotion. The first induction dose and the two challenge doses were placed under occlusive patches for 24 h; the remaining two induction doses were placed under occlusive patches for 6 h. One animal was found dead on day 18 (reason not stated). No erythema was observed after induction or challenge applications. 12% Ammonium Lactate lotion was not a sensitizer to guinea pigs.	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		No data	Repeated dose toxicity: oral: Weight of evidence: Experimental results:   Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/day. Read-across from the analogue Sodium Acetate, based on molecular weights:   The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.    Read-across from the analogue Citric acid, sodium salt, based on molecular weights:   The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
Genetic Toxicity in vitro	-         Gene mutation in bacteria	Negative	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 Phenoxyacetic 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		No data	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: No data DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data	TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.   DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day.   Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day.   Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.01_03 Ammonium lactate) with the analogue Ammonium Lactate, which is considered to be not irritating for guinea pigs, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Reference 5

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Scientific Review Article. Results according to OECD scoring but without induividual scores. No data on GLP.

Principles of method if other than guideline:

Results according to OECD scoring. No data provided on the method.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Remarks:

100%

Duration of treatment / exposure:

Single dose, occlusive conditions.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.62

Max. score:

8

Remarks on result:

other: PII=0.62, after 72h measured at 13 subjects

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

Ammonium stearate is non irritant for skin. PII=0.62 max.8).

Executive summary:

Ammonium stearate primary irritation index is P.I.I. =0.62 (max. 8). The substance is non irritant for skin.

Reference 6

Endpoint:

skin irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonium Stearate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the skin irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

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

GLP compliance:

not specified

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.62

Max. score:

8

Remarks on result:

other: PII=0.62, after 72h

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Other effects:

Based on the experimental results obtained with the analogue Ammonium Stearate, which is considered to be not irritating for guinea pigs, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

The analogue Ammonium lactate which has a very similar functional group to Ammonium acetate, also has comparable values for the relevant molecular properties. These properties are:
- a low log Pow value which is -3.84 for Ammonium lactate, and -2.79 for Ammonium acetate,
- a high water solubility which is 2247 g/L for Ammonium lactate, and 1480 g/L at 4 ºC for Ammonium acetate, and
- similar molecular weights which are 107.06 for Ammonium lactate, and 77.08 for Ammonium acetate.

The substance Ammonium Acetate is considered as not irritating under test conditions.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0.Presented results show that both substances have common (eco)toxicological behavior (attachment).

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.01_05 Ammonium stearate) with the analogue Ammonium Stearate, which is considered to be not irritating for guinea pigs, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The analogue Potassium Acetate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the eye irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from Letter of Access experimental data (test method similar to OECD 405) on the analogue Potassium Acetate.

GLP compliance:

no

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: Read across, result after 72h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: Read across, result after 72h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: Read across, result after 72h

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: Read across, mean value at 72h.

Other effects:

Based on the experimental results obtained with the analogue Potassium Acetate, which is considered to be not irritating for New Zealand White rabbits eyes, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating 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 similar water solubility which is 2.5 g/mL at 20 ºC for Potassium Acetate and 1480 g/L at 4 ºC for Ammonium Acetate, and
- similar molecular weights which are 98.14 for Potassium Acetate and 77.08 for Ammonium Acetate.

The substance Ammonium Acetate is considered as not irritating under test conditions.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.02_02 KAc) obtained with the analogue Potassium Acetate, which is considered to be not irritating for New Zealand White rabbits eyes, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1990-07-02 to 1990-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD guideline, with GLP compliance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG,
- Age at study initiation: 3-5 months
- Weight at study initiation: 3.4 - 4.1 kg
- Diet (e.g. ad libitum): Altromin 2123 (ca. 15 g/day)
- Water (e.g. ad libitum): deionized chlorinated water from automatic watering, ad libitum
- Housing:in fully air-condition, spaces in single cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 ºC
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12 hours

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of test substance Safeway KA

Duration of treatment / exposure:

Duration: 24 hours.

Observation period (in vivo):

Observation period: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Three animals were used.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiologic NaCl
- Time after start of exposure: after 24 hours.

SCORING SYSTEM:
CORNEA:
Opacity: degree of turbidity (for the evaluation is the densest place genom):
0. No ulceration or opacity
1. Scattered or diffuse opacity (other than slight turbidity ofnormal luster), details of iris clearly visible
2. Easily discernible translucent area, details of iris slightly shadowed
3. Pearly areas, no details of iris visible, size of pupil barely discernible
4. Opaque cornea, iris not discernible due to the opacity

IRIS:
0.Normal
1.Extremely depth wrinkles, congestion, swelling, slight circum-corneal hyperemia or injection, any of these symptoms, or a combina tion of the various symptoms, the iris still reacts to light (sluggish reaction is positive).
2.No reaction to light, haemorrhage, severe damage (one or all symptoms)

CONJUNCTIVAE
Redness, lids and / or nictitating
0. Blood vessels normal,
1. Some blood vessels show a marked hyperemia (injection)
2. Diffuse crimson color, individual vessels not easily discernible
3. Diffuse bright

Chemosis: lids and / or nictitating
0. No swelling
1. Any swelling above normal lying (including haw)
2. Obvious swelling with partial eversion of lids
3. Swelling with lids about half closed
4. Swelling with more than half-closed lids

TOOL USED TO ASSESS SCORE: fluorescein NaCl (0.01%) examined in UV light.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

1

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

1

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Based on the present study assessed Potassium acetate is therefore not considered to be irritating.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study assessed Potassium acetate is therefore not considered to be irritating.

Executive summary:

An eye irritation test (72 hours) using 3 rabbits has been performed on the test substance LP 1848 (50 % water solution of Potassium acetate) in accordance with guideline OECD Guideline 405 (Acute Eye Irritation / Corrosion).

Based on the present study assessed Potassium acetate is therefore not considered to be irritating.

In this test, the control parameters were within the recommended ranges based.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Results according to OECD scoring but without induividual scores. Scientific Review Article. No data on GLP.

Principles of method if other than guideline:

The test was performed according to Draize method and evaluation.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Observation period (in vivo):

72 hours

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is no irritating for eyes.

Executive summary:

Based on the presented results the substance is no irritating for eyes.

Reference 4

Endpoint:

eye irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

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

Adequacy of study:

key study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonium Stearate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the eye irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Draize method.

GLP compliance:

no

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

3

Remarks on result:

other: Data on analogue

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

1

Remarks on result:

other: data on analogue

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Remarks on result:

other: Data on analogue

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information given for analogue

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information given for analogue

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information given for analogue

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No information given for analogue

The substance Ammonium Acetate is considered as not irritating under test conditions.

The analogue Ammonium Stearate, shares the functional group with Ammonium Acetate, and also has comparable values molecular weights which are 301.52 for Ammonium Stearate, and 77.08 for Ammonium acetate. Ammonium Stearate is slightly soluble in water and Ammonium Acetate water solubility is 1480g/L.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0.Presented results show that both substances have common (eco)toxicological behavior (attachment).

Table 1. Data Matrix. Analogue Approach.

CAS Number		Source chemical 1002-89-7	Target chemical 631-61-8
CHEMICAL NAME		Ammonium stearate	Ammonium acetate
PHYSICO-CICAL DATA
Melting Point		Experimental data: 87 ºC	Experimental data: 114 ºC
Boiling Point		Experimental data: 259 ºC	Estimated data: 312.76 ºC
Density		Experimental data: 0.89 (22ºC)	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Estimated data: 2.54E-08mm Hg at 25 ºC	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Estimated data: 5.07	Estimated data: -2.79
Water solubility		Estimated data: 0.56mg/L	Experimental results: 1480 g/L at 4 ºC
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Estimated data: Readily biodegradable	Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:   Readily biodegradable
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		No data	Experimental data and read-across from Potassium Acetate, based on molecular weights:   LC50 = 392.70 mg/L.
Acute Toxicity to Aquatic Invertebrates		No data	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>5.0g/kg bw	Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
Acute Toxicity: Inhalation		No data	No data
Acute Toxicity: Dermal		Experimental data:   LD50>3.0g/kg bw	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: 100% substance , material applied in a single dose under occlusive conditions. PI1= 0.62 (max. = 8). Not irritant to skin.	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: 100% substance, eyes were rinsed. Scores were: 3, 1, 0 on days 1, 2, 3, respectively. No 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		No data	Repeated dose toxicity: oral: Weight of evidence: Experimental results:   Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day . Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL was 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:   The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.    Read-across from the analogue Citric acid, sodium salt, based on molecular weights:   The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
Genetic Toxicity in vitro	-         Gene mutation in bacteria	No data	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		No data	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: No data DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data	TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects.   Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.   DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day (body weight decreased by 16-27%).   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.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.02_03 Ammonium stearate) obtained with the analogue Ammonium Stearate, which is considered to be not irritating for the rabbits eyes, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Reference 5

Endpoint:

eye irritation: in vivo

Remarks:

other: read-across from in vivo experimental test with an analogue

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The analogue Ammonium Sulphate which shares the same functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties for the eye irritation endpoint.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See attached reporting format.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

The method used is similar to OECD 405 guideline. Draize scoring system was used.

GLP compliance:

no

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: data from the analogue, fully reversible in 8d

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

fully reversible

Remarks on result:

other: data from the analogue, fully reversible in 8d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

fully reversible

Remarks on result:

other: data from the analogue, fully reversible in 8d

The analogue Ammonium Sulphate, which shares the same ammonia/ammonium ion functional group with Ammonium Acetate, also has comparable values for the relevant molecular properties:

- a low log Pow value which is –5.1 at 25 ºC for Ammonium Sulphate and -2.79 for Ammonium Acetate,

- a similar water solubility which is 764 g/L at 20 ºC for Ammonium Sulphate and 1480 g/L at 4 ºC for Ammonium Acetate, and

- similar molecular weights which are 132.14 for Ammonium Sulphate and 77.08 for Ammonium Acetate.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0. Presented results show that both substances have common (eco)toxicological behavior (attachment).

Table 1. Data Matrix, Analogue approach.

CAS Number		Source chemical 7783-20-2	Target chemical 631-61-8
CHEMICAL NAME		Ammonium sulphate	Ammonium acetate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental data: Decomposes above 280 ºC	Experimental data: 114 ºC
Boiling Point		Experimental data: Decomposes above 280 ºC	Estimated data: 312.76 ºC
Density		Experimental data: 1.769 at 50 ºC	Experimental results: 1.07-1.17 g/cm3 at 20 ºC
Vapour Pressure		Experimental data: 4.053E-07 Pa (partial pressure of ammonia over solid (NH4)2SO4 at 25 ºC)	Estimated data: 0.02 Pa at 25 ºC
Partition Coefficient (log Kow)		Experimental data: –5.1 at 25 ºC	Estimated data: -2.79
Water solubility		Experimental data: 764 g/L at 20 ºC	Experimental data: 1480 g/L at 4 ºC
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Experimental data: In unsterilized soil, ammonium sulfate is mineralized fairly rapidly, and subsequently nitrified. Nitrification and de-nitrification processes also occur naturally in streams and rivers, as well as in many secondary sewage treatment processes	Experimental results on Ammonium Acetate, read-across from experimental data on Sodium Acetate and read-across from estimated data on Ammonia and Acetic Acid, based on functional group:   Readily biodegradable
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Experimental data: (96 h) LC50 > 100 mg/L (Pimephales promelas)	Experimental data and read-across from Potassium Acetate, based on molecular weights:   LC50 = 392.70 mg/L.
Acute Toxicity to Aquatic Invertebrates		Experimental data: (96 h) LC50 > 100 mg/L (Asellus Intermedius, Daphnia magna, Dugesia tigrina and Gammarus fasciatus)	Read-across from experimental data on analogues Sodium Acetate, Potassium Acetate and Ammonia, based on molecular weights:   EC50 = 108.81 - 939.66 mg/L
Toxicity to Aquatic Plants		Experimental data: (18 d) EC50 = ca. 25476 mg/L (ca. 2700 mg NH3/L) (Chlorella vulgaris)	Read-across from experimental data on analogues Acetic Acid, Potassium Acetate and Ammonium Sulphate, based on molecular weights: (72 h) EC50 > 392.70 mg/L; (72 h) NOEC = 392.70 mg/L.
MAMMALIAN TOXICITY
Acute Toxicity: Oral		Experimental data: LC50 >= 2000 mg/kg bw (rat, mouse) LC50 = 3040 mg/kg bw (mouse)	Weight of evidence: Read-across from experimental data on Potassium Acetate and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-3546.59 mg/kg bw
Acute Toxicity: Inhalation		Experimental data: (4 h) LC50 > 3.6 mg/m3 (rats) (1 h) LC50 > 2 mg/m3 (rabbits)	No data
Acute Toxicity: Dermal		Experimental data:   LC50 > 2000 mg/kg bw (rats, mice)	Weight of evidence: Read-across from experimental data on Fumaric Acid and Ammonium Sulphate, based on molecular weights: LD50 = 2333.28-26556.42 mg/kg bw
Skin Irritation/Corrosion		Experimental data: This substance was not irritating for rabbits. -         Single exposure for 20 hours, intact skin: no skin effects observed. -         Multiple exposures, 8 hrs/day for 5 consecutive days, intact skin: no skin effects observed.	Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate and Ammonium Lactate, and Ammonium Stearate based on functional group: The substance Ammonium Acetate is considered as not irritating for skin.
Eye Irritation/Corrosion		Experimental data: This substance was not irritating for rabbits (50 mm3 of undiluted substance).	Weight of evidence: Read-across approach from experimental data on analogues Potassium Acetate, Ammonium Sulphate, and Ammonium Stearate, based on functional group: The substance Ammonium Acetate is considered as not irritating for eyes.
Skin Sensitization		No data	Weight of evidence:   Read-across approach from experimental results on Citric Acid, Glycolic Acid, Sodium Glycolate, Lactic Acid, Ammonium Lactate, and Triacetin, based on functional group:   All this substances were not sensitising for human and guinea pigs. Based on these results, Ammonium acetate is considered to be not sensitizing.
Repeated Dose Toxicity		Experimental data: A 14-day inhalation study on rats exposed to 300 mg/m3, the only tested dose, did not report histopathological changes in the lower respiratory tract. As the respiratory tract is the target organ for inhalation exposure, the NOEL for toxicity to the lower respiratory tract is 300 mg/m3.   The NOAEL after feeding diets containing ammonium sulfate for 13 weeks to rats was 886 mg/kg bw/day. The only toxicity sign found was diarrhea in male animals of the high-dose group (LOAEL: 1792 mg/kg bw/day).	Repeated dose toxicity: oral: Weight of evidence: Experimental results:   Repeated dose toxicity: oral: 90 days withfemale Wistar rats. The NOAEL was 3150.4 mg/kg bw/day. Repeated dose toxicity: oral: 15 days study with female Wistar rats. The NOAEL 3102.2 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights:   The NOAEL >= 0.047 mg/kg bw/day, in male rats chronically treated for 8 months via drinking water. The NOAEL >= 3382.76 mg/kg bw/day, in male Wistar rats daily treated for 4 weeks by feed. The NOAEL >= 19.73 mg/kg bw/day, in male Long-Evans rats treated for 3 months in the diet. The NOAEL >= 0.0094 mg/kg bw/day, in male Wistar rats treated by drinking water for 112 days.    Read-across from the analogue Citric acid, sodium salt, based on molecular weights:   The NOAEL >= 54 mg/kg bw/day, in albino rats treated for ca. 1 year.
Genetic Toxicity in vitro	-         Gene mutation in bacteria	Experimental data: Ammonium sulfate was not mutagenic in bacteria (Ames test) and yeasts with and without metabolic activation systems.	Weight of evidence:   Read-across from Sodium Acetate (category analogue) based on functional group:   Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 with metabolic activation. Resultslead to the conclusion that Ammonium Acetate did not cause point mutations in the microbial systems. Read-across from Acetic Acid, based on functional group:   Ammonium Acetate is considered to be not mutagenic on S.typhimurium TA 98, TA 100, TA 1535, TA 97, and/or TA 1537, with and without metabolic activation. Read-across from experimental data on Ammonia, anhydrous, based on functional group: Ammonium acetate is considered to be not mutagenic on Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 1538, and Escherichia coli WP2uvrA, with and without metabolic activation.   Read-across from experimental data on Ammonia, aqueous solution, based on functional group: Ammonium acetate is considered not mutagenic on E. coli Sd-4-73, without metabolic activation.
	-         Mammalian gene mutation	No data	Weight of evidence: Read-across from the analogue Acetic anhydride, based on functional group: Ammonium acetate is considered to be not mutagenic on mouse lymphoma L5178Y cells, with and without metabolic activation. Read-across from the analogue Phenoxy acetic acid, based on functional group: Ammonium acetate is considered to be not mutagenic on Chinese hamster ovary cells, with and without metabolic activation.   Estimated data from Danish (Q)SAR Database: Ammonium acetate was not mutagenic in mammalian cell gene mutation assays on mouse lymphoma L5178Y cells nor on Chinese hamster ovary cells.
	-         Chromosomal aberration	Experimental data:   Ammonium sulfate did not induce chromosomal aberrations in mammalian or human cell cultures.	Weight of evidence: Read-across from Sodium Acetate (category analogue) based on functional group:   In an in vitro chromosomal aberration assay with a Chinese hamster fibroblast cell line, CHL, without metabolic activation systems, it is concluded that Ammonium acetate did not induce chromosomal aberrations(including gaps). Read-across from Acetic Acid, based on functional group:   Ammonium Acetate is considered as not clastogenic on Chinese hamster Ovary (CHO) cells, without metabolic activation. Read-across from Ammonium Sulfate, based on functional group: Ammonium Acetate is not considered mutagenic on Chinese Hamster Ovary cells, in the absence of a metabolic activation system.
Genetic Toxicity in vivo		No data	Key studies: Read-across from Sodium Acetate (category analogue) based on functional group:   The Testicular DNA-synthesis inhibition test (DSI test) on male mice provides evidence that Ammonium acetate is not genotoxic in animals (basis of the method: measuring 3H-thymidine incorporation). Test substance did not inhibit DNA replication in this assay.
Carcinogenicity		Experimental data: Similarly to other salts, high doses of ammonium sulfate may have the capability of tumor promotion in the rat stomach; it is, however, much less potent than sodium chloride when tested under identical conditions.	No data
Reproductive Toxicity		TOXICITY TO REPRODUCTION: Fischer 344 rats (10 rats/sex/dose) were exposed during 13 weeks to diets containing 0, 0.38, 0.75, 1.5 or 3 % ammonium sulfate (corresponding to 0, 222, 441, 886, 1792 mg/kg bw/day in males and to 0, 239, 484, 961, 1975 mg/kg bw/day in females). No effects on the reproductive organs were observed. Therefore, the NOAEL was 886 mg/kg bw/day for males and 1975 mg/kg bw/day for females.   DEVELOPMENTAL TOXICITY / TERATOGENICITY: No data.	TOXICITY TO REPRODUCTION: Weight of evidence: Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). A fertility test on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 722.25 mg/kg bw/day, and LOAEL greater than 722.25 mg/kg bw/day for reproductive effects. Read-across from the analogue Citric Acid, sodium salt, based on molecular weights: A fertility study on female rats daily treated by feed for several months. For Ammonium Acetate, the NOAEL is calculated to be 54.0 mg/kg bw/day, and LOAEL greater than 54.0 mg/kg bw/day for reproductive effects. Read-across from the analogue Ammonium sulfate, based on molecular weights: A study on male and female rats exposed for 13 weeks to diets with Ammonium Sulfate. For Ammonium Acetate, the NOAEL is calculated to be 1033.64 mg/kg bw/day for males, and 2304.12 mg/kg bw/day for females.   DEVELOPMENTAL TOXICITY / TERATOGENICITY: Weight of evidence: Experimental results: A study on female rats fed an ammonium-containing diet starting on day 1 of pregnancy until weaning (at posnatal day on 21). After weaning, pups were either fed a normal diet, with no ammonium acetate added, or continued on ammonium until sacrifice. The NOAEL for developmental toxicity was 4293 mg/kg bw/day . Read-across from the analogue Sodium Acetate, based on molecular weights: Pregnant CD-1 mice were treated by oral gavage with Sodium Acetate on days 8-12 of gestation. For Ammonium Acetate, theNOAEL is calculated to be939.66 mg/kg bw/day (based on maternal toxicity: mortality, pregnancy and resorption; and on neonatal effects: mortality and body weight). Read-across from the analogue Citric Acid, based on molecular weights: A study on rats and mice daily treated by feed before, during, and after mating. For Ammonium Acetate, the NOAEL is calculated to be equal or greater than 3009.37 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young). Read-across from the analogue substance Calcium Formate, based on molecular weights: A three-generation drinking water study was performed. For Ammonium Acetate, the NOAEL is calculated to be equal or higher than 236.96 mg/kg bw/day. Read-across from Acetic Acid, based on molecular weights: A one-generation study was performed on female mice, rats and rabbits with Acetic Acid. The read-across approach was applied and the NOAEL with the substance Ammonium acetate is calculated to be equal or greater than 2055.47 mg/kg bw/day for maternal and developmental toxicity in mice, rats, and rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance Ammonium Acetate is considered as not irritating under test conditions.

Executive summary:

Based on the experimental results (reported under the endpoint record 07.03.02_05 Ammonium sulphate) obtained with the analogue Ammonium Sulphate, which is considered to be not irritating for the rabbits eyes, and applying the read-across approach, the substance Ammonium Acetate is also considered as not irritating under test conditions.

Reference 6

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The method use is similar to OECD 405 guideline. No GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

According to "Description of methods used in BASF acute toxicity and skin/eye irritation studies before pertinent OECD/EU test guidelines were in place" (BASF AG, 2002)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.05mL

Duration of treatment / exposure:

The substance was not washed out.

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing
SCORING SYSTEM: Draize Score system

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Corneal opacity : 1 hr: none (0) ; 24 hrs : none (0) ; 8 days: none (0). Redness : 1 hr: + (1) ; 24 hrs : + (1) ; 8 days: none (0 ) Edema: I hr:+(1) ; 24 hrs : none(O) ; 8 days : none (0)

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Redness: I hr:+(1) ; 24 hrs : +(1) ; 8 days : none (0)

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Edema: I hr:+(1) ; 24 hrs : none(O) ; 8 days : none (0)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: After 24h score was 0, no data for 24 and 72h.

Corneal opacity : 1 hr: none (0) ; 24 hrs : none (0) ; 8 days: none (0). Findings occurred to a comparable extent in both animals.

Redness : 1 hr: + (1) ; 24 hrs : + (1) ; 8 days: none (0 )

Edema: I hr:+(1) ; 24 hrs : none(O) ; 8 days : none (0)

The treatment led to slight conjunctival edema and redness . All findings were reversible after 8 days of observation period . The control eyes which were treated with talcum showed slight redness after 1 and 24 hours, but were reversible after 8 days .

Interpretation of results:

GHS criteria not met

Conclusions:

Slight edema and conjunctival redness was noted at 1 hour after instillation of the test substance; no edema, but still slight redness was present at 24 hours. In the eyes treated with talcum, slight redness was also noted at 1 and 24 hours after exposure. No effects were noted at day 8.

Executive summary:

The ieye irritation test was performd in two rabbits. 0.05mL of indiluted substance were introduced and the eyes were not rinsed.Slight edema and conjunctival redness was noted at 1 hour after instillation of the test substance; no edema, but still slight redness was present at 24 hours. In the eyes treated with talcum, slight redness was also noted at 1 and 24 hours after exposure. No effects were noted at day 8. the substance is npot irritating for eyes.

Undiluted test substance was instilled into one eye of rabbits, the other eye was treated in the same way with 50 mm3 of talcum and served as control. The eyes were not rinsed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation/corrosion:

Weight of evidence: Read-across approach from experimental results obtained with Potassium Acetate, Ammonium Lactate, Ammonium Stearate, all not irritating for skin.

Ammonium Acetate is also considered as not irritating for skin.

Eye irritation/corrosion:

Weight of evidence: Read-across approach from experimental results obtained with Potassium Acetate, Ammonium Stearate, and Ammonium Sulphate, all not irritating for eyes.

Ammonium Acetate is also considered as not irritating for eyes.

Justification for classification or non-classification

Not irritant for skin and not irritant for eyes.