2

EXECUTIVE SUMMARY

EPA received a petition ( IN

- 10 604 ) from Exponent Inc., (1150 Connecticut Ave., Suite 1100 Washington, DC 20036) on behalf of the Gowan Company LLC (370 South Main Street, Yuma,
AZ 8536 7 ) requesting a tolerance exemptio n for use of ammonium acetate (CAS Reg No. 631

- 61

- 8) as an inert ingredient (buffering agent) limited to 15% in pesticide formulations under 40
CFR Part 180.920. EPA published the notice of filing for this petition in the Federal Register on December 30, 2013 ( 78 FR 79359 ). No substantial comments were received in response to this
notice. Ammonium acetate is currently approved as a n inert ingredient for non

- food use.

The following information in this decision document is reproduced from the petition submitted by the registrant (MRID 49160501), EPA document, Acetic acid and Salts summary
document , American Chemical Council (ACC) Acetic Acid and Acetate Panels High Production
V olume (HPV) Challenge Program

.

Ammonium acetate is an ammonium salt of ace tic acid. In aqueous solutions acetic acid and
its salt ammonium acetate dissociate into the acetate anion ( CH 3 COO

- ) and the respective cations (H+ and NH 4 + ). The cations and ammonia (also a human metabolite) are physiological components of the human bod y

. The chemical structures, physical

- chemical properties, environmental fate behavior, and aquatic and mammalian toxicity of ammonium acetate and
acetic acid are similar. Since limited data are available on ammonium acetate , toxicity data on
acetic acid were used to represent toxicity due to exposure to ammonium acetate.

Acetic acid is of low acute dermal and inhalation toxicity in rats

. T he acute dermal LD 50 was

> 1,060 mg/kg a nd the acute inhalation LC 50 was > 11.4 mg/L (equivalent to 2956 mg/kg)

. Der mal irritation was observed at > 100 mg/kg in mice and w as corrosive at > 60% in rabbits . It
was also ir ritating in the eyes of rabbits

.

A 90

- day oral toxicity study was available in rats administered acetic acid in drinking water. Although r educed body weight was observed at 390 mg/kg/day , t he reduction in weight gain was likely attributed to reduced appetite and food consumption observed in the study. The refore, this
was not considered adverse effect

. Rats treated for 8 months with 60 mg/kg bw/treatm ent (the only dose tested) of acetic acid ( 3 times/week ) via gavage

, exhibited hyperplasia in the esophagus and forestomach but did not have tumors

.

Several developmental toxicity studies were available with acetic acid. Fetal susceptibility

was not o bserved in any of the studi es. In rats, mice and rabbits maternal and developmental toxicity was not observed up to 1600 mg/kg/da y . Reproduction toxicity studies were not
available with acetic acid.

Tumors were not observed in r ats treated for 8 months with 60 mg/kg bw/treatment of acetic
acid in drinking water.

Acetic acid was not mutagenic in an Ames test nor was it clastogenic in a cytogenetic assay with Chinese hamster ovary K1 cells.3

In a toxicity study via the inhalation route of exposure, t oxicity was manifested as decreased activity, behavioral changes and reduced work capacity following 22 days of treatment with 15

ppm (equivalent to 10 mg/kg/day ) of acetic acid in rats and mice. The NOAEL was 11 ppm ( equivalent to 7 mg/kg/day ).

Neuroto xicity studies for ammonium acetate were not available for review. However, signs of neurotoxicity were observed in a study conducted by Satpute et.al. that is in the literature. Following 4 weeks of treatment with 100 mg/kg/day of ammonium acetate via g avage to Wistar rats

, mild chromatolysis of nuclear material, moderate gliosis, and occasional neuronal vacuolation and edema were observed in the cortex of the brain. In the hippocampal region, moderate neuronal degeneration and pyknosis in the nuclei of pyramidal neurons were observed. In the cerebellum, there was moderate pyknosis and necrosis in Purkinje neurons. A second study (conducted by the registrant) in rats was conducted following the Organization for Economic Co

- operation and Development (OE CD) and good laboratory practice (GLP) guidelines. In this study, Sprague Dawley rats were treated for 28 days with 100 mg/kg/day of ammonium acetate via gavage. There was no indication of systemic toxicity, neurotoxicity, neuropathological or histologic al lesions.

Immunotoxicity studies for acetic acid were not available for review. However, increased spleen weight was observed at 23

- 31 ppm (equivalent to 15

- 19 mg/kg/day ) of acetic acid in a toxicity study in rats via the inhalation route of exposure

. However, these effects are not due to
an immun otoxic response but due to red blood cell destruction rather than an immunotoxic

response . Theref

or e, there is no concern for potential immunotoxicity. In addition , according to
the American Conference of Governmental Industrial Hygenists, Inc. (ACGIH), the threshold limit value (TLV) for occupational exposure to acetic acid is 10 ppm via inhalation. Based on the requested use pattern, occupational inhalation exposure is not expected. With regard to
resid ential uses, exposure will be much lower because exposure is expected to occur for shorter periods to diluted acetic acid as compared to workers who are exposed for 8 hours continuously, to more concentrated acetic acid. Therefore, a qualitative assessmen t was conducted with regard to inhalation exposure.

Ammonium acetate is an ammonium salt of acetic acid. Acetic acid undergoes dissociation
to the acetate anion and the H+ cations in aqueous media at pHs commonly found in the environment. Also, it is a naturally

- occurring substance in plants and animals. In aerobic metabolism, acetic acid (as acetate) is a metabolite that combines with Co

- enzyme A to form acetyl Co

- A which subsequently enters into the Citric Acid Cycle, a common metabolic pathway
in whi ch food molecules are broken down to form energy. A major function of the Citric Acid Cycle is the oxidation of acetate. In animals, acetate is obtained from the b reakdown of glucose
molecules.

Since acetic acid dissociates to its salt , ammonium acetat e, in an aqueous environment, toxicity due to its exposure is expected to be similar to that of acetic acid exposure

. Therefore,
based on the absence of a toxicological endpoint of concern, the regulatory history of acetic acid and no new toxicological da ta to indicate concern regarding previous decisions

, a qualitative

assessment of ammonium acetate is appropriate for all pathways of human exposure (food, drinking water, and residential).4

Occupational exposure was qualitatively assessed based on the la ck of toxicity of ammonium

acetate

.

Ammonium acetate is not expected to be toxic to aquatic organisms, terrestrial mammals and birds. It does not persist in the environment.

Taking into consideration all available information on ammonium acetate , EP A concludes that there is a reasonable certainty that no harm will result to the general population or to infants and children from aggregate exposure to ammonium acetate . Therefore, the establishment of an exemption from tolerance under 40 CFR 180. 920 fo r residues of ammonium acetate as an inert ingredient (buffering agent) limited to 15 % in pesticide formulations for pre

- harvest use on

crops can be considered safe under section 408 of the FFDCA.

1

. BACKGROUND

The EPA received a petition (IN

- 10 604 ) fr om Exponent

, Inc., (1150 Connecticut Street, Suite
1 1 00 Washington, DC 20036) on behalf of Gowan Company LLC (370 S outh Main Street, Yuma, AZ 85367 ) requesting a tolerance exemption for use of ammonium acetate (CAS Reg No.
631

- 61

- 8) as an inert ingredient (buffering agent) limited to 15% in pesticide formulations under
40 CFR Part 180.920. EPA published the notice of filing for this petition in the Federal Register on December 30, 2013 (78 FR 79359). No substantial comments were received in response to

t his notice. Ammonium acetate is currently approved as a n inert ingredient for non

- food use.

Since ammonium acetate is an ammonium salt of acetic acid, toxicity data on acetic acid were used to characterize toxicity due to exposure to ammonium acetate. This document provides an assessment of the risk to human health and the environment for ammonium acetate when used as an inert ingredient in pesticide formulations. Information utilized from the petition submitted by the registrant (MRID 49160501), EPA documents (2008, Attachment I, 2010, Attachment II), American Chemical Council (ACC) Acetic Acid and Acetate Panels High Production Volume (HPV) Challenge Program (200la, b, Attachments III and IV) is reproduced
and referenced in this assessment.

2. Iner t Ingredient Profile

Some of the physical a nd chemical characteristics of ammonium acetate along with its structure and nomenclature, are found in Table 1.

Table 1

. Physical and Chemical Properties of Ammonium Acetate

Parameter Value Source

Structur e MRID 491605015 CAS # 631

- 61

- 8 Molecular Weight (g/mol) 77.08

Common Names Ammonium acetate

, Acetic acid, ammonium salt; Ammonium ethanoate Physic al State Clumpy white wet powder Melting Point (°C) 114 Boiling Point (°C) Decomposes above 160°C pH@20° C 2.5 for 50 g/L solution Vapor Pressure (mm Hg @

2 0 °C) 0.00014

Partition Coefficient (Log Kow )

- 2.79 Water Solubility (g/L at 23°C) 827.29

3

. Hazard A ssessment

Limited data are available on ammonium acetate. Since, it is an ammonium salt of acetic acid, toxicity data from acetic acid were used to bridge data gaps for ammonium acetate. The following studies were reproduced and refere nced from the petition submitted by the registrant (MRID 49160501), EPA document, Acetic acid and Salts summary document, American Chemical Council (ACC) Acetic Acid and Acetate Panels High Production Volume (HPV) Challenge Program

.

Acute Toxicity Studies

Table 2 Ac ute Toxicity Profile of Ammonium Acetate

Guideline No. Study Type Results

Acute

- rat s

intraperitoneal injection LD50= 632 mg/kg

Acute

- mouse

intravenous injection LD50= 98 mg/kg

Acute Toxicity Profile of Aceti c Acid

870.1000 Acute

- Oral

- rats LD50> 3,310 mg/kg

870.1000 Acute

- Oral

- mice LD50> 4,960 mg/kg

870.1100 Acute

- Dermal

- rats LD50> 1,0 60 mg/kg

870.1100 Acute

- Dermal

- mice > 1 00 mg/kg in mice produced
irritation6

870.1200 Acute

- Inhalation

- rats LC50> 11.4 mg/L (equivalent to 2956 mg/kg)

870.2400 Acute

- Eye Irritation

rabbits Irritating

870.2500 Acute

- Dermal

Irritation

- rabbits Corrosive at >60%

Toxicity studies with Ammonium Acetate

28 Day Oral

- Gavage

- Toxicity Study

- Rat

In the study conducted by Satpute et. al. (2014), male Wistar rats (10/group) were treated with
0 or 1 00 mg/kg/day of ammonium acetate for 4 weeks via gavage. Hematology, blood gas analysis and plasma ammonium were measured from blood samples collected at 1, 2 and 4 weeks of
treatment. Catal ase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione(GSH) and glutathione disulfide (GSSG) levels were measured. Plasma alkaline phosphatase (ALP), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and total bilirubin and were determined for liver function and plasma urea, uric acid and creatinine were measured for kidney function. The NH 3 concentration in plasma was also measured. The organ

–

body weight index (OBI) was calcu lated for the brain, liver and kidney of 6 animals from each group. Histological examination was conducted on the brain, liver and kidney of the remaining 4 animals from each group.

The OBI of the brain and liver were significantly increased by 48 and 23%, respectively, in rats treated with ammonium acetate. CAT, SOD, GPX, GR, GSH, GSH: GSSG levels were significantly reduced accompanied by a significant increase in malondialdehyde levels in the brain and liver when compared to controls. The levels of the aforementioned enzymes in the kidney of treated animals were comparable to the controls. Ammoniu m acetate caused a significant increase in the levels of plasma ALP, ALAT, ASAT (263%) and bilirubin (236%). Ammonia levels were also increased after
4 we eks of treatment with ammonium acetate. Urea, uric acid and creatinine levels and hematology parameters were comparable to controls.

Microscopic evaluation showed mild chromatolysis of nuclear material, moderate gliosis, and
occasional neuronal vacuol ation and edema in the cortex of the brain and animals treated with ammonium acetate. In the hippocampal region, moderate neuronal degeneration and pyknosis in the nuclei of pyramidal neurons were observed. In the cerebellum, there was moderate pyknosis and necrosis in Purkinje neurons. In the liver there was moderate hepatocellular degeneration, hepatic vacuolation, clumping of cytoplasm, necrosis and karyolysis in hepatocytes along with the infiltration of polymorphonuclear cells and desquamation of en dothelium of central canal. In the kidney there was moderate tubular degeneration, karyolysis, tubular dilation and renal parenchyma necrosis leading to vacuolative degeneration of convoluted tubules.

A second study was conducted by the registrant in re sponse to the Agency’s concern regarding the Sapute et.al. (2014) study, a summary of this study is below.7

Sprague Dawley rats (10/group) were treated with 0 or 1 00 mg/kg/day of ammonium acetate
for 28 days via gavage. The following parameters were eval uated: viability, clinical signs, body weights, body weight gain, clinical chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin), gross necropsy findings, organ weights and histopathology of the brain, liver and kidneys.

There were no test substance

- related clinical signs or effects on body weight, body weight gain, clinical chemistry, absolute or relative organ weights, and there were no findings at gross necropsy or in the histopathology o f the brain, liver or kidneys ( MR ID 4 9 7 0 3 2 0 1 )

.

Repeated Dose Toxicity studies with Acetic Acid

90

- Day oral

- Drinking W ater

- R at

A 90

- day feeding study in rats was conducted with acetic acid

. Rats administered up to 390 mg acetic acid/kg/day in drinking water for 2 to 4 months had a LOAEL of 390 mg/kg/day (based on weight loss) and a NOAEL of 195 mg/kg/day

. ( Hummel, S., 2/28/07, D344771 ). The reduction in weight gain was likely attributed to reduced appetite and food consumption observed in the study. Therefore, thi s effect was not considered adverse and the NOAEL is 390 mg/kg/day.

Developmental T oxicity Studies

Rat:

In a developmental toxicity study in albino Wistar rats

, mated female rats were administered acetic acid (5%) via gavage at 0, 16, 74, 345 and 1600 mg/kg/day on gestation days 6

- 16. On day 20, Caesarean sections were performed. The number of implantation sites, resorption sites
and live and dead fetuses were similar to the controls. Neither maternal nor fetal treatment related effects were observed up to 1600 mg/kg /day, the highest dose tested (HPV , 2001 )

.

Mouse:

In a developmental toxicity study in CD

- 1 mice, mated female mice were administered acetic acid (5%) via gavage at 0, 16, 74, 345 and 1600 mg/kg/day on gestation days 6

- 1 6

. On day 17, Caesarean sections were performed. The number of implantation sites, resorption sites and live
and dead fetuses were similar to the controls. Neither maternal nor fetal treatment related effects were observed up to 1 6 00 mg/kg /day, the highest dose tested (HPV, 2001)

.

Rabbit:

In a developmental toxicity study in Dutch

- belted rabbits

, artificially inseminated female
rabbits were administered acetic acid (5%) via gavage at 0, 16, 74, 345 and 1600 mg/kg/day on8

gestation days 6

- 19. On day 29, Caesarean se ctions were performed. The number of corpora lutea, implantation sites, resorption sites and live and dead fetuses were similar to the controls.
Neither maternal nor fetal treatment related effects were observed up to 1 6 00 mg/kg/day, the highest dose tes ted ( HPV, 2001 )

.

8

- Month

- Oral Toxicity / Carcinogenicity Study

- Rat

In an 8

- month oral toxicity study in rats

, the carcinogenic potential of acetic acid was evaluated. In this study

, nine outbred white male rats were administered 0.5ml of 3% water
solu tion of acetic acid ( equivalent to 60 mg/kg /treatment) via gavage three times per week for eight months. Rats were given N

- ni tro so sarcosin e ethyl ester (NSEE; a known carcinogen) alone
and NSEE with an acetic acid solution, or the acetic acid solution alo ne. Rats treated with the carcinogen and NSEE had high incidences of pre

- neoplastic lesions in the esophagus and forestomach as well as benign tumors, carcinomas and squamous cell cancer. Rats treated with
acetic acid and NSEE had an increase in the numb er of benign and malignant tumors and carcinomas in the esophagus. Rats treated with acetic acid alone had hyperplasia in the esophagus and forestomach but did not have tumors ( HPV, 2001 )

.

Genotoxicity Studies

In a bacterial reverse mutation assay S a lmonella typhimurium strains TA 98, TA 100, TA 1535, TA 97 and TA 1537 were treated with acetic acid at concentrations of 100, 333, 1000 3333, 6666 and 10,000 μg/plate with and without metabolic activation. No revertant colonies
were observed ( HPV, 2001 )

.

In a cytogenetic assay, Chinese hamster ovary K1 cells we re treated with acetic acid at concentrations up to 16mM. Acetic acid was not clastogenic ( HPV, 2001 ).

Inhalat ion Toxicity Study

Rats and mice were treated with 11

- 15 ppm ( equivalent to 7

- 10 mg/kg/day) of acetic acid via the inhalation route of exposure for 3

- 35 days. Groups of 10 rats and mice (sex unknown) were exposed to 15 ppm ( equivalent to 10 mg/kg/day) of acetic acid for 22 days or more exhibited decreased activity, behavioral changes a nd reduced work capacity. At 23

- 31 ppm ( equivalent to
1 5

- 19 mg/kg/day) , animals exhibited decreased growth, increased spleen weight, an increase of the level of iron stored in the spleen, signs of kidney damage and increased kidney weights. The
LOAEL was 15 ppm (equivalent to10 mg/kg/day) based on decreased activity, behavioral changes and reduced work capacity

. The NOAEL was 11 ppm ( equivalent to 7 mg/kg/day ) ( HPV, 2001 )

.

Neurotoxicity Study9

Neurotoxicity studies for ammonium acetate were not availabl e for review. However, signs of neurotoxicity were observed in a study conducted by Satpute et.al. that is in the literature. Following 4 weeks of treatment with 100 mg/kg/day of ammonium acetate via gavage

, mild chromatolysis of nuclear material, modera te gliosis, and occasional neuronal vacuolation and edema
were observed in the cortex of the brain in Wistar rats . In the hippocampal region, moderate neuronal degeneration and pyknosis in the nuclei of pyramidal neurons were observed. In the cerebellum, there was moderate pyknosis and necrosis in Purkinje neurons. A second study in rats
was conducted following OECD and GLP guidelines. In this study, Sprague Dawley rats were treated for 28 days with 100 mg/kg/day of ammonium acetate via gavage. There w as no indication of systemic toxicity, neurotoxicity, neuropathological or histological lesions.

Immunotoxicity Study

Immunotoxicity studies for ammonium acetate were not available for review. However, increased spleen weight was observed at 23

- 31 pp m (equivalent to 15

- 19 mg/kg/day) of acetic acid in a toxicity study in rats via the inhalation route of exposure. However, these effects are not due to an immunotoxic response but due to red blood cell destruction rather than an immunotoxic response . In addition, according to the American Conference of Governmental Industrial Hygenists, Inc. (ACGIH), the threshold limit value (TLV) for occupational exposure to acetic acid is 10 ppm via inhalation. Based on the requested use pattern, occupational inhalat ion exposure is not expected. With regard to residential uses, exposure will be much lower because exposure is expected to occur for shorter periods to diluted acetic acid as compared to workers who are exposed for 8 hours continuously, to more concentrat ed acetic acid. Therefore, there is no concern for potential immunotoxicity.

Metabolism

Ammonium acetate is an ammonium salt of acetic acid. In aqueous solution, ammonium acetate dissociates into the ammonium cation (NH4+) and acetate anion (CH3C OO

- ). The cations and ammonia (also a human metabolite) are physiological components of the human body. The toxicity assessment of the exposure and risk of acetic acid and acetate salts is driven by the acetate anion (which is also a human metabolite).

Acetic acid undergoes dissociation to the acetate anion and the H+ cations in aqueous media at pHs commonly found in the environment. Also, it is a naturally

- occurring substance in plants and animals. In aerobic metabolism, acetic acid (as acetate) is a metabolite that combines with
Co

- enzyme A to form acetyl Co

- A which subsequently enters into the Citric Acid Cycle, a common metabolic pathway in which food molecules are broken down to form energy. A major function of the Citric Acid Cycle is the oxid ation of acetate. In animals, acetate is obtained from the breakdown of glucose molecules.

Table 3 . Toxicology Profile for Ammonium Acetate

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results10

Table 3 . Toxicology Profile for Ammonium Acetate

Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

4 Week Oral

- Gavage

Toxicity

– Wista r

- Rat 0 and 100 mg/kg/day NOAEL was not established.

LOAEL = 100 mg/kg/day based histopathological lesions in the brain, liver and kidneys.

4 Week Oral

- Gavage

Toxicity

– Sprague Dawley

Rat 0 and 100 mg/kg/day NOAEL = 100 mg/kg/day.

LOAEL was not establish ed.

Table 4 . Toxicology Profile for Acetic Acid

Study Type Doses Results

3

- 35 Day

- inhalation

- rat 11

- 35 ppm ( equivalent to 7

- 23 mg/kg/day) The NOAEL = 11 ppm ( 7 mg/kg/day)

The LOAEL = 15 ppm ( equivalent to 10 mg/kg/day ) based
on decreased activit y, behavioral changes and reduced work capacity. 90 day oral

- F344 rats

drinking water 195 and 390 mg/kg/day NOAEL = 390 mg/kg/day

LOAEL was not established.

8

- Month

Oral/Carcinogenicity Toxicity Study

- Rat

- gavage ( equivalent to 96 days) 60 mg/kg/treatmen t The NOAEL was not established

. LOAEL = 60 mg/kg/ treatment based on hyperplasia in the esophagus and forestomach.

No tumors were observed. Developmental toxicity

- rat 0, 16, 74, 345 and 1600 mg/kg bw/day The NOAEL = 1600 mg/kg/day

. The LOAEL was not est ablished.

Developmental toxicity

mouse 0, 16, 74, 345 and 1600 mg/kg/day The NOAEL = 1600 mg/kg/day

. The LOAEL was not established.

Developmental toxicity

rabbit 0, 16, 74, 345 and 1600 mg/kg /day The NOAEL = 1600 mg/kg/day

. The LOAEL was not established.

Ames assay 100, 333, 1000 3333, 6666 and 10,000 μg/plate Negative

Cytogenetic assay < 16 mM Negative11

5. Toxicity Endpoint Selection

In an aqueous environment, acetic acid dissociates to its ammonium salt, ammonium

acetate. Therefore, it is appropr iate to expect toxicity due to exposure to ammonium acetate to be similar to that of acetic acid. Since there is no toxicological endpoint of concern for acetic acid, a qualitative assessment was appropriate for ammonium acetate for all pathways of human exposure (food, drinking water, and residential). A potential endpoint of concern for the inhalation route of exposure was identified in a toxicity study. Increased spleen weight due to
red blood cell destruction was observed at 23

- 31 ppm (equivalent to 1 5

- 19 mg/kg/day) of acetic acid in rats. However, according to the American Conference of Governmental Industrial Hygenists, Inc. (ACGIH), the threshold limit value (TLV) for occupational exposure to acetic acid is 10 ppm via inhalation. Residential expos ure to the proposed use of ammonium acetate via inhalation is not expected to exceed the TLV limit of 10 ppm because the residential use pattern would result in drastically lower opportunities for inhalation exposure than allowed occupational use patterns, which are limited to 10 ppm. In addition, residential exposure will be much lower because exposure is expected to occur for shorter periods to diluted acetic acid as compared to workers who are exposed for 8 hours continuously, to more concentrated aceti c acid. Therefore, a qualitative assessment was conducted with regard to inhalation exposure.

6. Sp ecial Considerations for Infants and Children

As part of its qualitative assessment, the Agency did not use safety factors for assessing risk,
and no additional safety factor is needed for assessing risk to infants and children. Based on the lack of toxicity of ammonium acetate in the available studies and its chemical properties, EPA has concluded that there are no toxicological endpoints of concern f or the U.S. population, including infants and children.

7

. Exposure Assessment

Dietary Exposure

In evaluating dietary exposure to ammonium acetate , EPA considered exposure under the petitioned for exemptions from the requirement of a tolerance. Sin ce no endpoint of concern was identified for the acute and chronic dietary exposure assessment and short and intermediate dermal and inhalation exposure, a quantitative risk assessment for ammonium acetate is not

necessary.

Cancer. A mmonium acetate is no t expected to be carcinogenic since there was no evidence of carcinogenicity in an oral toxicity study in rats and ther e was a negative response for mutagenicity. Since the Agency has not identified any concerns for carcinogenicity relating to
ammonium ac etate a cancer dietary exposure assessment was not performed.12

8

. Residential (Non

- Occupational) Exposure/Risk Characterization

Ammonium acetate may be used in pesticide and nonpesticide products that may be used
around the home

. However, based on the absence of a toxicological endpoint of c oncern, a qualitative assessment was conducted for residential exposure

.

9

. Occupational Exposure/Risk Pathway

The Agency believes that establishing a tolerance exemption to include 40 CFR Part 180.9 20
will no t significantly/measurably increase occupational exposure. In view of the regulatory history of acetic acid , its lack of toxicity and no new toxicological information to indicate otherwise, it is not necessary to quantitatively assess occupational exposur e. Therefore, occupational exposure to ammonium acetate was qualitatively assessed.

1 0

. Cumulative Exposure :

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the EPA consider "avai lable information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity." Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mech anism of toxicity, EPA has not made a common mechanism of toxicity finding as to ammonium acetate and any other substances and, this material does not appear to produce a toxic metabolite produced by other substances. For the purposes of this
tolerance ac tion, therefore, EPA has not assumed that ammonium acetate ha s a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the
cumulative ef

fects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://w ww.epa.gov/pesticides/cumulative/.

1 1

. Ecotoxic i ty and Environmental Fate

Based on the “Acetic Acid and Sodium Diacetate Proposed Interim Registration Review Decision (Dock et Number EPA

- HQ

- OPP

- 2008

- 0016), ammonium acetate is not expected to be
toxic to aquatic organisms, terrestrial mammals and birds . It does not persist in the environment. Therefore, the same is expected for ammonium acetate.

1 2

. Enviro n mental Justice

Potential areas of environmental justice concerns, to the extent possible, we re considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal13

Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimate s risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumptio n patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age , season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, n on

- dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. Further considerations are currently in develo pment as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

1 3 . Risk Charac terization

EPA received a petition ( IN

- 10 604 ) from Exponent Inc., (1150 Connecticut Ave., Suite 1100 Washington, DC 20036) on behalf of the Gowan Company LLC (370 S outh Main Street, Yuma,
AZ 85367 ) requesting a tolerance exemption for use of ammonium acet ate (CAS Reg No. 631

- 61

- 8) as an inert ingredient (buffering agent) limited to 15% in pesticide formulations under 40
CFR Part 180.920. EPA published the notice of filing for this petition in the Federal Register on December 30, 2013 (78 FR 79359). No s ubstantial comments were received in response to this
notice. Ammonium acetate is currently approved as a n inert ingredient for non

- food use.

Since

, i n an aqueous environment, acetic acid dissociates to its ammonium salt, ammonium

acetate , toxicity du e to its exposure is expected to be similar to that of acetic acid exposure. Therefore, based on the absence of a toxicological endpoint of concern, the regulatory history of
acetic acid and no new toxicological data to indicate concern regarding previous decisions

, a qualitative assessment was appropriate ammonium acetate for all pathways of human exposure (food, drinking water, and residential).

Neither aggre gate (i.e. residential) nor occupational exposure s is of concern.

Ammonium acetate is not expected to be toxic to aquatic organisms, terrestrial mammals and birds. It does not persist in the environment.

Taking into consideration all available information on ammonium acetate , EPA concludes that there is a reasonable certainty that no harm wi ll result to the general population or to infants and children from aggregate exposure to ammonium acetate . Therefore, the establishment of an exemption from tolerance under 40 CFR 180. 920 for residues of ammonium acetate as an inert14

ingredient (buffering agent) limited to 15 % in pesticide formulations for pre

- harvest use on

crops can be considered safe under section 408 of the FFDCA.15

REFERENCES

American Chemistry Council Acetic Acid and Salts Panel, 20 0 1 , U.S

. High Production Volume (HPV) Chemical C hallenge Program: Robust summaries for
Acetic acid and salts category.

B a rn et t

, Jr

. , Jo hn F. ( 20 1 5 )

. A 28

- D ay Or a l ( G a vag e ) Re p e ate d Do se S tud y of Am m o n iu m Ac e tat e in Ad ul t Rat s

. L a bor at ory P ro j ec t I D 2 00 7 36 69

. U n pu bli sh ed s tud y p rep a re d by C ha rle s Ri ve r L ab or ator i e s

. M RID 49 7 0 3 20 1

.

EPA. Hummel, S. ( 2007 ) Memorandum: Acetic Acid Registration Review Case No. 4001.DP Barcode D344771. November 28, 2007.

Petition for Exemption From the Requirement of a Tolerance For Residues of Ammonium Acetate (CAS# 631

- 61

- 8) as a Pesticide Inert Ingredient in Accordance with 40 CFR §180.920. June 13,
2013.

Satpute, R.M., Lomash, V., Hariharakrishnan, J., Roa, P., Singh, P., Gujar, N., and Bhattacharya,
R. ( 201 4 ). Oxidative Stress And Tissue Pathology Caused By Subacute Exposure To Ammonium Acetate In Rats And Their Response To Treatments With Alpha

- Ketoglutarate And
N

- Acetyl Cysteine

. Toxicology and Industrial Health: 30(1) 12

- 14

. MRID

. 49507001

.

U.S. Environmental Protection Agency (EPA), 20 08 . Acetic acid and salts summary document. Registration Review: Initial Docket, EPA

- HQ

- EPA

- OPP

- 2008

- 0016. Case #4001, www.regulations.gov

.

U.S. Environmental Protection Agency (EPA), 20 14

. Acetic Acid and Sodium Diacetate Proposed Interim Registration Review Decision . Registration Review: Initial Docket, EPA

- HQ

- EPA

- OPP

2008

- 0016. Case #4001, www.regulations.gov

.