TOXICOLOGICAL PROFILE FOR 

AMMONIA 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry 

September 2004 
AMMONIA ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
AMMONIA iii 

UPDATE STATEMENT 

A Toxicological Profile for Ammonia, Draft for Public Comment, was released in September 2002. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry

Division of Toxicology/Toxicology Information Branch 

1600 Clifton Road NE, 

Mailstop F-32 

Atlanta, Georgia 30333 


AMMONIA vi 

*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization 

Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to 

prepare toxicological profiles for hazardous substances most commonly found at facilities on the 

CERCLA National Priorities List and that pose the most significant potential threat to human health, as 

determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal Register on November 17, 1997 (62 FR 61332). For prior 

versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 FR 18744); April 

17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17, 

1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); and February 

28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR 

to prepare a toxicological profile for each substance on the list. 
AMMONIA vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length 

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects observed 

following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 498-0110 Fax: (770) 488-4178 

E-mail: atsdric@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 
AMMONIA viii 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident. Volumes I and II are planning guides to assist first responders and hospital emergency 

department personnel in planning for incidents that involve hazardous materials. Volume III— 

Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care 

professionals treating patients exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, 

GA 30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on 

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, 

Research Triangle Park, NC 27709 • Phone: 919-541-3212. 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 

• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, 

IL 60005 • Phone: 847-818-1800 • FAX: 847-818-9266. 
AMMONIA ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Nickolette Roney, MPH 

ATSDR, Division of Toxicology, Atlanta, GA 

Fernando Llados, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

Susan S. Little, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

David B. Knaebel, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1. Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

AMMONIA xi 

PEER REVIEW 

A peer review panel was assembled for ammonia. The panel consisted of the following members: 

1. Dr. Finis Cavender, Private Consultant, Greer, South Carolina; 

2. Dr. Jerold Last, Professor, Internal Medicine, University of California, Davis; 

3. Dr. Frederick Oehme, Professor of Toxicology, Medicine/Physiology, Kansas State University; 

and 

4. Dr. Martin Alexander, Professor, Department of Soil, Crop, and Atmospheric Sciences, Cornell 

University, New York. 

These experts collectively have knowledge of ammonia's physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and 

a list of unpublished documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 

AMMONIA xiii 

CONTENTS 

DISCLAIMER..............................................................................................................................................ii 

UPDATE STATEMENT .............................................................................................................................iii 

FOREWORD................................................................................................................................................v 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii 

CONTRIBUTORS.......................................................................................................................................ix 

PEER REVIEW ...........................................................................................................................................xi 

CONTENTS...............................................................................................................................................xiii 

LIST OF FIGURES ..................................................................................................................................xvii 

LIST OF TABLES.....................................................................................................................................xix 

1. PUBLIC HEALTH STATEMENT..........................................................................................................1 

1.1 WHAT IS AMMONIA?..............................................................................................................1 

1.2 WHAT HAPPENS TO AMMONIA WHEN IT ENTERS THE ENVIRONMENT?.................3 

1.3 HOW MIGHT I BE EXPOSED TO AMMONIA? .....................................................................3 

1.4 HOW CAN AMMONIA ENTER AND LEAVE MY BODY? ..................................................5 

1.5 HOW CAN AMMONIA AFFECT MY HEALTH? ...................................................................6 

1.6 HOW CAN AMMONIA AFFECT CHILDREN? ......................................................................7 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO AMMONIA? ..................7 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED 

TO AMMONIA? .........................................................................................................................8 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?.................................................................................................9 

1.10 WHERE CAN I GET MORE INFORMATION? .....................................................................10 

2. RELEVANCE TO PUBLIC HEALTH .................................................................................................13 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO AMMONIA IN THE 

UNITED STATES.....................................................................................................................13 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................15 

2.3 MINIMAL RISK LEVELS .......................................................................................................18 

3. HEALTH EFFECTS..............................................................................................................................23 

3.1 INTRODUCTION.....................................................................................................................23 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................23 

3.2.1 Inhalation Exposure ..............................................................................................................25 

3.2.1.1 Death ............................................................................................................................25 

3.2.1.2 Systemic Effects...........................................................................................................26 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................55 

3.2.1.4 Neurological Effects.....................................................................................................55 

3.2.1.5 Reproductive Effects....................................................................................................56 

3.2.1.6 Developmental Effects .................................................................................................56 

3.2.1.7 Cancer...........................................................................................................................56 

3.2.2 Oral Exposure........................................................................................................................57 

3.2.2.1 Death ............................................................................................................................57 

3.2.2.2 Systemic Effects...........................................................................................................58 

3.2.2.3 Immunological and Lymphoreticular Effects...............................................................67 

3.2.2.4 Neurological Effects.....................................................................................................68 

3.2.2.5 Reproductive Effects....................................................................................................69 
AMMONIA xiv 

3.2.2.6 Developmental Effects .................................................................................................69 

3.2.2.7 Cancer...........................................................................................................................69 

3.2.3 Dermal Exposure...................................................................................................................70 

3.2.3.1 Death ............................................................................................................................70 

3.2.3.2 Systemic Effects...........................................................................................................71 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................75 

3.2.3.4 Neurological Effects.....................................................................................................75 

3.2.3.5 Reproductive Effects....................................................................................................75 

3.2.3.6 Developmental Effects .................................................................................................75 

3.2.3.7 Cancer...........................................................................................................................75 

3.2.4 Other Routes of Exposure .....................................................................................................76 

3.3 GENOTOXICITY .....................................................................................................................76 

3.4 TOXICOKINETICS..................................................................................................................78 

3.4.1 Absorption.............................................................................................................................79 

3.4.1.1 Inhalation Exposure......................................................................................................79 

3.4.1.2 Oral Exposure...............................................................................................................79 

3.4.1.3 Dermal Exposure ..........................................................................................................80 

3.4.2 Distribution ...........................................................................................................................81 

3.4.2.1 Inhalation Exposure......................................................................................................81 

3.4.2.2 Oral Exposure...............................................................................................................81 

3.4.2.3 Dermal Exposure ..........................................................................................................82 

3.4.2.4 Other Routes of Exposure ............................................................................................82 

3.4.3 Metabolism............................................................................................................................83 

3.4.4 Elimination and Excretion.....................................................................................................83 

3.4.4.1 Inhalation Exposure......................................................................................................83 

3.4.4.2 Oral Exposure...............................................................................................................86 

3.4.4.3 Dermal Exposure ..........................................................................................................86 

3.4.4.4 Other Routes of Exposure ............................................................................................87 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models .............87 

3.5 MECHANISMS OF ACTION ..................................................................................................90 

3.5.1 Pharmacokinetic Mechanisms...............................................................................................90 

3.5.2 Mechanisms of Toxicity........................................................................................................90 

3.5.3 Animal-to-Human Extrapolations.........................................................................................91 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ..........................92 

3.7 CHILDREN’S SUSCEPTIBILITY...........................................................................................93 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ....................................................................96 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Ammonia.........................................97 

3.8.2 Biomarkers Used to Characterize Effects Caused by Ammonia...........................................97 

3.9 INTERACTIONS WITH OTHER CHEMICALS ....................................................................98 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE............................................99 

3.11 METHODS FOR REDUCING TOXIC EFFECTS..............................................................100 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................100 

3.11.2 Reducing Body Burden...................................................................................................101 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .........................................101 

3.12 ADEQUACY OF THE DATABASE.....................................................................................101 

3.12.1 Existing Information on Health Effects of Ammonia.....................................................102 

3.12.2 Identification of Data Needs ...........................................................................................102 

3.12.3 Ongoing Studies..............................................................................................................110 
AMMONIA xv 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................113 

4.1 CHEMICAL IDENTITY.........................................................................................................113 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................113 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................117 

5.1 PRODUCTION .......................................................................................................................117 

5.2 IMPORT/EXPORT .................................................................................................................121 

5.3 USE..........................................................................................................................................122 

5.4 DISPOSAL..............................................................................................................................122 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................123 

6.1 OVERVIEW............................................................................................................................123 

6.2 RELEASES TO THE ENVIRONMENT................................................................................127 

6.2.1 Air .......................................................................................................................................131 

6.2.2 Water...................................................................................................................................133 

6.2.3 Soil ......................................................................................................................................133 

6.3 ENVIRONMENTAL FATE....................................................................................................134

6.3.1 Transport and Partitioning...................................................................................................134 

6.3.2 Transformation and Degradation ........................................................................................136 

6.3.2.1 Air...............................................................................................................................136 

6.3.2.2 Water ..........................................................................................................................137 

6.3.2.3 Sediment and Soil.......................................................................................................138 

6.3.2.4 Other Media................................................................................................................138 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................138 

6.4.1 Air .......................................................................................................................................139 

6.4.2 Water...................................................................................................................................141 

6.4.3 Sediment and Soil ...............................................................................................................143 

6.4.4 Other Environmental Media................................................................................................143 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................143 

6.6 EXPOSURES OF CHILDREN...............................................................................................145 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................146 

6.8 ADEQUACY OF THE DATABASE......................................................................................147 

6.8.1 Identification of Data Needs ...............................................................................................147 

6.8.2 Ongoing Studies ..................................................................................................................149 

7. ANALYTICAL METHODS ...............................................................................................................153 

7.1 BIOLOGICAL MATERIALS.................................................................................................153 

7.2 ENVIRONMENTAL SAMPLES............................................................................................156 

7.3 ADEQUACY OF THE DATABASE......................................................................................160 

7.3.1 Identification of Data Needs ...............................................................................................160 

7.3.2 Ongoing Studies ..................................................................................................................161 

8. REGULATIONS AND ADVISORIES ...............................................................................................163 

9. REFERENCES ....................................................................................................................................171 

10. GLOSSARY ......................................................................................................................................217 

APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................................................A-1 
AMMONIA xvi 

B. USER'S GUIDE ..................................................................................................................................B-1 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS......................................................................C-1 

D. INDEX ................................................................................................................................................D-1
AMMONIA xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Ammonia and Ammonium Compounds—Inhalation ............. 41 

3-2. Levels of Significant Exposure to Ammonia and Ammonium Compounds—Oral....................... 63 

3-3. Glutamine Cycle ............................................................................................................................ 84

3-4. The Urea Cycle Showing the Compartmentalization of its Steps Within Liver Cells................... 85

3-5. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance ................................................................................................. 89

3-6. Existing Information on Health Effects of Ammonia .................................................................. 103

6-1. Frequency of NPL Sites with Ammonia Contamination ............................................................. 124

6-2. Simplified Schematic for the Microbial Processes of the Nitrogen Cycle................................... 125

AMMONIA xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Ammonia and Ammonium Compounds—Inhalation ............. 27 

3-2. Levels of Significant Exposure to Ammonia and Ammonium Compounds—Oral....................... 59 

3-3. Levels of Significant Exposure to Ammonia and Ammonium Compounds—Dermal.................. 72 

3-4. Genotoxicity of Ammonia In Vitro and In Vivo ............................................................................ 77

3-5. Ongoing Studies on the Health Effects of Ammonia................................................................... 111

4-1. Chemical Identity of Ammonia ................................................................................................... 114

4-2. Physical and Chemical Properties of Ammonia .......................................................................... 115

5-1. Facilities that Produce, Process, or Use Ammonia ...................................................................... 119

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Ammonia............... 129

6-2. Ongoing Studies on Environmental Fate and the Potential for Human Exposure to 

Ammonia ..................................................................................................................................... 150

7-1. Analytical Methods for Determining Ammonia in Biological Samples...................................... 154

7-2. Analytical Methods for Determining Ammonia in Environmental Samples............................... 157

7-3. Ongoing Studies on the Development of Analytical Approaches to the Study of Ammonia ...... 162

8-1. Regulations and Guidelines Applicable to Ammonia.................................................................. 165

AMMONIA 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about ammonia and the effects of exposure. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in 

the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for 

long-term federal clean-up activities. Ammonia has been found in at least 137 of the 

1,647 current or former NPL sites. Although the total number of NPL sites evaluated for this 

substance is not known, the possibility exists that the number of sites at which ammonia is found 

may increase in the future as more sites are evaluated. This information is important because 

these sites may be sources of exposure and exposure to this substance may harm you. 

When a substance is released either from a large area, such as an industrial plant, or from a 

container, such as a drum or bottle, it enters the environment. Such a release does not always 

lead to exposure. You can be exposed to a substance only when you come in contact with it. 

You may be exposed by breathing, eating, or drinking the substance, or by skin contact. 

If you are exposed to ammonia, many factors will determine whether you will be harmed. These 

factors include the dose (how much), the duration (how long), and how you come in contact with 

it. You must also consider any other chemicals you are exposed to and your age, sex, diet, 

family traits, lifestyle, and state of health. 

1.1 WHAT IS AMMONIA? 

Ammonia is a chemical that is made both by humans and by nature. It is made up of one part 

nitrogen (N) and three parts hydrogen (H3). The amount of ammonia manufactured every year 

by humans is almost equal to the amount produced by nature every year. However, when 

ammonia is found at a level that may cause concern, it was likely produced either directly or 

indirectly by humans. 
AMMONIA 2 

1. PUBLIC HEALTH STATEMENT 

Ammonia is a colorless gas with a very sharp odor. Ammonia in this form is also known as 

ammonia gas or anhydrous (“without water”) ammonia. Ammonia gas can also be compressed 

and becomes a liquid under pressure. The odor of ammonia is familiar to most people because 

ammonia is used in smelling salts, household cleaners, and window cleaning products. 

Ammonia easily dissolves in water. In this form, it is also known as liquid ammonia, aqueous 

ammonia, or ammonia solution. In water, most of the ammonia changes to the ionic form of 

ammonia, known as ammonium ions, which are represented by the formula NH4

+

 (an ion is an 

atom or a group of atoms that has acquired a net electric charge by gaining or losing one or more 

electrons). Ammonium ions are not gaseous and have no odor. Ammonia and ammonium ions 

can change back and forth in water. In wells, rivers, lakes, and wet soils, the ammonium form is 

the most common. Ammonia can also be combined with other substances to form ammonium 

compounds, including salts such as ammonium chloride, ammonium sulfate, ammonium nitrate, 

and others. 

Ammonia is very important to plant, animal, and human life. It is found in water, soil, and air, 

and is a source of much needed nitrogen for plants and animals. Most of the ammonia in the 

environment comes from the natural breakdown of manure and dead plants and animals. 

Eighty percent of all manufactured ammonia is used as fertilizer. A third of this is applied 

directly to soil as pure ammonia. The rest is used to make other fertilizers that contain 

ammonium compounds, usually ammonium salts. These fertilizers are used to provide nitrogen 

to plants. Ammonia is also used to manufacture synthetic fibers, plastics, and explosives. Many 

cleaning products also contain ammonia in the form of ammonium ions. 

For detailed information on the chemical properties of ammonia, see Chapter 4. Details on the 

production and use of ammonia are in Chapter 5, and more information on the environmental 

fate of ammonia and sources of human exposure is in Chapter 6. 
AMMONIA 3 

1. PUBLIC HEALTH STATEMENT 

1.2 WHAT HAPPENS TO AMMONIA WHEN IT ENTERS THE ENVIRONMENT? 

Since ammonia occurs naturally in the environment, we are regularly exposed to low levels of 

ammonia in air, soil, and water. Ammonia exists naturally in the air at levels between 1 and 

5 parts in a billion parts of air (ppb). It is commonly found in rainwater. The ammonia levels in 

rivers and bays are usually less than 6 parts per million (ppm; 6 ppm=6,000 ppb). Soil typically 

contains about 1–5 ppm of ammonia. The levels of ammonia vary throughout the day, as well as 

from season to season. Generally, ammonia levels are highest in the summer and spring. 

Ammonia is essential for mammals and is necessary for making DNA, RNA, and proteins. It 

also plays a part in maintaining acid-base balance in tissues of mammals. 

Ammonia does not last very long in the environment. Because it is recycled naturally, nature has 

many ways of incorporating and transforming ammonia. In soil or water, plants and 

microorganisms rapidly take up ammonia. After fertilizer containing ammonia is applied to soil, 

the amount of ammonia in that soil decreases to low levels in a few days. In the air, ammonia 

will last about 1 week. 

Ammonia has been found in air, soil, and water samples at hazardous waste sites. In the air near 

hazardous waste sites, ammonia can be found as a gas. Ammonia can also be found dissolved in 

ponds or other bodies of water at a waste site. Ammonia can be found attached to soil particles 

at hazardous waste sites. The average concentration of ammonia reported at hazardous waste 

sites ranges from 1 to 1,000 ppm in soil samples and up to 16 ppm in water samples. 

See Chapter 6 for more detailed information on the environmental fate of ammonia, ammonia 

levels in the environment, and exposure to ammonia. 

1.3 HOW MIGHT I BE EXPOSED TO AMMONIA? 

Ammonia is naturally produced and used by all mammals in their normal metabolism. Ammonia 

is produced within a person’s body each day. Most of this ammonia is produced by organs and 

tissues, but some is produced by bacteria living inside our intestines. 
AMMONIA 4 

1. PUBLIC HEALTH STATEMENT 

Ammonia is found naturally in the environment. You may be exposed to ammonia by breathing 

air, eating food, or drinking water that contains it, or through skin contact with ammonia or 

ammonium compounds. Exposure to ammonia in the environment is most likely to occur by 

breathing in ammonia that has been released into the air. 

Ammonia has a very strong odor that is irritating and that you can smell when it is in the air at a 

level higher than 50 ppm. Therefore, you will probably smell ammonia before you are exposed 

to a concentration that may harm you. Levels of ammonia in air that cause serious effects in 

people are much higher than levels you would normally be exposed to at home or work. 

However, low levels of ammonia may harm some people with asthma and other sensitive 

individuals. 

You can taste ammonia in water at levels of about 35 ppm. Lower levels than this occur 

naturally in food and water. Swallowing even small amounts of liquid ammonia in your 

household cleaner might cause burns in your mouth and throat. A few drops of liquid ammonia 

on the skin or in the eyes will cause burns and open sores if not washed away quickly. Exposure 

to larger amounts of liquid ammonia or ammonium ion in the eyes causes severe eye burns and 

can lead to blindness. 

Outdoors, you may be exposed to high levels of ammonia gas in air from leaks and spills at 

production plants and storage facilities, and from pipelines, tank trucks, railcars, ships, and 

barges that transport ammonia. Higher levels of ammonia in air may occur when fertilizer with 

ammonia or ammonium compounds is applied to farm fields. After fertilizer is applied, the 

concentration of ammonia in soil can be more than 3,000 ppm; however, these levels decrease 

rapidly over a few days. 

Indoors, you may be exposed to ammonia while using household products that contain ammonia. 

Some of these products are ammonia-cleaning solutions, window cleaners, floor waxes, and 

smelling salts. 
AMMONIA 5 

1. PUBLIC HEALTH STATEMENT 

Household and industrial cleaning solutions may contain ammonia, and use of these products at 

home or work may lead to exposure to ammonia. Both types of ammonia cleaning solutions are 

made by adding ammonia gas to water to form liquid ammonia. Household ammonia cleaners 

typically contain lower levels of ammonia (between 5 and 10%) compared to industrial cleaning 

solutions, which can contain higher levels of ammonia (up to 25%). 

Farmers can be exposed to ammonia when they work with or apply fertilizers containing 

ammonia to fields. Farmers, cattle ranchers, and people who raise other types of livestock and/or 

poultry can be exposed to ammonia from decaying manure. Some manufacturing processes also 

use ammonia. Some older refrigeration units used ammonia as the refrigerant. 

For more information on levels of exposure associated with effects, see Chapter 3. 

1.4 HOW CAN AMMONIA ENTER AND LEAVE MY BODY? 

Ammonia can enter your body if you breathe in ammonia gas or if you swallow water or food 

containing ammonium salts. If you spill a liquid containing ammonia on your skin, a small 

amount of ammonia might enter your body through your skin; however, more ammonia will 

probably enter as you breathe ammonia gas from the spilled ammonia. After you breathe in 

ammonia, you breathe most of it out again. The ammonia that is retained in the body is changed 

into ammonium compounds and carried throughout the body in seconds. If you swallow 

ammonia in food or water, it will get into your bloodstream and be carried throughout your body 

in seconds. Most of the ammonia that enters your body from food or water rapidly changes into 

other substances that will not harm you. The rest of this ammonia leaves your body in urine 

within a couple of days. For more information on how ammonia can enter and leave your body, 

see Chapter 3. 
AMMONIA 6 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN AMMONIA AFFECT MY HEALTH? 

Scientists use many tests to protect the public from harmful effects of toxic chemicals and to find 

ways for treating persons who have been harmed. 

One way to learn whether a chemical will harm people is to determine how the body absorbs, 

uses, and releases the chemical. For some chemicals, animal testing may be necessary. Animal 

testing may also help identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method for getting information needed to make wise 

decisions that protect public health. Scientists have the responsibility to treat research animals 

with care and compassion. Scientists must comply with strict animal care guidelines because 

laws today protect the welfare of research animals. 

Ammonia is a corrosive substance and the main toxic effects are restricted to the sites of direct 

contact with ammonia (i.e., skin, eyes, respiratory tract, mouth, and digestive tract). For 

example, if you spilled a bottle of concentrated ammonia on the floor, you would smell a strong 

ammonia odor; you might cough, and your eyes might water because of irritation. If you were 

exposed to very high levels of ammonia, you would experience more harmful effects. For 

example, if you walked into a dense cloud of ammonia or if your skin comes in contact with 

concentrated ammonia, your skin, eyes, throat, or lungs may be severely burned. These burns 

might be serious enough to cause permanent blindness, lung disease, or death. Likewise, if you 

accidentally ate or drank concentrated ammonia, you might experience burns in your mouth, 

throat, and stomach. There is no evidence that ammonia causes cancer. Ammonia has not been 

classified for carcinogenic effects by EPA, Department of Health and Human Services (DHHS) 

(NTP), or the International Agency for Research on Cancer (IARC). Ammonia can also have 

beneficial effects, such as when it is used as a smelling salt. Certain ammonium salts have long 

been used in veterinary and human medicine. For more information on how ammonia can affect 

your health, see Chapter 3. 
AMMONIA 7 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN AMMONIA AFFECT CHILDREN? 

This section discusses potential health effects from exposures during the period from conception 

to maturity at 18 years of age in humans. 

Children are less likely than adults to be exposed to concentrated ammonia because most 

exposures to concentrated ammonia occur in occupational settings. Children can still be exposed 

in the same way as adults to ammonia gas from spills or leaks from ammonia tanks or pipelines, 

especially on farms where it is used as a fertilizer. Children can also be exposed to dilute 

ammonia solutions from household cleaners containing ammonia. 

The effects of ammonia on children are likely to be the same as for adults. Ammonia is an 

irritant and the solution and gas can cause burns of the skin, eyes, mouth, and lungs. If a spill 

occurs, children may be exposed to ammonia for a longer time than adults because they may not 

leave the area as quickly. 

There is no evidence that exposure to the levels of ammonia found in the environment causes 

birth defects or other developmental effects. It is not known whether ammonia can be 

transferred from a pregnant mother to a developing fetus through the placenta or from a nursing 

mother to her offspring through breast milk. One study in animals showed that exposure of 

mothers to very high levels of ammonia during pregnancy caused their newborn offspring to be 

smaller than normal, but this occurred at levels of ammonia that also affected the mothers. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO AMMONIA? 

If your doctor finds that you have been exposed to significant amounts of ammonia, ask whether 

your children might also be exposed. Your doctor might need to ask your state health 

department to investigate. 

You can reduce your risk of exposure to ammonia by carefully using household products and by 

avoiding areas where ammonia is used or produced. At home, you can reduce your risk of 
AMMONIA 8 

1. PUBLIC HEALTH STATEMENT 

exposure to ammonia by careful handling of any household products that contain ammonia. For 

example, some cleaning products contain ammonia; so when you use them, you should be sure 

that rooms are adequately ventilated during the time you are using them. Avoid ammoniacontaining products in glass bottles since breakage could lead to a serious exposure. You should 

wear proper clothing and eye protection, because ammonia can cause skin burns and damage 

eyes if it is splashed on them. To lower the risk of your children being exposed to ammonia, you 

should tell them to stay out of the room when you are using it. While use of ammonia by a child 

is not recommended, any use by a child should be closely supervised by an adult. 

You can also reduce your risk of exposure to ammonia by avoiding areas where it is being used. 

Ammonia is used to fertilize crops, so you can lower your exposure to ammonia by avoiding 

these areas when it is being applied. You can also lower your exposure to ammonia by avoiding 

places where it is produced. Ammonia is found in many animal wastes, and it may be present in 

high concentrations in the air in livestock buildings. You can lower your exposure to ammonia 

by avoiding these buildings, especially if large numbers of animals are inside. 

If you are a worker who uses or applies ammonia for farming, you can reduce your exposure by 

using it according to the instructions and wearing proper clothing and protective gear. Be sure to 

follow all instructions and heed any warning statements. 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO AMMONIA? 

There are tests that measure ammonia/ammonium ion in blood and urine; however, these tests 

would probably not tell you whether you have been exposed because ammonia is normally found 

in the body. If you were exposed to harmful amounts of ammonia, you would notice it 

immediately because of the strong, unpleasant, and irritating smell, the strong taste, and because 

of skin, eye, nose, or throat irritation. Exposure detection levels and methods for determining 

ammonia levels in biological materials are discussed in Chapters 3 and 7. 
AMMONIA 9 

1. PUBLIC HEALTH STATEMENT 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. The EPA, the Occupational Safety and Health 

Administration (OSHA), and the Food and Drug Administration (FDA) are some federal 

agencies that develop regulations for toxic substances. Recommendations provide valuable 

guidelines to protect public health, but cannot be enforced by law. The Agency for Toxic 

Substances and Disease Registry (ATSDR) and the National Institute for Occupational Safety 

and Health (NIOSH) are two federal organizations that develop recommendations for toxic 

substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a 

toxic substance in air, water, soil, or food that do not exceed a critical value that is usually based 

on levels that affect animals; they are then adjusted to levels that will help protect humans. 

Sometimes these not-to-exceed levels differ among federal organizations because they used 

different exposure times (an 8-hour workday or a 24-hour day), different animal studies, or other 

factors. 

Recommendations and regulations are also updated periodically as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. Some regulations and recommendations for ammonia include the following: 

EPA regulates the ammonia content in waste water released by several industries. Any 

discharges or spills of ammonia of 100 pounds or more, or of ammonium salts of 1,000 or 

5,000 pounds (depending upon the compound), must be reported to EPA. 

Some restrictions have been placed on levels of ammonium salts allowable in processed foods. 

FDA states that the levels of ammonia and ammonium compounds normally found in food do 

not pose a health risk. Maximum allowable levels in processed foods are as follows: 0.04–3.2% 

ammonium bicarbonate in baked goods, grain, snack foods, and reconstituted vegetables; 2.0% 

ammonium carbonate in baked goods, gelatins, and puddings; 0.001% ammonium chloride in 
AMMONIA 10 

1. PUBLIC HEALTH STATEMENT 

baked goods and 0.8% in condiments and relishes; 0.6–0.8% ammonium hydroxide in baked 

goods, cheeses, gelatins, and puddings; 0.01% monobasic ammonium phosphate in baked goods; 

and 1.1% dibasic ammonium phosphate in baked goods, 0.003% in nonalcoholic beverages, and 

0.012% in condiments and relishes. 

OSHA has set an 8-hour exposure limit of 25 ppm and a short-term (15-minute) exposure limit 

of 35 ppm for ammonia in the workplace. NIOSH recommends that the level in workroom air be 

limited to 50 ppm for 5 minutes of exposure. 

Further information on governmental recommendations can be found in Chapter 8. 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses that result from exposure to 

hazardous substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You 

may request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the toll-free information 

and technical assistance number at 1-888-42ATSDR (1-888-422-8737), by e-mail at 

atsdric@cdc.gov, or by writing to: 

 Agency for Toxic Substances and Disease Registry 

 Division of Toxicology 

 1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 
AMMONIA 11 

1. PUBLIC HEALTH STATEMENT 

Organizations for-profit may request copies of final Toxicological Profiles from the following: 

National Technical Information Service (NTIS) 

5285 Port Royal Road 

Springfield, VA 22161 

Phone: 1-800-553-6847 or 1-703-605-6000 

Web site: http://www.ntis.gov/ 

AMMONIA 13 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO AMMONIA IN THE UNITED 

STATES 

Ammonia is a natural compound, as well as a manufactured compound. In nature, most ammonia 

probably comes from decomposing animal excreta, with the decay of organic materials from plants, dead 

animals, and the like also contributing significant amounts. It is also exhaled by animals. Production of 

fixed nitrogen (NH3) by plants and microorganisms is estimated at 90 to 130 metric tons annually. 

Manufacture of ammonia within the United States was 9.5 million metric tons in 2001, which is down 

from 16.6 million metric tons in 1999. Commercially produced ammonia is used primarily as fertilizer, 

with plastics, synthetic fibers and resins, explosives, and other uses accounting for most of the remainder. 

Ammonia is released to the atmosphere by natural processes such as the decay of organic matter and 

animal excreta, or by volcanic eruptions. It can also be released to the atmosphere by anthropogenic 

activities such as fertilizer use; spillage or leakage from storage or production facilities; or loss from 

waste water effluents. The average global ammonia concentration in the atmosphere ranges from 0.3 to 

6 ppb, with concentrations sometimes higher in the vicinity of agricultural or industrial areas. For 

example, near industrial sources or manure heaps in Germany, ammonia concentrations ranged from 

10.3 to 89 ppb. Concentrations may be orders of magnitude higher near some types of livestock areas, 

such as pigpens, where local atmospheric concentrations have been reported to be as high as 47 ppm. 

Elevated concentrations of ammonia in water are usually due to effluent discharges from sewage 

treatment plants or industrial processes, or runoff from fertilized fields or livestock areas. Ammonia 

concentrations can therefore vary widely in aquatic environments, with concentrations being lower in 

bodies of water that are unimpacted by residential, industrial, or farming effluents, compared to those that 

are impacted (where concentrations can be orders of magnitude higher). In unimpacted waterways, 

ammonia concentrations have been reported to range from 8.5 to 43 ppb, whereas in impacted waterways, 

concentrations as high as 16 ppm have been reported. 

Soils usually obtain additional ammonia from natural or synthetic fertilizer application, animal excreta, 

decaying organic matter, or natural fixation from the atmosphere. Soils have been reported to have 

background concentrations of ammonia ranging from 1 to 5 ppm. Immediately following application of 
AMMONIA 14 

2. RELEVANCE TO PUBLIC HEALTH 

fertilizer or manure, however, ammonia concentrations can rise to 2–3,000 ppm, with levels dropping 

after 5 days to 2–850 ppm. These high ammonia concentrations are usually limited to the upper few 

centimeters of topsoil. 

In the atmosphere, ammonia can react with acidic substances in the air to produce ammonium aerosols, 

which can be subject to dry or wet deposition. The best estimate of the half-life of atmospheric ammonia 

is a few days. In water, ammonia can volatilize to the atmosphere, be removed by microbial processes, or 

adsorb to sediment and suspended organic material. In soil, ammonia can volatilize to the atmosphere, 

adsorb to soil particles, undergo microbial transformation to nitrate or nitrite anions, or be taken up by 

plants. 

For the general population, the most likely source of exposure to elevated levels of ammonia is from the 

use of household cleaners containing ammonia or ammonium salts. People who live near farms, who 

visit farms during the application of fertilizer, or who live near cattle feedlots, poultry confinement 

buildings, or other areas where animal populations are concentrated can also be exposed to ammonia. 

Local atmospheric concentrations in these agricultural settings have been reported to range from 280 to 

88,000 ppb. 

There is also the possibility for exposure to ammonia via water and food ingestion. If untreated surface 

water is ingested, the average uptake would be 0.36 mg/day (assuming an ammonia concentration in 

untreated water of 0.18 mg/L and a consumption rate of 2 L/day). For most sources of drinking water, 

however, adsorption, nitrification, and the conversion of ammonia to chloramines upon chlorination will 

result in negligible levels of ammonia in most drinking water supplies. Food ingestion can also lead to an 

exposure to ammonia, primarily due to the use of various ammonium salts as food stabilizers; the 

estimated exposure from these food additives is 18 mg/day. 

Populations that live or work near a hazardous waste site that contains ammonia or ammonium salts could 

be exposed to above-average levels of ammonia in soil, water, or air in similar concentrations as those in 

agricultural settings. While these exposures may occur, the half-life of ammonia in nature is probably 

very short. Ammonia has been identified in at least 137 of 1,647 National Priority List (NPL) hazardous 

waste sites. 
AMMONIA 15 

2. RELEVANCE TO PUBLIC HEALTH 

2.2 SUMMARY OF HEALTH EFFECTS 

Ammonia is an essential mammalian metabolite for DNA, RNA, and protein synthesis and is necessary 

for maintaining acid-base balance. Ammonia is produced and used endogenously in all mammalian 

species. It has been estimated that up to 17 grams of ammonia are produced in humans daily. Of these 

17 grams, approximately 4 grams are produced in the gut by intestinal bacteria, where it enters the portal 

circulation and is metabolized rapidly in the liver to urea. Ammonia is excreted primarily as urea and 

urinary ammonium compounds through the kidneys. Levels of ammonia in the blood from healthy 

humans range from 0.7 to 2 mg/L. 

The most important injurious effects of exposure to excessive amounts of ammonia on humans are due to 

its irritative and corrosive properties. Exposures to ammonia gas cause chemical burns of the respiratory 

tract, skin, and eyes. Ammonia dissolves in the water present in skin, mucous membranes, and eyes and 

becomes ammonium hydroxide, which is a highly ionized weak base that causes necrosis of the tissues. 

Specifically, ammonium hydroxide causes saponification of cell membrane lipids resulting in cell 

disruption and death. Additionally, it extracts water from the cells, and initiates an inflammatory 

response, which further damages the surrounding tissues. Contact with liquid ammonia (not ammonium 

salts) results in cryogenic injury in addition to the alkali burns. Airway blockage and respiratory 

insufficiency may be lethal outcomes of exposure to anhydrous ammonia vapors or concentrated aerosols. 

Ingestion of concentrated ammonium solutions may produce severe burns and hemorrhage of the upper 

gastrointestinal tract. Survival of the initial insult may be compromised by infections, scarring, and other 

complications that may develop days or weeks following inhalation or ingestion. Effects that have been 

observed in humans exposed to ammonia gas and ammonium salt aerosols have also been observed in 

animals. Hepatic and renal effects have also been reported in animals and humans; however, ammonia 

does not appear to be a primary liver or kidney toxicant. 

Increased systemic ammonia/ammonium salts/ion, or hyperammonemia, is generally not seen following 

inhalation or dermal exposure, but can result from ingestion and from certain disease states such as 

cirrhosis of the liver, acute liver failure, and congenital deficiencies of any of the urea cycle enzymes. 

Liver disease can result in decreased metabolism of ammonia with resultant increased levels of ammonia 

in the bloodstream and in the brain, which can produce neurological effects such as seizures and coma, 

and eventually death. In chronic liver failure, arterial ammonia concentrations may reach approximately 

3.6 mg/L, whereas arterial ammonia in acute liver failure may rise as high as 8 mg/L. The most likely 

and significant effects of exposure to elevated levels of ammonia are discussed below. 
AMMONIA 16 

2. RELEVANCE TO PUBLIC HEALTH 

Respiratory Effects. Ammonia is an upper respiratory irritant in humans. Exposures to levels 

exceeding 50 ppm result in immediate irritation to the nose and throat; however, tolerance appears to 

develop with repeated exposure. Exposure to an air concentration of 250 ppm is bearable for most 

persons for 30–60 minutes. Acute exposure to higher levels (500 ppm) have been shown to increase 

respiratory minute volume. Accidental exposures to concentrated aerosols of ammonium salts or high 

concentrations of ammonia gas have resulted in nasopharyngeal and tracheal burns, airway obstruction 

and respiratory distress, and bronchiolar and alveolar edema. Ammonia vapor readily dissolves in the 

moisture present on the skin, eyes, oropharynx and lungs forming ammonium hydroxide which 

dissociates to yield hydroxyl ions. Chronic occupational exposure to low levels of airborne ammonia 

(<25 ppm) had little effect on pulmonary function or odor sensitivity in workers at some factories, but 

studies of farmers exposed to ammonia and other pollutants in livestock buildings indicated an 

association between exposure to pollutants, including ammonia, and an increase in respiratory symptoms 

(such as bronchial reactivity/hyperresponsiveness, inflammation, cough, wheezing, or shortness of breath) 

and/or a decrease in lung function parameters. The contribution of ammonia to these respiratory 

symptoms is unclear. 

Dermal Effects. Skin is extremely sensitive to airborne ammonia or ammonia dissolved in water. 

The topical damage caused by ammonia is probably due mainly to its reactivity and irritation properties. 

Its high water solubility allows it to dissolve in moisture on these surfaces, react with fatty substances, be 

absorbed into deeper layers, and inflict extensive damage. Reports of skin damage in humans are 

numerous, but good quantitative data are lacking. The severity of the damage is proportional to the 

concentration and duration of exposure; flushing with water immediately after contact alleviates or 

prevents effects. 

Dermal exposures to liquid ammonia or concentrated solutions and/or ammonia gas are frequently 

occupationally related and produce cutaneous burns, blisters, and lesions of varying degrees of severity. 

Unlike acid burns, which cause a coagulation necrosis, ammonia causes alkali burns, resulting in 

liquification of the tissue and deeper penetrations. Burns can be severe enough to require skin grafting, 

and loss of the epidermal layer increases body fluid loss and incidence of infection. While most ammonia 

exposures are occupational, household products containing ammonia can also cause dermal injury. 

Several cases of young children (2–3 years old) who bit into ammonia pellets/capsules and sustained oral 

and esophageal lesions have been reported in the literature. 
AMMONIA 17 

2. RELEVANCE TO PUBLIC HEALTH 

Very limited animal data regarding dermal effects of exposure to ammonia support the findings in 

humans. 

Ocular Effects. Reported ocular effects in humans following ammonia gas exposure increased in 

severity with dose and duration. Good quantitative data are lacking, but symptoms progress as follows: 

inflamed eyes, lacrimation, swelling of the eyelids, hyperemic conjunctiva, blurred vision, possible 

transient blindness, corneal abrasions, and sustained corneal damage. Ammonia is slightly irritating to 

human eyes in a brief exposure at concentrations of 100 ppm, and immediately irritating to the eyes and 

throat at 698 ppm. Exposure to an air concentration of 250 ppm is bearable for most persons for 30– 

60 minutes. 

Limited animal data regarding ocular effects of exposure to ammonia support the findings in humans. 

Neurological Effects. Neurological effects in humans following inhalation or dermal exposure to 

ammonia are usually limited to blurred vision, most likely due to direct contact, but more severe 

exposures, which result in significant elevation of blood ammonia levels (hyperammonemia), can result in 

diffuse nonspecific encephalopathy, muscle weakness, decreased deep tendon reflexes, and loss of 

consciousness. Hyperammonemia in humans can result from certain disease states such as cirrhosis of the 

liver, acute liver failure, and congenital deficiencies of any of the urea cycle enzymes; hyperammonemia 

may lead to encephalopathy. Some have suggested that ammonia may be involved in the generation of 

the symptomatology and progression of Alzheimer’s disease as a result of pathological ammonia 

metabolism in the brain. Cerebral edema and herniation and intracranial hypertension have been noted in 

animal models of hyperammonemia. The mechanism of ammonia-induced encephalopathies has not been 

definitively elucidated. It is thought to involve the alteration of glutamate metabolism in the brain with 

resultant increased activation of N-methyl-D-aspartate (NMDA) receptors, which causes decreased 

protein kinase C-mediated phosphorylation of Na+

/K+ ATPase, increased activity of Na+/K+ ATPase, and 

depletion of ATP. Additional evidence of altered energy levels includes changes in some TCA cycleassociated components including acetoacetate, and NAD+

/NADH ratio, 2-oxoglutarate, and 

3-hydroxybutarate. This reduced ATP level may be involved in ammonia-induced coma and death. A 

disruption in neurotransmission has also been suggested by alteration of brain tubulin, which is an 

essential component of the axonal transport system. 
AMMONIA 18 

2. RELEVANCE TO PUBLIC HEALTH 

2.3 MINIMAL RISK LEVELS 

Inhalation MRLs 

• An MRL of 1.7 ppm has been derived for acute-duration inhalation exposure (14 days or less) to 

ammonia. 

This MRL is based on a lowest-observed-adverse-effect level (LOAEL) of 50 ppm for mild irritation to 

the eyes, nose, and throat in humans exposed to ammonia as a gas for 2 hours (Verberk et al. 1977). In 

that study, a group of 16 subjects were tested, 8 of them (experts) knew the effects of ammonia from the 

literature, but had no personal contact, whereas the remaining 8 subjects (non-experts) were students from 

a non-science faculty and were not familiar with ammonia or experiments in laboratory situations. All 

members of a group were exposed on the same day to one of the concentrations tested (50, 80, 110, or 

140 ppm). The testing was repeated with a 1-week interval. Immediately before and after exposure, vital 

capacity, forced expiratory volume, and forced inspiratory volume were measured. During exposure, 

each subject recorded subjective feelings every 15 minutes as no sensation (0), just perceptible (1), 

distinctly perceptible (2), nuisance (3), offensive (4), or unbearable (5). No statistical analysis was 

performed and there was no group exposed to air only. Results of the pulmonary function tests after 

exposure were not statistically significantly different from pre-exposure values. For the non-experts, 

there was a clear increase in the number of reported symptoms for smell, eye irritation, throat irritation, 

cough, and general discomfort as the exposure concentration increased. The latter was not as clear for the 

experts. It should also be mentioned that the subjective responses appeared more pronounced in the nonexpert group than in the expert group. The LOAEL was divided by an uncertainty factor of 30 (10 to 

protect sensitive individuals and 3 for the use of a minimal LOAEL). A study of piggerie workers 

exposed to a mean level of 7.9 ppm ammonia measured pulmonary function change over a workshift; a 

small but borderline significant decrease in pulmonary function was noted (Heederik et al. 1990). This 

study was not used as a basis for MRL derivation because the workers were also exposed to other 

potential respiratory toxicants (dust and endotoxins). Although the Verberk et al. (1977) study has 

limitations (no statistical analysis, subjective end points, no control group), it demonstrates that 

concentrations of 50 ppm ammonia produce minimal discomfort in healthy members of the general 

population and therefore, should be avoided. A more detailed discussion of additional information 

supporting the findings of Verberk et al. (1977) is presented in Appendix A. 

No intermediate-duration inhalation MRL was derived for ammonia. The only available intermediateduration inhalation study in humans is that of Ferguson et al. (1977). In that study, a group of 6 healthy 
AMMONIA 19 

2. RELEVANCE TO PUBLIC HEALTH 

volunteers, not previously accustomed to working in an ammonia environment, were exposed 

5 days/week to 25 ppm (2 hours/day), 50 ppm (4 hours/day), or 100 ppm (6 hours/day) of ammonia, or to 

50 ppm of ammonia 6 hours/day for 6 weeks. End points monitored included subjective and objective 

measures of eye and throat irritation as well as pulse rate, respiration rate, pulmonary function (FVC, 

FEV), assessment of neurological function (reflex, balance, and coordination), and body weight. The 

exposure protocol consisted of a pre-exposure evaluation by a physician, 3 hours of exposure (this 

conflicts with exposure data on table 2 of the study and mentioned above), a mid-point physician’s 

observation, lunch break, 3 additional hours of exposure, and a third physician’s observation 30 minutes 

after exposure ceased. The conjunctiva and mucosa of the nose and throat were examined by a physician 

before and after each daily exposure and the degree of irritation noted was described as mild, moderate, or 

marked. Exposure to ammonia had no significant effect on the measures of respiratory function or in the 

neurological tests conducted. The results of the evaluations of irritation conducted by the physician 

showed no significant differences between the exposure groups, including the 0 ppm exposure group (preexposure). All subjects experienced some watering of the eyes and a sensation of dryness in the nose and 

throat, and there was one observation of definite redness in the mucosa of the nose after a 6-hour 

exposure to 100 ppm during which time, there was an excursion to 200 ppm ammonia. No redness was 

observed in this subject the following morning. Throughout the study, the physician observed 6 cases of 

eye irritation, 20 of nose irritation, and 9 of throat irritation, and most cases appeared to have occurred the 

first week of the study during exposure to 50 ppm. It is difficult to determine in this study a no-observedadverse-effect level (NOAEL) or LOAEL for irritation due to the different exposure durations 

experienced by the subjects. In general, studies in animals have used higher exposure concentrations and 

the overall quality of the studies is less than desirable. For ammonia, a corrosive irritant gas that affects 

the portal of entry and produces irritation of eyes and respiratory tract, use of human data should be 

preferred over animal studies. 

• An MRL of 0.1 ppm has been derived for chronic-duration inhalation exposure (365 days or 

more) to ammonia. 

This MRL supersedes the previous chronic inhalation MRL of 0.3 ppm derived in the 2002 draft for 

public comment version of this profile. The MRL is based on a NOAEL of 9.2 ppm for sense of smell, 

prevalence of respiratory symptoms (cough, bronchitis, wheeze, dyspnea, and others), eye and throat 

irritation, and lung function parameters (FVC, FEV1, FEV1/FVC, FEF50, and FEF75) in humans exposed 

for an average of 12.2 years in a soda ash plant (Holness et al. 1989); no LOAEL was determined. The 

cohort consisted of 52 workers and 35 controls. The subjects were assessed on two workdays: on the first 

workday of their workweek and on the last workday of their workweek. Spirometry was performed at the 
AMMONIA 20 

2. RELEVANCE TO PUBLIC HEALTH 

beginning and end of each work shift, so that each worker had four tests done. To determine the exposure 

levels, exposed and control workers were sampled over one work shift; the average sample collection 

period was 8.4 hours. All of the participants in the study were males. Analysis of the results showed no 

significant differences in the prevalence of reported symptoms, but the exposed workers reported that 

exposure in the plant aggravated some of their reported symptoms (cough, wheeze, nasal complaints, eye 

irritation, and throat discomfort). Odor threshold was not affected by exposure to ammonia and there 

were no significant differences in baseline lung functions between exposed and control subjects. Analysis 

of each worker separately showed no significant relationship between the level of ammonia exposure and 

changes in lung function. Also, when the workers were divided into groups of individuals that were 

exposed to low (<6.25 ppm), medium (6.25–12.5 ppm), and high (>12.5 ppm) ammonia levels, no 

significant association was found between reporting of symptoms, decline in baseline function, or 

increasing decline in function over the work shift and exposure to ammonia. Furthermore, no association 

was evident between increasing years of exposure and decreasing lung function. However, the power of 

the indices of both level and length of exposure is low because only eight workers were in areas with 

relatively high ammonia exposure. The MRL was calculated by adjusting the mean TWA exposure 

concentration of 9.2 ppm for continuous exposure (8/24 hours x 5/7 days) and dividing by an uncertainty 

factor of 10 to protect sensitive individuals. A modifying factor of 3 was added for the lack of 

reproductive and developmental studies. 

Oral MRLs 

No oral MRLs were derived for ammonia because of two main reasons. In the first place, the overall 

quality and/or usefulness of the oral database is limited. The only human acute oral studies available 

were case reports with no exposure levels (Klein et al. 1985; Klendshoj and Rejent 1966; Lopez et al. 

1988). Animal studies were limited to a food intake study (Noda and Chikamori 1976), single-exposure 

studies with no effect, serious effects, or unsupported effects (Benyajati and Goldstein 1975; Koenig and 

Koenig 1949), a gavage study that lacked study details (Boyd and Seymour 1946), and a 6-day drinking 

water study with effects at high levels (Barzel 1975). Rats exposed to 3,102 mg NH4

+

/kg/day in the diet 

and drinking water for 7 days had statistically significantly reduced body weight gain (64% less) 

compared to a control group that consumed only 22 mg NH4

+

/kg/day (Boyano-Adánez et al. 1996). Such 

a high dose of ammonium (as acetate) is equivalent to a 70 kg human ingesting approximately 1.4 lb of 

ammonium acetate daily. No human studies or reports of intermediate-duration oral exposure to 

ammonia were located. Intermediate-duration animal studies have reported decreases in body weight gain 

in rats exposed via drinking water (Gupta et al. 1979) or diet (Boyano-Adánez et al. 1996). It should be 
AMMONIA 21 

2. RELEVANCE TO PUBLIC HEALTH 

mentioned that Gupta et al. (1979) administered ammonium sulfamate to the rats. Ammonium sulfamate 

is an herbicide whose herbicide properties reside in the sulfamate portion of the salt and for which there is 

little toxicity information in the open literature. The EPA (IRIS 2004) has derived an oral RfD for the 

sulfamate moiety based on the results of Gupta et al. (1979). Following gavage administration of 

ammonium salts, bone, blood pressure, adrenal gland, and renal effects have been observed in early 

studies, generally inadequate by current standards (Bodansky et al. 1932; Fazekas 1939; Seegal 1927). 

No chronic-duration oral data were located. 

An additional reason not to derive oral MRLs for ammonia is because of the role played by the anion of 

the salt administered. Briefly, in many animal studies, the animals were administered ammonium 

chloride. Ammonium chloride is commonly used to induce metabolic acidosis in experimental animals. 

The acidosis is due to the formation of hydrogen ions from the metabolism of ammonium ions to urea. 

WHO (1986) notes that the ingestion of ammonium chloride in doses around 500–1,000 mg/kg/day for 1–

8 days (longer treatment would worsen the condition) has induced metabolic acidosis in mice, guinea 

pigs, rats, rabbits, and dogs. Metabolic acidosis can result in a variety of nonspecific changes in 

neurological, cardiovascular, pulmonary, gastrointestinal, and musculoskeletal function, as well as in 

changes in hematological and clinical chemistry parameters. Acidosis following the administration of 

ammonium chloride is due to the formation of hydrogen chloride and although it will occur with any 

ammonium salt, the degree of acidosis (and associated consequences) will be determined by the ability of 

the kidneys to excrete the specific anion. DeSousa et al. (1974) showed that administration of 

hydrochloric acid to dogs induced a significantly greater decrease in plasma bicarbonate than 

administration of equivalent quantities of H+

 as nitric or sulfuric acid. This means that it would be 

inappropriate to extrapolate findings obtained with ammonium chloride (or any ammonium salt) to 

equivalent amounts of ammonium, but derived from a different salt. 

Finally, as discussed by WHO (1986), the amount of excess ammonia (over and above the amount 

normally produced in the body) that can be safely ingested and assimilated is difficult to define. 

However, data from human and animals suggest that that amount may be substantial based on the 

existence of various efficient ways by which the body can dispose of ammonia. 

AMMONIA 23 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of ammonia. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 

considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these end points. ATSDR 

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between 

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 
AMMONIA 24 

3. HEALTH EFFECTS 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for ammonia. An MRL is defined as an estimate of daily human exposure to a substance that is 

likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of 

exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of 

effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. 

MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can 

be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. 

Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 
AMMONIA 25 

3. HEALTH EFFECTS 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

There are many reports in the literature of human deaths resulting from inhalation of ammonia (Arwood 

et al. 1985; Burns et al. 1985; Close et al. 1980; Couturier et al. 1971; George et al. 2000; Heifer 1971; 

Price et al. 1983; Sobonya 1977; Walton 1973; Weiser and Mackenroth 1989; Yang et al. 1987). Most of 

these reports are of acute accidental exposure to ammonia gas. A review of the early literature on 

ammonia toxicity cites acute exposure to 5,000–10,000 ppm as being rapidly fatal in humans (Henderson 

and Haggard 1927; Mulder and Van der Zalm 1967) and exposure to 2,500–4,500 ppm as being fatal in 

about 30 minutes (Helmers et al. 1971; Millea et al. 1989). Immediate deaths resulting from acute 

exposure to ammonia appear to be caused by airway obstruction while infections and other secondary 

complications are lethal factors among those who survive for several days or weeks. Chemical burns and 

edema of exposed tissues, including the respiratory tract, eyes, and exposed skin, are often observed after 

exposure to lethal levels. Post-mortem findings in the fatal case described by Walton (1973) included 

extensive edema and burns affecting the mouth, faces, trunk, arms, and upper part of the trunk. The 

airway at the larynx was almost blocked and the lungs were greatly distended and congested. 

Histological examination of the lungs showed acute congestion and edema. The bronchial walls were 

stripped of their epithelial lining, and some smaller bronchi contained plugs of debris, which included 

epithelial cells, red blood cells, and dust cells. No reports of human death due to intermediate or chronic 

exposure to ammonia were located. 

Studies in animals indicate that the acutely lethal exposure concentration depends on the exposure 

duration. The lethal concentration in rats and mice increases 5–10 times as the exposure duration 

decreases from 16 hours to several minutes (Hilado et al. 1977, 1978; Kapeghian et al. 1982; Morgan 

1997; Prokop'eva et al. 1973; Weedon et al. 1940). Exposure frequency also appears to be an important 

factor in determining lethality. Continuous exposure to 653 ppm for 25 days resulted in nearly 64% 

lethality in rats, whereas intermittent exposure (5 days/week, 8 hours/day) to nearly twice this 

concentration was tolerated for 42 days (Coon et al. 1970). It appears that male rats are more sensitive 

than female rats to the lethal effects of ammonia (Appelman et al. 1982; Stupfel et al. 1971). Animals 

exposed to acutely lethal concentrations show severe lesions in the respiratory tract that are similar to 

those observed in humans. Less severe lesions of the liver, heart, and kidney have been observed 

following continuous long-term exposure to lethal concentrations in rats, guinea pigs, rabbits, and dogs 

(Coon et al. 1970). However, these may represent secondary complications from chronic respiratory tract 

injury. 
AMMONIA 26 

3. HEALTH EFFECTS 

3.2.1.2 Systemic Effects 

Respiratory Effects. Ammonia is an upper respiratory irritant in humans. Exposures to levels 

exceeding 30 ppm result in immediate irritation to the nose and throat (Industrial Bio-Test Laboratories 

1973; MacEwen et al. 1970; Sekizawa and Tsubone 1994; Verberk 1977). Four out of six human subjects 

described moderate irritation of the nose and eyes when exposed to 50, but not 30, ppm ammonia gas for 

10 minutes (MacEwen et al. 1970). Twenty to 30% of subjects exposed to 72, but not 50, ppm ammonia 

gas for 5 minutes experienced eye, nasal, and throat irritation (Industrial Bio-Test Laboratories 1973). 

However, tolerance appears to develop with repeated exposure (Sekizawa and Tsubone 1994; Verberk 

1977). Thus, subjects exposed to 50 ppm ammonia 6 hours/day, 5 days/week for 6 weeks experienced 

nose and throat irritation only during the first week (Ferguson et al. 1977). Acute exposure to higher 

levels (500 ppm) has been shown to alter respiratory minute volume (Cole et al. 1977; Silverman et al. 

1949). Buff and Koller (1974) suggest that this is due to an effect on "irritant receptors" in the lungs 

resulting in increased activity of reflex respiratory muscles. This mechanism is also suggested by Cole et 

al. (1977), who exposed men to 100–331 ppm ammonia gas for 8–11 minutes while they were exercising 

on a stationary bicycle. Respiratory minute volume was decreased at concentrations of 150–331 ppm (but 

not at 100 ppm), and tidal volume was increased at 100 ppm ammonia, but decreased at higher 

concentrations (Cole et al. 1977). Accidental exposures to concentrated aerosols of ammonium solutions, 

high concentrations of ammonia gas, or anhydrous ammonia fumes have resulted in nasopharyngeal and 

tracheal burns, airway obstruction and respiratory distress, and bronchiolar and alveolar edema (Burns et 

al. 1985; Close et al. 1980; Couturier et al. 1971; de la Hoz et al. 1996; George et al. 2000; Hatton et al. 

1979; Heifer 1971; Kass et al. 1972; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; 

Millea et al. 1989; Morgan 1997; O’Kane 1983; Price et al. 1983; Sobonya 1977; Taplin et al. 1976; 

Walton 1973; Weiser and Mackenroth 1989). Chronic occupational exposure (about 14 years) to low 

levels of airborne ammonia (12.5 ppm) had no significant effect on pulmonary function or odor sensitivity 

in a group of workers at a soda ash factory compared to a control group from the same factory that was 

not exposed to ammonia (Holness et al. 1989). An acute-duration inhalation MRL of 1.7 ppm was 

derived from the Verberk (1977) study, and a chronic inhalation MRL of 0.1 ppm was derived from the 

Holness et al. (1989) study; MRLs are presented in Table 3-1 and Figure 3-1 and are discussed in 

Section 2.3. 

One human study with somewhat controlled exposure to ammonia showed that pulmonary function was 

not affected by low levels (25–100 ppm) of ammonia (Ferguson et al. 1977). Transient nose and throat 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

ACUTE EXPOSUREDeath

1

322

5000

5000 (rapidly fatal)

1 d0.5 hr/d

Human 

2

80

17401

17401 (LC50)

1 d15 min/d

Rat 

3

108

1000

1000 (LC50)

1 d16 hr/d

Rat 

4

53

21430

21430 (LC50)

1 d30 min/d

Mouse 

5

59

4230

4230 (LC50)

1 d1 hr/d

Mouse 

6

78

11299

11299 (LC50)

1 d60 min/d

Mouse 

7

107

1000

1000 (LC50)

1 d16 hr/d

Mouse 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

8

11

5025

5025 (LC50)

1 d1 hr/d

Rabbit 

9

9

5025

5025 (LC50)

1 d1 hr/d

Cat 

Systemic

10

100

Resp 100 M

388

150

150 M (decreased minute volume;

increased tidal volume)

Human 8-11 min 

11

50

Resp 50

389

72

72 (nasal and throat irritation)

Human 5 min 

12

30

Resp 30

386

50

50 (moderate nasal irritation)

Human 10 min 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

13

Resp

155

500

500 M (nasal and throat irritation;

increased minute volume andrespiratory rate)

1 d30 min/d

Human 

500

Cardio 500 M

500

Hemato 500 MOcular

500

500 M (lacrimation)

14

Resp

172

50

50 (urge to cough; irritation to nose

and throat)

1 d b2 hr/d

Human 

Ocular

50

50 (irritation to eyes)

15 Ocular

391

100

100 (eye irritation)

4 wk24 hr/d (Sherman)

Rat 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

16

Resp

89

500

500 (irritation)

1 wk24 hr/d (OFA)

Rat 

Renal

500

500 (increased kidney weight)

Bd Wt

500

500 (body weight and food intake

decreased 21%)

17

714

Resp 714

93

Rat 7 d 

714

Gastro 714Hemato

15

15 (slight increase blood pO2)

714

Renal 714

714

Dermal 714

714

Other 714
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

18

Resp

63

3440

3440 M (dyspnea; nasal irritation)

4220

4220 M (congestive intraalveloar

hemorrhage, 24% increasedrelative lung weight)

1 d1 hr/d (ICR)

Mouse 

Hepatic

3440

3440 M (degenerative changes;

increased relative liver weight)

3440

Bd Wt 3440 M

4220

4220 M (12% reduction in body weight)

19

218.6

Resp 218.6 M

46

1085.7

1085.7 M (temporary dyspnea during first

week of exposure)

1 wk5 d/wk8 hr/d (Beagle)

Dog 

20

218.6

Resp 218.6 M

43

1085.7

1085.7 M (temporary dyspnea during first

week of exposure)

1 wk5 d/wk8 hr/d (New Zealand)

Rabbit 

218.6

Ocular 218.6 M

1085.7

1085.7 M (temporary lacrimation)

21

Resp

92

5000

5000 (acute pulmonary edema)

1 d1 hr/d

Rabbit 

Cardio

2500

2500 (bradycardia)

5000

5000 (hypertension, acidosis, EKG

change)
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

22

Resp

385

1000

1000 (dyspnea; rhonchi; rales)

1 x10 min(IT)

(Mongrel)Cat 

23

50

Resp 50 M

348

100

100 M (decreased pulmonary vascular

response to endotoxinchallenge)

6 d

(BelgianLandrace)Pig 

50

Cardio 50 M

100

100 M (decreased pulmonary vascular

response to endotoxinchallenge)

100

Hemato 100 M

100

Endocr 100 M

25

Bd Wt 25 M

50

50 M (3% weight loss)

24

10

Resp 10

97

50

50 (frequent coughing)

1-2 wk

(Duroc)Pig 

10

Dermal 10

50

50 (oral and nasal irritation)

10

Bd Wt 10

50

50 (reduced weight gain and food

intake)
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

Immuno/ Lymphoret

25

91

500

500 M (decreased resistance to

infection)

7 d24 hr/d

Mouse 

26

50

50 M

349

100

100 M (decreased pulmonary response

to endotoxin challenge)

6 d

(BelgianLandrace)Pig 

Neurological

27

103

100

100 (sensory irritation)

1 d6 hr/d

Rat 

28

102

100

100 (sensory irritation)

1 d6 hr/d

Mouse 

INTERMEDIATE EXPOSUREDeath

29

22

641.6

641.6 (98% lethality) Rat 90 d 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

Systemic

30

25

Resp 25

151

50

50 (transient irritation of nose and

throat)

6 wk5 d/wk6 hr/d

Human 

100

Cardio 100

25

Ocular 25

50

50 (transient eye irritation)

31

Resp

40

218.6

218.6 M (focal pneumonitis)

6 wk5 hr/wk8 hr/d (Squirrel monkey)

Monkey 

1085.7

Cardio 1085.7 M

1085.7

Hemato 1085.7 M

1085.7

Hepatic 1085.7 M

1085.7

Renal 1085.7 M

1085.7

Dermal 1085.7 M

32

Resp

13

250

250 (nasal lesions, epithelial

hyperplasia)

5-10 wk24 hr/d (Sherman)

Rat 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

33

218.6

Resp 218.6

21

1085.7

1085.7 (nonspecific inflammation)

6 wk5 d/wk8 hr/d

Rat 

1085.7

Cardio 1085.7

1085.7

Hemato 1085.7

1085.7

Hepatic 1085.7

1085.7

Renal 1085.7

1085.7

Ocular 1085.7

34

179.1

Resp 179.1

24

369.4

369.4 (mild nasal discharge in 25% of

animals) 641.6

641.6 (interstitial pneumonitis)

90 or 114 d

(SpragueDawley)Rat 

369.4

Cardio 369.4

641.6

641.6 (myocardial fibrosis)

369.4

Hepatic 369.4

641.6

641.6 (fatty changes of liver plate

cells)

369.4

Renal 369.4

641.6

641.6 (renal tubular calcification)
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

35

218.6

Resp 218.6

18

1085.7

1085.7 (non specific inflammation)

6 wk5 d/wk8 hr/d

Gn Pig 

1085.7

Cardio 1085.7

1085.7

Hemato 1085.7

1085.7

Hepatic 1085.7

1085.7

Renal 1085.7

1085.7

Dermal 1085.7

36

90

Resp 90

101

3 wk24 hr/d (Hartley)

Gn Pig 

90

Hemato 90

90

Ocular 90

90

Bd Wt 90
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

37

170

Resp 170

106

18 wk5 d/wk6 hr/d

Gn Pig 

170

Cardio 170

170

Gastro 170Hemato

170

170 (increased hemosiderin)

Hepatic

170

170 (congestion)

Renal

170

170 (congestion)
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

38

57

Resp 57

27

Rabbit 114 d 

57

Cardio 57

57

Hemato 57

57

Hepatic 57

57

Renal 57

57

Dermal 57

39

Resp

52

100

100 (excessive nasal secretion,

coughing, trachealinflammation)

4 wks

(NS)Pig 

Ocular

50

50 (excessive lacrimation)

50

Bd Wt 50

100

100 (18.6% reduction in final body

weight)

Immuno/ Lymphoret

40

45

25

25 (increased severity of infection

by mycoplasma)

4 wk24 hr/d (Sherman and

Fischer)Rat 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

41

87

500

500 M (reduced resistance to infection)

3 wk24 hr/d

Rat 

42

100

90

90 (significantly reduced

delayed-type response totuberculin)

3 wk24 hr/d (Hartley)

Gn Pig 

50

50

43

70

100

100 (decreased serum concentration

of gamma globulin)

31-45 d24 hr/d (NS)

Pig 

Neurological

44

1085.7

1085.7 M

39

6 wk5 hr/wk8 hr/d (Squirrel monkey)

Monkey 

45

1085.7

1085.7

17

6 wk5 d/wk8 hr/d

Gn Pig 
LOAEL

NOAEL Serious Less Serious a

System

Key to

figure

Table 3-1 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation (continued)

(ppm) (ppm) (ppm) 

Exposure/

Duration/

Frequency

(Specific Route) Species (Strain)

46

50

50

51

100

100 (lethargy) Pig 4 wks 

CHRONIC EXPOSURESystemic

47

9.2

9.2

c

Resp

338

12.2 yr5 d/wk8 hr/d

Human 

9.2

Ocular 9.2

a The number corresponds to entries in Figure 3-1.b Used to derived an acute-duration inhalation MRL of 1.7 ppm; the MRL was derived by dividing the LOAEL of 50 ppm by an uncertainty factor of 30 (10 for vamong humans and 3 for use of a minimal LOAEL).c Used to derive a chronic-duration inhalation MRL of 0.1 ppm; the MRL was derived by adjusting the NOAEL of 9.2 ppm for continuous exposure (9.2 x 8/24 dividing by an uncertainty factor of 30 (10 for the protection of sensitive individuals, and 3 for the lack of reproductive and developmental studies).Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = female; gastro = gastrointestinal; hemato = hematological; hr = hour(s); LOlowest-observed-adverse-effect level; M = male; metab = metabolic; min = minute; mo = month(s); NOAEL = no-observed-adverse-effect level; NS = not specrespiratory; wk = week(s)
1

10

100

1000

10000

100000

Death

9c 1

4m5m6m7m2r

3r8h

Respiratory

22c19d

19d1010111112

1213

1418m18m16r17r20h20h21h23p

23p24p

24p

Cardiovascular

1321h21h23p23p

Gastrointestinal

17r

Hematological

1317r23p

Hepatic

18m

R

ppm

Figure 3-1. Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inha

Acute (≤14 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Systemic
1

10

100

1000

10000

100000

Immuno/Lymphor

25m26p26p

Neurological

28m 27r

ppm

Figure 3-1. Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation 

Acute (≤14 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Dermal

17r24p24p

Ocular

131415r20h20h

Body Weight

18m18m16r

23p

23p

24p24p

Other

17r

Systemic
10

100

1000

10000

Death

29r

Respiratory

35g35g36g37g3030

31k32r33r

33r34r34r34r38h39p

Cardiovascular

35g37g30

31k 33r

34r34r38h

Gastrointestinal

37g

Hematological

35g36g37g

31k 33r

38h

3537

ppm

Figure 3-1. Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation 

Intermediate (15-364 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Systemic
10

100

1000

10000

39p

Body Weight

36g39p39p

Immuno/Lymphor

42g42g40r41r43p

Ne

45g 

ppm

Figure 3-1. Levels of Significant Exposure to Ammonia And Ammonium Compounds - Inhalation 

Intermediate (15-364 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Renal

35g37g

31k 33r

34r34r38h

Dermal

35g 31k

38h

Ocular

36g303033r

Systemic
0.1

1

10

Respiratory

47

Ocular

47

ppm

Figure 3-1. Levels of Significant Exposure to Ammonia And Ammonium Compounds- Inhalation 

Chronic (≥365 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Systemic
AMMONIA 46 

3. HEALTH EFFECTS 

irritation was noted the first week of exposure in male and female volunteers exposed to 50 ppm, but not 

25 ppm ammonia 5 days/week, for 6 weeks. No significant differences were noted between exposed and 

control groups for pulmonary function tests, physical examinations, or performance of normal job duties 

(Ferguson et al. 1977). 

A number of occupational cohort studies that examined farmers who worked in enclosed livestock 

buildings have been conducted. These studies all included measurements of ammonia in the livestock 

confinement buildings, as well as measurements of one or more of the following: total dust, respirable 

dust, carbon dioxide, total endotoxins, respirable endotoxins, fungi, bacteria, and molds (Choudat et al. 

1994; Cormier et al. 2000; Donham et al. 1995, 2000; Heederik et al. 1990, 1991; Melbostad and Eduard 

2001; Reynolds et al. 1996; Vogelzang et al. 1997, 2000). Of the pollutants measured, ammonia and dust 

were most frequently associated with respiratory effects, many of which were temporary and disappeared 

with cessation of exposure. Ammonia levels ranged from 2.3 to 20.7 ppm and total dust levels from 

0.04 to 5.64 mg/m3

. Most of these studies reported an association between exposure to pollutants, 

including ammonia, in livestock confinement buildings and an increase in respiratory symptoms (such as 

bronchial reactivity/hyperresponsiveness, inflammation, cough, wheezing, or shortness of breath) and/or a 

decrease in pulmonary function (such as forced expiratory volume in the first second [FEV1.0], maximum 

expiratory flow rates [MEF50 and MEF75], and maximal mid-expiratory flow rate [MMEF]) (Choudat et 

al. 1994; Cormier et al. 2000; Donham et al. 1995, 2000; Heederik et al. 1990; Reynolds et al. 1996; 

Vogelzang et al. 1997, 2000). One study, however, reported correlations only between total dust, fungal 

spore, and endotoxin mean exposure levels and task-specific prevalences (Melbostad and Eduard 2001). 

Another study reported no significant correlations between lung function or chronic respiratory symptoms 

and dust or ammonia levels, but suggested that endotoxins and bacteria levels may play a role (Heederik 

et al. 1991). Most studies adjusted for confounding factors, such as smoking and number of years worked 

on a farm, in their statistical analyses. All of the studies concluded that prevalence of respiratory 

symptoms of some type was higher in the farmer cohort than in the respective control group. It is not 

clear from these studies what the contribution of ammonia is to the respiratory changes, but the 

cumulative data indicate that ammonia may contribute to transient respiratory distress in farmers working 

in enclosed livestock facilities. 

A cross-sectional study of male workers at two fertilizer factories in Saudi Arabia showed a significant 

association between exposure to ammonia gas and respiratory symptoms including bronchial asthma 

(Ballal et al. 1998). Workers in factory one were exposed to air ammonia levels of 2.82–183.86 ppm 

(2.0–130.4 mg/m3

), and workers in factory two were exposed to 0.03–9.87 ppm (0.02–7.0 mg/m3). 
AMMONIA 47 

3. HEALTH EFFECTS 

However, continuous exposure levels for workers could not be calculated because the number of days 

worked per week was not provided by the study authors. Logistic regression analysis showed that 

ammonia concentration was significantly related to cough, phlegm, wheezing (with and without shortness 

of breath), and asthma, whereas smoking was only a factor for wheezing and phlegm. Additionally, those 

workers exposed to ammonia levels above the American Conference of Governmental Industrial 

Hygienists (ACGIH) threshold limit value (TLV) of 25.4 ppm (18 mg/m3

) had significantly higher 

relative risks for cough, phlegm, wheezing, dyspnea, and asthma than workers exposed to levels below 

the TLV. Incidence of wheezing was also elevated in workers exposed to ammonia levels below the 

TLV. Cumulative ammonia concentration (CAC) of >50 mg/m3

-years also showed a significantly 

increased relative risk for all of the above symptoms compared to workers with a CAC of 

≤50 mg/m3

-years. None of the relative risks for workers in the second factory (ammonia levels 

<25.4 ppm) were significant. 

Other occupational studies also evaluated the effects of ammonia exposure and pulmonary function. 

Firefighters who reported exposure to ammonia while working had a rate of decline of FEV1 of 1.7 times 

that of nonexposed firefighters over a period of 6–10 years (Tepper et al. 1991). 

Children (8–9 years old) who attended two schools in the vicinity of a fertilizer plant had higher 

incidences of acute respiratory diseases than children of the same age who attended a school 

20 kilometers away (Gomzi and Šarić 1997). Incidence was related to levels of measured pollutants 

(ammonia, hydrogen fluoride, nitrogen dioxide, total suspended particulate matter, and smoke) in the 

inside and outside air. Forced expiratory volumes were not statistically different between the three 

schools. These results indicate that exposure to low levels of ammonia (0.04–0.23 ppm) and other airborne pollutants may not cause functional respiratory deficits, but may lower the resistance to respiratory 

pathogens in children. These effects may be due in part or in whole to toxicants other than ammonia, 

such as nitrogen dioxide. 

Case reports of individuals acutely exposed to anhydrous or aqueous ammonia reported respiratory effects 

including nasal irritation; epiglottic, laryngeal, pharyngeal, tracheal, and pulmonary edema; dyspnea; 

wheezing; coughing; rhonchi; pneumonia; and cardio-respiratory arrest (de la Hoz et al. 1996; George et 

al. 2000; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; Lee et al. 1993; Millea et 

al. 1989; Morgan 1997; Prudhomme et al. 1998; Weiser and Mackenroth 1989). de la Hoz et al. (1996) 

described the initial and residual effects of three adult males who had been acutely exposed to ammonia 
AMMONIA 48 

3. HEALTH EFFECTS 

gas in separate incidents. All three men complained of burning eyes, throat, and skin, cough, and 

wheezing, and all had been treated at hospitals shortly after exposure. Follow-up examinations 

2–21⁄2 years later showed persistent dyspnea, cough, and wheezing at rest and/or on exertion, which is 

consistent with restrictive lung disease secondary to acute ammonia inhalation injury. Another man 

exposed to anhydrous ammonia gas experienced pharyngeal and laryngeal edema, dyspnea, chest 

tightness, copious bronchial secretions, and wheezing (Leduc et al. 1992); 12 years postexposure, he 

continued to have cough, exertional dyspnea, and recurrent bronchial infections. Similar cases were 

reported by Kerstein et al. (2001) and Latenser and Lucktong (2000); no follow-up reports were available. 

A more severe exposure was reported by George et al. (2000). An adult male was found unconscious 

next to a burst pipe carrying liquefied ammonia. He had ocular and cutaneous burns and severe difficulty 

breathing. Over the next 27 days, he suffered many medical setbacks, including attacks of bradycardia, a 

complete circulatory collapse from which he was resuscitated, and finally, a fatal cardiac arrest from 

severe bleeding. Another similar severe exposure resulted in the death of the patient 13 days 

postexposure due to treatment-resistant bronchopneumonia; histological examination showed massive, 

hemorrhagic pulmonary edema, regions of emphysema, and edema of the epiglottis and glottis (Weiser 

and Mackenroth 1989). 

Reports of apparently rare effects have been found. A man exposed occupationally for 5 months to low 

levels of ammonia gas (8–15 ppm) from ammonia-containing silver polish developed asthma-like 

symptoms (Lee et al. 1993). Separate specific bronchial provocation tests to the silver polish and to 

12 ppm ammonia produced asthmatic reactions, implicating the ammonia in the silver polish as the cause. 

Another study reported hyposmia (loss of the sense of smell) in a man following acute inhalation 

exposure (for several hours) to an unknown concentration of ammonia gas; the hyposmia had not resolved 

30 months after exposure (Prudhomme et al. 1998). 

Studies in animals have demonstrated similar dose-effect and duration-effect patterns for the respiratory 

tract. Acute exposures (1 hour to 1 week) to low concentrations of ammonia (≤1,000 ppm) irritate the 

upper respiratory tract whereas exposures (3 hours to 2 weeks) to high concentrations (≥4,000 ppm) result 

in severe damage to the upper and lower respiratory tract and alveolar capillaries (Coon et al. 1970; 

Kapeghian et al. 1982; Mayan and Merilan 1972; Richard et al. 1978a, 1978b; Schaerdel et al. 1983; 

Stombaugh et al. 1969). Prolonged or repeated exposures to lower levels (≥150 ppm) produce 

inflammation and lesions of the upper respiratory tract (Broderson et al. 1976; Coon et al. 1970). 
AMMONIA 49 

3. HEALTH EFFECTS 

Clinical and histological effects have been seen in the lungs of animals following exposure to ammonia 

gas (Dodd and Gross 1980; Gaafar et al. 1992; Sjöblom et al. 1999). Cats exposed to 1,000 ppm 

ammonia gas for 10 minutes and observed for up to 35 days showed a biphasic course of respiratory 

pathology (Dodd and Gross 1980). Effects seen at 24 hours post-exposure included severe dyspnea, 

anorexia, and dehydration, with rhonchi and coarse rales evident upon auscultation. Microscopy of lung 

samples on day 1 showed necrotizing bronchitis in the large conducting airways, and necrosis and 

sloughing of the epithelium and acute inflammatory reaction in the bronchi. On day 7, the mucosal 

lesions had resolved, but on day 35, varying degrees of bronchitis and early bronchopneumonia with areas 

of bulbous emphysema were seen. Gross pathology revealed varying degrees of congestion, hemorrhage, 

edema, interstitial emphysema, and collapse of the lungs at all time points. Pulmonary resistance was 

increased throughout the study (Dodd and Gross 1980). Swiss mice exposed to 909 ppm, but not 

303 ppm, ammonia gas 6 hours/day, 5 days/week for 4–14 days had histological lesions in the respiratory 

epithelium in the nasal cavity (Zissu 1995); no lesions were observed in the trachea or lungs. Nasal 

mucosa was adversely affected in adult male mice exposed to vapor of 12% ammonia solution for 

15 minutes/day, 6 days/week for 4, 5, 6, 7, or 8 weeks (Gaafar et al. 1992). Histological changes 

progressed from weeks 4–8 from crowding of cells forming crypts and irregular arrangements to 

epithelial hyperplasia, patches of squamous metaplasia, loss of cilia, and dysplasia of the nasal 

epithelium. One animal that had loss of polarity of the epithelium, hyperchromatism, and mitotic figures 

with an intact basement membrane also had a carcinoma in situ in one nostril. At week 8, one mouse had 

an invasive adenocarcinoma of the nasal mucosa. Histochemical results were also abnormal. The levels 

and cell locations of succinic dehydrogenase, acid phosphatase, alkaline phosphatase, and nonspecific 

esterase activities were altered, indicating altered cell metabolism and energy production, cell injury, 

proliferation, and possibly chronic inflammation and neoplastic transformation (Gaafar et al. 1992). 

Anesthetized, mechanically ventilated rabbits exposed to high levels of nebulized ammonia (2 mL of 

23–27% ammonia solution; estimated by the study authors as peak ammonia concentrations of 

35,000–39,000 ppm) for 4 minutes had a decrease in blood oxygen saturation and an increase in airway 

pressure (a measure of changes in airway resistance) (Sjöblom et al. 1999). Arterial oxygen tension 

decreased from 23.3 (±3.6) to 11.0 (±3.6) kPa and peak airway pressure increased from 13 (±2) to 17 (±2) 

cm H2O. At baseline and 5 and 15 minutes after ammonia administration, measurements were taken via a 

catheter in the left auricular artery, which monitored pressure and sampled for arterial blood gases, and 

via transducers in the ventilator. Thirty and 150 minutes after ammonia exposure, rabbits received 

inhalation therapy of either 0.5 mg budesonide (a steroid) or a placebo, and airway pressure, 

hemodynamics, and gas exchange were measured every 30 minutes for 6 hours. Slight, gradual 
AMMONIA 50 

3. HEALTH EFFECTS 

improvement of blood gas parameters was noted over the 6-hour observation period in all rabbits, with or 

without steroid treatment; however, no parameters approached normal during that time period. 

Other studies examined pigs in normal swine production facilities (Donham 1991) or in environmentally 

regulated enclosures (Diekman et al. 1993; Gustin et al. 1994; Urbain et al. 1994). Donham (1991) 

investigated the correlation of housing air environment (in the finishing barn) to swine diseases and 

productivity over 12 months on 28 swine farms. Total dust, respirable dust, endotoxin activity of the 

dust, and hydrogen sulfide levels were determined, and area dust and microbial counts were monitored at 

1.2 meters above the floor (the human breathing zone). Ammonia and carbon dioxide levels were 

determined 1.2 meters and 20 cm (swine breathing zone) above the floor. The average ammonia 

concentration in the human breathing zone for all farms was 9.1 ppm; the mean concentration in the swine 

breathing zone was 14.5 ppm. The mean concentrations of environmental contaminants were calculated 

for the most productive farrowing operations and the least productive ones and compared with lower 

production variables (Donham 1991). Ammonia concentration was related to number of pigs weaned per 

litter, and total and respirable dust concentrations were related to prolonged age to reach a weight of 

25 kg. Another comparison involved the stratification of the finishing farms into quartiles according to 

percentage of pigs with specified disease conditions and comparison of mean concentrations of various 

environmental contaminants for each farm in each strata (Donham 1991). Levels of ammonia (in the 

animal breathing zone) greater than 25, 29, and 23 ppm were associated with buildings in which 

pneumonia, pleuritis, and arthritis, respectively, were greater than the mean value for the group. Overall, 

respirable dust (>0.8 mg/m3

), ammonia (>23 ppm in the animal breathing zone), and carbon dioxide 

(>2,000 ppm) levels were most often associated with increased disease. Possible study shortcomings 

noted by the study author were that pre-existing conditions could have been present in the pigs (before 

they entered the finishing barns) and that nasal turbinates were not routinely examined for abnormalities. 

These data suggest that ammonia may contribute to respiratory and other pathological conditions in pigs 

raised in crowded, enclosed conditions, but the exact contribution of ammonia is difficult to assess. 

The lungs of young pigs exposed continuously to 0, 25, 50, or 100 ppm ammonia gas for 6 days in airpollutant exposure chambers were removed, ventilated, and perfused, and the pulmonary vascular 

hemodynamics and permeability and the endotoxin-induced vascular response were assessed (Gustin et 

al. 1994). In lungs from pigs exposed to 100 ppm, but not 25 or 50 ppm ammonia, the endotoxin-induced 

vascular response seen in lungs from control pigs was abolished. The study authors suggested that this is 

due to a modification of the balance between vasodilators (such as cyclooxygenase products and platelet 

activating factor) and vasoconstrictors (such as prostacyclin). Since vasoconstriction, as induced by 
AMMONIA 51 

3. HEALTH EFFECTS 

endotoxin, may serve as a protective mechanism in the lungs and attenuate edema formation, the effective 

abolishment of this effect by ammonia may be detrimental. 

Young pigs exposed continuously to ammonia vapors (0, 25, 50, or 100 ppm) for 6 days in air-pollutant 

exposure chambers had increased numbers of neutrophils in nasal lavage fluid in all exposure groups 

(Urbain et al. 1994) and increased porcine serum albumin at 100 ppm. 

Not all studies have shown adverse respiratory effects from intermediate exposure to ammonia vapors. 

Groups of gilts (virgin female pigs) were raised from the age of 2–4.5 months in a conventional grower 

unit where they were naturally exposed to mycoplasmal and bacterial pathogens that cause enzootic 

pneumonia and atrophic rhinitis (Diekman et al. 1993). The pigs were then transferred to 

environmentally regulated rooms, where they were exposed continuously to low (mean 7 ppm) or 

moderate (mean 35 ppm) levels of ammonia for 6 weeks. No statistically significant differences were 

seen in the percent of lung tissue containing lesions or in snout grade (Diekman et al. 1993). Ninety-five 

percent of all gilts had lung lesions, with a wide range of degree of severity. Snouts were graded at the 

level of the second deciduous premolar as having normal turbinates (grade of 0), slight to moderate 

degeneration (grade of 1–3), or severe degeneration to complete loss of turbinates (grade of 4 or 5). Some 

of the gilts were continuously exposed through puberty and breeding (around 205 days of age) and the 

lungs and turbinates were examined at 30 days of gestation. No statistically significant differences were 

observed in percent of lung tissue containing lesions or in snout grade (Diekman et al. 1993). 

A number of cattle were acutely exposed to anhydrous ammonia when a pipeline running through their 

pasture ruptured and leaked 1,800 barrels of ammonia in a short period of time (Morgan 1997). The 

ammonia combined with moisture and formed a white cloud (ammonia aerosol), which drifted south 

across two additional fields containing cattle. In the field where the rupture occurred, four head of cattle 

were found dead and two others were euthanized because of blindness and respiratory distress. Cattle in 

the adjacent pasture had runny eyes and noses and were coughing and wheezing. Eight days after the 

pipeline rupture, the cloud of ammona aerosol, which had apparently settled in a low-lying protected area, 

blew back up the valley and exposed the remaining cattle again and also exposed a horse in the same 

pasture. All animals had respiratory distress, elevated body temperatures, and one cow and the horse had 

swollen tongues and enlarged lymph glands. All cattle were given antibiotics and some were treated 

specifically for respiratory problems. No measurements or estimations of ammonia concentrations were 

provided and no follow-up examinations were available to assess long-term effects from the exposures. 
AMMONIA 52 

3. HEALTH EFFECTS 

All reliable LOAELs and highest NOAELs are presented in Table 3-1 and Figure 3-1. 

Cardiovascular Effects. Acute exposure to highly concentrated aerosols of ammonium compounds 

may cause elevated pulse and blood pressure, bradycardia, and cardiac arrest in humans (George et al. 

2000; Hatton et al. 1979; Montague and Macneil 1980; White 1971). These effects did not occur after 

acute exposure to 500 ppm ammonia or repeated exposure to 100 ppm ammonia (Ferguson et al. 1977;

Silverman et al. 1949). 

Cardiovascular changes that may be analogous to those observed in humans have been observed in rabbits 

exposed to high concentrations of ammonia (Richard et al. 1978b). Bradycardia was seen at 2,500 ppm, 

and hypertension and cardiac arrhythmias leading to cardiovascular collapse followed acute exposures to 

concentrations exceeding 5,000 ppm. Pathological correlates for these effects have not been 

demonstrated. Atrophy of pericardial fat has been observed in mice exposed to 4,000 ppm ammonia 

(Kapeghian et al. 1982). Myocardial fibrosis has been observed in rats, guinea pigs, rabbits, dogs, and

monkeys after prolonged (90 days) continuous exposure to 653 ppm (Coon et al. 1970). The contribution 

of these lesions to the morbidity and mortality of affected animals has not been determined. 

Exposure of pigs in vivo to up to 100 ppm ammonia for 6 days did not alter the baseline values of any

hemodynamic or permeability parameters (arterial, pre- or postcapillary, or venous blood flow resistance, 

or total pulmonary blood flow resistance), but did eliminate the hemodynamic response to 

Escherichia coli endotoxins in the lungs (Gustin et al. 1994). This may affect the ability of the lungs to 

resist bacterial infection. The pulmonary blood flow resistance measurements were taken in vitro in 

ventilated and perfused lungs from pigs exposed to ammonia in vivo (Gustin et al. 1994). Reliable 

LOAELs and highest NOAELs for cardiovascular effects are presented in Table 3-1 and Figure 3-1. 

Gastrointestinal Effects. Exposure to highly concentrated aerosols of ammonium compounds can 

produce burns of the lips, oral cavity, and pharynx, along with edema of these areas (Hatton et al. 1979; 

Kass et al. 1972; Leduc et al. 1992; Levy et al. 1964; Price et al. 1983; Stroud 1981; Ward et al. 1983; 

Yang et al. 1987). Gastrointestinal effects of ammonia in animals have not been reported. As shown in 

Table 3-1, pathological changes in the gastrointestinal tract were not observed in guinea pigs exposed 

repeatedly to 170 ppm ammonia (Weatherby 1952). 
AMMONIA 53 

3. HEALTH EFFECTS 

Hematological Effects. Cyanosis, elevated white blood cell count, and pulmonary artery thrombosis 

have been observed in humans exposed to highly concentrated aerosols of ammonium compounds 

(Sobonya 1977; Taplin et al. 1976; Voisin et al. 1970; Ward et al. 1983; White 1971). 

Standard hematological measurements, including blood hemoglobin and differential cell counts, have 

been reported for a few animal species. As shown in Table 3-1 and Figure 3-1, acute hematological 

effects of ammonia have not been demonstrated (Doig and Willoughby 1971; Gustin et al. 1994). Pigs 

exposed to up to 100 ppm ammonia for 6 days had no statistically significant differences from controls in 

total leukocytes or percent lymphocytes, neutrophils, or eosinophils (Gustin et al. 1994). Repeated 

exposure to 1,100 ppm had no effect on hematological parameters in guinea pigs, rats, and rabbits (Coon 

et al. 1970). Weatherby (1952) reported increased concentrations of hemosiderin in the spleen of guinea 

pigs exposed to 170 ppm ammonia for 18 weeks. This suggests the possibility of increased turnover of 

red blood cells; however, this has not been corroborated. 

Musculoskeletal Effects. Spasms of muscles of the extremities have resulted from an acute 

exposure of a man to anhydrous ammonia gas (White 1971), but this was probably caused by an effect of 

ammonia on the nervous system. 

Hepatic Effects. Hemorrhagic necrosis of the liver was observed in an individual exposed to a lethal 

concentration of ammonia gas and liquid for a short period of time (<45 minutes) (Heifer 1971). No other 

cases of hepatic effects have been reported in humans. Hepatic effects are usually not seen in animals 

exposed to ammonia gas. As shown in Table 3-1, liver necrosis has been observed following acute lethal 

exposure of mice to 3,440 ppm ammonia for 1 hour (Kapeghian et al. 1982). Fatty changes of liver plate 

cells were seen in rats following continuous long-term exposure to 642 ppm ammonia for 90 days, but no 

such changes were seen in rats, squirrel monkeys, and guinea pigs exposed to 1,086 ppm ammonia 

8 hours/day, 5 days/week for 6 weeks (Coon et al. 1970). 

Renal Effects. No studies were located regarding renal effects in humans after inhalation exposure to 

ammonia. In animals, renal effects do not appear to be an important feature of the toxicity of inhaled 

ammonia. Effects reported have not been corroborated or cannot be interpreted. Mild abnormalities in 

the renal tubules have been described in guinea pigs exposed to 170 ppm for 12 weeks, 5 days/week, 

6 hours/day; however, renal effects at this relatively low level have not been corroborated (Weatherby 

1952). Exposure to more than 6 times this concentration for 6 weeks, 5 days/week, 8 hours/day did not 
AMMONIA 54 

3. HEALTH EFFECTS 

result in pathological changes to the kidney (Coon et al. 1970). Renal tubular calcification (severity not 

reported) has been reported in rats continuously exposed to near lethal levels (Coon et al. 1970). 

Endocrine Effects. Adrenaline levels in urine, 17-oxycorticosteroids in the urine, and 11-oxycorticosteroid levels in blood were increased in humans exposed to 3.0 ppm ammonia for 37 days (Kalandarov et 

al. 1984). Exposure to 7.2 ppm for 17 days also increased adrenaline levels in urine and 17-oxycorticosteroids in the urine, and increased free, but not total, 11-oxycorticosteroid levels in blood (Kalandarov et 

al. 1984). Experimental details were lacking in this study; additionally, no clinical or histological data 

were provided for this or other end points in this study and no supporting data are available in the 

literature. Therefore, the significance of these effects is unclear. Exposure of pigs to up to 100 ppm 

ammonia for 6 days did not significantly alter the plasma cortisol concentration (Gustin et al. 1994). No 

statistically significant difference was seen in adrenal gland weight of female pigs exposed to about 

35 ppm ammonia for 6 weeks or for 6 weeks plus through day 30 of gestation compared to pigs exposed 

for similar time frames to about 7 ppm ammonia (Diekman et al. 1993). No unexposed controls were 

included in that study. The endocrine system does not appear to be a primary target of inhaled ammonia. 

Dermal Effects. Ammonia gas and aerosols of ammonium compounds derived from anhydrous 

ammonia are dermal irritants in humans and animals. These effects are described in the discussion of 

dermal effects associated with dermal exposure (Section 3.2.3.2). 

Ocular Effects. Ammonia gas and aerosols of ammonium compounds derived from anhydrous 

ammonia are ocular irritants in humans and animals. These effects are described in the discussion of 

ocular effects associated with dermal exposure (Section 3.2.3.2). 

Body Weight Effects. Reduced body weight has been observed in rats exposed via inhalation to 

500 ppm (Richard et al. 1978a) and in pigs exposed to 50 ppm or more ammonia for 6 days (Gustin et al. 

1994; Urbain et al. 1994). Pigs gained less weight and showed decreased food consumption when 

exposed to 100 ppm ammonia for 4 or 5 weeks (Drummond et al. 1980; Stombaugh et al. 1969). Female 

pigs exposed to about 35 ppm for 6 weeks gained less weight than those exposed to only about 7 ppm 

(Diekman et al. 1993). However, females that were continuously exposed to about 7 or 35 ppm ammonia 

from 6 weeks before breeding until day 30 of gestation had no statistically significant difference in body 

weight (Diekman et al. 1993); however, no controls were included in this study. 
AMMONIA 55 

3. HEALTH EFFECTS 

3.2.1.3 Immunological and Lymphoreticular Effects 

Several case reports describe occupational asthma that developed due to exposure to aerosols that 

contained ammonium compounds (Ballal et al. 1998; Lee et al. 1993; Weir et al. 1989). 

Secondary infections often complicate the clinical outcome of burns and respiratory lesions related to 

exposure to highly concentrated aerosols derived from anhydrous ammonia (Sobonya 1977; Taplin et al. 

1976). However, there is no evidence that the decreased immunological resistance represents a primary 

impairment of the immune system in humans following exposure to ammonia. Nevertheless, as shown in 

Table 3-1 and Figure 3-1, studies in animals have shown that acute and long-term exposure to ammonia 

can decrease the resistance to bacterial infection and decrease immune response to infection. A 

significant increase in mortality was observed in mice exposed to ammonia for 168 hours followed by 

exposure to the LD50 of Pasteurella multocida (Richard et al. 1978a). Exposure of rats to ammonia at 

≥25 ppm for 4–6 weeks following inoculation with Mycoplasma pulmonis intranasally significantly 

increased the severity of respiratory signs characteristic of murine respiratory mycoplasmosis (Broderson 

et al. 1976). Guinea pigs exposed to 90 ppm ammonia for 3 weeks developed a significant decrease in the 

cell-mediated immune response to challenge with a derivative of tuberculin (Targowski et al. 1984). 

Furthermore, the response of blood and bronchial lymphocytes to mitogens (phytohemagglutinin, 

concanavalin A, purified protein derivative of tuberculin) was markedly reduced. The hemodynamic 

response (increased total pulmonary blood flow resistance) to E. coli endotoxins in the lungs of pigs was 

eliminated by exposure to up to 100 ppm ammonia for 6 days, which may affect the ability of the lungs to 

resist bacterial infection (Gustin et al. 1994). Also, a reduction in gamma globulin concentration was 

reported in pigs exposed to 100 ppm ammonia for 31–45 days (Neumann et al. 1987). 

3.2.1.4 Neurological Effects 

Case reports of accident victims exposed to highly concentrated aerosols derived from anhydrous 

ammonia describe blurred vision, diffuse nonspecific encephalopathy, loss of consciousness, muscle 

weakness, and decreased deep tendon reflexes (George et al. 2000; Hatton et al. 1979; Latenser and 

Lucktong 2000; White 1971). Acute exposure to low levels of ammonia (100 ppm) has been shown to 

depress free-access wheel running behavior in rodents (Tepper et al. 1985). No overt symptoms of 

neurological disorders were reported in guinea pigs or monkeys that were exposed to up to 1,105 ppm 

ammonia for 6 weeks (Coon et al. 1970). Exposure of the nasal mucosa to ammonia-saturated air elicited 

vasodilatation and corresponding increased blood flow and reflex hypertension in the lower lip of cats 
AMMONIA 56 

3. HEALTH EFFECTS 

(Izumi and Karita 1993). Stimulation of the nasal mucosa by chemical irritants has been shown to elicit 

changes in the respiratory system, such as apnea, laryngeal spasm, and bronchoconstriction, and in the 

cardiovascular system, such as bradycardia and variable blood pressure changes (Izumi and Karita 1993). 

Brain glutamine levels have also been shown to increase in rats that inhaled 25 or 300 ppm ammonia 

vapor for 6 hours/day for 5 days, which is likely a result of ammonia metabolism by the astrocytic 

glutamate-glutamine cycle (Manninen and Savolainen 1989; Manninen et al. 1988). 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to ammonia. 

No statistically significant differences were noted in ovarian or uterine weights of pigs exposed to about 

7 or 35 ppm ammonia for 6 weeks (Diekman et al. 1993). Female pigs that were continuously exposed to 

about 35 ppm ammonia from 6 weeks before breeding until day 30 of gestation had no statistically 

significant differences in age at puberty, number of live fetuses, or fetus-to-corpus luteum ratio compared 

to pigs exposed to only about 7 ppm (Diekman et al. 1993). No unexposed controls were included in that 

study. 

3.2.1.6 Developmental Effects 

No information was located regarding developmental effects of ammonia in humans following inhalation 

exposure. No statistically significant difference in fetal length was evident at 30 days of gestation in 

offspring of pig dams that were continuously exposed to about 7 or 35 ppm ammonia from 6 weeks 

before breeding until day 30 of gestation (Diekman et al. 1993). 

3.2.1.7 Cancer 

Carcinogenic potential of ammonia by the inhalation route has not been assessed in humans or animals. 

One case report was found of an individual who developed epidermal carcinoma of the nasal septum 

6 months after being badly burned by accidental contact with a refrigeration ammonia-oil mixture 

(Shimkin et al. 1954). However, the role of ammonia is impossible to ascertain and no conclusion can be 

drawn from this study. Shimkin et al. (1954) indicated that “no single case can prove a general principle, 

and it is only by the publication of additional reports of similar cases that enough data can become 

available for critical analysis.” No other such reports were located, although other cases of inhalation 
AMMONIA 57 

3. HEALTH EFFECTS 

exposure to ammonia from spills have been followed for more than 6 months after exposure. One of 

10 adult male mice exposed to ammonia gas for 15 minutes/day 6 days/week for 8 weeks had mitotic 

figures with an intact basement membrane and a carcinoma in situ in one nostril and one mouse had an 

invasive adenocarcinoma of the nasal mucosa (Gaafar et al. 1992). Again, there is no conclusive 

evidence that ammonia played a role in the induction of the carcinoma. Gaafar et al. (1992) provided an 

alternate explanation by stating that “prolonged exposure to ammonia may interfere with the normal 

protective reflexes of the respiratory nasal mucosa resulting in the accumulation of particulate matter 

initiating or promoting a neoplastic process.” However, the plausibility of tumor formation in only 

8 weeks by a weak carcinogen such as particulate matter is debatable. 

3.2.2 Oral Exposure 

As discussed in Chapter 4, ammonia in aqueous solution exists in equilibrium with ammonium hydroxide, 

a weak base, which is partially ionized in water. Degree of ionization is dependent on pH; at 

physiological pH, ammonium hydroxide is 99% ionized, but at pH 9.25, is only 50% ionized. 

Information available for humans exposed to ammonia by the oral route usually involved case reports of 

people who swallowed household ammonia (ammonium hydroxide). Studies by the oral route in animals 

generally have used ammonium salts or ammonium hydroxide. For these reasons, oral doses are 

expressed as mg NH4

+

/kg/day, given as the particular ammonium compound. 

In many animal studies, the animals were administered ammonium chloride. Ammonium chloride is 

commonly used to induce metabolic acidosis in experimental animals. The acidosis is due to the 

formation of hydrogen ions from the metabolism of ammonium ions to urea. WHO (1986) notes that the 

ingestion of ammonium chloride in doses around 500–1,000 mg/kg/day for 1–8 days (longer treatment 

would worsen the condition) has induced metabolic acidosis in mice, guinea pigs, rats, rabbits, and dogs. 

Metabolic acidosis can result in a variety of nonspecific changes in neurological, cardiovascular, 

pulmonary, gastrointestinal, and musculoskeletal function, as well as in changes in hematological and 

clinical chemistry parameters. 

3.2.2.1 Death 

Human deaths due to ingestion of household ammonium salts have been reported (Klein et al. 1985; 

Klendshoj and Rejent 1966), but no quantitative data for oral exposure in humans were located. A 
AMMONIA 58 

3. HEALTH EFFECTS 

69-year-old woman who ingested an unknown quantity of lemon ammonia (3% ammonium ion) was 

found semi-conscious and making gurgling respiratory sounds (Klein et al. 1985). Radiographic results 

were consistent with aspiration pneumonia, and endoscopy showed laryngeal and epiglottic edema and a 

friable, erythematous esophagus with severe corrosive injury. The woman died several days later after 

developing acute respiratory distress syndrome and renal failure (Klein et al. 1985). A 57-year-old man 

was found dead with a glass containing dilute ammonium hydroxide (2.4% ammonium ion) nearby 

(Klendshoj and Rejent 1966); autopsy showed hemorrhagic esophagus, stomach, and duodenum. As 

shown in Table 3-2 and Figure 3-2, 303 mg ammonium/kg as ammonium chloride is a lethal dose in 

guinea pigs when given as single gavage dose (30/40 died) (Koenig and Koenig 1949). Death, in this 

study, resulted from pulmonary edema. No deaths were seen in cats, rabbits, guinea pigs, or rats after a 

similar dose of ammonium (337 mg ammonium/kg given as ammonium chloride) (Boyd and Seymour 

1946). 

3.2.2.2 Systemic Effects 

No information was located regarding dermal or ocular effects of ammonia or ammonium compounds in 

humans or animals following oral exposure. 

Respiratory Effects. No information was located regarding respiratory effects of ammonia or 

ammonium compounds in humans following oral exposure. Guinea pigs that received a single gavage 

dose of ammonium chloride developed serious respiratory effects including increased rate and depth of 

respiration, pulmonary edema, and death by respiratory failure (Koenig and Koenig 1949). Because the 

blood pH of the guinea pigs decreased after administration of ammonium chloride, adjustments in 

respiratory rate and depth may have been a compensatory mechanism for acidosis. Similarly, 

administration of ammonium chloride in doses of approximately 100 mg of NH4

+

/kg/day (as ammonium 

chloride) or higher for up to a year to rabbits resulted in metabolic acidosis and compensatory changes in 

respiratory rate and tidal volume (Seegal 1927). The low blood pH results in increased lung ventilation, 

which increases the elimination of carbon dioxide from the blood, and therefore, can be considered a 

compensatory response to acidosis rather than a direct effect of ammonium ion on the lungs or respiratory 

system. 

Cardiovascular Effects. No information was located regarding cardiovascular effects of ammonia 

or ammonium compounds in humans following oral exposure. No pathological abnormalities were noted 

in the hearts of adult and weanling rats fed doses of up to 79 mg ammonium/kg/day as ammonium 
LOAEL

NOAEL Less Serious Serious a

System

Key to

figure

Reference

Table 3-2 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Oral

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form

Exposure/

Duration/

Frequency

(Specific Route)

Species

(Strain)

ACUTE EXPOSURE

Death

1

317

286

286 (death due to pulmonary edema)

Gn Pig 1 d Koenig & Koenig 1949

NH4CL

Systemic

2

Hemato

113

2325

2325 (elevated serum calcium)

6 d

(Sprague- (W)

Dawley)

Rat Barzel 1975

NH4Cl

3

22

Bd Wt 22 F

367

3150.4

3150.4 F (10% reduction in final body

weight)

3 or 7 d

(Wistar) (F)

Rat Bodega et al. 1993

ammonium acetate

4

22

Bd Wt 22

373

3102.2

3102.2 (final body weight decreased by

15%)

3 or 7 d

(Wistar) (F)

Rat Boyano-Adanez et al. 1996

ammonium acetate

5

Renal

135

433

433 (renal enlargement due to cell

hypertrophy)

7 d

(Sprague- Gavage - NS

Dawley)

Rat Janicki 1970

NH4Cl

6

Resp

122

303

303 (pulmonary edema)

1 d

Gavage - NS

Gn Pig Koenig & Koenig 1949

NH4CL
LOAEL

NOAEL Less Serious Serious a

System

Key to

figure

Reference

Table 3-2 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Oral (continued)

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form

Exposure/

Duration/

Frequency

(Specific Route)

Species

(Strain)

Neurological

7

22

22

372

3102.2

3102.2 (decreased binding of

somatostatin to receptors in

frontoparietal cortex and

hippocampus)

3 or 7 d

(Wistar) (F)

Rat Boyano-Adanez et al. 1996

ammonium acetate

INTERMEDIATE EXPOSURE

Systemic

8

Musc/skel

114

991

991 (reduced calcium less fat-free

solid)

330 d

(W)

Rat Barzel & Jowsey 1969

NH4Cl

Bd Wt

991

991 (reduced body weight)

9

22

Bd Wt 22 F

392

3150

3150 F (15% reduction in final body

weight after 90 days)

90 d

(Wistar) (F)

Rat Bodega et al. 1993

ammonium acetate

10

22

Bd Wt 22

375

3102.2

3102.2 (final body weight gain

decreased by 10%)

15 d

(Wistar) (F)

Rat Boyano-Adanez et al. 1996

ammonium acetate

11

412

Renal 412

118

3 wk

(W)

Rat Freedman & Beeson 1961

NH4CL
LOAEL

NOAEL Less Serious Serious a

System

Key to

figure

Reference

Table 3-2 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Oral (continued)

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form

Exposure/

Duration/

Frequency

(Specific Route)

Species

(Strain)

12

79

Cardio 79 F

120

90 d

6 d/wk

(W)

(albino)

Rat Gupta et al. 1979

NH4NH2SO3

79

Gastro 79 F

79

Hemato 79 F

79

Hepatic 79 F

79

Renal 79 F

39.5

Bd Wt 39.5 F

79

79 F (body weight decreased by 16%)

13

Musc/skel

134

337

337 (bone deformity and softening)

11 wk

Gavage - NS

Dog Bodansky et al. 1932

NH4Cl

Neurological

14

22

22

374

3102.2

3102.2 (decreased binding of

somatostatin to receptors in

frontoparietal cortex and

hippocampus)

15 d

(Wistar) (F)

Rat Boyano-Adanez et al. 1996

ammonium acetate
LOAEL

NOAEL Less Serious Serious a

System

Key to

figure

Reference

Table 3-2 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Oral (continued)

(mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form

Exposure/

Duration/

Frequency

(Specific Route)

Species

(Strain)

Developmental

15

a The number corresponds to entries in Figure 3-2.

Bd Wt = body weight; Cardio = cardiovascular; d = day(s); DW = drinking water; (F)= feed; F = female; Gd = gestation day; G = gavage; gastro = gastrointestinal; hemato =

hematological; hr = hour(s); LOAEL = lowest-observed-adverse-effect level;min = minute(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified;

Resp = respiratory; NS = not specified; wk = week(s)

380

4293

4293 (BW decreased by 16-27%;

decreased NMDA receptor

function in neurons)

Gd 1-ppd 21

(Wistar) (F)

Rat Minana et al. 1995

NH3CH3CO2
10

100

1000

10000

Death

1g

Respiratory

6g

Hematological

2r

Renal

5r

Body Weight

3r3r

4r4r

Neurolo

7r7r

mg/kg/day

Figure 3-2. Levels of Significant Exposure to Ammonia And Ammonium Compounds - O

Acute (≤14 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Systemic
10

100

1000

10000

Cardiovascular

12r

Gastrointestinal

12r

Hematological

12r

Musculoskeletal

13d8r

Hepatic

12r

Renal

11r12r

Body Weight

8r9r9r

10r10r12r12r

Neurologic

14r14r

mg/kg/day

Figure 3-2. Levels of Significant Exposure to Ammonia And Ammonium Compounds - Oral (C

Intermediate (15-364 days)

c-Catd-Dog r-Ratp-Pig q-Cow

 -Humansk-Monkey m-Mouseh-Rabbita-Sheep

f-Ferretj-Pigeon e-Gerbils-Hamsterg-Guinea Pig

n-Minko-Other

 Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals

 Cancer Effect Level-Humans LOAEL, More Serious-Humans LOAEL, Less Serious-Humans NOAEL - Humans

Systemic
AMMONIA 65 

3. HEALTH EFFECTS 

sulfamate for 90 days in drinking water (Gupta et al. 1979). These data are presented in Table 3-2 and 

Figure 3-2. 

Gastrointestinal Effects. Several cases have been described of young children (2–3 years old) who 

bit into ammonia pellets/capsules (Lopez et al. 1988; Rosenbaum et al. 1998). Two of the children 

drooled and had ulcerative lesions on the tongue and/or on the buccal mucosa; one child had superficial 

ulcerations on the posterior esophageal wall and the other child had edematous, erythematous upper and 

lower lips with areas of desquamation, eschar of the hard palate, and edema and erythema of the 

supraglottic structures and upper trachea (Rosenbaum et al. 1998). All of the children experienced one or 

more of the following symptoms: vomiting, drooling, dysphagia, cough, or oral or pharyngeal burns 

(Lopez et al. 1988; Rosenbaum et al. 1998). None of the children had esophageal or respiratory burns and 

all healed within a few days. Esophageal lesions and edema were reported in five persons who ingested 

household ammonia (ammonium hydroxide), one of whom experienced acute respiratory obstruction 

(Christesen 1995; Klein et al. 1985). These observations were not quantified. The effects are probably 

due to the alkaline nature of ammonium hydroxide. A single case report described a self-administered 

ammonia solution enema that resulted clinically in anal pain, diffuse abdominal colic, and tenesmus (da 

Fonseca et al. 1998). Sigmoidoscopy showed diffuse erythematous friable mucosa with large ulcerations 

covered by yellowish exudate that receded in a few days, but chronic inflammation and fibrosis of the 

rectum and sigmoid colon was noted 3 months postexposure (da Fonseca et al. 1998). 

No histopathological abnormalities of the gastrointestinal tract were observed in adult or weanling rats 

administered doses of up to 79 mg ammonium/kg/day as ammonium sulfamate for 90 days via drinking 

water (Gupta et al. 1979). Likewise, a 3% solution of ammonium chloride administered to rats via gastric 

tube produced no gastric mucosal damage in 1 hour and a 10% solution produced only a minimum of 

hemorrhagic lesions (about 9 mm2

) (Takeuchi et al. 1995). However, similar administration of 1 or 3% 

ammonium hydroxide in rats produced severe hemorrhagic lesions (about 26.6 or 97.7 mm2

, respectively) 

(Takeuchi et al. 1995). Gavage administration in rats of 0.3% ammonia (33.3 mg/kg) produced gastric 

mucosal lesions within 5 minutes with corresponding decreases in gastric wall immunoreactive 

endothelin-1 (ET-1) and immunoreactive thyrotropin-releasing hormone (TRH) concentrations and 

increases in gastric juice ET-1 and TRH concentrations (Mori et al. 1998). In situ gastric exposure has 

also shown ammonia-induced gastric mucosal damage (Murakami et al. 1995; Nagy et al. 1996). These 

lesions are exacerbated by neutrophil products, especially hypochlorous acid (Murakami et al. 1995) and 

cysteine proteases, such as some of the cathepsins (Nagy et al. 1996). Administration of 0.01% ammonia 

in drinking water to rats (approximately 42 mg/kg/day) for 8 weeks resulted in acceleration of cell 
AMMONIA 66 

3. HEALTH EFFECTS 

migration leading to mucosal atrophy in the stomach antrum, increased labeling indices, and enlargement 

of the proliferative zone in the antral and body mucosa (Tsujii et al. 1993). 

Hematological Effects. No information was located regarding the hematological effects of ammonia 

or ammonium compounds in humans following oral exposure. Repeated exposure to ammonium chloride 

in animals resulted in metabolic acidosis with related changes in bone metabolism and serum calcium. 

For example, rats fed diets containing high levels of ammonium chloride had increased serum calcium 

(Barzel 1975). The increased serum calcium resulted from enhanced demineralization of bone in 

response to chronic acidosis. This effect was not found to be a specific effect of ammonium and was 

reported to occur in states of chronic metabolic acidosis produced from repeated doses of acidifying 

agents (e.g., hydrochloric acid, sulfuric acid). Decreased blood pH was seen in cats fed an acidifying diet 

containing ammonium chloride for several weeks (Kienzle and Wilms-Eilers 1994). As shown in 

Table 3-2 and Figure 3-2, no effects on blood hemoglobin or blood cell counts were observed in adult or 

weanling rats that received doses of up to 79 mg ammonium/kg/day administered as ammonium 

sulfamate in drinking water (Gupta et al. 1979). 

Musculoskeletal Effects. No information was located regarding musculoskeletal effects of 

ammonia or ammonium compounds in humans following oral exposure. Guinea pigs and rats that 

received lethal gavage doses of ammonium chloride developed muscle weakness, fasciculation, and 

incoordination (Koenig and Koenig 1949). In other animal studies, repeated ingestion of ammonium salts 

resulted in metabolic acidosis, which stimulated bone demineralization. As is shown in Table 3-2 and 

Figure 3-2, repeated ingestion of ammonium chloride in drinking water resulted in net bone resorption in 

rats and bone deformities in dogs (Barzel and Jowsey 1969; Bodansky et al. 1932). This effect can be 

anticipated with repeated exposure to any acidifying agent. 

Hepatic Effects. No information was located regarding hepatic effects of ammonia or ammonium 

compounds in humans following oral exposure. As shown in Table 3-2 and Figure 3-2, no toxic effects 

were noted in livers of adult or weanling rats fed doses of up to 79 mg ammonium/kg/day as ammonium 

sulfamate for 90 days in drinking water (Gupta et al. 1979). 

Renal Effects. Renal failure was identified as the cause of death in humans after ingestion of an 

unknown amount of household ammonia (ammonium hydroxide) (Klein et al. 1985). It is not certain if 

this represents a primary effect of ammonium or is secondary to massive burns to the gastrointestinal 

tract. 
AMMONIA 67 

3. HEALTH EFFECTS 

Renal effects have been observed in animals following repeated oral doses of ammonium chloride. These 

effects may be secondary to chronic acidosis produced from the interaction of ammonium chloride with 

water (which results in an increased H+

 concentration) rather than from a direct effect of ammonium ion 

on the kidney. Renal enlargement, increased blood ammonia content, and increased urinary ammonia 

have been reported in rats exposed to 180–433 mg/kg/day for 3–7 days (Benyajati and Goldstein 1975; 

Janicki 1970; Lotspeich 1965;), but are unlikely to be indicative of renal pathology. The highest 

NOAELs and LOAELs are presented in Table 3-2 and Figure 3-2. 

Endocrine Effects. No information was located regarding endocrine effects of ammonia or 

ammonium compounds in humans following oral exposure. Enlarged adrenal glands were observed in 

rabbits that received 124 mg ammonium/kg/day as ammonium hydroxide by gavage in water for 

17 months (Fazikas 1939). These limited data suggest that the endocrine system is not a primary target 

for ammonia or ammonium compounds. 

Body Weight Effects. Decreased body weight or weight gain has been observed in animals 

following oral exposure to ammonium ion (Barzel and Jowsey 1969; Bodega et al. 1993; Boyano-Adánez 

et al. 1996; Gupta et al. 1979; Noda and Chikamori 1976). Rats exposed to ammonium ion in utero and 

during lactation (dams received 4,293 mg ammonium/kg/day in the diet from gestational day 1 through 

lactation day 21) and then received a normal diet had showed reduced body weight gain (Miñana et al. 

1995); body weight gain was reduced by 25 and 16% in male and female offspring, respectively, at 

120 days of age. Rats that were continued on the same ammonia diet as their dams had an even greater 

reduction in body weight gain (27 and 26% for males and females, respectively) (Miñana et al. 1995). 

Birth weights were not reported in the Miñana et al. (1995) study. Gupta et al. (1979) noted increased 

water intake and reduced food intake in weanling rats, and decreased body weight in adults but not 

weanlings fed 79 mg ammonium/kg/day in drinking water for 90 days as ammonium sulfamate. This 

represents the LOAEL for this effect. A NOAEL of 39.5 mg ammonium/kg/day was also identified in 

this study (see Table 3-2 and Figure 3-2). 

3.2.2.3 Immunological and Lymphoreticular Effects 

No information was located regarding immunological effects of ammonia or ammonium compounds in 

humans or animals after oral exposure. 
AMMONIA 68 

3. HEALTH EFFECTS 

3.2.2.4 Neurological Effects 

No information was located regarding neurological effects of ammonia or ammonium compounds in 

humans after oral exposure. 

Guinea pigs that received lethal gavage doses of ammonium chloride (303.5–404.7 mg NH4

+

/kg) 

developed neuromuscular effects including fasciculation; incoordination; hyperexcitability to tactile, 

auditory, and painful stimuli; and tonic convulsions (Koenig and Koenig 1949). 

A number of studies have indicated that increased ammonium ion levels in the brain may disrupt energy 

production and modify the availability of some receptors that are involved in neurotransmission. 

Administration of 20% ammonium acetate in the diet of rats for 20 days resulted in statistically significant 

increases in brain ammonium ion (12.8-fold), glutamine (37%), and alanine (93%) and in some TCA 

cycle-associated components in the brain including glucose, lactate, and pyruvate, and decreases in brain 

cytosolic NAD+

/NADH ratio, β-hydroxybutarate, and ATP content (Kosenko et al. 1993). Rats with high 

NH4

+

 intake from administration of 20% ammonium acetate in the diet and 5 mM ammonium acetate in 

the water for up to 15 days had a decreased number of available somatostatin receptors in the 

frontoparietal cortex and hippocampus (Boyano-Adánez et al. 1996). Since somatostatin hyperpolarizes 

neurons in the cerebral cortex, the study authors speculated that this reduction in available receptors may 

contribute to the alteration of electrophysiological properties of neural tissue caused by excess NH4

+ 

(Boyano-Adánez et al. 1996). Binding of [H3

]MK-801 (an NMDA receptor antagonist) to NMDA 

receptors was reduced by approximately 60% in cerebellar cell cultures from 8-day-old rats exposed to 

NH4

+ in utero and during lactation (dams received 4,293 mg ammonium/kg/day in the diet from 

gestational day 1 through lactation day 8) (Miñana et al. 1995). Additionally, aspartate aminotransferase 

(AST) induction was absent in treated neurons (occurred in neurons from control rats), which also 

indicates impairment of NMDA receptors. Treated neurons were much more resistant to the toxic effects 

of glutamate than control neurons; since glutamate toxicity is mediated by NMDA receptors, attenuation 

of glutamate toxicity is indicative of impaired NMDA receptor function (Miñana et al. 1995). Loss of 

glial fibrillary acidic protein (GFAP) has been shown to occur in human spontaneous hyperammonemia 

(Kimura and Budka 1986; Kretzschmar et al. 1985; Sobel et al. 1981) and in other hyperammonemia 

models, such as portacaval shunt rats (Bodega et al. 1991; Suárez et al. 1992), but was not evident after 

exposure of rats to ammonium acetate (20% ammonium acetate in the diet and 5 mM ammonium acetate 

in the water for up to 90 days) (Bodega et al. 1993). Rats fed 19.5% ammonium acetate in the diet had 

increased NH4

+

 levels in the brain and altered assembly and disassembly of tubulin, an essential 
AMMONIA 69 

3. HEALTH EFFECTS 

component of the axonal transport system in the brain (Miñana et al. 1989a). The amount of polymerized 

tubulin increased but the amount of free tubulin was not affected. In vitro experiments using brains of 

rats fed a diet high in NH4

+

 indicated that the cause of the alteration might be a modification of the tubulin 

(and not the microtubule-associated proteins [MAPs], which modulate polymerization of the tubulin), 

which may result in a disruption in neurotransmission (Miñana et al. 1989a). Additional studies in rats 

brain showed that tubulin was significantly increased specifically in the septum, ventral hippocampus, 

dorsal hippocampus, hypothalamus, reticular formation, and frontal cortex, but not in the temporal 

amigdala, mammillary nucleus, locus coeruleus, caudate nucleus, or cingulate cortex after 2 months on 

the high ammonia diet (Miñana et al. 1989b). 

3.2.2.5 Reproductive Effects 

No information was located regarding reproductive effects of ammonia or ammonium compounds in 

humans or animals following oral exposure. 

3.2.2.6 Developmental Effects 

No information was located regarding the developmental effects of ammonia or ammonium compounds 

in humans. Rats exposed to NH4

+ in utero and during lactation (dams received 4,293 mg 

ammonium/kg/day in the diet from gestational day 1 through lactation day 21), which then received a 

normal diet, had a statistically significant reduction in body weight gain (Miñana et al. 1995); body 

weight was reduced by 25 and 16% in male and female offspring, respectively, at 120 days of age. Rats 

that were continued on the same ammonia diet as their dams had an even greater decrease in body weight 

gain (27 and 26% for males and females, respectively) at 120 days of age (Miñana et al. 1995). No 

information was provided in the study regarding the health of the dams, but it is likely that the high 

ammonium dietary concentration made them hyperammonemic. Body weights and food consumption by 

the dams throughout the study were not reported. 

3.2.2.7 Cancer 

No information was located regarding carcinogenic effects of ammonia or ammonium compounds in 

humans following oral exposure. Exposure of mice to 193 mg ammonium/kg/day as ammonium 

hydroxide in drinking water for 2 years did not produce carcinogenic effects, nor did it affect spontaneous 
AMMONIA 70 

3. HEALTH EFFECTS 

development of breast cancer, which is common to C3H female mice (Toth 1972). No evidence of a 

carcinogenic effect was found in mice treated by gavage with ammonia dissolved in water alone at a dose 

of 42 mg NH4

+

/kg/day for 4 weeks or with diethyl pyrocarbonate alone, but 9 of 16 mice treated with a 

combination of ammonium and pyrocarbonate developed lung tumors (Uzvolgyi and Bojan 1980). The 

ammonia and pyrocarbonate may have reacted in vivo to form the carcinogen, urethane. In a group of 

mice treated with urethane, the incidence of lung tumors was 9 of 9. Data from studies in vitro cited by 

Uzvolgyi and Bojan (1980) demonstrated the formation of urethane from diethyl pyrocarbonate added to 

beverages containing ammonia. No lung tumors were observed in the offspring of mice exposed similarly 

to NH4

+

 and diethyl pyrocarbonate during pregnancy or during lactation (Uzvolgyi and Bojan 1985). In 

another study, Tsujii et al. (1992a, 1995) tested the hypothesis that ammonia produced in the stomach in 

humans infected with Helicobacter pylori may play a role in the development of gastric cancer. Rats 

pretreated with the initiator N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in the drinking water for 

24 weeks before receiving 0.01% ammonia solution in the drinking water for 24 weeks had a statistically 

significantly greater incidence of gastric cancer (70% of rats) and number of tumors per tumor-bearing rat 

(2.1) than rats receiving only MNNG and tap water (31% and 1.3 tumors/rat) (Tsujii et al. 1992a). 

Additionally, the size, depth, and metastasis of the MNNG-initiated tumors were enhanced in the rats 

treated with ammonia (Tjusii et al. 1995). It can be estimated that the dose of ammonia received by the 

rats was approximately 42 mg/kg/day (the daily intake from food and water for the general population is 

approximately 0.3 mg/kg/day [WHO 1986]). The relevance of these studies to assess the cancer risk of 

oral exposure to ammonia is uncertain. 

3.2.3 Dermal Exposure 

Dermal exposure to ammonia may also result in some inhalation exposure. Therefore, based on the 

available data, it is not always clear to what extent each route of exposure contributes to the toxicity 

observed in dermal exposure studies. 

3.2.3.1 Death 

Human and animal deaths involving dermal exposure to ammonia and ammonium have been reported 

(Prokop'eva et al. 1973; Slot 1938; Sobonya 1977), but the extent of exposure is not known, and effects 

were probably due to inhalation exposure as well. A 25-year-old woman exposed to ammonia gas from a 

broken pipe had burns on her face, arms, and torso, and had difficulty breathing and swallowing (Slot 
AMMONIA 71 

3. HEALTH EFFECTS 

1938). She was treated symptomatically and with supportive treatment, but died about a month after 

exposure (Slot 1938). Autopsy showed edematous, inflamed, hemorrhagic epiglottis, trachea, and lungs. 

Petechial hemorrhages were found on the heart and the kidneys were congested with hemorrhagic 

nephritis. A 25-year-old man died after a tank of anhydrous ammonia exploded near him while he was 

farming (Sobonya 1977). Immediately after exposure he had mild bilateral conjunctival edema, burns 

over about 30% of his body surface, bilateral pulmonary edema, and severe respiratory distress. He 

developed pneumonia and died on the sixtieth day post-exposure. In rats, LC50 values of 112, 71.9, and 

48.4 mg ammonia/L were determined for exposures of 15, 30, and 60 minutes, respectively (Prokop’eva 

et al. 1973). These data are presented in Table 3-3. 

3.2.3.2 Systemic Effects 

No information was located on hematological, musculoskeletal, hepatic, endocrine, or body weight effects 

in humans or animals after dermal exposure to ammonia or ammonium. 

Dermal or multiple route exposure to ammonia or ammonium has produced respiratory, cardiovascular, 

gastrointestinal, renal, dermal, and ocular effects. 

Respiratory Effects. Respiratory effects have been reported in humans from exposure to massive 

amounts of ammonia gas, but no quantitative data were located. It is also unclear as to what extent the 

effects were a result of inhalation and dermal exposure. Tracheitis, bronchitis, edema, and 

bronchopneumonia were reported by Slot (1938). Lung infection and respiratory distress were reported in 

one case (Sobonya 1977). Dyspnea, rales, rhonchi, and blocked airways were found by Levy et al. 

(1964). The effects probably resulted from concurrent inhalation and dermal exposure. No information 

was located regarding respiratory effects of ammonia or ammonium in animals following dermal or 

ocular exposure. 

Cardiovascular Effects. Elevated pulse, shock, and cardiac failure were reported in humans from 

accidental exposures to massive amounts of ammonia gas, but the extent of exposure was not quantified 

(Slot 1938). No information was located regarding cardiovascular effects of ammonia or ammonium in 

animals following dermal or ocular exposure. 

Gastrointestinal Effects. Persistent vomiting was noted by Slot (1938) in human accidental massive 

exposure cases, but the extent of exposure was not quantified. Oral and pharyngeal burns and edema 
LOAEL

Table 3-3 Levels of Significant Exposure to Ammonia And Ammonium Compounds - Dermal

Species

(Strain) System

NOAEL Less Serious Serious 

Exposure/

Duration/

Frequency

(Specific Route)

ACUTE EXPOSURE

Death

Rat

(LC50)

71.9

mg/L

mg/L

Pr

188

1 d30 min/d

Rat

(LC50)

48.4

mg/L

mg/L

Pr

83

1 d60 min/d

Systemic

Human Ocular 50

ppm

ppm

(eye irritation)

72

ppm

ppm

In

390

5 min

Human Ocular 30

ppm

ppm

(moderate ocularirritation)

50

ppm

ppm

M

387

10 min

(Duroc)Pig Ocular 10

ppm

ppm

(ocular irritation)

50

ppm

ppm

St

205

5 wkmin/d

INTERMEDIATE EXPOSURE

Systemic

Human Ocular 25

ppm

ppm

d = day(s); hr = hour; LOAEL = lowest-observed-adverse-effect level; min = minute(s); NOAEL = no-observed-adverse-effect level; wk = week(s)

(transitory eye irritation)

50

ppm

ppm

Fe

197

6 wk5 d/wk6 hr/d
AMMONIA 73 

3. HEALTH EFFECTS 

were reported by Levy et al. (1964) in four human males accidentally exposed to an unknown quantity of 

anhydrous ammonia. Inhalation exposure may have contributed to these effects also. 

Renal Effects. Renal congestion and hemorrhagic nephritis were reported by Slot (1938) in six cases 

of accidental human exposures to highly concentrated aerosols of ammonium derived from anhydrous 

ammonia. The exposure level cannot be determined from the available data. 

Dermal Effects. Skin and eyes are extremely sensitive to airborne ammonia or ammonium in water. 

The topical damage caused by ammonia is probably due mainly to its alkaline properties. Its high water 

solubility allows it to dissolve in moisture on these surfaces, react with fatty substances in the corneal 

layer, be absorbed into deeper layers, and inflict extensive damage (Jarudi and Golden 1973). Reports of 

skin damage in humans are numerous, but good quantitative data are lacking. The severity of the damage 

is proportional to concentration and duration of exposure; flushing with water immediately after contact 

alleviates or prevents effects. Burns, blisters, and lesions of the skin have been reported (Close et al. 

1980; Flury et al. 1983; Shimkin et al. 1954; Slot 1938; Taplin et al. 1976; Walton 1973). Exposure 

levels associated with dermal effects are presented in Table 3-3. 

Several case reports described exposure of individuals to ammonia liquid and/or gas that resulted in 

cutaneous burns (Amshel et al. 2000; da Fonseca et al. 1998; George et al. 2000; Kerstein et al. 2001; 

Latenser and Lucktong 2000; Leduc et al. 1992; Rosenbaum et al. 1998; Weiser and Mackenroth 1989). 

All exposures were occupationally related. Total body surface area burned ranged from 14 to 45% and 

most had at least small areas of full-thickness burns that required skin grafting. A summary of 12 case 

reports of liquid anhydrous ammonia injuries reported a range of percent body surface area burned of 

3–22%, with 25% of the patients having full-thickness burn injuries (Millea et al. 1989). One case report 

included a skin litmus paper test that showed the pH of the skin to be 10 at the time of hospital admission 

(Amshel et al. 2000). Infection of the burn wounds was not uncommon, with most of the patients 

responding to antibiotic treatment. One person had facial and neck hyperemia, erythematous petechiae on 

one ear, and edematous and peeling lips (Latenser and Lucktong 2000). The individual with 45% total 

body surface area burned had additional severe injuries, including respiratory and ocular, and developed 

circulatory and hematological problems, which led to his death (George et al. 2000). 

Rosenbaum et al. (1998) described two cases of young children (2–3 years old) who bit into ammonia 

pellets/capsules. Both children drooled and had ulcerative lesions on the tongue and/or on the buccal 

mucosa. One child had superficial ulcerations on the posterior esophageal wall and the other child had 
AMMONIA 74 

3. HEALTH EFFECTS 

edematous, erythematous upper and lower lips with areas of desquamation, eschar of the hard palate, and 

edema and erythema of the supraglottic structures and upper trachea. Both children recovered without 

incident. 

A single case report described a self-administered ammonium solution enema that resulted in anal pain, 

diffuse abdominal colic, and tenesmus (da Fonseca et al. 1998). Sigmoidoscopy showed diffuse 

erythematous friable mucosa with large ulcerations covered by yellowish exudate. Six days later, the 

ulcers had receded, but the colon was still erythematous. Three months postexposure, biopsies showed 

chronic inflammation and fibrosis of the rectum and sigmoid colon, but no stenosis. 

Animal data regarding dermal and ocular effects of exposure to ammonia support the findings in humans. 

A number of cattle were acutely exposed to anhydrous ammonia fumes when a pipeline running through 

their pasture ruptured and leaked 1,800 barrels of ammonia in a short period of time (Morgan 1997). The 

ammonia combined with moisture in the air and formed a white cloud, which drifted south across two 

additional fields containing cattle. The noses of the cattle in the field with the pipeline turned black and 

peeled and the horns of cattle in an adjacent field turned black and peeled. Hair coats on all livestock 

within a 2-mile radius of the rupture were singed. 

Ocular Effects. Reported ocular effects in humans following ammonia or ammonium exposure 

increase in severity with dose and duration. Good quantitative data are lacking, but symptoms progress as 

follows: inflamed eyes, lacrimation, swelling of the eyelids (Beare et al. 1988; Caplin 1941; Close et al. 

1980; Ferguson et al. 1977; Jarudi and Golden 1973; Legters et al. 1981; Montague and Macneil 1980; 

O’Kane 1983; Price et al. 1983; Silverman et al. 1949; Stombaugh 1969; Verberk 1977; Ward et al. 

1983), hyperemic conjunctiva (Caplin 1941; Hatton et al. 1979; Levy et al. 1964; Slot 1938; Sobonya 

1977), transient blindness, blurred vision, and corneal abrasions (Latenser and Lucktong 2000), and 

sustained corneal damage (Caplin 1941; Grant 1974: Kass et al. 1972; McGuinness 1969; Stroud 1981; 

Yang et al. 1987). Ammonia is slightly irritating to human eyes at concentrations of 100 ppm (Ferguson 

et al. 1977), and immediately irritating to the eyes and throat at 698 ppm (Henderson and Haggard 1927). 

Exposure to an air concentration of 250 ppm is bearable for most persons for 30–60 minutes (Withers et 

al. 1986). Exposure levels associated with ocular effects are presented in Table 3-3. 

Animal data regarding ocular effects of exposure to ammonium support the findings in humans. Corneal 

opacity has been observed in rabbits following brief exposures (2 seconds) to a solution of 28.5% 

ammonium hydroxide (Grant 1974). Volume administered was not reported. Cattle in an adjacent field 
AMMONIA 75 

3. HEALTH EFFECTS 

to a pipeline that ruptured and released 1,800 barrels of ammonia had runny eyes; two cows in the same 

field with the ruptured pipeline were euthanized because of blindness and respiratory distress (Morgan 

1997). 

3.2.3.3 Immunological and Lymphoreticular Effects 

Secondary infections often complicate the clinical outcome of burns and respiratory lesions related to 

exposures to highly concentrated aerosols derived from anhydrous ammonia in which dermal and ocular 

exposure accompanies inhalation exposure (Sobonya 1977; Taplin et al. 1976). However, there is no 

evidence that the decreased immunological resistance represents a primary impairment of the immune 

system in humans. No information was located regarding the immunological effects of ammonia or 

ammonium in animals following dermal or ocular exposure. 

No information was located regarding the following effects of ammonia or ammonium compounds in 

humans or animals following dermal or ocular exposure: 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

Carcinogenic potential of ammonia has not been established in humans or animals by the dermal route of 

exposure. One case report was found of a person who developed epidermal carcinoma of the nasal 

septum 6 months after being badly burned by accidental contact with a refrigeration ammonia-oil mixture 

(Shimkin et al. 1954). It is unclear whether ammonia played a role in this tumor development. No other 

reports were located, although many cases of contact with ammonia from spills have been followed for 

more than 6 months after exposure. 
AMMONIA 76 

3. HEALTH EFFECTS 

3.2.4 Other Routes of Exposure 

There are limited in vitro data suggesting that ammonium ion may affect fetal development (Lane and 

Gardner 1994). Mouse embryos (conceived in vivo) were cultured in modified mouse tubal fluid medium 

(mMTF) or mMTF supplemented with 300 μmol/L ammonium ion for 48, 69, or 93 hours before being 

transferred to pseudopregnant mouse dams (Lane and Gardner 1994). Examination on gestational 

day 15 showed an apparent relationship between the duration of exposure and the incidence of 

exencephaly. Embryos that were cultured with various concentrations of ammonium ion before being 

transferred to recipient dams showed increased incidence of exencephaly with increased ammonium 

concentration (38–300 μmol/L) and decreased percentage of implantation sites with increased ammonium 

concentration. It is unclear how embryos might be exposed to ammonia or ammonium in vivo or if in 

vivo exposure would affect fetal development and implantation in a way similar to that described in the 

Lane and Gardner (1994) study. 

3.3 GENOTOXICITY 

A single study examined the genotoxic effect of ammonia in humans (Yadav and Kaushik 1997). 

Analysis of blood samples from 22 workers exposed to ammonia in a fertilizer factory and 42 control 

workers not exposed to ammonia showed increased frequency of chromosomal aberrations (CAs) and 

sister chromatid exchanges (SCEs), increased mitotic index (MI), and increased frequency of CAs and 

SCEs with increasing length of exposure. 

Swiss albino mice administered a single dose of 12, 25, or 50 mg/kg ammonium intraperitoneally had an 

increased frequency of micronuclei compared to controls (Yadav and Kaushik 1997). 

All remaining tests of ammonia's mutagenicity consist of studies in E. coli, chick fibroblast cells, and 

Drosophila melanogaster (Table 3-4). Demerec et al. (1951) noted positive effects in a reverse mutation 

test in E. coli, but only in treatments using toxic levels of NH4

+

 (98% lethality). Lobasov and Smirnov 

(1934) found slight mutagenic activity in Drosophila following exposure to ammonia gas, but once again, 

survival after treatment was <2%. Auerbach and Robson (1947) tested Lobasov and Smirnov's results 

and noted 0.5% sex-linked lethals. The authors concluded that although their data did not support the 

earlier study's findings, it is possible that ammonia has a very slight mutagenic action. In their data 

presentation, however, they report their findings as negative, qualifying it as doubtful and probably 

negative. 
AMMONIA 77 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Ammonia In Vitro and In Vivo 

Results 

Species (test 

system) End point Form 

Activation 

system 

With 

activation 

Without 

activation Reference 

In vitro: 

Escherichia Reverse NH3 NT + (at toxic Demerec et al. 

coli mutation levels) 1951 

Chick Chromosomal NH4Cl+ NT + Rosenfeld 

fibroblasts aberrations NH4OH buffer 1932 

Mouse Reduced cell NH3 

+

NH4Cl NT + Visek et al. 

fibroblasts division 1972 

Mouse Reduced cell NT + Capuco 1977 

fibroblasts division 

(3T3) 

Mouse DNA repair NH4Cl NT + Capuco 1977 

fibroblasts inhibition 

In vivo: 

Drosophila Mutagenic NH3 + NT Lobasov and 

melanogaster lethality Smirnov 1934 

D. Sex-linked NH3 – (doubtful, NT Auerbach and 

melanogaster recessive lethal probably Robson 1947 

mutations negative) 

D. Dominant NH3 – NT Auerbach and 

melanogaster lethality Robson 1947 

Mouse ileal Decreased rate NH4Cl NT + Zimber and 

and colonic of DNA Visek 1972a 

mucosa cells synthesis 

– = negative result; + = positive result; (+) = weakly positive result; DNA = deoxyribonucleic acid; NH3 = ammonia; 

NH4Cl = ammonia chloride; NH4OH = ammonium hydroxide; NT = not tested 
AMMONIA 78 

3. HEALTH EFFECTS 

In vitro tests of chick fibroblast cells showed that buffered ammonia-ammonium chloride solutions can 

induce clumping of chromosomes, inhibit spindle formation, and result in polyploidy (Rosenfeld 1932). 

Visek et al. (1972) noted reduced cell division in mouse fibroblasts cultured in media to which ammonia 

and ammonium chloride were added. The effect was noted in cultures irrespective of pH. Decreased rate 

of DNA synthesis was noted in mouse mucosal cells in the ileum and colon when serum NH4

+

 levels were 

significantly elevated over normal levels; these elevated levels were induced by intraperitoneal injection 

of urease or infusion of ammonium chloride (Zimber and Visek 1972a). 

Iwaoka et al. (1981), responding to controversy regarding mutagenicity in fried hamburgers, found that 

extraction of organic ingredients from fried hamburger and refrigerated biscuit products with ammonium 

hydroxide or ammonium sulfate increased mutagenic activities in Salmonella typhimurium T98 and 

TA1538 Ames' microsomal systems, while negative results were obtained from extraction with sodium 

sulfate. The mode of action is unclear; ammonium salts may in some way affect the mutagenic activities 

of some agents, or they may simply be more efficient extractors of mutagenic components from these 

foods. 

Taken together, the data indicate that ammonia and ammonium ion may have clastogenic and mutagenic 

properties. 

3.4 TOXICOKINETICS 

Studies suggest that ammonia can be absorbed by the inhalation and oral routes of exposure, but there is 

less certainty regarding absorption through the skin. Absorption through the eye has been documented. 

Most of the inhaled ammonia is retained in the upper respiratory tract and is subsequently eliminated in 

expired air. Almost all of the ammonia produced endogenously in the intestinal tract is absorbed. 

Exogenous ammonia is also readily absorbed in the intestinal tract. Ammonia that reaches the circulation 

is widely distributed to all body compartments although substantial first pass metabolism occurs in the 

liver where it is transformed into urea and glutamine. Ammonia or ammonium ion reaching the tissues is 

taken up by glutamic acid, which participates in transamination and other reactions. The principal means 

of excretion of ammonia that reaches the circulation in mammals is as urinary urea; minimal amounts are 

excreted in the feces and in expired air. 
AMMONIA 79 

3. HEALTH EFFECTS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Experiments with volunteers show that ammonia, regardless of its tested concentration in air (range, 57– 

500 ppm), is almost completely retained in the nasal mucosa (83–92%) during short-term exposure, i.e., 

up to 120 seconds (Landahl and Herrmann 1950). However, longer-term exposure (10–27 minutes) to a 

concentration of 500 ppm resulted in lower retention (4–30%), with 350–400 ppm eliminated in expired 

air by the end of the exposure period (Silverman et al. 1949), suggesting an adaptive capability or 

saturation of the absorptive process. Nasal and pharyngeal irritation, but not tracheal irritation, suggests 

that ammonia is retained in the upper respiratory tract. Unchanged levels of blood-urea-nitrogen (BUN), 

non-protein nitrogen, urinary-urea, and urinary-ammonia are evidence of low absorption into the blood. 

Exposure to common occupational limits of ammonia in air (25 ppm) with 30% retention (and assuming 

this quantity is absorbed into the blood stream) would yield an increase in blood ammonium 

concentration of 0.09 mg/L (calculated by WHO 1986). This calculated rise is only 10% above fasting 

levels, as reported by Conn (1972). 

Animal data provide supporting evidence for high-percentage nasal retention, thus protecting the lower 

respiratory tract from exposure (Dalhamn [1963] and Boyd et al. [1944], rabbit; Egle [1973], dog). 

Continuous exposure of rats for 24 hours to concentrations up to 32 ppm resulted in significant increase in 

blood ammonia levels (Schaerdel et al. 1983). Exposures to 310–1,157 ppm led to significantly increased 

blood concentrations of ammonia within 8 hours of exposure initiation, but blood ammonia returned to 

pre-exposure values within 12 hours of continuous exposure and remained so over the remaining of the 

24-hour exposure period. This suggests an adaptive response mechanism may be activated with longerterm exposure (Schaerdel et al. 1983). 

3.4.1.2 Oral Exposure 

Case reports of human ingestion of household ammonia (ammonium hydroxide) provide evidence of its 

absorption by this route, but few provide quantitative data. For example, in a fatal case of a man who 

drank an unknown amount of a 2.4% solution of ammonium hydroxide, analysis of the contents of the 

stomach and blood showed ammonium ion concentrations of 153 and 33 ppm, respectively (Klendshoj 

and Rejent 1966). In a study of volunteers, ingestion of a single ammonium chloride tablet 

(approximately 15 mg NH4

+

/kg/day) led to a small transient increase (33% above fasting levels) in arterial 
AMMONIA 80 

3. HEALTH EFFECTS 

blood concentrations of ammonium ion in 11 out of 20 subjects (Conn 1972); no change was noted in the 

remaining nine subjects in this group. Among 50 cirrhotic patients, increases of about 150% were noted 

in arterial blood concentrations of ammonium ion and return to normal levels was slow (Conn 1972). 

These data indicate that ingested ammonia is readily absorbed from the digestive tract and that the liver 

plays a large role in removing it from the blood (Conn 1972). Analysis of urine samples from subjects on 

high and low protein diets and given 15N-ammonium chloride, showed that 30–65% of labeled nitrogen 

from 15N-ammonium chloride is absorbed and metabolized (Richards et al. 1975). Oral administration of 

15NH4Cl to a group of six subjects for six days resulted in absorption of at least 38.7% of the administered 

radioactivity as determined by the amount of 15N that appeared in urinary urea within 24 hours of the last 

15NH4Cl ingestion (Metges et al. 1999). 

Ammonium ion is endogenously produced in the human digestive tract, much of it arising from the 

bacterial degradation of nitrogenous compounds from ingested food. About 4,200 mg/day are produced, 

greater than 70% of which is synthesized or liberated within the colon and its fecal contents. The total 

amount absorbed is about 4,150 mg/day, or 99% of the amount produced (Summerskill and Wolpert 

1970); absorption after oral loading of NH4

+

 is similarly complete (Fürst et al. 1969). Evidence from 

Castell and Moore (1971) and Mossberg and Ross (1967) suggests that absorption of NH4

+

 increases as 

the pH of the contents of the lumen increases, and that the ammonium ion is actively transported at the 

lower pH levels (pH 5 was lowest detected absorption). Ammonium ion absorbed from the 

gastrointestinal tract travels via the hepatic portal vein directly to the liver, where in healthy individuals, 

most of it is converted to urea and glutamine. Human and animal data show that little of it reaches the 

systemic circulation as ammonia or ammonium compounds, but that it is a normal constituent of plasma 

at low levels (Brown et al. 1957; Pitts 1971; Salvatore et al. 1963; Summerskill and Wolpert 1970). 

Analysis of plasma drawn from 10 healthy young male subjects yielded endogenously derived NH4

+ 

concentrations ranging from 30 to 55 μg NH3/100 mL, with a mean of 39 μg/100 mL (Brown et al. 1957). 

3.4.1.3 Dermal Exposure 

Quantitative data on absorption from exposure by the dermal route were not located in the available 

literature. Human case reports of dermal exposure describe local damage (burns, irritations). One report 

of case histories of five persons exposed to an exploding, bursting anhydrous ammonia gas pipe indicated 

there was systemic toxicity (vomiting, renal congestion, delirium), but exposure was by inhalation as well 

as dermal route, and it is impossible to delineate a systemic dermal exposure contribution (Slot 1938). 
AMMONIA 81 

3. HEALTH EFFECTS 

WHO (1986) concluded that systemic effects from skin and eye exposure are not quantitatively important. 

Ammonia is readily absorbed into the eye; it was found to diffuse within seconds into cornea, lens, 

drainage system, and retina (Beare et al. 1988; Jarudi and Golden 1973). However, amounts absorbed 

were not quantified, and absorption into systemic circulation was not investigated. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

No quantitative reports of distribution of ammonia from inhalation exposure were found in the available 

literature. Absorption data from human inhalation exposure suggest that only small amounts of ammonia 

are absorbed into the systemic circulation (Silverman et al. 1949; WHO 1986). Initial retention of inhaled 

ammonia in the mucus of the upper respiratory tract may be 80% or more, but after equilibrium is 

established (within 30 minutes) 70–80% of inspired ammonia is expired in exhaled air (Silverman et al. 

1949). The lack of change in blood nitrogen compounds and urinary-ammonia compounds lends further 

support to a limited absorption into the systemic circulation (Silverman et al. 1949). Toxic effects 

reported from inhalation exposure suggest local damage, or changes resulting from necrotic tissue 

degradation, rather than the presence of elevated levels of NH4

+

, per se, in tissues other than the 

respiratory/pharyngeal tissues. Information on the distribution of endogenously-produced ammonia 

suggests that any NH4

+

 absorbed through inhalation would be distributed to all body compartments via the 

blood, where it would be used in protein synthesis or as a buffer, and that excess levels would be reduced 

to normal by urinary excretion, or converted by the liver to glutamine and urea. If present in quantities 

that overtax these organs, NH4

+

 is distributed to other tissues and is known to be detoxified in the brain 

(Takagaki et al. 1961; Warren and Schenker 1964). 

3.4.2.2 Oral Exposure 

Human oral exposure data for NH4

+

 clearly indicate that it readily enters the portal circulation and is 

delivered to the liver (Conn 1972; Fürst et al. 1969), as has been shown to be the case for endogenously 

produced NH4

+

 (Pitts 1971; Summerskill and Wolpert 1970). In nitrogen-deficient persons, NH4

+

 (as 

ammonium acetate) administered orally was absorbed and carried directly to the liver where most of it 

was converted to urea and excreted in the urine; little change in the negative nitrogen balance was 

observed (Fürst et al. 1969). Output of urea from the liver corresponded to the amount of NH4

+

 ingested 

(Fürst et al. 1969). 
AMMONIA 82 

3. HEALTH EFFECTS 

Un-ionized ammonia is freely diffusible, whereas the ammonium ion is less so and is relatively confined 

to the extracellular compartment (Stabenau et al. 1958). However, ammonium ion is in dynamic 

equilibrium with dissolved ammonia. Therefore, ammonium compounds that enter the circulatory system 

or other body fluids can thus freely penetrate tissue cells as ammonia. In hypophysectomized rats that 

were administered 15N-ammonium citrate orally by gavage, labeled protein was found in liver, kidney, 

spleen, heart, and skeletal muscle 6–72 hours after 15N-ammonium citrate administration (Vitti et al. 

1964). The percentages of ingested label absorbed and then excreted as urea in the urine were not 

provided (Vitti et al. 1964). 

3.4.2.3 Dermal Exposure 

No quantitative data on distribution of ammonia from dermal exposure were located in the available 

literature. Toxic effects from dermal exposure suggest that little or no ammonia gains entry into the 

systemic circulation by this route. 

3.4.2.4 Other Routes of Exposure 

Intravenous administration of NH4

+

 (as ammonium salts) to people with a nitrogen deficiency (in negative 

nitrogen balance) resulted in an increase in the peripheral blood NH4

+

 level and a shift in the nitrogen 

balance from negative to positive; no increase in urinary urea was seen (Fürst et al. 1969). The nitrogen 

from NH4

+

, which gains entry into the general circulation, is distributed to cells throughout the body and 

incorporated into tissues (Fürst et al. 1969; Vitti et al. 1964). After intraperitoneal injection of 

ammonium chloride in mice, ammonia distributes to brain tissues within 20 seconds (Warren and 

Schenker 1964), and in rats, brain concentrations increase dramatically within 5 minutes (Salvatore et al. 

1963). Tissues other than blood and brain were not analyzed by these researchers. Comparative patterns 

of distribution of 15N-labeled ammonium citrate indicate that the amount of NH4

+

 taken up by tissues 

other than the liver is greatest by subcutaneous injection, less by intraperitoneal injection, and least 

following intragastric administration. Intravenous administration of 15N-labeled ammonium salts leads to 

rapid distribution of 15N-labeled metabolites throughout the body, with the highest levels of labeled urea 

appearing in the kidney and liver, and lesser amounts in heart, spleen, brain, testes, and carcass. Highest 

levels of labeled glutamine were found in heart and liver, with lesser amounts in brain, spleen, carcass, 

kidney, and testes (Duda and Handler 1958). 
AMMONIA 83 

3. HEALTH EFFECTS 

3.4.3 Metabolism 

Quantitative data on human metabolism of exogenously introduced ammonia were not located in the 

available literature. Ammonia and ammonium ion are metabolized to urea and glutamine mainly in the 

liver by the process diagrammed in Figures 3-3 and 3-4 and described by Fürst et al. (1969) and Pitts 

(1971). However, it can be rapidly converted to glutamine in the brain and other tissues as well 

(Takagaki et al. 1961; Warren and Schenker 1964). The nitrogen is released from glutamine within tissue 

cells and used for protein synthesis as needed (Duda and Handler 1958; Fürst et al. 1969; Richards et al. 

1975; Vitti et al. 1964). Ingestion of ammonium salts leads to almost complete conversion of ammonium 

ion into urea in the liver, whereas exposure by other routes may lead to its metabolism in body tissues to 

glutamine or tissue protein (Fürst et al. 1969; Vitti et al. 1964). 

Duda and Handler (1958) administered 0.03 mg/kg body weight of 15N-ammonium acetate intravenously 

to rats and noted that 90% was converted to glutamine and urea within 30 minutes, with glutamine being 

the major early product. Labeled nitrogen was also found in amino acids, purines, pyrimidines, and other 

nitrogenous compounds. Morimoto et al. (1988) found that the amount of 15N from an intravenous 

injection of ammonium chloride to rats that was taken up into glutamine-amide-N and urea-N reached a 

peak at 5 minutes and decreased gradually from 15 to 60 minutes after the injection. This finding 

suggests that urea synthesis and glutamine synthesis occurred simultaneously within minutes after the 

injection, and glutamine-amide-N is gradually transferred to the urea cycle from 15 to 60 minutes 

following dosing. Low amounts (0.008% of a 17 mg oral dose) of 15N-ammonium chloride administered 

repeatedly to rats were converted to 15N-nitrate in the urine (Saul and Archer 1984). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Studies using low levels of ammonia show that inhaled ammonia is temporarily dissolved in the mucus of 

the upper respiratory tract, and then a high percentage of it is released back into the expired air. 

Following exposure to 500 ppm ammonia for 10–27 minutes, healthy male subjects eliminated 70–80% 

of the inspired ammonia by this route (Silverman et al. 1949). Analysis of endogenous ammonia levels in 

the expired air of rats showed concentrations ranging from 10–353 ppb (mean=78 ppb) in nose-breathing 

animals (Barrow and Steinhagen 1980). 
AMMONIA 84 

3. HEALTH EFFECTS 

Figure 3-3. Glutamine Cycle 

Glutaminase 

NH4+ 

Glutamine 

Synthetase 

GLU -N GLU 

GLU -N GLU 

NH4+ 

GLU = Glutaminate; GLU-N = Glutamine 

Source: Brunner and Thaler 1981 
AMMONIA 85 

3. HEALTH EFFECTS 

Figure 3-4. The Urea Cycle Showing the Compartmentalization of its Steps Within 

Liver Cells 

Incoming amine group (via 

NH3 – C – NH3 

O 

Urea 

Ornithine 

5 

Specific ornithine 

membrane 

transport system 

Ornithine 

dehydrogenase) 

2ATP + CO2 + NH3 + H2O 

Citrulline 

Citrulline 

2ADP + P1 

1 

Carbamoyl 

Phosphate 

2 

P1 

Matrix 

Mitochondrion 

Inner 

membrane 

Arginine 

Argininosuccinate 

4 

3 

Asparate 

AMP + PP1 

ATP 

Enzymes catalyzing each reaction are: 1) carbamoyl 

Cytosol mitochondrial glutamate 

H2O 

Fumarate 

-NH3 phosphate synthetase (ammonia); 2) ornithine 

Incoming amine group (via carbamoyl transferase; 3) argininosuccinate 

transamination from glutamate) synthetase; 4) argininosuccinate lyase; 5) arginase 

Source: Lehninger 1975 
AMMONIA 86 

3. HEALTH EFFECTS 

The quantitative difference between inspired and expired ammonia suggests that small amounts are 

absorbed across the nasopharyngeal membranes into the systemic circulation. Absorbed ammonia is 

excreted by the kidneys as urea and urinary ammonium compounds (Gay et al. 1969; Pitts 1971; Richards 

et al. 1975; Summerskill and Wolpert 1970), as urea in feces (Richards et al. 1975), and as components of 

sweat (Guyton 1981; Wands 1981), but quantitative data are lacking. Toxic levels do not develop as a 

result of chronic inhalation exposure because the body has multiple effective mechanisms for detoxifying 

and excreting it. 

3.4.4.2 Oral Exposure 

Excretion data for humans orally exposed to ammonia have been quantified with respect to excretion of 

isotope from 15N-labeled ammonium salts, thus providing an indication of the turnover rate of the 

compound within the body and excretion route of its metabolites. Approximately 72% of a dose of 15N 

was excreted in the urine of three subjects within 3 days of ingestion of ammonium salts in drinking 

water; 25% (24% urinary urea and 1% urinary NH4

+

) was eliminated within the first 6 hours after 

exposure. Ammonium salt administered by gavage to humans led to a corresponding increase in blood 

urea concentration transported out of the liver, leading the authors (Fürst et al. 1969) to conclude that 

orally ingested ammonium salt is quickly and almost completely converted in the liver and eliminated 

from the body as urinary urea. Analysis of urine samples from subjects on high and low protein diets 

showed higher cumulative excretion of 15N (percent of dose) in the urine of the high protein group 

(approximately 70%) than that of the low protein group (35%). Small amounts of labeled nitrogen were 

also excreted as urea in feces (Richards et al. 1975). 

These data correspond to that for excretion of endogenously produced ammonia (Davies and Yudkin 

1952; Muntwyler et al. 1956; Summerskill and Wolpert 1970; Van Slyke et al. 1943). Ammonia is also 

known to be excreted via sweat (Guyton 1981; Wands 1981) and expired air (Barrow and Steinhagen 

1980; Larson et al. 1980; Robin et al. 1959; Utell et al. 1989); quantitative data are unavailable for 

excretion via sweat. 

3.4.4.3 Dermal Exposure 

Data regarding excretion of ammonia absorbed following dermal exposure were not located in the 

available literature. 
AMMONIA 87 

3. HEALTH EFFECTS 

3.4.4.4 Other Routes of Exposure 

Data are available on exposure of humans and dogs to ammonium salts by intravenous injection. 

Excretion of isotope after 15N-ammonium lactate injection in three human subjects yielded 5–7% of 

isotope excreted as urinary NH4

+

 in the first 6 hours postexposure, and another 2% within 3 days. 

Approximately 6% of the isotope was excreted as urea in urine in the first 6 hours. An average of 

approximately 60% of the dose of label was excreted in urine within 3 days. These data are considerably 

different from that resulting from oral loading (as described in Section 3.4.4.2). Intravenous loading led 

to decreased labeling of urinary urea and grossly increased labeling of urinary ammonia; the differences 

are attributed by the authors to a "first pass" effect from oral loading (Gay et al. 1969). The hepatic 

transformation of ammonium ion to urea is so efficient that relatively little unconverted ammonium salt is 

released to the general circulation. 

Intravenous exposure of seven dogs to 107 mg/kg ammonium acetate led to amounts ranging from 

0.044 to 0.073 mg ammonia excreted in expired air. No measurable amount of ammonia was present in 

expired air during the pre-exposure control period (Robin et al. 1959). 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 
AMMONIA 88 

3. HEALTH EFFECTS 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-5 shows a conceptualized representation of a PBPK model. 

No data regarding PBPK models for ammonia were located. 
AMMONIA 89 

3. HEALTH EFFECTS 

Figure 3-5. tation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by 

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Lungs 

Liv e r 

Fat 

S lo w ly 

per f u sed 

t is s ues 

R ic h ly 

per f u sed 

t is s ues 

K idney 

Sk in 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V ma x K m 

I nges t ion 

I n haled che m ic al E x hale d che m ic al 

GI 

Tr ac t 

Fec e s 

Ur in e 

C h em ic als in air 

co n tacting skin 

Conceptual Represen
AMMONIA 90 

3. HEALTH EFFECTS 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Data regarding the pharmacokinetic mechanisms of ammonia were not located in the available literature. 

3.5.2 Mechanisms of Toxicity 

Ammonia is an irritant and the primary and most immediate effect of ammonia exposure is burns to the 

skin, eyes, and respiratory tract. The topical damage caused by ammonia is probably due mainly to its 

alkaline properties. Its high water solubility allows it to dissolve in moisture on the mucous membranes, 

skin, and eyes, forming ammonium hydroxide, which causes liquefaction necrosis of the tissues (Jarudi 

and Golden 1973). Specifically, ammonium hydroxide causes saponification of cell membrane lipids, 

resulting in cell disruption and death. Additionally, it extracts water from the cells and initiates an 

inflammatory response, which further damages the surrounding tissues (Amshel et al. 2000). Contact 

with liquid ammonia results in cryogenic injury in addition to the alkali burns (Amshel et al. 2000; 

Wibbenmeyer et al. 1999). 

Excess circulating levels of ammonia (hyperammonemia) can cause serious neurological effects. 

Hyperammonemias can be inherited (i.e., inborn errors of urea cycle enzymes) or acquired (i.e., liver 

toxicity caused by ingested toxins, viral infections, autoimmune disease) (Felipo and Butterworth 2002). 

An extensively studied neuropsychiatric disorder known as hepatic encephalopathy develops when liver 

function is impaired and the organ cannot metabolize ammonia. This results in an increased 

concentration of ammonia in the blood and brain. The mechanism of ammonia-induced encephalopathies 

has not been definitively elucidated, but is thought to involve the alteration of glutamate metabolism in 

the brain and resultant increased activation of NMDA receptors (Felipo et al. 1993; Marcaida et al. 1992), 

which causes decreased protein kinase C-mediated phosphorylation of Na+

/K+ ATPase, increased activity 

of Na+

/K+ ATPase, and depletion of ATP (Kosenko et al. 1994). Antagonists of NMDA receptors, 

agonists of metabotropic glutamate receptors, agonists of muscarinic receptors, and inhibitors of protein 

kinase C, calcineurin, or nitric oxide synthase prevent glutamate toxicity, indicating that all of these play 

a role in acute ammonia neurotoxicity (Felipo et al. 1998). Additional evidence of altered energy levels 

include changes in some TCA cycle-associated components including acetoacetate, and NAD+

/NADH 

ratio, 2-oxoglutarate, and 3-hydroxybutarate (Kosenko et al. 1993). A disruption in neurotransmission 
AMMONIA 91 

3. HEALTH EFFECTS 

has also been suggested by alteration of brain tubulin, which is an essential component of the axonal 

transport system (Miñana et al. 1989a, 1989b). 

During certain disease states that result in renal tubular injury, NH4

+

 production by renal proximal tubules 

may increase in order to maintain net acid excretion. However, this may also contribute to further renal 

damage by modifying the third component of complement and initiating the alternative complement 

pathway (Clark et al. 1990). Ammonia can chemically interact with an internal thiolester bond of 

complement 3 (C3), resulting in an amide linkage and a subsequent conformational change of the C3. 

The altered C3 then activates the alternative complement pathway, which causes the release of 

chemoattractants and the assembly of the membrane attack complex of complement (Clark et al. 1990). 

Amidated C3 can also bind directly to phagocyte complement receptors, which causes the release of toxic 

oxygen species (Clark et al. 1990). It has also been suggested that NH4

+

 depresses protein degradation in 

renal cells and inhibits renal cell replication, which supports the findings of renal hypertrophy in renal 

injury and indicates that NH4

+

 may inhibit recovery from injury (Rabkin et al. 1993). 

Ammonium ion may also contribute to adverse effects of Helicobacter pylori on the stomach. H. pylori 

produces urease, which breaks down urea that is normally present in the stomach into ammonia (Mégraud 

et al. 1992; Tsujii et al. 1992a). An in vitro study that examined the effects of ammonia produced by 

H. pylori on HEp2 cells showed increased cell vacuolation and viability of the cells compared to a ureasenegative variant of the same cells (Mégraud et al. 1992). An in vivo study suggested that NH4

+

 also 

causes macroscopic gastric lesions and increases the release of endothelin-1 (ET-1) and thyrotropin 

releasing hormone (TRH) from the gastric mucosa, probably via an endothelin A (ETA) receptor, which 

exerts ulcerogenic action on the gastric mucosa (Mori et al. 1998). Ammonia may also trigger the release 

of cysteine proteases in the stomach that contribute to the development of gastric hemorrhagic mucosal 

lesions (Nagy et al. 1996). Neutrophils that migrate to the gastric mucosa in response to the presence of 

H. pylori may release hypochlorous acid, which can interact with NH4

+

 to produce the powerful cytotoxic 

oxidizing agent monochloramine (Murakami et al. 1995). 

3.5.3 Animal-to-Human Extrapolations 

The primary effects of ammonia in humans are due to its corrosive and irritative properties. Exposure to 

ammonia gas causes damage to the respiratory tract, eyes, and skin when the ammonia combines with 

water to become ammonium hydroxide, which results in liquefaction necrosis of the tissues, cell structural 

breakdown, and inflammatory damage (Amshel et al. 2000; Wibbenmeyer et al. 1999). Animal studies 
AMMONIA 92 

3. HEALTH EFFECTS 

have indicated similar types of injuries of the respiratory tract (Coon et al. 1970; Kapeghian et al. 1982; 

Mayan and Merilan 1972; Richard et al. 1978a, 1978b; Schaerdel et al. 1983; Stombaugh et al. 1969), 

eyes, and skin (Morgan 1997). 

Oral exposure of humans to high concentrations of ammonia and ammonium hydroxide has been shown 

to result in buccal, esophageal, and upper tracheal burns and edema (Christesen 1995; Klein et al. 1985; 

Rosenbaum et al. 1998), but no reports of the effects of ammonia on the stomach or upper gastrointestinal 

tract in humans have been found. One report of an ammonia enema in a human showed diffuse 

erythematous, friable mucosa, and large exudative ulcerations in the sigmoid colon and rectum (da 

Fonseca et al. 1998). Gavage studies in rats have shown similar lesions of the gastric mucosa with 

notable histopathological effects (Mori et al. 1998; Takeuchi et al. 1995; Tsujii et al. 1993). Rats, 

therefore, appear to be an adequate model for the primary effects of ammonia in humans. However, 

humans are unlikely to be orally exposed to amounts of ammonia that would result in the gastric lesions 

seen in rats. Elevated levels of endogenously produced ammonia resulting from disease states apparently 

may cause or contribute to gastric pathology (Mégraud et al. 1992; Mori et al. 1998; Tsujii et al. 1992a). 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Colborn and Clement (1992), was also used in 1996 when Congress mandated the 

Environmental Protection Agency (EPA) to develop a screening program for “...certain substances 

[which] may have an effect produced by a naturally occurring estrogen, or other such endocrine 

effect[s]...”. To meet this mandate, EPA convened a panel called the Endocrine Disruptors Screening and 

Testing Advisory Committee (EDSTAC), which in 1998 completed its deliberations and made 

recommendations to EPA concerning endocrine disruptors. In 1999, the National Academy of Sciences 

released a report that referred to these same types of chemicals as hormonally active agents. The 

terminology endocrine modulators has also been used to convey the fact that effects caused by such 

chemicals may not necessarily be adverse. Many scientists agree that chemicals with the ability to disrupt 

or modulate the endocrine system are a potential threat to the health of humans, aquatic animals, and 

wildlife. However, others think that endocrine-active chemicals do not pose a significant health risk, 

particularly in view of the fact that hormone mimics exist in the natural environment. Examples of 
AMMONIA 93 

3. HEALTH EFFECTS 

natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et 

al. 1992). These chemicals are derived from plants and are similar in structure and action to endogenous 

estrogen. Although the public health significance and descriptive terminology of substances capable of 

affecting the endocrine system remains controversial, scientists agree that these chemicals may affect the 

synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body responsible 

for maintaining homeostasis, reproduction, development, and/or behavior (EPA 1997). Stated differently, 

such compounds may cause toxicities that are mediated through the neuroendocrine axis. As a result, 

these chemicals may play a role in altering, for example, metabolic, sexual, immune, and neurobehavioral 

function. Such chemicals are also thought to be involved in inducing breast, testicular, and prostate 

cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding toxicity mediated through the endocrine axis in humans after exposure 

to ammonia. Two studies examined the effects of induced hyperammonemia (with infusion of 

ammonium chloride) in steers on circulating and portal-drained visceral flux of metabolites and on 

pancreatic hormones (Fernandez et al. 1988, 1990). Plasma glucose increased 12% during infusion of 

ammonium chloride (Fernandez et al. 1988, 1990). Plasma insulin decreased up to 46% during 

ammonium chloride infusion, and then increased up to 122% after infusion was halted (Fernandez et al. 

1988); portal-drained visceral release of insulin did not increase during ammonium chloride infusion even 

with the rise in plasma glucose levels, but increased 109% after cessation of infusion (Fernandez et al. 

1990). These data indicate that hyperammonemia in steers may cause reduced hepatic glucose output and 

glucose-mediated pancreatic insulin release. 

No in vitro studies were located regarding toxicity mediated through the endocrine axis by ammonia. 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 
AMMONIA 94 

3. HEALTH EFFECTS 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 
AMMONIA 95 

3. HEALTH EFFECTS 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Human and animal data indicate that the primary effects of ammonia are irritation and burns and that the 

primary targets of ammonia are the respiratory tract, eyes, and skin (Burns et al. 1985; Close et al. 1980; 

Couturier et al. 1971; de la Hoz et al. 1996; Flury et al. 1983; George et al. 2000; Hatton et al. 1979; 

Heifer 1971; Holness et al. 1989; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; 

Millea et al. 1989; Morgan 1997; Price et al. 1983; Shimkin et al. 1954; Slot 1938; Sobonya 1977; Taplin 

et al. 1976; Verberk 1977; Weiser and Mackenroth 1989). There are limited data on the toxicity of 

ammonia in children and no information on effects in adults who were exposed as children. Children 

(8–9 years old) who attended two schools in the vicinity of a fertilizer plant had higher incidences of 

acute respiratory diseases than children who attended a school 20 kilometers away (Gomzi 1999; Gomzi 

and Šarić 1997). Incidence was related to levels of measured pollutants (ammonia, hydrogen fluoride, 

nitrogen dioxide, total suspended particulate matter, and smoke) in the inside and outside air (Gomzi and 

Šarić 1997). Forced expiratory volumes were not statistically different between the three schools (Gomzi 

and Šarić 1997). These results indicate that exposure to low levels of ammonia (0.04–0.23 ppm) or other 

airborne pollutants may not cause functional respiratory deficits, but may lower the resistance to 

respiratory pathogens in children. There is no indication that children are more susceptible to the effects 

of ammonia than adults. However, children have greater surface area to body weight and lung surface 

area to body weight ratios, and increased minute volume to weight ratio, so they may receive a higher 

dose than adults in the same situation. Children may also tend to be exposed longer than adults because 

they may not be as quick as adults to evacuate a contaminated area. 

There are no studies that indicate that metabolism of ammonia differs between children and adults. 

Ammonia is eliminated from the body mainly by processing through the urea cycle in the liver, and urea 

is then eliminated in the urine and feces. The urea cycle is fully functional in infants at birth; therefore, it 

is not expected that infants or children are at greater risk of hyperammonemia. Neurotoxicity resulting 

from hyperammonemia involves alteration of levels of some components of the citric acid cycle, which 

leads to depletion of ATP, and starvation of brain cells, and depletion of glutamate, a precursor to the 

neurotransmitter γ-aminobutyrate (GABA). It is not expected that children are more susceptible than 

adults to ATP depletion via this mechanism. 

Infants under 6 months of age may be more sensitive than adults to the effects of high levels of nitrates 

(from nitrification of ammonia in fertilizers) that may be present in groundwater and well water (Payne 
AMMONIA 96 

3. HEALTH EFFECTS 

1981). Infants who consume formula and food made with contaminated water from these sources may 

develop methemoglobinemia, which results in decreased delivery of oxygen to the tissues. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to ammonia are discussed in Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by ammonia are discussed in Section 3.8.2. 
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3. HEALTH EFFECTS 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10 “Populations That Are Unusually Susceptible”. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Ammonia 

There are no known specific biomarkers of exposure for ammonia. Identification of biomarkers of 

exposure to ammonia is confounded because large amounts of ammonia are produced endogenously. 

Pharmacokinetic studies reveal that after inhalation exposure to low levels of ammonia, BUN, nonprotein 

nitrogen, urinary-urea, and urinary-ammonia levels do not change (Silverman et al. 1949). Exposure to 

common occupational limits of ammonia in air (25 ppm) yield increased blood-ammonia levels only 10% 

above fasting levels (WHO 1986). In one human study, oral ingestion of ammonium chloride tablets 

(approximately 15 mg NH4

+

/kg) yielded only a transient increase in blood-ammonia above fasting levels 

in 11 out of 20 subjects tested; no increase was observed in the remaining 9 subjects (Conn 1972). 

3.8.2 Biomarkers Used to Characterize Effects Caused by Ammonia 

Effect biomarkers of ammonia exposure are limited to site-of-contact tissue injuries. Upon inhalation 

exposure, distribution of ammonia is usually limited to the respiratory tract and involves irritation and, at 

higher concentrations, pulmonary edema and necrosis (Kapeghian et al. 1982; Richard et al. 1978b; 

Silverman et al. 1949). Oral exposure to high doses of ammonium chloride has produced pulmonary 

edema in animals (Koenig and Koenig 1949). Dermal exposure to ammonia causes skin and eye irritation 

and, at higher concentrations, necrosis (Amshel et al. 2000; da Fonseca et al. 1998; George et al. 2000; 

Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; Rosenbaum et al. 1998; Weiser and 

Mackenroth 1989). The severity of injuries by all routes of exposure are dose-related. Unfortunately, 

these effect biomarkers are not specific for ammonia and can be caused by a variety of caustic substances. 

The tissues and organs most sensitive to ammonia exposure are mainly dependent on route of exposure. 

After inhalation exposure, which can involve a significant dermal exposure, the skin and eyes and the 

respiratory tract, including the lungs, are most sensitive. Direct dermal exposure produces dose-related 

effects from irritation to necrosis. Ingestion of ammonium hydroxide has resulted in oral, pharyngeal, and 
AMMONIA 98 

3. HEALTH EFFECTS 

esophageal lesions (Christesen 1995; Klein et al. 1985). The tissue and organ injuries produced by 

ammonia, however, are of limited value as biomarkers to characterize the effects caused by ammonia 

because many other caustic chemicals can produce similar injuries. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Exposure to substances that would increase the pH of exposed tissues could be expected to enhance the 

alkalotic effects of ammonia, and vice versa. Agents acting to elevate the intestinal-tract pH would 

increase its local irritant effect, and would promote its absorption as well (Castell and Moore 1971). 

Co-administration of ammonia and diethyl pyrocarbonate induced lung tumors in Kid:CFLP mice, while 

neither agent administered intragastrically and separately was carcinogenic; this effect is believed to be a 

result of a compound, urethane (a known carcinogen), produced by their interaction (Uzvolgyi and Bojan 

1980, 1985). Sprague-Dawley rats given intrarectal doses of N-methyl-N’-nitro-N-nitrosoguanidine 

(MNNG) and ammonium acetate had a higher incidence of tumors than did controls that were 

administered distilled water in place of ammonium acetate (Clinton et al. 1988). The role of acetate was 

not ruled out. Ammonia acted synergistically with potassium ions on pyruvate kinase, a known Ehrlich 

ascites tumor enzyme (Olavarria et al. 1986). 

Some compounds play a synergistic role with ammonia in producing hepatic coma. Simultaneous 

injection of an ammonium salt and a fatty acid in Holtman or Sprague-Dawley rats produced coma at 

lower plasma levels than did injection of either compound separately. Inhalation of methanethiol or 

injection with sodium octanoate blocked metabolism of an injected dose of ammonium acetate and led to 

elevated blood ammonia levels (Zieve et al. 1974). 

Data regarding exposure to mixtures of atmospheric contaminants indicate that, contrary to what might be 

expected, increased carbon dioxide concentration (up to 5% in air) does not alter the hyperventilatory rate 

induced by hyperammonemia in dogs (Herrera and Kazemi 1980). Ammonia in expired air may 

neutralize inhaled acid aerosols (EPA 1979; Larson et al. 1980; Utell et al. 1989). 

Other substances to which people have been exposed have been shown to alter the toxic effects of 

ammonia. Methionine sulfoximine, administered by intraperitoneal injection, suppressed the tonic 

convulsions produced by intravenous injection of ammonium chloride in mice (Hindfelt and Plum 1975; 

Warren and Schenker 1964). Intraperitoneal injection of alpha-methylglutamic acid also exerts a 
AMMONIA 99 

3. HEALTH EFFECTS 

protective effect against hyperammonemia in rats (Lamar 1970). Nicotinohydroxamic acid and neomycin 

administered orally reduce blood ammonia levels and increase excretion of urea in treated rats (Harada et 

al. 1985). Ethanol exerted a protective effect on acute ammonia intoxication in mice (O'Connor et al. 

1982), although ethanol was reported to increase ammonia concentrations in body tissues of treated rats 

(Mohanachari et al. 1984). 

Sodium benzoate decreased urea production in ammonia challenged rats (Maswoswe et al. 1986) and 

hyperammonemic mice (O'Connor et al. 1987). Valproate, a widely used antiepileptic drug, has a 

hyperammonemic effect in Wistar rats (Ferrier et al. 1988) and may therefore predispose to ammonia 

intoxication. Ammonia interferes with the metabolism of pent-4-enoic acid in cultured rat hepatocytes 

and may dramatically potentiate its toxicity (Coude and Grimber 1984). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to ammonia than will most persons 

exposed to the same level of ammonia in the environment. Reasons may include genetic makeup, age, 

health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These 

parameters result in reduced detoxification or excretion of ammonia, or compromised function of organs 

affected by ammonia. Populations who are at greater risk due to their unusually high exposure to 

ammonia are discussed in Section 6.7, Populations With Potentially High Exposures. 

Persons who suffer from severe liver or kidney disease may be susceptible to ammonia intoxication, as it 

is chiefly by the actions of these organs that NH4

+

 is biotransformed and excreted (Córdoba et al. 1998; 

Gilbert 1988; Jeffers et al. 1988); individuals with hereditary urea cycle disorders are also at risk 

(Schubiger et al. 1991). In these individuals, the levels produced endogenously are sufficient to produce 

toxicity. Levels that are likely to be encountered in the environment, with the exception of those resulting 

from high-level accidental exposures, are insignificant, due to the low absorption rate, in comparison with 

levels produced within the body (WHO 1986). 

Since ammonia is a respiratory tract irritant, persons who are hyperreactive to other respiratory irritants, 

or who are asthmatic, would be expected to be more susceptible to ammonia inhalation effects. The 

results of an epidemiological study of a group of workers chronically exposed to airborne ammonia 

indicate that ammonia inhalation can exacerbate existing symptoms including cough, wheeze, nasal 

complaints, eye irritation, throat discomfort, and skin irritation (Ballal et al. 1998). 
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3. HEALTH EFFECTS 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to ammonia. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to ammonia. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 

for medical advice. The following texts provide general information about treatment following exposures 

alkalies: 

Ellenhorn MJ, Barceloux DG. 1997. Medical toxicology: Diagnosis and treatment of human poisoning. 

New York, NY: Elsevier. 

Haddad LM, Shannon MW, Winchester JF, eds. 1998. Clinical management of poisoning and drug 

overdose. 3rd ed. Philadelphia, PA: W.B. Sanders Company. 

3.11.1 Reducing Peak Absorption Following Exposure 

Absorption of ammonia via dermal exposure is not sufficient to be of concern, but immediate flushing of 

exposed skin with water or saline will limit dermal damage and reduce dermal absorption of ammonia. It 

is highly unlikely that enough ammonia could be ingested to be of danger via absorption from the 

intestines; however, in individuals with liver disease, endogenous production of ammonia may cause 

toxicity. Emesis should not be induced in case of ingestion of ammonia, but administration of activated 

charcoal, gastric lavage, or neutralization with weak acids is recommended HSDB (2003). Elimination of 

urease-producing enteric bacteria with oral antibiotics decreases the amount of ammonia absorbed from 

the gut (Gilbert 1988). Because ammonia is readily soluble in water at low concentrations, very little may 

reach and be absorbed in the lungs. Instead, ammonia at low concentrations may be absorbed in the 

mucosa of the upper respiratory tract and swallowed. Movement to an area of fresh air as quickly as 

possible would limit respiratory damage and absorption via the lungs. 
AMMONIA 101 

3. HEALTH EFFECTS 

3.11.2 Reducing Body Burden 

No experimental data regarding methods for reducing the ammonia body burden were located. In healthy 

people, ammonia is efficiently metabolized via the urea cycle, primarily in the liver, and eliminated in the 

urine and feces (Fürst et al. 1969; Richards et al. 1975). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The primary effects of ammonia are related to its alkalinity and its solubility in water, which results in 

rapid and severe tissue damage. It is extremely important to get to an area free of ammonia gas and to 

remove all clothing contaminated with ammonia as quickly as possible. Skin and eyes should be irrigated 

with water for at least 15–20 minutes at the time of exposure and periodically for 24 hours after exposure 

(Millea et al. 1989). Irrigation of the eye should continue until the pH of the conjunctival sac is less than 

8.5 (Grant 1974). This should be followed with proper medical treatment for respiratory symptoms and 

dermal and ocular burns. 

3.12 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of ammonia is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of ammonia. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 
AMMONIA 102 

3. HEALTH EFFECTS 

3.12.1 Existing Information on Health Effects of Ammonia 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

ammonia are summarized in Figure 3-6. The purpose of this figure is to illustrate the existing information 

concerning the health effects of ammonia. Each dot in the figure indicates that one or more studies 

provide information associated with that particular effect. The dot does not necessarily imply anything 

about the quality of the study or studies, nor should missing information in this figure be interpreted as a 

“data need”. A data need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific 

Data Needs Related to Toxicological Profiles (Agency for Toxic Substances and Disease Registry 1989), 

is substance-specific information necessary to conduct comprehensive public health assessments. 

Generally, ATSDR defines a data gap more broadly as any substance-specific information missing from 

the scientific literature. 

Information regarding health effects of ammonia in humans consists largely of case reports of fatalities or 

illnesses following massive inhalation and/or dermal exposures resulting from accidental explosions or 

leakages. A few controlled studies have been conducted on inhalation and oral exposure effects. Health 

effects of ammonia in animals have been investigated in numerous inhalation studies, and a few oral and 

dermal exposure studies. Clearly, ammonia is an acutely toxic chemical in high concentrations. As 

indicated in Figure 3-6, available data address these concerns, both in humans and animals. The data 

indicate that airway blockage, edema, burns, and lesions of tissues directly exposed to ammonia or NH4

+ 

are the most prominent ammonia-related effects. Secondary effects include liver and kidney damage, 

along with decreased resistance to infection. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. The available human and animal data provide strong evidence that 

acute-duration exposure to ammonia can result in site-of-contact lesions primarily of the skin, eyes, and 

respiratory tract. In some cases, exposure to very high ammonia concentrations has resulted in death 

(Arwood et al. 1985; Walton 1973). Respiratory tract irritation (Burns et al. 1985; Close et al. 1980; 

Couturier et al. 1971; de la Hoz et al. 1996; Ferguson et al. 1977; George et al. 2000; Hatton et al. 1979; 

Heifer 1971; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; Millea et al. 1989; 

Morgan 1997; Price et al. 1983; Sekizawa and Tsubone 1994; Sobonya 1977; Taplin et al. 1976; Verberk 

1977; Weiser and Mackenroth 1989) and impaired pulmonary function (Kass et al. 1972; Silverman et al. 

1949) have been observed in humans acutely exposed to ammonia gas. Animal studies support the 
AMMONIA 103 

3. HEALTH EFFECTS 

Figure 3-6. Existing Information on Health Effects of Ammonia 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Geno toxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunolo gic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Geno toxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 
AMMONIA 104 

3. HEALTH EFFECTS 

identification of the respiratory tract as a sensitive target of toxicity (Coon et al. 1970; Kapeghian et al. 

1982; Mayan and Merilan 1972; Richard et al. 1978a, 1978b; Schaerdel et al. 1983; Stombaugh et al. 

1969). Nonrespiratory tract effects (e.g., cardiovascular effects, renal effects) have also been observed 

following inhalation exposure. However, these effects were not consistently observed or may be 

secondary to the respiratory tract damage. Additional studies would be useful to assess the potential 

toxicity of NH4

+

 to remote tissues. The available acute data were considered adequate to derive an acuteduration inhalation MRL (Verbeck et al. 1977). No acute-duration oral MRL was derived for NH4

+

. The 

acute-duration oral database consists of case reports with no dose information (Klein et al. 1985; 

Klendshoj and Rejent 1966; Lopez et al. 1988) and several animal studies that examined a limited number 

of end points (Noda and Chikamori 1976), involved a single exposure resulting in no effect, serious 

effects, or unsupported effects (Benyajati and Goldstein 1975; Koenig and Koenig 1949), and a repeated 

exposure study that found effects at high dosages (Barzel 1975). In addition, many animal studies have 

been conducted with ammonium chloride, a substance widely used experimentally to induce metabolic 

acidosis in animals. Metabolic acidosis is not a consequence of the ammonium ion, but is due to the 

formation of hydrogen chloride. Metabolic acidosis can affect the lungs, kidney, nervous system, liver, 

and bone. Ingestion of concentrated ammonia will cause irritation and damage to the mouth, throat, and 

gastrointestinal tract. Given the levels of ammonia in the environment, such exposure scenario is 

unlikely. Additional oral exposure studies do not seem warranted at this time. The available data on the 

dermal toxicity of ammonia suggest that the skin is a sensitive target of toxicity. Cutaneous burns have 

been reported in humans exposed to ammonia liquid and/or airborne ammonia (Amshel et al. 2000; da 

Fonseca et al. 1998; George et al. 2000; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 

1992; Rosenbaum et al. 1998; Weiser and Mackenroth 1989). Ocular effects (inflamed eyes, lacrimation, 

swelling of the eyelids, transient blindness, blurred vision, and corneal abrasions) have been reported in 

humans exposed to ammonia (Beare et al. 1988; Caplin 1941; Close et al. 1980; Ferguson et al. 1977; 

Grant 1974; Hatton et al. 1979; Jarudi and Golden 1973; Kass et al. 1972; Latenser and Lucktong 2000; 

Legters et al. 1981; Levy et al. 1964; McGuinness 1969; Montague and Macneil 1980; Price et al. 1983; 

Silverman et al. 1949; Slot 1938; Sobonya 1977; Stombaugh 1969; Stroud 1981; Verberk 1977; Ward et 

al. 1983; Yang et al. 1987). Additional studies to examine the dermal toxicity of ammonia are unlikely to 

provide new key information. 

Intermediate-Duration Exposure. Information on the toxicity of inhaled ammonia in humans 

exposed for an intermediate duration is limited to a case report of an individual who developed asthmalike symptoms following exposure to ammonia gas for 5 months (Lee et al. 1993) and a study with 

volunteers exposed intermittently for 5–6 weeks (Ferguson et al. 1977). The latter study found no 
AMMONIA 105 

3. HEALTH EFFECTS 

significant changes in pulmonary function in subjects exposed to up to 100 ppm ammonia, but eye and 

throat irritation occurred at ≥50 ppm. Because some uncertainties regarding the study design and 

reporting, the Fergusson et al. (1977) study could not be used as basis for an intermediate-duration 

inhalation MRL. Several animal studies examined the toxicity of ammonia following intermittent or 

continuous exposure to ammonia. As with acute-duration exposure, these studies suggest that the 

respiratory tract is the most sensitive target of toxicity. Symptoms of irritation, nasal lesions, dyspnea, 

and pulmonary inflammation have been observed in several animal species (Broderson et al. 1976; Coon 

et al. 1970; Drummond et al. 1980; Gaafar et al. 1992; Sjöblom et al. 1999; Stombaugh et al. 1969). In 

general, the concentrations used in these studies were higher than the lowest adverse effect levels 

identified for acute-duration exposure. No intermediate-duration oral MRL was derived for some of the 

same reasons mentioned under acute-duration exposure. No human studies or reports of intermediateduration oral exposure to NH4

+

 were located. Animal studies have reported decreases in body weight gain 

in rats exposed via drinking water (Gupta et al. 1979) or diet (Boyano-Adanez et al. 1996). It should be 

mentioned that Gupta et al. (1979) administered ammonium sulfamate to the rats. Ammonium sulfamate 

is an herbicide for which there is little toxicity information in the open literature. The EPA (IRIS 2004) 

has derived an oral RfD for the sulfamate moiety based on the results of Gupta et al. (1979). Following 

gavage administration of ammonium salts, bone, blood pressure, adrenal gland, and renal effects have 

been observed in early studies of generally poor quality (Bodansky et al. 1932; Fazekas 1939; Seegal 

1927). Additional intermediate-duration oral low to moderate dose studies are unlikely to provide new 

valuable information. No intermediate-duration dermal exposure studies were identified. Based on the 

irritant properties of ammonia, it is reasonable to assume that direct contact of the skin with ammonia for 

a prolonged time will produce irritation. 

Chronic-Duration Exposure and Cancer. Several studies have examined the relationship between 

chronic exposure to ammonia in the air and respiratory effects. Studies of farmers working in enclosed 

livestock facilities provide evidence that ammonia may contribute to transient respiratory distress 

(Choudat et al. 1994; Cormier et al. 2000; Donham et al. 1995, 2000; Heederik et al. 1990, 1991; 

Melbostad and Eduard 2001; Reynolds et al. 1996; Vogelzang et al. 1997, 2000); however, co-exposure 

to total dust, respirable dust, carbon dioxide, total endotoxins, respirable endotoxins, fungi, bacteria, 

and/or molds complicates the interpretation of these studies. A study of workers at a fertilizer production 

facility found an association between respiratory effects and ammonia exposure at levels of ammonia 

higher than 25 ppm (Ballal et al. 1998). Another long-term study of workers exposed to an average of 

9.2 ppm ammonia did not find respiratory effects (Holness et al. 1989). A chronic-duration inhalation 

MRL was derived based on the findings of Holness et al. (1989). Animal studies examining the chronic 
AMMONIA 106 

3. HEALTH EFFECTS 

toxicity of inhaled ammonia were not identified. No chronic-duration oral or dermal data were located. 

A need for such studies is not apparent at this time. 

There are limited data to assess the carcinogenic potential of ammonia. Nasal cancer was reported in an 

individual accidentally exposed to a refrigeration-oil mixture, but the role of ammonia, if any, is unknown 

(Shimkin et al. 1954). Animal carcinogenicity data consist of several oral exposure studies. Ammonia 

was not found to increase the occurrence of tumors following oral exposure to relatively low doses (Toth 

1972; Uzvolgyi and Bojan 1980). Another study found evidence that ammonia administered as drinking 

fluid may act as a cancer promoter (Tsujii et al. 1992a, 1995). The dose of ammonia administered can be 

estimated at 200 mg/day, compared to the estimated 0.36 mg/day from water ingestion for the general 

population (WHO 1986). The relevance of these studies to exposures in humans is unknown. The 

available information does not suggest that ammonia is carcinogenic, but well-designed studies in animals 

have not been conducted and may be warranted. 

Genotoxicity. Data on the genotoxicity of ammonia in humans are limited to a study of workers at a 

fertilizer factory that found an increase in clastogenic effects (Yadav and Kaushik 1997). In vivo animal 

data consist of a study in mice that found alterations in the occurrence of micronuclei (Yadav and 

Kaushik 1997) and several studies in D. melanogaster that resulted in a positive response for mutagenic 

lethality (Lobasov and Smirnov 1934), but negative responses for sex-linked recessive lethal mutations 

and dominant lethality (Auerbach and Robson 1947). In vitro studies revealed positive responses for 

genotoxicity in E. coli (Demerec et al. 1951), and chick (Rosenfeld 1932) and mouse (Capuco 1977; 

Visek et al. 1972) fibroblasts. It would be valuable to further assess the genotoxicity of ammonia with 

mutagenicity assays in S. typhimurium and in vitro and/or in vivo tests for chromosomal aberrations in 

mammalian systems. 

Reproductive Toxicity. No information was located regarding reproductive effects of ammonia in 

humans. Reproductive toxicity data in animals are limited to a study in pigs exposed prior to mating and 

until gestation day 30 (Diekman et al. 1993). This study did not find alterations in fetus-to-corpus luteum 

ratio, number of live fetuses, or ovarian or uterine weights (6 weeks of exposure only). This study is not 

adequate for assessing reproductive toxicity because very low concentrations were used, there were no 

unexposed controls, and only females were exposed to ammonia. Additional studies are needed to assess 

ammonia’s potential to induce reproductive effects. 
AMMONIA 107 

3. HEALTH EFFECTS 

Developmental Toxicity. No information was located regarding developmental effects of ammonia 

in humans and very limited data were located for animals. No alterations in number of live fetuses or 

fetal length were observed in a study of pigs exposed to a relatively low concentration of ammonia for 

6 weeks prior to mating and until gestation day 30 (Diekman et al. 1993). A reduction in body weight 

gain was observed in the offspring of rats orally exposed to high doses of ammonia, but no information 

was provided regarding the health of the dams (Miñana et al. 1995). Developmental toxicity studies are 

needed to assess the potential of ammonia to damage the developing organism. 

Immunotoxicity. Secondary infection has been observed in humans who have received severe burns 

from exposure to highly concentrated aerosols derived from ammonia (Sobonya 1977; Taplin et al. 1976). 

It is not known if this represents a primary effect on the immune system in humans since necrosis of 

exposed tissues facilitates infection by pathogenic organisms. Animal studies have shown that exposure 

to airborne ammonia may impair immune function (Broderson et al. 1976; Gustin et al. 1994; Richard et 

al. 1978a; Targowski et al. 1984). No oral immunotoxicity data were located. The available data provide 

suggestive evidence that ammonia may be an immunotoxicant. It would be valuable to assess the 

potential for immunotoxicity of ammonia with a battery of immune function tests. 

Neurotoxicity. Neurological effects have been observed in humans who received extensive and 

serious burns from exposure to anhydrous ammonia (George et al. 2000; Hatton et al. 1979; Latenser and 

Lucktong 2000; White 1971). These effects may be secondary to trauma, rather than direct effects of 

ammonia on the central nervous system. There are limited data on the potential of NH4

+

 to induce overt 

neurological effects in animals. A decrease in motor activity has been observed in rodents following an 

acute exposure to low levels of airborne ammonia (Tepper et al. 1985); no overt signs of neurological 

impairment were observed following sublethal inhalation exposure (Coon et al. 1970). However, 

numerous animal studies have found evidence that orally administered ammonia may disrupt normal 

energy production in the brain and impair neurotransmitter receptors (Bodega et al. 1991; Boyano-Adánez 

et al. 1996; Kimura and Budka 1986; Kosenko et al. 1993; Kretzschmar et al. 1985; Miñana et al. 1989b; 

Sobel et al. 1981; Suárez et al. 1992). Additional studies following inhalation and oral exposure would be 

useful to determine if the neurochemical alterations would result in clinical impairment. No dermal 

studies examining neurological end points were identified. 

Epidemiological and Human Dosimetry Studies. Several studies have examined the toxicity of 

airborne ammonia in workers (Ballal et al. 1998; Choudat et al. 1994; Cormier et al. 2000; Donham et al. 

1995, 2000; Heederik et al. 1990, 1991; Holness et al. 1989; Melbostad and Eduard 2001; Reynolds et al. 
AMMONIA 108 

3. HEALTH EFFECTS 

1996; Vogelzang et al. 1997, 2000). These studies have primarily focused on the respiratory tract, which 

is the most sensitive target of toxicity. Interpretation of many of these studies is complicated by coexposure to other chemicals and microorganisms. In addition to these studies, there are reports of acuteduration exposure to ammonia via inhalation (Burns et al. 1985; Close et al. 1980; Couturier et al. 1971; 

de la Hoz et al. 1996; Ferguson et al. 1977; George et al. 2000; Hatton et al. 1979; Heifer 1971; Kass et 

al. 1972; Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; Millea et al. 1989; Morgan 

1997; O’Kane 1983; Price et al. 1983; Sekizawa and Tsubone 1994; Sobonya 1977; Taplin et al. 1976; 

Verberk 1977; Weiser and Mackenroth 1989), ingestion (Klein et al. 1985; Klendshoj and Rejent 1966; 

Lopez et al. 1988), dermal contact (Amshel et al. 2000; da Fonseca et al. 1998; George et al. 2000; 

Kerstein et al. 2001; Latenser and Lucktong 2000; Leduc et al. 1992; Rosenbaum et al. 1998; Weiser and 

Mackenroth 1989), or ocular contact (Beare et al. 1988; Caplin 1941; Close et al. 1980; Ferguson et al. 

1977; Grant 1974; Hatton et al. 1979; Jarudi and Golden 1973; Latenser and Lucktong 2000; Legters et 

al. 1981; Levy et al. 1964; McGuinness 1969; Montague and Macneil 1980; Price et al. 1983; Silverman 

et al. 1949; Slot 1938; Sobonya 1977; Stombaugh 1969; Stroud 1981; Verberk 1977; Ward et al. 1983; 

Yang et al. 1987). These studies suggest that the most sensitive target is the site of contact. The 

carcinogenic potential of ammonia has not been assessed in humans. There are several subpopulations of 

individuals exposed to higher than normal levels of ammonia; these groups include farmers and 

communities living near fertilizer plants. Studies of these groups that involved examination for a variety 

of potential effects could provide useful information on the toxicity of ammonia in humans. In addition, 

if the study group included both children and adults, these data would address the issue of age-related 

differences in toxicity. 

Biomarkers of Exposure and Effect. 

Exposure. There are no known specific biomarkers of exposure for ammonia in humans or animals. 

Furthermore, no evidence for alterations in clinical indices of body ammonia or nitrogen levels after 

exposure to exogenous ammonia has been reported. It does not seem useful at this time to develop 

biomarkers of exposure for ammonia because after exposure to low levels, ammonia is either rapidly 

cleared from the body or metabolized to compounds found endogenously at appreciable levels. Exposure 

to high concentrations is immediately and overtly toxic, which eliminates the need for a more subtle 

biomarker. 
AMMONIA 109 

3. HEALTH EFFECTS 

Effect. There are no known specific biomarkers of effect for ammonia in humans or animals. Lesions 

produced by exposure to high concentrations of ammonia are similar to those produced by other caustic 

substances. 

Absorption, Distribution, Metabolism, and Excretion. Measurement of ammonia absorption is 

complicated by the appreciable levels of endogenously produced ammonia. Although, most of the 

inhaled ammonia is retained in the tissues of the upper respiratory tract, inhalation exposure to low levels 

of ammonia can result in a small amount of absorption (Silverman et al. 1949). As the ammonia 

concentration increases, the ability of the upper respiratory tract to retain ammonia is saturated, and a 

larger percentage is absorbed into the blood stream (Silverman et al. 1949). Absorption into the systemic 

circulation after oral exposure is limited (Metges et al. 1999). Ammonium ions absorbed from the 

gastrointestinal tract travels via the hepatic portal vein directly to the liver where, in healthy individuals, 

most of it is converted to urea and glutamine. Although it has not been extensively studied, dermal 

absorption of ammonia does not occur to a great extent; WHO (1986) concluded that systemic effects 

from skin and eye exposure to ammonia are not quantitatively important. Data are not available to assess 

the distribution of ammonia in humans or animals. Studies examining the distribution of ammonia would 

be useful for identifying potential targets of toxicity. Studies on endogenously produced ammonia, 

however, indicate that it is distributed to most of the organs and tissues of the body. Extensive work has 

been completed on the metabolism of ammonia and its participation in the glutamine cycle and the urea 

cycle (Duda and Handler 1958; Fürst et al. 1969; Richards et al. 1975; Vitti et al. 1964). Data regarding 

excretion are limited but it is known that ammonia inhaled at low levels is excreted primarily unchanged 

in the expired breath (Silverman et al. 1949); NH4

+

 absorbed from the gastrointestinal tract is excreted 

primarily in the urine as urea and other urinary nitrogen compounds (Gay et al. 1969; Pitts 1971; Richards 

et al. 1975; Summerskill and Wolpert 1970). No information regarding excretion after dermal exposure 

was located. 

Comparative Toxicokinetics. Available data indicate that ammonia has similar targets of toxicity 

in humans and animals. Ammonia is most hazardous as a site-of-contact toxicant; therefore, the 

respiratory system is most vulnerable after inhalation exposure, the gastrointestinal tract is most 

vulnerable after oral exposure, and the skin and eyes are most vulnerable after dermal/ocular exposure. 

Limited human and animal data are available for toxicokinetics; however, these data indicate that humans 

and animals are probably very similar regarding the toxicokinetic disposition of ammonia. Furthermore, 

it is reasonable to expect, especially given the biochemical importance of ammonia, that humans and 

animals would handle this compound similarly. 
AMMONIA 110 

3. HEALTH EFFECTS 

Methods for Reducing Toxic Effects. There are limited specific data on reducing the toxic effects 

of ammonia. Many of the methods are generic approaches, such as getting to an area with fresh air and 

removal of contaminated clothing. No methods were identified for reducing the body burden or 

interfering with the mechanisms of toxicity. Studies designed to identify methods for interfering with the 

damage associated with direct contact with ammonia would be useful. 

Children’s Susceptibility. There are limited data on the toxicity of ammonia in children and no 

information on effects in adults who were exposed as children. A higher incidence of respiratory diseases 

was found in school children exposed to airborne ammonia and other chemicals (Gomzi 1999; Gomzi and 

Šarić 1997). There is no indication that children are more susceptible to the effects of ammonia than 

adults; studies of children and adults exposed to ammonia would be useful for assessing potential agerelated differences in ammonia toxicity. 

Child health data needs relating to exposure are discussed in Section 6.8.1 Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

Ongoing studies pertaining to ammonia have been identified and are shown in Table 3-5. 
AMMONIA 111 

3. HEALTH EFFECTS 

Table 3-5. Ongoing Studies on the Health Effects of Ammonia 

Investigator Affiliation Research description Sponsor 

Seashore MR Yale University 

Wall SM University of Texas 

Health Science Center 

Matthews JB University of Cincinnati 

Wall SM University of Texas 

Health Science Center 

Weiner ID University of Florida 

Raushel FM Texas A&M University 

System 

Hammon DS Utah State University, 

Animal Dairy and Vet 

Science 

Nagami GT Department of Veterans 

Affairs, Medical Center 

West Los Angeles, 

California 

Nagami GT Department of Veterans 

Affairs, Medical Center 

West Los Angeles, 

California 

Feldman GM Department of 

Veterans Affairs, 

Medical Center 

Richmond, Virginia 

Walsch PJ University of Miami 

Weiner ID Department of 

Veterans Affairs, 

Medical Center 

Gainesville, Florida 

Sastrasinh S Department of Veterans 

Affairs, Medical Center 

East Orange, New 

Jersey 

Sodium phenylbutyrate treatment of 

inborn errors of ammonia metabolism 

NH4+ transport in renal inner 

medullary collecting duct 

Intestinal secretion and inflammation; 

impact of ammonia 

Renal net acid secretion and 

Na+

/K+/2Cl- cotransporter 

Localization of ammonia transporters 

in human liver 

Mechanism and control of urea 

biosynthesis 

Gamete and embryo toxic effects of 

ammonium in cattle 

Effect of angiotensin II on ammonia 

production by tubule cells. Effect of 

acidosis on renin-angiotensin system 

Ammonia production and transport by 

the proximal tubule 

Colonic transport of bicarbonate, 

ammonium and small organic anions 

Mechanism of tolerance of extreme 

ammonia 

Effect of ammonia on IMCD H-KATPase. Expression of an ammoniasensitive protein in brain that mediates 

ammonia’s neurological effects 

Na+

/H+ antiport in renal mitochondria 

National Center for 

Research Resources 

National Institute of 

Diabetes and Digestive 

and Kidney Diseases 

National Institute of 

Diabetes and Digestive 

and Kidney Diseases 

National Institute of 

Diabetes and Digestive 

and Kidney Diseases 

National Institute of 

Diabetes and Digestive 

and Kidney Diseases 

National Institute of 

Diabetes and Digestive 

and Kidney Diseases 

Animal Health Award 

Department of Veterans 

Affairs, Research and 

Development, 

Washington, DC 

Department of Veterans 

Affairs, Research and 

Development, 

Washington, DC 

Department of Veterans 

Affairs, Research and 

Development, 

Washington, DC 

National Institute of 

Environmental Health 

Sciences 

Department of Veterans 

Affairs, Research and 

Development, 

Washington, DC 

Department of Veterans 

Affairs, Research and 

Development, 

Washington, DC 

Source: FEDRIP (2003) 

AMMONIA 113 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Data pertaining to the chemical identity of ammonia are presented in Table 4-1. These data are for 

ammonia in its pure gaseous state (i.e., anhydrous ammonia). Ammonia is also commercially and 

commonly available as an aqueous solution; the most common commercial formulation is 28–30% NH3

(Weast et al. 1988). At this concentration, ammonia forms a nearly saturated solution in water. Data on 

ammonia in aqueous solution, ammonium hydroxide, and ammonium ion are also included in Table 4-1 

where appropriate. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Ammonium hydroxide is a weak base that is partially ionized in water according to the equilibrium: 

NH3 + H20 o [NH4OH] o NH4

+

 + OHThe dissociation constant, Kb, is 1.774x105

 at 25 °C (pKb is 4.751) and increases slightly with increasing 

temperature (Weast et al. 1988). At pH 9.25 half of the ammonia will be un-ionized (NH3) and half will 

be ionized (NH4

+

). At pH 8.25 and 7.25, 90, and 99% of the ammonia will be ionized, respectively. 

Therefore, at most environmentally significant pHs, ammonia will be largely ionized; the fraction of unionized ammonia will become increasingly more important at pHs above 7. As a result, many physical 

and chemical properties will be a function of pH. For example, the solubility of ammonia in water will 

increase with decreasing pH. The volatility of ammonia increases with increasing pH; therefore, it 

volatilizes freely from solution at high pH values. Ammonium salts such as chloride, nitrate, and sulfate 

are strongly dissociated and very soluble in water (Weast et al. 1988); therefore, changes in pH will not 

normally result in the formation of ammonium precipitates. 

The physical and chemical properties of ammonia are presented in Table 4-2. Also included are some 

chemical and physical properties of ammonia in solution. Ammonia in solution is widely available, and it 

is often referred to as ammonium hydroxide and has been also historically referred to as “spirit of 

hartshorn” (Windholz 1983). 
AMMONIA 114 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Ammonia 

Characteristic Information Reference 

Chemical name 

Synonym(s) 

Registered trade name(s) 

Chemical formula 

Chemical structure 

Identification numbers: 

CAS Registry 

NIOSH RTECS 

anhydrous ammonia 

aqueous solution 

aqua ammonia 

EPA Hazardous Waste 

OHM/TADS 

DOT/UN/NA/IMCO shipping 

anhydrous 

solution (10–35%) 

solution (35–50%) 

solution (>50%) 

HSDB 

NCI 

Ammonia 

Anhydrous ammonia, AM-FOL, 

Ammonia gas, Liquid ammonia, 

Nitro-sil, R 717, Spirit of hartshorn 

No data 

NH3 

H 

H 

HN 

7664-41-7 

B00875000 

B00875000 

B00875000 

B00875000 

No data 

7216584 

UN 1005 

UN 2672 

UN 2073 

UN 1005 

162 

No data 

EPA 1987a; Windholz 1983 

HSDB 2003 

NIOSH 2002a 

OHM-TADS 1988 

NIOSH 2002a 

HSDB 2003 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency;

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RTECS = Registry of Toxic Effects of Chemical Substances
AMMONIA 115 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Ammonia 

Property Value Reference 

Molecular weight 

Color 

Physical state 

Melting point

Boiling point 

Density:

Gas 

Aqueous solution (28%) 

Liquid 

Vapor density 

Specific gravity (25 °C) 

Odor 

Odor threshold: 

Air 

Water 

pKa 

Solubility: 

Water 

at 0 °C 

at 15 °C 

at 20 °C 

at 25 °C 

at 30 °C 

at 50 °C 

Organic solvent(s) 

at 0 °C 

at 25 °C 

Partition coefficients: 

Log Kow 

17.03 

Colorless 

Gas at room temperature 

-77.7 °C

-33.35 °C

0.7710 g/L 

0.89801 (20 °C) g/L 

0.6818 g/L (-33.35 °C, 1 atm) 

0.5967 (air=1) 

0.747 g/L 

Sharp, intensely irritating 

25 ppm (18 mg/m3

) 

48 ppm (34 mg/m3

) 

53 ppm (38 mg/m3

) 

1.5 ppm 

9.25 (25°C) 

42.8% (w/w) 

47% (w/w) 

38% (w/w) 

33.1% (w/w) 

34% (w/w) 

34% (w/w) 

31% (w/w) 

28% (w/w) 

18% (w/w) 

20% (w/w) in absolute ethanol 

10% (w/w) in absolute ethanol 

16% (w/w) in methanol 

Soluble in chloroform and ether 

0.23 (estimated) 

LeBlanc et al. 1978 

LeBlanc et al. 1978 

LeBlanc et al. 1978 

LeBlanc et al. 1978 

LeBlanc et al. 1978 

Weast et al. 1988 

Windholz 1983 

Windholz 1983 

Windholz 1983 

Lide 1998 

Sax and Lewis 1987 

Amoore and Hautala 1983

Leonardos et al. 1969 

Budavari et al. 1996 

Amoore and Hautala 1983

Lide 1998 

LeBlanc et al. 1978 

Budavari et al. 1996 

Budavari et al. 1996 

LeBlanc et al. 1978 

Budavari et al. 1996 

LeBlanc et al. 1978 

Budavari et al. 1996 

Budavari et al. 1996 

Budavari et al. 1996 

Budavari et al. 1996 

Budavari et al. 1996 

Budavari et al. 1996 

Budavari et al. 1996 

EPIWIN 2000
AMMONIA 116 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Ammonia 

Property Value Reference 

Log Koc 

Vapor pressure: 

Anhydrous NH3 

Aqueous NH3 (28%) 

Henry's law constant 

Autoignition temperature 

Flashpoint 

Flammability limits in air 

Conversion factors 

ppm (v/v) to mg/m3

 in air 

(20 °C) 

mg/m3

 to ppm (v/v) in air 

(20 °C) 

pH in water 

Explosive limits 

1.155 (estimated) 

8.5 atm (20 °C) 

10.2 atm (25 °C) 

2.9 atm (25 °C) 

1.6x10-5 atm-m3

/mol (25 °C) 

7.3x10-6 atm-m3

/mol (pH 7, 23.4 °C)a

1.60x10-5 atm-m3

/mol (25 °C)

b

5.01x10-6 atm-m3

/mol (5 °C) 

650 °C

Not available

16–25% 

1 ppm (v/v) = 0.707 mg/m3 

1 mg/m3 = 1.414 ppm (v/v) 

11.6 (1 N) 

11.1 (0.1 N) 

10.6 (0.01 N) 

Not available 

EPIWIN 2000 

Sax and Lewis 1987 

Daubert and Danner 1989 

Daubert and Danner 1989 

Betterton 1992 

Ayers et al. 1985 

Yoo et al. 1986 

Brimblecombe and Dawson 

1984 

LeBlanc et al. 1978 

LeBlanc et al. 1978 

Verschueren 1983 

Windholz 1983 

a

Unitless constant extrapolated from cited data. b

Unconverted value of 0.0168 kg-atm/mol was calculated from equation in citation. 

pKa = The dissociation constant of the conjugate acid 
AMMONIA 117 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Ammonia is both a natural and a manufactured chemical. It is a key intermediate in the nitrogen cycle in 

nature, and microbial production is a major source of ammonia in the world. Recent reports, however, 

have emphasized the significant influence that humans are having on the global nitrogen budget. At the 

beginning of the 20th century, most nitrogen was fixed into usable forms (e.g., NH3) by lightning strikes 

and microbial nitrogen fixation, with an estimated 90–130 teragrams (Tg; 1 teragram is equivalent to one 

million metric tons) fixed per year. Human production of fixed nitrogen (NH3) is now estimated to be 

140 Tg N per year, an amount that is similar to non-anthropogenic sources (NSF 1999; Socolow 1999). 

This increase in human-related ammonia emissions is considerably higher than earlier estimates of the 

total annual commercial production of ammonia, wherein the anthropogenic emission of ammonia 

represented approximately 1–5% of nature's global ammonia emission budget (ApSimon et al. 1987; 

Buijsman et al. 1987; Crutzen 1983; Galbally 1985; Rosswall 1981; Socolow 1999). 

The largest amount of naturally produced ammonia is thought to arise from soil. Ammonia from 

decomposing animal excreta probably accounts for the largest proportion of the ammonia produced, with 

the decay of organic materials from plants, dead animals, and the like contributing significant amounts 

(Crutzen 1983; Dawson 1977; Dawson and Farmer 1984; Galbally 1985; Irwin and Williams 1988). 

Manufacture of ammonia within the United States has declined steadily over the past several years, with 

one of the outcomes being the closure of several production plants. The U.S. annual commercial 

production capacity for ammonia was 16.6 million metric tons in 1999 (CMR 1999), 15.7 million metric 

tons in 2000 (SRI 2000), but only 9.5 million metric tons in 2001 (Kramer 2002). Production levels 

increased slightly to 10.8 million metric tons in 2002 (Kramer 2003). High natural gas costs, along with 

weather-related decreases in demands, contributed to the lower production output in the years leading up 

to 2002. However, natural gas prices became lower in 2002, and ammonia production increased that year. 

In 1999, four plant closings eliminated a combined production capacity of 1.2 million tons, some of 

which was replaced by new facilities (CMR 1999). In 2000, an additional seven plants were completely 

shut down, and five plants were partially closed due to market conditions (Kramer 2000). In 2002, the 

largest producer of ammonia in the United States filed for Chapter 11 bankruptcy, leading to the 
AMMONIA 118 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

permanent closing of three large production plants (with a combined production capacity of just over 

980,000 metric tons) (Kramer 2003). 

While ammonia production decreased over the past few years and some ammonia plants were closed, the 

states and companies that have historically produced most of the ammonia remained relatively constant. 

In 2000, 2001, and 2002, Louisiana, Oklahoma, and Texas were the three major producing states, 

contributing over 50% of the total U.S. ammonia production. Six companies (Farmland Industries Inc., 

Terra Industries Inc., PCS Nitrogen Inc., Agrium Inc., CF Industries Inc., and Koch Nitrogen) produced 

73% of the nation’s ammonia in 2002 (Kramer 2003). 

There are 2,338 facilities that manufacture or process ammonia in the United States (Table 5-1). The 

amounts manufactured or processed range from relatively small production activities (from 0 to 

99,999 pounds) in Hawaii to very large formulation and processing activities (up to 499,999,999 pounds) 

in Alaska, Florida, Iowa, Kansas, Louisiana, Nebraska, and Texas (TRI01 2003). As mentioned 

previously, three states, Louisiana, Oklahoma, and Texas, produce more than 50% of the nation’s total 

NH3 output. 

The major method for commercial production of anhydrous ammonia is a modified Haber-Bosch process. 

This process was first demonstrated in 1909 (Kramer 2000), and was commercially developed in 1913 in 

Germany. The first U.S. plant to use this process was built in Syracuse, New York, in 1921 (DOI 1985). 

The basic Haber-Bosch methodology was still responsible for 98% of the industrially produced ammonia 

in the United States in 1979 (EPA 1980; HSDB 2003). In this process, nitrogen (obtained from the 

atmosphere) and hydrogen (obtained from natural gas) are mixed together in a 1 to 3 ratio and passed over 

a catalyst at high pressure and high temperature. The ammonia thus produced is collected by various 

means, and any unreacted feed gases are recirculated through the reactor. 

Small amounts of ammonia are produced industrially as a by-product of the coking of coal. The largest 

proportion of industrial ammonia production occurs in areas where natural gas is cheap and plentiful 

because ammonia is synthesized using natural gas. Large pipelines stretching from Louisiana to 

Nebraska and from Texas to Minnesota carry anhydrous ammonia from its site of production to 

agricultural areas where it is used as fertilizer (LeBlanc et al. 1978). These pipelines are capable of 

transporting or storing 3 million metric tons of ammonia per year, and have a storage capacity of 

1.5 million metric tons (Kramer 2000, 2003). Ammonia can also be shipped in large refrigerated, low 
AMMONIA 119 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Ammonia 

Number Minimum Maximum 

of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AK 6 1,000 499,999,999 1, 3, 4, 5, 6, 10, 11, 12 

AL 69 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13 

AR 45 100 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AS 1 10,000 99,999 11 

AZ 16 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

CA 161 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 15 0 999,999 1, 5, 6, 7, 9, 11, 12 

CT 24 0 999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12 

DC 2 100,000 999,999 12 

DE 14 0 999,999 1, 3, 5, 6, 7, 11, 12 

FL 54 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

GA 87 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

HI 6 0 99,999 1, 3, 5, 6, 10, 12, 13, 14 

IA 54 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

ID 16 100 49,999,999 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 

IL 108 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

IN 72 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

KS 36 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 

KY 34 100 9,999,999 1, 2, 3, 5, 6, 7, 9, 10, 11, 12, 13, 14 

LA 73 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 10, 11, 12, 13, 14 

MA 34 0 999,999 1, 2, 3, 5, 6, 7, 10, 11, 12 

MD 16 1,000 999,999 1, 3, 5, 6, 7, 8, 10, 11, 12, 13, 14 

ME 13 0 999,999 1, 2, 3, 5, 6, 10, 11, 12, 13 

MI 72 0 999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13, 14 

MN 39 0 9,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MO 50 1,000 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MS 44 100 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MT 12 0 9,999,999 1, 3, 5, 6, 10, 11, 12 

NC 86 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

ND 7 0 999,999 1, 3, 5, 6, 10, 11, 12 

NE 35 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

NH 14 0 9,999,999 1, 3, 4, 5, 6, 7, 10, 11, 12 

NJ 58 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NM 6 100 99,999 1, 5, 7, 11, 12 

NV 11 100 9,999,999 1, 2, 3, 4, 5, 6, 10, 11, 12, 13 

NY 63 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OH 123 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 26 100 99,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14 
AMMONIA 120 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Ammonia 

Number Minimum Maximum 

of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

OR 46 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

PA 108 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

PR 15 100 999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12 

RI 13 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12 

SC 64 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

SD 4 1,000 999,999 1, 5, 10, 11 

TN 56 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

TX 191 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 28 100 9,999,999 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12 

VA 57 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

1 100,000 999,999 1, 2, 3, 5, 6, 10, 12 

VT 2 1,000 99,999 1, 5, 11, 12 

WA 38 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

WI 68 100 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

WV 33 0 49,999,999 1, 3, 5, 6, 7, 9, 10, 11, 12, 13 

WY 12 0 99,999,999 1, 3, 4, 5, 6, 7, 10, 13 

Source: TRI01 2003 (Data are from 2001) 

a

Post office state abbreviations used b

Amounts on site reported by facilities in each state c

Activities/Uses:

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

VI 
AMMONIA 121 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

pressure tanks (holding between 4 and 30 thousand tons) or smaller (holding approximately 210 tons), 

pressurized tanks (Farm Chemicals Handbook 1987). Barges are often used for refrigerated shipments 

because of their lower cost. Ammonia can be stored in refrigerated tanks holding up to 36,000 tons for 

use in the ammonia market. Smaller amounts of ammonia are stored in pressurized tanks. 

The supply of ammonia for domestic uses has been historically met by domestic production. The ability 

to meet the ammonia demand depends on the amount of crop acres planted, the price of imported 

fertilizers, the cost of natural gas, and the availability of ammonia via import from abroad. In 2000, 

3.9 million metric tons of anhydrous ammonia were imported; in 2001, this amount increased to more 

than 5.5 million metric tons. In 2000, domestic sources supplied 15.7 million metric tons of ammonia, 

whereas international sources provided 3.9 million metric tons; imports represented 20% of the total 

supply. In 2001 by comparison, domestic production dropped to 9.5 million metric tons, while imports 

increased 5.5 million metric tons; imports in 2001 represented almost 37% of the supply of ammonia 

(Kramer 2002). The amount of ammonia imported in 2002 held steady—the amount imported was just 

under 5.7 million metric tons (Kramer 2003)—while domestic production rose slightly to 10.8 million 

metric tons. Imports in 2002 represented 35% of the domestic need. The increases in imported ammonia, 

along with decreased domestic production, resulted in a substantial increase in reliance on foreign sources 

during these 3 years. 

5.2 IMPORT/EXPORT 

The import and export of ammonia have fluctuated slightly over the last few years. In 2000, the amount 

of ammonia imported into the United States was slightly less than 3.9 million metric tons. In both 2001 

and 2002, the amount of ammonia imported into the United States was slightly more than 5.5 million 

metric tons (Kramer 2003). These years reflect a 41% increase in the amount of ammonia imported 

compared to 2000. U.S. exports of ammonia fell during the years following the change in domestic 

production and import from abroad. Exports in 2000 were approximately 0.66 million metric tons, and in 

2001, 0.65 million metric tons were exported. Exports then dropped to 2/3 of those reported in the 

previous years. In 2002, when domestic production dropped and imports increased, only 0.44 million 

metric tons of ammonia were exported. 
AMMONIA 122 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.3 USE 

The largest and most significant use of ammonia and ammonium compounds is the agricultural 

application of fertilizers. Ammonia and ammonium compounds used as fertilizer represent 89–90% of 

the commercially produced ammonia, with plastics, synthetic fibers and resins, explosives, and other uses 

accounting for most of the remainder (Kramer 2002, 2004). Direct uses of ammonia as fertilizer can be 

broken down into the following categories (percentages based on mass of nitrogen in each compound): 

anhydrous ammonia, 26%; urea/ammonium nitrate solutions, 23%; urea, 20%; ammonium nitrate, 4.5%; 

ammonium sulfate, 2%; other forms, 3%; and multiple nutrient forms, 21% (Kramer 2003). Most 

ammonium compounds and nitric acid, which are produced from anhydrous ammonia, are used directly in 

the production of fertilizers. 

The small proportion of commercially produced ammonia not incorporated into fertilizers is used as a 

corrosion inhibitor, in the purification of water supplies, as a component of household cleaners, and as a 

refrigerant. It is also used in the pulp and paper, metallurgy, rubber, food and beverage, textile, and 

leather industries. Ammonia is used in the manufacture of pharmaceuticals and explosives, and in the 

production of various chemical intermediates (LeBlanc et al. 1978; Sax and Lewis 1987). 

5.4 DISPOSAL 

Solutions of ammonia can be highly diluted with water, or alternatively, diluted with water and 

neutralized with HCl and then routed to the sewer system. The amount released to the receiving stream 

should not exceed the established limits for ammonia. Limited amounts of gaseous ammonia may be 

discharged to the atmosphere. Federal, state, and local guidelines should be consulted before disposal. 

Disposal of liquefied ammonia or of large quantities of gaseous or aqueous ammonia directly into water is 

not desirable, because of the large amount of heat generated. This generation of heat could increase 

exposure to personnel involved in the process. Recovery of ammonia from aqueous waste solutions is a 

viable option for many industries (HSDB 2003). 
AMMONIA 123 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Ammonia has been identified in at least 137 of the 1,647 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (HazDat 2004). However, the number of sites 

evaluated for ammonia is not known. The frequency of these sites can be seen in Figure 6-1. Of these 

sites, 135 are located within the United States and 2 are located in the Commonwealth of Puerto Rico (not 

shown). 

Ammonia is a naturally-occurring compound that is an intermediate in the global nitrogen cycle. It is 

essential for many biological processes and is a central compound in all living organisms. Nitrogen is 

converted from atmospheric N2 to other forms by different processes. Nitrogen fixation (the process of 

converting atmospheric N2 to NH3) occurs naturally due to biological processes. Lightning strikes also 

“fix” atmospheric nitrogen, but they produce nitrogen oxides, not ammonia. The current amount of 

nitrogen fixation that occurs by industrial processes equals that of natural, terrestrial nitrogen fixation. 

Both natural and anthropogenic sources produce a total of approximately 230–270 million metric tons of 

NH3 per year. 

Because of its role in natural processes and cycles, ammonia is found at low concentrations in most 

environmental media. When ammonia is found at a local concentration that is higher than these 

background levels, it is often a result of human influence. Ammonia is hazardous only when exposure is 

to high levels. In determining the environmental fate of ammonia, several factors should be considered, 

the primary one being that ammonia is the most abundant alkaline gas in the environment. An acid-base 

reaction between water and ammonia occurs such that the dominant form of ammonia in water, at 

environmentally relevant pHs, is the ammonium ion. In media where water is usually present, such as 

soil, plants, biological tissue, and water itself, ammonia and ammonium are in dynamic equilibrium. 

Ammonia is a key intermediate in the nitrogen cycle, a natural cycle that is coupled with other important 

biological cycles (i.e., the sulfur cycle and carbon cycle). An understanding of the role of ammonia in the 

nitrogen cycle, at least on a generalized level, is important in determining the environmental fate of 

ammonia. A simplified schematic of the microbial processes of the nitrogen cycle that involves ammonia 

can be found in Figure 6-2. Microorganisms perform four processes in the nitrogen cycle that result in 
AMMONIA 124 

6. NTIAL FOR HUMAN EXPOSURE 

Figure 6-1. of NPL Sites with Ammonia Contamination 

1-2

3-4

5-6

7-8

9

16

Derived from HazDat 2004

Frequency of

NPL Sites

POTE

Frequency
AMMONIA 125 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Simplified Schematic for the Microbial Processes of the 

Nitrogen Cycle 

ATMOSPHERE 

NH4 

+ 

NO2 

– 

SOIL, AQUATIC ENVIRONMENTS 

Organic N 

(Biota) 

Denitrification 

N2O 

NO 

Nitrification 

N2 ATMOSPHERE 

NH4 

+ 

NO2 

– 

SOIL, AQUATIC ENVIRONMENTS 

Organic N 

(Biota) 

Uptake 

Ammonification 

Denitrification 

N2O 

NO 

N itrification 

Nitrogen Fixation 

N2 

NO3 

– 
AMMONIA 126 

6. POTENTIAL FOR HUMAN EXPOSURE 

production or transformation of ammonia: nitrogen fixation, nitrification, denitrification, and 

ammonification. As part of this cycle, nitrogen gas and oxidized forms of nitrogen are transformed and 

returned to the biological world. Nitrogen fixation is the process whereby atmospheric nitrogen gas is 

converted to ammonia, which is then assimilated into amino acids; it has been found that there is only a 

small proportion of all genera of microorganisms that can fix nitrogen. Denitrification is the process 

whereby the nitrogen oxides (i.e., nitrate and nitrite) are reduced under anaerobic conditions to N2 and 

N2O, which can escape to the atmosphere. Nitrification is the biological oxidation of ammoniacal 

nitrogen to nitrate, with nitrite as the intermediate. Ammonification (or nitrogen mineralization) is the 

conversion of organic nitrogen into ammonia. 

Ammonia may be released to the atmosphere by volatilization from the following sources: decaying 

organic matter; livestock excreta; fertilizers applied to soils; venting of gas, leaks, or spills during 

commercial synthesis, production, transportation, or refrigeration equipment failure; sewage or waste 

water effluent; burning of coal, wood, and other natural products; and volcanic eruptions. 

Ammonia may be released to water through effluent from sewage treatment plants, effluent from 

industrial processes, runoff from fertilized fields, and runoff from areas of concentrated livestock. This 

usually occurs when the organic N compounds present in these sources enter the water and are converted 

microbiologically to ammonia. 

Ammonia may be released to soils by natural or synthetic fertilizer application, animal (including 

livestock) excrement degradation, decay of organic material from dead plants and animals, and indirectly 

from natural fixation of atmospheric nitrogen. In this latter case, ammonia releases can occur following 

nitrogen fixation by free-living microbes and plants (those that are symbiotic nitrogen-fixing bacteria), 

which subsequently die and release ammonia (or compounds that are converted to ammonia) to the soils. 

In the atmosphere, ammonia can be removed by rain or snow washout. Reactions with acidic substances, 

such as H2SO4, HCl, HNO3, or N oxides (all produced in high concentrations from anthropogenic 

activities) produce ammonium aerosols, which can undergo dry or wet deposition. The gas phase reaction 

of ammonia with photochemically produced hydroxyl radicals is thought to contribute about 10% to the 

overall atmospheric removal process. The best estimate of the half-life of atmospheric ammonia is a few 

days. 
AMMONIA 127 

6. POTENTIAL FOR HUMAN EXPOSURE 

In water, ammonia volatilizes to the atmosphere, is transformed to other nitrogenous compounds, or may 

be bound to materials in the water. Volatilization is highly pH-dependent, and can also depend on other 

factors such as temperature, wind speed, and atmospheric ammonia concentration. Transformation of 

ammonia in water occurs primarily by the microbial processes of nitrification and to lesser extents, 

denitrification. Nitrification yields nitrate and nitrite anions; the former species can be responsible for 

methemoglobinemia in human infants if the contaminated water is ingested. Removal of ammonium 

from water can also occur by adsorption to sediments or suspended organic material. 

In soil, ammonia may either volatilize to the atmosphere, adsorb to particulate matter, or undergo 

microbial transformation to nitrate or nitrite anions. Uptake by plants can also be a significant fate 

process. Ammonia at natural concentrations in soil is not believed to have a very long half-life. If 

ammonia is distributed to soil in large concentrations (e.g., following an application of an 

ammonia-containing fertilizer), the natural biological transformation processes can be overwhelmed, and 

the environmental fate of ammonia will become dependent upon the physical and chemical properties of 

ammonia, until the ammonia concentration returns to background levels. 

Occupational exposure to ammonia may occur in industries involved in its synthesis, formulation, 

processing, transportation, and use. Occupational exposure to ammonia can also occur during the use of 

an extensive number of cleaning products that contain ammonia. Farmers may be exposed during the 

application of fertilizers containing anhydrous ammonia or liquid ammonia, or manures high in ammonia. 

Workers at cattle feedlots, poultry confinement buildings, or other industries that have a high 

concentration of animals may also be exposed. 

Exposure of the general population to elevated levels of ammonia is most commonly from the use of 

household cleaners that contain ammonia. People who live near farms or who visit farms during the 

application of fertilizer that contain or release ammonia may also be exposed. People living near cattle 

feedlots, poultry confinement buildings, or other areas where animal populations are concentrated can 

also be exposed to ammonia, in addition to other gases generated by putrefaction. Ammonia has been 

identified at 137 out of 1,647 NPL hazardous waste sites (HazDat 2004). 

6.2 RELEASES TO THE ENVIRONMENT 

Ammonia is commercially produced for many processes, but most production is for agricultural uses, 

primarily crop fertilizer. As a result of most it being formulated for agricultural practices, ammonia is 
AMMONIA 128 

6. POTENTIAL FOR HUMAN EXPOSURE 

commonly distributed to the environment during its intended use as a crop fertilizer. Release data 

generated for the Toxics Release Inventory (TRI) (see Table 6-1) provide detailed information regarding 

environmental releases related to industrial activities, but should be used with caution because only

certain types of facilities are required to report, and data from these reports do not represent an exhaustive 

list of all commercial releases. It should be noted that for ammonia, since it is one of the most widelyused agricultural fertilizer chemicals in the United States, the TRI data represent only a small fraction of 

the environmental release, and do not include releases that occur during farming or other agriculture 

practices. 

Table 6-1 shows the 2001 TRI releases of ammonia from manufacturing or processing facilities to 

different environmental compartments. Most of the ammonia released to the environment from these 

facilities was the result of air releases, followed by releases via underground injection. The greatest air 

releases occurred in the state of Louisiana (12,304,532 pounds), which was almost 2 million more pounds 

released than the second highest releasing state, Ohio (10,505,480 pounds). Texas released the most 

ammonia via underground injection (15,014,490 pounds), which was more than 3 times the second 

highest releasing state, Louisiana (4,446,211 pounds). For all on-site releases, the two states releasing the 

most ammonia were the adjacent states of Louisiana and Texas (Louisiana released 17,742,736 pounds 

and Texas released 21,354,611 pounds). 

Release of ammonia from production and processing facilities has changed from year to year, with 

amounts generally decreasing since the early 1990s. Reported air releases have ranged from a high of 

254,542,289 pounds in 1989 to a low of 122,057,546 pounds in 2001. Surface water releases have ranged 

from a high of 48,138,279 pounds in 1990 to a low of 6,621,166 pounds in 2001. Land releases (surface 

releases) have shown a similar trend, with the highest amount (17,782,641 pounds) released in 1990, and 

the lowest amount (2,868,728 pounds) released in 1999. The general trend is that less and less ammonia 

has been released to the environment each year, such that the total amount released in 2001 

(158,521,046 pounds) was less than a third of the amount released in 1990 (548,828,735 pounds). 

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list. 

In addition to releases related to agricultural or other anthropogenic usage, ammonia has been identified 

in several environmental compartments including surface water, groundwater, soil, and sediment 

collected at 135 of the 1,647 current or former NPL hazardous waste sites in the United States, and in 
AMMONIA 129 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or 

Use Ammoniaa 

Reported amounts released in pounds per yearb 

Number Under- Total on- Total off- Total on and 

of 

Statec facilities Aird

 Water 

ground 

injection Land 

site 

releasee 

site 

releasef 

off-site 

release 

AK 7 

AL 75 

AR 48 

AS 1 

AZ 18 

CA 178 

CO 19 

CT 28 

DC 2 

DE 14 

FL 72 

GA 95 

HI 7 

IA 60 

ID 16 

IL 136 

IN 82 

KS 38 

KY 40 

LA 78 

MA 48 

MD 17 

ME 15 

MI 81 

MN 56 

MO 55 

MS 49 

MT 14 

NC 101 

ND 9 

NE 38 

NH 15 

NJ 67 

NM 5 

NV 13 

NY 71 

1,427,011 32,428 5 95,950 1,555,394 0 1,555,394 

3,192,615 180,703 0 57,288 3,430,606 145,305 3,575,911 

3,672,621 209,122 0 372 3,882,115 18,078 3,900,193 

6,920 No data 0 0 6,920 0 6,920 

107,967 5 0 260 108,232 350 108,582 

6,362,240 37,470 41,236 264,004 6,704,950 18,728 6,723,678 

291,922 12,899 0 4,019 308,840 148 308,988 

169,071 10,035 0 0 179,106 8 179,114 

0 487 0 0 487 0 487 

109,356 3,804 0 7,937 121,097 0 121,097 

5,646,496 148,226 293,106 124,914 6,212,742 122,755 6,335,497 

8,291,371 171,670 0 13,140 8,476,181 154,582 8,630,763 

47,492 660 2,059 30,368 80,579 0 80,579 

4,686,900 133,403 0 3,829 4,824,132 166,223 4,990,355 

2,705,639 5,874 0 182,369 2,893,882 21,731 2,915,613 

2,366,356 56,440 0 68,423 2,491,219 1,108,621 3,599,840 

1,294,431 55,681 824,984 61,545 2,236,641 23,002 2,259,643 

3,285,064 36,461 22,555 270,459 3,614,539 42,129 3,656,668 

1,218,869 83,020 0 4,000 1,305,889 1,483 1,307,372 

12,304,532 917,883 4,446,211 4,816 17,673,442 69,294 17,742,736 

591,589 6 0 0 591,595 33,235 624,830 

482,934 25,246 0 18,569 526,749 4,587 531,336 

813,198 39,047 0 0 852,245 0 852,245 

1,579,680 141,346 40,307 68,851 1,830,184 12,981 1,843,165 

1,790,288 43,283 0 36,315 1,869,886 3,315 1,873,201 

548,485 319,685 0 11,624 879,794 34,796 914,590 

4,452,540 394,837 0 46,552 4,893,929 255 4,894,184 

543,332 10,920 0 9,685 563,937 0 563,937 

3,054,435 287,555 0 30,750 3,372,740 18,711 3,391,451 

305,283 17,106 0 88,654 411,043 340 411,383 

804,872 245,587 0 377,539 1,427,998 243,327 1,671,325 

128,420 551 0 0 128,971 966 129,937 

1,144,702 165,642 0 0 1,310,344 18,406 1,328,750 

9,780 5 29,497 670 39,952 0 39,952 

428,880 2,710 0 311,810 743,400 0 743,400 

1,387,982 61,780 0 8,266 1,458,028 1,540 1,459,568 
AMMONIA 130 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or 

Use Ammoniaa 

Reported amounts released in pounds per yearb 

Number Under- Total on- Total off- Total on and 

of 

Statec facilities Aird

 Water 

ground 

injection Land 

site 

releasee 

site 

releasef 

off-site 

release 

OH 136 

OK 28 

OR 51 

PA 131 

PR 16 

RI 22 

SC 68 

SD 9 

TN 58 

TX 209 

UT 29 

VA 64 

1 

VT 2 

WA 45 

WI 83 

WV 36 

WY 12 

10,505,480 98,996 2,006,500 52,964 12,663,940 93,861 12,757,801 

5,995,915 81,112 0 25,716 6,102,743 1,850 6,104,593 

1,769,989 43,747 0 106,233 1,919,969 1,882 1,921,851 

2,346,403 229,268 0 13,469 2,589,140 23,359 2,612,499 

1,938,727 306 0 0 1,939,033 600 1,939,633 

84,982 3,573 0 0 88,555 0 88,555 

2,559,694 162,782 0 39,741 2,762,217 5,627 2,767,844 

86,361 684 0 225 87,270 29,223 116,493 

4,865,087 487,650 0 796 5,353,533 78,192 5,431,725 

5,206,675 518,396 15,014,390 199,710 20,939,171 415,440 21,354,611 

458,197 8,800 0 911,305 1,378,302 503 1,378,805 

7,866,819 93,001 0 35,707 7,995,527 129,614 8,125,141 

77,675 42,154 0 0 119,829 0 119,829 

47,582 4,450 0 0 52,032 0 52,032 

857,165 137,956 0 22,488 1,017,609 80,200 1,097,809 

589,027 89,624 0 3,107 681,758 78,850 760,608 

961,276 758,661 14,387 0 1,734,324 42,951 1,777,275 

587,219 8,429 239,000 6,610 841,258 0 841,258 

Total 2,668 122,057,546 6,621,166 22,974,237 3,621,049 155,273,998 3,247,048 158,521,046 

Source: TRI01 2003 (Data are from 2001) 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number. b

Data in TRI are maximum amounts released by each facility. c

Post office state abbreviations are used. d

The sum of fugitive and stack releases are included in releases to air by a given facility. e

The sum of all releases of the chemical to air, land, water, and underground injection wells. f

Total amount of chemical transferred off-site, including to publicly owned treatment works (POTW). 

VI 
AMMONIA 131 

6. POTENTIAL FOR HUMAN EXPOSURE 

groundwater and soil samples at 2 sites in Puerto Rico (HazDat 2004). Furthermore, ammonia is a key 

intermediate in nature's nitrogen cycle, and considerable amounts are released to the environment as a 

result of natural processes. As a result of inputs from natural sources and from anthropogenic sources, 

ammonia concentrations in nature are in dynamic equilibrium. When ammonia is found at elevated 

concentrations, however, it is usually a result of anthropogenic activity. 

6.2.1 Air 

Large amounts of ammonia are released to the atmosphere worldwide by domesticated farm animals 

(ApSimon et al. 1987; Asman and Janssen 1987; Buijsman et al. 1987; Kramer 2000, 2002; Ryden et al. 

1987). Ammonia emissions due to the decay of livestock manure are a source for ammonia release in 

areas that have artificially high concentrations of animals, such as cattle feedlots and poultry-confinement 

buildings (Brinson et al. 1994; Hutchinson et al. 1982; Langland 1992; Liao and Bundy 1995; Olivier et 

al. 1998; Sunesson et al. 2001). In Germany, over 90% of the measured NH3 emissions originated from 

agricultural sources (Strogies and Kallweit 1996). In Russia, estimated NH3 emissions from fertilizer 

applications and livestock sources accounted for 94% of the total NH3 emissions from all anthropogenic 

sources (Tsibulski et al. 1996). The use of high nitrogen content feed for farm animals and the trend 

toward larger feedlots have been responsible for increased emissions in developed countries. 

The application of fertilizer to soil, as ammonia, ammonium compounds, or ammonia precursors (such as 

urea), is a well documented source of ammonia release to the atmosphere (ApSimon et al. 1987; Beyrouty 

et al. 1988; Buijsman et al. 1987; Kucey 1988; Olivier et al. 1998; Reynolds and Wolf 1988). The rate of 

ammonia emission from ground sources, such as freshly fertilized fields and cattle feedlots, is dependent 

on variables such as the pH, temperature, soil characteristics, rainfall, method of application, wind speed, 

etc. (Bouwmeester and Vlek 1981; Brunke et al. 1988; Denmead et al. 1982; Hoff et al. 1981; Kucey 

1988; Nason et al. 1988; Reynolds and Wolf 1988). Ammonia can volatilize from sewage sludge that has 

been spread on the surface of the soil (Beauchamp et al. 1978; Ryan and Keeney 1975) as well as from 

poultry litter (Brinson et al. 1994). In the latter case, composted poultry litter released far less volatile 

NH3 to the atmosphere (0–0.24% of applied) than did fresh poultry litter (17–23%) (Brinson et al. 1994). 

In contrast, the crops themselves are often minor sources of atmospheric NH3. Harper and Sharpe (1995) 

demonstrated almost no net atmospheric NH3 flux in corn crops, due to their relatively similar emission 

and uptake rates of NH3 over the growing season. 
AMMONIA 132 

6. POTENTIAL FOR HUMAN EXPOSURE 

For much of the history of the Earth, biological activity in soil and natural waters was the primary global 

source of atmospheric ammonia (Dawson 1977; Dawson and Farmer 1984; National Science Foundation 

1999), but this has changed over the last century. Crutzen (1983) suggested that the decay of organic 

material arising from dead plant, animal, and microbial biomass generates most of the atmospheric 

ammonia, while Galbally (1985) and Irwin and Williams (1988) suggested that domestic-animal 

excretions represent the dominant source of atmospheric ammonia. Lee et al. (1997) estimated that 

grasslands contributed 40% of the total global NH3 emissions, with domestic animal wastes contributing 

42.3% of that. Recent studies, however, provided fairly uniform estimates of ~40% of global NH3 

emissions being due to excreta from domestic animals (Asman et al. 1998; Bouwman et al. 1997; Olivier 

et al. 1998). Current measurements and estimates, however, indicate that the amount of ammonia 

produced as a result of anthropogenic activities is equivalent to the amount produced by natural processes 

(National Science Foundation 1999). 

In addition to livestock-related releases, ammonia can be released to the atmosphere through the venting 

of gases during the production, storage, and transportation of ammonia, and during its formulation or 

incorporation into secondary products (Buijsman et al. 1987). Long pipelines are used to transport 

ammonia from its site of manufacture to agricultural areas where it is used as fertilizer (Farm Chemicals 

Handbook 1987; Kramer 2000; LeBlanc et al. 1978). Releases to the atmosphere could occur at pumping 

stations and points of transfer along these pipelines, or from leaks. Large refrigerated tanks are used to 

store ammonia, and release to the environment can occur while venting the pressure in these tanks, or 

from leaks. 

Ammonia can also enter the atmosphere by volatilization from the waste water of industrial processes that 

involve its production or use, and from the volatilization from the effluent of waste water treatment plants 

(Buijsman et al. 1987; Langland 1992; Roy and Poricha 1982; Wilkin and Flemal 1980). Ammonia has 

been found in the exhaust of automobile and diesel engines (Asman et al. 1998; Plerson and Brachaczek 

1983). Release to the atmosphere can occur during the burning of coal (Bauer and Andren 1985; Olivier 

et al. 1998). The latter process, however, is not thought to account for a significant proportion of the total 

anthropogenic ammonia released to the atmosphere (Olivier et al. 1998; Strogies and Kallweit 1996). 

Natural sources of ammonia emissions to the atmosphere are volcanic eruptions, forest fires, and the 

decomposition of nitrogenous compounds arising from microbially-fixed nitrogen (Galbally 1985; Hegg 

et al. 1987; National Science Foundation 1999). Excreta from household pets, wild animals, and humans 

are also contributing sources (Asman and Drukker 1988; Buijsman et al. 1987; Crutzen 1983). 
AMMONIA 133 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

The major point source of release to surface waters is from the effluents of waste water-treatment plants 

(Barica 1990; Crumpton and Isenhart 1988; Wilkin and Flemal 1980). Ammonia can enter surface waters 

through the effluent of commercial processes in which ammonia is used or produced (Effler et al. 2001; 

Huddleston et al. 2000; Matthews et al. 2000; Roy and Poricha 1982). Runoff from fertilized farmland 

and from areas of concentrated livestock production can also result in the transfer of ammonia to surface 

water (Corsi et al. 2000; Jingsheng et al. 2000; Wilkin and Flemal 1980). Surface water can absorb 

ammonia directly from the atmosphere near cattle feedlots, areas where the local atmospheric 

concentration may be high (Fangmeier et al. 1994; Hutchinson and Viets 1969). Ammonium can also be 

released to water when N2-fixing cyanobacteria (also called blue-green algae) die and are decomposed. 

6.2.3 Soil 

Ammonia enters soil through different processes, primarily human practices (e.g., fertilizer applications, 

animal husbandry), and natural biological processes. Direct application of fertilizers represents a major 

influx of ammonia into soils. Of the total U.S. production of anhydrous ammonia, 30% is applied directly 

to the soil under pressure (Kramer 2000). Approximately 80% of the U.S. production of ammonia is 

applied to soil in fertilizer formulations designed to release ammoniacal nitrogen. Application of natural 

fertilizers obtained from livestock excreta will also result in the release of ammonia to the soil (Asman et 

al. 1998; Beauchamp et al. 1982; Hoff et al. 1981; Olivier et al. 1998). High levels of ammonia in soils 

can result from the decomposition of animal wastes on cattle feedlots or other confinement areas, as well 

as from the land disposal of livestock and poultry waste. Ammonia in soil can also arise from the decay 

of organic material arising from plant, animal, and microbial byproducts and biomass (Dawson 1977; 

Dawson and Farmer 1984). Microbial fixation of nitrogen from the atmosphere is a natural and continual 

source of ammonia in soil, which can be released to soil after the microorganisms die (Galbally 1985; 

National Science Foundation 1999). 

In nature, there are many pathways for incorporation of ammonia into soil. Natural sources include 

microbial decomposition of dead plants and animals, and hydrolysis or breakdown of urea and 

nitrogenous waste products in animal excretions. Several species of microorganisms can produce 

ammonia by the fixation of N2, and these organisms are widely dispersed throughout the soil (Atlas and 
AMMONIA 134 

6. POTENTIAL FOR HUMAN EXPOSURE 

Bartha 1998; Crutzen 1983); ammonia is released to the soil only after these microorganisms die. While 

several species of microbes can perform nitrogen fixation, this capability would not be one that is 

considered common for most microorganisms. 

6.3 ENVIRONMENTAL FATE 

In considering the environmental fate of ammonia, it is necessary to emphasize that ammonia is very 

important in nature and in nature's biological cycles. In our limited understanding of fluxes between these 

cycles, ammonia is considered a key intermediate. Nature has incorporated many mechanisms and 

“rules” for altering the distribution of ammonia through the biological system, as circumstances dictate. 

An in-depth discussion of these phenomena is outside the scope of this document; however, it is 

important to understand that for ammonia, all organisms contribute, either directly or indirectly, to the 

direction and distribution of the various environmental-fate processes. 

An important consideration that affects the transport and partitioning of ammonia in the environment is 

that ammonia is a base. As a base, the physical and chemical properties of ammonia are pH-dependent, 

and thus, environmental-fate processes that influence the transport and partitioning of NH3 will also be 

pH-dependent. For some environmental fate processes, a change in pH may only affect the relative rate 

of a process, while for others, it could change the direction or overall result of that process. The influence 

of pH on the environmental fate of ammonia will be discussed where appropriate. Temperature is also an 

important consideration in the environmental fate of ammonia. Temperature, although to a lesser extent 

than pH, affects the ammonia-ammonium equilibrium. 

6.3.1 Transport and Partitioning 

Atmospheric ammonia can be readily removed from the air by rain or snow washout (Adamowicz 1979; 

Asman et al. 1998; Kumar 1985). It can dissolve in the water found in clouds (Asman et al. 1998; 

Brimblecombe and Dawson 1984; Sprenger and Bachmann 1987) or fog (Johnson et al. 1987). Ammonia 

can be removed from the atmosphere through the direct absorption by surface waters in areas where the 

local atmospheric concentration is high (Hutchinson and Viets 1969) and by wet deposition onto soils and 

surface waters (Asman et al. 1998; Cuesta-Santos et al. 1998; Goulding et al. 1998). Uptake of 

atmospheric ammonia by different species of plants also occurs (Harper and Sharpe 1995; Nason et al. 

1988; Rogers and Aneja 1980). Depending on the local atmospheric concentration, however, plants can 
AMMONIA 135 

6. POTENTIAL FOR HUMAN EXPOSURE 

also release ammonia to the atmosphere (Harper and Sharpe 1995; Lee et al. 1997; O'Deen and Porter 

1986; Parton et al. 1988). By use of 15NH3, it has been demonstrated that minerals and dry soil can 

rapidly and effectively adsorb NH3 from air containing trace quantities of this gas (Bremner 1965). 

Ammonia is the predominant basic gas in the atmosphere (Allen et al. 1989). As such, it is capable of 

rapidly reacting with atmospheric H2SO4, HNO3, or HCl, forming ammonium aerosols, which can then 

undergo dry deposition (Allen et al. 1989; Irwin and Williams 1988). 

If released to surface water, ammonia can volatilize to the atmosphere or be taken up by aquatic plants. 

The rate of volatilization of ammonia from water will increase with increasing pH (generally only 

important above pH values of ~7.0) and temperature, and can be influenced by other environmental 

factors. Gaseous or liquid ammonia added to water will increase the pH of the medium; the rate of 

volatilization may increase dramatically if large amounts are released to relatively small static bodies of 

water, such as rice paddies (DeDatta 1995). Agitation will also increase the rate of volatilization. Georgii 

and Gravenhorst (1977) calculated the equilibrium concentration of ammonia above the Pacific Ocean. 

Using a constant concentration of 3 pmol/L, the ammonia concentration above the ocean as a result of 

increased volatilization was calculated to change from approximately 2.8 to 7 ppb as the pH was 

increased from 8.1 to 8.4 (at 25 °C). Volatilization of ammonia from flooded rice paddies was found to 

increase with increasing ammoniacal nitrogen concentration, pH, temperature, and wind velocity 

(Bouwmeester and Vlek 1981; DeDatta 1995; Tian et al. 2001). Ammonia can also be taken up by 

aquatic plants as a source of nutrients (Kemp and Dodds 2002). 

In water, adsorption of ammonia to sediment and suspended organic material can be important under 

proper conditions (Ankley et al. 1990). Adsorption to sediment should increase with increasing organic 

content, increased metal ion content, and decreasing pH. Ammonia, however, can be produced in, and 

subsequently released from, sediment (Jones et al. 1982; Malcolm et al. 1986). 

The uptake of ammonia by fish can also occur under the proper conditions (Hargreaves 1998; Mitz and 

Giesy 1985). Ammonia is the final breakdown product of nitrogenous-compound metabolism for catfish, 

and it is normally released through the gills into the surrounding water, driven by a concentration 

gradient. If the water concentration is abnormally high, the direction of passive ammonia transport is 

reversed. 

A complete discussion of the factors influencing the transport and partitioning of ammonia in soil is 

outside the scope of this document. Adsorption of ammonia occurs in most moist or dry soils, and 
AMMONIA 136 

6. POTENTIAL FOR HUMAN EXPOSURE 

ammonia is predominantly, but not exclusively, held as the ammonium ion. Generally, adsorption will 

increase with increasing organic-matter content of the soil, and will decrease with increasing pH. Other 

factors that influence the adsorption of ammonia to soil are the presence of metallic ions, the predominant 

microbial populations and communities present, and its rate of uptake by plants. The ammonia 

concentration, temperature, and wind speed can also subtly affect the adsorption process by influencing 

the rate of volatilization (Bouwman et al. 1997; Bouwmeester and Vlek 1981; Brunke et al. 1988; 

Denmead et al. 1982; Galbally 1985; Goulding et al. 1998; Hoff et al. 1981; Kucey 1988; Nason et al. 

1988; Reynolds and Wolf 1988; Socolow 1999). To demonstrate the influence of pH on the volatilization 

of ammonia (which, as indicated above, influences the potential for ammonia adsorption), ammonia loss 

was measured in greenhouse experiments using soils that had been adjusted to different pH values. 

Following the application of manure to the soil surface, ammonia volatilization was found to be 14% of 

the applied ammonium at a soil pH of 6.4 (manure pH=6.4). At a soil pH of 7.0 (manure pH=7.8), 65% 

was lost by volatilization (Hoff et al. 1981). In a study of the effects of SO2 deposition on soils, it was 

found that the threshold pH at which ammonia volatilization from soil was drastically reduced did not 

occur until the pH was reduced to between pH 3.5 and 4.0 (Mahendrappa 1982). This is a relatively 

unrealistic and unrepresentative pH value for most soils; the results, however, indicate that volatilization 

will be an important process that affects the transport and partitioning of ammonia in most soils. 

Because ammonia, as ammonium ion, is the nutrient of choice for many plants (Kramer 2000; Rosswall 

1981), uptake of soil ammonia by living plants is an important fate process. The rate of uptake by plants 

varies with the growing season. At normal environmental concentrations, ammonia does not have a very 

long residence time in soil. It is either rapidly taken up by plants, bioconverted by the microbial 

population, or volatilized to the atmosphere. Because of these processes, and because ammonia generally 

exists in soils as NH4

+

 (which binds to soils particles), ammonia does not leach readily through soil; thus, 

it is rarely found as a contaminant of groundwater (Barry et al. 1993). In soil, ammonia that results from 

the application of fertilizers is usually found in the top 10 inches of the soil (Beauchamp et al. 1982). 

However, nitrate derived from ammonia may leach to groundwater. 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

In air, a dominant fate process for ammonia is the reaction with acid air pollutants. Formation of 

particulate NH4

+

 compounds by reactions with HNO3 and H2SO4 is rapid (Bouwman et al. 1997; Irwin 
AMMONIA 137 

6. POTENTIAL FOR HUMAN EXPOSURE 

and Williams 1988). The extent to which this process serves as a removal mechanism depends on the 

concentrations of these acidic compounds (Goulding et al. 1998). Thus, it is likely more important in 

areas of high industrial activity or a high density of automobile traffic, but of lesser importance over rural 

areas. These ammonium compounds can then be removed by dry or wet deposition. 

The vapor-phase reaction of ammonia with photochemically produced hydroxyl radicals is known to 

occur. The rate constants for this reaction have been determined to be 1.6x10-13

 cm3/molecule-sec, which 

translates to a calculated half-life of 100 days at a hydroxyl radical concentration of 5x105

 molecules/cm3 

(Graedel 1978). This process reportedly removes 10% of atmospheric ammonia (Crutzen 1983). Since 

ammonia is very soluble in water, rain washout is expected to be a dominant fate process. The half-life 

for ammonia in the atmosphere was estimated to be a few days (Brimblecombe and Dawson 1984; 

Crutzen 1983; Dawson 1977; Galbally and Roy 1983; Moller and Schieferdecker 1985). The reaction of 

atmospheric ammonia with acidic substances in the air results in the formation of ammonium aerosols 

that can subsequently be removed from the atmosphere by dry or wet deposition. In general, dry 

deposition processes predominate where there are high amounts of NH3 emissions; where NH3 emissions 

are lower, wet deposition of particulate NH4

+

 predominates (Asman et al. 1998). 

6.3.2.2 Water 

In surface water, groundwater, or sediment, ammonia can undergo sequential transformation by two 

processes in the nitrogen cycle, nitrification and denitrification, which would produce ionic nitrogen 

compounds, and from these, elemental nitrogen. The ionic nitrogen compounds formed from the aerobic 

- process of nitrification, NO2 and NO3, can leach through the sediment or be taken up by aquatic plants or 

other organisms. High concentrations of nitrate in groundwater can cause methemoglobinemia in infants 

when contaminated water is ingested (Messinga et al. 2003, Payne 1981). Elemental nitrogen formed 

from the anaerobic process of denitrification is lost by volatilization to the atmosphere. 

In water, ammonia is in equilibrium with the ammonium ion, NH4

+

. The ammonia-ammonium ion 

equilibrium is highly dependent on the pH and, to a lesser extent, the temperature of the medium. In 

acidic waters and neutral waters, the equilibrium favors the ammonium ion. 
AMMONIA 138 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.3 Sediment and Soil 

In soil, ammonia can serve as a nutrient source for plants, which can be taken up by plants and 

microorganisms and converted to organic-nitrogen compounds. Ammonia in soil can be rapidly 

transformed to nitrate by the microbial population through nitrification (Atlas and Bartha 1998; Payne 

1981). The nitrate formed will either leach through the soil or be taken up by plants or other 

microorganisms. Very high localized concentrations of ammonia, such as those that might occur after a 

spill, or an excessive application, of ammonia-containing fertilizers can be toxic to plants, other 

organisms, or microbiota, which if inhibited or killed, will result in a decrease of the rates of any related 

nitrogen transformation processes. Under these conditions, other fate processes dictated by the physical 

and chemical properties of ammonia will dominate until the ammonia concentration returns to a 

background level. These physical and chemical processes include binding to soil particles (including 

organic carbon) or undergoing volatilization to the atmosphere. 

6.3.2.4 Other Media 

No data exist for the transformation or degradation of ammonia in other media, apart from biological 

tissues. These transformations are discussed in more detail in Chapter 3. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

In discussing the concentration of ammonia monitored in the environment, it is important to consider both 

ammonia and its conjugate acid, the ammonium ion. Independent determination of these compounds 

cannot always be achieved. In an analysis of the literature, it is difficult to separate aqueous ammonia 

concentration from aqueous ammonia-ammonium concentrations unless the investigators made a special 

effort to determine the amount of un-ionized ammonia. In this section of the document, ammonia will 

refer to the ammonia and ammonium concentration, and un-ionized ammonia will refer specifically to the 

ammonia concentration. 

In the atmosphere, ammonia can exist in its gaseous state, be dissolved in rain, the water of fog, or clouds, 

or be found as ammonium in particulates and aerosols. These species can be analyzed separately. For 

this reason, atmospheric ammonia concentrations reported in this document will refer to the concentration 

of gaseous ammonia, and not to the concentrations of ammonium compounds. 
AMMONIA 139 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.1 Air 

Ammonia has a worldwide atmospheric background concentration. Estimates of the average global 

ammonia concentration are approximately 0.6–3 ppb (Aneja et al. 1998; Crutzen 1983; Georgii and 

Gravenhorst 1977). Dawson and Farmer (1984) reported that the average concentration of ammonia in 

the southwestern United States is 0.9 ppb, which may be considered a representative background value 

because at the site of these measurements, the prevalent winds came from the Pacific Ocean and there 

were no known urban or agricultural ammonia sources nearby. Fangmeier et al. (1994) reported similar 

values in a review of effects of atmospheric ammonia on vegetation. Values measured at sea or at high 

altitude provided a background range of 0.06–1.0 ppb (n=9 reports). When atmospheric ammonia levels 

have been determined to be above background levels, the measurements can often be correlated with 

industrial, agricultural, or other activities that might occur in nearby areas (Fangmeier et al. 1994). 

The concentrations of ammonia in the atmosphere vary across the United States, with concentrations 

being higher in the Midwest as compared to either the west or east coasts. Based on early data on the 

concentration of ammonia in rain, Lau and Charlson (1977) determined a trend for the atmospheric 

ammonia concentration across the United States. The estimation of atmospheric ammonia content 

increased progressively starting from the east coast to the mid-west and on to the western states. Upon 

reaching the Pacific coast, the atmospheric ammonia concentration decreases. It should be noted that the 

values obtained in this study (ppt levels over the eastern seaboard and pacific coasts, and low ppb levels 

in the midwest and western United States) tend to be lower than those determined by more recent 

experiments. For example, Aneja et al. (1998) measured concentrations of both NH3 and NH4

+

 at Mount 

Mitchell (North Carolina) over 2 years; concentrations averaged 1–2 ppb. Fangmeier et al. (1994) 

provided atmospheric ammonia values derived from five studies conducted in the United States, with an 

average NH3 concentration of 3.3 ppb. The general conclusion of Lau and Charlson (1977) however, 

appears valid, and is indicative of the trends found for the ammonia concentrations in the atmosphere. 

Atmospheric ammonia concentrations are expected to be highest near intense agricultural or livestock 

production areas because of ammonia emissions from fertilizer and animal excreta, respectively. Lower 

concentrations are generally expected in more industrialized areas because of diminished sources of 

agricultural emissions and the atmospheric reaction of ammonia with acidic compounds known to be 

produced in industrial emissions and automobile exhaust. Data summarized in Fangmeier et al. (1994) 

indicate that industrial regions may have significant ammonia concentrations, but these are orders of 

magnitude lower than concentrations in regions with some agricultural applications. Concentrations 
AMMONIA 140 

6. POTENTIAL FOR HUMAN EXPOSURE 

determined near industrial sources in Germany (10.3–39.1 ppb) were in the same order of magnitude as 

concentrations near manure heaps (89 ppb), but were three orders of magnitude lower than emissions near 

pigpens (4.7x104

 ppb). 

Ground-level ammonia concentrations taken at urban Hampton and rural Langley, Virginia, ranged from 

0.2 to 4.0 and from 1.5 to 4.0 ppb, respectively, in the fall of 1979 (Harward et al. 1982). Ammonia 

concentrations obtained in December of 1979 on Long Island, New York, ranged from approximately 

80 to 200 nmol/m3

 (1.9–4.8 ppb) (Tanner 1982). The ground level ammonia concentrations in Claremont, 

Los Angeles, and Anaheim, California, were <25 ppb (Russell et al. 1988). In Riverside and Rubidoux, 

California, areas near dairy feedlots, the ground level ammonia concentrations were 37–132 ppb and 

approximately 10–100 ppb, respectively. Rural-area concentrations, however, in Massachusetts and New 

York were considerably lower (0.2–1.1 ppb) (Fangmeier et al. 1994). 

The ambient concentrations of ammonia determined at Whiteface Mountain, New York, in 1982 ranged 

from approximately 0.3 to 5 ppb, with the hourly median and mean values both determined as 2.2 ppb 

(Kelly et al. 1984). Ammonia concentrations in rural Thurber, Nevada, ranged from approximately 0.5 to 

2 ppb (Farmer and Dawson 1982). In the atmosphere over the world's oceans, ammonia concentrations 

ranged from approximately 0.28 to 5.6 ppb (Georgii and Gravenhorst 1977). 

Several investigators have studied the seasonal variation of ammonia concentrations in the atmosphere. 

In Hampton, Virginia, the ground level ammonia concentrations during the spring and summer were 

10 and 1 ppb, respectively (Levine et al. 1980). The difference in concentration may have been due to 

volatilization of ammonia resulting from springtime application of fertilizer in nearby agricultural areas. 

In Warren, Michigan, the average ammonia concentrations measured during the summer, fall, winter, and 

spring were 0.85, 0.37, 0.10, and 0.16 ppb, respectively. The difference in concentrations was attributed 

to fluctuations in emissions from livestock excreta, since natural ammonia emissions are much higher in 

the summer than in the winter (Cadle 1985; NRC 1979). Additionally, in colder weather, microbial 

activity would be expected to decrease, and thus, ammonia emissions from the decay of organic matter 

would also be expected to decrease. Ammonia emissions from animal excretions also fluctuate with the 

time of day (Beauchamp et al. 1982; Brunke et al. 1988). 

The concentration of ammonia in the atmosphere decreases with altitude. Levine et al. (1980) found that 

an ammonia concentration of 10 ppb measured at ground level decreased to a concentration of 1.5–3 ppb 

at a height of 10 km. In a historical modeling study on the European production of ammonia, levels based 
AMMONIA 141 

6. POTENTIAL FOR HUMAN EXPOSURE 

on ammonia release from livestock, fertilizer production and application, human and domestic animals, 

and sewage sludge resulted in average atmospheric ammonia concentrations ranging from 0.6 to 1.4 ppb 

for 1970 and from 0.7 to 5.6 ppb for 1980. The greatest increase occurred between 1950 and 1980, when 

synthetic fertilizer application and high nitrogen content feed grains were widely used (Asman and 

Drukker 1988). The ammonia concentration over a field during the application of gaseous ammonia 

fertilizer was as high as 300 ppb (Denmead et al. 1982). Over cattle feedlots, atmospheric ammonia 

concentrations have been measured at 520–2,160 ppb (Hutchinson et al. 1982). 

6.4.2 Water 

The concentration of ammonia in the Ochlocknee River at the head of Ochlocknee Bay, Florida, ranged 

from approximately 31 to 43 ppb, and concentrations of approximately 8.5 to 26 ppb were determined at 

the mouth of the bay (Seitzinger 1987). The concentration determined in the Ochlocknee River is 

consistent with levels reported for unpolluted tropical rivers (Meybeck 1982). Typical ammonia levels in 

the South Skunk River, Iowa, upstream from a municipal sewage-treatment facility were <1 ppm 

(Crumpton and Isenhart 1988). Downstream of the facility, ammonia levels peaked at approximately 

16 mg/L (16 ppm), with levels of un-ionized ammonia ranging from <1.0 to 2.2 ppm. The levels of 

undissociated ammonia were directly related to pH fluctuations in the river. The authors did not discuss 

why the upstream concentration was so high. In the same study, it was noted that ammonium and unionized ammonia concentrations fluctuated in a diurnal pattern in the river, with peaks in ammonia 

(approximately 1 mg/L) occurring around noon, and low concentrations (0.5 mg/L) occurring usually 

after midnight (Crumpton and Isenhart 1988). The mean ammonia concentration in three Illinois rivers 

ranged from 0.28 mg/L (0.28 ppm) to 6.08 mg/L (6.08 ppm). The lower values were associated with 

agricultural sampling points and the higher values were associated with urban sampling points (Wilkin 

and Flemal 1980). 

The ammonia concentration measured in Hamilton Harbour, Ontario, Canada was typically 0.1–3 mg/L 

(0.1–3 ppm) in the early 1980s. This body of water is used for water transportation (e.g., boat and barge 

traffic), as a source for industrial cooling water, and as a receptor for waste water disposal (Snodgrass and 

Ng 1985). Measurements made a few years later (1987–1988), in contrast, showed much lower 

concentrations. Measured concentrations, however, were still greater than the International Joint 

Commission objective of 20 :g/L (20 ppb) for more than half the year, and concentrations often exceeded 

the chronic toxicity threshold of 300 :g/L (300 ppb) (Barica 1990). This work reported that ammonia 
AMMONIA 142 

6. POTENTIAL FOR HUMAN EXPOSURE 

loadings into Hamilton Harbor had decreased over the late 1970s and 1980s, and the measured 

concentrations may reflect that change. 

Some representative data regarding the concentration of ammonia in groundwater indicate that natural 

concentrations are generally low, but that agricultural practices can, at times, lead to higher levels. Low 

levels of ammonia have been found in groundwater wells under cattle and poultry feed lots, and in 

shallow wells. Wells 3–6 m deep showed little variation in ammonia concentration over a 3-year period 

where varying amounts of chicken manure were spread over agricultural plots, except when excessive 

amounts (54–179 metric ton/ha) were applied (Liebhardt et al. 1979). Groundwater levels of ammonia 

were also determined in an area in Idaho that had previously been noted as having high nitrogenous 

compound concentrations in the water. In this study, ammonium concentrations varied from 2.5 ppb in a 

municipal drinking water well to 3.25 ppm in a deep, private well (Wicherski 2000). Shallow wells in 

North Carolina had typical ammonia concentrations of 0.1–1 ppm, which were independent of land use, 

plant type, and amount of fertilization (Gilliam et al. 1974). Water samples from wells on four 

schoolyards in Michigan that used septic tank sewage systems had ammonia concentrations ranging from 

0 to 733 ppb (Rajagopal 1978). In the Netherlands, the ammonium concentration detected in sample cups 

buried 1.2 m in the ground near forests ranged from 0 to 2.3 ppm (Krajenbrink et al. 1988), but no 

ammonia was detected in deeper wells (12.6 meters) analyzed in this study. The high adsorptivity of 

ammonium to soil and the rapid conversion of ammonia to nitrate by microbial action are both consistent 

with the usual finding of very low ammonia concentrations in groundwater. 

Ammonia was measured in rain and snow samples from three sites in northern Michigan in 1978–1979. 

Concentrations ranged from 23.8 to 3,500 ppb, with mean values for each site of 816, 572, and 632 ppb, 

respectively. Concentrations were generally greatest in the spring and fall and were lowest during the 

winter (Munger 1982). Ammonia concentrations in bulk precipitation obtained in the Netherlands had 

median values ranging from 1.33 ppm in ocean areas to 5.09 ppm in bodies of water near heavily 

agricultural areas (Schuurkes et al. 1988). 

Ammonia concentrations in the influent to sewage-treatment plants, and thus the effluent from sewer 

systems, typically range from 10 to 20 ppm (Englande et al. 1978; Hauser 1984; U.S. Army Corps of 

Engineers 1980). Waste water-treatment plant effluent is one of the few types of point sources of 

ammonia emissions to surface water. In a study of several waste water-treatment plants, eight of nine 

plants exceeded the guideline ammonia concentration (0.5 mg/L), with measured median values at these 

sites ranging from 0.08 to 15 mg/L (0.08–15 ppm) (Englande et al. 1978). 
AMMONIA 143 

6. POTENTIAL FOR HUMAN EXPOSURE 

No data were located in the available literature regarding ammonia concentrations in drinking water. This 

may be attributed to the rapid reaction between ammonia (and ammonium) and the chlorinating agents 

used in water treatment plants (Morris 1978). 

6.4.3 Sediment and Soil 

A 4-year study on ammonia levels in the soil (0–10 cm deep) of an open field (samples obtained in early 

May of each year) showed that ammonia concentrations ranged from 1 to 5 ppm (Beauchamp et al. 1982). 

The day after application of a slurry of liquid cow manure, the soil concentration ranged from 2 to 

3,349 ppm. Five days after application, the concentration of ammonium ranged from 2 to 848 ppm. The 

greatest ammonia concentration was in the uppermost 4 cm of soil. 

Ammonia was found at 137 of 1,647 hazardous waste sites on the NPL of highest priority sites for 

possible remedial action (HazDat 2004). 

6.4.4 Other Environmental Media 

The ammonia concentrations measured in the plumes of seven forest fires in the western United States 

ranged from 7 to 130 ppb; the median value of the 13 measurements was 37 ppb (Hegg et al. 1987, 1988). 

Fangmeier et al. (1994) reported a slightly higher value for smoke from a forest fire in Canada, 250 ppb. 

Ammonia has been found in the exhaust of automobile and diesel engines (Plerson and Brachaczek 1983). 

Ammonia has also been determined to be a component of tobacco and cigarette smoke (Sloan and Morie 

1974). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The most probable routes by which the general population is exposed to ammonia are by the inhalation of 

ammonia that has volatilized from common household cleaning products and through dermal contact 

during the use of these products. Inhalation exposure to ammonia by some members of the rural 

population may occur for those who are near agricultural areas during the fertilizer-application period, 

those near animal feedlots or confinement areas, and those who apply anhydrous ammonia or ammoniaproducing fertilizers to fields. There is also the possibility for exposure to ammonia via water and food 
AMMONIA 144 

6. POTENTIAL FOR HUMAN EXPOSURE 

ingestion. If untreated surface water is ingested, the average uptake would be 0.36 mg/day (assuming an 

ammonia concentration in untreated water of 0.18 mg/L and a consumption of 2 L/day) (WHO 1986). 

Food ingestion could lead to an exposure to ammonia, primarily from the use of various ammonium salts 

as stabilizers; the estimated exposure from these food additives is 18 mg/day (WHO 1986). 

In the National Occupational Hazard Survey (NOHS) of 1972–1974, it was statistically estimated that 

2,524,678 workers are exposed to ammonia in the United States (RTECS 1988). According to the 

National Occupational Exposure Survey (NOES), in 1989, 681,780 workers (231,208 of whom were 

female) were estimated to be exposed to ammonia (NOES 1989). A correlation of data from the EPA Air 

Toxics Emission Inventory with industrial source codes (SIC codes) shows that volatile emissions of 

ammonia are associated with 212 different industrial classifications (EPA 1987b). 

Workers in swine- and poultry-confinement buildings may be exposed to elevated levels of ammonia 

(Attwood et al. 1987; Crook et al. 1991; Donham and Popendorf 1985; Jones et al. 1984; Leonard et al. 

1984; Liao and Bundy 1995). Average ammonia concentrations in the air of these buildings depend on 

numerous factors; representative values ranged from 0.28 to 42.2 ppm (280–42,200 ppb) (Attwood et al. 

1987; Fangmeier et al. 1994), but in buildings with slow ventilation rates, concentrations exceeded 

80 ppm (Liao and Bundy 1995). It should be noted that workers in these buildings may also be exposed 

to other materials in addition to ammonia, including particulate material (small dessicated manure 

particles), endotoxin, and others which may lead to combined exposures. 

Ammonia levels in air at an ammonium phosphate fertilizer-production plant ranged from 3 to 75 ppm 

(3,000–75,000 ppb) (NIOSH 1987). In a Finnish plywood factory, short-term ammonia concentrations 

during the mixing of urea-formaldehyde glue were 50–70 ppm (50,000–70,000 ppb) (Kauppinen 1986). 

Ammonia concentrations at 42 facilities using a blue-line printing system were 1–40 ppm (1,000– 

40,000 ppb) (Tuskes et al. 1988). Workers at coal-gasification units may be exposed occupationally to 

ammonia (Jin et al. 1999; Van Hoesen et al. 1984). Workers at ammonia transportation and storage 

facilities can be exposed to ammonia during the transfer between facilities, from the venting of built-up 

pressure in tanks, and during leaks or spills. 

Farmers can be exposed to ammonia when applying fertilizer. The ammonia concentration over a field 

during the application of gaseous anhydrous ammonia fertilizer was as high as 213 μg/m3

 (300 ppb) 

(Denmead et al. 1982). Workers at cattle production facilities (e.g., feedlots, farms) and those who work 

under conditions where volatilization from animal excreta would be enhanced may be occupationally 
AMMONIA 145 

6. POTENTIAL FOR HUMAN EXPOSURE 

exposed to ammonia. Over cattle feedlots, atmospheric ammonia concentrations have been measured at 

373–1,540 μg/m3

 (520–2,160 ppb) (Hutchinson et al. 1982). Exposure to ammonia can occur by 

inhalation in the liquid manure-storage facilities of swine-confinement buildings. Ambient air levels have 

been measured at up to 50 ppm (50,000 ppb) in these facilities (Donham et al. 1982). 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Three recent studies focused on the exposure of children to ammonia or the effects that exposure may 

have on children, all of which noted little effect on the children’s health (Gomzi 1999; Gomzi and Saric 

1997; Suh et al. 1992). One of the studies focused on the respiratory effects among people living near a 

fertilizer plant, another study investigated the effects of living in an urban vs. rural area, and a third study 

investigated the general effects of acid aerosols on children living in a semi-rural area. In general, these 

studies noted that exposure to low levels of ammonia had very little impact on the health of the children. 

The studies did find that other factors, such as parental smoking, had more profound effects on the 

children’s respiratory health. 

One study compared the effects of living near a fertilizer factory on the respiratory health of 8–9-year-old 

children (Gomzi and Saric 1997). The study found that the air quality near a fertilizer plant was within 

acceptable limits for most of the measurement period, with only a few fluctuations beyond acceptable 

limits. While these fluctuations correlated somewhat with health parameters measured on children living 

nearby, the rate of respiratory disease was more influenced by indoor air pollution sources than by 
AMMONIA 146 

6. POTENTIAL FOR HUMAN EXPOSURE 

outdoor sources. No significant effect was observed due to exposure to ammonia at the concentrations 

seen in the study. 

A second study of 223 children (8–10 years old) living in Croatia found that indoor air quality had a 

slightly greater effect on respiratory health in urban areas compared to those living in rural areas (Gomzi 

1999). The differences, however, were not significant. The study found no influence of ammonia on the 

children’s respiratory health, but did find that parental smoking had a significant negative impact on their 

respiratory health. 

A third study evaluated SO4

2- and H+

 exposure to 24 children (ages were not provided) living in 

Uniontown, Pennsylvania (Suh et al. 1992). This study did not focus on ammonia exposure per se, but on 

other airborne contaminant concentrations in aerosols found outdoors, indoors, and by personal monitors. 

It sought to determine how personal exposures to these aerosols correlated with indoor and outdoor 

concentrations. Ammonia concentrations were measured in order to assess their potential for neutralizing 

H+

 found in aerosols. Ammonia concentrations were found to be highest near the children (detected by 

the personal monitors), followed by indoor concentrations, and were minimal outdoors. It was proposed 

that a large proportion of the H+

 found in indoor aerosols are neutralized by NH3, and would thus lower 

the children’s exposure to acid aerosols. The authors noted that more research is needed to fully model 

the influence of factors, including NH3, on indoor acid aerosol exposure. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Workers in industries that commonly use ammonia, especially if there are no adequate safety and/or 

venting systems, may be at risk for potentially high exposure to ammonia. Examples of these might 

include farm workers who are employed in inadequately-ventilated, enclosed spaces with high 

concentrations of animals. Other examples include workers who process ammonia or transfer it from 

shipping containers to pipelines. The general population is at risk to high levels of exposure if cleaning 

products containing concentrated solutions of ammonia are used in small, enclosed, or unventilated 

rooms. 
AMMONIA 147 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of ammonia is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of ammonia. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of ammonia have all 

been well documented, and there do not appear to be any data needs in this area. 

Production, Import/Export, Use, Release, and Disposal. The large amounts of ammonia 

produced in nature and in household products indicate that the risk for human exposure to ammonia 

exists. Data regarding the commercial production, disposal, and use of ammonia are well understood. 

Data regarding the production of ammonia by natural organisms, and its global and regional 

concentrations are not as well understood, nor are the influences of different process strategies on 

livestock ammonia emissions. This information would be useful in determining the contribution of 

anthropogenic ammonia to the global budget of this compound, which would help in determining the 

human influence on the global cycle. 

According to the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA), (§313), 

(Pub. L. 99-499, Title III, 9313), industries are required to submit release information to the EPA. The 

TRI contains release information for 2001. This database is be updated yearly and provides a more 

reliable estimate of industrial production and emission. 
AMMONIA 148 

6. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. Since ammonia is a key intermediate in the nitrogen cycle, the environmental 

fate of ammonia should be interpreted in terms of its involvement in this cycle. Information available on 

the environmental fate of ammonia is sufficient to define the basic trends, and data are available regarding 

the direction of changes in these trends resulting from changes in the key variables. There are many 

subtle facets of the fate of ammonia in the environment that depend on nature and its cycles. Thus, 

accurately predicting the environmental fate of ammonia is not possible with our present knowledge. 

An understanding of the environmental fate of ammonia is important when considering that human 

contribution to the global ammonia budget has grown over the years. A complete understanding of the 

environmental fate of ammonia will then allow an understanding of any changes that might occur from 

the role of ammonia in the nitrogen cycle. Since all living organisms depend on the nitrogen cycle, either 

directly or indirectly, this information would allow any decisions concerning ammonia to be made in an 

informed and prudent manner. 

Bioavailability from Environmental Media. The bioavailability of ammonia from air and water 

has been examined rather extensively in animals. Bioavailability from soil has not been studied, although 

it is not a likely source of exposure. 

Food Chain Bioaccumulation. Ammonia is a naturally-occurring compound and a key 

intermediate in the nitrogen cycle. Since it is continually recycled in the environment, bioaccumulation, 

as it is usually considered, does not occur. Thus, data on this process are not warranted. 

Exposure Levels in Environmental Media. As an intermediate in the nitrogen cycle, ammonia is 

naturally present in environmental media. Measurements of ammonia in environmental media are 

sufficient to distinguish between background concentrations and elevated concentrations. Data regarding 

ammonia levels in soil samples, however, appear not to be as complete as the database for air and water. 

Determining low level concentrations of atmospheric ammonia in the presence of ammonium salts is 

difficult. Recently, investigators have been establishing new methods for the analysis of ammonia in the 

presence of ammonium compounds (see Chapter 7, Analytical Methods). If highly accurate values for 

low levels of ammonia are necessary, then a re-evaluation of older literature values might be necessary. 

Exposure Levels in Humans. Data regarding the exposure levels of ammonia are sufficient for 

understanding the sources and approximate magnitudes of human exposure. Quantitative monitoring data 
AMMONIA 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

for specific circumstances, occupations, or events, as reported in the current literature, might be 

considered to be lacking. Monitoring data for ammonia concentrations in the average household are 

generally adequate. Reports indicate that while background indoor concentrations of chemicals such as 

ammonia are sometimes higher inside than outside the home, the levels of exposure do not generally have 

effects on residents. This exposure, however, would be expected to be higher when ammonia-containing 

cleaning products are used, or when other ammonia-containing compounds are used in the household, and 

effects under these conditions would depend on the exposure concentration and duration. 

Exposures of Children. Data regarding the exposure levels of ammonia to children were not 

extensive enough for evaluating the sources and approximate exposures to children. As was found with 

data in the section for Exposure Levels in Humans above, quantitative monitoring data might be 

considered lacking. A few recent studies indicate that exposures to, and effects of, ammonia on children 

are generally minimal, and do not influence the respiratory health of the children studied. However, more 

studies could be conducted to verify these findings. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2 Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for ammonia were located. This compound is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry (Agency for Toxic Substances and Disease Registry 1999). The compound will be considered in 

the future when chemical selection is made for subregistries to be established. The information that is 

amassed in the National Exposure Registry facilitates the epidemiological research needed to assess 

adverse health outcomes that may be related to exposure to this compound. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2003) database and Current Research Information System 

(CRIS) database (USDA 2003) provide additional information obtainable from a few ongoing studies that 

may fill some of the data needs identified in Section 6.8.1. These studies are summarized below and in 

Table 6-2. Most of the studies are investigating approaches that reduce exposures to ammonia, emissions 

of ammonia during agricultural practices, and novel systems to reduce those emissions. 
AMMONIA 150 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Ongoing Studies on Environmental Fate and the Potential for 

Human Exposure to Ammonia 

Investigator Affiliation Research description Sponsor 

Bazemore RA; 

Chen TC 

Harper LA; 

Sharpe RR 

Hristov AN 

Walsh JL Jr. 

Mississippi 

State 

University 

ARS, Athens, 

Georgia 

University of 

Idaho 

Georgia 

Institute of 

Technology 

Wilhelm LR et al. University of 

Tennessee at 

Knoxville 

Evaluation of effectiveness of five substances Hatch 

(copper chlorophyllin complex, chitosan, 

activated carbon, kenaf, and paper mill sludge) 

in reducing ammonia emissions from animal 

waste compost. 

Investigation of the generation and deposition of USDA 

ammonia aerosols from swine waste, which is in-house 

then compared to meteorological fluxes, with the 

objective being to reduce short-term and longterm ammonia losses that affect the local 

environment.

This proposal seeks, through dietary means, NRI comp. 

better capture of ruminal ammonia-nitrogen into grant 

microbes and consequently into milk. This will 

increase the efficiency of utilization of feed N 

and reducing N excretions in the dairy cow. 

The objective is to develop an integrated-optics U.S. DOE 

(IO) sensor capable of measuring gaseous 

ammonia concentrations in the range of 

100 ppb. This will be used to measure losses

from agricultural croplands after application of 

nitrogen fertilizers. 

Emission data and production information will be Hatch 

gathered from facilities country-wide for poultry 

and swine buildings. Evaluation of factors 

related to ammonia emissions will be conducted, 

and cost-effective approaches for reducing 

emissions considered and evaluated. 

Source: CRIS 2003; FEDRIP 2003 

ARS = Agricultural Research Service; NRI = National Research Institute; USDA = U.S. Department of Agriculture; 

U.S. DOE = U.S. Department of Energy 
AMMONIA 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

Several studies are being conducted to lessen exposures to ammonia. Researchers at the University of 

Kentucky are investigating methods to reduce emissions of ammonia from poultry houses by improving 

manure handling. In a different approach, researchers at the University of Idaho are investigating changes 

in animal diet as a means to improve the abilities of livestock to more completely incorporate ruminal 

ammonia nitrogen into milk and protein. If successful, both will result in lower exposures to excreted 

ammonia. Furthermore, both approaches will lead to more knowledge regarding the efficient 

transformation of ammonia into useful products, either compostable manure or food products. 

A considerable number of studies are being conducted to provide better determinations of atmospheric 

transport and deposition of ammonia, either on a local scale or a global scale, and for reducing ammonia 

effluents from animal waste. The U.S. Department of Agriculture (USDA) at Watkinsville and Athens, 

Georgia, in conjunction with the University of Tennessee at Knoxville, is investigating approaches to 

reduce ammonia emissions from poultry, dairy, and swine facilities, with the objective being to reduce 

short- and long-term ammonia losses that affect indoor and outdoor air quality. The USDA in 

Fayetteville, Arkansas is testing different approaches to reduce ammonia emissions from poultry, swine, 

and dairy facilities via evaluation of the efficacy of alum treatments. Other research efforts being 

conducted by the USDA include the evaluation of the best use and application practices of animal 

manures that contain ammonia to reduce emissions and favor nutrient transfer to crop soils. Mississippi 

State University researchers are evaluating the quality of poultry effluents and swine litter for use as 

manure-based fertilizers for crops, wherein the efficiency of manure nutrient (including ammonia) 

transfer to the crop soils is being evaluated. Research is also being conducted at Mississippi State 

University to evaluate the use of cellulosic materials (i.e., kenaf) to decrease ammonia and odor emissions 

from poultry waste. Kenaf has several attractive characteristics as a biosorbent for ammonia, and is 

therefore being evaluated for the removal of odors and ammonia from waste streams. In another study 

being conducted at Mississippi State University, five treatments (copper chlorophyllin, chitosan, activated 

carbon, kenaf, and paper mill sludge) are being compared for their effects on reducing emissions from 

poultry litter. The findings indicate that the materials have different efficiencies for reducing overall odor 

emissions, but no report has been provided about their specific effects on ammonia emissions. 

AMMONIA 153 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring ammonia, its metabolites, and other biomarkers of exposure and effect to 

ammonia. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to 

identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

When ammonia is found in biological materials at physiological pH (7.2), most of it (99%) will be found 

as ammonium ion, due to its pKa of 9.2. This is an important consideration for any subsequent analysis. 

The determination of ammonia (as dissolved NH3 and ammonium ion) in blood, plasma, or serum is of 

value in detecting existing or impending hepatic coma and Reyes Syndrome (Meyerhoff and Robins 

1980; Tietz 1970). The determination of ammonia in urine had historically been used as an indicator of 

the kidney's ability to produce ammonia; however, this procedure has been replaced by more modern and 

accurate tests for kidney function. Procedures for the determination of ammonia in biological samples are 

found in Table 7-1. Ammonia is also tested for in calculi (abnormal concretions in the body formed of 

mineral deposits, often found in the gall bladder, kidney, or bladder) (Tietz 1970); however, the test 

described therein is not quantitative and is not included in Table 7-1. 

The amount of ammonia in collected blood, urine, saliva, or other biological fluid samples can be affected 

by several mechanisms that may lead to erroneous ammonia concentration determinations. These effects 

can be minimized by proper sample storage and handling. The ammonia content of freshly drawn blood 

rises rapidly on standing because of the deamination of labile amides such as glutamine (Henry 1964); at 

room temperature, the ammonia content can increase by a factor of two or three in several hours. 

Therefore, it is important to both keep the specimen cold (on ice) and perform the analysis as soon as 

possible. If the sample cannot be analyzed quickly, it may be frozen (-20 °C). The ammonia content of 
AMMONIA 154 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Ammonia in Biological Samples 

Sample Analytical Sample 

matrix Preparation method method detection limit 

Urine 24-Hour specimen, add Colorimetric Not reported 

HCl, refrigerate (Berthelot 

reaction) 

Urine 24-Hour specimen Indophenol Not reported 

analyzed immediately, or reaction 

stored up to 8 weeks at 

-20 °C 

Saliva Freeze at -20 °C for up to Membrane Not reported 

2 weeks, or store for 1 hour based 

at 4 °C, or analyze ammoniaimmediately selective 

electrode 

Serum, Freeze, then store at -15 °C Colorimetric Not reported 

plasma, for several days, or store assay based 

whole blood on ice (4 °C) for 30– on indophenol 

60 minutes, or analyze production 

immediately 

Serum, Freeze, then store at -15 °C Titration Not reported 

plasma, for several days, or store 

whole blood on ice (4 °C) for 30– 

60 minutes, or analyze 

immediately 

Serum, Freeze at -30 °C or store Membrane Not reported 

plasma, on ice, or analyze based 

whole blood immediately ammoniaPercent 

recovery Reference 

Not reported Tietz 1970 

Not reported Huizenga et 

al. 1994 

Not reported Huizenga et 

al. 1994 

Not reported Huizenga et 

al. 1994 

Not reported Huizenga et 

al. 1994 

-7.0–14% error, Meyerhoff 

102% average and Robins 

recovery 1980 

selective 

electrode 
AMMONIA 155 

7. ANALYTICAL METHODS 

iced (4 °C) blood samples remains constant for up to 60 minutes, whereas the ammonia content of frozen 

(-20 °C) blood samples remains constant for several days (Huizenga et al. 1994; Tietz 1970). For blood 

samples collected from a healthy person (and stored on ice), the ammonia content should be measured 

within 30–60 minutes of collection. For persons suspected of suffering from liver disease, however, the 

blood samples should be analyzed within 15 minutes (Huizenga et al. 1994). This more rapid assessment 

is necessary because some liver diseases result in high levels of γ-glutamyl transferase, an enzyme that 

hydrolyzes glutamine; the enzyme’s activity will increase the concentration of ammonia in the sample to 

levels higher than was present at the time of collection (Huizenga et al. 1994). Other erroneously high 

measured ammonia levels can result from ammonia contamination of reagents or pick-up of ammonia 

from the atmosphere, including from technicians that have recently smoked a cigarette (Huizenga et al. 

1994). The presence and activities of bacteria in samples can also cause changes in the concentrations of 

ammonia. The natural presence of bacteria present in some samples (e.g., saliva) or their presence in 

infected tissues (e.g., bladder infections) can lead to erroneously high ammonia concentrations, due to the 

presence of bacterial ureases that hydrolyze urea present in the biological samples. This reaction is the 

chief cause for the formation of ammonia in unacidified urine on standing (Henry 1964). Furthermore, 

contamination of samples by environmental bacteria following the collection of the sample may also lead 

to increases in ammonia concentrations. Therefore, use of sterile collection bottles for sample collection 

and storage is recommended if there is potential for storage of the sample prior to analysis (Huizenga et 

al. 1994). 

In the determination of ammonia or ammonium ion in biological samples, ammonia is first liberated by 

distillation, aeration, ion-exchange chromatography, microdiffusion, or deproteinization (Huizenga et al. 

1994). Deproteinization methods involve treatment of blood or plasma fluids with trichloroacetic acid (or 

perchloric acid or tungstate-sulfuric acid), followed by centrifugation. The protein-free supernatant can 

be assayed colorimetrically for ammonia. Traditionally, Kjeldahl distillation methods have been used to 

determine ammonia levels in biological tissue, but other methods (e.g., colorimetric or ion-specific 

electrodes) are also available. In the Kjeldahl distillation, ammonia is distilled and subsequently trapped 

in acid and analyzed titrametrically or colorimetrically. High values sometimes result because of the 

cleavage of protein amino groups and also the formation of ammonia by deamination reactions (Parris 

and Foglia 1983). Other techniques use the ammonia-selective electrode and enzymatic assays. 

Discrepancies have been reported between results using electrodes and those using more specific 

enzymatic procedures because the ammonia electrode responds to both ammonia and volatile amines 

(Parris and Foglia 1983). Chromatographic separation of ammonia and volatile amines after 

derivatization has also been used to obtain specificity (Huizenga et al. 1994; Parris 1984). Ammonia in 
AMMONIA 156 

7. ANALYTICAL METHODS 

urine has been measured by Nesslerization, as well as by enzymatic assays and chromatographic 

approaches (Huizenga et al. 1994). 

7.2 ENVIRONMENTAL SAMPLES 

Water and waste water samples can be analyzed for ammonia by EPA Test Methods 1689 (EPA 2001a), 

1690 (EPA 2001b), and 349.0 (EPA 1997). Analogous procedures (i.e., Method APHA 4500) have been 

approved and published jointly by the American Public Health Association, American Water Works 

Association, and Water Pollution Control Association. These methods are suitable for drinking, surface, 

and saline waters, and domestic and industrial effluent, and can be applied to biosolids. These and other 

methods for determining ammonia in environmental samples are listed in Table 7-2. Ammonia is 

reported as ammonia nitrogen. Two methods that are suitable for water employ colorimetric techniques, 

Nesslerization, and phenate methods. Nessler's reagent, an alkaline mixture of mercuric and potassium 

iodide, produces a yellow to brown color with ammonia, whereas the phenate reagent, alkaline phenol, 

and hypochlorite produce a blue color (EPA 2001a, 2001b; Greenberg et al. 1985). In the titrimetric 

method, the distillate is titrated with standard sulfuric acid with an appropriate indicator. The ammonia 

electrode employs a hydrophobic gas-permeable membrane to separate the sample solution from an 

internal ammonium chloride solution: ammonia diffusing through the membrane changes the pH of the 

internal solution and is sensed by a pH electrode. For determining NH3-N concentrations above 5 mg/L, 

the titrimetric and ammonia-selective electrode methods are preferred. In contrast, gas chromatography/ 

mass spectrometry methods have been developed that permit NH3 detection at concentrations near 

20 μg/L for environmental waters (Mishra et al. 2001). Methods for determining ammonia in water and 

soil measure ammoniacal nitrogen, the sum of NH3 and NH4

+

. In the determination of ammoniacal 

nitrogen in soil, exchangeable ammonium should be distinguished from nonexchangeable ammonium. 

The former is usually defined as that which can be extracted with KCl (or K2SO4) at room temperature 

(Bremner 1965). Nonexchangeable ammonium ion is defined as nitrogen held by clays and not displaced 

by 2M KCl (Bremner 1965). In the determination of nonexchangeable ammonium, organic forms of 

ammonia are first removed, the minerals containing the nonexchangeable ammonium are then 

decomposed with HF, and the ammonium ions released. In colorimetric procedures, turbidity and sample 

color may lead to interference. To eliminate interference, the pH of the sample may be raised and the 

ammonia distilled. Care should be taken to prevent losses in water samples due to volatilization and 

microbial transformation. To prevent such losses, samples should be acidified soon after collection and 

refrigerated. Care should also be taken during storage and treatment of soil samples to prevent ammonia 
AMMONIA 157 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Ammonia in Environmental 

Samples 

Sample 

matrix 

Preparation 

method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference

Air Passive collection Method 6701, ion No bias between 

using 0.01 N H2SO4 chromatography, 6.9 and 48 ppm; 

in liquid sorbent conductivity +19% at 

badge detection 148 ppm 

1 μg 

NH3/sample 

NIOSH 

1987 

Air Air samples from 

stack emissions 

collected through an 

in-stack filter to 

remove particulates 

and ammonium 

salts, and then 

bubbled through 

0.1 N H2SO4 

EPA Method 30; 

ion chromatography 

1 μg 

NH3/sample 

98.5±1.3%; Bias 

of 0.996 ppm for 

a spiked sample 

of 6.43 ppm. 

Correction factor 

of 0.87 needs to 

be applied 

Eaton et al. 

1996 

Air 0.8 μm prefilter may 

be used; ammonia 

trapped on sulfuric 

acid silica gel 

NIOSH method 

6015, Colorimetric 

determination of 

indophenol by 

visible light 

spectrophotometry 

0.5 μg 

NH3/sample 

Not determined NIOSH 

1994 

Air 0.8 μm prefilter may 

be used; ammonia 

trapped on sulfuric 

acid silica gel 

NIOSH method 

6016. Ion 

chromatography 

2 μg 

NH3/sample 

102±3.8% NIOSH 

1996 

Air Chromatomembrane 

cells preextract and 

preconcentrate 

sample 

Ion chromatography with 

conductivity 

detection 

6 μg 

NH3/sample 

Not reported Erxleben et 

al. 2000 

Air Collection in H2SO4-

coated activated 

carbon beads in 

sampling tube 

Ion chromatography 2 μg 

NH3/sample 

95–110% 

recovery 

Bishop et 

al. 1986 

Air Known volume of air 

drawn through 

prefilter and H2SO4-

treated silica gel 

NIOSH S347, 

ammonia-specific 

electrode 

Not reported 97.6% mean 

recovery 

SRI 1988 

Water Sample mixed with 

borate buffer 

Method 1689, ion 

selective probe 

0.1 mg/L Not reported EPA 2001a 
AMMONIA 158 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Ammonia in Environmental 

Samples 

Sample Preparation Analytical Sample 

matrix method method detection limit 

Water Sample collected, Method 1690, 0.2 mg/L 

preserved with colorimetric 

H2SO4, and chilled determination of 

to 4 °C. Samples indophenol blue, 

should not be stored following reaction 

for >28 days of any ammonia 

with alkaline 

phenol and hypochlorite 

Water None Method 350.1 0.1 mg/L 

colorimetric, 

automated 

phenate 

Estuarine and Samples filtered Method 349.0, 0.3 μg/L 

coastal water through 0.45 μm automated 

membrane filter, colorimetric 

refrigerated and determination by 

analyzed within reactions that form 

3 hours indophenol blue 

Water Removal of residual Method 350.2 0.05 mg N/L for 

chlorine with sodium Nessier reagent, colorimetric and 

thiosulfate, colorimetric, potentiometric; 

distillation titrimetric; or 1.0 mg N/L for 

ammonia specific titrametric 

electrode 

Water None Method 350.3 ion 0.03 mg N/L 

selective electrode 

Soil, exchange- Extract soil with 2N Method 84-3, Not reported

able KCl steam distillation 

ammonium with MgO, titration 

Soil, non- Pretreat soil with Method 84-7, Not reported

exchangeable KOBr-KOH, shake steam distillation 

(fixed) with 5 N HF-1N HCl with KOH, titration 

ammonium for 24 hours 

Percent 

recovery 

Not reported 

107 and 99% 

recoveries at 

0.16 and 

1.44 mg 

NH3-N/L, 

respectively 

92.2–109.1% 

recovery, n=14 

28.12 to -0.46R 

bias between 

0.21 and 

1.92 mg N/L 

96 and 91% 

recoveries at 

0.19 and 

0.13 mg N/L, 

respectively 

Not reported 

Not reported 

Reference 

EPA 2001b 

EPA 1983 

EPA 1997a 

EPA 1983 

EPA 1983 

Bremner 

1965 

Bremner 

1965 
AMMONIA 159 

7. ANALYTICAL METHODS 

loss or gain. It has been demonstrated that dry soil can rapidly adsorb trace amounts of ammonia from the 

atmosphere and that extensive amounts of ammonia can be lost during air drying (Bremner 1965). 

Additionally, in samples containing both ammonium and nitrite, losses during air drying may occur due to 

the reaction between these ions and the resulting formation and release of nitrogen gas (Bremner 1965). 

The detection limit of analytical methods for determining ammonia in air depends on the amount of air 

collected in a liquid or solid adsorbent. Sampling is performed with passive samplers or by drawing a 

volume of air through the adsorbent using a pump. Particulate contaminants such as ammonium salts 

may be removed by a prefilter. For determination of ammonia in the ambient atmosphere, larger volumes 

of air must be sampled than those appropriate for determinations of ammonia in occupational settings 

(e.g., industrial, agricultural) where ammonia levels are higher. Improvements in methodologies have led 

to development of techniques that permit continuous monitoring of atmospheric ammonia down to 

0.1 μg/m3

 (Pranitis and Meyerhoff 1987). Several passive monitoring systems report detection limits of 

0.05–1.0 μg/m3

 and have collection rates ranging from 2.7 to 2,000 mL/minute (Kirchner et al. 1999). 

One method used for ambient atmospheric sampling employs a specially designed flow-through, 

ammonia-selective electrode with a sniffer tube, whereas the methods used for occupational settings often 

use passive collectors with media (usually acids impregnated onto filters) housed within protective cases. 

Ammonia concentrations on these passive collectors are then determined by a wide range of methods, 

including colorimetric assays (e.g., indophenol determination), the Berthelot reaction, or ion 

chromatography (Kirchner et al. 1999). 

Ammonia may be present in air in both the vapor phase as ammonia gas and in the particulate phase as 

ammonium salts. While some analytical methods may distinguish between these phases, most standard 

methods do not. Methods have been developed that determine gaseous ammonia alone or gaseous and 

particulate forms of ammoniacal nitrogen separately. These methods use filter packs or sampling tubes 

coated with a selective adsorbent (denuder tube) to separate the phases (Dimmock and Marshall 1986; 

Knapp et al. 1986; Rapsomanikis et al. 1988). In these methods, gaseous ammonia is trapped by acids 

that act as adsorbents (e.g., citric acid, oxalic acid, phosphoric acid) on a coated filter or denuder tube 

(Kirchner et al. 1999). In filter methods, errors may arise due to ammonia interactions occurring on the 

filter and volatilization of retained ammonium salt (Dimmock and Marshall 1986; Rapsomanikis et al. 

1988). There is evidence that ammonium nitrate in particulate matter is in equilibrium with ammonia. 

The presence of ammonium nitrate may lead to overestimation of the actual concentration of ammonia, 

but underestimation of the concentration of ammonium (Doyle et al. 1979). For additional review of the 
AMMONIA 160 

7. ANALYTICAL METHODS 

methodologies for determining ammonia in water and air, see MacCarthy et al. (1987) and Fox (1987), 

respectively. 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of ammonia is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of ammonia. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. No known unique biomarkers 

for exposure or effects exist for ammonia. Until one has been identified, methodology for the 

determination of biomarkers must be preceded by an experimental determination of a unique biomarker of 

human exposure or effect. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods for determining ammoniacal nitrogen in environmental media are well developed and 

adequate. Standardized methods are available from EPA, NIOSH, and other sources. Analytical methods 

are also well developed for oxidation products of ammonia. Since there are multiple sources of these 

compounds in the environment, their analysis is not generally used to study the disappearance of 

ammonia. 
AMMONIA 161 

7. ANALYTICAL METHODS 

7.3.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2003) database provides additional information obtainable 

from a few ongoing studies that may fill some of the data needs identified in Section 7.3.1. These studies 

are summarized below and in Table 7-3. By and large, most of the studies that were reported were related 

to the detection and measurement of atmospheric ammonia concentrations. Many of these focused on the 

development of novel sensor devices, which would provide better data for estimating ammonia emission 

and deposition rates. A company in Atlanta, Georgia is developing an optical ammonia sensor to measure 

agricultural emissions. This sensor is capable of detecting ammonia concentrations at the 100 ppb range 

and above. Similarly, the Georgia Institute of Technology is developing an optical sensor that will permit 

measurements of ammonia in the atmosphere at the 100 ppb range. Another company in Burlington, 

Massachusetts is developing a diode laser absorption remote sensor for measuring ammonia at trace 

concentrations, but no detection ranges have been specified. Another company in Massachusetts is 

developing a solid-state electrochemical sensor that is based on ionomer (i.e., an ion-containing polymer) 

membrane technology. This technology, however, is not intended for atmospheric ammonia sampling, 

but for instrument monitoring where ammonia gas may have negative impacts. This particular 

application seeks to produce these monitors for use in fuel cell systems, where free ammonia can 

negatively impact performance. 
AMMONIA 162 

7. ANALYTICAL METHODS 

Table 7-3. Ongoing Studies on the Development of Analytical Approaches to the 

Study of Ammonia 

Investigator Affiliation Research description Sponsor 

Attar AJ Perfect View, Inc., 

Raleigh, North 

Carolina 

Edwards J Photonic Sensors, 

Atlanta, Georgia 

Goldstein N Spectral Sciences, 

Burlington, 

Massachusetts 

Laconti AB Giner, Inc., 

Waltham, 

Massachusetts 

Ozanich RM Northwest Instrument 

Systems, Richland, 

Washington 

Walsh JL Jr. Georgia Institute of 

Technology, 

Atlanta, Georgia 

Development of a low-cost ammonia detector 

(a small detector panel, about the size of a 

credit card, that changes color in response to 

ammonia in the atmosphere) for use in animal 

production facilities. 

Development of an optical ammonia sensor to 

measure agricultural emissions. This sensor 

is capable of detecting ammonia 

concentrations at the 100 ppb range. 

Development of a diode laser absorption 

sensor for measurement of trace 

concentrations of ammonia, for potential 

applications in atmospheric chemistry and 

pollution monitoring. 

Development of a solid-state electrochemical 

sensor that is based on ionomer membrane 

technology for instrument monitoring where 

ammonia gas may have negative impacts. 

Development of an online system for 

analyzing ammonia (and other nitrogen 

containing chemicals) in water systems. 

Development of an optical ammonia sensor to 

measure agricultural emissions. This sensor 

is capable of detecting ammonia 

concentrations at the 100 ppb range, and 

would be useful for real-time monitoring of the 

injection of anhydrous ammonia fertilizer onto 

crops. 

SBIR 

Cooperative 

Agreement 

U.S. DOE 

SBIR 

SBIR 

U.S. DOE 

Source: FEDRIP 2002, 2003 

SBIR = Small Business Innovative Research; U.S. DOE = U.S. Department of Energy
AMMONIA 163 

8. REGULATIONS AND ADVISORIES 

International guidelines for ammonia were not located. National and state regulations and guidelines 

pertinent to human exposure to ammonia are summarized in Table 8-1. 

ATSDR has derived an acute-duration inhalation MRL of 1.7 ppm for ammonia based on a minimal 

LOAEL of 50 ppm for eye, nose, and throat irritation in a study with volunteers (Verberk et al. 1977). No 

NOAEL was identified in that study. An uncertainty factor of 30 (3 for the use of a minimal LOAEL and 

10 to protect sensitive individuals) was applied to the LOAEL. 

ATSDR has derived a chronic-duration inhalation MRL of 0.1 ppm for ammonia based on a NOAEL of 

9.2 ppm for sense of smell, prevalence of respiratory symptoms (cough, bronchitis, wheeze, dyspnea, 

etc.), eye and throat irritation, and pulmonary function parameters in workers exposed for approximately 

12 years in a soda ash plant (Holness et al. 1989). No LOAEL was defined in that study. The NOAEL 

was duration-adjusted, and divided by an uncertainty factor of 10 to protect sensitive individuals. A 

modifying factor of 3 was added for the lack of reproductive and developmental studies. This MRL 

supersedes the previous chronic inhalation MRL of 0.3 ppm derived in the 2002 draft for public comment 

version of this profile. 

EPA derived an inhalation reference concentration (RfC) of 1E-1 mg/m3

 (0.14 ppm) for ammonia based 

on a NOAEL of 6.4 mg/m3

 (9.2 ppm) defined in the Holness et al. (1989) study (IRIS 2004). EPA used 

an uncertainty factor of 30 (10 to protect sensitive individuals and 3 for data base deficiencies). 

Ammonia has not undergone a complete evaluation under EPA’s IRIS program for evidence of human 

carcinogenic potential. 

Ammonium ion is regulated by the Clean Water Effluent Guidelines for the following industrial point 

sources: ferroalloy manufacturing; fertilizer manufacturing; glass manufacturing; inorganic chemicals; 

iron and steelmaking; landfills; nonferrous metals manufacturing; nonferrous metals forming and metal 

powder; paper and paperboard; petroleum refining; pharmaceutical manufacturing; pulp, meat products; 

and transportation equipment cleaning (EPA 2002j). 
AMMONIA 164 

8. REGULATIONS AND ADVISORIES 

The FDA (1973) determined that concentrations of ammonia and ammonium compounds normally 

present in food do not suggest a health risk; ammonia and ammonium ions are recognized to be integral 

components of normal metabolic processes. However, some restrictions have been placed on levels of 

ammonium salts allowable in processed of foods. Maximum allowable levels in processed foods are as 

follows: 0.04–3.2% ammonium bicarbonate in baked goods, grain, snack, foods and reconstituted 

vegetables; 2.0% ammonium carbonate in baked goods, gelatins and puddings; 0.001% ammonium 

chloride in baked goods and 0.8% in condiments and relishes; 0.6–0.8% ammonium hydroxide in baked 

goods, cheeses, gelatins and puddings; 0.01% monobasic ammonium phosphate in baked goods; and 

1.1% dibasic ammonium phosphate in baked goods, 0.003% in nonalcoholic beverages, and 0.012% for 

condiments and relishes. 
AMMONIA 165 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Ammonia 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

IARC 

WHO 

NATIONAL 

Carcinogenicity classification 

Drinking water quality guideline 

Ammonia 

Threshold odor concentration 

Threshold taste concentration 

Health-based guideline 

Regulations and Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 

Ammonia 

Ammonium chloride fume 

STEL (15-minute TWA) 

Ammonia 

Ammonia chloride fume 

EPA Accidental release prevention; 

toxic endpoint 

Ammonia (anhydrous) 

Ammonia (>20% concentration) 

Regulated toxic substance for 

accidental release prevention 

under Section 112(r) of the Clean 

Air Act; threshold quantity 

Ammonia (anhydrous) 

Ammonia (>20% concentration) 

AEGL 1 (interim) 

NIOSH REL (10-hour TWA) 

Ammonia 

Ammonium chloride fume 

STEL (15-minute TWA) 

Ammonia 

Ammonium chloride fume 

IDLH 

Ammonia 

Ammonium chloride fume 

OSHA PEL (8-hour TWA) for general 

industry 

Ammonia 

No data 

1.5 mg/L 

35 mg/L 

None proposed 

25 ppm 

10 mg/m3 

35 ppm 

20 mg/m3 

0.14 mg/L 

0.14 mg/L 

10,000 pounds 

20,000 pounds 

30 ppm 

25 ppm 

10 mg/m3 

35 ppm 

20 mg/m3 

300 ppm 

No data 

50 ppm 

WHO 2002 

ACGIH 2001 

ACGIH 2001 

EPA 2002b 

40CFR68, 

Appendix A 

EPA 2002a 

40CFR68.130, 

Table 1 

EPA 2004 

NIOSH 2002b 

NIOSH 2002b 

NIOSH 2002b 

OSHA 2002d 

29CFR1910.1000, 

Table Z-1 
AMMONIA 166 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Ammonia 

Agency Description Information References 

NATIONAL (cont.) 

OSHA PEL (8-hour TWA) for construction 

industry 

Ammonia 

PEL (8-hour TWA) for shipyard 

industry 

Ammonia 

Highly hazardous chemical, toxic, 

and reactive for general industry; 

threshold quantitya 

Ammonia 

Ammonia solutions (>44% of 

ammonia by weight) 

Highly hazardous chemical, toxic, 

and reactive for construction 

industry; threshold quantitya 

Ammonia 

Ammonia solutions (>44% of 

ammonia by weight) 

Occupational safety and health 

standards; storage and handling 

of anhydrous ammonia 

Occupations involved in 

agriculture that are particularly 

hazardous for the employment of 

children below the age of 16 

Safety and health regulations for 

construction; blasting and use of 

explosives; common blasting 

agent is a mixture of ammonium 

nitrate and carbonaceous 

combustibles 

b. Water 

EPA Hazardous substance designated 

pursuant to Section 311(b)(2)(A) 

of the Clean Water Act 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

EPA Reportable quantity of hazardous 

substances designated pursuant 

to Section 311 of the Clean Water 

Act 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

50 ppm 

50 ppm 

10,000 pounds 

15,000 pounds 

10,000 pounds 

15,000 pounds 

Transporting, 

transferring, or applying 

anhydrous ammonia 

100 pounds 

5,000 pounds 

100 pounds 

1,000 pounds 

OSHA 2002c 

29CFR1926.55, 

Appendix A 

OSHA 2002a 

29CFR1915.1000 

OSHA 2002e 

29CFR1910.119, 

Appendix A 

OSHA 2002f 

29CFR1926.64, 

Appendix A 

OSHA 2002g 

29CFR1910.111 

OSHA 1998 

29CFR570.71(a)(11) 

OSHA 2002b 

29CFR1926.914(e) 

EPA 2002h 

40CFR116.4, 

Table A 

EPA 2002i 

40CFR117.3 
AMMONIA 167 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Ammonia 

Agency Description Information References 

NATIONAL (cont.) 

USC Assurances of availability of Ammonia 

adequate supplies of chemicals 

necessary for treatment of water 

c. Food 

EPA Residues from ammonium 

chloride, ammonium hydroxide, 

and ammonium sulfate are 

exempted from the requirement of 

a tolerance when used in 

accordance with good agricultural 

practice as inert (or occasionally 

inactive) ingredients in pesticide 

formulations applied to growing 

crops or to raw agricultural 

commodities after harvest 

Ammonium nitrate is exempt from 

the requirement of a tolerance 

when used in accordance with 

good agricultural practice as inert 

(or occasionally active) ingredients 

in pesticide formulations applied to 

growing crops only 

The fungicide ammonia is 

exempted from the requirement of 

USC 2002a 

42USC300j 

EPA 2002e 

40CFR180.1001(c) 

EPA 2002e 

40CFR180.1001(d) 

EPA 2002f 

40CFR180.1003 

FDA 2001a 

21CFR184.1138 

FDA 2001b 

21CFR184.1139 

FDA 2001c 

21CFR184.1143 

FDA 2001d 

21CFR310.545(a) 

FDA 2001e 

21CFR573.180 

FDA 2001f 

21CFR582.1139 

a tolerance when used after 

harvest on the raw agricultural 

commodities grapefruit, lemons, 

oranges, and corn grain for feed 

use only 

FDA Direct food substances affirmed 

as generally recognized as safe 

Direct food substances affirmed 

as generally recognized as safe 

FDA Direct food substances affirmed 

as generally recognized as safe 

Drug products containing certain 

active ingredients offered overthe-counter 

Expectorant drug product 

Fever blister and cold sore 

treatment drug product 

Ammonium chloride 

Ammonium hydroxide 

Ammonium sulfate 

Ammonium chloride 

Ammonia solution 

Ammonia solution and 

Insect bite and sting drug products Ammonium hydroxide 

Food additives permitted in feed Anhydrous ammonia 

and drinking water of animals 

Substance generally recognized Ammonium hydroxide 

as safe when used in accordance 

with good manufacturing or

feeding practices 
AMMONIA 168 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Ammonia 

Agency Description Information References 

NATIONAL (cont.) 

Substance generally recognized 

as safe when used in accordance 

with good manufacturing or 

feeding practices 

d. Other 

CPSC Federal Caustic Poison Act 

Ammonia water and any 

preparation containing free or 

chemically uncombined 

ammonia, including ammonium 

hydroxide and “hartshorn”, in a 

concentration of 5% or more 

EPA Ammonia 

Carcinogenicity classification 

RfC 

RfD 

CERCLA hazardous substance 

designated pursuant to 

Section 311(b)(4) of the Clean 

Water Act 

Reportable quantity 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

EPA Extremely hazardous substance 

Ammonia 

Reportable quantity 

Threshold planning quantity 

Toxic chemical release reporting; 

Community right-to-know; 

effective date for reporting 

Ammoniab 

Ammonium nitrate (solution) 

USC Imposition of Superfund tax on 

any taxable chemical sold by the 

manufacturer, producer, or 

importer 

Ammonia 

Refund or credit of Superfund tax 

paid when ammonia is used as a 

fertilizer 

Superfund taxable substance 

STATE 

Regulations and Guidelines: 

a. Air 

Ammonium sulfate FDA 2001g 

21CFR582.1143 

CPSC 2001 

16CFR1500.129(1) 

IRIS 2004 

No data 

1x10-1 mg/m3 

No data 

EPA 2002d 

40CFR302.4(a) 

100 pounds 

5,000 pounds 

100 pounds 

1,000 pounds 

EPA 2002c 

40CFR355, 

100 pounds Appendix A 

500 pounds 

EPA 2002g 

01/01/87 40CFR372.65(a) 

01/01/87c 

USC 2002d 

$2.64 per ton 26USC4661 

USC 2002b 

26USC4662 

Ammonium nitrate USC 2002c 

26USC4672 

No data 
AMMONIA 169 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Ammonia 

Agency Description Information References 

STATE (cont.) 

b. Water 

c. Food 

d. Other 

Florida Toxic substance 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium nitrate 

Ammonium sulfate 

Massachusetts Hazardous substance 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

Ammonium nitrate 

Ammonium sulfate 

Minnesota Hazardous substance 

Ammonia 

No data 

No data 

No data 

BLR 2002 

BLR 2002 

BLR 2002 

BLR 2002 

BLR 2002 

BLR 2002 

Ammonium chloride, fume 

New Jersey Hazardous substance 

Ammonia 

New York Hazardous substance 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

Pennsylvania Hazardous substance 

Ammonia 

Ammonium chloride 

Ammonium fluoride 

Ammonium hydroxide 

a

Potential for a catastrophic event at or above the threshold quantity. b

Ammonia: includes anhydrous ammonia, aqueous ammonia from water, dissociable ammonium salts, and other 

sources; 10% of total aqueous ammonia is reportable under this listing. c

Ammonium nitrate (solution) is removed from this listing; the removal is effective 07/02/95, for the 1995 reporting 

year.

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = acute exposure guideline value: 

BLR = Business & Legal Reports, Inc. CERCLA = Comprehensive Environmental Response, Compensation, and 

Liability Act; CFR = Code of Federal Regulations; CPSC = Consumer Protection Safety Commission; 

EPA = Environmental Protection Agency; FDA = Food and Drug Administration; IARC = International Agency for 

Research on Cancer; IDLH = immediately dangerous to life and health; IRIS = Integrated Risk Information System; 

NIOSH = National Institute of Occupational Safety and Health; OSHA = Occupational Safety and Health 

Administration; PEL = permissible exposure limit; ppm = parts per million; REL = recommended exposure limit; 

RfC = inhalation reference concentration; RfD = oral reference dose; STEL = short-term exposure limit; 

TLV = threshold limit value; TWA = time-weighted average; USC = United States Code; WHO = World Health

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AMMONIA 217 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 
AMMONIA 218 

10. GLOSSARY 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 
AMMONIA 219 

10. GLOSSARY 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(Lo) (LCLo)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(Lo) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a 

chemical is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 
AMMONIA 220 

10. GLOSSARY 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
AMMONIA 221 

10. GLOSSARY 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL, from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 
AMMONIA 222 

10. GLOSSARY 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed group. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The absorption, distribution, and elimination of toxic compounds in the living organism. 
AMMONIA 223 

10. GLOSSARY 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 

AMMONIA A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 
AMMONIA A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agency-wide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop F-32, Atlanta, Georgia 30333. 
AMMONIA A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Ammonia 

CAS Number: 7664-41-7 

Date: July 2004 

Profile Status: Third Draft Post-Public 

Route: [ X ] Inhalation [ ] Oral 

Duration: [ X ] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 14 

Species: Human 

Minimal Risk Level: 1.7 [ ] mg/kg/day [ X ] ppm

Reference: Verberk MM. 1977. Effects of ammonia in volunteers. Int Arch Occup Environ Health 

39:73-81. 

Experimental design: The study examined the effects of exposure to ammonia in a group of 

16 volunteers. Eight of them (experts) knew the effects of ammonia from the literature, but had had no 

personal contact, whereas the remaining eight subjects (non-experts) were students from a non-science 

faculty and were not familiar with ammonia or experiments in laboratory situations. All members of a 

group were exposed on the same day to one of the concentrations tested (50, 80, 110, or 140 ppm). The 

testing was repeated with a 1-week interval. Immediately before and after exposure, vital capacity, forced 

expiratory volume, and forced inspiratory volume were measured. During exposure, each subject 

recorded subjective feelings every 15 minutes as no sensation (0), just perceptible (1), distinctly 

perceptible (2), nuisance (3), offensive (4), or unbearable (5). No statistical analysis was performed and 

there was no group exposed to air only. A few weeks after the experiments, the subjects were tested to 

measure (pre-existing) non-specific reactivity of the airways to exogenous stimuli. 

Effects noted in study and corresponding doses: None of the participants was hypersusceptible to nonspecific irritants. Results of the pulmonary function tests after exposure were not statistically 

significantly different from pre-exposure values. For the non-experts, there was a clear increase in the 

number of reported symptoms for smell, eye irritation, throat irritation, cough, and general discomfort as 

the exposure concentration increased. The latter was not as clear for the experts. The number of 

symptoms recorded with a score >3 (nuisance) for smell, eye irritation, nose, throat, and urge to cough for 

the 50, 80, 110, and 140 ppm exposure groups was 2, 2, 7, and 11 , respectively, for the experts and 6, 12, 

18, and 29, respectively, for the non-experts. It should also be mentioned that the subjective responses 

appeared more pronounced in the non-expert group than in the expert group. 

Dose and end point used for MRL derivation: 50 ppm for mild irritation to the eyes, nose, and throat in 

humans exposed to ammonia gas for 2 hours. 

Because the effects observed were local irritation effects, they were not time-dependent (but rather 

concentration-dependent), an adjustment to 24-hour exposure was not necessary. 

[ ] NOAEL [ X ] LOAEL 
AMMONIA A-4 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ X ] 3 for use of a minimal LOAEL 

[ ] 10 for extrapolation from animals to humans 

[ X ] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? 

N/A 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

N/A 

Other additional studies or pertinent information which lend support to this MRL: Although the Verberk 

et al. (1977) study has limitations (no statistical analysis, subjective end points, no control group), it 

demonstrates that concentrations of 50 ppm ammonia can produce minimal discomfort in healthy 

members of the general population and therefore, should be avoided. Additional relevant information is 

provided by a study by Ferguson et al. (1977). In that study, a group of six healthy volunteers, not 

previously accustomed to working in an ammonia environment, were exposed 5 days/week to 25 ppm 

(2 hours/day), 50 ppm (4 hours/day), or 100 ppm (6 hours/day) of ammonia, or to 50 ppm of ammonia 

6 hours/day for 6 weeks. End points monitored included subjective and objective measures of eye and 

throat irritation as well as pulse rate, respiration rate, pulmonary function (FVC, FEV), assessment of 

neurological function (reflex, balance, and coordination), and body weight. The exposure protocol 

consisted of a pre-exposure evaluation by a physician, 3 hours of exposure (this conflicts with exposure 

data on table 2 of the study and mentioned above), a mid-point physician’s observation, lunch break, 

3 additional hours of exposure, and a third physician’s observation 30 minutes after exposure ceased. The 

conjunctiva and mucosa of the nose and throat were examined by a physician before and after each daily 

exposure and the degree of irritation noted was described as mild, moderate, or marked. Exposure to 

ammonia had no significant effect on the measures of respiratory function or in the neurological tests 

conducted. The results of the evaluations of irritation conducted by the physician showed no significant 

differences between the exposure groups, including the 0 ppm exposure group (pre-exposure). All 

subjects experienced some watering of the eyes and a sensation of dryness in the nose and throat and there 

was one observation of definite redness in the mucosa of the nose after a 6-hour exposure to 100 ppm 

during which time, there was an excursion to 200 ppm ammonia. No redness was observed in this subject 

the following morning. Throughout the study, the physician observed 6 cases of eye irritation, 20 of nose 

irritation, and 9 of throat irritation, and most cases appeared to have occurred the first week of the study 

during exposure to 50 ppm. It is difficult to determine in this study a NOAEL or LOAEL for irritation 

due to the different exposure durations experienced by the subjects, but it would appear that an exposure 

concentration of 100 ppm ammonia for 6 hours caused no significant changes in the vital functions 

measured and that 50 ppm can cause eye, nose, and throat irritation. 

NIOSH (1974) reviewed 15 studies of case reports in which subjects were exposed to very high, but 

unquantified, concentrations of ammonia. The 15 reports provided a representative array of documented 

clinical findings including death, permanent eye lesions, and chronic respiratory symptoms, as well as 

acute lower and upper respiratory symptoms. The only quantitative information available was that a 

worker died 6 hours after estimated exposure to 10,000 ppm ammonia for an unspecified time (Mulder 

and Van der Zalm 1967). Studies with volunteers, also reviewed by NIOSH (1974), generally used 

concentrations of ammonia much higher than those in the studies by Verberk et al. (1977) or Ferguson et 

al. (1977) and/or exposure durations of only minutes. For example, exposure to a concentration of 

500 ppm for 30 minutes caused respiratory irritation graded as severe by 2 out 7 subjects (Silverman et al. 

1949). Four out of 6 volunteers exposed to 50 ppm ammonia for 10 minutes graded the irritation as 

“moderate” and none described it as “discomforting” or “painful” (MacEwen et al. 1970). All of the 
AMMONIA A-5 

APPENDIX A 

subjects rated the odor as “highly penetrating” at 50 ppm and 3 subjects gave the same rating to 30 ppm. 

IBT (1973) exposed 10 subjects to 32, 50, 72, and 134 ppm for 5 minutes and the frequency of positive 

findings was as follows: at 32 ppm, 1 subject complained of dryness of the nose; at 50 ppm, 2 subjects 

complained of dryness of the nose; at 72 ppm, 3 subjects experienced eye irritation, 2 had nasal irritation, 

and 3 had throat irritation; and at 134 ppm, 5 subjects had signs of lacrimation, 5 had eye irritation, 7 had 

nasal irritation, 8 had throat irritation, and 1 had chest irritation. 

Collectively, the available information from studies in humans supports the 50 ppm exposure level from 

the Verberk et al. (1977) study as a minimal LOAEL for irritation in acute studies. In general, studies in 

animals have used higher exposure concentrations. For ammonia, a corrosive irritant gas that affects the 

portal of entry and produces irritation of the eyes and respiratory tract, use of human data should be 

preferred over animal studies. 

Agency Contact (Chemical Manager): Nickolette Roney, MPH 
AMMONIA A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Ammonia and Ammonium Compounds 

CAS Number: 7664-41-7 

Date: July 2004 

Profile Status: Third Draft Post Public 

Route: [ X ] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [ X ] Chronic 

Graph Key: 47 

Species: Humans 

Minimal Risk Level: 0.1 [ ] mg/kg/day [ X ] ppm 

Reference: Holness DL, Purdham JT, Nethercott JR. 1989. Acute and chronic respiratory effects of 

occupational exposure to ammonia. Am Ind Hyg Assoc J 50:646-650. 

Experimental design: The study evaluated sense of smell, prevalence of respiratory symptoms (cough, 

bronchitis, wheeze, dyspnea, and others), eye and throat irritation, and lung function parameters (FVC, 

FEV1, FEV1/FVC, FEF50, and FEF75) in humans exposed for an average of 12.2 years in a soda ash plant 

(Holness et al. 1989). The cohort consisted of 52 workers and 35 controls. The subjects were assessed on 

two workdays: on the first workday of their workweek and on the last workday of their workweek. 

Spirometry was performed at the beginning and end of each work shift, so that each worker had four tests 

done. To determine the exposure levels, exposed and control workers were sampled over one work shift; 

the average sample collection period was 8.4 hours. All of the participants in the study were males. 

Effects noted in study and corresponding doses: Analysis of the results showed no significant differences 

in the prevalence of reported symptoms, but the exposed workers reported that exposure in the plant 

aggravated some of their reported symptoms (cough, wheeze, nasal complaints, eye irritation, and throat 

discomfort). Odor threshold was not affected by exposure to ammonia and there were no significant 

differences in baseline lung functions between exposed and control subjects. Analysis of each worker 

separately showed no significant relationship between the level of ammonia exposure and changes in lung 

function. Also, when the workers were divided into groups of individuals that were exposed to low 

(<6.25 ppm), medium (6.25–12.5 ppm), and high (>12.5 ppm) ammonia levels, no significant association 

was found between reporting of symptoms, decline in baseline function, or increasing decline in function 

over the work shift and exposure to ammonia. Furthermore, no association was evident between 

increasing years of exposure and decreasing lung function. However, the power of the indices of both 

level and length of exposure is low because only eight workers were in areas with relatively high 

ammonia exposure. 

The MRL was calculated by adjusting the NOAEL of 9.2 ppm (the mean TWA exposure concentration) 

for continuous exposure (9.2 x 8/24 hours x 5/7 days) and dividing by an uncertainty factor of 10 for the 

protection of sensitive individuals. A modifying factor of 3 was used for the lack of reproductive and 

developmental studies. 

Dose and end point used for MRL derivation: 9.2 ppm for no significant alterations in lung function in 

chronically exposed workers. 

[ X ] NOAEL [ ] LOAEL 
AMMONIA A-7 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

 [ ] 10 for use of a LOAEL 

 [ ] 10 for extrapolation from animals to humans 

 [X] 10 for human variability 

Modifying Factors used in MRL derivation: 

 [X] 3 for lack of reproductive and developmental studies 

Was a conversion used from ppm in food or water to a mg/body weight dose? 

N/A. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose: 

N/A. 

Other additional studies or pertinent information which lend support to this MRL: Earlier studies 

summarized by NIOSH (1974) found that workers accustomed to 20 ppm ammonia did not complain of 

irritation symptoms, but showed slight redness in the conjunctiva. Those not accustomed had eye and 

respiratory discomfort and irritation. Another report stated that air levels below 5 ppm were associated 

with barely noticeable eye irritation. In yet an additional report, concentrations of 15–28 ppm in the work 

area produced slight eye irritation. More recent data reported respiratory effects associated with chronicduration exposure to pollutants, including ammonia, in livestock confinement buildings and an increase in 

respiratory symptoms (such as bronchial reactivity/hyperresponsiveness, inflammation, cough, wheezing, 

or shortness of breath) and/or a decrease in lung function (such as forced expiratory volume in the first 

second [FEV1.0], maximum expiratory flow rates [MEF50 and MEF75], and maximal mid-expiratory flow 

rate [MMEF]) in farmers exposed to ammonia levels of 2.3–20.7 ppm (Choudat et al. 1994; Cormier et al. 

2000; Donham et al. 1995, 2000; Heederik et al. 1990; Reynolds et al. 1996; Vogelzang et al. 1997, 

2000). The farmers were also exposed to other possible respiratory toxins, such as dust and endotoxins. 

A cross-sectional study of male workers at two fertilizer factories in Saudi Arabia showed a significant 

association between exposure to ammonia gas and respiratory symptoms and bronchial asthma (Ballal et 

al. 1998). No continuous exposure levels could be calculated for these workers because the number of 

days worked per week was not provided. There were no chronic-duration inhalation studies in animals. 

Agency Contact (Chemical Manager): Nickolette Roney, MPH 

AMMONIA B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 
AMMONIA B-2 

APPENDIX B 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
AMMONIA B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1) Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2) Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3) Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4) Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5) Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6) Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7) System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8) NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 
AMMONIA B-4 

APPENDIX B 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 

(9) LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10) Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11) CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13) Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14) Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15) Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16) NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17) CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
AMMONIA B-5 

APPENDIX B 

(18) Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19) Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE 

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

Exposure LOAEL (effect) 

Key to frequency/ NOAEL Less serious Serious (ppm) figurea Species duration System (ppm) (ppm) Re

10 

↓

9 

↓

8 ↓

7 ↓

6 ↓

5 

↓

INTERMEDIATE EXPOSURE 

Systemic 

→→

2 3 4 

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk Nit

6 hr/d 

CHRONIC EXPOSURE Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 

7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 

6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 

6 hr/d 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 


AMMONIA C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index

BMD benchmark dose 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency

CAS Chemical Abstract Services

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy

DOL Department of Labor 

DOT Department of Transportation 
AMMONIA C-2 

APPENDIX C 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

L 
AMMONIA C-3 

APPENDIX C 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram

mL milliliter 

mm millimeter 

mmHg millimeters of mercury

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram

NHANES National Health and Nutrition Examination Survey

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey

NOHS National Occupational Hazard Survey

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 
AMMONIA C-4 

APPENDIX C 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes

PEL permissible exposure limit 

pg picogram

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States

USDA United States Department of Agriculture 

USGS United States Geological Survey

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
AMMONIA C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta μm micrometer 

μg microgram

* 

q1 cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

AMMONIA D-1 

APPENDIX D. INDEX 

absorbed dose ..............................................................................................................................................................97 

adenocarcinoma.....................................................................................................................................................49, 57 

adrenal gland ...........................................................................................................................................21, 54, 67, 105 

adsorption ............................................................................................................................................14, 127, 135, 136 

aerobic .......................................................................................................................................................................137 

anaerobic............................................................................................................................................................126, 137 

aspartate aminotransferase (see AST)..........................................................................................................................68 

AST (see aspartate aminotransferase)..........................................................................................................................68 

bioaccumulation ........................................................................................................................................................148 

bioavailability ............................................................................................................................................................148 

biomarker......................................................................................................................... 96, 97, 98, 108, 109, 153, 160 

blood cell count .....................................................................................................................................................53, 66 

body weight effects..........................................................................................................................................54, 67, 71 

breast milk .............................................................................................................................................................7, 145 

burns .............................4, 6, 7, 8, 15, 16, 25, 26, 48, 52, 55, 65, 66, 70, 71, 73, 75, 80, 90, 92, 95, 101, 102, 104, 107 

cancer.........................................................................................................................................................6, 70, 94, 106 

carcinogen........................................................................................................................................................57, 70, 98 

carcinogenic...................................................................................................................6, 23, 24, 69, 98, 106, 108, 163 

carcinogenicity ..........................................................................................................................................................106 

carcinoma ........................................................................................................................................................49, 56, 75 

cardiac arrhythmia .......................................................................................................................................................52 

cardiovascular........................................................................................................................21, 52, 56, 57, 58, 71, 104 

cardiovascular effects ..............................................................................................................................52, 58, 71, 104 

chromosomal aberrations.....................................................................................................................................76, 106 

death ................................................................................................................ 6, 15, 17, 23, 25, 48, 58, 66, 73, 90, 102 

deoxyribonucleic acid (see DNA)................................................................................................................................77 

dermal effects ............................................................................................................................................16, 17, 54, 73 

DNA (see deoxyribonucleic acid)..........................................................................................................3, 15, 77, 78, 96 

dyspnea......................................................................................................................................19, 47, 48, 49, 105, 163 

endocrine .............................................................................................................................................54, 67, 71, 92, 93 

endocrine effects....................................................................................................................................................54, 67 

erythema ................................................................................................................................................................65, 74 

fertilizer .........................................2, 3, 4, 7, 13, 14, 46, 47, 76, 95, 105, 106, 108, 118, 122, 126, 127, 131, 132, 133, 

139, 140, 141, 143, 144, 145, 162, 163, 168 

fetus ...........................................................................................................................................................7, 56, 93, 106 

gastrointestinal effects .....................................................................................................................................52, 65, 71 

general population ..................................................................................................... 14, 18, 70, 96, 106, 127, 143, 146 

genotoxic ...............................................................................................................................................................23, 76 

genotoxicity ...............................................................................................................................................................106 

groundwater.........................................................................................................................95, 128, 131, 136, 137, 142 

half-life ..........................................................................................................................................14, 96, 126, 127, 137 

hematological effects.............................................................................................................................................53, 66 

hepatic effects........................................................................................................................................................53, 66 

hydrolysis ..................................................................................................................................................................133 

hydroxyl radical.................................................................................................................................................126, 137 

hyperammonemia ..............................................................................................................15, 17, 68, 90, 93, 95, 98, 99 

immune system..............................................................................................................................................55, 75, 107 

immunological...........................................................................................................................................23, 55, 67, 75 

immunological effects ...........................................................................................................................................67, 75 

irritation ......................................................................... 6, 8, 16, 18, 19, 26, 46, 47, 79, 95, 97, 99, 102, 104, 105, 163 

Kow .............................................................................................................................................................................115 

LD50 .............................................................................................................................................................................55 
AMMONIA D-2 

APPENDIX D 

livestock............................................................. 5, 8, 13, 16, 46, 74, 105, 126, 131, 132, 133, 139, 140, 141, 147, 151 

manure ........................................................................................... 2, 5, 13, 14, 131, 136, 140, 142, 143, 144, 145, 151 

metabolic acidosis..............................................................................................................................21, 57, 58, 66, 104 

micronuclei..........................................................................................................................................................76, 106 

milk....................................................................................................................................................................150, 151 

muscarinic receptor......................................................................................................................................................90 

musculoskeletal effects..........................................................................................................................................53, 66 

neoplastic...............................................................................................................................................................49, 57 

neurobehavioral ...........................................................................................................................................................93 

neurochemical............................................................................................................................................................107 

neurotransmitter...................................................................................................................................................95, 107 

nitrate..........................................................2, 14, 83, 113, 122, 126, 127, 136, 137, 138, 142, 159, 166, 167, 168, 169 

nitrite ...................................................................................................................................................14, 126, 127, 159 

nitrogen cycle ............................................................................................................................117, 123, 131, 137, 148 

nitrogen fixation ................................................................................................................................117, 123, 126, 134 

ocular effects .......................................................................................................................................17, 54, 58, 71, 74 

pharmacodynamic........................................................................................................................................................87 

pharmacokinetic...................................................................................................................................87, 88, 89, 90, 94 

placenta..........................................................................................................................................................................7 

poultry ............................................................................................................. 5, 14, 127, 131, 133, 142, 144, 150, 151 

pulmonary function................................................................................................ 16, 18, 19, 26, 46, 47, 102, 105, 163 

rate constant...............................................................................................................................................................137 

renal effects .........................................................................................................................15, 21, 53, 66, 73, 104, 105 

retention.................................................................................................................................................................79, 81 

solubility..........................................................................................................................................16, 73, 90, 101, 113 

toxicokinetic ........................................................................................................................................................23, 109 

urea ...............15, 17, 21, 57, 78, 79, 80, 81, 82, 83, 86, 87, 90, 91, 95, 97, 99, 101, 109, 111, 122, 131, 133, 144, 155 

vapor phase................................................................................................................................................................159 

volatility.....................................................................................................................................................................113 

volatilization...................................................................................... 126, 132, 135, 136, 137, 138, 140, 144, 156, 159 

weanling ....................................................................................................................................................58, 65, 66, 67