TOXICOLOGICAL PROFILE FOR
 

SULFUR TRIOXIDE AND SULFURIC ACID
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry 

December 1998 
SULFUR TRIOXIDE AND SULFURIC ACID ii 

DlSCLAlMER 

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. 
SULFUR TRIOXIDE AND SULFURIC ACID iii 

UPDATE STATEMENT 

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 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 IW, E-29
 

Atlanta, Georgia 30333
 



___________________________________________________________________ 

SULFUR TRIOXIDE AND SULFURIC ACID 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: Health Effects: Specific health effects of a given hazardous compound are reported by route 

of exposure, by type of health effect (death, systemic, immunologic, reproductive), 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 2.6 Children’s Susceptibility 

Section 5.6 Exposures of Children 

Other Sections of Interest: 

Section 2.7 Biomarkers of Exposure and Effect 

Section 2.10 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: l-800-447-1544 (to be replaced by l-888-42-ATSDR in 1999)

 or 404-639-6357 Fax: 404-639-6359 

E-mail: atsdric@cdc.gov Internet: httnllatsdrl .atsdr.cdc.gov:8080 

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 

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

Toxicity; and numerous chemical-specific case studies. 
_____________________________________________________________ 

_____________________________________________________________ 

SULFUR TRIOXIDE AND SULFURIC ACID viii 

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 z Phone: 

770-488-7000 z 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 z Phone: 800-356-4674 or NIOSH Technical Information Branch, Robert 

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

800-35NIOSH. 

The National Znstitute 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 z 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 z Phone: 202-347-4976 z FAX: 202-

347-4950 z e-mail: aoec@dgs.dgsys.com z AOEC Clinic Director: http://occ-envmed. 

mc.duke.eduloem/aoec.htm. 

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 z Phone: 847-

228-6850 z FAX: 847-228-1856. 
SULFUR TRIOXIDE AND SULFURIC ACID ix

CONTRIBUTORS

CHEMICAL MANAGER(S)/AUTHOR(S): 

Joseph D. Little, MSPH
 

ATSDR, Division of Toxicology, Atlanta, GA
 

John Liccione, Ph.D.
 

Sciences International, Inc., Alexandria, VA
 

Annette Iannucci, MS.
 

Sciences International, Inc., Alexandria, VA
 

Carol Eisenmann, Ph.D.
 

Sciences International, Inc., Alexandria, VA
 

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. Quality Assurance Review. The Quality Assurance Branch assures that consistency across profiles 

is maintained, identifies any significant problems in format or content, and establishes that Guidance 

has been followed. 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID xi 

PEER REVIEW 

A peer review panel was assembled for sulfur trioxide and sulfuric acid. The panel consisted of the following 

members: 

1. Dr. Arthur Gregory, Private Consultant, Luray, VA 

2 . Dr. Frederick Oehme, Comparative Toxicology Laboratories, Manhattan, KS 

3 . Dr. Lyman Skory, Private Consultant, Midland, MI 

These experts collectively have knowledge of sulfur trioxide’s and sulfuric acid’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(1)(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. 









SULFUR TRIOXIDE AND SULFURIC ACID 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about sulfur trioxide and sulfuric acid and the effects of 

exposure. 

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

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for 

long-term federal cleanup. Sulfur trioxide and sulfuric acid have been found in at least 47 of the 

1,467 current or former NPL sites. As more sites are evaluated, the sites with sulfur trioxide or 

sulfuric acid may increase. This is important because exposure to these substances may harm you 

and because these sites may be sources of exposure. 

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

such as a drum or bottle, it enters the environment. This release does not always lead to 

exposure. You are 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 sulfur trioxide or sulfuric acid, many factors determine whether you’ll 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 the other chemicals you’re exposed to and your age, 

sex, diet, family traits, lifestyle, and state of health. 

1.1 WHAT ARE SULFUR TRIOXIDE AND SULFURIC ACID? 

Sulfur trioxide is generally a colorless liquid but can also exist as ice- or fiber-like crystals or as a 

gas. When sulfur trioxide is exposed to air, it rapidly takes up water and gives off white fumes. It 

combines with water, releasing considerable heat while forming sulfuric acid. It also reacts 

violently with some metal oxides. Sulfur trioxide is also called sulfuric oxide and sulfuric 

anhydride. It is used as an intermediate in the production of sulfuric acid, other chemicals, and 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 2 

1. PUBLIC HEALTH STATEMENT 

explosives. Sulfur trioxide is unlikely to exist in the environment except for very short periods 

when it may be present in the air as a gas. In the air, sulfur trioxide can be formed slowly from 

sulfur dioxide. Once formed, sulfur trioxide will react with water in the air to form sulfuric acid. 

Both sulfur dioxide and sulfuric acid are more likely to be found in air than sulfur trioxide. If you 

are interested in learning more about sulfur dioxide, the Agency for Toxic Substances and Disease 

Registry has developed a separate profile about it 

Sulfuric acid is a clear, colorless, oily licluid that is very corrosive. An odor threshold of sulfuric 

acid in air has been reported to be 1 milligram per cubic meter of air (mg/m3

). If you are exposed 

to concentrated sulfuric acid in air, your nose will be irritated and it may seem like sulfuric acid 

has a pungent odor. When concentrated sulfuric acid is mixed with water, the solution gets very 

hot. Concentrated sulfuric acid can catch fire or explode when it comes into contact with many 

chemicals including acetone, alcohols, and some finely divided metals. When heated it emits 

highly toxic fumes, which include sulfur trioxide. It is also called sulphine acid, battery acid, and 

hydrogen sulfate. More sulfuric acid is produced in the United States than any other chemical. It 

is used in the manufacture of fertilizers, explosives, other acids, and glue; in the purification of 

petroleum; in the pickling of metal; and in lead-acid batteries (the type commonly used in motor 

vehicles). Sulfuric acid can be found in the air as small droplets or it can be attached to other 

small particles in the air. 

Fuming sulfuric acid, also called oleum, is a solution of 10-70% sulfur trioxide in sulfuric acid. 

Oleum is the form of sulfuric acid that is often shipped in railroad cars. For more information, see 

Chapters 3 and 4. 

1.2 WHAT HAPPENS TO SULFUR TRIOXIDE AND SULFURIC ACID WHEN THEY 

ENTER THE ENVIRONMENT? 

Much of the sulfuric acid in the air is formed from sulfur dioxide released when coal, oil, and gas 

are burned. The released sulfur dioxide slowly forms sulfur trioxide, which reacts with water in 

the air to form sulfuric acid. Sulfuric acid dissolves in the water in air and can remain suspended 

for varying periods of time; it is removed from the air as rain. Sulfuric acid in rain contributes to 
SULFUR TRIOXIDE AND SULFURIC ACID 3 

1. PUBLIC HEALTH STATEMENT 

the formation of acid rain. Sulfuric acid in water separates to form hydrogen ions and sulfate. 

The ability of sulfuric acid to change the acidity (pH) of water is dependent on the amount of 

sulfuric acid and the ability of other substances in the water to neutralize the hydrogen ions 

(buffering capacity). For more information about sulfur trioxide and sulfuric acid in the 

environment, see Chapters 4 and 5. 

1.3 HOW MIGHT I BE EXPOSED TO SULFUR TRIOXIDE OR SULFURIC ACID? 

You may be exposed to sulfur trioxide or sulfuric acid at your job if you work in the chemical or 

metal plating industry; if you produce detergents, soaps, fertilizers, or lead-acid batteries; or if you 

work in printing and publishing, or photography shops. Because sulfur trioxide forms sulfuric 

acid when it contacts the moist surfaces of your respiratory tract or your skin, the effects caused 

by sulfur trioxide and sulfuric acid are similar. In occupational settings, breathing small droplets 

of sulfur trioxide or sulfuric acid or touching it with your skin are the most likely ways you would 

be exposed to sulfuric acid. According to estimates from a survey conducted by the National 

Institute for Occupational Safety and Health (NIOSH) more than 56,103 U.S. workers may be 

exposed to sulfur trioxide, and more than 775,348 U.S. workers may be exposed to sulfuric acid. 

However, this survey used estimates from small samples, so the number of workers exposed to 

sulfur trioxide and sulfuric acid may be overestimated. 

You may also be exposed to sulfuric acid by breathing outdoor air containing this compound. As 

mentioned before, sulfuric acid droplets can form in the air when sulfur dioxide is released from 

the burning of coal, oil, and gas. This released sulfur dioxide slowly forms sulfur trioxide and 

then reacts with water in the air to form sulfuric acid. While sulfuric acid could be present in the 

air during episodes of high pollution, all air pollution is not due to sulfuric acid contamination. 

The effects of other pollutants in air may be of greater concern to the general population. 

Likewise, there are relatively few sulfuric acid air pollution episodes today. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 4 

1. PUBLIC HEALTH STATEMENT 

People living near hazardous waste sites that contain sulfuric acid are at greater risk of exposure 

by breathing contaminated air than is the general public. For these people, spending time 

outdoors, especially exercising, could increase their risks of being exposed. 

You can also be exposed to sulfuric acid when you touch the material that forms on the outside of 

your car battery. Sulfuric acid is formed when some toilet bowl cleaners mix with water. 

Therefore, if these products touch skin or are accidentally swallowed, you could be exposed to 

sulfuric acid. When you cut onions a chemical called propanethiol S-oxide is released into the air. 

When this chemical reaches your eyes, it reacts with the water in your eyes to form sulfuric acid, 

which causes your eyes to water. People have also been exposed following accidental spills of 

sulfuric acid or oleum. These accidents occurred more frequently at a site than while the 

substances were being transported. For more information on the ways people might be exposed 

to sulfuric acid, see Chapter 5. 

1.4 HOW CAN SULFUR TRIOXIDE AND SULFURIC ACID ENTER AND LEAVE MY

 BODY? 

If you breathe in sulfur trioxide, small droplets of sulfuric acid will form when the sulfur trioxide 

contacts water. Small droplets of sulfuric acid may also enter the respiratory tract when you 

breathe. Where the droplets will deposit in the respiratory tract depends on their size and how 

deeply you are breathing. Smaller droplets will deposit deeper into the lung. If you breathe 

through your mouth, more droplets will deposit in your lungs than if you breathe only through 

your nose. Extra sulfur dioxide breakdown products are excreted in the urine. 

Sulfuric acid causes its effects by direct action on tissues that it touches. With the exception of 

how sulfuric acid droplets deposit in the lungs, how sulfur trioxide and sulfuric acid enter and 

leave your body does not alter the effects of sulfuric acid. For more information, see Chapter 2. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 5 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN SULFUR TRIOXIDE AND SULFURIC ACID AFFECT MY HEALTH? 

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people 

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and 

released by the body; for some chemicals, animal testing may be necessary. Animal testing may 

also be used to identify health effects such as cancer or birth defects. Without laboratory animals, 

scientists would lose a basic method to get iuformation needed to make wise decisions to protect 

public health. Scientists have the responsibility to treat research animals with care and 

compassion. Eaws today protect the welfare of research animals, and scientists must comply with 

strict animal care guidelines. 

Sulfuric acid and other acids are very corrosive and irritating and cause direct local effects on the 

skin, eyes, and respiratory and gastrointestinal tracts when there is direct exposure to sufficient 

concentrations. Breathing sulfuric acid mists can result in tooth erosion and respiratory tract 

irritation. Drinking concentrated sulfuric acid can burn your mouth and throat, and it can erode a 

hole in your stomach; it has also resulted in death. If you touch sulfuric acid, it will burn your 

skin. If you get sulfuric acid in your eyes, it will burn your eyes and cause them to water. The 

term “burn” used in these sections refers to a chemical burn, not a physical burn resulting from 

contacting a hot object. People have been blinded by sulfuric acid when it was thrown in their 

faces. 

Breathing small droplets of sulfuric acid at levels that might be in the air on a day with high air 

pollution may make it more difficult to breathe. This effect is more likely to occur if you have 

been exercising or if you have asthma. This effect may also be more likely to occur in children 

than adults. Breathing sulfuric acid droplets may affect the ability of your respiratory tract to 

remove other small particles that you have inhaled. If you breathe sulfur trioxide, it turns into 

sulfuric acid in your upper respiratory tract, and the effects you may experience will be similar to 

those of sulfuric acid inhalation. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 6 

1. PUBLIC HEALTH STATEMENT 

Studies in people who breathed high concentrations of sulfuric acid at work have shown an 

increase in cancers of the larynx. However, most oftbe cancers were in smokers who were also 

exposed to other acids and other chemicals. There is no information that exposure to sulfuric acid 

by itself is carcinogenic. The carcinogenicity of sulfuric acid has not been studied in animals. The 

EPA and the U.S. Department of Health and Human Services (DHHS) have not classified sulfur 

trioxide or sulfuric acid for carcinogenic effects. Based on very limited human data, the International 

Agency for Research on Cancer (IARC) believes that evidence is sufficient to state that 

occupational exposure to strong inorganic acid mists containing sulfuric acid is carcinogenic to 

humans. IARC has not classified pure sulfuric acid for its carcinogenic effects. 

For more information on the health effects of sulfuric acid, see Chapter 2. 

1.6 HOW CAN SULFUR TRIOXIDE OR SULFURIC ACID AFFECT CHILDREN? 

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

to maturity at 18 years of age in humans. Potential effects on children resulting from exposures of 

the parents are also considered. 

Children may be exposed to sulfur trioxide and sulfuric acid in the same manner as adults, with the 

exception of chemical encounters in the workplace. Sulfur trioxide is only used in industry as an 

intermediate in the production of chemicals such as sulfuric acid and quickly converts to sulfuric 

acid when it contacts water in air. Therefore, children will most likely only be at risk of exposure 

from sulfuric acid, not sulfur trioxide. Exposure to sulfuric acid may occur through skin contact, 

eye contact, ingestion, and breathing contaminated air. Sulfuric acid can cause severe skin burns, 

it can burn the eyes, burn holes in the stomach if swallowed, irritate the nose and throat, and 

cause difficulties breathing if inhaled. 

Exposure to sulfuric acid from accidental contact with or misuse of sulfuric acid-containing 

consumer products is the most likely way your child could be exposed. Household products that 

contain sulfuric acid include drain and toilet bowl cleaners, and some acid car batteries. The 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 7 

1. PUBLIC HEALTH STATEMENT 

national estimate (derived by United States Consumer Product Safety Commission, USCPSC) for 

injuries related to drain cleaners over a 5-year period ending January 1996 is between 2,800 and 

3,150 injuries per year. Inquisitive toddlers may get into unsealed or improperly stored containers 

of sulfuric acid-containing products. Transfer of cleaning agents containing sulfuric acid into 

containers not designed for their storage can allow leakage from the container. Improper flushing 

of areas recently cleaned with a sulfuric acid-containing product can lead to inadvertent skin 

exposure to both children and adults. 

While younger children are most at risk from accidental swallowing, skin contact, or eye contact 

with sulfuric acid in household products, teenagers might have jobs in which they may contact 

sulfuric acid. If teenagers must use acid cleaners in their jobs or work in car repair where they 

may contact car batteries, they might be exposed. Furthermore, there have been reports of older 

children using sulfuric acid-containing solutions as weapons, thereby causing severe skin damage 

when intentionally splashed on others. 

Small droplets of sulfuric acid may exist in the outdoor air. You and your children have the 

greatest chances of inhaling the compound during times of high air pollution with sulfuric acid. 

This may lead to difficulty breathing. If you live near electrical, metal processing, or paper 

processing industries, you may also have a greater chance of exposure to sulfuric acid. When 

sulfuric acid is inhaled into the lungs in the form of small droplets that exist in air, these droplets 

are deposited within the lung and the ability of your respiratory tract to remove other small, 

unwanted particles may be decreased. A study has shown that children can have greater 

deposition of sulfuric acid in their lungs than adults due to children’s smaller airway diameters. 

Also, because children breathe more air per kilogram of body weight than adults, children may 

take in more sulfuric acid when they breathe the same contaminated air. Increased sensitivity has 

been witnessed in both animal studies with young guinea pigs and in human studies of asthmatic 

adolescents. This evidence suggests that children may be more vulnerable than adults to the 

health effects associated with breathing sulfuric acid. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 8 

1. PUBLIC HEALTH STATEMENT 

No studies examining effects on unborn children following a mother’s exposure to sulfuric acid 

during pregnancy were identified in humans. limited evidence in animals indicates that sulfuric 

acid is not a hazard to unborn children. Birth defects have not been observed in animals that 

breathed high levels of sulfuric acid mist. Exposing pregnant rabbits to sulfuric acid did not 

significantly affect the body weights or cause malformations in their offspring. Again, because 

sulfuric acid causes adverse effects at its point of contact with the body, the acid, as such, is not 

expected to be absorbed or distributed throughout the body. Sulfuric acid is not expected to be 

transported across a mother’s placenta into her developing baby or into breast milk. Therefore, 

an exposed mother most likely will not threaten her unborn or nursing child. Since sulfuric acid’s 

effects occur at the point of contact, it is not likely that it will reach a mother’s egg or father’s 

sperm. Therefore, parents exposure to sulfuric acid or sulfur trioxide should not affect their 

unborn children. 

For more information see Sections 2.6 and 5.6. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SULFUR

 TRIOXIDE OR SULFURIC ACID? 

If your doctor finds that you have been exposed to significant amounts of sulfur trioxide or 

sulfuric acid, ask if children may also be exposed. When necessary your doctor may need to ask 

your State Department of Public Health to investigate. 

Sulfuric acid is a highly corrosive chemical that is potentially explosive in concentrated form. It 

can cause severe skin burns, can irritate the nose and throat and cause difficulties breathing if 

inhaled, can burn the eyes and possibly cause blindness, and can burn holes in the stomach if 

swallowed. 

Concentrated sulfuric acid is commonly used in the United States as a drain and toilet bowl 

cleaner. Children and adults have suffered full thickness skin burns upon accidental contact or 

intentional assault with sulfuric acid in this form. Additionally, sulfuric acid is formed when some 

toilet bowl cleaners mix with water, so care should be taken not to breathe associated vapors or 
 

SULFUR TRIOXIDE AND SULFURIC ACID 9 

1. PUBLIC HEALTH STATEMENT 

splash any liquid on the skin or in the eyes. All household chemicals containing sulfuric acid 

should be stored in their original, labeled containers, kept in locked cabinets away from children, 

kept away from fire, and should be used only for their intended purposes. The material that forms 

on the outside of a car battery is also a source of sulfuric acid and you should avoid touching it. 

Wear safety glasses and use chemical resistant gloves to avoid this type of exposure. Upon any 

exposure to sulfuric acid, the contacted body part should be immediately flushed with plentiful 

water and then the Poison Control Center contacted. Keep your Poison Control Center’s number 

by the phone. If sulfuric acid is spilled in the home, the local Fire Department should be contacted 

for assistance in handling the spill. 

When levels of air pollution are high, families are advised to stay indoors as much as possible and 

to avoid exercising outdoors. Families can be aware of levels of air pollution by paying attention 

to news bulletins and air pollution advisories, most of which are issued by the EPA 

(Environmental Protection Agency). This is particularly important for individuals with respiratory 

conditions and asthmatic children. Staying indoors during times of sulfuric acid air pollution will 

help you avoid breathing sulfuric acid droplets. 

Adults may be occupationally exposed to sulfuric acid if they work in the chemical or metal 

plating industry; produce detergents, soaps, fertilizers, or lead-acid batteries; or work in printing 

or publishing, or photography shops. It is not anticipated that workers in such industries can 

expose their families at home (through their clothing, skin, or breath) to sulfuric acid contacted at 

work. 

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

EXPOSED TO SULFUR TRIOXIDE OR SULFURIC ACID? 

There is no medical test to determine whether you have been exposed to sulfur trioxide or sulfuric 

acid. Breathing in acids, including sulfuric acid, will increase the acidity of your saliva. 

Measuring the acidity of saliva may determine whether you have been exposed to acid but cannot 

determine which acid. For more information on where and how sulfuric acid can be detected in 

your body after you have been exposed, see Chapters 2 and 6. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 10 

1. PUBLlC 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. Federal agencies that develop regulations for toxic 

substances include the Environmental Protection Agency (EPA), the Occupational Safety and 

Health Administration (OSHA), and the Food and Drug Administration (FDA). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by 

law. Federal organizations that develop recommendations for toxic substances include the 

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for 

Occupational Safety and Health (NIOSH). 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals; then they are adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated 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 sulfur trioxide and sulfuric acid include 

the following: 

EPA limits the amount of sulfur dioxide that can be released into the air. This limits the amount 

of sulfur trioxide and sulfuric acid that form from sulfur dioxide in the air. 

OSHA limits the amount of sulfuric acid that can be present in workroom air to 1 mg/ m3

. NIOSH 

also recommends a time-weighted average limit of 1 mg/ m3

. For more information on regulations 

and guidelines to protect human health, see Chapter 7. 
SULFUR TRIOXIDE AND SULFURIC ACID 11 

1 PUBLIC HEALTH STATEMENT 

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: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road NE, Mailstop E-29
 

Atlanta, GA 30333
 

* Information line and technical assistance 

Phone: l-800-447- 1544
 

Fax: (404) 639-6359
 

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

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

hazardous substances. 

* To order toxicological profiles. contact: 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22 16 1
 

Phone: (800) 553-6847 or (703) 487-4650
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 13 

2. HEALTH EFFECTS 

2.1 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 of the toxicology of sulfur trioxide/sulfuric acid. 

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. 

This profile does not discuss studies regarding exposure to sulfur dioxide, from which sulfur trioxide and 

sulfuric acid are formed. Studies regarding effects of sulfur dioxide are discussed in a separate ATSDR 

profile (ATSDR 1997). 

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

2.2 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 lowest-observedadverseeffect 

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 
 

SULFUR TRIOXIDE AND SULFURIC ACID 14 

2. HEALTH EFFECTS 

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 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. LOABLs 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 (LOAEL) or exposure Bevels 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. 

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. 

2.2.1 Inhalation Exposure 

Few studies were identified regarding the toxic effects of sulfur trioxide. Within the respiratory tract, sulfur 

trioxide reacts rapidly with water to form sulfuric acid (IARC 1992). Therefore, the adverse effects of sulfur 

trioxide are expected to be the same as those of sulfuric acid. 

There are many factors, in addition to exposure concentration, that determine the response to the inhalation of 

sulfuric acid aerosols. One factor is aerosol size which determines the location in the respiratory tract where 

sulfuric acid aerosols will deposit and result in effects. Humidity, both in the environment and in the 

respiratory tract, helps to determine the aerosol size. 

Growth of sulfuric acid aerosols in response to humidity in airways results in greater respiratory deposition 

compared to deposition of inert particles (Carabine and Maddock 1976). Likelihood of pulmonary deposition 

is increased by depth of penetration and particle growth. Because small sulfuric acid particles grow upon 

contact with humidified airways, they will penetrate deeper into the lung than inert particles of the same size 

as the enlarged, humidified particles. Growth of acid particles also increases retention because they may 
 

SULFUR TRIOXIDE AND SULFURIC ACID 15 

2. HEALTH EFFECTS 

initially enter small airways, but following expansion, may be too large for exhalation through the same 

airways. Therefore deposition will also be greater as compared to that of inert particles of the same size as 

the original acid particle prior to inhalation. 

Inert aerosols, which do not change size as they enter the respiratory tract, deposit in the nasopharyngeal 

region by inertial impaction if they are 5-30 μm in diameter; in the tracheobronchial region by sedimentation 

if they are l-5 μm in diameter; and in the alveolar region by diffusion if they are ≤ 1 μm in diameter (Wits&i 

and Last 1996). 

Aerosols are usually a range of sizes that approximate a log-normal distribution. This size distribution is 

most frequently described by the median or geometric mean and the geometric standard deviation (Witschi 

and Last 1996). For studies of sulfuric acid aerosols, the diameters often reported are the mass median 

diameter (MMD) and the mass median aerodynamic diameter (MMAD) which takes into account both the 

density of the particle and the aerodynamic drag. Several inhalation studies of sulfuric acid aerosol report 

aerosol size as count median diameter (CMD) or volume median diameter (VMD). Aerosol size in pm is 

presented in the inhalation LSE table (Table 2-B), and the type of measurement is indicated. In Figure 2-1, 

aerosol sizes are indicated with footnotes as ultrafine (II) <0.1 μm, small (S) 0. l-<l μm, medium (M) 

l-<5 μm, and large (L) 5-30 μm. Acid aerosols typically found in the ambient air have an MMAD of 

0.3-0.6 μm, while industrial aerosols can have MMADs as large as 14 μm (Lippmann et al. 1987). 

In addition to aerosol size, conditions of exposure are very important for determining the effect of sulfuric 

acid. For example, breathing rate, which is affected by physical activity, and the method of breathing (e.g., 

nose, mouth, or oronasal) help to determine where in the respiratory tract the aerosol deposits; the site of 

deposition determines the effect of the aerosol. How much of the acid is neutralized by ammonia or other 

alkaline substances, both in the ambient environment and within the respiratory tract, also determines the 

effects of sulfuric acid aerosols. Ammonia is emitted in breath and sweat, with concentrations of 

120-1280 ppb measured in the exhaled air of humans (Suh et al. 1992). Therefore, as sulfuric acid enters the 

breathing zone it may be neutralized which results in lower personal exposure. More information about 

sources of ammonia can be found in the ATSDR profile on ammonia (ATSDR 1990). 

The acid neutralization capacity of the respiratory mucus may also determine whether or not inhalation of 

sulfuric acid aerosols will result in a response. For example, it has been suggested that asthmatics are more 

sensitive to sulfuric acid because the pH of their mucus is lower than normal subjects (Holma 1985). In the 
SULFUR TRIOXIDE AND SULFURIC ACID 16 

2. HEALTH EFFECTS 

discussions that follow, conditions of exposure, especially in human exposure studies, will be presented. 

Exposures were whole-body chamber exposures unless indicated otherwise. In addition, in the inhalation 

LSE table (Table 2-l), studies in which the volunteers were asthmatics are indicated as “human-a.” The nonasthmatic subjects are designated as “human-n.” 

2.2.1.1 Death 

Studies regarding death of humans following acute- and intermediate-duration inhalation exposure to sulfuric 

acid aerosols were not identified in recent years Increased mortality, especially of elderly persons and those 

with preexisting cardiac and respiratory disease, has been reported during or shortly after air pollution 

episodes (Costa and Amdur 1996). Because it is not possible to clearly separate the effects of sulfuric acid 

aerosols from other pollutants, including particulates, sulfur dioxide, and ozone, these studies are not 

discussed. In general, increased mortality seems to correlate more closely with particulate matter, including 

sulfuric acid aerosols. In a study that tried to separate the effects of sulfuric acid aerosols from sulfur dioxide 

and from British smoke (a measure of particulates), the log of sulfuric acid aerosol concentrations in London 

was more strongly correlated with total mortality than either sulfur dioxide or British smoke (Thurston et al. 

1989). The authors of the study concluded that their results were consistent with the hypothesis that sulfuric 

acid is the portion of the particulate mass with greatest health significance. No association between mortality 

and environmental sulfate concentrations was observed among 6,340 nonsmoking persons living in California 

(Abbey et al. 1995). Overall mortality of workers was not associated with acid exposure at steel factories 

(Beaumont et al. 1987) or at a sulfuric acid plant (Englander et al. 1988). 

Numerous studies are available concerning the mortality of animals following inhalation exposure to sulfuric 

acid. One-hour LC50s of 347 and 420 ppm fuming sulfuric acid have been reported for female and male rats, 

respectively (Vernot et al. 1977). Fuming sulfuric acid is sulfuric acid with up to 80% free sulfur trioxide 

(Budavari 1989). The percentage of sulfur trioxide in the Vemot et al. (1977) study was not stated. The 

LC50 values expressed as mg sulfur trioxide/ m3

 were 1,136 and 1,375 for female and male rats, respectively. 

Because fuming sulfuric acid was used in this study, the Vernot et al. (1977) study is not presented in 

Table 2- 1 or Figure 2- 1. 

The lowest concentration of sulfuric acid aerosols that resulted in the death of rats was 383 mg/ m3

 (Treon et 

al. 1950). One rat died during the first day of a 7-hour exposure, and one rat died on the second day of a 

7-hour exposure. Following one 7-hour exposure, 2 of 2 rats died at 699 mg/m3

, while all rats survived a 7­
 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 17 

2. HEALTH EFFECTS 

hour exposure to sulfuric acid aerosols at 461 mg/ m3 (Treon et al. 1950). Following one 3.5-hour sulfuric 

acid aerosol exposure, 2 of 2 rats died at 1,470 mg/ m3

 with no deaths observed at 718 mg/ m3 (Treon et al. 

1950). The aerosol size used in the Treon et al. (1950) study was described as being in the range of l-2 μm . 

In a 5-day exposure study in which the duration of the exposure each day was not stated, no rats died during 

exposure to 100 mg/ m3

 sulfuric acid aerosols at an MMAD of 0.72 μm (Cavender et al. 1977). 

Mice were more susceptible to sulfuric acid aerosol exposure (diameter l-2 μm) than rats (Treon et al. 

1950). Following 5 daily 7-hour exposures, 4 of 5 mice died at 383 mg/ m3

, with all surviving at 203 mg/ m3. 

Exposure for 7 hours resulted in the deaths of 2 of 5 mice at 699 mg/ m3

, with all surviving at 461 mg/ m3, 

while exposure for 3.5 hours resulted in the deaths of 2 of 5 at 549 mg/ m3

. Lower concentrations of sulfuric 

acid were not studied in mice exposed for 3.5 hours. 

Among the species tested, guinea pigs are the most sensitive to exposure to sulfuric acid aerosols. During a 

1-hour exposure to 52-6 1 mg/ m3

 sulfuric acid (MM/D 0.8-2.1 μm), about 6% of the exposed guinea pigs 

died (Stengel et al. 1993). The lowest concentration of the range is shown in Table 2-l and Figure 2-l. The 

number of guinea pigs exposed was not stated. Before death, the guinea pigs developed labored breathing. 

Exposure of guinea pigs to 87 mg/ m3

 sulfuric acid aerosols in the range of l-2 ym resulted in the death of all 

3 exposed animals within 2.75 hours (Treon et al. 1950). The deaths of guinea pigs were attributed to an 

acute respiratory response to the acid exposure. 

Younger guinea pigs are more sensitive to sulfuric acid aerosols than older guinea pigs. For guinea pigs 

exposed to sulfuric acid aerosols with a mean aerosol size of 1 μm, 8-hour LC50s of 18 and 50 mg/ m3

 were 

reported for 1-2-month-old and 1.5-year-old guinea pigs, respectively (Amdur et al. 1952a). During a 72­

hour exposure to 12 mg/m3

 sulfuric acid aerosols (mean particle size 1 pm), approximately 10% of the 

exposed guinea pigs died during the first 8 hours, with no additional deaths occurring (Amdur et al. 1952a). 

No guinea pigs exposed to 8 mg/m3

 sulfuric acid aerosol for 72 hours died. The effects observed in the 

guinea pigs that died included gross areas of hemorrhage in the lungs, which were frequently most 

pronounced around the hilar regions, surface hemorrhage of the adrenal glands, and nasal bleeding at higher 

concentrations. Microscopically, hemorrhage and edema were observed in the lungs, with leukocytes and 

erythrocytes in the alveolar spaces. Congestion of the bronchi, alveoli, and blood vessels was also observed. 

The effect of aerosol size on survival of guinea pigs exposed to sulfuric acid aerosols has been studied. 

Following exposure to sulfuric acid aerosols with MMADs of 0.8 and 0.4 μm, LC50s of 30.3 and 
SULFUR TFilOXlDE AND SULFURIC ACID 18 

2. HEALTH EFFECTS 

>109 mg/ m3, respectively, were reported for guinea pigs exposed for 8 hours (Wolff et al. 1979). In another 

study, 8-hour LC50,s of 59.8 and 27.3 mg/ m3

 were reported for aerosols with MMADs of 0.8 and 2.7 μm, 

respectively (Pattle et al. 1956). Pattle et al. (1956) also showed that a lowered ambient temperature 

enhanced the toxicity of sulfuric acid aerosols in guinea pigs. For an aerosol of MMAD 0.8 μm, the LC50s 

were 59.8 and 46.9 mg/ m3

 at 20°C and 0°C respectively. 

Following exposure of rabbits to sulfuric acid aerosols with a diameter in the range of l-2 μm, 1 of 2 died 

following a 3.5-hour exposure to 1,470 mg/ m3

, 1 of 2 died following a 7-hour exposure to 1,610 mg/ m3, and 

2 of 2 died following five daily 7-hour exposures to 383 mg/ m3 (Treon et al. 1950). No deaths of rabbits 

occurred at 718 mg/m” for 3.5 hours, 699 mg/m3

 for 7 hours, or 203 mg/ m3 for 5 daily 7-hour exposures. 

Among the exposed rabbits that died, most of the deaths were attributed to infectious pneumonia that 

occurred after the chemical injury, rather than an acute respiratory response as observed in guinea pigs. From 

their results in rats, mice, guinea pigs, and rabbits, Treon et al. (1950) concluded that at relatively high 

concentrations of sulfuric acid aerosols, the duration of exposure was more important in determining lethality 

than exposure concentration. 

No effect on survival was observed in cynomolgus monkeys or guinea pigs exposed to sulfuric acid aerosols 

23.3 hours/day, 7 days/week, for 78 weeks (monkeys) or 52 weeks (guinea pigs) (Alarie et al. 1973). The 

monkeys were exposed at concentrations of 0,0.38,0.48,2.43, or 4.79 mg/ m3

 (MMDs of 2.15,0.54,3.6, 

and 0.73 μm, respectively), and the guinea pigs were exposed at concentrations of 0,0.08, or 0.1 mg/ m3 

(MMDs of 0.84 and 2.78 μm, respectively). 

All LOAEL and LC50 values from each reliable study for death in each species for acute exposure are 

recorded in Table 2- 1 and plotted in Figure 2- 1. 

2.2.1.2 Systemic Effects 

The highest NOAEL and representative LOAEL values from reliable studies for systemic effects in each 

species and duration category are recorded in Table 2- 1 and plotted in Figure 2-l. 






















SULFUR TRIOXIDE AND SULFURIC ACID 41 

2. HEALTH EFFECTS 

No studies were located regarding gastrointestinal, musculoskeletal, or dermal effects in humans or animals 

after inhalation exposure to sulfur trioxide or sulfuric acid. 

Respiratory Effects. Respiratory tract irritation was noted by 12 persons working next to a chemical 

plant that emitted sulfur trioxide (Stueven et al. 1993). The subjects were exposed to an unspecified 

concentration for approximately 2 hours, and 9 of 12 subjects went to the hospital. The symptoms reported 

included pleuritic chest pain in two subjects, chest tightness in three subjects, vague chest discomfort in one 

subject, cough in one subject, and an acidic taste in the mouth and nasal irritation in one subject. All subjects 

were asymptomatic 6 hours after the exposure when they were released from the hospital. Adult respiratory 

distress syndrome was reported in a man accidentally exposed to high concentrations of sulfuric acid fumes 

(Knapp et al. 199 1). Effects noted upon initial hospital admission included hypotension and a crackling 

sound from his lungs. A chest X-ray revealed diffuse confluent opacities consistent with chemical 

pneumonia. Less than 24 hours later, a chest X-ray revealed a pneumomediastinum and a right 

pneumothorax. After 12 days in the hospital he was released feeling weak but without a cough or exertional 

dyspnea. After 3 days at home he returned to the hospital with an abscess in his lung. He was treated with 

antibiotics and released after 1 week. No permanent deficits in lung function were noted. 

A case was also reported of a previously healthy 40-year old male worker who was accidentally sprayed in the 

face with 35% fuming sulfuric acid (equivalent to 108.04% sulfuric acid) (Goldman and Hill 1953). 

Immediately after the accident, the man rinsed himself off in a safety shower for eight minutes, during which 

time he inhaled sulfuric acid mists and vapors. Acute respiratory symptoms included difficulty breathing and 

cough with the production of bloody sputum. Moist rails were audible in both lungs and X-rays revealed 

pulmonary congestion and inflammation. Pulmonary damage was permanent and was characterized by 

chronic cough, difficulty breathing, reduced respiratory performance, and bronchiectasis. Fibrosis and 

emphysema developed within a 7-l 8 month period. 

Numerous studies are available regarding lung function in volunteers (healthy and asthmatic) exposed to 

sulfuric acid aerosols for short periods of time. In these studies lung function is often assessed using 

spirometry, which measures lung volumes and flows. Spirometric methods require subject cooperation and 

effort. Some of the most frequent measurements reported are forced vital capacity (FVC), forced expiratory 

volume in 1 second (FEV1), and forced expiratory volume at 50% or 75% (FEV50%, FEV75%). FVC is the 

volume (in liters) of air that can be exhaled forcefully and rapidly after a maximal inspiration. FEV1 is the 

volume of air that can be forcefully exhaled in 1 second. FEV50%and FEV75% are the volumes at 50% and 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 42 

2. HEALTH EFFECTS 

75% of the FEV curves (EPA 1994). Additional lung function tests can be completed using a whole-body 

plethysmograph. With this method, specific airway resistance (SRaw), the product of airway resistance and 

thoracic gas volume, can be determined. 

The effect of relative humidity on sulfuric acid-induced respiratory tract symptoms has been studied. Twelve 

normal male volunteers were exposed to 39.4 mg/m3

 sulfuric acid aerosols at a relative humidity of 62% for 

1 hour, or to 20.8 mg/m3

 at a relative humidity of 91% for 30 minutes (Sim and Pattle 1957). The MMD for 

both humidity conditions was 0.99 pm. The exposure at 62% relative humidity was well tolerated. There 

was some coughing on entering the chamber, which wore off within a few minutes. Resistance to airflow was 

increased 36-100% above normal in all 12 exposed subjects. At a relative humidity of 91%, the study 

authors indicated that the ‘mist was almost intolerable at the onset but the men were able to continue for a 

period of 30 minutes.” Intense coughing was observed throughout the experimental period, and resistance to 

air flow was increased 43-150%. The study authors note that during the chamber exposures, the men were 

“allowed to walk around or smoke if they wished.” Because exposure conditions were not well controlled, 

this study is not presented in Table 2-l or Figure 2-l. 

The pattern of respiration was studied in an unspecified number of normal male volunteers exposed to 

sulfuric acid aerosols (mean particle size 1 μm) with a face mask for 5-15 minutes at 0.35-5 mg/m3

 (Amdur 

et al. 1952b). Changes in respiration were observed at all concentrations. At 0.35 mg/m3

, a 35% increase in 

respiration rate and a 20% decrease in maximum flow rate occurred and continued throughout the exposure 

period. At 5 mg/m3

, the major response was a decrease in minute volume. 

No effects on minute volume, tidal volume, respiratory frequency, or minute ventilation were noted in 

7 healthy male volunteers exposed to 0.471 mg/m3

 sulfuric acid (MMAD 10 pm) for 1 hour using a head 

dome (Bowes et al. 1995). The l-hour exposure consisted of 40 minutes of rest, followed by 20 minutes of 

moderately heavy exercise. The 10-μm aerosol size used in this study would not reach the lungs without oral 

breathing. In a 2-hour exposure study, no effects on pulmonary function were observed in 9 normal male 

subjects exposed to 1.2-l .6 mg/m3

 sulfuric acid (MMD 0.05 μm) with intermittent exercise (Horvath et al. 

1987). Additional acute-duration exposures of normal humans have also not caused any adverse effects on 

pulmonary function tests (Anderson et al. 1992; Avol et al. 1988; Frampton et al. 1992; Koenig et al. 1993; 

Kulle et al. 1982; Laube et al. 1993; Leikauf et al. 1981, 1984; Linn et al. 1994; Newhouse et al. 1978; Stacy 

et al. 1983; Utell et al. 1984). All of the studies, except those by Leikauf et al. (1981, 1984) and Utell et al. 

(1984), used intermittent periods of exercise during exposure periods that lasted from 16 minutes to 4 hours. 
SULFUR TRIOXIDE AND SULFURIC ACID 43 

2. HEALTH EFFECTS 

Studies of both normal and asthmatic subjects indicate that asthmatics are more sensitive to sulfuric acid 

exposures. A concentration-related increase in specific airway resistance (SRaw) was observed in asthmatics 

(12 men, 9 women) exposed to sulfuric acid aerosols (MMD 0.9 pm) at 0,0.396,0.999, and 1.46 mg/m3

 for 

1 hour with three 10-minute exercise periods (Avol et al. 1988). The effect was significant at 0.999 mg/m3

, 

and the lowest concentration is considered a NOAEL. No effects on pulmonary function were observed in 

normal subjects (14 men, 7 women) exposed to sulfuric acid aerosols at concentrations as high as 

1.578 mg/m3

 (Avol et al. 1988). Self-reported respiratory symptoms also showed a concentration-related 

increase in asthmatics, with no clear effect in normal subjects. 

Decreased specific airway conductance was observed in 17 asthmatics exposed to sulfuric acid aerosols 

(MMAD 0.8 l.μm) through a mouthpiece at 0.45 mg/m3

, while at rest for 16 minutes (Utell et al. 1983). At a 

concentration of 1 mg/m3, a reduction in FEV1 was also observed. No effects on pulmonary function were 

observed when these subjects were exposed to 0.1 mg/m3

. Reductions in FEV1 and maximum expiratory 

flow rates at 60% of total lung capacity were observed in 15 asthmatic volunteers exposed to sulfuric acid 

aerosols (MMAD 0.8 μm) through a mouthpiece at 0.35 mg/ m3

 for 30 minutes (Utell et al. 1989). The 

response was greater when the subjects reduced ammonia concentrations in the mouth (tooth brushing, 

gargling with citrus juice) just before the exposure. 

Acute-duration exposure studies of volunteers indicate that adolescent asthmatics are generally more sensitive 

to inhalation of sulfuric acid aerosols than healthy older individuals. In a study of 22 adolescent (age 12-19) 

asthmatics exposed to 0.07 mg/m3

 sulfuric acid aerosols (MMAD 0.71 pm) through a mouthpiece, transient 

decreases in FVC and FEV1 were observed (Hanley et al. 1992). During the 4045minute exposures, the 

subjects exercised for 10 or 30 minutes. The investigators indicated that the response was small and was no 

longer significant 20 minutes after the end of the exposure. No effects on maximal flow at 50% or 75% of 

expired vital capacity or on total respiratory resistance were observed. Self-reported respiratory symptoms 

were not consistently related to exposure. Increased respiratory resistance, decreased maximum flow at 50% 

and 75% of vital capacity, and decreased FEV1 were observed in 10 asthmatic adolescents exposed to 

0.1 mg/m3

 sulfuric acid (MMAD 0.6 μm) through a mouthpiece while wearing noseclips or through a face 

mask that allowed oronasal breathing (Koenig et al. 1985). Exposures were for 30 minutes at rest, followed 

by 20 minutes with moderate exercise. There were no statistically significant differences in pulmonary 

function between the two methods of exposure. A significant (p=0.03) decrease in FEV1 of 6.1% was 

observed in 14 adolescent asthmatics that were exposed to 0.035 mg/m3 sulfuric acid (MMAD 0.6 μm) for 

45 minutes (Koenig et al. 1992). During the exposures, the subjects exercised for alternating 15minute 
SULFUR TRIOXIDE AND SULFURIC ACID 44 

2. HEALTH EFFECTS 

periods. No significant effects on lung function were observed after 90 minutes of exposure at 0.035 mg/ m3, 

or after 45 or 90 minutes of exposure at a concentration of 0.07 mg/ m3

. Therefore, the 0.07-mg/ m3 

concentration is presented as a NOAEL in Table 2-l and Figure 2-1. Lung function, assessed by measuring 

SRaw and FEV1,was not affected in exercising asthmatic volunteers (20 male and 12 female, age 6-16) 

exposed to sulfuric acid aerosols (MMAD 0.5 μm) oronasally at up to 0.127 mg/m3

, or orally at 0.134 mg/m3 

for 1 hour (Avol et al. 1990). The study authors noted that in 1 subject, SRaw, increased by 14.2 cm H2Osecond 

during the oronasal study, and by 8.4 cm H2O-second in the oral study, suggesting that there may be 

an acid-sensitive subpopulation of young asthmatics. 

Exposure of 9 asthmatic and 8 healthy seniors (age 60-75) to 0.07 mg/m3

 sulfuric acid (MMAD 0.6 μm) 

through a mouthpiece while wearing noseclips (30 minutes at rest, 10 minutes of exercise) did not have any 

significant effects on FVC, FEV1, or total respiratory resistance in either group of subjects (Koenig et al. 

1993). No effects on SRaw were observed in 9 asthmatics exposed to sulfuric acid aerosols for 16 minutes 

through a mouthpiece at 3 mg/m3

 using aerosols of VMDs of 0.4 or 6 pm (Arks et al. 1991). Exposure of 

10 asthmatics to 1.4 mg/m3

 sulfuric acid aerosols (VMD 6 μm) for 1 hour with exercise during alternating 

15-minute periods also had no effect on SRaw (Aris et al. 1991). Compared to exercise in clean an-, no effects 

on SRaw or forced expiratory function were observed in 27 asthmatics exposed to 0.41 mg/m3

 sulfuric acid 

aerosols (MMAD 0.5 μm) in a chamber for 1 hour with alternating l0minute periods of exercise (Linn et al. 

1986). 

Compared to exposure to sodium chloride aerosols (0.105 mg/ m3

; MMAD 0.64 μm), a 3-hour exposure of 

30 asthmatic or 30 normal volunteers to 0.107 mg/ m3

 sulfuric acid (MMAD 0.64 μm) had no significant 

effects on FVC or FEV1 (Frampton et al. 1995). During the exposures, the subjects exercised intermittently. 

Changes in pulmonary function tests (thoracic gas volume, airway resistance, FVC, FEV1, specific airway 

conductance) were not observed in 12 normal volunteers immediately after and 18 hours after a 2-hour 

exposure to 1 mg/ m3

sulfuric acid (MMAD 0.9 μm) (Frampton et al. 1992). Bronchoscopy, completed 

18 hours after the exposure, did not reveal any effects on the appearance of the airways or the bronchial 

mucosa. Collection of bronchial secretions from these subjects for 12 hours after sodium chloride or acid 

exposure did not reveal any changes in airway mucin glycoproteins or other closely associated proteins (Culp 

et al. 1995). 

Changes in SRaw FVC, and FEV1, were not observed in 30 asthmatic or 15 normal subjects exposed to 

0.1 mg/m3

 sulfuric acid (MMAD 1 μm) for 6.5 hours per day for 2 days (Linn et al. 1994). The subjects 
SULFUR TRIOXIDE AND SULFURIC ACID 45 

2. HEALTH EFFECTS 

exercised during the first 50 minutes of each exposure hour and then rested for 10 minutes, during which 

pulmonary function tests were completed. Not all subjects were fit enough to exercise through six 50minute 

periods. It is not stated whether these were normal or asthmatic subjects. In a study of asthmatic and normal 

volunteers exposed to 0.1 mg/m3

 sulfuric acid aerosols (MMAD 0.5 μm) for 1 hour with alternating 

10-minute exercise periods, only 1 of 14 asthmatics responded with a fall in FEV1 during the first 15 minutes 

of exposure (Anderson et al. 1992). This study provides further evidence that there may be a subgroup of 

asthmatics that are more sensitive to sulfuric acid aerosol exposure. 

The response to unbuffered sulfuric acid aerosols compared to glycine-buffered sulfuric acid aerosols, both at 

pH 2, was studied by Fine et al. (1987). The 8 asthmatic subjects were exposed to the aerosols (MMD 

5.3 μm) through a mouthpiece during 3 minutes of tidal breathing. The exposure concentration was not 

stated, but the nebulizer had a mean liquid water output of 5.7 g/minute. SRaw was not increased after 

inhalation of unbuffered sulfuric acid at pH 2, while a >50% increase was observed in 7 of 8 subjects 

exposed to the glycine-buffered sulfuric acid at pH 2. This study demonstrated that titratable acidity, which 

measures total available hydrogen ion level, has a greater effect on bronchoconstriction than pH, which 

measures total free hydrogen ion concentration. A Bonger duration of bronchoconstriction is also expected 

from buffered acids because of a gradual release of available hydrogen ion. 

A number of human exposure studies suggest that exposure to sulfuric acid aerosols may have more of an 

effect on clearance of particles than on pulmonary function tests. The results reported in these studies are not 

only dependent on the sulfuric acid aerosol size but also on the size of the test particles. The aerodynamic 

size and density of the test particles determines where in the respiratory tract they will deposit. Sulfuric acid 

appears to have different effects on clearance in different regions of the respiratory tract. Enhanced clearance 

of a 99mtechnetium-tagged albumin saline aerosol (MMD 3 μm) was noted in 10 humans exposed by mouth to 

1 mg/m3 sulfuric acid aerosol (MMD 0.5 μm) for 2 hours (Newhouse et al. 1978). Compared to exposure to 

water mist, bronchial clearance 2 hours after the exposure was increased by about 15%. Exposure to 

1 mg/m3

sulfuric acid aerosol had no effects on vital capacity, FEV1, or FEV50%-75%. The study authors 

cautioned that enhanced bronchial clearance should not be considered a beneficial effect, and they attributed 

the effect to a patho-physiological response of the airways to inhaled irritants. The authors also suggested 

that longer term exposure may decrease clearance. 

Enhanced tracheal and lung clearance of 3.4 pm 99m technetium-tagged sulfur colloid was observed in 7 men 

exposed to 0.471 mg/ m3

 sulfuric acid (MMAD 10.3 μm) 60 minutes/day for 4 days (Laube et al. 1993). 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 46 

2. HEALTH EFFECTS 

Pulmonary function tests were not affected in these subjects. The study authors indicated that the mechanism 

underlying the observed changes in clearance was not known. 

In studies of clearance of 99m technetium-tagged ferric oxide particles, subjects were exposed nose only to 

ferric oxide particles at an MMD of 7.6 μm (n=10) (Leikauf et al. 1981) or 4.2 μm (n=8) (Leikauf et al. 

1984), followed by nose-only exposure to sulfuric acid aerosols (MMD 0.5 μm) for 1 hour at about 0, 0.1, 

0.3, or 1 mg/m3

. No effects on tracheal mucociliary transport rate were noted for either particle size, but 

differences in bronchial clearance were observed. For the 7.6~μm particles, a significant decrease (p<0.05) in 

the mean bronchial clearance time, from 80 to 50 minutes, occurred in the low exposure group. However, in 

the high dose group, a significant increase (p<0.05) in the mean bronchial clearance time, 118 minutes, was 

observed (Leikauf et al. 1981). The values were significantly different (p<0.05) from air exposure at the low 

and high concentrations. The study authors noted two response patterns in the subjects of this study. Six 

persons with slower clearance had significant alterations in bronchial clearance, while four subjects with 

faster clearance did not respond to sulfuric acid aerosol exposure. For the 4.2-μm particles, bronchial 

clearance half-times were 80, 110, 106, and 142 minutes at 0, 0.1,0.3, and 1 mg/m3

, respectively (Leikauf et 

al. 1984). The values were significantly reduced (p<0.05) from air exposure at the low and high 

concentrations. In a comparison of their two studies, the authors stated that the inhibitory effect of the high 

concentration started sooner and lasted longer in the group inhaling the smaller radiolabelled ferric oxide 

particles. The high concentration had a greater effect on clearance from the tracheobronchial region 

compared to clearance from the nasopharyngeal region. After exposure to the low concentration, clearance 

half-time was longer than air exposure in the group inhaling the smaller ferric oxide particles, and faster than 

air exposure in the group inhaling the larger iron oxide particles. The low concentration decreased clearance 

in the tracheobronchial region and enhanced clearance in the nasopharyngeal region. 

Slower clearance was also reported in 10 male volunteers exposed to 0.1 mg/m3

 sulfuric acid aerosols 

(MMAD 0.5 μm) for 1 or 2 hours (Spektor et al. 1989). The subjects were exposed to 198gold-tagged iron 

oxide before the sulfuric acid exposures and 99m technetium-tagged iron oxide particles after the exposures. 

Both labeled particles had a size of about 5.2 μm. Clearance of the particles deposited after the exposure was 

slower compared to that of particles deposited before the sulfuric acid exposure. After 2 hours of exposure to 

sulfuric acid aerosols, the clearance half-time tripled compared to air exposure, and reduced clearance was 

still noted 3 hours after the end of the exposure. After 1 hour of exposure, clearance half-time was doubled 

compared to air exposure, and the reduced rate of clearance lasted for 2 hours after the exposure. The results 

of this study suggest a cumulative response of duration of exposure to sulfuric acid aerosols. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 47 

2. HEALTH EFFECTS 

In conclusion, several factors could explain the variability in results for the clearance studies. Clearance is 

affected by the location of respiratory deposition which depends on both the aerodynamic size and density of 

sulfuric acid droplets and test particles. Sulfuric acid appears to have different effects on clearance in 

different regions of the respiratory tract. Differences in exposure concentrations and times may also have 

varying effects on clearance. 

In addition to experimental exposure studies in humans, the effect of sulfuric acid exposure has been studied 

after pollution episodes and following occupational exposure. Hospital admissions for respiratory effects in 

southern Ontario, Canada, were increased on days with high sulfate concentrations (Bates and Sizto 1987). 

This association was observed in the summer but not the winter. In an asthma episode in Japan in which 

more than 600 cases of chronic bronchitis, allergic asthma bronchitis, pulmonary emphysema, and sore throat 

were reported, measurements revealed the presence of acid mist particles and a sulfur trioxide/sulfur dioxide 

ratio of 0.48, indicative of sulfuric acid mist (Kitagawa 1984). The study authors concluded that the 

respiratory symptoms were a result of concentrated sulfuric acid mist with an MMD of 0.7-3.3 μm. 

Concentrations of sulfuric acid were estimated to be 0.8-12.8 mg/m3

. In a large study of nonsmokers in 

California, the development of asthma symptoms and severity of airway obstructive disease was significantly 

associated with ambient concentrations of sulfate (Abbey et al. 1993, 1995). However, correlation between 

levels of sulfates and total suspended particulates (TSPs) suggested that TSPs may have been responsible for 

the observed effects. Air pollution studies are limited because it is difficult to separate effects associated with 

various air pollutants. 

In Uniontown, PA the association was examined between particle-strong acidity (extractable acidity from 

sulfate particles composed partially of sulfuric acid and ammonium bisulfate) and respiratory function in 4th 

and 5th grade children (60 asthmatic and 23 healthy) (Neas et al. 1995). When weighted for time spent 

outdoors, a 12-hour exposure to each 125 nmol/m3

 (0.012 mg/m3 sulfuric acid) increase in particle-strong 

acidity was associated with a 2.5 L/min decrease in evening peak expiratory flow rate (PEFR) in asthmatic 

children. Incidence of cough in healthy and asthmatic children was also associated with particle-strong 

acidity levels. A second group of investigators attempted to simulate the Uniontown air pollution mixture in 

a chamber study of 41 children aged 9-12 years (15 healthy, 26 asthmatic or atopic) (Linn et al. 1997). 

With the exception of ozone, exposure to air pollutants (sulfuric acid with MMAD=0.6 μm and sulfur 

dioxide) were three times the levels of Uniontown so that the total dose in 4 hours was equivalent to a 

12 exposure of the Uniontown pollutant mixture. The ozone level could not be increased because a higher 

concentration would have resulted in irritation Bxposure to the air pollution mixture did not result in 
SULFUR TRIOXIDE AND SULFURIC ACID 48 

2. HEALTH EFFECTS 

significant adverse effects on respiratory performance (FVC, FEV1, and PEFR). Possible reasons for the 

discrepancies between the two studies included differences in the composition of the air pollution mixture, 

differences in exposure time, and psychological effects of chamber exposure. 

Lead-acid battery workers (n=225) were studied for evidence of changes in acute pulmonary function after an 

8-hour shift (Gamble et al. 1984a). The average sulfuric acid exposure concentration was 0.18 mg/m3

, with a 

range of 0.08-0.35 mg/m3 (MMAD 5 μm). Lung function tests (FVC, FEV1, FEV 50%, FEV 75%) completed 

before and after the shift provided no evidence of acute pulmonary effects. 

A slight increase in bronchitis was observed in 460 battery factory workers exposed to sulfuric acid aerosols 

at an average concentration of 1.4 mg/m3

 for up to 40 years (Williams 1970). No effects on FVC or FEV1 

were observed. A small decrease in FVC was observed in 248 workers exposed to an average sulfuric acid 

aerosol concentration of 0.21 mg/m3

 compared to workers exposed to an average concentration of 0.1 mg/m3 

(Gamble et al. 1984b). The FVC was 4.83 L in the high-exposure group, and 5.11 L in the low-exposure 

group, and the difference was statistically significant (p=0.02). The workers were exposed for an average of 

12.2 years. No other significant changes in lung function tests (FEV1, peak flow) were noted. Effects on 

FEV1 were not observed in workers exposed to acid aerosofs (hydrochloric acid, 2.1 mg/m3

; sulfuric acid, 

0.5 mg/m3) for a maximum of 4.5 years (n=ll9-180) (Kremer et al. 1994), or to sulfuric acid aerosols 

(12.6-35 mg/m3

) for from 1 to >15 years (n=20-33) (El-Sadik et al. 1972). For presentation in the 

Table 2-l and Figure 2-l only the low end of the concentration range is shown for the El-Sadik et al. (1972) 

study. 

Among the animal species studied, guinea pigs are most sensitive to sulfuric acid aerosol exposure. During 

l-hour nose-only exposures to 52-61 mg/m3

 sulfuric acid aerosols in the size range of 0.8-1.2 μm (MMAD), 

guinea pigs developed labored breathing and about 6% of the animals died (total number exposed was not 

stated) (Stengel et al. 1993). Excised lung gas volume (an indicator of in viva airway obstruction and hyperresponsiveness) was increased in guinea pigs killed directly after the exposure but not 24 or 72 hours later. 

Labored breathing and hyperinflated lungs (resulting from reflex bronchoconstriction) were reported in 

guinea pigs (8 male, 8 female) exposed to sulfuric acid aerosols for 8 hours (Wolff et al. 1979). The effects 

were observed at 17.4 mg/m3

 for aerosols with an MMAD of 0.8 μm, and at 37.2 mg/m3 for aerosols with an 

MMAD of 0.4 μm. Hemorrhage and transudation of the lungs were also observed following exposure to the 

large, but not the small, aerosol size. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 49 

2. HEALTH EFFECTS 

Dyspnea and cyanosis were observed in 20 guinea pigs within 10-30 minutes of a 4 hour exposure to 32.6 

mg/m3

 sulfuric acid aerosol (MMAD 1.0μ, RH 70-90%), but were not observed 24 hours following exposure 

(Brownstein et al. 1980). Lungs of guinea pigs sacrificed immediately after exposure contained areas which 

were hyperinflated and other areas which were collapsed. Interstitial edema was noted in the hyperinflated 

areas and alveolar edema was observed in the collapsed regions. Desquamation was observed primarily in 

the terminal bronchioles of collapsed regions. In Pungs of guinea pigs killed 24 hours after exposure, 

hyperinflated areas were less pronounced but collapsed regions were more defined. Also noted were 

infiltration of leukocytes in alveolar sacs and septums and fibrin deposits in areas where desquamation 

occurred. 

The effect of aerosol size on lung function was studied in guinea pigs (n=5-11) exposed head-only to sulfuric 

acid while the animals were in a body plethysmograph (Amdur 1958). Control measurements for each guinea 

pig were completed during the 30 minutes before the 1 -hour exposure. In guinea pigs exposed to an aerosol 

size of 0.8 μm (MMD), resistance increased about 1.5-fold at 1.9 mg/m3

, and about 2.2-fold at 42 mg/ m3. 

Exposure to 2.5μm aerosols resulted in resistance increases of about 1.4-fold at 2.3 mg/ m3

 and 4.2-fold at 

43.6 mg/m3

. Increased lung weights and edema were also observed at the high concentration of 2.5-μm 

aerosols. Resistance was increased about 1.4-fold in guinea pigs exposed to 30.5 mg/ m3

 sulfuric acid 

aerosols with an aerosol size of 7 μm. In a comparison of the toxicity of the two smaller aerosol sizes, 

Amdur (1959) indicated that at higher concentrations the larger aerosols produced a greater response, while at 

the lower concentrations the smaller aerosols produced the greater response. The time course of the response 

to the two particle sizes was also different. The response to the smaller aerosol began at once, and after 

10-l 5 minutes of exposure reached the final degree of response present at the end of the hour. Following 

exposure to the larger aerosol, there was little initial response; the effect occurred during the last 

15-20 minutes of the exposure. Amdur (1958, 1959) suggested different mechanisms of response for the 

different aerosol sizes. The small aerosol (0.8 μm) which would reach the more peripheral regions of the 

lungs may result in simple bronchoconstriction. The 2.5-μm aerosols would have their major action on the 

main bronchi and may have resulted in local irritation of the larger air passages causing mucosal swelling, 

increased secretion, and possibly exudation of fluid leading to complete obstruction of major air passages. 

The larger aerosols (7 μm) had little effect because they would not be expected to penetrate beyond the upper 

respiratory tract. 

In an additional study of the effect of aerosol size on the response to sulfuric acid aerosols, Amdur et al. 

(1978) exposed 20-25 guinea pigs head-only to sulfuric acid aerosols with MMDs of 0.3 or 1 μm. 
SULFUR TRIOXIDE AND SULFURIC ACID 50 

2. HEALTH EFFECTS 

Pulmonary function measurements completed before and during the 1 -hour exposures included pulmonary 

flow resistance, pulmonary compliance, tidal volume, respiratory frequency, and minute volume. No changes 

in tidal volume, respiratory frequency, or minute volume were noted. Pulmonary resistance was significantly 

increased by all exposures, with the smaller particles producing a greater response. For the 0.3-μm aerosols, 

resistance was increased 41%, 60%, and 78% at 0.1, 0.51, and 1 mg/m3

, respectively. For the l-μm aerosols, 

resistance was increased 14%, 30%, 47%, and 60% at 0.11, 0.4, 0.69, and 0.85 mg/m3

, respectively. The 

resistance returned to control levels by the end of the 0.5-hour post-exposure period only at the lowest 

concentration of 1 μm. Compliance was significantly decreased at all concentrations during exposure to 0.3­

μm aerosols (-27%, -33%, -40% at 0.1, 0.51 and 1 mg/m3

, respectively), and at the two highest 

concentrations during exposure to 1 pm aerosols (-25% and -28% at 0.69 and 0.85 mg/m3

, respectively). 

No effect on SRaw was observed in 18 guinea pigs exposed to 3.2 mg/m3

 sulfuric acid aerosols (MMAD 

0.5 μm) continuously for 3,7, 14, or 30 days (Kobayashi and Shinozaki 1993). Transient changes in airway 

responsiveness to inhaled histamine were observed. After 3 days of exposure, a significant decrease in 

airway responsiveness was noted. An increase in responsiveness was noted after 14 days of exposure. The 

response to histamine was normal after 7 and 30 days of exposure. Increased airway responsiveness to 

acetylcholine was observed in 6-9 guinea pigs exposed head-only to sulfuric acid aerosols (MMD 0.06 μm) 

at 0.2 mg/ m3

 for 1 hour (Chen et al. 1992b). No effects were observed at 0.03 mg/ m3. Increased 

responsiveness to acetylcholine and histamine in vitro was observed in bronchial rings taken from 5 rabbits 

exposed nose-only to 0.075 mg/m3

 sulfuric acid (MMD 0.3 μm) for 3 hours (El-Fawal and Schlesinger 

1994). No effects were observed at 0.05 mg/m3

. 

Bronchoprovocation challenge with intravenous acetylcholine was studied in 4-12 rabbits exposed nose-only 

to 0 or 0.25 mg/m3

 sulfuric acid aerosols (MMD 0.3 μm) 1 hour per day, 5 days per week, for 4, 8, or 

12 months (Gearhart and Schlesinger 1986). Sulfuric acid exposure resulted in increased bronchial 

sensitivity at all exposure durations. The doses of acetylcholine that resulted in an increase in pulmonary 

resistance 150% of baseline (ED150%) in μg/kg/minute were 0, 18.7, 2, 1.5, and 1.2 at 0, 2, 4, 8, and 

12 months of exposure, respectively. Values at all time points were significantly different from the controls 

but not from each other. Exposure to sulfuric acid had no effects on dynamic compliance or respiratory rate. 

The study authors suggest that the lack of effect on dynamic compliance suggests that the site of increased 

airway responsiveness induced by sulfuric acid may have been predominantly the larger bronchi. 
SULFUR TRIOXIDE AND SULFURIC ACID 51 

2. HEALTH EFFECTS 

A significant (p=0.0l) decrease in carbon monoxide diffusion capacity was observed in 4 beagle dogs 

exposed to 0.755 mg/m3

 sulfuric acid (90% of the particles were <0.5 μm in diameter) 21 hours per day for 

225 days (Lewis et al. 1969). The diffusion capacity was 6.3 mL/mmHg/min in exposed dogs and 

7.4 mL/mmHg/min in control dogs Residual volume was 163±11 mL and 182±12 mL in control and 

exposed dogs, respectively. A statistical test for residual volume was not provided. 

Clearance of particles has also been studied in animals. Clearance of 51chromium-labeled microspheres 

(activity median aerodynamic diameter [AMAD] 1.9 μm) from the head was not affected in 10 ferrets 

exposed nose-only to 0.5 or 1 mg/m3

 sulfuric acid aerosols (MMAD 0.3 μm) for 4 hours (Mannix et al. 

1991). Clearance from the lungs was significantly accelerated. The half-time of clearance was 1,126 hours 

in air-exposed ferrets, 773 hours at 0.5 mg/m3

, and 630 hours at 1 mg/m3. Decreased clearance of 

85strontium-labeled latex microspheres (MMAD 3.5 μm) from the respiratory region of the lungs was 

observed in 3 rabbits exposed to 0.05 mg/m3

 sulfuric acid aerosols (MMAD 0.3 μm) 4 hours per day for 

14 days (Schlesinger 1990a). Increased alveolar clearance of 3.5-μm latex particles was observed in 

4 rabbits exposed to sulfuric acid aerosols (MMD 0.3 μm) at 0.25 mg/m3

 for 1 hour per day, 5 days per 

week, for 1,57, or 240 days (Schlesinger and Gearhart 1986). 

The mucociliary clearance of 99mtechnetium-labeled ferric oxide particles (MMAD 4.5 μm) was studied in 

groups of 8 rabbits exposed to sulfuric acid aerosols (MMAD 0.3 μm) for 1 hour via an oral delivery tube. A 

concentration range of 0.1-1.084 mg/m3

 was studied by Schlesinger et al. (1984), and a concentration range 

of 0.260-2.155 mg/ m3 was studied by Chen and Schlesinger (1983). In these studies each rabbit was 

exposed multiple times. A series of 10 air-sham exposures was completed before any sulfuric acid aerosol 

exposures. Tests at each concentration were completed twice for each rabbit, and the order of exposure was 

randomized. The results of both studies, in terms of mean residence times, were presented in the Schlesinger 

et al. (1984) report. The complete data set was subjected to polynomial regression analysis, and the threshold 

concentration for no effects on clearance was 0.1 mg/m3

. At 0.2 mg/m3, clearance was significantly 

increased, while at 1.5 mg/ m3

 clearance was significantly decreased. The study authors suggested that the 

increase in clearance at low concentrations and the decrease at higher concentrations may be a result of 

differential effects on the upper and lower bronchial tree. At low concentrations, sulfuric acid can stimulate 

mucus transport in the proximal airways of the bronchial tree where only small amounts of the aerosol are 

deposited, while it may slow transport in more distal airways. 
 

 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 52 

2. HEALTH EFFECTS 

The effect of sulfuric acid exposure on particle clearance has been studied in donkeys and rabbits following 

intermediate or chronic exposure. For mucociliary clearance, donkeys are considered to closely model 

humans. A trend toward erratic and slower bronchial clearance of 99m technetium-tagged ferric oxide particles 

(MMAD 5 μm) was observed in 4 donkeys exposed nose-only to about 0.1 mg/ m3 sulfuric acid aerosols 

(MMAD 0.5 μm) 1 hour per day, 5 days per week, for 6 months (Schlesinger et al. 1979). Each of the 

donkeys studied served as its own control. The effects on clearance were more prominent in 2 of the donkeys 

that had been used in a previous study involving twelve l-hour sulfuric acid exposures. There was no 

evidence for persistence of effects from the earlier study. Effects on clearance of 99m technetium-tagged ferric 

oxide particles (MMAD 4.5 μm) were not observed during the exposure period in 5 rabbits exposed to 

0.125 mg/ m3

 sulfuric acid (MMD 0.3 μm) 2 hours per day, 5 days per week, for 4,8, or 12 months 

(Schlesinger et al. 1992a). During a 6-month recovery period, decreased clearance was observed in rabbits 

exposed for 12 months. 

In rabbits (4/group) exposed to 0.25 mg/ m3

 sulfuric acid (MMD 0.3 μm) 1 hour/day, 5 days/week for 4, 8, or 

12 months, a decrease in the clearance rate of 99m technetium-tagged ferric oxide particles was observed one 

week into the exposure period (Gearhart and Schlesinger 1989). The clearance rate continued to decrease 

throughout the exposure period and during a 3-month recovery period following the 12-month exposure time. 

Additional observations included progressive increases in the ratio of small to large airways, the number of 

secretory cells, and the acid glycoprotein content of mucous. During the 3-month recovery period, the 

numbers of secretory cells and the acid glycoprotein content of the mucous remained high, but the ratio of 

small to large airways no longer differed significantly from those of controls. The study demonstrated the 

persistence of certain sulfuric acid-induced effects up to three months past exposure. 

The effects of sulfuric acid exposure on tracheal mucus were studied in rats and guinea pigs exposed in a 

chamber for 4 hours (Lee et al. 1995). Six rats were exposed to a concentration of 94.1 mg/ m3

 (MMD 

0.8 μm), and 5 guinea pigs were exposed to a concentration of 43.3 mg/ m3

 (MMD 0.93 μm). Surface tension 

of the mucus was not affected by sulfuric acid exposure in either species, but electron microscopy indicated 

that the mucus layer was five or more times thicker in both species following sulfuric acid exposure, with a 

greater effect observed in guinea pigs. In water-exposed control guinea pigs the mucus layer was about 1 l.trn, 

while it was 5-40 μm in acid-exposed guinea pigs. The mucus of both species contained granular material 

and membrane-bound vesicles. Despite the changes in mucus, the acid aerosol exposure did not affect the 

ability of the mucus to submerge other particles. Some of the guinea pigs developed pulmonary edema, but 

further details were not provided. 
 

SULFUR. TRIOXIDE AND SULFURIC ACID 53 

2. HEALTH EFFECTS 

The effect of aerosol size on the levels of total protein, p-glucuronidase, and lactate dehydrogenase in lung 

lavage fluid has been studied in 6 guinea pigs exposed nose-only for 3 hours to filtered air or to 0.3 mg/m3 

sulfuric acid aerosols with an MMD of 0.3 or 0.04 μm (Chen et al. 1992a). The 3-hour exposure to the 

0.3-μm aerosols resulted in increases in total protein, β-glucuronidase, and lactate dehydrogenase, while only 

P-glucuronidase was increased after exposure to the 0.04-μm aerosol. The increases were observed 

immediately after the exposure and were not observed 24 hours later. Lung lavage fluid levels of lactate 

dehydrogenase, prostaglandin E2, and prostaglandin F2α were not affected in 5 rabbits exposed to 

0.125 mg/m3

 sulfuric acid aerosols (MMD 0.3 μm) for 3 hours (Schlesinger et al. 1992b). Lactate 

dehydrogenase in lung lavage fluid was also not affected in 5 rabbits exposed to 0.5 mg/m3

 sulfuric acid 

(MMD 0.3 μm) for 2 hours (Zelikoff and Schlesinger 1992). Lactate dehydrogenase and protein were 

increased in lung lavage fluid 24 hours after 5 rabbits were exposed to 1 mg/m3

 sulfuric acid aerosols (MMD 

0.3 μm) 2 hours per day for 4 days (Zelikoff et al. 1994). No significant effects on the protein in the lung 

lavage fluid or on the lung tissue protein content were observed in 4-36 rats exposed to 1.29 mg/m3

 sulfuric 

acid aerosols (MMAD 0.4 pm) for 23.5 hours per day for 3 or 7 days (Warren and Last 1987). The collagen 

synthesis rate of the lungs was not affected in 12-41 rats exposed to 1.09 mg/m3

 sulfuric acid (MMAD 

0.4 μm) 23.5 hours per day for 7 days (Warren and Last 1987). 

Arachidonic acid metabolites (prostaglandins E2 [PGE2]and F2α [PGF2α], thromboxane B2 and leukotriene 

B4) were measured in the lung lavage fluid of 5 rabbits exposed to sulfuric acid (MMD 0.3 μm) 1 hour per 

day for 5 days at 0, 0.25, 0.5, or 1 mg/m3

 (Schlesinger et al. 1990b). Sulfuric acid exposure resulted in a 

reduction in PGE2 production that was statistically significant beginning at 0.5 mg/m3

, a reduction in PGF2α

production that was statistically significant at 1 mg/m3, and a statistically significant reduction in 

thromboxane B2 production at all exposure concentrations. No change in leukotriene B4 production was 

observed. The significance of the effect of the reduction in these arachidonic acid metabolites that act as 

vasoconstrictors is not known. 

In an 8-hour LC50 study of groups of 5-12 guinea pigs exposed to l-μm sulfuric acid aerosols in the range of 

8-85 mg/m3

, effects observed in the lungs of animals that survived for up to 3 weeks after the exposure 

included spotty areas of old hemorrhage and some areas of consolidation especially around the hilar regions 

(Amdur et al. 1952a). Adherence of the lungs to the diaphragm and pleural walls was sometimes observed. 

Microscopic pneumonic changes, fibrosis, thickening of the alveolar walls, atelectasis, and congestion of the 

alveolar space and bronchi were observed. The study authors indicated that the changes were consistent with 

a severe inflammatory process that had subsided. The concentrations at which the effects were observed were 
SULFUR TRIOXIDE AND SULFURIC ACID 54 

2. HEALTH EFFECTS 

not stated. Microscopic lesions of the respiratory tract of the rats, mice, guinea pigs, and rabbits that died in 

the Treon et al. (1950) study were described as degenerative changes of the epithelium, pulmonary hyperemia 

and edema, some cases of focal pulmonary hemorrhages, and areas of atelectasis and emphysema. The 

microscopic changes were not described in relation to exposure concentration. 

Diffuse regional alveolitis and varying degrees of septal edema were observed in 20 guinea pigs exposed to 

10 mg/ m3

sulfuric acid aerosols (MMD 0.89 μm) for 5, 7, 14, 21, or 28 days (Cavender et al. 1977). 

Microscopic examination of the lungs did not reveal any effects in 20 rats exposed to 100 mg/ m3

 sulfuric acid 

for 5 days (Cavender et al. 1977). The number of hours the guinea pigs and rats were exposed each day was 

not stated. Edema and hemorrhage were observed in the lungs of 10 male and 10 female guinea pigs exposed 

to 25 mg/ m3

 sulfuric acid aerosols (MMD 1 μm) 6 hours per day for 2 days (Cockre11 et al. 1978). 

Transmission electron microscopy showed an increased number of type II alveolar cells; alveolar 

macrophages in the alveoli, and vacuoles were observed in type I cells. Lesions were not observed in the 

more proximal segments of the airways including the bronchi, trachea, or larynx. 

Gross and microscopic examination of the nasal turbinates, trachea, and lungs of 35 mice exposed to 

20 mg/m3

 sulfuric acid aerosols (CMD 2.4μm) 7 hours per day on gestation days 6-l 5 revealed no evidence 

of toxicity that could be attributed to the exposure (Murray et al. 1979). Subacute rhinitis and tracheitis were 

observed in 20 rabbits exposed to 20 mg/m3

 sulfuric acid (CMD 2.4 μm) 7 hours per day on gestation 

days 6-18 (Murray et al. 1979). 

The effect of aerosol size on pathological changes in the respiratory tract was studied in groups of 

6-19 guinea pigs exposed to sulfuric acid aerosols for 32-139 days (Thomas et al. 1958). Exposure 

concentrations were 0,2, or 25 mg/ m3

 for the 0.5-μm aerosols, and 0 or 2-4 mg/ m3 for the 0.9- and 4-pm 

aerosols. The guinea pigs, including controls, were sacrificed with chloroform, which may also have caused 

some lung effects. Microscopic examinations of pulmonary tissues were scored on a scale of 0-4, with 

4 indicating the most severe effects. The alterations that were scored were atelectasis, emphysema, 

hyperemia, edema, hemorrhage, thrombosis of the alveolar capillaries, perivenous lymphocytic infiltration, 

distention of the lymph channels, extent and density of alveolar exudate, and the presence or absence of 

fibrosis. The medium aerosol size caused more effects in the lungs than the other sizes, while the large 

aerosol size caused greater effects in the upper respiratory tract. In the lungs, the average histological scores 

were 0.15, 0.63, and 0.28 for the small, medium, and large aerosols, respectively. In the upper respiratory 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 55 

2. HEALTH EFFECTS 

tract, the average histological scores were 0.1, 0.04, and 0.76 for the small, medium, and large aerosols, 

respectively. The scores for individual histopathological changes never exceeded 2. 

In a study using three aerosol sizes, histopathological changes in the respiratory tract were not observed in 

guinea pigs (50 male, 50 female) exposed to sulfuric acid 23 hours per day, 7 days per week, for 52 weeks 

(Alarie et al. 1973, 1975). No effects were observed at 0.9 mg/m3

 at an MMD of 0.49 μm, at 0.08 mg/m3 at 

an MMD of 0.84 μm, or at 0.1 mg/m3

 at an MMD of 2.78 μm. In cynomolgus monkeys (groups of 4-5 of 

each sex) exposed to sulfuric acid aerosols 23.3 hours per day, 7 days per week, for 78 weeks, 

histopathological changes were reported in the respiratory tract (Alarie et al. 1973). For the smaller aerosol 

size, moderate-to-severe bronchial epithelial hyperplasia and thickening of the walls of the respiratory 

bronchioles were observed in all 9 monkeys exposed at 4.79 mg/m3

 (MMD 0.73 μm), with no effects at 

0.48 mg/m3

 (MMD 0.54 μm). In the monkeys exposed at 4.79 mg/m3, no change in arterial oxygen was 

observed. For the larger aerosol size, moderate bronchiolar epithelial hyperplasia, thickening of the walls of 

the respiratory bronchioles, increases in the thickness of the alveolar walls, and hyperplasia and hypertrophy 

of the alveolar epithelial cells were observed in all 9 monkeys exposed to 2.45 mg/m3

 (MMD 3.6 μm). 

Because these effects were associated with decreased arterial oxygen (from 102 mmHg before exposure to 

70 mmHg at 77 weeks) and a blood pH of 7.26-7.30, the 2.45-mg/ m3

 concentration is considered a serious 

LOAEL. At a concentration of 0.38 mg/m3

 (MMD 2.15 μm), slight bronchiolar epithelial hyperplasia was 

observed in 5 of 9 monkeys, and slight thickening of the walls of the respiratory bronchioles was observed in 

3 of 9 monkeys. No effects on alveoli or on arterial oxygen were observed at 0.38 mg/ m3

. 

Cardiovascular Effects. An electrocardiogram revealed abnormal ventricular activity in a previously 

healthy 40-year old male worker 7 months after he was accidentally sprayed in the face with 35% fuming 

sulfuric acid (equivalent to 108.04% sulfuric acid) and was exposed to sulfuric acid mists and vapors for 8 

minutes while he rinsed himself off in a safety shower (Goldman and Hill 1953). The subject suffered 

permanent pulmonary damage which eventually led to the development of fibrosis and emphysema, but there 

was no discussion as to whether the cardiac effect was secondary to pulmonary injury. Heart rate at the time 

of transition between nasal and oronasal breathing was not affected in 7 exercising healthy human subjects 

exposed head-only to 0.471 mg/ m3

 sulfuric acid aerosols (MMAD 10 μm) for 1 hour (Bowes et al. 1995). 

An association between ambient sulfate concentrations and myocardial infarctions was observed among 

6,340 nonsmokers in California only with exceedance frequencies greater than 6 μg / m3

 of sulfate (Abbey et 

al. 1995). Interpretation of air pollution studies requires caution because it is difficult to separate effects 

associated with individual air pollutants. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 56 

2. HEALTH EFFECTS 

Histopathological changes in the heart were not observed in 9 cynomolgus monkeys exposed to sulfuric acid 

aerosols at up to 4.79 mg/ m3

, 23.3 hours per day, 7 days per week, for 78 weeks (Alarie et al. 1973), or in 

guinea pigs (groups of 50 of each sex) at concentrations up to 0.9 mg/ m3

, 23 hours per day, 5 days per week, 

for 52 weeks (Alarie et al. 1973, 1975). 

Hematological Effects. Red blood cell glutathione reductase level was unaffected in 18 healthy males 

exposed to 0.1 mg/m3

 sulfuric acid (MMD 0.5 μm) for 4 hours (Chaney et al. 1980). 

Changes in hematocrit, hemoglobin, red blood cell counts, and white blood cell counts were not observed in 

9 cynomolgus monkeys exposed to sulfuric acid aerosols at up to 4.79 mg/m3

, 23.3 hours per day, 7 days per 

week, for 78 weeks (Alarie et al. l973), or in guinea pigs at concentrations up to 0.9 mg/m3

, 23 hours per 

day, 5 days per week, for 52 weeks (Alarie et al. %973,1975). 

Hepatic Effects. Biochemical blood parameters, such as serum glutathione, 2,3-diphosphoglycerate, 

serum glutamic oxaloacetic acid transaminase, and serum vitamin E were unaffected in 18 healthy males 

exposed to 0.1 mg/ m3

 sulfuric acid (MMD 0.5 μm) for 4 hours (Chaney et al. 1980). 

No effects on liver weight were noted in mice or rabbits exposed to 20 mg/ m3

 sulfuric acid aerosols (CMD 

2.4 μm) 7 hours per day on gestation days 6-15 for 35 mice and days 6-18 for 20 rabbits (Murray et al. 

1979). Microscopic changes in the liver and treatment-related changes in serum levels of liver enzymes were 

not observed in cynomolgus monkeys exposed to sulfuric acid aerosols at up to 4.79 mg/ m3

, 23.3 hours per 

day, 7 days per week, for 78 weeks (Alarie et al. 1973), or in guinea pigs at concentrations up to 0.9 mg/ m3

, 

23 hours per day, 5 days per week, for 52 weeks (Alarie et al. 1973, 1975). Aspartate aminotransferase 

(AST) and alanine aminotransferase (ALT) were measured in both species; lactic acid dehydrogenase and 

alkaline phosphatase were also measured in monkeys. The liver enzyme data were not presented in the paper. 

However, the authors stated that enzyme levels were highly variable in all groups of monkeys and there were 

no trends suggesting effects related to exposure. 

Renal Effects. No studies were located regarding renal effects in humans after inhalation exposure to 

sulfur trioxide or sulfuric acid. 

Treatment-related microscopic changes in the kidneys were not observed in 9 cynomolgus monkeys (Alarie et 

al. 1973) or in guinea pigs (50 of each sex) (Alarie et al. 1973, 1975) exposed chronically to sulfuric acid 
 

SULFUR TRIOXIDE AND SULFURIC ACID 57 

2. HEALTH EFFECTS 

aerosols. The monkeys were exposed to sulfuric acid aerosols at up to 4.79 mg/ m3 23.3 hours per day, 7 days 

per week, for 78 weeks (Alarie et al. 1973). The guinea pigs were exposed at concentrations up to 0.9 mg/m3 

23 hours per day, 5 days per week, for 52 weeks (AParie et al. 1973, 1975). 

Dermal Effects. No studies were located regarding dermal effects in humans or animals after inhalation 

exposure to sulfur trioxide or sulfuric acid. 

Ocular Effects. Lacrimation was reported in volunteers exposed to sulfuric acid aerosols (MMD 1.54 μm) 

at 20.8 mg/ m3

 (Sim and Pattle 1957). The exposures, completed at a relative humidity of 91%, were almost 

intolerable at the onset. Eye irritation was not reported by subjects exposed to a concentration of 39.4 mg/ m3 

(MMD 0.99μm ) at a relative humidity of 63%. This study is of limited value because the subjects were 

allowed to smoke during the exposures. Minor eye irritation was significantly increased in asthmatics 

exposed to 0.999 and 1,460 mg/ m3

 sulfuric acid mist (MMD 0.9 μm) for 1 hour (Avol et al. 1988). 

However, statistically significant increases in eye irritation were not reported by healthy subjects exposed to 

concentrations as high as 1,578 mg/m3

 under the same conditions. 

No studies were located regarding ocular effects in animals after inhalation exposure to sulfur trioxide or 

sulfuric acid. 

Body Weight Effects. No effects on body weight gain were noted in mice or rabbits exposed to 20 mg/m3 

sulfuric acid aerosols (CMD 2.4 μm) 7 hours per day on gestation days 6-15 for mice and days 6-18 for 

rabbits (Murray et al. 1979). Effects on body weight were not observed in rabbits exposed to 0.125 mg/ m3 

sulfuric acid aerosols (MMD 0.3 μm) 2 hours per day, 5 days per week, for 4,8, or 12 months (Schlesinger et 

al. 1992a). Chronic exposure to sulfuric acid aerosols also had no effect on body weights of cynomolgus 

monkeys (Alarie et al. 1973) or guinea pigs (Alarie et al. 1973, 1975). The monkeys were exposed to 

sulfuric acid aerosols at up to 4.79 mg/m3

 23.3 hours per day, 7 days per week, for 78 weeks (Alarie et al. 

1973). The guinea pigs were exposed at concentrations up to 0.9 mg/ m3 23 hours per day, 5 days per week, 

for 52 weeks (Alarie et al. 1973, 1975). 
SULFUR TRIOXIDE AND SULFURIC ACID 58 

2. HEALTH EFFECTS 

Other Systemic Effects. Studies of workers indicate that exposure to sulfuric acid aerosols can result in 

lowered pH of the saliva (El-Sadik et al. 1972), erosion of the teeth (El-Sadik et al. 1972; Gamble et al. 

1984b; Malcolm and Paul 196 l), and increased prevalence of periodontal pockets (Tuominen 199 1). The 

subjects in the El-Sadik et al. (1972) study were exposed to concentrations of 12.6-35 mg/ m3

. Only the low 

end of the concentration range is shown in Table 2- 1 and Figure 2- 1. The lowest average concentration at 

which effects on the teeth were noted was 0.21 mg/ m3

 for 248 workers exposed an average of 12.2 years 

(Gamble et al. 1984a). Malcolm and Paul (196 1) indicated that the front teeth of the 63 exposed workers in 

their study were the teeth most often affected, suggesting the effect was the result of direct impingement of 

acid mist on the teeth. 

No studies were located regarding other systemic effects in animals after inhalation exposure to sulfur 

trioxide or sulfuric acid. 

2.2.1.3 Immunological and Lymphoreticular Effects 

The function of alveolar macrophages was studied in cells collected by lung lavage 18 hours after 

12 volunteers were exposed to 1 mg/ m3

 sulfuric acid and sodium chloride aerosol (MMAD 0.9 μm) for 

2 hours each (Frampton et al. 1992). The sulfuric acid and sodium chloride exposures were separated by at 

least 2 weeks. Sulfuric acid exposure had no effect on cell recovery in the lavage fluid, providing no evidence 

of an inflammatory response. The ability of alveolar macrophages to lyse antibody-coated red blood cells 

showed a small increase following sulfuric acid exposure. This effect was not considered to be adverse. The 

ability of alveolar macrophages to become associated with and inactivate influenza virus was not significantly 

affected by sulfuric acid exposure. 

Increased mortality was not observed in 80 mice challenged for 20 minutes with an aerosol of Streptococcus 

pyrogens directly after head-only exposures to ultrafine (VMD <0.1 μm) sulfuric acid aerosols (Grose et al. 

1982). The mice were exposed to sulfuric acid for 2 hours at 0.543 mg/ m3

 or for 2 hours per day for 5 days 

at 0.365 mg/ m3

. 

Additional animal studies have examined the in vitro function of immune cells collected by lung lavage from 

animals exposed to sulfuric acid aerosols. Intracellular pH of alveolar macrophages was decreased in guinea 

pigs 15.6% following a single 3-hour chamber exposure and by 23.5% after five 3-hour exposures to 

0.97 mg/ m3

 sulfuric acid (MMD 0.3 μm) (Qu et al. 1993). Decreased intracellular pH of alveolar 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 59 

2. HEALTH EFFECTS 

macrophages was also observed in macrophages from rabbits exposed nose-only to 0.125 mg/ m3 sulfuric acid 

aerosols (MMD 0.3 μm) for 3 hours (Chen et al. 1995). No effect was observed at 0.05 mg/ m3

. Intracellular 

pH must be maintained within a narrow range to ensure normal cell functions such as regulation of the cell 

cycle and signal transduction (Chen et al. 1995; Qu et al. 1993). 

A single 3-hour exposure of guinea pigs to 0.3 mg/ m3 sulfuric acid aerosol with an MMD of 0.3 ym 

enhanced the phagocytic activity of alveolar macrophages 24 hours after exposure (Chen et al. 1992a). A 

single 3-hour exposure to 0.3 mg/ m3

 sulfuric acid aerosol with an MMD of 0.04 μm depressed the ability of 

alveolar macrophages to phagocytize particles. The study authors suggested that, compared to larger 

droplets, smaller droplets deliver a higher dose to the alveolar macrophages. Endotoxin-stimulated 

production of tumor necrosis factor (TNF) by alveolar macrophages was significantly increased by four daily 

3-hour exposures to 0.3 mg/ m3

 sulfuric acid at MMDs of both 0.04 and 0.3 μm (Chen et al. 1992a). 

A series of studies has been completed in which macrophage function has been studied in rabbits following 

exposure to sulfuric acid aerosols with an MMD of 0.3 μm (Schlesinger 1987; Schlesinger et al. 1990a, 

1992b; Zelikoff and Schlesinger 1992; Zelikoff et al. 1994). A 2-hour exposure to 0,0.05,0.075,0.125, or 

0.5 mg/ m3

 sulfuric acid aerosols had no effect on the number of cells recovered in lavage fluid, the percentage 

of polymorphonuclear cells, or macrophage viability (Zelikoff and Schlesinger 1992). At the three highest 

concentrations, sulfuric acid exposure significantly reduced macrophage TNF cytotoxic activity directed 

towards a tumorigenic target cell and reduced zymosan-stimulated production of superoxide anion. The 

effects at the three highest concentrations were not significantly different from each other. Following a 3­

hour exposure to 0.075 mg/ m3

, decreased phagocytic activity, production of superoxide anion, and TNF 

activity were observed, with no effects at 0.05 mg/ m3 (Schlesinger et al. 1992b). Macrophage-mediated 

immunity was suppressed following 4 daily 2-hour exposures to 0.75 mg/ m3

 (Zelikoff et al. 1994), 5 daily lhour exposures to 1 mg/ m3 (Schlesinger et al. 1990a), and 13 daily 2-hour exposures to 0.5 mg/ m3 

(Schlesinger 1987). Based on the results of their studies of macrophage function, Zelikoff et al. (1994) 

concluded that there was an absence of a concentration-response relationship. Once a critical level of acid 

was reached, no further effects were observed. 

The release of histamine from antigen- or A23 187-induced mast cells was studied in cells collected from 

guinea pigs exposed continuously to 0,0.3, 1, or 3.2 mg/ m3

 sulfuric acid aerosols with MMDs in the range of 

0.55-0.73 μm for 2 or 4 weeks (Fujimaki et al. 1992). Sulfuric acid exposure did not have any effects on the 

number of mast cells in the lavage fluid. Antigen-induced histamine release from mast cells was significantly 
SULFUR TRIOXIDE AND SULFURIC ACID 60 

2. HEALTH EFFECTS 

enhanced at 1 and 3.2 mg/m3 following 2 weeks of exposure, but not after 4 weeks of exposure. A23187­

induced histamine release was enhanced at 1 mg/ m3

 following 2 weeks of exposure but was suppressed at 

3.2 mg/m3

 following 4 weeks of exposure. No effects on mast cell function were noted at 0.3 mg/m3. 

The highest NOAEL values and all LOAEL values from each reliable study for immunological and 

lymphoreticular effects in each species and duration category are recorded in Table 2-l and plotted in 

Figure 2-1. 

2.2.1.4 Neurological Effects 

Lightheadedness and dizziness were reported by 3 of 12 persons accidentally exposed to sulfur trioxide for 

approximately 2 hours (Stueven et al. 1993). The exposure concentrations were not stated. 

Fatigue and headaches were reported more frequently in 21 asthmatic volunteers exposed to sulfuric acid 

aerosols at 0.999 mg/m3

 (MMD 0.9 μm) for 1 hour (Avol et al. 1988). These subjective symptoms were not 

reported at 0.396 mg/m3

, nor were they reported by 21 normal volunteers exposed to sulfuric acid aerosol 

concentrations as high as 1.578 mg/m3

. 

Uncoordinated movements were observed in three guinea pigs following a 15minute exposure to 165 mg/m3 

sulfuric acid mist (l-2 μm) but were not reported following exposure to higher doses (Treon et al. 1950). 

The NOAELs and LOAEL for neurological effects in humans identified in the Avol et al. (1988) study are 

recorded in Table 2-l and plotted in Figure 2-1a 

2.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to sulfur trioxide 

or sulfuric acid. 

No significant effects on the mean numbers of implants/dam or resorptions/litter were noted in 35 mice or 

20 rabbits exposed to 20 mg/m3

 sulfuric acid aerosols (CMD 2.4 μm) 7 hours per day on gestation days 6-15 

for mice and 6-18 for rabbits (Murray et al. 1979). 
SULFUR TRIOXIDE AND SULFURIC ACID 61 

2. HEALTH EFFECTS 

The NOAEL values for mice and rabbits for reproductive effects are recorded in Table 2- 1 and plotted in 

Figure 2-1. 

2.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans after inhalation exposure to sulfur 

trioxide or sulfuric acid. 

No significant effects on fetal body weights or on the incidence of major or minor malformations were noted 

in the offspring of 35 mice or 20 rabbits exposed to 20 mg/ m3

 sulfuric acid aerosols (CMD 2.4 μm) 7 hours 

per day on gestation days 6-15 for mice and 6-18 for rabbits (Murray et al. 1979). 

The NOAEL values for mice and rabbits for developmental effects are recorded in Table 2-l and plotted in 

Figure 2- 1. 

2.2.1.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals after inhalation exposure to sulfur 

trioxide or sulfuric acid. 

Genotoxicity studies are discussed in Section 2.5. 

2.2.1.8 Cancer 

In a study regarding the effect of air pollutants in nonsmokers, sulfates were not shown to be associated with 

cancer (Abbey et al. 1995). Increases in respiratory tract cancers were not observed among a cohort of 

400 male workers at a sulfuric acid plant in Sweden (Englander et al. 1988). The men were exposed to 

sulfuric acid aerosols at concentrations of <0.1-2.9 mg/ m3

 for at least 6 months. There was a significant 

(p=0.006) increase in bladder cancer in this population. The study authors suggested that bladder cancer in 

this population may not be a result of sulfuric acid aerosol exposure but may have been a result of chance or 

smoking or other factors such as diet. 
SULFUR TRIOXIDE AND SULFURIC ACID ` 62 

2. HEALTH EFFECTS 

A case of laryngeal cancer was reported in a man (life-long nonsmoker) exposed to sulfuric acid from poorly 

maintained batteries used to operate an electric forklift truck (Houghton and White 1994). The man operated 

a fork lift truck for 11 years Exposure concentrations were not stated, but the man described the surface of 

the batteries as always being wet with sulfuric acid; he often suffered bums on his legs and clothing damage. 

Employment history did not reveal exposure to any other industrial carcinogens. Three cases of laryngeal 

cancer were reported among 78 workers at a factory that pickled stainless steel pipes (Ahlborg et al. 1981). 

Based on cancer registry data, 0.05 laryngeal cancer cases would have been expected in this population. All 

three persons with laryngeal cancer were moderate smokers. Exposures included sulfuric acid, nitric acid, 

oxalic acid, ammonium bifluoride, soap, sodium thiosulfate, sodium hydrosulfite, hydrogen fluoride, and low 

levels of chromium, nickel, and asbestos. 

Occupational studies of isopropyl alcohol production workers (Alderson and Rattan 1980), soap production 

workers (Forastiere et al. 1987), and refinery and chemical plant workers (Soskolne et al. 1982, 1984, 1992) 

have reported small increases of upper respiratory tract cancers (nasal, laryngeal) and lung cancers in workers 

exposed to sulfuric acid aerosols. Exposure concentrations were not well characterized in these studies. In a 

study of workers from two battery manufacturers and two steel works in Britain, a small increase in upper 

respiratory tract cancers (e.g., lip, retromolar area, tongue, nasopharynx, tonsil, larynx, gum, and nasal sinus) 

was observed (Coggon et al. 1996). The study authors indicated that a small increase in risk occurred at 

1 mg/ m3

, but not at lower concentrations. Although this study provides limited evidence that the risk of 

cancer in the upper respiratory and digestive system is increased, the risk estimate was based on a small 

number of cases, and the excess was not significant. The study does not provide any information on alcohol 

or tobacco use. There is also no information about exposure before 1970. 

In a study of male steel workers exposed to acid mists during pickling operations at an average concentration 

of 0.2 mg/ m3

 for an average of 9.5 years, a statistically significant increase in laryngeal cancer was observed 

(Steenland et al. 1988). Nine of 879 workers were diagnosed with laryngeal cancer, while after adjusting for 

smoking, 3.44 cases of laryngeal cancer were expected. All cases were either current or former smokers. 

Quantitative individual sulfuric acid exposure data were not provided. The study authors indicated that the 

pickling process did not generate appreciable levels of metal particulates. This population has also been 

studied for lung cancer (Beaumont et al. 1987; Steenland and Beaumont 1989). A total of 41 lung cancers in 

a cohort of 1,165 steelworkers were identified (Steenland and Beaumont 1989). The standardized mortality 

ratio (SMR) for lung cancer after adjusting for smoking for those with 20 years or more since first exposure 

was 1.5, with a 95% confidence interval of 1.05-2.27 (Steenland and Beaumont 1989). There was little 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 63 

2. HEALTH EFFECTS 

evidence of a duration-response effect, and possible confounders such as exposure to nickel and silica were 

not considered in this study. 

A case control study was conducted of 352 white males with laryngeal cancer and 1,050 white male controls 

admitted to a hospital between 1957 to 1965. Exposure to sulfuric acid was estimated through a review of 

occupational history. The risk of developing laryngeal cancer was significantly greater in heavy smokers with 

occupational exposures to sulfuric acid than in heavy smokers with no sulfuric acid exposure. Relative risks 

for laryngeal cancer were 2.43 and 2.05 in heavy smokers exposed to sulfuric acid for ≥20 years and heavy 

smokers exposed to sulfuric acid for <20 years, respectively (Cookfair et al. 1985). The study is limited 

because actual exposure concentrations were not known. 

No studies were located regarding cancer in animals after inhalation exposure to sulfur trioxide or sulfuric 

acid. 

2.2.2 Oral Exposure 

No studies in humans or animals were located regarding oral exposure to sulfur trioxide. 

2.2.2.1 Death 

Mineral acids, including sulfuric acid, are commonly used as cleaning agents in India. In a report of 

10 human cases of sulfuric acid ingestion from January 1978 to December 1980,2 died (Dilawari et al. 

1984). One person died of gastric perforation, and the second person died of bronchopneumonia. Although 

the concentration of sulfuric acid ingested by these subjects was not stated, the concentration of sulfuric acid 

available in India is in the range of 26.4-35.4 Normal (N). 

The LD50 in rats treated by gavage with reagent grade sulfuric acid in water at a concentration of 0.25 g/mL 

was reported as 2,140 mg/kg (Smyth et al. 1969). No deaths were reported in chicks fed sulfuric acid in the 

diet at 11,117 mg/kg/day for 14 days (Capdevielle and Scanes 1995b), or mallard ducklings fed sulfuric acid 

in the diet at 12,393 mg/kg/day for 15 days (Capdevielle and Scanes 1995a). These studies indicate that a 

much larger dose of sulfuric acid can be tolerated if it is given in the food compared to gavage treatment. 

When sulfuric acid is added to food, some will be neutralized. 
SULFUR TRIOXIDE AND SULFURIC ACID 64 

2. HEALTH EFFECTS 

The LD50 for rats is recorded in Table 2-2 and plotted in Figure 2-2. 

2.2.2.2 Systemic Effects 

No studies were located regarding cardiovascular, hematological, dermal, or ocular effects in humans or 

animals after oral exposure to sulfuric acid. 

Respiratory Effects. In a report of 10 humans who ingested sulfuric acid, 2 died (Dilawari et al. 1984). 

One person died of bronchopneumonia. The amount of sulfuric acid ingested by this subject was not 

provided. 

No studies were located regarding respiratory effects in animals after oral exposure to sulfuric acid. 

Gastrointestinal Effects. A 2-year-old boy who ingested an unspecified amount of sulfuric acid required 

surgery to replace his stomach with a jejunal pouch (Aktug et al. 1995). In a report from India regarding 

10 humans who ingested sulfuric acid, 2 died (Dilawari et al. 1984). The cause of death was gastric 

perforation in 1 person. Endoscopy was completed in ah 10 subjects and the gastrointestinal lesions were 

graded as follows: I) mild mucosal hyperaemia; II) moderate superficial ulcerations; and IU) severe, 

extensive, deep ulcerations. Among the survivors, there were 4 cases each with esophageal lesions of grade II 

and grade III. Stomach lesions of grade III were observed in 6 survivors, and grade II in 2 survivors. 

Grade III lesions were observed only in the duodenum of the 2 subjects who died. Duodenal lesions were 

grade I in 3 survivors, with no duodenal lesions observed in the other 5 survivors. The amount and 

concentration of the acid consumed by the individuals were not known, but the study authors estimated that 

the amount was in the range of 15-50 mL, and the concentration was up to 26.4-35.4 N, which is the 

concentration of acid readily available in India. 

No studies were located regarding gastrointestinal effects in animals after oral exposure to sulfuric acid. 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after oral 

exposure to sulfuric acid. 

As an indication of growth, tibia length was measured in chicks (Capdevielle and Scanes 1995b) and mallard 

ducklings (Capdevielle and Scanes 1995a) fed sulfuric acid in the diet. Decreased tibia length, associated 


SULFUR TRIOXIDE AND SULFURIC ACID 67 

2. HEALTH EFFECTS 

with an 18% decrease in food intake, was observed in chicks fed 11 ,117 mg/kg/day for 14 days, with no 

effects at 2,338 mg/kg/day (Capdevielle and Scanes 1995b). No effect on tibia length or food intake was 

observed in mallard ducklings fed sulfuric acid at 12,393 mg/kg/day for 15 days (Capdevielle and Scanes 

1995a). The study authors suggested that the difference between chickens and ducks may be a result of the 

eating habits of ducks. Ducks often dip toxicant-treated food into water before eating it, which may have 

diluted the acid, thus minimizing the effects on ducks 

Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to 

sulfuric acid. 

No changes in liver weight were observed in chicks fed 11) 117 mg/kg/day of sulfuric acid in the diet for 

14 days (Capdevielle and Scanes 1995b) or in mallard ducklings fed 12,393 mg/kg/day sulfuric acid in the 

diet for 15 days (Capdevielle and Scanes 1995a). 

Renal Effects. No studies were located regarding renal effects in humans after oral exposure to sulfuric 

acid. 

No changes in kidney weights were observed in chicks fed 11 ,117 mg/kg/day of sulfuric acid in the diet for 

14 days (Capdevielle and Scanes 1995b) or in mallard ducklings fed 12,393 mg/kg/day of sulfuric acid in the 

diet for 15 days (Capdevielle and Scanes 1995a). 

Endocrine Effects. No studies were located regarding endocrine effects in humans after oral exposure to 

sulfuric acid. 

No changes in plasma growth hormone, insulin-like growth factor, and insulin-like growth factor binding 

proteins were observed in chicks fed 11 ,117 mg/kg/day of sulfuric acid in the diet for 14 days (Capdevielle 

and Scanes 1995b) or in mallard ducklings fed 12,393 mg/kg/day of sulfuric acid in the diet for 15 days 

(Capdevielle and Scanes 1995a). The lack of an endocrine effect suggests that the decreases in growth 

observed in chicks were a result of the decreased food intake. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 68 

2. HEALTH EFFECTS 

Body Weight Effects. Decreased body weight gain associated with an 18% decrease in food intake was 

observed in chicks fed 11 ,117 mg/kg/day sulfuric acid in the diet for 14 days, with no effects at 

2,338 mg/kg/day (Capdevielle and Scanes 1995b). No effect on body weight gain or food intake was 

observed in mallard ducklings fed sulfuric acid in the diet at 12,393 mg/kg/day for 15 days (Capdevielle and 

Scanes 1995a). The study authors suggest that the differeuce between chickens and ducks may be a result of 

different eating habits of ducks. Ducks often dip toxicant-treated food into water before eating it, which may 

have diluted the acid, thus minimizing the effects on the ducks 

2.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological and lymphoreticular effects in humans or animals following 

oral exposure to sulfuric acid. 

2.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans or animals following oral exposure to 

sulfuric acid. 

2.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to sulfuric acid. 

Changes in testes weights were not observed in chicks fed 11,117 mg/kg/day of sulfuric acid in the diet for 

14 days (Capdevielle and Scanes 1995b) or in mallard ducklings fed 12,393 mg/kg/day of sulfuric acid in the 

diet for 15 days (Capdevielle and Scanes 1995a). 

2.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to sulfuric acid. 

As indicated under musculoskeletal effects and body weight effects, decreased growth (decreased tibia length 

and decreased body weight gain) associated with an 18% decrease in food intake was observed in chicks fed 

11 ,117 mg/kg/day sulfuric acid in the diet for 14 days, with no effects at 2,338 mg/kg/day (Capdevielle and 
 

SULFUR TRIOXIDE AND SULFURIC ACID 69 

2. HEALTH EFFECTS 

Scanes 1995b). This effect on growth was not accompanied by changes in plasma growth hormone, insulinlike 

growth factor, or insulin-like growth factor binding protein. No effect on growth or food intake was 

observed in mallard ducklings fed sulfuric acid in the diet at 12,393 mg/kg/day for 15 days (Capdevielle and 

Scanes 1995a). The study authors suggest that the difference between chickens and ducks may be a result of 

different eating habits of ducks. Ducks often dip toxicant-treated food into water before eating it, which may 

have diluted the acid, thus minimizing the effects on the ducks. 

2.2.2.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans or animals after oral exposure to sulfuric acid. 

Genotoxicity studies are discussed in Section 2.5. 

2.2.2.8 Cancer 

No studies were located regarding cancer in humans or animals after oral exposure to sulfuric acid. 

2.2.3 Dermal Exposure 

No studies in humans or animals were located regarding dermal exposure to sulfur trioxide. 

2.2.3.1 Death 

Death can occur from dermal burns from chemicals including sulfuric acid. In a report of burns from 

chemicals that included sulfuric acid and that occurred in Jamaica as a result of assault, Branday et al. (1996) 

indicated that deaths occurred in people whose chemical burn injuries exceeded 50% of the total body surface 

area. The death of a man 5 days after he was deliberately splashed with a solution containing concentrated 

sulfuric acid (concentration not reported) was attributed to extensive burns and chemical damage to the 

respiratory tract (Schultz et al. 1968). The man was splashed over his face and body, and he received seconddegree burns over 60% of his body and third-degree burns over 20% of his body. 

No studies were located regarding deaths in animals after dermal exposure to sulfuric acid. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 70 

2. HEALTH EFFECTS 

2.2.3.2 Systemic Effects 

The highest NOAEL and all LOAEL values from each reliable study for systemic effects in each species and 

duration category are recorded in Table 2-31 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, or body weight effects in humans or animals after dermal exposure to sulfuric 

acid. 

Dermal Effects. Direct application of concentrated sulfuric acid to the skin resulted in chemical burns in 

exposed humans (Branday et al. 1996; Schultz et al. 1968). The effects reported included coagulative 

necrosis and third-degree burns (Schultz et al. 1968). The concentration required to result in dermal bums in 

humans has not been determined. Dermal exposure of humans for 4 hours to a 10% sulfuric acid solution 

was considered nonirritating (Nixon et al. 1975). The sulfuric acid was applied to both intact and abraded 

skin on a 4-cm area on the back of each person. The sites were evaluated for erythema and edema on a scale 

of 0-4 at 4,24, and 48 hours after the application. Additional details about the methods were not provided by 

the study authors, although they indicate that the test was completed by a procedure proposed by the FDA in 

1972. The mean score for humans was 0.2 for both intact and abraded skin. 

Sulfuric acid placed directly on the skin is corrosive. Available animal studies do not agree on the 

concentration required to produce direct skin effects. Erosion of the skin at 10%, erythema and edema at 5%, 

and no effects at 2.5% were reported in rats and mice in which 1 mL/kg of the acid was placed on the electric 

razor-shaved skin of the back (Sekizawa et al. 1994). The application area was left unoccluded, and the 

animals wore collars and were caged separately to prevent licking. The skin was examined for 1 week after 

the application. In comparison to the Sekizawa et al. (1994) study, no skin effects were observed in guinea 

pigs or rabbits in which a 10% sulfuric acid solution was applied to the skin for 4 hours (Nixon et al. 1975). 

The sites were evaluated for erythema and edema on a scale of 0-4 at 4,24, and 48 hours after the 

application. Additional details about the methods were not provided by the study authors, although they 

indicate that the test was completed by a procedure proposed by the FDA in 1972. The mean score was 0 for 

both intact and abraded skin in guinea pigs and for intact skin in rabbits. The mean score was 0.1 for abraded 

skin in rabbits. During a 4-hour exposure, sulfuric acid was not corrosive to the skin when 0.5 mL of a 4% 

solution was placed on the backs of rabbits that were clipped of hair 24 hours before exposure (Vemot et al. 

1977). 


 

SULFUR TRIOXIDE AND SULFURIC ACID 73 

2. HEALTH EFFECTS 

Ocular Effects. Accidental contact of the eyes with concentrated sulfuric acid is very destructive and 

results in devastating injuries including dissolution of the anterior segment of the globe (Grant 1974). 

Additional complications that have been reported include glaucoma and cataracts. Ocular damage that was 

limited to external structures (reported as edematous corneas with necrotic epithelium of the cornea, 

conjunctival, and lids) was reported in a man deliberately splashed with a solution containing concentrated 

sulfuric acid (Schultz et al. 1968). With the exception of light detection, the man lost vision the day after the 

exposure. During the next several days his vision improved. The man died from extensive burns and 

chemical damage to the respiratory tract 5 days after the exposure. Eye damage as a result of contact with 

sulfuric acid from car batteries has been reported (Holekamp and Becker 1977). Among 93 cases of eye 

injuries, 9 cases were serious, requiring hospitalization or resulting in permanent damage. In this series of 

cases, the most common injuries were conjunctival and cornea1 chemical burns, and iritis. Two-thirds of the 

injuries occurred when a battery exploded. 

As indicated in the section regarding inhalation exposure, contact with sulfuric acid aerosols in air results in 

ocular irritation. Lacrimation was reported in volunteers exposed to sulfuric acid aerosols (MMD 1.54 μm) 

at 20.8 mg/ m3

 (Sim and Battle 1957). The exposures, completed at a relative humidity of 91%, were almost 

intolerable at the onset. Eye irritation was not reported by subjects exposed to a concentration of 39.4 mg/ m3 

(MMD 0.99 μm) at a relative humidity of 63%. Because the subjects may have smoked during the 

exposures, this study is not presented in Table 2-3. Minor eye irritation was significantly increased in 

asthmatics exposed to 0.999 and 1,460 mg/ m3

 sulfuric acid mist (MMD 0.9 μm) for 1 hour (Avol et al. 

1988). However, statistically significant increases in eye irritation were not reported by healthy subjects 

exposed to concentrations as high as 1,578 mg/ m3

 under the same conditions. 

Sulfuric acid placed directly in the eyes is corrosive. Available animal studies do not agree on the 

concentration of sulfuric acid required to produce direct eye effects. A 10% (0.1 mL) sulfuric acid solution 

was considered nonirritating to the eyes when examined in a Draize test in rabbits (Jacobs 1992). Swelling of 

the iris and “diffuse cornea” were observed in both rats and mice in which 0.01 mL, of a 2.5% sulfuric acid 

solution was placed in one eye (Sekizawa et al. 1994). The other eye was treated with saline as a control. 

After treatment, the eyes were kept open for 30 seconds. No effects were observed at concentrations of 

l-1.25%. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 74 

2. HEALTH EFFECTS 

In a study in rabbits, 0.1 mL of a 5% (0.5 1 M; pH 0.6) or 10% (1.02 M; pH 0.1) sulfuric acid solution was 

placed directly on the cornea of the right eye (Murphy et al. 1982). The left eye served as a control. Directly 

after treatment, the lid was closed for about 1 second, then released. In 6 of the exposed rabbits at each 

concentration, the eyes were gently washed for 2 minutes with 300 mL of tap water 30 seconds after 

exposure. The eyes of another 6 rabbits at each concentration were not washed. Washing had no effect at 

10%, a concentration at which severe corneal opacities were observed in 12 of 12 animals. At 5%, minimal 

cornea1 opacities were observed in 1 of 6 washed eyes and 2 of 6 unwashed eyes. The effect at 5% was 

considered minimal and was no longer present 7 days after the exposure. Although washing did not affect the 

severity of the effect, it did tend to result in an earlier effect following exposure to 5% sulfuric acid. Because 

the composition of acid is more completely described in the Murphy et al. (1982) study, it is presented in 

Table 2-3. 

No studies were located regarding the following health effects in humans or animals after dermal exposure to 

sulfuric acid. 

2.2.3.3 Immunological and Lymphoreticular Effects 

2.2.3.4 Neurological Effects 

2.2.3.5 Reproductive Effects 

2.2.3.6 Developmental Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.5. 

2.2.3.8 Cancer 

No studies were located regarding cancer in humans or animals after dermal exposure to sulfuric acid. 

2.3 TOXICOKINETICS 

Toxicokinetic studies regarding sulfur trioxide were not identified. Because sulfur trioxide reacts with water 

to form sulfuric acid, the toxicokinetics of sulfur trioxide would be expected to be the same as sulfuric acid. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 75 

2. HEALTH EFFECTS 

Sulfuric acid is a direct irritant that results in adverse effects at the site of contact. The effects of sulfuric acid 

are a result of pH change rather than a result of sulfate. The important toxicokinetic issue is where in the 

respiratory tract sulfuric acid aerosols will deposit. Factors that help determine the site of deposition in the 

respiratory tract include environmental conditions, especially relative humidity which affects aerosol size, and 

physiological factors of the subject including breathing rate, depth of breathing, and method of breathing, 

e.g., mouth, nose, or oronasal. The effect of hygroscopic growth on deposition within the respiratory tract has 

been modeled in adults (Martonen and Pate1 1981) and children (Martonen and Zhang 1993). Once in the 

lung, the sulfur from sulfuric acid has been shown to be rapidly absorbed into the blood stream (Dahl et al. 

1983). Sulfate is a metabolite of sulfur amino acids, and excess sulfate is excreted in the urine (Vander et al. 

1975). 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

The retention of sulfuric acid mist was studied in humans exposed through a face mask to 0.4-1 mg/ m3 

sulfuric acid mist with an average aerosol size of 1 μm (Amdur et al. 1952b). During the 5-15minute 

exposures, the average retention of the acid aerosols was 77%, with a range of 50-87%. 

The clearance of 35sulfur-labeled sulfuric acid aerosols from the respiratory tract was studied in rats, guinea 

pigs, and dogs exposed nose-only to l-20 mg/m3

 (MMAD 0.4-l .2 μm) for 30 seconds, and in rats and 

guinea pigs following intranasal installation (Dahl et al. 1983). The results indicated that the sulfur from 

sulfuric acid is rapidly cleared from the lungs into the blood following inhalation exposure. The lung 

clearance half-times were 170,230, and 261 seconds in rats, guinea pigs, and dogs, respectively. Very little 

of the sulfur from the sulfuric acid placed in the nose was absorbed into the rest of the body. Five minutes 

after treatment, 97.1% and 96.8% of the dose remained in the nose of rats and guinea pigs, respectively. To 

further study absorption of sulfuric acid by the respiratory tract of dogs, 35sulfur-labeled sulfuric acid was 

instilled in one dog l-2 cm past the nares, in a second generation bronchus of another dog, and in a seventh 

generation bronchus of a third dog. Clearance from the nasal region was insignificant. Clearance half-time 

from the second generation bronchus was 200 seconds; from the seventh generation bronchus it was 

110 seconds. 
SULFUR TRlOXlDE AND SULFURIC ACID 76 

2. HEALTH EFFECTS 

2.3.1.2 Oral Exposure 

No studies were identified regarding the absorption of sulfuric acid following oral exposure of humans or 

animals. 

2.3.1.3 Dermal Exposure 

No studies were identified regarding the absorption of sulfuric acid following dermal exposure of humans or 

animals. 

2.3.2 Distribution 

Sulfate is a normal constituent of the blood, with concentrations of 0.8-1.2 mg/dL normally found in the 

serum of humans (Hensyll990). Concentrations of sulfates in urine range from 53 pmol/dL/Kg in l-day-old 

infants to 500 umol/dL/Kg in young men (Lentner 1981). The level of urinary sulfate is a measure of the 

quantity and quality of proteins in the diet. Studies in which sulfate in blood or urine were measured 

following exposure to sulfuric acid were not identified. 

2.3.2.1 Inhalation Exposure 

The dose of hydrogen ion delivered to the lungs was estimated in 7 healthy male adults exposed to 

0.471 mg/ m3

 sulfuric acid aerosols (MMAD 10 μm) using a head dome that allowed continuous measurement 

of breathing frequency, tidal volume, and minute ventilation, as well as the onset and persistence of oronasal 

breathing (Bowes et al. 1995). The 1 -hour exposure period consisted of 40 minutes of rest followed by 

20 minutes of moderately heavy exercise on a bicycle ergometer. The amount of hydrogen ion delivered to 

the lungs was estimated from the total time in minutes of oronasal breathing, the ventilation rate during oral 

nasal breathing, the hydrogen ion concentration, and the estimated fraction of inhaled air that entered the oral 

passage during oronasal breathing. Based on an earlier study by this group regarding the lung distribution of 

10-μm fog droplets following oronasal breathing, the fractional deposition was assumed to be 85.4% for the 

oropharynx and 14.6% for the lower airways. The investigators estimated that about 55% of each breath was 

inhaled orally during oronasal breathing. The estimated amount of hydrogen ion inhaled orally was 

6,466±1,778 nmol, with 942±259 nmol penetrating to the lower airways including the larynx, trachea, and 

bronchopulmonary region. Of the parameters used to estimate the dose delivered to the lung, the 
SULFUR TRIOXIDE AND SULFURIC ACID 77 

2. HEALTH EFFECTS 

investigators estimated that the combined physiologic parameters accounted for 70% of the variability 

(minute ventilation during oronasal breathing, 36%; time in minutes of oronasal breathing, 34%), and the 

environmental hydrogen ion concentrations accounted for 30% of the variation. 

Dosimetric models that examine the effect of hygroscopic growth (increase in aerosol size upon absorption of 

moisture) within the human respiratory tract on the deposition of sulfuric acid aerosols have been developed. 

Martonen and Pate1 (1981) modeled sulfuric acid aerosol deposition in the adult, while Martonen and Zhang 

(1993) modeled deposition in both children and adults at different breathing rates. Both models use the 

Weibel model A of the human lung which assumes a symmetric dichotomously branching network of airways. 

In the Martonen and Pate1 (1981) model, it was assumed that the sulfuric acid droplets reached equilibrium 

size and density at the entrance to the trachea. Relative humidity in the respiratory tract was assumed to be 

100%. Compared to smaller droplets, larger droplets were predicted to grow more as they traversed the 

respiratory tract. For droplets with initial geometric diameters of 0.01, 0.1, and 1 μm the estimated 

equilibrium geometric diameters in the respiratory tract were 0.0220.72, and 16 μm, respectively. At an 

inspiratory flow rate of 30 L/minute, the model indicated that total tracheobronchial deposition would be 

increased for particles with an initial geometric diameter of >0.1 μm. The increase would result because of 

increased efficiency of inertial impaction and sedimentation mechanisms. For particles with an initial 

geometric diameter of <0.1 μm the model predicted that tracheobronchial deposition would decrease because 

of reduced efficiency of diffusion with increased particle size. 

In the Martonen and Zhang (1993) model, growth of a sulfuric acid droplet was assumed to occur in the first 

11 generations of the tracheobronchial tree, with relative humidities increasing from 90% in generation 0, to 

99.5% in generation 10. Five subject ages (7, 22, 48, 98, and 240 months) were considered, and the 

respiratory parameters used for each age are shown in Table 2-4. The model focused on mouth breathing, 

and sulfuric acid deposition was compared to the deposition of nonhygroscopic iron oxide particles. Total 

deposition of sulfuric acid droplets in the respiratory tract was greatest for 7-, 22-, and 48-month-old 

children, and decreased monotonically as the lungs matured. Deposition was also dependent on particle size. 

When breathing at rest, for particles with an initial geometric diameter of 0.3 μm, hygroscopicity decreased 

deposition, while for larger particles hygroscopicity increased deposition. For initial particle sizes of 

l-2.5 μm, hygroscopicity almost doubled the probability of deposition in the lung. Increased breathing rate 

through exertion increased the differences in total deposition between children and adults. 

SULFUR TRIOXIDE AND SULFURIC ACID 79 

2. HEALTH EFFECTS 

The effects of hygroscopicity and age on the regional deposition of particles were also studied (Martonen and 

Zhang 1993). At resting respiration rates, deposition of iron oxide particles in the alveolated compartment of 

the lung peaked at a particle size of 3-5 μm (Mar-toner-r and Zhang 1993). While for hygroscopic particles, 

deposition in the alveolar compartment of the lung peaked at an initial particle size of l-l.5 μm. Deposition 

in the alveolar compartment did not change monotonically with age; deposition was highest for the adult and 

lowest for the 4%month-old child. Breathing rate also changed the regional deposition of particles. For 

example, in a 4%month-old child at resting breathing rates, deposition of hygroscopic particles with an initial 

diameter of 1 μm was greatest in the alveolar compartment. During exertion, deposition was greatest in the 

tracheobronchial region. 

The Martonen and Zhang (1993) model indicates that, in addition to particle size, subject age and exertion 

level should be considered in studies of the health effects of sulfuric acid particles. The model also suggests 

that children are a sensitive subpopulation for exposure to sulfuric acid aerosols. Martonen and Zhang 

(1993) cautioned that few general observations regarding the effect of hygroscopicity, age, and breathing rate 

on the deposition of sulfuric acid aerosols could be made, and that respiratory tract deposition should be 

considered on a case-by-case basis. 

2.3.2.2 Oral Exposure 

No studies were identified regarding the distribution of sulfuric acid following oral exposure of humans or 

animals. 

2.3.2.3 Dermal Exposure 

No studies were identified regarding the distribution of sulfuric acid following dermal exposure of humans or 

animals. 

2.3.3 Metabolism 

Sulfur trioxide in contact with water forms sulfuric acid with the evolution of heat. Further contact with 

water results in the dissociation of sulfuric acid into hydrogen ions and hydrated sulfate ions, which can 

combine with other ions that are present in the body. Sulfate does not need to be further metabolized to be 

excreted in the urine. Route-specific studies of the metabolism of sulfuric acid were not identified. 
SULFUR TRIOXIDE AND SULFURIC ACID 80 

2. HEALTH EFFECTS 

2.3.4 Elimination and Excretion 

Sulfate, which is a normal metabolite of sulfur-containing amino acids, is excreted in the urine (Vander et al. 

1975). 

2.3.4.1 Inhalation Exposure 

No studies were identified regarding the excretion of sulfuric acid following inhalation exposure of humans or 

animals. 

2.3.4.2 Oral Exposure 

No studies were identified regarding the excretion of sulfates following oral exposure of humans or animals 

to sulfuric acid. 

2.3.4.3 Dermal Exposure 

No studies were identified regarding the excretion of sulfuric acid following dermal exposure of humans or 

animals. 

2.3.5 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 
SULFUR TRlOXlDE AND SULFURIC ACID 81 

2. HEALTH EFFECTS 

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 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 199Os, 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 substance-specific 

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 2-3 shows a 

conceptualized representation of a PBPK model. 

 

SULFUR TRIOXIDE AND SULFURIC ACID 83 

2. HEALTH EFFECTS 

If PBPK models for sulfur trioxide and sulfuric acid exist, the overall results and individual models are 

discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and 

species extrapolations. 

PBPK models for sulfur trioxide and sulfuric acid were not identified. Dosimetric models that examine the 

effect of hygroscopic growth within the respiratory tract on deposition of sulfuric acid aerosols in the lungs 

are discussed in Section 2.3.2.1. 

2.4 MECHANISMS OF ACTION 

2.4.1 Pharmacokinetic Mechanisms 

Sulfuric acid is a direct irritant that results in adverse effects at the site of contact. The concentration of 

sulfuric acid is important in determining effects For example, a small amount of concentrated sulfuric acid 

will erode and possibly cause perforation of the gastrointestinal tract if swallowed. The same amount of acid 

diluted sufficiently will have no effects. The effects of sulfuric acid are thought to be a result of pH change 

rather than a result of sulfate. If there is enough acid-neutralizing capacity at the site of contact with sulfuric 

acid, there will be no effects. 

For inhalation exposure to sulfuric acid aerosols, the important issues are where in the respiratory tract the 

aerosols deposit and the duration of exposure. Factors that determine the site of deposition in the respiratory 

tract include environmental conditions, especially relative humidity which affects aerosol size, and 

physiological factors of the subject including breathing rate and depth, and method of breathing, e.g., mouth, 

nose, or oronasal. The effect of hygroscopic growth on deposition within the respiratory tract has been 

modeled in adults (Martonen and Pate1 1981) and children (Martonen and Zhang 1993). Children may be 

more sensitive to the respiratory tract effects of sulfuric acid aerosols because pulmonary deposition is 

increased as a result of smaller airway diameter. 

2.4.2 Mechanisms of Toxicity 

Sulfuric acid aerosol toxicity is dependent on the hydrogen ion content of the aerosol. One mechanism by 

which sulfuric acid may produce its toxicity is by changing extracellular and intracellular pH. There is 

evidence that pH plays a critical role in growth control and cell differentiation, and that disrupting the control 
SULFUR TRIOXIDE AND SULFURIC ACID 84 

2. HEALTH EFFECTS 

of pH may lead to adverse effects (Soskolne et al. 1989). A sufficiently low pH is genotoxic to some cell 

systems. Therefore, a significant change in pH produced by sulfuric acid exposure could potentially lead to 

cellular changes if hydrogen ions reached susceptible targets. A preliminary in vitro study that exposed a 

human tracheal epithelial cell line to sulfuric acid aerosols of 0.75, 1.4, or 3.28 μm for 10 minutes revealed 

that intracellular pH decreased, and, that at equal mass concentrations, the change in pH was greater for the 

smaller particle sizes (Chen et al. 1993). 

Respiratory mucus serves as a barrier to the penetration of hydrogen ions into the tissue. The buffering 

capacity and pH of a person’s mucus may determine whether there will be a response to a sulfuric acid aerosol 

exposure. The pH of mucus is generally in the range of 7.4-8.2, and it shows diurnal and day-to-day 

variations. Asthmatics have been reported to have lower pH mucus, in the range of 5.3-7.6. In vitro studies 

have shown that when the pH of mucus is lowered below about 7.4 the viscosity increases (Holma 1985). 

Mucus with greater viscosity would serve to decrease mucociliary clearance. It has been estimated that 

persons with normal mucus buffer capacity and protein content can accommodate about 300 μg/ m3

 of 

sulfuric acid per 30 minutes (Holma 1989). 

Rather than a change in viscosity, an animal study suggests that increased mucus thickness may affect 

clearance. Changes in mucus viscosity were not observed in rats exposed to 94.4 mg/m3

 for 4 hours, or in 

guinea pigs exposed to 43.3 mg/m3

 for 4 hours (Lee et al. 1995). The thickness of the mucus layer was 

increased in these animals. 

Mechanisms of sulfuric acid-induced pulmonary injury have also been studied. Atropine was administered to 

12 guinea pigs in order to inhibit reflex-mediated bronchoconstriction and the animals were exposed to 32.6 

mg/m3

 sulfuric acid aerosol (MMAD 1.0 μ, RH 70-90%) for 4 hours (Brownstein 1980). Unlike guinea pigs 

who were exposed to sulfuric acid without atropine pre-treatment, the atropine-treated animals had no signs 

of pulmonary injury, such as epithelial desquamation. It was concluded that pulmonary injury following 

sulfuric acid exposure may be due in part to mechanical forces generated during reflex-mediated 

bronchoconstriction. 

The genotoxic effects of significantly lowered pH may contribute to the ability of sulfuric acid to produce 

respiratory tract tumors. It has also been postulated that sulfuric acid may promote carcinogenesis by 

inducing chronic tissue irritation (Soskolne et al. 1989). Chronic inflammation results in the release of free 

radicals which have a genotoxic action. In addition, chronic inflammation may increase susceptibility to 
 

SULFUR TRIOXIDE AND SULFURIC ACID 85 

2. HEALTH EFFECTS 

infection which may contribute to a carcinogenic response. However, the mechanism of carcinogenesis 

remains to be proven. 

2.4.3 Animal-to-Human Extrapolations 

Guinea pigs, which are the most sensitive animal species, are thought to react to sulfuric acid aerosol 

exposures in a manner similar to asthmatics, the most sensitive segment of the human population (Amdur 

1989a). Studies have demonstrated that sulfuric acid has similar effects on mucociliary clearance in rabbits, 

donkeys, and humans, thus suggesting that these animals may be useful models for extrapolation to humans 

(Gearhart and Schlesinger 1989; Schlesinger et at 1979). 

2.5 RELEVANCE TO PUBLIC HEALTH 

Issues relevant to children are explicitly discussed in 2.6 Children’s Susceptibility and 5.6 Exposures of 

Children. 

Overview 

Sulfuric acid, which forms in the atmosphere from sulfur dioxide, is a common atmospheric pollutant. Sulfur 

trioxide is an intermediate in the formation of sulfuric acid from sulfur dioxide. The effects of sulfuric acid 

are a result of hydrogen ion and not sulfate. The potential for other substances, especially ammonia, in the 

atmosphere to neutralize sulfuric acid determines whether or not humans are exposed to sulfuric acid 

aerosols. 

Numerous experimental acute-duration exposure studies of humans and animals indicate that exposure to 

sulfuric acid aerosols can result in changes in lung function and can affect clearance of particles from the 

respiratory tract. In addition to exposure concentration, the response to sulfuric acid is also dependent on the 

size of the aerosol, relative humidity (Sim and Pattle 1957), the buffering capacity of the aerosol (Fine et al. 

1987), respiratory tract ammonia levels (Utell et al. 1989), as well as the breathing pattern of the subject 

(Bowes et al. 1995). Children are generally more sensitive to sulfuric acid aerosols than adults, and asthmatic 

individuals are more sensitive than healthy subjects. The lowest concentrations and exposure durations 

resulting in transient changes in pulmonary function tests in asthmatics were a 40-45minute exposure to 

0.07 mg/ m3

 (MMAD 0.72 μm) (Hanley et al. 1992) and a 50-minute exposure to 0.1 mg/ m3 (MMAD 
 

SULFUR TRIOXIDE AND SULFURIC ACID 86 

2. HEALTH EFFECTS 

0.6 μm) (Koenig et al. 1985). The effects noted included a transient decrease in FVC, a decrease in FEV1, 

and increased respiratory resistance. Other studies of pulmonary function in asthmatics exposed to similar 

concentrations of sulfuric acid have not shown adverse effects (Anderson et al. 1992; Avol et al. 1990; 

Koenig et al. 1992; Utell et al. 1983). The most sensitive effect in normal subjects is clearance of test 

particles of sizes in the range of 3-7.6 μm. A concentration of about 0.1 mg/ m3

 has resulted in a reduced rate 

of bronchial mucociliary clearance in normal subjects (Laube et al. 1993; Spektor et al. 1989). 

Acute studies in animals exposed to sulfuric acid aerosols have also shown changes in pulmonary function 

tests (Amdur 1958; Amdur et al. 1978) and clearance of test particles (Chen and Schlesinger 1983; Gearhart 

and Schlesinger 1989; Mannix et al. 1991; Schlesinger et al. 1984). Guinea pigs are more sensitive to 

changes in pulmonary function than other species and are thought to respond in a manner similar to asthmatic 

humans (Amdur 1989a). 

In the United States, sulfuric acid or hydrogen ion (as sulfuric acid) levels in the atmosphere are generally 

below 0.005 mg/ m3

 (Lioy and Waldman 1989), ahhough higher concentrations, up to about 0.7 mg/ m3, can 

occur during pollution episodes (Amdur 1989b). Epidemiological studies do not provide clear evidence 

linking environmental exposure to sulfuric acid aerosols alone to adverse health effects in humans (Lioy and 

Waldman 1989). 

More sulfuric acid is produced in the United States than any other chemical (C&EN 1996). Therefore, there 

is a high potential for accidental and occupational exposure to sulfuric acid. Among states reporting 

accidental events during the time period 1990-1996 (5 states 1990-1991, 9 states 1992-1994, 14 states 

1995-l 996) 905 events occurred which involved only sulfuric acid and oleum (3 oleum releases), and 

173 events occurred which involved mixtures or multi-chemical releases that included sulfuric acid or oleum 

(HSEES 1997). Among the events in which only sulfuric acid and oleum were released, 53 required 

evacuation (information not available for 39 events), there was 1 death, and a total of 203 victims. Chemical 

burns (38.5%), respiratory irritation (21.6%), and eye irritation (15.4%) were the most frequently reported 

effects following these releases. Among the mixture or multi-chemical releases that included sulfuric acid or 

oleum, 40 required evacuation (information not available for 3 events), there were 3 deaths, and a total of 

322 victims. The most frequently reported effects following the release of mixtures were respiratory irritation 

(56.5%), eye irritation (17.8%), and nausea and vomiting (5.1%). 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 87 

2. HEALTH EFFECTS 

Industries with potential exposure to sulfuric acid include fertilizer, sulfuric acid, isopropanol, synthetic 

ethanol, and detergent production; building and construction; electric and electronic equipment; food 

products; health services; leather; oil and gas extraction; petroleum and coal products; photography shops; 

printing and publishing; paper and allied products; rubber and plastic products; steel; and textile products 

(IARC 1992). In occupational settings, exposure can be above 0.5 mg/ m3

, with the highest concentrations 

generally found in metal pickling operations. Effects observed in persons occupationally exposed to sulfuric 

acid included a slight increase in bronchitis without a change in lung function (Williams 1970), a small 

decrease in FVC (Gamble et al. 1984b), tooth erosion (El-Sadik et al. 1972; Gamble et al. 1984b; Malcolm 

and Paul 1961), and an increase in periodontal pockets (Tuominen 1991). The lowest average concentration 

resulting in effects in these occupational studies was 0.2 mg/ m3

 (Gamble et al. 1984b). However, in the 

remaining occupational studies, effects were observed primarily at concentrations which exceeded the OSHA 

permissible exposure limit (1996) for sulfuric acid aerosols of 1 mg/ m3

 (El-Sadik et al. 1972; Malcolm and 

Paul 1961; Williams 1970). 

Chronic-duration inhalation studies in monkeys exposed to sulfuric acid aerosols reported histopathological 

changes in the lungs at 0.38 mg/ m3

 (MMD 2.15 μm), 2.45 mg/ m3 (MMD 3.6 μm), and 4.79 mg/ m3 (MMD 

0.73 pm), with no effects at 0.48 mg/ m3

 (MMD 0.54 μm) (Alarie et al. 1973). Arterial oxygen was affected 

only at 2.45 mg/ m3

 (MMD 3.6 μm), the only exposure concentration utilized in these studies that resulted in 

histopathologic changes in the alveoli. Chronic exposure of guinea pigs at concentrations up to 0.9 mg/m3 

(MMD 0.49 μm) did not result in any histopathologicaI changes in the lungs (Alarie et al. 1973, 1975). 

Additional treatment-related adverse effects on other organ systems were not observed in either monkeys or 

guinea pigs, although all the data were not presented. 

Inhalation exposure to sulfuric acid aerosols has not been shown to result in reproductive or developmental 

effects in mice or rabbits (Murray et al. 1979). Because sulfuric acid is a direct-acting toxicant and not likely 

to reach reproductive organs or the fetus, reproductive and developmental effects are unlikely to occur in 

humans exposed to sulfuric acid. 

Occupational exposure to mineral acid aerosols including sulfuric acid has been associated with respiratory 

tract cancers (Alderson and Rattan 1980; Beaumont et al. 1987; Coggon et al. 1996; Cookfair et al. 1985; 

Forastiere et al. 1987; Houghton and White 1994; Soskolne et al. 1982, 1984, 1992; Steenland and 

Beaumont 1989; Steenland et al. 1988). However, most of the cancers were in smokers who were also 

exposed to other chemicals. There is no information that exposure to sulfuric acid by itself is carcinogenic, 
 

SULFUR TRIOXIDE AND SULFURIC ACID 88 

2. HEALTH EFFECTS 

and there is no clear data on exposure concentrations of sulfuric acid associated with cancer in humans. 

DHHS (1994) and EPA have not classified sulfur trioxide or sulfuric acid for carcinogenic effects. Based on 

the limited human data, which associate occupational exposure to mineral acid aerosols with the development 

of lung and laryngeal cancers, IARC (1992) considers occupational exposure to strong inorganic acid mists 

containing sulfuric acid carcinogenic to humans (Group 1). The carcinogenicity of sulfuric acid alone has not 

been classified by IARC. The carcinogenicity of sulfuric acid has not been studied in animals. 

In addition to inhalation exposure to sulfuric acid aerosols, there is potential for accidental oral or dermal 

exposure to concentrated sulfuric acid. Sulfuric acid is found in lead-acid batteries and concentrated drain 

cleaners. Some home cleaners (especially toilet bowl cleaners) contain compounds that release sulfuric acid 

when they contact water. Therefore, the general population may come into contact with sulfuric acid when 

using these products. At sufficient concentrations, sulfuric acid has been shown to corrode the 

gastrointestinal tract when swallowed (Aktug et al 1995; Dilawari et al. 1984) and corrode the skin (Branday 

et al. 1996) and eyes (Grant 1974; Holekamp and Becker 1977; Schultz et al. 1968) on contact. 

Minimal Risk Levels for Sulfur Trioxide/Sulfuric Acid 

Inhalation MRLs 

No inhalation MRLs were derived for sulfur trioxide or sulfuric acid exposure. The only inhalation study 

regarding sulfur trioxide exposure is a report of respiratory irritation in persons accidently exposed (Stueven 

et al. 1993). Exposure concentrations were not provided in this report. 

Several acute-duration human exposure studies have reported respiratory effects including 

bronchoconstriction resulting in changes in lung function tests and changes in bronchial mucociliary 

clearance. The lowest concentration that resulted in changes in lung function tests was 0.07 mg/ m3

 (MMAD 

0.72 μm), a concentration at which transient decreases in FVC and FEV1 were observed in asthmatics 

exposed for 40-45 minutes with intermittent exercise (Hanley et al. 1992). Increased respiratory resistance, 

decreased maximum flow at 50% and 75% of total vital capacity, and decreased FEV1 have also been 

reported in asthmatics exposed to 0.1 mg/ m3 (MMAD 0.6 μm) for 50 minutes with exercise (Koenig et al. 

1985). Although asthmatics are considered more sensitive to changes in lung function following exposure to 

sulfuric acid, all studies have not reported changes in lung function tests in asthmatics exposed to sulfuric 

acid aerosols. For example, changes in lung function tests were not observed in asthmatics exposed to 
 

SULFUR TRIOXIDE AND SULFURIC ACID 89 

2. HEALTH EFFECTS 

0.01 mg/m3 sulfuric acid aerosols (MMAD 0.5 μm) for 1 hour with intermittent exercise (Anderson et al. 

1992). Lung function was affected in 1 of the 15 exposed subjects leading the study authors to conclude that 

there may be a subgroup of asthmatics that are more sensitive to sulfuric acid exposure. Bronchial 

mucociliary clearance has only been studied in normal individuals. Decreased clearance was observed in 

subjects exposed to sulfuric acid aerosols (MMD 0.5 μm) with a nasal mask for 1 hour at 0.98 mg/ m3

 for test 

particles of 7.6 μm (Leikauf et al. 1981), and at 0.108 mg/ m3

 for test particles of 4.2 pm (Leikauf et al. 

1984). 

These studies are not being used as the basis of an MRL because physiological factors and conditions under 

which humans are exposed are just as important in determining the response to sulfuric acid aerosols as the 

aerosol concentration and aerosol size. Factors which will affect the response to sulfuric acid include aerosol 

size, relative humidity, condition of the subject (e.g., asthmatic), amount of ammonia present in the mouth, 

breathing rate, and depth of breathing. Difficulties in estimating doses of hydrogen ion were demonstrated by 

Bowes et al. (1995). The hydrogen ion dose to the lower airways of healthy male adults was estimated 

following exposure to 0.471 mg/ m3

 sulfuric acid aerosol (MMAD 10 μm) through a head dome for 1 hour 

(40 minutes of rest and 20 minutes of exercise). Concentrations of sulfuric acid and physiological 

parameters, such as respiratory rate, tidal volume, minute ventilation and duration of oronasal breathing, were 

factors used in calculations to estimate doses. Estimated doses of hydrogen ion were variable among 

subjects, and about 30% of the variability was due to inconsistencies in the sulfuric acid concentrations of 

aerosols. The majority of variability, 70%, was due to physiological parameters, primarily duration of and 

minute ventilation during oronasal breathing. The authors stated the importance of calculating hydrogen ion 

doses in such studies in order to avoid false impressions of increased sensitivity in subjects who receive larger 

doses. Because the response to sulfuric acid aerosol exposure is so dependent on individual factors rather 

than exposure concentrations it would be very difficult to identify a NOAEL for human exposure. 

Intermediate-duration inhalation studies are limited to animal studies (Fujimaki et al. 1992; Gear-hart and 

Schlesinger 1986; Lewis et al. 1969; Schlesinger et al. 1979; Thomas et al. 1958), and chronic-duration 

inhalation studies include human occupational studies (El-Sadik et al. 1972; Gamble et al. 1984; Kitagawa 

1984; Kremer et al. 1994; Malcolm and Paul 1961; Williams 1970) and animal studies (Alarie et al. 1973, 

1975; Schlesinger et al. 1992a). Because the occupationa studies identified NOAELs higher than LOAELs 

in acute-duration studies they were not considered appropriate for MRL derivation. The methodology for 

extrapolating from inhalation exposure of animals to hygroscopic aerosols has yet to be developed (EPA 

1994). Therefore, inhalation MRLs could not be developed from animal studies. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 90 

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Oral MRLs 

No oral MRLs for sulfuric acid were derived. Although bigh concentrations of sulfuric acid are corrosive to 

the gastrointestinal tract (Aktug et al. 1995; Dilawari et al. 1984), there were insufficient data regarding oral 

exposure to sulfuric acid for the development of oral MRLs. This profile did not consider the oral toxicity of 

sulfites, which are used as food preservatives, or the oral toxicity of sulfate-containing compounds. 

Death 

Studies regarding death of humans following acute- and intermediate-duration inhalation exposure to sulfuric 

acid aerosols were not identified. Increased mortality, especially of elderly persons and those with preexisting 

cardiac and respiratory disease, has been reported during or shortly after air pollution episodes (Costa and 

Amdur 1996). Because it is not possible to clearly separate the effects of sulfuric acid aerosols from other 

pollutants including particulates, sulfur dioxide, and ozone, these studies are not discussed further. Deaths of 

humans have been reported following acute oral (Dilawari et al. 1984) and dermal exposure (Branday et al. 

1996; Schultz et al. 1968). 

One-hour LC50s of 347 and 420 ppm fuming sulfuric acid have been reported for female and male rats, 

respectively (Vernot et al. 1977). The lowest concentration of sulfuric acid aerosols that resulted in the death 

of rats was 383 mg/ m3

 (Treon et al. 1950). Mice were more susceptible to sulfuric acid aerosol exposure 

(diameter l-2 μm) than rats (Treon et al. 1950). Among the species exposed to sulfuric acid aerosols, guinea 

pigs are the most sensitive. During a l-hour exposure to 52-61 mg/ m3

 sulfuric acid (MMAD 0.8-2.1 μm), 

about 6% of the exposed guinea pigs died (Stengel et al. 1993). Younger guinea pigs are more sensitive to 

sulfuric acid aerosols than older guinea pigs (Amdur et al. 1952a). 

The effect of aerosol size on survival of guinea pigs exposed to sulfuric acid aerosols has been studied. 

Following exposure to sulfuric acid aerosols with MMADs of 0.8 and 0.4 μm, LC50s of 30.3 and 

>109 mg/ m3

, respectively, were reported for guinea pigs exposed for 8 hours (Wolff et al. 1979). Eight-hour 

LC50s of 59.8 and 27.3 mg/ m3

 were reported for aerosols of MMADs of 0.8 and 2.7 μm, respectively (Pattle 

et al. 1956). 

No effect on survival was observed in cynomolgus monkeys or guinea pigs exposed to sulfuric acid aerosols 

23.3 hours/day, 7 days/week, for 78 weeks (monkeys) or 52 weeks (guinea pigs) (Alarie et al. 1973). 
SULFUR TRIOXIDE AND SULFURIC ACID 91 

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The LD50 in rats treated by gavage with reagent grade sulfuric acid in water at a concentration of 0.25 g/mL 

was reported as 2,140 mg/kg (Smyth et al. 1969). Deaths of laboratory animals following longer-term oral 

exposure to sulfuric acid were not reported. No studies were located regarding deaths in animals after dermal 

exposure to sulfuric acid. Deaths are unlikely to occur at concentrations of sulfuric acid normally found in the 

environment or at hazardous waste sites. 

Systemic Effects 

Respiratory Effects. Acute inhalation exposure to sulfur trioxide and sulfuric acid results in respiratory tract 

irritation in humans (Sim and Pattle 1957; Stueven et al. 1993) and animals (Stengel et al. 1993; Wolff et al. 

1979). At lower concentrations acute inhalation exposure adversely affects pulmonary function tests in both 

humans (Avol et al. 1988; Hanley et al. 1992; Koenig et al. 1992; Utell et al. 1983) and animals (Amdur 

19.58, 1959; Amdur et al. 1978; Kobayashi and Shinozaki 1993). Adolescent asthmatics are the humans 

most sensitive to sulfuric acid aerosol exposure (Hanley et al. 1992; Koenig et al. 1992), and guinea pigs, 

which are thought to react in a manner similar to asthmatic humans, are the most sensitive of animal species 

tested (Amdur 1989a). The lowest concentrations and exposure durations resulting in transient changes in 

pulmonary function tests in adolescent asthmatics were a 40-45-minute exposure to 0.07 mg/m3

 (Hanley et 

al. 1992) and a 50minute exposure to 0.1 mg/ m3 (Koenig et al. 1985). The effects noted included a transient 

decrease in FVC, a decrease in FEV1, and increased respiratory resistance. Other studies of pulmonary 

function in asthmatics exposed to similar concentrations of sulfuric acid have not shown adverse effects 

(Anderson et al. 1992; Avol et al. 1990; Koenig et al. 1992). Factors that affect the respiratory response to 

sulfuric acid aerosols include aerosol size, relative humidity (Sim and Pattle 1957), the buffering capacity of 

the aerosol (Fine et al. 1987), respiratory tract ammonia levels (Utell et al. 1989), as well as the breathing 

pattern of the subject (Bowes et al. 1995). 

A sensitive effect of sulfuric acid exposure in healthy subjects is clearance of test particles. Exposure to 

concentrations of 0.98-0.11 mg/m3

 has resulted in a reduced rate of bronchial mucociliary clearance in 

healthy subjects (Leikauf et al. 1981, 1984; Spektor et al. 1989). Clearance of test particles has also been 

shown to be adversely affected in animals following both acute- and intermediate-duration exposures (Chen 

and Schlesinger 1983; Gearhart and Schlesinger 1989; Mannix et al. 1991; Schlesinger and Gearhart 1986; 

Schlesinger et al. 1979,1984). It has been suggested that decreased clearance induced by some exposures to 

sulfuric acid aerosols may contribute to the development of chronic bronchitis (Lippmann et al. 1982). 
 

SULFUR TRIOXIDE AND SULFURIC ACID 92 

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Epidemiological studies do not provide clear evidence of adverse respiratory effects in humans following 

environmental exposure to sulfuric acid (Abbey et al. 1993,1995; Lioy and Waldman 1989). Respiratory 

effects observed in persons occupationally exposed to sulfuric acid aerosols include a slight increase in 

bronchitis without a change in lung function (Williams 1970) and a small decrease in FVC (Gamble et al. 

1984b). The lowest average concentration resulting in effects in these occupational studies was 0.2 mg/m3 

(Gamble et al. 1984b). 

Chronic-duration inhalation studies in monkeys exposed to sulfuric acid aerosols reported histopathological 

changes in the lungs at 0.38 mg/m3

 (MMD 2.15 μm), 2.45 mg/m3 (MMD 3.6 μm), and 4.79 mg/m3 (MMD 

0.73 pm). with no effects at 0.48 mg/m3

 (MMD 0.54 μm) (Alarie et al. 1973). The 2.45mg/m3 exposure 

concentration also resulted in decreased arterial oxygen and was the only exposure in which the 

histopathological changes also involved the alveoli. Chronic exposure of guinea pigs at concentrations up to 

0.9 mg/m3

 (MMD 0.49 μm) did not result in any histopathological changes in the lungs (Alarie et al. 1973, 

1975). 

In the United States, sulfuric acid or hydrogen ion (as sulfuric acid) levels in the atmosphere are generally 

below 0.005 mg/m3 (Lioy and Waldman 1989), although bigher concentrations, up to about 0.7mg/ m3

, can 

occur during pollution episodes (Amdur 1989b). Therefore, during some pollution episodes, asthmatic 

subjects may respond with decrements in pulmonary function tests, and decreases in mucociliary clearance 

may occur in both normal and asthmatic subjects. Exercise, which increases breathing rate and oral 

breathing, increases the response to sulfuric acid aerosols. 

Following oral exposure to sulfuric acid, death resulting from bronchopneumonia occurred in one subject 

(Dilawari et al. 1984). This case suggests that oral exposure to sulfuric acid could result in aspiration of the 

acid into the lungs leading to respiratory effects. Respiratory effects have not been reported following dermal 

exposure to sulfuric acid. 

Cardiovascular Effects. Acute occupational exposure to 35% fuming sulfuric acid has resulted in abnormal 

ventricular activity (Goldman and Hill 1953). However, limited human studies (Abbey et al. 1995; Bowes et 

al. 1995), and the lack of histopathological changes in the hearts of monkeys and guinea pigs exposed 

chronically, suggest that inhalation exposure to atmospheric concentrations of sulfuric acid aerosols does not 

result in cardiovascular effects. No studies were identified regarding cardiovascular effects of sulfur trioxide 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 93 

2. HEALTH EFFECTS 

or sulfuric acid following exposure via other routes. Sulfuric acid is a direct-acting toxicant. Therefore, 

cardiovascular effects are not likely to occur following exposure to sulfuric acid pollution in air. 

Gastrointestinal Effects. Studies reporting accidental ingestion of concentrated sulfuric acid by humans 

indicate that it erodes the gastrointestinal tract if it is swallowed (Aktug et al. 1995; Dilawari et al. 1984). 

The concentration of acid required to cause gastrointestinal erosion has not been studied. Gastrointestinal 

effects have not been studied in animals, nor have they been studied following exposure via other routes. 

Because sulfuric acid is not likely to be present at high concentrations in the environment, environmental 

exposure to sulfur trioxide or sulfuric acid is unlikely to result in gastrointestinal tract effects. 

Hematological Effects. Hematological effects have not been reported in humans following acute inhalation 

exposure to sulfuric acid (Chaney et al. 1980). There are no known studies of hematological effects 

following oral or dermal exposure. Hematological effects have not been reported in monkeys (Alarie et al. 

1973) or guinea pigs (Alarie et al. 1973, 1975) following chronic inhalation exposure to sulfuric acid 

aerosols. Because sulfuric acid is a direct-acting toxicant, hematological effects are not likely to occur 

following exposure to sulfur trioxide or sulfuric acid by any route. 

Musculoskeletal Effects. Musculoskeletal effects have not been studied in humans exposed to sulfur 

trioxide or sulfuric acid, nor have they been studied by any other route of exposure. Because sulfuric acid is a 

direct-acting toxicant, musculoskeletal effects are not likely to occur following exposure by any route. 

The effect of sulfuric acid on growth, including tibia length, has been studied in chicks (Capdevielle and 

Scanes 1995b) and ducklings (Capdevielle and Scanes 1995a) treated with the acid in the diet. Decreased 

tibia length associated with decreased food intake was observed in chicks but not ducklings. The objective of 

these studies was to determine whether aluminum (or acid, which increases aluminum levels in the 

environment) affects the growth of birds. Aluminum was shown to have an effect on growth of chickens that 

could not be attributed to the changes in food intake, while the effects of acid were attributed to decreased 

food intake. Although sulfuric acid may not have a direct effect on growth, including bone length, in the 

environment, lowered pH may lead to secondary effects by increasing levels of metals including aluminum. 

Hepatic Effects. Hepatic effects have not been reported in humans following acute inhalation exposure of 

sulfuric acid (Chancy et al. 1980). There are no known studies of hepatic effects following oral or dermal 

exposure. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 94 

2. HEALTH EFFECTS 

Effects on the liver have not been observed in mice or rabbits following inhalation exposure to sulfuric acid 

during gestation (Murray et al. 1979), or in monkeys (Alarie et al. 1973) or guinea pigs (Alarie et al. 1973, 

1975) following chronic inhalation exposure to sulfuric acid. Liver weights were not affected in chicks 

(Capdevielle and Scanes 1995b) or ducklings (Capdevielle and Scanes 1995a) fed sulfuric acid in the diet. 

Because sulfuric acid is a direct-acting toxicant, hepatic effects are not likely to occur following exposure by 

any route. 

Renal Effects. Renal effects have not been studied in humans exposed to sulfur trioxide or sulfuric acid by 

any route. 

Microscopic changes in the kidneys were not observed in monkeys (Alarie et al. 1973) or guinea pigs (Alarie 

et al. 1973, 1975) following chronic inhalation exposure to sulfuric acid. Kidney weights were not affected in 

chicks (Capdevielle and Scanes 1995b) or ducklings (Capdevielle and Scanes 1995a) fed sulfuric acid in the 

diet. Because sulfuric acid is a direct-acting toxicant, renal effects are not likely to occur following exposure 

by any route. 

Endocrine Effects. Endocrine effects have not been studied in humans exposed to sulfur trioxide or sulfuric 

acid by any route of exposure. 

Changes in growth hormone, insulin-like growth factor, and insulin-like growth-factor binding proteins were 

not observed in chicks (Capdevielle and Scanes 1995b) or ducklings (Capdevielle and Scanes 1995b) fed 

sulfuric acid in the diet. The objective of these studies was to determine whether aluminum (or acid, which 

increases aluminum levels in the environment) affects the growth of birds. High doses of aluminum were 

shown to reduce the levels of insulin-like growth factor in chicks. Although sulfuric acid may not have a 

direct effect on growth, in the environment, lowered pH may lead to secondary effects by increasing levels of 

metals including aluminum. Because sulfuric acid is a direct-acting toxicant, endocrine effects are not likely 

to occur in humans following exposure by any route. 

Dermal Effects. Direct application of concentrated sulfuric acid to the skin or eyes can result in burns in 

humans (Branday et al. 1996; Schultz et al. 1968) and animals (Sekizawa et al. 1994). The concentration 

required to result in dermal burns has not been clearly determined. Dermal exposure of humans to a 10% 

sulfuric acid solution was considered nonirritating (Nixon et al. 1975). 
SULFUR TRIOXIDE AND SULFURIC ACID 95 

2. HEALTH EFFECTS 

Erosion of the skin at 10%, erythema and edema at 5%, and no effects at 2.5% were reported in rats and mice 

in which sulfuric acid was placed on the electric razor-shaved skin of the back (Sekizawa et al. 1994). No 

skin effects were observed in guinea pigs or rabbits in which a 10% sulfuric acid solution was applied to the 

skin (Nixon et al. 1975). During a 4-hour exposure, sulfuric acid was not corrosive to the skin when 0.5 mL 

of a 4% solution was placed on the backs of rabbits, whose hair was clipped 24 hours before exposure 

(Vemot et al. 1977). In an in vitro study, application of a 40% solution to rat skin caused a large fall in the 

transcutaneous electrical resistance (Botham et al. 1992). This response correctly predicts that sulfuric acid 

is corrosive (Botham et al. 1992). 

Dermal effects have not been studied by other routes of exposure. Very high concentrations of sulfur trioxide 

or sulfuric acid aerosols in the air could potentially result in direct skin irritation. Because these same 

concentrations would also result in respiratory tract and eye irritation, skin effects would be the prominent 

effect of sulfuric acid aerosols only if the exposed persons were using respiratory and eye protective 

equipment. 

Ocular Effects. Direct exposure of the eyes to concentrated sulfuric acid can result in devastating destruction 

of the eye (Grant 1974; Holekamp and Becker 1977; Schultz et al. 1968). Direct exposure of the eyes to 

lower concentrations results in transient injury with complete recovery (Grant 1974). Eye irritation including 

lacrimation has been reported in humans exposed to sulfuric acid in air (Avol et al. 1988; Sim and Pattle 

1957). The effect was worse at high humidity than at low humidity (Sim and Pattle 1957). 

Animal studies indicate that direct application of sulfuric acid into the eyes is corrosive (Murphy et al. 1982; 

Sekizawa et al. 1994). The concentration of sulfuric acid required to result in direct eye effects has not been 

clearly defined. A concentration of 10% was considered nonirritating in rabbits in one study (Sekizawa et al. 

1994) while a 10% concentration resulted in severe comeal opacities in rabbits with minimal effects 

observed at 5% in a second study (Murphy et al. 1992). Ocular effects are unlikely to occur at the levels of 

sulfuric acid that are found in the environment. However, during episodes of high pollution, levels of sulfuric 

acid could be high enough to cause eye irritation. 

Body Weight Effects. No effects on body weight were observed in mice or rabbits following inhalation 

exposure to sulfuric acid aerosols during gestation (Murray et al. 1979), or in monkeys (Alarie et al. 1973) or 

guinea pigs (Alarie et al. 1973, 1975) following chronic exposure to sulfuric acid aerosols. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 96 

2. HEALTH EFFECTS 

Decreased body weight gain associated with decreased food intake was observed in chicks (Capdevielle and 

Scanes 1995b) but not ducklings (Capdevielle and Scanes 1995a) fed sulfuric acid in the diet. The objective 

of these studies was to determine if aluminum (or acid, which increases aluminum levels in the environment) 

affects the growth of birds. Aluminum was showu to have an effect on growth of chickens that could not be 

attributed to changes in food intake; while the effects of acid were attributed to decreased food intake. 

Although sulfuric acid may not have a direct effect on growth, in the environment, lowered pH may lead to 

secondary effects by increasing levels of metals including aluminum. 

Body weight changes have not been studied in animals dermally exposed to sulfuric acid. Because sulfuric 

acid is a direct toxicant, body weight changes are unlikely following dermal exposure, except possibly as a 

secondary effect as a result of the stress of dermal burns. 

Other Systemic Effects. Studies of workers indicate that exposure to sulfuric acid aerosols can result in 

lowered pH of the saliva (El-Sadik et al. 1972), erosion of the teeth (El-Sadik et al. 1972; Gamble et al. 

1984b; Malcolm and Paul 196l), and increased prevalence of periodontal pockets (Tuominen 1991). 

Malcolm and Paul (1961) indicated that the front teeth were the teeth most often affected, suggesting that the 

effect was the result of direct impingement of acid mist on the teeth. Tooth erosion is unlikely to occur at 

sulfuric acid concentrations generally found in the environment. 

Immunological and Lymphoreticular Effects. The function of alveolar macrophages collected from 

humans following inhalation exposure to sulfuric acid aerosols for 2 hours was not affected (Frampton et al. 

1992). Alveolar macrophage function was affected in animals following inhalation exposure to sulfuric acid 

aerosols, resulting in decreased intracellular pH (Chen et al. 1995) depressed phagocytic activity (Chen et al. 

1992a; Schlesinger et al. 1992b), and reduced TNF cytotoxic activity and zymosan-stimulated production of 

superoxide anion (Schlesinger et al. 1992b; Zelikoff and Schlesinger 1992). These effects on alveolar 

macrophage function have not been shown to be concentration related. Once a critical level of sulfuric acid 

was reached, no further effects were observed. Effects were greater following exposure to smaller aerosols 

(MMD 0.04 μm versus 0.3 μm), leading Chen et al. (1992a) to suggest that the smaller droplets deliver a 

higher dose to the macrophages than the larger droplets. 

Inhalation exposure to sulfuric acid aerosols has also been shown to enhance antigen-induced histamine 

release from mast cells collected from exposed guinea pigs (Fujimaki et al. 1992). Mice challenged with 
SULFUR TRIOXIDE AND SULFURIC ACID 97 

2. HEALTH EFFECTS 

Streptococcus pyrogens directly after ultrafine sulfuric acid aerosol exposure (2 hours/day for 5 days) did not 

show increased mortality (Grose et al. 1982). 

The studies of immune system function in animals suggest that although sulfuric acid exposure may adversely 

affect in vitro function of macrophages collected from exposed animals, the ability to defend against bacterial 

infections may not be adversely affected by inhalation exposure to sulfuric acid aerosols. Immunological and 

lymphoreticular effects have not been studied following oral or dermal exposure to sulfuric acid. Because 

sulfuric acid is a direct-acting toxicant, system-wide effects on the immune system are not likely following 

exposure to sulfuric acid by any route. 

Neurological Effects. Lightheadedness and dizziness have been reported by persons accidentally exposed 

to unspecified concentrations of sulfur trioxide (Stueven et al. 1993). Fatigue and headaches were reported 

more frequently in asthmatic volunteers when they were exposed to sulfuric acid aerosols at 0.999 but not 

0.396 mg/ m3

 for 1 hour (Avol et al. 1988). In guinea pigs, uncoordinated movement was reported after 

exposure to 165 mg/ m3

 of sulfuric acid mists but not higher concentrations. Neurological effects have not 

been studied following oral or dermal exposure of humans and animals to sulfuric acid. Because sulfuric acid 

is a direct-acting toxicant, neurological effects other than subjective symptoms and reflex response to pain are 

not likely following exposure to sulfuric acid by any route. 

Reproductive Effects. No significant effects on the mean numbers of implants/dam or resorptions/litter 

were noted in mice or rabbits exposed by inhalation to sulfuric acid aerosols during gestation (Murray et al. 

1979). Changes in testes weight were not observed in chicks (Capdevielle and Scanes 1995b) or ducklings 

(Capdevielle and Scanes 1995a) fed sulfuric acid in the diet. Additional studies regarding reproductive 

effects of sulfuric acid in humans or animals exposed by any route were not identified. Because sulfuric acid 

is a direct-acting toxicant, reproductive effects are not likely following exposure to sulfuric acid by any route. 

Developmental Effects. Significant effects on fetal body weights or on the incidence of major or minor 

malformations were not observed in mice or rabbits exposed by inhalation to sulfuric acid aerosols during 

gestation (Murray et al. 1979). No additional studies were identified regarding developmental effects of 

sulfuric acid in humans or animals following exposure by any route. In vitro studies have shown that sulfuric 

acid, or decreased pH, can induce chromosomal aberrations. Because sulfuric acid is a direct-acting toxicant, 

developmental effects in mammals are not likely following exposure by any route. Genotoxicity is possible 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 98 

2. HEALTH EFFECTS 

only if hydrogen ions come into direct contact with a cell. During inhalation or dermal exposure, hydrogen 

ions are not absorbed and distributed throughout the systemic circulation, and will not contact germ cells. 

However, developing organisms that are in direct contact with the environment (e.g., insects, amphibians) 

could be adversely affected if there are sufficient levels of sulfuric acid to result in decreased pH. 

Genotoxic Effects. In viva studies regarding the genotoxicity of sulfuric acid were not identified. In vitro 

studies regarding the genotoxicity of sulfuric acid are summarized in Table 2-5. Sulfuric acid did not increase 

gene mutation in Escherichia coli, which was tested only without metabolic activation (Demerec et al. 1951). 

In Salmonella typhimurium (strains TA97, TA98, Tal00, TA102, and TA1535) sulfuric acid was negative 

both with and without rat S9 metabolic activation (Cipollaro et al. 1986). 

Increases in chromosomal aberrations were observed in root meristimatic tissue of the plant Viciafuba (Zura 

and Grant 198 1) and in Chinese hamster ovary cells (Morita et al. 1989) exposed to sulfuric acid. In a study 

on the effect of pH on the induction of mitotic aberrations in sea urchins (Sphuerechinus granduris, 

Purucentrotus lividus), an increase in aberrations was observed at pH ≤6.5 (Cipollaro et al. 1986). A similar 

genotoxic effect was observed with sulfuric acid, hydrochloric acid, and phosphoric acid. These results 

indicate that pH rather than sulfate was responsible for the effect. 

Studies have demonstrated that genotoxicity is associated with an acidic pH level. At pH values (pH adjusted 

with lactic acid) of 6.5-7.0 the number of chromosomal anomalies in human lymphocytes in vitro was 

significantly increased compared with cells cultured at pH 7.5 (Shimada and Ingalls 1975). The anomalies 

observed included hypodiploidies, hyperdiploidies, and endoreduplications. In mouse lymphoma L5178Y 

TK+/- cells, pH of 6-6.8 (adjusted with hydrochloric acid) plus S9 resulted in an increase in mutations and 

chromosomal aberrations (Cifone et al. 1987). A transformed-like morphology was induced in Syrian 

hamster cells grown at pH values <6.9 (LeBoeuf and Kerckaert 1986). 

Cancer. Occupational exposure to sulfuric acid aerosols along with other chemicals has been associated 

with the development of respiratory tract cancers, especially laryngeal and lung cancers (Alderson and Rattan 

1980; Beaumont et al. 1987; Coggon et al. 1996; Cookfair et al. 1985; Forastiere et al. 1987; Houghton and 

White 1994; Soskolne et al. 1982, 1984, 1992; Steenland and Beaumont 1989; Steenland et al. 1988). 

However, most of the cancers were in smokers who were also exposed to other chemicals. Following a review 

of 25 epidemiological studies, Sathiakumar et al. (1997) concluded that there is a moderate association 

between sulfuric acid exposure and laryngeal cancer. Most studies were limited because of unquantified 

 

SULFUR TRIOXIDE AND SULFURIC ACID 100 

2. HEALTH EFFECTS 

exposure levels and insufficient control of confounding factors However, the association could not be 

explained by chance or study deficiencies alone, and an apparent dose response relationship was observed in 

some studies. Because of study limitations and the lack of a biologically plausible mechanism, it was 

concluded that there is insufficient evidence to establish a causal relationship between sulfuric acid exposure 

and laryngeal cancer. There is no information that exposure to sulfuric acid by itself is carcinogenic, and there 

are no clear data on exposure concentrations of sulfuric acid associated with cancer in humans. The U.S. 

DHHS (1994) and EPA have not classified sulfur trioxide or sulfuric acid for carcinogenic effects. Based on 

the human data, which associate occupational exposure to inorganic acid mists containing sulfuric acid with 

the development of lung and laryngeal cancers, IARC (1992) considers occupational exposure to strong 

inorganic acid mists containing sulfuric acid carcinogenic to humans (Group 1). Environmental exposure of 

humans to sulfuric acid has not been associated with cancer (Abbey et al. 1995). The carcinogenicity of 

sulfuric acid has not been studied in animals after exposure by any route. 

Environmental concentrations of sulfuric acid are generally much lower than those found in occupational 

settings and are unlikely to result in respiratory tract cancers. 

2.6 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 due to maternal exposure during gestation and lactation. Relevant animal and in vitro 

models are also discussed. 

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 5.6 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 pre-natal and post-natal life and a particular structure or 
 

SULFUR TRIOXIDE AND SULFURIC ACID 101 

2. HEALTH EFFECTS 

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 (Widdowson and Dickerson 

1964; Foman et al 1982; Owen and Brozek 4966; Ahman and Dittmer 1974; Foman 1966). The infant also 

has an immature blood-brain barrier (Adinolfi 1985; Johanson 1980) and probably an immature blood-testis 

barrier (Setchell, BP and Waites GMH 1975). Many xenobiotic metabolizing enzymes have distinctive 

developmental patterns and 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 (Leeder and Keams 1997; Komori 1990; Vieira et al 1996; NRC 1993). Whether differences in 

xenobiotic metabolism make the child more or less susceptible also depend 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 the newborn who has a low glomerular filtration rate and has not 

developed efficient tubular secretion and resorption capacities (Altman and Dittmer 1974; West et al 1948; 

NRC 1993). Children and adults may differ in their capacity to repair damage from chemical insults. 

Children also have a longer 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 while others may 

decrease susceptibility to the same chemical. For example, the fact that infants breathe more air per kilogram 

of body weight than adults may be somewhat counterbalanced by their alveoli being less developed, so there 

is a disproportionately smaller surface area for absorption (NRC 1993). 

The lowest sulfuric acid concentration to produce a respiratory effect was noted in a study of 22 asthmatic 

adolescents (age 12-19) (Hanley et al. 1992). A transient decrease in FVC and FEV1 was noted following 

exposure to 0.07 mg/ m3

 sulfuric acid (MMAD 0.71 μm) while subjects exercised for 10-30 minutes of the 

40-45 minute exposure period. No significant changes in respiratory function were noted in asthmatic 

adolescents (age 13-18) who were exposed to 0.07 mg/ m3

 sulfuric acid (MMAD 0.6 μm) for 90 minutes with 

alternating periods of rest and exercise (Koenig et al. 1992). In another study, increased respiratory 

resistance, decreased maximum flow at 50% and 75% of vital capacity, and decreased FEV1 were observed in 
 

SULFUR TRIOXIDE AND SULFURIC ACID 102 

2. HEALTH EFFECTS 

10 asthmatic adolescents (age 14-18) who were exposed to 0.1 mg/ m3 sulfuric acid (MMAD 0.6 μm) through 

a mouthpiece or face mask while exercising for 20 minutes of the 50 minute exposure period (Koenig et al. 

1985). In a comparison of results obtained in their studies of asthmatic adolescents and asthmatic seniors, it 

was concluded by Koenig et al. (1993) that responses differ between the two age groups. Asthmatic seniors 

(aged 65-75 years) experienced no statistically significant changes in lung function following exposure to 

0.07 mg/ m3

 sulfuric acid (MMAD 0.6 μm) during 30 minutes of rest and 10 minutes of exercise (Koenig et 

al. 1993). Increased mean levels of oral ammonia in seniors (600 ppb) compared to asthmatic adolescents 

(317-334 ppb) was discussed as a possible reason for the decreased response in seniors (Hanley et al. 1992; 

Koenig et al. 1993). 

A possible mechanism for increased sensitivity in asthmatic children is limited buffering capacity of hydrogen 

ions due to lower mucous pH in airways (Holma 1985). Increased susceptibility in infants is also possible 

due to incomplete development of the mucosa and mucous during the first few months after birth (Holma 1985; 

Reid 1974). 

Experiments in 9 atopic adolescents have demonstrated that exposure to 0.1 ppm sulfur dioxide in 

combination with 0.068 mg/m3

 sulfuric acid (MMAD 0.6 um)s while exercising for 10 minutes of a 

40 minute exposure period, resulted in no additional decrease in FEV1, which was observed following 

exposure to sulfuric acid alone (6% decrease, p<0.05) (Koenig et al. 1989). Exposure to each individual 

compound did not result in a statistically significant increase in total respiratory resistance, but a statistically 

significant 15% increase in total respiratory resistance was observed following exposure to the mixture of 

compounds. Therefore, sulfur dioxide may potentiate some sulfuric acid-induced effects. 

In Uniontown, PA a 2.5 L/min decrease in evening peak expiratory flow rate (PEFR) was observed in 

60 asthmatic children (in grades 4 and 5) following 12 hour exposures (weighted for time spent outdoors) to 

each 125 nmo/m3

 (0.012 mg/ m3 sulfuric acid) increase in particle-strong acidity (extractable acidity from 

sulfate particles composed partially of sulfuric acid and ammonium bisulfate) (Neas et al. 1995). Incidence 

of cough in healthy and asthmatic children was also associated with particle-strong acidity levels. However, 

air pollution studies are difficult to interpret because of confounding effects from numerous air pollutants. 

Respiratory function parameters were not affected in 41 children aged 9-12 years (15 healthy, 26 asthmatic 

or atopic) who were exposed for 4 hours in a chamber to a pollution mixture designed to simulate that of the 

Uniontown study (Linn et al. 1997). With the exception of ozone, exposure to air pollutants (sulfuric acid 

MMAD=0.6 μm and sulfur dioxide) were three times the levels of Uniontown so that the total dose in 4 hours 
 

SULFUR TRIOXIDE AND SULFURIC ACID 103 

2. HEALTH EFFECTS 

was equivalent to a 12 hour exposure of the Uniontown pollutant mixture. The ozone level could not be 

increased because a higher concentration would have resulted in irritation. Chemical differences in the 

composition of the pollution mixture, differences in time course of exposure, and psychological effects of 

chamber exposure were all discussed as possible reasons for the discrepancies between the studies. 

Increased sensitivity to sulfuric acid has been observed in young guinea pigs. Exposure of 5-12 guinea pigs 

to sulfuric acid (1 μm) for 8 hours resulted in LC50s of 18 mg/ m3

 in 1-2-month-old animals and 50 mg/ m3 in 

1.5-year-old animals (Amdur et al. 1952a). Due to similarities in sulfuric acid-induced respiratory responses 

between guinea pigs and asthmatics, guinea pigs are considered a suitable model for extrapolating test results 

to asthmatics (Amdur 1989a). 

Age-related differences in the distribution of sulfuric acid within the lung have been observed. A model was 

used to determine total and regional sulfuric acid deposition within the respiratory tract during mouth 

breathing in subjects aged 7,22,47,98, and 240 months (Martonen and Zhang 1993). No consistent, agerelated 

differences were noted for deposition of sulfuric acid within the alveolar compartment. However, total 

respiratory deposition was greatest in the 7-, 22-, and 48-month-old children, and decreased monotonically as 

the lungs matured. The increased deposition resulted from smaller airway diameters of children. Differences 

between adults and children were more pronounced with increased breathing rate, which can occur during 

exercise. Models were also used to study the deposition of hygroscopic particles in a 48-month-old child 

under different breathing conditions. Deposition of hygroscopic particles in the 48-month-old child (original 

diameter 1 μm) was greatest in the alveolar region during restful breathing but was greatest in the 

tracheobronchial region during exerted breathing. The models of Martonen and Zhang ( 1993) suggest 

increased sensitivity in children, due to increased deposition resulting from smaller airway, and that subject 

age and breathing parameters need to be addressed in health studies. 

Following exposure through any route (e.g., inhalation, oral, dermal, or ocular) it is unlikely that sulfuric acid 

would reach germ cells, cross the placenta, or be excreted into breast milk. When sulfuric acid contacts 

tissues, it dissociates into hydrogen and sulfate ions. Hydrogen ions are responsible for the toxic effects, 

which occur only at the point of contact with sulfuric acid. Studies, which evaluate developmental effects in 

humans, are not available. However, a limited number of studies in animals have indicated that sulfuric acid 

is not a developmental hazard (Capdevielle and Scanes 1995a, 1995b; Murray et al. 1979). 
 

SULFUR TRIOXIDE AND SULFURIC ACID 104 

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In conclusion, a limited number of studies have suggested that asthmatic adolescents may be more susceptible 

to transient sulfuric acid-induced changes in respiratory function than asthmatic adults, but more studies are 

needed before definite conclusions can be made. Increased susceptibility of children may be due to increased 

pulmonary deposition, as a result of smaller airway diameter (Maronen and Zhang 1993), and limited 

buffering capacity, resulting from incomplete development of mucous and mucosa (Holma et al. 1985). 

Additional studies are needed to better characterize susceptibility in children, 

2.7 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 sulfur trioxide and sulfuric acid are discussed in Section 2.7.1. 

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 (NAWNRC 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 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 105 

2. HEALTH EFFECTS 

health impairment (e.g., DNA adducts). Biomarkers of effects caused by sulfur trioxide sulfuric acid are 

discussed in Section 2.7.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organisms 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 2.9, Populations That Are Unusually Susceptible. 

2.7.1 Biomarkers Used to Identify or Quantify Exposure to Sulfur Trioxide/Sulfuric Acid 

There are no established biomarkers of exposure for sulfur trioxide or sulfuric acid. The pH of saliva has 

been shown to decrease in persons occupationally exposed to sulfuric acid (El-Sadik et al. 1972). The pH of 

respiratory mucus may also decrease following inhalation exposure to sulfuric acid (Holma 1985). Because 

many things can affect the pH of saliva and respiratory mucus, a decrease in pH would not be a biomarker 

unique to sulfuric acid exposure. 

2.7.2 Biomarkers Used to Characterize Effects Caused by Sulfur Trioxide/Sulfuric Acid 

Changes in pulmonary function tests, observed minutes following acute inhalation exposure of humans to 

sulfuric acid (Avol et al. 1988; Hanley et al. 1992; Koenig et al. 1985, 1992; Utell et al. 1984), and tooth 

etching following occupational exposure to sulfuric acid, have been reported (El-Sadik et al. 1972; Gamble et 

al. 1984b; Malcolm and Paul 1961). The average exposure duration associated with tooth etching is five 

years, but etching has also been observed with only three to four months of exposure (Malcolm and Paul 

1961). These effects are not unique to sulfuric acid exposure, and clear, concentration-response relationships 

have not been established for these effects. Because the effects of sulfuric acid exposure are dependent on 

many factors in addition to concentration, including aerosol size, relative humidity, and breathing factors, a 

population-based, concentration-response relationship for these effects would be difficult to establish. 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (1990), and for information on biomarkers 

for neurological effects see OTA (1990). 
 

SULFUR TRIOXIDE AND SULFURIC ACID 106 

2. HEALTH EFFECTS 

2.8 INTERACTIONS WITH OTHER CHEMICALS 

In. the environment, sulfuric acid exposure most freqluently occurs in combination with exposure to other air 

pollutants including small metal particles, ozone, sulfur dioxide, and nitrogen oxides. Therefore, there are 

numerous studies that examine the effects of sulfuric acid in combination with other air pollutants. 

Exposure of 19 normal human volunteers to 0.37 ppm ozone, 0.37 ppm sulfur dioxide, and 0.1 mg/ m3 

sulfuric acid aerosols (MMAD 0.5 μm) for 2 hours of alternating 15minute periods of exercise and rest 

resulted in a 3.7% depression in FEV1 (Kleinman et al. 1981). The investigators indicated that exposure to 

ozone alone, under the same conditions, depressed FEV1 by about 2.8%. A 3-hour exposure to sulfuric acid 

(0.107 mg/ m3

; MMAD 0.64 μm) 24 hours before a 3-hour exposure to ozone at 0.08,0.12, or 0.18 ppm 

significantly enhanced the effect of ozone in asthmatics (Frampton et al. 1995). An ozone concentrationrelated 

response was observed for both FVC and FEV1, with the effect observed immediately after exposure 

for FVC, and 4 hours after exposure for FVC and FEV1. Significant deficits in lung function were not 

observed in 30 young (1l-l 8 years old) asthmatics exposed to sulfuric acid (0.127 mg/ m3

; MMAD 

0.66 pm), nitrogen dioxide (0.3 ppm), and ozone (0.2 ppm) for 90 minutes (Linn et al. 1995); the subjects 

exercised during the exposures. Exposure of 9 atopic adolescents (aged 12-18) to a mixture of 0.068 mg/ m3 

sulfuric acid (MMAD 0.6 μm) and 0.1 ppm sulfur dioxide by mouth, while exercising for 10 minutes of a 40­

minute exposure period, did not result in a further decrease in FEV1, which was observed following exposure 

to sulfuric acid alone (6% decrease, p<0.05) (Koenig et al. 1989). However, exposure to 0.068 mg/ m3 

sulfuric acid alone resulted in a nonsignificant, 12% increase in total respiratory resistance, but a significant 

15% increase in total respiratory resistance was observed following exposure to the 0.068 mg/m3

 sulfuric 

acid and 0.1 ppm sulfur dioxide mixture. 

Sulfuric acid as a surface layer on aerosols of zinc oxide was more potent in decreasing the diffusing capacity 

of carbon monoxide in guinea pigs than sulfuric acid aerosol alone (Amdur 1989b). Adsorption of acids to 

carbon particles may increase toxicity because it restricts neutralization by ammonia in the airways or 

buffering systems in epithelium (Jakab et al. 1996). Some studies indicate that sulfuric acid potentiates the 

response to ozone. For example, potentiation of ozone has been observed in rats at sulfuric acid 

concentrations as low as 40 μg/ m3

 (Amdur 1989a). Kimmel et al. (1997) reported a synergistic effect in rats 

exposed to both sulfuric acid and ozone. The rats were exposed for 4 hours per day, for 2 days, to 0.6 ppm 

ozone and 0.5 mg/ m3

sulfuric acid with MMDs of 0.3 μm (fine) or 0.06 μm (ultrafine). Exposure to the fine 

aerosol resulted in significantly increased cell proliferation in the acinar region, an effect not observed with 
 

SULFUR TRIOXIDE AND SULFURIC ACID 107 

2. HEALTH EFFECTS 

the ultrafine aerosol. Exposure to the ultrafine aerosol resuhed in an increase in the volume percentage of 

markedly-to-severely injured tissue, an effect not observed with the fine aerosol. This study indicates that 

aerosol size also has a role in determining whether or not an interaction between sulfuric acid and other 

toxicants will occur. 

Combined exposure to sulfuric acid and ozone has also been shown to have no potentiating effects compared 

to exposure to either substance alone. El-Fawal et al. (1995) exposed rabbits nose-only to both ozone (0.1, 

0.3, or 0.6 ppm) and sulfuric acid (MMD 0.3 μm; 50,75, or 125 μg /m3

) for 3 hours. After the exposures, 

sections of bronchi were removed and the responsiveness to acetylcholine was determined in an in vitro 

assay. The combination of ozone and sulfuric acid reduced the responsiveness to acetylcholine that was 

observed following ozone exposure alone. 

The effects of a 4-hour combined exposure of rats to ozone (0.5 ppm), nitric acid (0.7 mg/ m3

), and sulfuric 

acid (0.6 mg/ m3

) were not greater than the effects of a 4-hour ozone exposure (Mautz et al. 1991). Toxicity 

was assessed through the measurement of breathing patterns, metabolic rates, fatty acid composition of 

pulmonary surfactant, nasal epithelial injury, oxidant-induced lung parenchymal lesions, and changes in total 

protein lung in lavage fluid. 

Last and Pinkerton exposed rats (6/group) to mixtures of 0.2 ppm ozone and 0.020 mg/m3

 sulfuric acid (0.4­

0.8 μm) for 12 hours/day, 7 days/week for 30 or 90 days or 0.2 ppm ozone and 0.150 mg/ m3

 sulfuric acid 

(0.4-0.8 μm) 23.5 hours/day, 7 days/week for 30 or 90 days. Sulfuric acid did not potentiate an increase in 

alveolar density, which was observed following exposure to ozone alone (Last and Pinkerton, 1997) 

Compared to results in rats exposed to 5 ppm nitrogen dioxide for 1 day, protein in lavage fluid was 

significantly increased in rats exposed to both 5 ppm nitrogen dioxide and sulfuric acid at 0.5 mg/ m3

 for 

1 day (MMAD 0.4 μm) (Last and Warren 1987). This increased response was not observed after 3 days of 

exposure. Rats were not exposed to sulfuric acid aerosols alone in this study. 

Guinea pigs exposed to sulfuric acid at 8 mg/ m3

 (mean diameter 1 μm) and sulfur dioxide at 89 ppm for 

8 hours showed effects that were more severe than those of exposure to either substance alone (Amdur 1954). 

Body weight gain, lung pathology, and labored breathing were all more severe following the combined 

exposure, while the study author noted that exposure to either substance alone at the concentrations used was 

ineffective in producing a respiratory response. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 108 

2. HEALTH EFFECTS 

To examine the ability of air pollutants to act as a promoter, rats were exposed to nitrogen dioxide (0.4 ppm) 

and sulfuric acid aerosols (MMAD 0.7 1 μm; 1 mg/ m3

) for 13 months followed by an 11 -month observation 

period, with and without pretreatment with a single intraperitoneal injection of N-bis(2-hydroxypropyl) 

nitrosamine (BHPN; 0.5 g/kg) (Ichinose and Sagai 1992). Nitrogen dioxide exposures were for 24 hours per 

day, and sulfuric acid aerosol exposures were for 10 hours per day. Treatment with BHPN alone did not 

result in any tumors, while treatment with nitrogen dioxide and sulfuric acid following BHPN treatment 

resulted in lung tumors (adenomas and adenocarcinomas) in 3 of 36 rats. This study suggests that the 

combination of nitrogen dioxide and sulfuric acid can act as a lung tumor promotor. 

There is evidence of a possible synergistic relationship between sulfuric acid and smoking in the development 

of laryngeal cancer. A case control study was conducted of 352 white males with laryngeal cancer and 1050 

white male controls. The risk of developing laryngeal cancer was significantly greater in heavy smokers with 

occupational exposures to sulfuric acid than in heavy smokers with no sulfuric acid exposure. Relative risks 

for the low (<20 years) and high (>20 years) sulfuric acid exposure categories were 2.05 and 2.43, respectively 

(Cookfair et al. 1985). The study is limited because actual exposure concentrations were not known. 

The relationship between smoking and laryngeal cancer appears to be associated primarily with cigarette 

smoking. Although an excess risk of laryngeal cancer has been reported among pipe and cigar smokers, pipe 

and cigar smoke were not found to be confounding factors in a study of laryngeal cancer among workers 

exposed to sulfuric acid mists (Steenland et al. 1988). 

2.9 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to sulfur trioxide and sulfuric acid than 

will most persons exposed to the same level of sulfur trioxide and sulfuric acid 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 may result in reduced detoxification or excretion of sulfur trioxide and 

sulfuric acid or compromised function of target organs affected by sulfur trioxide and sulfuric acid. 

Populations who are at greater risk due to their unusually high exposure to sulfur trioxide and sulfuric acid 

are discussed in Section 5.7, Populations With Potentially High Exposure. 

Asthmatics are more sensitive to sulfuric acid exposure. One reason for their enhanced sensitivity is that the 

pH of their mucus mass is lower (5.3-7.6) than in normal subjects (7.4-8.2). Thus ofcan neydrogen ions before 

the pH of the mucus is changed significantly, resulting 
SULFUR TRIOXIDE AND SULFURIC ACID 109 

2. HEALTH EFFECTS 

in pH changes in the surrounding tissue. Lowering the pH of mucus increases its vicosity (Holma 1985), 

which would decrease mucociliary clearance. 

Other persons, who have an innately low mucus pH would also be more sensitive to sulfuric acid. The mucus 

of smokers contains higher levels of lysozyme and total protein, and their mucus may also have a lower 

capacity to neutralize hydrogen ions (Holma 1989). Because mucus production is not fully developed in 

infants, they may also be more sensitive to sulfuric acid exposure (Holma 1985; Reid 1974). 

In addition to effects on mucus, smokers, and possibly those exposed to second hand smoke, may be at 

greater risk of the effects of sulfuric acid exposure because mucociliary clearance is already compromised 

(Albert et al. 1971). Other persons with compromised lung function would also be more sensitive to 

inhalation exposure to sulfuric acid aerosols Children are a potentially sensitive subgroup and are discussed 

under Section 2.6. 

2.10 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to sulfur trioxide and sulfuric acid. 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 sulfur 

trioxide and sulfuric acid. When specific exposures have occurred, poison control centers and medical 

toxicologists should be consulted for medical advice. The following texts provide specific information about 

treatment following exposures to sulfur trioxide and/or sulfuric acid: Bronstein AC, Currance PL. 1988. 

Emergency Care for Hazardous Materials Exposure; Ellenhorn MJ, Barceloux DG. 1988. Medical 

Toxicology; Gosselin RE, Smith RP, Hodge HC. 1984. Clinical Toxicology of Commercial Products; 

Haddad LM, Winchester H. 1990. Clinical Management of Poisoning and Drug Overdose; Stutz DR, Ulin S. 

1992. Hazardous Materials Injuries. 

2.10.1 Reducing Peak Absorption Following Exposure 

Human exposure to sulfur trioxide or sulfuric acid aerosols can occur by inhalation. Moving the subject to 

fresh air is the best way to reduce exposure to sulfur trioxide and sulfuric acid aerosols following inhalation 

exposure. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 110 

2. HEALTH EFFECTS 

Human exposure to sulfuric acid can also occur via ingestion or direct contact with the skin or eyes. After 

ingestion, emesis should not be induced (Ellenhorn and Barceloux 1988), although gastric suction has been 

recommended (Haddad and Winchester 1990). Dilution with cold water or milk or neutralization with 

antacids are recommended only if the acid is not concentrated (Gosselin et al. 1984). If the acid is 

concentrated, dilution will produce considerable heat which may cause further damage to the gastrointestinal 

tract (Haddad and Winchester 1990). Following direct contact with the skin or eyes, the affected area should 

be irrigated continuously with water to help alleviate the increase in temperature (Gosselin et al. 1984). 

Continuous irrigation with saline has also been recommended (Ellenhorn and Barceloux 1988). Dilution of 

concentrated sulfuric acid with saline may produce less heat than dilution with water. 

2.10.2 Reducing Body Burden 

Sulfur trioxide and sulfuric acid are direct-acting toxicants that do not need to be absorbed into the 

bloodstream to result in adverse effects. Methods for reducing body burden are not applicable for these 

direct-acting substances. Preventing sulfuric acid from contacting tissues will prevent the adverse effects of 

sulfuric acid. 

2.10.3 Interfering with the Mechanism of Action for Toxic Effects 

Because sulfuric acid acts directly on tissues by changing pH, preventing this pH change by dilution or 

neutralization would reduce or prevent the effects of sulfuric acid. As discussed in Section 2.10.1, dilution 

must be used with caution if concentrated sulfuric acid is ingested because the heat that is produced could 

produce additional damage (Haddad and Winchester 1990). 

2.11 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 sulfur trioxide and sulfuric acid 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 sulfur trioxide and sulfuric acid. 
 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 111 

2. HEALTH EFFECTS 

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. 

2.11.1 Existing Information on Health Effects of Sulfur Trioxide and Sulfuric Acid 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to sulfur 

trioxide and sulfuric acid are summarized in Figure 2-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of sulfuric acid. 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 qluality 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 (ATSDR 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. 

Because sulfur trioxide reacts with water to form sulfuric acid, studies of the health effects of sulfuric acid are 

applicable to sulfur trioxide. Therefore, a separate figure for the limited studies of sulfur trioxide is not 

presented. 

2.11.2 Identification of Data Needs 

On contact with water, sulfur trioxide forms sulfuric acid. Therefore, exposure to sulfur trioxide results in 

effects that are the same as observed following exposure to sulfuric acid. The following discussion on data 

needs focuses on studies of sulfuric acid. Separate studies of the effects of sulfur trioxide are not needed. 

Acute-Duration Exposure. Sulfuric acid is a direct-acting toxicant, resulting in effects in the tissues with 

which it comes into contact. There are numerous acute-duration inhalation studies regarding the respiratory 

effects of sulfuric acid in both asthmatic (Anderson et al. 1992; Aris et al. 1991; Avol et al. 1988, 1990; Fine 

et al. 1987; Frampton et al. 1995; Hanley et al 1992; Koenig et al. 1985,1992, 1993; Linn et al. 1986, 

1994; Utell et al. 1983, 1989) and healthy volunteers (Amdur et al. 1952b; Anderson et al. 1992; Avol et al. 

 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 113 

2. HEALTH EFFECTS 

1988; Bowes et al. 1995; Culp et al. 1995; Frampton et al. 1992, 1995; Gamble et al. 1984a; Horvath et al. 

1987; Knapp et al. 1991; Kulle et al. 1982; Laube et al. 1993; Leikauf et al. 1981, 1984; Linn et al. 1994; 

Newhouse et al. 1978; Sim and Battle 1957; Spektor et al. 1989; Stacy et al. 1983; Utell et al. 1984). These 

studies indicate that asthmatics are more sensitive to respiratory effects following sulfuric acid exposure than 

healthy subjects. These studies also indicate that aerosol size; relative humidity; and subject factors, 

including breathing rate and depth, method of breathing (e.g., oral, nasal, oronasal), and respiratory tract 

ammonia, all influence the response to inhalation of sulfuric acid aerosols. A study in healthy asthmatics 

demonstrated changes in pulmonary function at a sulfuric acid concentration of 0.45 mg/ m3

, but not 

0.1 mg/ m3 (Utell et al. 1983). 

Accidental acute oral exposure of humans to concentrated sulfuric acid indicates that it is highly corrosive to 

the gastrointestinal tract (Aktug et al. 1995; Dilawari et al. 1984). Dermal corrosions result when the skin of 

humans comes into contact with sulfuric acid of sufficient concentration (Branday et al. 1996; Schultz et al. 

11968). In an experimental study, no skin effects were observed when 10% sulfuric acid was placed on the 

skin of volunteers (Nixon et al. 1975). 

There are numerous acute-duration inhalation studies in animals regarding the respiratory effects of sulfuric 

acid (Amdur 1958,1959; Amdur et al. 1952a, 1978; Cavender et al. 1977; Chen et al. 1992a, 1992b; 

Cockrell et al. 1978; El-Fawal and Schlesinger 1994; Grose et al. 1982; Kobayashi and Shinozaki 1993; Lee 

et al. 1995; Mannix et al. 1991; Schlesinger 1990a; Schlesinger and Gearhart 1986; Schlesinger et al. 1984, 

1990b; Stengel et al. 1993; Warren and Last 1987; Wolff et al. 1979; Zelikoff and Schlesinger 1992; 

Zelikoff et al. 1994). These studies indicate that guinea pigs are the most sensitive species and that the 

measurement of mucociliary clearance of tracer particles is a more sensitive technique than pulmonary 

function tests. Studies in animals also indicate that the effects of inhalation of sulfuric acid aerosols are 

dependent on aerosol size. Acute-duration oral studies concerning the concentration of sulfuric acid required 

to cause gastrointestinal tract effects were not identified. A 14-day study of chicks fed sulfuric acid in the 

diet revealed that this route of exposure to sulfuric acid was relatively well tolerated (Capdevielle and Scanes 

1995b). Acute-duration dermal studies of sulfuric acid do not agree on the concentration that results in 

dermal effects. One study reported erosion of the skin at 10% with no effects at 2.5% (Sekizawa et al. 1994), 

while another study reported no dermal effects at 10% (Nixon et al. 1975). Following direct application of 

sulfuric acid to the eyes of animals, one study reported severe cornea1 opacities at 10% with minimal effects 

at 5% (Murphy et al. 1982), while a second study reported no effects at 10% (Jacobs 1992). 
 

SULFUR TRIOXIDE AND SULFURIC ACID 114 

2. HEALTH EFFECTS 

Although there are numerous acute-duration inhalation studies of sulfuric acid in both humans and animals, 

an acute-duration MRL was not derived. An MRL was not derived because the methodology for derivation 

does not incorporate all the variables in addition to concentration that determine the response to sulfuric acid. 

Rather than additional acute-duration inhalation studies, more work regarding methodology for developing 

MRLs for hygroscopic aerosols and acute inhalation irritants is needed. Further development of models that 

examine the effect of aerosol size on the deposition of sulfuric acid aerosols in the lungs (Martonen and Pate1 

198 1; Martonen and Zhang 1993) would also be useful for development of an acute-duration inhalation 

MRL. Data are not sufficient for the development of an acute-duration oral MRL for sulfuric acid. 

Additional studies to determine the concentration of sulfuric acid that can be tolerated by the gastrointestinal 

tract would be of value to poison control centers. Additional dermal and ocular studies that clarify the 

threshold sulfuric acid concentration resulting in skin and eye irritation are needed. 

Intermediate-Duration Exposure. There are no intermediate-duration inhalation, oral, or dermal studies 

of sulfuric acid in humans. Respiratory effects have been studied in animals following intermediate-duration 

inhalation exposure. The focus of these studies has been histopathological changes in the respiratory tract 

(Cavender et al. 1977; Thomas et al. 1958) and clearance of test particles (Schlesinger and Gearhart 1986; 

Schlesinger et al. 1979, 1992a). The only intermediate-duration oral study is a 15-day study in which no 

systemic growth (liver, kidney, endocrine) effects were observed in ducklings fed sulfuric acid in the diet 

(Capdevielle and Scanes 1995a). No intermediate-duration dermal studies in animals were identified. 

The data are not sufficient for developing an intermediate-duration inhalation MRL. A study that examines 

pulmonary function in persons occupationally exposed to sulfuric acid, in which the exposure conditions are 

well defined (e.g., concentrations, aerosol size, and relative humidity), is needed. This study should examine 

changes in pulmonary function over time, including intermediate-duration exposure. Data are not sufficient 

for the development of an intermediate-duration oral MRL for sulfuric acid. Additional acute studies that 

clarify the threshold sulfuric acid concentration resulting in direct irritation of the gastrointestinal tract, skin, 

and eyes, should also identify thresholds that would be protective for intermediate-duration exposure. 

Chronic-Duration Exposure and Cancer. Chronic occupational exposure to sulfuric acid aerosols has 

been associated with a small decrease in FVC (Gamble et al. 1984b), increased reports of bronchitis 

(Kitagawa 1984; Williams 1970), increased tooth erosion (El-Sadik et al. 1972; Gamble et al. 1984b; 

Malcolm and Paul 196 l), and an increase in periodontal pockets (Tuominen 199 1). No chronic-duration 

studies were identified regarding the effects of sulfuric acid in humans following oral or dermal exposure. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 115 

2. HEALTI-i EFFECTS 

The only animal studies that examine a wide range of systemic effects in addition to respiratory effects (e.g., 

cardiovascular, hematological, hepatic, renal, body weight) are chronic studies in cynomolgus monkeys 

(Alarie et al. 1973) and guinea pigs (Alarie et al. 1973, 1975). The effects noted in these studies were 

histopathological changes in the lungs of monkeys at 4.79 mg/ m3

 (MMD 0.73 μm) and 0.38 mg/ m3 (MMD 

2.15 μm). At a concentration of 2.43 mg/ m3

 (MMD 3.6 μm) histopathological changes were observed in the 

alveoli as well as the bronchioles in exposed monkeys, and a decrease in arterial oxygen was also observed. 

No effects, including histopathological changes in the respiratory tract, were observed in guinea pigs who 

were exposed to a maximum concentration of 0.9 mg/m3

 (MMD 0.49 μm) (Alarie et al. 1975). Although 

these studies clearly report effects that were treatment-related, data for end points that did not show 

treatment-related effects, for example liver enzyme data, were not reported. Increased bronchial sensitivity to 

acetylcholine (Gearhart and Schlesinger 1986) and decreased clearance of test particles (Gearhart and 

Schlesinger 1989; Schlesinger et al. 1992a) were reported following a 1 -year exposure of rabbits to sulfuric 

acid aerosols. No chronic-duration studies were identified regarding the effects of sulfuric acid in animals 

following oral or dermal exposure. 

The data are not sufficient for developing a chronic-duration inhalation MRL. A study that examines 

pulmonary function in persons occupationally exposed to sulfuric acid for chronic durations, in which the 

exposure conditions are well defined (e.g., concentrations, aerosol size, relative humidity), is needed. This 

study should examine changes in pulmonary function over time and should include chronic-duration 

exposure. Data are not sufficient for the development of a chronic-duration oral MRL for sulfuric acid. 

Additional studies that clarify the threshold sulfuric acid concentration resulting in direct irritation of the 

gastrointestinal tract, skin, and eyes, should also identify thresholds that would be protective for chronicduration exposure. 

Occupational exposure to mineral acid aerosols containing sulfuric acid has been associated with the 

development of respiratory tract cancers, especially laryngeal and lung cancers (Alderson and Rattan 1980; 

Beaumont et al. 1987; Coggon et al. 1996; Cookfair et al. 1985; Forastiere et al. 1987; Houghton and White 

1994; Soskolne et al. 1982, 1984,1992; Steenland and Beaumont 1989; Steenland et al. 1988). However, 

most of the cancers were in smokers who were also exposed to other chemicals. There is no information that 

exposure to sulfuric acid by itself is carcinogenic, and there are no clear data on exposure concentrations of 

sulfuric acid associated with cancer in humans. Environmental exposure of humans to sulfuric acid has not 

been associated with cancer (Abbey et al. 1995). The carcinogenicity of sulfuric acid alone has not been 

studied in animals after exposure by any route. Combined sulfuric acid and nitrogen dioxide exposure has 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 116 

2. HEALTH EFFECTS 

been shown to act as a promoter of lung tumors in rats (Ichinose and Sagai 1992). Based on the limited 

human data, which associate occupational exposure to sulfuric acid aerosols with the development of lung 

and laryngeal cancers, IARC (1992) considers occupational exposure to strong-inorganic-acid mists 

containing sulfuric acid carcinogenic to humans (Group 1). The DHHS (1994) and EPA have not classified 

sulfuric acid for carcinogenic effects. Because repeated irritation of the lungs by sulfuric acid exposure is 

likely to act as a promoter, and because sulfuric acid exposure generally occurs in the presence of other 

pollutants, further research on the ability of sulfuric acid aerosols to act as a promoter is needed. The 

carcinogenicity of sulfuric acid has not been studied after exposure by any other route. Because chronic-duration 

oral and dermal exposure to irritating concentrations of sulfuric acid is unlikely, cancer studies 

following exposure by these routes are not needed. 

Genotoxicity. In vivo studies regarding the genotoxicity of sulfuric acid were not identified. Sulfuric acid 

did not increase gene mutation in bacteria (Cipollaro et al. 1986; Demerec et al. 1951). Increases in 

chromosomal aberrations were observed in root meristimatic tissue of the plant Viciafaba (Zura and Grant 

1981), in Chinese hamster ovary cells (Morita et al. 1989), and in sea urchins (Cipollaro et al. 1986) exposed 

to sulfuric acid. Other in vitro studies in which pH was adjusted with other acids indicate that acidic pH is 

genotoxic, resulting in chromosomal anomalies in human lymphocytes (Shimada and Ingalls 1975) and 

mouse lymphoma cells (Cifone et al. 1987) and a transformed-like morphology in Syrian hamster cells 

(LeBoeuf and Kerckaert 1986). Further studies regarding the mechanism of genotoxic effects following 

exposure to low pH are needed to determine if mutations induced by low pH is a mechanism in the 

development of laryngeal cancer. 

Reproductive Toxicity. Reproductive effects following exposure to sulfuric acid by any route have not 

been studied in humans. No significant effects on the mean numbers of implants/dam or resorptions/litter 

were noted in mice or rabbits exposed by inhalation to sulfuric acid aerosols during gestation (Murray et al. 

1979). Changes in testes weight were not observed in chicks (Capdevielle and Scanes 1995b) or ducklings 

(Capdevielle and Scanes 1995a) fed sulfuric acid in the diet. No additional studies were identified regarding 

reproductive effects of sulfuric acid in animals following exposure by any route. Because sulfuric acid is a 

direct-acting toxicant, and because it is unlikely to reach reproductive organs, reproductive effects in 

mammals are not likely following exposure to sulfuric acid by any route. Therefore, additional reproductive 

studies are not needed at this time. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 117 

2. HEALTH EFFECTS 

Developmental Toxicity. The developmental effects of sulfuric acid have not been studied in humans by 

any route of exposure. No significant effects were observed on fetal body weights or on the incidence of 

major or minor malformations in mice or rabbits exposed by inhalation to sulfuric acid aerosols during 

gestation (Murray et al. 1979). Because sulfuric acid is a direct-acting toxicant, and because it is unlikely to 

reach developing mammals, developmental effects in mammals are not likely following exposure to sulfuric 

acid by any route. Therefore, additional developmental toxicity studies of sulfuric acid are not needed at this 

time. 

Immunotoxicity. The function of alveolar macrophages collected from humans following inhalation 

exposure to sulfuric acid aerosols for 2 hours was not affected (Frampton et al. 1992). Immunological effects 

have not been studied in humans following exposure by other routes. Alveolar macrophage function has been 

shown to be affected in animals following inhalation exposure to sulfuric acid aerosols (Chen et al. 1992a, 

1995; Schlesinger et al. 1992b; Zelikoff and Schlesinger 1992). The effects on alveolar macrophage function 

were not concentration related. Once a critical level of sulfuric acid was reached, no further effects were 

observed. Effects were greater following exposure to smaller sized aerosols (MMD 0.04 μm versus 0.3 μm), 

leading Chen et al. (1992a) to suggest that the smaller droplets deliver a higher dose to the macrophages than 

the larger droplets. Inhalation exposure to sulfuric acid aerosols has also been shown to enhance antigen-induced 

histamine release from mast cells collected from exposed guinea pigs (Fujimaki et al. 1992). Mice 

challenged with Streptococcus pyrogens directly after ultrafine sulfuric acid aerosol (2 hours/day for 5 days) 

exposure did not experience increased mortality (Grose et al. 1982). Additional studies regarding 

susceptibility of animals to respiratory infections (bacterial, viral) following intermediate- and chronicduration 

exposure to sulfuric acid exposure are needed. 

Immunological and lymphoreticular effects have not been studied following oral or dermal exposure to 

sulfuric acid. Because sulfuric acid is a direct-acting toxicant, system-wide effects on the immune system are 

not likely following exposure to sulfuric acid by any route. 

Neurotoxicity. Fatigue and headaches were reported more frequently in asthmatic volunteers when they 

were exposed to sulfuric acid aerosols (Avol et al. 1988). In guinea pigs, uncoordinated movement was 

reported after exposure to 165 mg/m3

 of sulfuric acid mists but not higher concentrations. Neurological 

effects have not been studied following oral or dermal exposure of humans or animals, Because sulfuric acid 

is a direct-acting toxicant, neurological effects other than subjective symptoms associated with irritation and 
 

SULFUR TRIOXIDE AND SULFURIC ACID 118 

2. HEALTH EFFECTS 

pulmonary function changes are not likely following exposure to sulfuric acid by any route. Studies of 

neurological effects following sulfuric acid exposure are not needed at this time. 

Epidemiological and Human Dosimetry Studies. Increased mortality, especially of elderly persons 

and those with preexisting cardiac and respiratory disease, has been reported during or shortly after air 

pollution episodes (reviewed in Costa and Amdur 1996). In general, increased mortality in these studies 

correlates more closely with particulate matter, including sulfuric acid aerosols. In a study that tried to 

distinguish the effects of sulfuric acid aerosols from those of sulfur dioxide and of British smoke (a measure 

of particulates), the log of sulfuric acid aerosol concentrations in London was most strongly correlated with 

total mortality than that of sulfur dioxide or British smoke (Thurston et al. 1989). The authors of the study 

concluded that their study was consistent with the hypothesis that sulfuric acid is the portion of the particulate 

mass with the greatest health significance. An association between mortality and environmental sulfate 

concentrations was not observed among 6,340 nonsmokers living in California (Abbey et al. 1995). An 

increase in asthma symptoms has been associated with increases in environmental sulfate concentrations 

(Abbey et al. 1993, 1995). Overall mortality of workers was not associated with acid exposure at steel 

factories (Beaumont et al. 1987) or at a sulfuric acid plant (Englander et al. 1988). Additional studies that 

examine environmental sulfuric acid concentration and death and respiratory effects in humans would be 

useful if exposure to other pollutants is taken into consideration. 

Occupational exposure to mineral acid aerosols including sulfuric acid has been associated with the 

development of respiratory tract cancers, especially laryngeal and lung cancers (Alderson and Rattan 1980; 

Beaumont et al. 1987; Coggon et al. 1996; Forastiere et al. 1987; Houghton and White 1994; Soskolne et al. 

1984, 1992; Steenland and Beaumont 1989; Steenland et al. 1988). However, most of the cancers were in 

smokers who were also exposed to other chemicals. There is no information that exposure to sulfuric acid by 

itself is carcinogenic, and there are no clear data on exposure concentrations of sulfuric acid associated with 

cancer in humans. Additional studies of cancer in persons occupationally exposed to sulfuric acid aerosols, 

especially in a population with detailed exposure information, are needed. 

Exposure models for sulfate and hydrogen ions have been developed to provide better predictions of human 

exposure compared to outdoor air concentrations alone (Suh et al. 1993). When the sulfate model was 

compared to actual personal exposure data, it was found that sulfate exposure could be adequately predicted 

by the outdoor concentration, activity of the person, and their use of air conditioning. The hydrogen ion 

model included a neutralization term and was better at predicting personal exposure when indoor air 
 

 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 119 

2. HEALTH EFFECTS 

concentrations of hydrogen ion and personal ammonia levels were also included. Because of the importance 

of personal ammonia levels for predicting hydrogen ion exposure, and because of similar difficulties in 

measuring personal ammonia and hydrogen ion concentrations, the study authors suggested that direct 

measurement of personal hydrogen ion exposure may be the only method to accurately determine personal 

hydrogen ion exposure. Additional studies that examine personal exposure to sulfuric acid are needed to 

determine the relationship between ambient exposure concentrations and personal exposures. 

Biomarkers of Exposure and Effect 

Exposure. There are no established biomarkers of exposure for sulfur trioxide or sulfuric acid. The pH of 

saliva is decreased in persons occupationally exposed to sulfuric acid (El-Sadik et al. 1972). The pH of 

respiratory mucus may also decrease following inhalation exposure to sulfuric acid (Holma 198.5). 

Additional research examining the relationship between sulfuric acid exposure concentration and saliva pH is 

unlikely to be useful. 

Effect. Changes in pulmonary function tests following acute inhalation exposure of humans to sulfuric acid 

(Avol et al. 1988; Hanley et al. 1992; Koenig et al. 1985, 1992; Utell et al. 1984), and tooth etching 

following occupational exposure to sulfuric acid, have been reported (El-Sadik et al. 1972; Gamble et al. 

1984b; Malcolm and Paul 1961). These effects are not unique to sulfuric acid exposure, and clear 

concentration-response relationships have not been established for these effects. Because the effects of 

sulfuric acid exposure are dependent on many factors in addition to concentration, including aerosol size, 

relative humidity, and breathing factors, a population-based concentration-response relationship for these 

effects would be difficult to establish. 

Absorption, Distribution, Metabolism, and Excretion. Sulfuric acid inhaled by humans is retained 

by the lungs (Amdur et al. 1952b). The regional deposition of sulfuric acid in the lungs is determined by 

aerosol size as well as the method (oral, nasal, oronasal) and rate of breathing (Bowes et al. 1995). The effect 

of hygroscopic growth within the respiratory tract on the deposition of sulfuric acid aerosols has been 

modeled in adults (Martonen and Pate1 198 1) and children (Martonen and Zhang 1993). Excess sulfate is 

excreted in the urine (Vander et al. 1975). Sulfur from instilled sulfuric acid is readily absorbed from the 

lungs but poorly absorbed from the nose of dogs (Dahl et al. 1983). Additional studies and/or models 

regarding the deposition of sulfuric acid aerosols in the lungs would be useful. Because sulfuric acid is a 
SULFUR TRIOXIDE AND SULFURIC ACID 120 

2. HEALTH EFFECTS 

direct-acting toxicant, additional studies regarding absorption into the bloodstream, distribution within the 

body, metabolism, and excretion would not provide insight into the toxic effects of sulfuric acid. 

Comparative Toxicokinetics. Models that compare the deposition of sulfuric acid aerosols in various 

species were not identified. Additional models that examine the effect of aerosol size and of hygroscopic 

growth within the respiratory tract are needed to examine the effects of sulfuric acid aerosols in the various 

species tested. 

Methods for Reducing Toxic Effects. The toxicity of sulfuric acid can be reduced or prevented if the 

acid is neutralized or diluted (Gosselin et al. 1984). Further research regarding the best first aid method to 

dilute sulfuric acid is necessary. Water generates heat; saline or another solution may generate less heat and 

leave less tissue damage. 

Children’s Susceptibility. Because sulfur trioxide is converted to sulfuric acid upon contact with water, 

health effects are consistent with those observed with sulfuric acid exposure. Therefore, the discussion on 

data needs for children will focus on sulfuric acid. Additional data is not required for sulfur trioxide. 

A limited number of studies have examined respiratory responses in asthmatic adolescents following 

exposure to sulfuric acid (Hanley et al. 1992; Koenig et al. 1992, 1985) and it has been suggested that 

asthmatic adolescents may be more sensitive than asthmatic senior citizens (Koenig et al. 1993). Additional 

studies which compare sulfuric acid-induced responses in healthy and asthmatic children of various ages to 

healthy and asthmatic adults would be useful in determining the sensitivity of children. 

Models have indicated increased deposition of sulfuric acid within the respiratory tracts of children, especially 

during periods of exertion (Martonen and Zhang 1993). Additional studies or models which examine 

distribution of sulfuric acid within the respiratory tract of young versus mature humans or animals would be 

useful in determining the impact on children’s health. Studies which compare deposition of sulfuric acid 

with different breathing rates would also be useful. 

However, studies which examine absorption into the bloodstream, systemic distribution, metabolism, and 

excretion in immature or pregnant animals would not likely be useful because sulfuric acid is a direct acting 

toxicant. A lack of developmental effects has been demonstrated in a limited number of studies (Capdevielle 

and Scanes 1995a, 1995b; Murray et al. 1979) and additional studies are not needed. 
SULFUR TRIOXIDE AND SULFURIC ACID 121 

2. HEALTH EFFECTS 

Child health data needs relating to exposure are discussed in 5.8.1 Data Needs: Exposures of Children. 

2.11.3 Ongoing Studies 

Dockery at Harvard University is continuing his research concerning the adverse effects of acid aerosols 

including sulfuric acid on urban populations (CRISP 1996). Speizer at Harvard University is researching the 

respiratory health effects of acid air pollutants on children (FEDRIP 1998). His research is a follow-up study 

of late adolescents living in 15 communities with variable acid aerosol levels in the United States and Canada. 

Additional ongoing studies regarding the health effects of sulfur trioxide and sulfuric acid were not identified. 

SULFUR TRIOXIDE AND SULFURIC ACID 123 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of sulfur trioxide, sulfuric acid, and oleum (fuming sulfuric acid) 

is located in Table 3-1. 

The acid strength of sulfuric acid is designated as percentage sulfuric acid or degrees Baume (oBé) (IARC 

1992). Degrees Baume is a mathematical relationship with specific gravity (Bé = 145 - [145/specific 

gravity]) that is consistent at concentrations below 93.2% sulfuric acid. At higher concentrations, the acid is 

referred to in terms of percentage sulfuric acid. The strength of oleum is indicated by the percentage of free 

dissolved sulfur trioxide, or as the equivalent percentage of 100% sulfuric acid. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of sulfur trioxide, sulfuric acid, and oleum 

(fuming sulfuric acid) is located in Table 3-2. 



SULFUR TRIOXIDE AND SULFURIC ACID 127 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

4.1 PRODUCTION 

Table 4-l lists the facilities in each state that manufacture or process sulfuric acid, the intended use, and the 

range of maximum amounts of sulfuric acid that are stored on site. The data listed in Table 4-l are derived 

from the Toxics Release Inventory (TRI) (TR196 1998). Only certain types of facilities were required to 

report. Therefore, this is not an exhaustive list. According to the 1996 TRI, 707 facilities in the United 

States and 7 facilities in the Commonwealth of Puerto Rico manufactured or processed sulfuric acid in 1996 

(TR196 1998). Similar data were not available for sulfur trioxide. Because sulfur trioxide is produced as a 

precursor to sulfuric acid in the principal method of producing sulfuric acid, sulfur trioxide is likely to be 

present at the facilities listed in Table 4-l. 

From 1972 until 1993, the quantity of sulfuric acid produced in the United States increased; 2.83x107

 metric 

tons were produced in 1972,2.94 x107

 metric tons were produced in 1975, and 3.60 x107 metric tons were 

produced in 1985. Production from 1990 to 1993 varied from 2.99 x107

 metric tons to 3.35 x107metric tons. 

In 1995, sulfuric acid was the most produced chemical in the United States at 3.56 x107 metric tons which 

was a significant increase over 1994 production (3.34 x107

 metric tons) (C&EN 1996). 

There are two major processes that have been used to produce sulfuric acid, the chamber process and the 

contact process. The chamber process was once the predominant method for sulfuric acid production in 

North America and western Europe; however, its use in these regions has dropped from 80% in 1910 to 15% 

in 1960 to virtually zero (IARC 1992). In the chamber process, sulfur dioxide is oxidized to sulfur trioxide, 

which combines with water vapor to form sulfuric acid in the following way: 2N0 + 02 → 2 NO2, 2 NO2+ 2 

SO2 + 2H2O → 2H2SO4 + 2N0. Nitrogen dioxide acts as the oxidant. The end products of this process are 

sulfuric acid and nitrogen oxides. With this process, sulfuric acid of a concentration of about 78% can be 

produced. 

Sulfuric acid can also be produced by the contact process. This process is based on technology that was 

developed around 1900 and has become the primary method of sulfuric acid production (IARC 1992). The 

principal steps in the contact process are (1) oxidation of sulfur to sulfur dioxide with dry air, (2) cooling of 

the gases, (3) conversion or oxidation of the sulfur dioxide to sulfur trioxide, (4) cooling of the sulfur trioxide 

SULFUR TRIOXIDE AND SULFURIC ACID 129 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

gas, and (5) absorption of the sulfur trioxide in water to produce sulfuric acid. The heart of the contact 

process is the converter in which sulfur dioxide is converted catalytically to sulfur trioxide. A variety of 

catalysts can be used including platinum, oxides of iron, chromium, copper, manganese, titanium, vanadium, 

and other metals. Presently, vanadium catalysts in various forms are most widely used. Current methods 

allow for conversion rates as high as 99.5-99.7% (IARC 1992). Sulfuric acid is most commonly marketed in 

four grades: commercial, electrolyte (high purity for batteries), textile (low organic content), and chemically 

pure or reagent grades (IARC 1992). 

Fuming sulfuric acid (oleum) is produced at contact process plants in special towers by adding sulfur trioxide 

to sulfuric acid (IARC 1992). 

4.2 IMPORT/EXPORT 

Import/export data for the 1990s indicate that the United States imports more sulfuric acid and fuming 

sulfuric acid (oleum) than it exports. During 1990-1994, U.S. imports of sulfuric acid and fuming sulfuric 

acid in million metric tons were 1.7, 1.8,2,2.4, and 2.1 in 1990, 1991, 1992, 1993, and 1994, respectively 

(NTDB 1996). Import data for 1995 were not available. During 1991-1995, U.S. exports of sulfuric acid 

and fuming sulfuric acid in metric tons were 147,470, 139,790, 144,865, 136,874, and 170,201 in 1991, 

1992,1993,1994, and 1995, respectively (NTDB 1996). 

4.3 USE 

Sulfur trioxide is primarily used as an intermediate in the production of sulfuric acid. It is also used for 

sulfonation in the formation of additional compounds with amines and in the manufacture of explosives 

(Budavari 1989). Sulfur trioxide can also be used in the sulfonation of organic compounds (especially nonionic 

detergents), as a component of solar energy collectors, and as a powerful but indiscriminate oxidizing 

agent (HSDB 1998). 

In the United States, the main use of sulfuric acid is in phosphate fertilizer production where it used to 

convert phosphate rock to phosphoric acid (IARC 1992). Sulfuric acid is consumed in the production of 

fertilizer, while in many other uses the sulfuric acid can be recovered and reused. Sulfuric acid is also used in 

the manufacture of explosives, dyestuffs, other acids, parchment paper, glue, purification of petroleum, and 

the pickling of metals (Budavari 1989; IARC 1992). It is also used in electroplating baths, nonferrous 
 

SULFUR TRIOXIDE AND SULFURIC ACID 130 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

metallurgy, in the production of rayon and film, as a laboratory reagent and etchant, and in storage batteries 

(HSDB 1998). Sulfuric acid is also a general purpose food additive (HSDB 1998). In the United States in 

1988, the percentages of sulfuric acid used in various processes were estimated as 68% for phosphate 

fertilizers; 7% for petroleum refining; 4% for ore processing; 3.5% for industrial organic chemicals; 2.5% for 

synthetic rubber and plastics; 2.5% for pulp and paper; and 9% for other unidentified uses (IARC 1992). 

4.4 DISPOSAL 

Sulfuric acid is listed as a toxic substance under Section 3 13 of the Emergency Planning and Community 

Right to Know Act (EPCRA) under Title III of the Superfund Amendments and Reauthorization Act (SARA) 

(EPA 1998f). Disposal of wastes containing sulfuric acid is controlled by a number of federal regulations 

(see Chapter 7). 

Spent sulfuric acid can often be reprocessed to obtain a product of virgin quality. Enormous amounts of 

spent sulfuric acid are reprocessed since most of the sulfuric acid used for industrial processes acts only as a 

reagent and does not form part of the final product; one exception is the fertilizer industry (IARC 1992). It 

has been suggested that waste sulfuric acid can also be recycled using sulfate-reducing bacteria to produce 

hydrogen sulfide (Stucki et al. 1993). 

It is not recommended that sulfuric acid or sulfur trioxide be placed in a landfill. Environmental regulatory 

agencies should be consulted for acceptable disposal practices (HSDB 1998). Sulfuric acid has been 

disposed of by being placed in sealed containers and by being absorbed in vermiculite, dry sand, or earth. 

Sulfuric acid may also be diluted and then neutralized. One method of neutralization is to add the acid slowly 

to a solution of soda ash and slaked lime, and to then flush with a large volume of water. Once sulfuric acid 

is diluted, and neutralized it can be discharged to a sewer. When diluting, the acid should always be added to 

a large volume of water because the heat released when a small bolus of water is added can cause the water to 

turn to steam, and the resulting effervescence can splatter the acid. 
SULFUR TRIOXIDE AND SULFURIC ACID 131 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Sulfuric acid is a common chemical that is widely used in industry and is found in consumer products (e.g., 

car batteries, cleaning products). In the United States sulfuric acid is ranked number one in terms of 

production volume. Sulfur trioxide is a precursor to the production of sulfuric acid. Oleum (fuming sulfuric 

acid) is sulfur trioxide absorbed in concentrated sulfuric acid. Sulfur trioxide and sulfuric acid are sometimes 

released to the environment during production and use. Sulfur dioxide released during the burning of fossil 

fuels is also a major source of atmospheric sulfuric acid. In the atmosphere, sulfuric acid is generally in the 

form of small droplets, or it is adsorbed onto small particles. Sulfuric acid leaves the air through dry and 

wet deposition processes. Because of it’s widespread use, and the widespread release of sulfur dioxide, the 

potential for human exposure to sulfuric acid is substantial. 

Sulfuric acid has been found in at least 47 of the 1,467 current or former EPA National Priorities List (NPL) 

hazardous waste sites (HazDat 1998). The frequency of these sites within the United States can be seen in 

Figure 5- 1. 

5.2 RELEASES TO THE ENVIRONMENT 

According to the TRI, in 1996, releases of sulfuric acid to the environment from 714 large processing 

facilities totaled 15,077,944 kg (33,246,867 pounds) (TR196 1998). Table 5-l lists ranges of the amounts 

released from these facilities. The TRI data should be used with caution because only certain types of 

facilities are required to report. This is not an exhaustive list. 

5.2.1 Air 

According to the TRI, in 1996, releases of sulfuric acid to the air from 7 14 large processing facilities totaled 

8,929,868 kg (19,690,359 pounds) (TR196 1998). Table 5-l lists amounts released from these facilities. 

The TRI data should be used with caution because only certain types of facilities are required to report. This 

is not an exhaustive list. 



SULFUR TRlOXlDE AND SULFURIC ACID 135 

5. POTENTIAL FOR HUMAN EXPOSURE 

Additional data concerning the release of sulfur trioxide or sulfuric acid to the air were not identified. Data 

regarding emissions of sulfur dioxide, which reacts with water in air to form sulfuric acid, were identified and 

are summarized below. 

Emissions of sulfuric compounds from the earth and the atmosphere are approximately 1,100x1012

 g 

(natural) and 200x1012 g (human) (Grzesiak et al. 1997). The largest natural direct source of sulfur dioxide 

is volcanic eruptions. Major volcanic eruptions which inject sulfur dioxide into the stratosphere are the 

dominant source of sulfuric acid aerosol in the stratosphere (Hofmann 1990). Gas emissions by vulcanism 

have shown estimates which vary due to methods of measurement and vulcanism variability. The annual 

volcanic sulfur emissions range was between 0.75 and 42 Tg S (Tg = 1012 g; S = sulfur). However, the more 

well known median estimates were between 9 and 24 Tg S/yr, with the average annual value being ≥ 9 Tg S 

(DOE 1996). In the stratosphere, at temperatures ranging from -80°C to –45oC, aqueous spherical droplets 

are generally composed of 60-80% sulfuric acid. The oceans, which contain about 2.65 mg sulfate/g of 

water, are also an important source of atmospheric sulfate (Kellogg et al. 1972). Since water covers 70% of 

the earth’s surface, biogenic gas emissions are the largest natural source of sulfur emissions to the 

atmosphere. Airborne sea spray and marine and coastal organisms are all responsible for introducing sulfur 

into the atmosphere. These emissions are estimated at 11.9 and 15.4 Tg S gases/yr, according to the 

Department of Energy (DOE 1996). 

In the United States, much of the sulfur dioxide is emitted from electric plants in rural sites. These plants 

have high stacks and emit plumes with low particle concentrations; these conditions facilitate the production 

of sulfuric acid in gas and aqueous phases and facilitate the long-range transport of acid aerosols (Spengler et 

al. 1990). The production of acid aerosols is principally a summertime occurrence because it is driven by 

photochemistry and the demand for electricity for air conditioning (Spengler et al. 1990). 

Aerosols formed from coal combustion have a high concentration of sulfates at the surface (Amdur et al. 

1986). This occurs because sulfates condense late, concentrating on the surface. Sulfate concentrations 

increase with decreasing particle size. Some of the sulfate associated with the aerosols is in the form of 

sulfuric acid. The amount of sulfuric acid formed is dependent on coal type and the temperature history of 

particles in the furnace. The differences among coal types are attributed to differences in the ability of the ash 

to catalyze the oxidation of sulfur dioxide and neutralize the resulting acid. Acid production is highest at a 

furnace temperature of 1,000 oK. In an experimental furnace that produced zinc oxide particles, water vapor 

was shown to be required for the production of sulfuric acid. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 136 

5. POTENTIAL FOR HUMAN EXPOSURE 

The estimated amount of sulfur dioxide emitted in the United States has gone down in recent years (EPA 

1995a). In the early 1970s the estimated total emission of sulfur dioxide in the United States was about 

28 million metric tons. In 1994 the level had declined to about 18 million metric tons, which is approximately 

the same amount that was emitted in 1940. The decreases are in part a result of emission controls and 

a switch to low-sulfur coal by electric utilities. Trends show that in the United States between 1986 and 

1995, the national composite SO2 average decreased 27% and SO2 emissions decreased 18%. Between 1994 

and 1995 SO2 emissions decreased 13%, and mean national concentrations decreased 17% (EPA 1995a). 

When sulfur dioxide emissions were at their maximum, it was estimated that approximately 95% of the sulfur 

emitted to the atmosphere by anthropogenic operations was in the form of sulfur dioxide (Kellogg et al. 

1972). Much of this (about 70%) resulted from the burning of coal. It was estimated that about 93.5% of the 

sulfur dioxide was produced in the Northern Hemisphere, with only about 6.5% produced in the Southern 

Hemisphere. Kellogg et al. (1972) concluded that anthropogenic operations were contributing about half as 

much as nature to the total sulfur burden of the atmosphere. 

Atmospheric emissions of sulfur dioxide by 25 countries in Asia east of Afghanistan and Pakistan were 

estimated based on fuel consumption, sulfur content in fuels, and emission factors for the fuels in each 

emission category (Kato and Akimoto 1992). From 1975 to 1987 the emission of sulfur dioxide in these 

countries increased by a factor of 1.59 (from 18.3x106

 to 29.1x106 tons). The six countries of China, India, 

South Korea, Japan, Thailand, and Taiwan accounted for 92% of the sulfur dioxide released in Asia. 

5.2.2 Water 

The three major sources of sulfur compounds in bodies of water are rocks, fertilizers, and the atmosphere 

(Kellogg et al. 1972). The largest contribution is thought to be from the atmosphere. A correlation between 

sulfate in surface water and sulfate concentrations in precipitation has been observed over a wide range of 

concentrations (EPA 1985). Background sulfate concentrations in North American lakes are estimated at 

20-40 microequivalents/L (μeq/L). In eastern North America where acid deposition occurs, sulfate 

concentrations are 80-100 μeq/L. Surface water closer to sources of emission has even higher 

concentrations. For example, lakes near Sudbury, in Ontario, Canada, have concentrations of about 

400 μeq/L, and lakes east of the Rhine-Rhone industrial region of Germany can have concentrations of 

>l,000 μeqL (EPA 1985). 
SULFUR TRIOXIDE AND SULFURIC ACID 137 

5. POTENTIAL FOR HUMAN EXPOSURE 

According to the TRI, in 1996, releases of sulfuric acid to water from 7 14 large processing facilities totaled 

576 kg (1,271 pounds) (TR196 1998). Table 5-l lists amounts released from these facilities. The TRI data 

should be used with caution because only certain types of facilities are required to report. This is not an 

exhaustive list. 

5.2.3 Soil 

According to the TRI, in 1996, releases of sulfuric acid to the soil from 7 14 large processing facilities totaled 

23,904 kg (52,709 pounds) (TR196 1998). Table 5-l lists amounts released from these facilities. The TRI 

data should be used with caution because only certain types of facilities are required to report. This is not an 

exhaustive list. 

Additional data regarding the release of sulfuric acid to soil were not identified. As indicated, releases to 

water, rocks, fertilizers, and fallout from the atmosphere would be expected to contribute to the release of 

sulfuric acid to soil. 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Factors that affect the dispersion of sulfur compounds and other air pollutants include the temperature and 

efflux velocity of the emissions, stack height, topography and the proximity of other buildings, and 

meteorology. Meteorological conditions that result in temperature inversions can result in the trapping of 

pollutants, which increases concentrations up to several hundred times the concentrations usually found 

(WHO 1979). 

Sulfates, including sulfuric acid, are removed from the air by both dry and wet deposition processes. Wet 

deposition processes including rainout (a process that occurs within the clouds) and washout (removal by 

precipitation below the clouds) contribute to the removal of sulfate from the atmosphere (Kellogg et al. 

1972). In the stratosphere, sulfuric acid aerosols have lifetimes of about 14 and 2.4 days at altitudes of 

15 and 20 km, respectively (Kellogg et al. 1972). At cloud level, the residence time is about 6 days, with 

shorter residence times in surface air. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 138 

5. POTENTIAL FOR HUMAN EXPOSURE 

In a study of rain chemistry in southwestern Pennsylvania in August of 1983, Pierson et al. (1987a) 

concluded that on average about half of the rain sulfate resulted from scavenging of sulfur dioxide, while the 

rest was from scavenging of aerosol sulfate. The site where the study was completed was about 150 km 

downwind of the highest density of sulfur dioxide emissions in the United States. 

Sulfuric acid is soluble in water. In water, sulfuric acid dissociates, and the sulfate anion may combine with 

other cations. In soil, the ions from sulfuric acid can adsorb to soil particles or leach into surface water and 

groundwater. Sulfates can be taken up by plants and be incorporated into the parenchyma of the plant. 

A recent study compares dry acid deposition in Florida at two different sites. Sampling was conducted at 

ground level at one site and above the forest canopy at the other site in order to compare ground level to 

elevated dry acid deposition. The particulate sulfate levels at both sites were similar, therefore indicating that 

under these conditions, the deposition is independent of site and elevation (Kim et al. 1997). 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Sulfuric acid is formed in the atmosphere from sulfur dioxide. Both gaseous and aqueous phase reactions can 

occur, with gas phase reactions accounting for only about 5% of the sulfur dioxide oxidized during the 

summer (Pienaar and Helas 1996). In the process of sulfuric acid formation, sulfur trioxide is formed. After 

sulfur trioxide is formed, it rapidly reacts with water vapor to form sulfuric acid, so that processes that form 

sulfur trioxide in moist atmospheres are equivalent to the formation of sulfuric acid (Pienaar and Helas 

1996). In the gaseous phase, substances that react with sulfur dioxide resulting in the production of sulfuric 

acid include O, HO•, HO2•, and CH2O3•. Substances that result in the oxidation of sulfur dioxide in the 

aqueous phase include ozone and hydrogen peroxide. Metal ions including CI-O4

2-, VO2+, Fe2+ , Fe3+, Mn2+, 

and Ni 2+ could also directly oxidize SO3

2-, or catalyze SO32- oxidation by molecular oxygen. In a study using 

electron spin resonance, spin trapping, and high-performance liquid chromatography, Shi (1994) found that 

reactions of SO3 

2- with NO2-

also generate SO3 

•

 radicals. The major reactions that form sulfuric acid from 

sulfur dioxide require light. Therefore, levels of sulfuric acid in the atmosphere show both seasonal and 

diurnal variations. 
 

SULFUR TRIOXIDE AND SULFURIC ACID 139 

5. POTENTIAL FOR HUMAN EXPOSURE 

The production of sulfuric acid from sulfur dioxide can become limited if the concentrations of oxidants are 

less than the concentrations of sulfur dioxide. Oxidant limitations of the formation of sulfuric acid were 

shown in a study of sulfur dioxide and hydrogen peroxide concentrations over Columbus, Ohio; the study 

authors suggested that similar conditions exist over a large area of the eastern United States (Kleinman and 

Daum 199 1). A deficiency of hydrogen peroxide relative to sulfur dioxide was also shown in a study 

completed at Whiteface Mountain, NY (Dutkiewicz et al. 1995). These results suggest that there would be a 

nonlinear relationship between sulfur dioxide emissions and downwind acid precipitation in the northeastern 

United States where aqueous-phase oxidation by hydrogen peroxide is the principal mechanism for forming 

sulfuric acid. The aqueous oxidation of sulfur dioxide to sulfuric acid in precipitation has been estimated to 

account for 50-80% of the sulfuric acid found in precipitation (Fung et al. 1991). 

Acid aerosols react with gaseous ammonia to form partially neutralized ammonium salts. If ammonia is 

present, sulfuric acid will react to form ammonium sulfate, which is considered neutral for most practical 

purposes (Wyzga and Folinsbee 1995). The intermediate reaction products ammonium bisulfate and 

ammonium hemisulfate, which are fairly stable and may be present in abundance, are acidic. Aerosol 

neutralization is dependent on the rate of sulfur dioxide oxidation to sulfate and on the ambient 

concentrations of ammonia (Lui et al. 1996). Among three sites in Pennsylvania with varying degrees of 

urbanization, H+

was the lowest and ammonia was the highest in the most urbanized area. Concentrations of 

both H+

and sulfate were higher during the daytime, probably a result of daytime conversion of sulfur dioxide 

to sulfate. Diurnal variations in ammonia concentrations were not observed. 

The effect of wind speed on the ammonia neutralization of sulfuric acid was studied under chamber 

conditions (Clark et al. 1995). During exposure to an average sulfate ion concentration of 0.105 mg/m3

, 

about 25% of the breathing-zone acid was neutralized without wind, while 10% was neutralized with a wind 

of 4 or 16 km/hour. 

In air, submicron-sized sulfuric acid aerosol droplets rapidly take up water from the atmosphere. For 

example, the growth of a sulfuric acid droplet (original sulfuric acid concentration of 98% and size of 1 pm) 

was complete in 0.01 second after exposure to an atmosphere of relative humidity 50% at 20°C (Carabine 

and Maddock 1976). 
SULFUR TRIOXIDE AND SULFURIC ACID 140 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3.2.2 Water 

In water, sulfuric acid dissociates. The sulfate anion may associate with other cations including calcium, 

magnesium, and aluminum. Sulfur that is in water may be oxidized to sulfuric acid by sulfur bacteria 

(Thiobacilli) that use sulfur to obtain energy for growth (Takeuchi and Suzuki 1994). Sulfate in water can 

also be reduced. Because sulfur dioxide and sulfate are transformed through similar pathways in water, the 

effect of sulfur on aquatic systems is not dependent on the chemical or physical form of deposition (wet or 

dry) (EPA 1985). 

In the surface layer of the ocean the sulfate anion may be formed from dissolved sulfur dioxide, which is 

transformed to sulfurous acid (H,SO,) and subsequently oxidized. Because of the relative lack of salt in 

freshwater, the oxidation of sulfur dioxide to sulfate is less likely to occur in freshwater. In the depths of the 

ocean, sulfate is reduced to sulfur dioxide, sulfur, and hydrogen sulfide by bacteria (Kellogg et al. 1972). 

5.3.2.3 Sediment and Soil 

The ions (sulfate, hydrogen) can adsorb to soil particles or be converted to gases (EPA 1985). Anaerobic 

bacteria in sediments and soil can reduce sulfate to sulfur and hydrogen sulfide (Kellogg et al. 1972). 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to sulfuric acid depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. In reviewing data on 

sulfuric acid levels monitored or estimated in the environment, it should also be noted that the amount of 

chemical identified analytically is not necessarily equivalent to the amount that is bioavailable. 

5.4.1 Air 

Air monitoring results are often reported in terms of hydrogen ion or sulfate concentrations, or sulfuric acid 

equivalents, rather than sulfuric acid concentrations. The local concentration of acidity is dependent on the 

balance between acids and bases and is difficult to estimate using meteorological dispersion models (Lipfert 

et al. 1989). Peak sulfuric acid concentrations that have been reported include 240 μg / m3

 in the Los Angeles 
SULFUR TRlOXlDE AND SULFURIC ACID 141 

5. POTENTIAL FOR HUMAN EXPOSURE 

area in 1950, an hourly average of 678 μg /rn3 in London during an episode in 1962, and an hourly average of 

50 μg / m3

 in Ontario during the summer of 1986 (Amdur 1989b). 

The highest concentrations of aerosol acidity are found in the eastern United States and southern Ontario, 

Canada. This results because of the major power plants in the Ohio River Valley region and the ability of the 

acid precursors to be transported. (Spengler et al. 1990). Usually, acid aerosol concentrations are higher 

during the day than at night and higher during the summer. Acid concentrations may be higher in rural areas 

because of higher ammonia emissions that result in greater neutralization of the acid. Arithmetic annual 

average sulfate concentrations measured from 1964 to 1968 were 13.5 μg/m3

 for urban sites in the eastern 

United States and 6.4 μg/m3

 for urban sites in the western United States (Altshuller 1973). At eastern sites, 

7% of the annual averages were above 20 μg/m3g while no annual averages were above 20 μg/m3 at western 

sites. The minimum detectable concentration of sulfate during this study period was 0.6 μg/m3

. The average 

ratio of sulfur dioxide to sulfate was 4.7: 1, witb a ratio of 4.9: 1 at eastern urban sites, and a ratio of 3.4: 1 for 

western urban sites (Altshuller 1973). A review of studies of the measurement of sulfuric acid or hydrogen 

ion (as sulfuric acid) in the United States from 1974 to 1986 indicated that the concentrations were generally 

below 5 μg / m3

 (Lioy and Waldman 1989). The highest concentration reported in these studies was a 1 -hour 

average of 41 μg /m3

 in 1984 at a site in St. Louis, MO. Lioy and Waldman (1989) cautioned that periods of 

high acid do not necessarily occur at the same time as periods of high atmospheric sulfate. For example, in a 

study of hydrogen ion and sulfuric acid, the median level of sulfuric acid was about 15% of the median level 

of hydrogen ion (Lipfert et al. 1989). 

Outdoor, indoor, and personal sulfate, hydrogen ion, and ammonia levels were measured in State College, PA 

(Suh et al. 1993). The samples were collected over 12-hour daytime periods. The indoor samples were taken 

from 47 homes; 21 had air conditioning. As indicated in Table 5-2, the outdoor concentrations of sulfate and 

hydrogen ion were greater than the indoor concentrations, while the personal values were close to the results 

from indoor measurements. Ammonia levels were higher inside than outside, and personal ammonia 

monitors indicated even higher levels of exposure. 

Daily distributions of acid aerosol concentrations were examined in Kingston, TN, and St. Louis, MO, in 

1986, and in Steubenville, OH, and Portage, WI, in 1987 (Spengler et al. 1989). Elevated acid aerosol 

concentrations occurred more frequently in the summer months. Approximately 50% of the days, acid 

aerosol concentrations expressed as equivalents of sulfuric acid in μg/m3

 were about 1,0.2,0.6, and 0.1 in 

 

SULFUR TRIOXIDE AND SULFURIC ACID 143 

5. POTENTIAL FOR HUMAN EXPOSURE 

Kingston, St. Louis, Steubenville, and Portage, respectively. The maximum concentrations in μg/ m3 were 

about 10, 3.5, 10.5, and 2.5 in Kingston, St. Louis, Steubenville, and Portage, respectively. 

Measurements of sulfuric acid aerosols in the stratosphere over Laramie, WY, indicate increases of about 

5±52% per year from 1979 to 1990 (Hofmann 1990). It is not yet known whether this increase is a result of 

natural or anthropogenic sources. Above the Atlantic Ocean, sulfate concentrations of 2-5 μg / m3

 have been 

reported (Kellogg et al. 1972). 

A study was conducted among 24 United States communities to study air pollution patterns. The 

communities were placed into four different categories based on location. A strong correlation between 

particle mass and sulfate concentrations, and sulfate and hydrogen ion concentrations was found in Ohio, 

Pennsylvania, Virginia, Tennessee, and Kentucky. Concentrations in these areas ranged between 

85-126 nmol/ m3

 in the summer, the highest being in Ohio, Pennsylvania, and Kentucky. Due to the 

meteorological conditions, acidic pollution is highest in the summer months in these areas. Sulfur dioxide is 

converted to acid sulfates without the presence of ammonia during this time (Spengler et al. 1996). 

Acidic acid aerosols were measured in Erfurt in east Germany and Sokolov in the Czech Republic during 

December 1990 until June 1992 (Cyrys et al. 1995). Concentrations of sulfur dioxide, sulfate, and H+

 (as 

H2SO4) in μg/ m3

 averaged 84.6,9.6, and 0.3, respectively, in Erfurt, and 62.1, 8.8, and 0.4, respectively, in 

Sokolov. These results and other studies reviewed by the study authors indicate that acidity in Europe is 

generally lower than in North America. The investigators noted that in eastern Europe sulfur dioxide and 

ammonia are emitted at the same height so that acidic sulfate will be neutralized. In the European cities, days 

with noticeable acidity were more prevalent during the winter than during the summer. 

Measurements of acid aerosols at 8 sites in the Netherlands from October 1987 to April 1990 showed 

concentrations occasionally in excess of 1 μg / m3

, but never exceeding 10 μg/m3 (Hoek et al. 1996). 

The size range of acid droplets collected in the environment is large. Acid droplets can be found on all stages 

of a cascade impactor (0.5-23 μm). The larger droplets often appear to be associated with solid particles 

(Waller 1963). The largest number of droplets is usually collected at relative humidities of about 90%. 
SULFUR TRIOXIDE AND SULFURIC ACID 144 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.4.2 Water 

The levels of sulfate in the water are highly dependent on nearby emissions of sulfur containing compounds 

which can be converted to sulfuric acid. Background sulfate concentrations in North American lakes are 

estimated at 20-40 μeq/L (EPA 1985). In eastern North America where acid deposition occurs, sulfate 

concentrations are 80-100 μeq/L. Surface water closer to sources of emission has even higher 

concentrations. For example, lakes near Sudbury in Ontario, Canada, have concentrations of about 

400 μeq/L. In Europe, lakes east of the Rhine-Rhone industriaP region of Germany can have concentrations 

of >1 ,000 μeqL (EPA 1985). 

5.4.3 Sediment and Soil 

Data regarding the levels of sulfuric acid in sediment and soil were not identified. 

5.4.4 Other Environmental Media 

Data regarding the levels of sulfuric acid in other environmental media were not identified. 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Occupational exposures to sulfuric acid mists (particle size measurements not available) in pickling, 

electroplating, and other acid treatment of metals are frequently above 0.5 mg/ m3

, with lower concentrations 

generally found in the production of phosphate fertilizer and in the manufacture of lead-acid batteries (IARC 

1992). Sulfuric acid exposure also occurs when it is manufactured and when isopropanol, synthetic ethanol, 

and detergents are produced. Other industries where there is potential exposure to sulfuric acid include 

building and construction, electric and electronic equipment, food products, health services, instruments, 

leather, oil and gas extraction, petroleum and coal products, photography shops, printing and publishing, 

paper and allied products, rubber and plastic products, steel, and textile products (IARC 1992). 

The National Occupational Exposure Survey (NOES), conducted by NIOSH from 1981 to 1983, estimated 

that 56,103 and 775,348 U.S. workers may be exposed to sulfur trioxide and sulfuric acid, respectively 

(NOES 1990). The NOES database does not contain information regarding the frequency, concentration, or 
SULFUR TRIOXIDE AND SULFURIC ACID 145 

5. POTENTIAL FOR HUMAN EXPOSURE 

duration of exposure; the survey provides only estimates of workers potentially exposed to chemicals in the 

workplace, and is based on sample populations only. 

At five lead-acid battery plants in the United States, the average sulfuric acid concentration was 0.18 mg/ m3 

with a range of nondetectable (detection limit not stated) to 1.7 mg/ m3 (Jones and Gamble 1984). The 

MMAD of the sulfuric acid mist was about 5 pm. Low levels of stibine, amine, and arsenic in particulate 

form were also detected. The average lead concentration was 0.72 mg/ m3

. Workers at two battery 

manufacturing plants in Egypt were exposed to sulfuric acid vapor at concentrations of 12.55-35.02 mg/ m3 

(El-Sadik et al. 1972). The particle sizes were not provided. 

A study of kerosene heaters indicates that they can be a source of acidic aerosols in indoor air. The emission 

rate for acid aerosols calculated as sulfuric acid ranged from 0.6 to 63.1 μg /g of fuel (Leaderer et al. 1990). 

The particles produced by the 4 heaters used in this study were less than 2.5 ym in diameter. The 

investigators noted that the heater that produced the highest levels of acid aerosols “showed evidence of 

considerable use and may have been maltuned.” 

The following three accidental exposure cases examine the effects of a single exposure to H,SO,. A worker 

was exposed to fumes caused by the addition of water to oleum, and he was hospitalized and treated for bums 

and respiratory problems. Six months later, the worker was readmitted for bronchiectasis and diffuse 

intersitital fibrosis. This case supports the idea that one single exposure to sulfuric acid can cause 

progressive lung damage (Griffiths 1996). A man suffered chemical pneumonitis, infection, and a lung 

abscess when a 95% sulfuric acid mixture was released from a drain. A later chest X-ray revealed no 

permanent damage to the lungs (Griffiths 1996). Nine people suffered symptoms ranging from chest pain to 

nasal irritation following a 2 hour exposure to sulfur trioxide. All of the patients were treated and released 

within six hours (Griffiths 1996). 

Measurements of personal exposure to hydrogen ion and sulfate were completed for 24 days during the 

summer of 1988 in Boston, MA, and were compared to nearby outdoor stationary site sampling data (Brauer 

et al. 1989). The total number of persons involved in this study was not stated, but there were a total of 

3 1 indoor 24-hour sulfate samples and a total of 13 indoor 24-hour hydrogen ion samples. Personal 

measurements of sulfate were similar to those at the outdoor site. Personal measurements of hydrogen ion 

were lower than the outdoor samples as a result of neutralization of acidic particles and of the incomplete 

penetration into indoor locations. Similar results were observed for hydrogen ion and sulfate when personal 
 

SULFUR TRIOXIDE AND SULFURIC ACID 146 

5. POTENTIAL FOR HUMAN EXPOSURE 

monitors were used by 24 children living in Uniontown, PA (Suh et al. 1992). Air conditioning was found to 

reduce indoor hydrogen ion concentrations, a result of increased ammonia levels resulting from reduced air 

exchange rates. 

Exposure models for sulfate and hydrogen ion have been developed to provide better predictions of exposure 

relative to outdoor air concentrations of sulfate and hydrogen ion (Suh et al. 1993). These models were 

developed and validated using air monitoring data and data from children living in rural and semi-rural 

environments (Uniontown and State College, PA). Because the models were developed in specific 

environments, the authors cautioned that the models were only applicable to those environments, and that 

before being used in an urban setting, the model should be validated with urban data. When the sulfate model 

was compared to actual personal exposure data, it was found that sulfate exposure could be adequately 

predicted by the outdoor concentration, activity of the person, and use of air conditioning. This model 

accounted for about 9 1% of the variability in personal sulfate exposure. The hydrogen ion model included a 

neutralization term and was better at predicting personal exposure when indoor air concentrations of 

hydrogen ion and personal ammonia levels were also included. With all the information included in the 

model, the model accounted for 63% of the variability in personal hydrogen ion exposure. When outdoor 

concentrations and activity data were used in the model, with the assumption that indoor air concentrations 

were zero, the model explained only 47% of the variability in measured personal hydrogen ion exposure. 

Because of the importance of personal ammonia levels on predicting hydrogen ion exposure, and because of 

similar difficulties in measuring personal ammonia and hydrogen ion concentrations, the study authors 

suggest that direct measurement of personal hydrogen ion exposure may be the only method to accurately 

determine personal hydrogen ion exposure. 

The RASP model was developed to study the release of sulfur trioxide vapors from a sulfur trioxide pool or 

oleum. The model is dependent on release rate, minimum pool depth, wind speed, maximum pool radius, 

water film thickness, duration of spill, and duration of release (Griffiths 1996). 

The TOEM model calculates wind drive release rates from sulfur trioxide or oleum spills. The model is 

dependent on wind speed, quantity spilt, release rate, maximum pool radius, spill duration, and total time of 

release (Griffiths 1996). 

The relationship between hydrogen ion, sulfate, ozone, and population density has been examined using 

measurements from across the United States and Canada (Ozkaynak et al. 1996). Significant site-specific 
SULFUR TRIOXIDE AND SULFURIC ACID 147 

5. POTENTIAL FOR HUMAN EXPOSURE 

and regional relationships between hydrogen ion and sulfate and population density were observed. The 

relationships were stronger in the eastern United States compared to the west or midwest, where local 

pollution, agricultural activities, and industrial sources of ammonia had a greater impact on the lower 

hydrogen ion levels. The relationships were also stronger during the summer compared to the winter. The 

study authors concluded that reasonable estimates of hydrogen ion levels could be made using sulfate data 

and data on local population density. 

Exposure to sulfuric acid and oleum can also occur through accidental releases. Among states reporting 

accidental events during the time period 1990-1996 (5 states 1990-1991, 9 states 1992-1994, 14 states 

1995-1996) 905 events occurred that involved only sulfuric acid and oleum (3 oleum releases), and 

173 events occurred that involved mixtures or multi-chemical releases that included sulfuric acid or oleum 

(HSEES 1997). The 14 states that are presently participating are Alabama, Colorado, Iowa, Minnesota, 

Missouri, Mississippi, New Hampshire, New York, North Carolina, Oregon, Rhode Island, Texas, 

Washington, and Wisconsin. The majority of the releases occurred at a fixed facility rather than a result of a 

transportation accident. For events with sulfuric acid or oleum alone, 78.7% of the events occurred at fixed 

facilities, while 81.5% of the events with mixtures including sulfuric acid or oleum occurred at fixed facilities. 

A spill was the most frequent type of release (85.1% sulfuric acid or oleum only; 63.6% mixture including 

sulfuric acid or oleum). Among the events in which only sulfuric acid and oleum were released, 53 required 

evacuation (information not available for 39 events), there was 1 death, and a total of 203 victims. Chemical 

bums (38.5%), respiratory irritation (21.6%), and eye irritation (15.4%) were the most frequently reported 

effects following these releases. Among the mixture or multi-chemical releases that included sulfuric acid or 

oleum, 40 required evacuation (information not available for 3 events), there were 3 deaths, and a total of 

322 victims. The most frequently reported effects following the release of mixtures were respiratory irritation 

(56.5%), eye irritation (17.8%), and nausea and vomiting (5.1%). 

In Richmond, CA, 1993, a 12,000 gallon rail tanker leaked oleum into the environment. The release formed a 

330 m high by 13 km wide cloud in a highly populated area, and between 2,000 and 22,000 people were 

treated for effects (Griffiths 1996). 

DuPont conducted a spill test in 1992 that tested water chemicals, dry chemicals, and commercial foams on 

small oleum spills in Nevada. The test found which products treated the spill the best and in the least time. 

The foam products treated the spill in half the time of the water and dry chemicals. Foam products also kept 

the temperature of acid in the pool down (Griffiths 1996). 
SULFUR TRIOXIDE AND SULFURIC ACID 148 

5. POTENTIAL FOR HUMAN EXPOSURE 

The general population can also be exposed to sulfuric acid through the use of lead-acid batteries (including 

car batteries) and cleaners (especially toilet bowl cleaners that contain sodium bisulfate, which produces 

sulfuric acid when it contacts water). People can also be exposed to sulfuric acid when they cut onions. 

Cutting onions releases the compound propanethiol S-oxide which reacts with water in the eyes to form 

sulfuric acid, which causes the eyes to water (Hillman 1989). 

5.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans and briefly considers 

potential preconception exposure to germ cells. Differences from adults in susceptibility to hazardous 

substances are discussed in 2.6 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, and 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 humans 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; they put things in their mouths; they may 

ingest inappropriate things such as dirt or paint chips; they spend more time outdoors. Children also are 

closer to the ground, and they do not have the judgement of adults in avoiding hazards (NRC 1993). 

Sulfur trioxide gas is an intermediate used in the manufacture of chemicals such as sulfuric acid. With the 

exception of large accidental releases from chemical plants, exposure of children to sulfur trioxide is unlikely. 

Because small amounts of sulfur trioxide rapidly combine with moisture in air to produce sulfuric acid, 

children living near industries that utilize sulfur trioxide may be exposed to increased levels of sulfuric acid in 

air. Sulfuric acid is also present in air because it forms upon reaction with sulfur dioxide and water. 

Therefore, increased exposure to sulfuric acid aerosols in air is expected for children living in areas in which 

large amounts of sulfur dioxide are released by industries, such as electrical, metal processing, and paper 

manufacturing. Decreased respiratory performance in asthmatics and reduced mucocilliary clearance in 

healthy individuals are the primary effects associated with exposure to sulfuric acid aerosols. Concentrations 

as low as 0.07 mg/ m3

 (MMAD 0.7 1 μm) have produced transient reductions in the pulmonary function of 

exercising asthmatic adolescents in chamber studies (Hanley et al. 1992). 
SULFUR TRIOXIDE AND SULFURIC ACID 149 

5. POTENTIAL FOR HUMAN EXPOSURE 

Sulfuric acid is used in household products, such as drain and toilet bowl cleaners and car batteries. Children 

are most likely to be exposed to high concentrations of sulfuric acid through ingestion, eye contact, or skin 

contact. There are no exposure pathways that are unique to children. However, young children are more 

prone to accidents involving ingestion or eye and skin contact with cleaners containing sulfuric acid. Eye and 

skin exposure in teenagers is possible through the use of sulfuric acid in chemistry lab courses in high 

schools. Occupational exposure to sulfuric acid is also possible for teenagers who have jobs which require 

them to use acid cleaners. Teenagers who have jobs in automotive repair could also be exposed to sulfuric 

acid from car batteries. Depending on the concentration of the sulfuric acid solution, direct contact with 

tissues can result in severe chemical burns and death. There is no clear evidence available which indicates 

the minimum concentration that will cause chemical burns in tissues. 

Significant exposures of children are not anticipated through diet, structural building materials, or the 

clothing, skin, or breath of occupationally exposed parents. 

There are no studies in which the levels of sulfuric acid were measured in the blood of children, in maternal 

reproductive organs during pregnancy, or in breast milk. Because sulfuric acid is a direct acting toxicant, 

which exerts its effect at the point of contact, significant absorption and distribution throughout the body is 

unlikely. Upon inhalation exposure, the weight-adjusted intake of sulfuric acid in the respiratory system is 

expected to be greater in children because they bream more air per kilogram of body weight than adults. I n 

addition, a model has indicated that total deposition of sulfuric acid in the respiratory tract is greater in 

children than adults (Martonen and Zhang 1993). Numerous factors determine pulmonary exposure to 

sulfuric acid aerosols including the aerosol size, relative humidity, and physiological breathing factors, such 

as rate or percentage of time breathing through the nose or mouth. Additional research involving these 

factors is required before the weight adjusted intake of sulfuric acid can be determined. 

In vitro experiments have demonstrated that sulfuric acid can induce chromosomal aberrations (Cipollaro et 

al. 1986; Morita et al. 1989; Zura and Grant 1981). However, it is unlikely that sulfuric acid would reach 

germ cells and there should be no concern regarding exposure of parental germ cells. Exposure of fetuses is 

also unlikely, and developmental studies have demonstrated a lack of adverse effects (Murray et al. 1979). 

Refer to section 2.6 for a more detailed discussion about genotoxicity and developmental effects. 
SULFUR TRIOXIDE AND SULFURIC ACID 150 

5. POTENTIAL FOR HUMAN EXPOSURE 

Pharmacokinetics studies which examine whether sulfuric acid is stored in maternal tissues are not available. 

Because absorption of significant amounts of sulfuric acid is not expected, storage in maternal tissue and 

subsequent release during pregnancy or lactation is very unlikely. 

Reduction of sulfuric acid exposure in children primarily involves preventing direct contact with tissues. 

Following the use of sulfuric acid cleaners, surfaces and surrounding areas should be thoroughly rinsed. 

Exposures in small children can be avoided by storing sulfuric acid cleaners in original, labeled, intact 

containers within locked cabinets. If teenagers must use sulfuric acid or sulfuric acid-based cleaners, 

exposure to the eyes and skin can be prevented with the use of eye goggles and chemical resistant gloves. Eye 

protection is also recommended for teenagers working with car batteries. If sulfuric acid contacts the skin or 

eyes, the affected area should be immediately flushed with water. A poison control center must be 

immediately contacted in cases where the acid is ingested. Inhalation exposure to sulfuric acid pollution can 

be reduced in children by limiting the time spent outdoors, especially during periods of high pollution. 

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

In addition to persons working in industries where sulfuric acid is used, persons living in industrialized areas, 

especially those living near electric power plants, may be exposed to higher levels of sulfuric acid. Persons 

who frequently work with car batteries and other lead-acid batteries may also be exposed to higher levels of 

sulfuric acid. Toilet bowl cleaners often contain sodium bisulfate which produces sulfuric acid when it 

contacts water. Therefore, misuse of these products may result in higher-than-normal exposure to sulfuric 

acid. 

Sulfuric acid levels are generally lower indoors than outdoors. Therefore, persons who spend most of their 

time outside may be exposed to higher levels. This may be especially true for persons who engage in 

considerable outdoor physical activity. Physical activity not only increases breathing rate but increases the 

amount of oral breathing which would increase the amount of sulfuric acid aerosols reaching the lungs. 

Although increased exposure is expected in persons who spend a great deal of time outside, it does not 

necessarily mean that those individuals will be exposed to harmful levels of sulfuric acid mists. Unacceptable 

exposure levels are potentially possible in persons who are outdoors for extended periods during episodes of 

high pollution. 
SULFUR TRIOXIDE AND SULFURIC ACID 151 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.8 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 sulfur trioxide/sulfuric acid is available. Where adequate information is 

not available, ATSDR, in conjunction with the 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 sulfur trioxide and sulfuric acid. 

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. 

5.8.1 identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of sulfur trioxide, sulfuric 

acid, and fuming sulfuric acid are generally well characterized (HSDB 1998; NIOSH 1994b). Further 

research on the aerosol size of sulfuric acid at occupational settings and in the environment is needed. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency Planning 

and Community Right-to-Know Act of 1986,42 U.S.C. Section 11023, industries are required to submit 

substance release and off-site transfer information to the EPA. The Toxics Release Inventory (TRI), which 

contains this information for 1996, became available in May of 1998. This database is updated yearly and 

should provide a list of industrial production facilities and emissions. However, the TRI data is not 

exhaustive because certain types of facilities are not required to report releases. Additional information 

would be useful about quantities and frequencies of releases from exempt facilities, especially those that may 

release sulfuric acid or sulfur trioxide levels resulting in 5- and 10-minute peak exposures to high 

concentrations. 
SULFUR TRIOXIDE AND SULFURIC ACID 152 

5. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. Once sulfuric acid enters the environment, the sulfur enters the natural sulfur cycle 

which is well defined (Kellogg et al. 1972). Additional research regarding the environmental fate of sulfuric 

acid does not appear to be necessary at this time. 

Bioavailability from Environmental Media. As part of the natural sulfur cycle, sulfur compounds can 

be taken up by plants. The adsorption of sulfuric acid on small particles increases the toxicity of sulfuric acid 

(Amdur 1989b). This effect is thought to result, at least in part, from a change in the deposition of sulfuric 

acid in the respiratory tract, not an increase in bioavaila0ility. Because sulfuric acid is a direct-acting 

toxicant, rather than a substance that causes toxic effects after being absorbed into the blood stream, 

bioavailability from different media is not an important issue for sulfur trioxide and sulfuric acid. 

Food Chain Bioaccumulation. Sulfur is an important constituent of normal biomolecules. Food chain 

bioaccumulation is not an important issue for either sulfur trioxide or sulfuric acid. 

Exposure Levels in Environmental Media. Air is the environmental media most relevant to human 

exposure to sulfuric acid. Air monitoring results are often reported in terms of hydrogen ion or sulfate 

concentrations, or sulfuric acid equivalents, rather than sulfuric acid concentrations. Additional data 

concerning the aerosol size of sulfuric acid in air is needed. 

Reliable monitoring data for the levels of sulfuric acid in contaminated media at hazardous waste sites are 

needed so that the information obtained on levels of sulfuric acid in the environment can be used to assess 

the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Models for personal sulfate and hydrogen ion exposure have been 

developed (Suh et al. 1993). Improvement in personal ammonia monitoring would improve the ability to 

predict personal hydrogen ion exposure. This information is necessary for assessing the need to conduct 

health studies on these populations. 

There is no specific biomarker for human exposure to sulfuric acid. The only potential biomarker may be 

measurement of pH in saliva. Because saliva has some buffering capacity, decreases in saliva pH would only 

be apparent at relatively high-level sulfuric acid exposures, and decreases in pH can occur following exposure 

to other acids. 
 

 

SULFUR TRIOXIDE AND SULFURIC ACID 153 

5. POTENTIAL FOR HUMAN EXPOSURE 

This information is necessary for assessing the need to conduct health studies on these publications. 

Exposures of Children. Children are exposed to sulfuric acid through ingestion or direct contact with 

specific cleaners or battery acid. Inhalation of sulfuric acid air pollution is another source of exposure. There 

are no exposure pathways which are unique to children and studies to address this issue are not required. 

Exposure through any route is not likely to result in significant absorption and distribution. Therefore, 

studies regarding body burden in children are not required. Reduction of exposure involves preventing direct 

contact of solutions with tissues or limiting time spent outdoors during periods of high air pollution to 

decrease the quantity inhaled. Research in exposure reduction is not required. Deposition and distribution of 

sulfuric acid aerosols within the respiratory tract are Iikely to differ between adults and children due to 

differences in respiratory performance. Therefore, studies in the pulmonary weight-adjusted intake of sulfuric 

acid and distribution within the respiratory system in children would be useful. 

Exposure Registries. No exposure registries for sulfuric acid were located. This substance is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The substance 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 

substance. 

5.8.2 Ongoing Studies 

The production of sulfuric acid by various reactions in the upper troposphere and lower stratosphere is being 

studied further by Somorjai and Johnston (FEDRIP 1996). Tabatabai is studying wet deposition, including 

sulfuric acid deposition in central Iowa (FEDRIP 1996). Xiong and coworkers at the New York University 

Medical Center in Tuxedo, New York, are studying the effect of organic films on the reactivity and 

hygroscopicity of sulfuric acid aerosols (Xiong et al. 1997). 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID 155 

6. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or 

measuring, and/or monitoring sulfur trioxide and sulfuric acid, its metabolites, and other biomarkers of 

exposure and effect to sulfur trioxide and sulfuric acid. 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 

6.1 BIOLOGICAL SAMPLES 

No methods for determining sulfur trioxide or sulfuric acid in biological materials were located. Studies in 

which plasma sulfate was measured after exposure to sulfuric acid were not identified. Sulfate is a normal 

constituent in the blood found at concentrations of 0.8-l .2 mg/dL in humans (Hensyl 1990). Increases in 

blood sulfate would result in increased sulfate excretion in the urine. Therefore, the measurement of plasma 

sulfate would not be a very useful indicator of sulfuric acid exposure. 

A decrease in saliva pH has been observed in persons occupationally exposed to sulfuric acid (El-Sadik et al. 

1972). However, a decrease in saliva pH is not specific to sulfuric acid exposure. 

6.2 ENVIRONMENTAL SAMPLES 

Methods for measuring sulfur trioxide and sulfuric acid in air, and sulfate in water, are summarized in 

Table 6-1. Sulfuric acid in air is usually measured as H2SO4 or as titratable hydrogen ion (Lioy and Waldman 

1989). Measurements are usually made by the collection of aerosols on filters, with subsequent analysis of 

the concentration of sulfate and other ions, or by continuous analysis. A cascade impactor, which has stages 

to separate aerosols of different sizes, is often used to measure aerosol size. 
SULFUR TRIOXIDE AND SULFURIC ACID 158 

6. ANALYTICAL METHODS 

Because of the reactive nature of sulfuric acid, air sampling poses some unique challenges. Difficulties 

encountered in collecting samples for acid measurements include reversible or irreversible sorption losses 

onto filters, and equilibrium-driven loss or gain of species as a result of nonsteady-state conditions in the 

atmosphere of the time period of measurement (Lioy and Waldman 1989). To help avoid sorption losses, 

treated quartz and teflon filters are recommended rather than glass-fiber filters, which contain a larger number 

of free basic sites. The loss of strong acid by reactions between co-collected basic and acidic particles can be 

eliminated by using a coarse particle separator (e.g., a cyclone or impactor inlet) or by sampling for shorter 

time periods. To prevent neutralization, a denuder is used to scavenge neutralizing species. 

Following collection of the sample, acid aerosols are most often quantitated by extracting the aqueous 

particles from the filter and then measuring levels of ions in the extract by methods such as ion 

chromatography, pH measurement, or titration (Lipfert et al. 1989). NIOSH recommends ion 

chromatography (Method 7903) for the determination of sulfuric acid in ambient air (NIOSH 1994a). 

Method 7903 is a method for the determination of inorganic acids. This method measures the total 

concentration of six airborne anions. Particulate salts of all of the acids will give a positive interference 

(NIOSH 1994a). The working range is approximately 0.01-5 mg/ m3

 for a 50-L air sample (NIOSH 1994a). 

Most of the acid aerosol measurements are completed on a 12- or 24-hour basis. With 24-hour sampling, 

peaks may be underestimated by as much as 50%, and Lipfert et al. (1989) recommend that ambient 

sampling be conducted for the shortest practical averaging times on an every-day basis. 

Sulfuric acid in air may also be determined using a continuous flame photometric detector with a diffusion 

denuder tube for sulfur dioxide removal before the detector (Appel et al. 1987). The time resolution for this 

method is about 6-8 minutes (Lioy and Waldman 1989). The sensitivity of this method is enhanced if sulfur 

hexafluoride-doped hydrogen gas is used (Lioy and Waldman 1989). The advantages of using flame 

photometric detector analysis include low maintenance, high sensitivity, fast response, and no interference 

from nonsulfur species. However, this method is unable to discriminate between sulfur species. 

A method has been developed for measuring personal exposure to sulfate, strong acidity (strong H+

), as well 

as other gases including sulfur dioxide and ammonia (Brauer et al. 1989; Koutrakis et al. 1988, 1989). In 

this method, air is collected by a pump at a rate of 4 L/minute and passes through a borosilicate glass 

impactor that collects coarse particles, through two glass denuders that collect the gases, and through a Teflon 


SULFUR TRIOXIDE AND SULFURIC ACID 159 

6. ANALYTICAL METHODS 

filter pack that collects the fine aerosols. The filters are then analyzed for ions using ion chromatography. 

The personal monitors can be worn in a backpack with a total weight of about 5 pounds (Suh et al. 1992). 

In water, sulfate can be measured by calorimetry anion chromatography (EPA 1993). Sulfur trioxide is not 

found in water because it is hydrated to sulfuric acid in water. Calorimetric analyzers are simple and highly 

sensitive. Calorimetric analyzers measure a solutions optical absorbance spectrophotometrically; the 

absorbance is proportional to the concentration of the colored species. However, color intensity is sensitive 

to temperature, pH, development time, purity of reagents, and age of solutions. Specificity may improve with 

development time but does not allow a fast response. EPA (1993) recommends that for the ion 

chromatography method, the samples be stored at 4°C for a maximum of 28 days before analysis. 

6.3 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 sulfur trioxide and sulfuric acid is available. Where adequate information 

is not available, ATSDR, in conjunction with the 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 sulfur trioxide and sulfuric acid. 

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. 

6.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Biomarkers that show a 

concentration-related response have not been developed for exposure to sulfuric acid. The pH of saliva is 

decreased in persons occupationally exposed to sulfuric acid (El-Sadik et al. 1972). Further studies to 

examine the relationship between air concentrations of sulfuric acid and saliva pH are not needed because 

such saliva tests are not specific for sulfuric acid. 
SULFUR TRIOXIDE AND SULFURIC ACID 160 

6. ANALYTICAL METHODS 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods are available for measuring sulfur trioxide and sulfuric acid in air (Appel et al. 1987; 

Knapp et al. 1987; NIOSH 1977, 1979, 1994a; Simon and Dasgupta 1995) and sulfuric acid in water (EPA 

1993). The development of additional methods to distinguish between sulfuric acid in air and ammonium 

bisulfate (sulfuric acid partially neutralized by ammonia) are needed (Lioy and Waldman 1989). 

6.3.2 Ongoing Studies 

Dr. Beverly S. Cohen’s group at New York University Medical Center is developing a method to measure 

ambient acidic particles with a diameter less than 0.05 μm (Cohen 1997). 
 

SULFUR TRIOXIDE AND SULFURIC ACID 161 

7. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding sulfur trioxide and sulfuric acid in 

air, water, and other media are summarized in Table 7- 1. 

The DHHS (1994) and EPA have not classifed sulfur trioxide or sulfuric acid for carcinogenic effects. 

IARC considers occupational exposure to strong inorganic mists containing sulfuric acid to be carcinogenic 

to humans (Group 1) (IARC 1992). ACGIH has classified sulfuric acid as a suspected human carcinogen 

(Group A2) (ACGIH 1998). 

Sulfuric acid is on the list of chemicals in “Toxic Chemicals Subject to Section 3 13 of the Emergency 

Planning and Community Right-to-Know Act”’ (EPA 1998f). 

The occupational permissible exposure limit (PEL) for sulfuric acid is 1 mg/ m3

 (OSHA 1998). The NIOSH 

recommended exposure limit (REL) is also 1 mg/m3

 (NIOSH 1997). ACGIH recommends a threshold limit 

value time-weighted average (TLV-TWA) of 1 mg/m3

 and a short-term exposure limit (STEL) of 3 mg/m3 

(ACGIH 1998). 

No MRLs have been derived for sulfur trioxide or sulfuric acid. EPA has not derived an oral reference dose 

(RfD) or an inhalation reference concentration (RfC) for sulfur trioxide or sulfuric acid. 



__________________________ 

SULFUR TRIOXIDE AND SULFURIC ACID 165 

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SULFUR TRIOXIDE AND SULFURIC ACID 187 

9. GLOSSARY 

Acute Exposure-Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological
 

Profiles.
 

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 a 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.
 

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.
 

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 caucer.
 

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.
 

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.
 

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 occurred. The terms, as used here, include malformations and variations, altered growth, and in utero
 

death.
 

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.
 

Immediately Dangerous to Life or Health (IDLH)-The maximum environmental concentration of a
 

contaminant from which one could escape within 30 min without any escape-impairing symptoms or
 

irreversible health effects.
 

Intermediate Exposure-Exposure to a chemical for a duration of 15-364 days, as specified in the
 

Toxicological Profiles.
 
 

SULFUR TRIOXIDE AND SULFURIC ACID 188 

9. GLOSSARY 

Immunologic Toxicity-The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

In Vitro-Isolated from the living organism and artificially maintained, as in a test tube. 

In Viva-Occurring within the living organism. 

Lethal Concentrationno(10) (LCLO)-The lowest concentration of a chemical in air which has been reported to 

have caused death in humans or animals I 

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(10) (LDLO)-The lowest dose of a chemical introduced by a route other than inhalation that is 

expected to have caused death in humans or animals. 

Lethal Dose(50) ( LD50)-The dose of a chemical which 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 dose 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. 

Malformations-Permanent structural changes that may adversely affect survival, development, or function. 

Minimal Risk Level-An estimate of daily human exposure to a dose of a chemical that is likely to be 

without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. 

Mutagen-A substance that causes mutations. A mutation is a change in the genetic material in a body cell. 

Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity-The occurrence of adverse effects on the nervous system following exposure to chemical. 

No-Observed-Adverse-Effect Level (NOAEL)-The dose of 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. 

Permissible Exposure Limit (PEL)-An allowable exposure level in workplace air averaged over an S-hour 

shift. 
SULFUR TRIOXIDE AND SULFURIC ACID 189 

9. GLOSSARY 

q1 *-The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The ql* 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). 

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 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 

CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount 

established by regulation either under CERCLA or under Sect. 3 11 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 t&e 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. 

Short-Term Exposure Limit (STEL)-The maximum concentration to which workers can be exposed for 

up to 15 min continually. No more than four excursions are allowed per day, and there must be at least 60 

min between exposure periods. The daily TLV-TWA may not be exceeded. 

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)-A concentration of a substance to which most workers can be exposed 

without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA)-An allowable exposure concentration averaged over a normal S-hour 

workday or 40-hour workweek. 

Toxic Dose (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. 

Uncertainty Factor (UF)-A factor used in operationally deriving the RfD 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 LOAEL data rather 

than NOAEL data. Usually each of these factors is set equal to 10. 

 

SULFUR TRIOXIDE AND SULFURIC ACID 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. 99-4991, 

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 (l-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. 
 

SULFUR TRIOXIDE AND SULFURIC ACID A - 2 

APPENDlX 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 contam 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 a hundredfold below levels that Rave 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 agencywide 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, Mailstop E-29, Atlanta, Georgia 30333. 
 

 

 

 

SULFUR TRIOXIDE AND SULFURIC ACID B-l 

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 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-l ) 2-2, and 2-3) and figures (2-l and 2-2) 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, minimal risk levels (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,OOO,OOO. 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 No-Observed-Adverse- Effect Levels (NOAELs), 

Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 2-l and Figure 2-l are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 2-1 

(1) Route of Exnosure 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. When sufficient data 
SULFUR TRIOXIDE AND SULFURIC ACID	 B - 2 

APPENDIX B 

exists, 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 Table 2-1, 

2-2, and 2-3, respectively). LSE figures are limited to the inhalation (LSE Figure 2-l) and oral (LSE 

Figure 2-2) 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, Rotate 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 Iinks 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 2 “18r” data 

points in Figure 2-l). 

(5) Species The test species, whether animal or human, are identified in this column. Section 2.5 , 

“‘Relevance to Public Health,” covers the relevance of animal data to human toxicity and Section 2.3, 

“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 Freauency/Duration The duration of the study and the weekly and daily exposure regimen 

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 I ,1,2,2-tetrachloroethane via inhalation for 

6 hours per day, 5 days per week, for 3 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. 198 1. 

(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, 1 systemic effect (respiratory) was investigated. 

(8) NOAEL A No-Observed-Adverse-Effect Level (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 
SULFUR TRIOXIDE AND SULFURIC ACID	 B - 3 

APPENDIX B 

the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 0.005 

ppm (see footnote ‘lb”). 

(9) LOAEL A Lowest-Observed-Adverse-Effect Level (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 

endpoint 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 8 of the profile. 

(11) CEL A Cancer Effect Level (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 the NOAEL of 3 ppm in key number 18 was used to derive an MRL 

of 0.005 ppm. 

LEGEND 

See Figure 2-1 

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) Exnosure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic 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, 18r NOAEL is the critical endpoint for which an intermediate inhalation 

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates to a 
 

SULFUR TRIOXIDE AND SULFURIC ACID B - 4 

APPENDIX B 

NOAEL for the test species-rat. 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 “lb” in the LSE table). 

(17) CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond 

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to the 

entry in the LSE table. 

(18) Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the upper-bound 

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 (ql *). 

(19) Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 

The Relevance to Public Health section provides a health effects summary based on evaluations of existing 

toxicologic, epidemiologic, and toxicokinetic information This summary is designed to present interpretive, 

weight-of-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 section covers end points in the same order they appear within the Discussion of Health Effects by Route 

of Exposure section, by route (inhalation, oral, 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 section. If 

data are located in the scientific literature, a table of genotoxicity information is included. 

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 Data Needs section. 


 

SULFUR TRIOXIDE AND SULFURIC ACID B - 7 

APPENDIX B 

Chapter 2 (Section 2.5) 

Relevance to Public Health 

Interpretation of -1 Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not 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. They 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 2.5, 

“Relevance to Public Health,” contains basic information known about the substance. Other sections such as 

2.8, “Interactions with Other Substances,” and 2.9, “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 the Environmental Protection Agency (EPA) provides (Barnes 

and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

To derive an MRL, ATSDR generally selects the most sensitive endpoint 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 endpoint are available, ATSDR derives an MRL using the most sensitive species (when 

information from multiple species is available) with the highest 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 (UP) 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 LSE Tables.