United States

 Environmental Protection Office of Water EPA 815-R-99-002

 Agency 4607 January 1999

 

Health Effects from Exposure to 

Sulfate in Drinking Water Workshop
IRBINFO# EHHEHSB979

 CDC Protocol # 1779

HEALTH EFFECTS FROM EXPOSURE TO

SULFATE IN DRINKING WATER

WORKSHOP 

Sponsored by

Centers for Disease Control and Prevention

September 28, 1998

Atlanta, Georgia
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Table of Contents

Executive Summary ........................................................ 3

Introduction .............................................................. 6

Speakers ................................................................. 7

Opening/Welcome

Michael McGeehin ............................................. 7

EPA's Scientific Work and Regulatory Background

Charles Abernathy ............................................. 8

Sulfate Biochemistry

David Cole ................................................... 11

Intestinal Physiology of Sulfate

Marie Cassidy ................................................ 12

Effects of High Sulfate Exposures

Marilyn Morris ............................................... 14

Gastrointestinal Effects of Sulfate in Drinking Water: Baby Pig Study

Guillermo Gomez ............................................. 16

Health Effects from Exposure to High Levels of Sulfate in Drinking Water

Lorraine Backer .............................................. 18

Evaluation of The Association Between Infant Diarrhea and Elevated Levels of

Sulfate in Drinking Water: A Case-Control Investigation in South Dakota

Lorraine Backer .............................................. 22

Discussion of Key Issues ................................................... 24

Literature Cited .......................................................... 33

Appendix A: Workshop Agenda ............................................ 35

Appendix B: List of Participants ............................................ 37
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Executive Summary

In the 1996 amendments to the Safe Drinking Water Act, Congress mandated that the

U.S. Environmental Protection Agency (EPA) determine, by August 2001, whether to

regulate sulfate in drinking water. If EPA decides to regulate sulfate, the agency must

propose the Maximum Contaminant Level (MCL) by August 2003 and issue a final standard

by February 2005. Congress also directed EPA to conduct a study with the Centers for

Disease Control and Prevention (CDC) to establish a reliable dose-response relationship for

health effects from exposure to sulfate and to examine effects in sensitive subpopulations

(infants and transients). The directive indicated that the study must “be based on the best

available, peer-reviewed science and supporting studies conducted in accordance with sound

and objective scientific practices,” “be conducted in consultation with interested States,” and

be completed by February 1999.

CDC researchers had to cancel a planned community-based study of the frequency of

diarrhea in infants exposed to varying levels of sulfate naturally occurring in drinking water

because they could not identify a sufficiently large group of exposed infants. CDC did not

find an association between exposure to sulfate in drinking water and diarrhea in adult

volunteers. As a supplement to their studies and literature review, CDC and EPA organized a

workshop to review CDC’s sulfate studies and discuss the most relevant scientific literature

examining the health effects from exposure to sulfate in drinking water.

The workshop began with presentations. Dr. Charles Abernathy, from the EPA Office

of Water, presented the results of selected studies on the health effects of sulfate, a regulatory

history of sulfate, a time line of the actions EPA has taken on sulfate, and an estimate of the

types and numbers of drinking water systems that would be affected by the regulation of

sulfate in drinking water. 

There were three presentations describing the biochemistry and physiology of sulfate

absorption and excretion. Dr. David Cole, of the University of Toronto, presented

information on the importance of sulfate as a component of membranes and many compounds

in humans, the medical effects of sulfate deficiency, and how membrane transport and

regulation contribute to sulfate homeostasis. Dr. Marie Cassidy, of George Washington

University, presented information on intestinal physiology, including osmotic and bacterial

diarrhea, and reasons why elderly people may be susceptible to diarrhea. Dr. Marilyn Morris,

of the State University of New York (SUNY)-Buffalo, discussed the transport mechanisms

used in the body to regulate inorganic sulfate levels and the relative importance of the

different mechanisms at different developmental stages. Dr. Guillermo Gomez, of North

Carolina State University, presented a study on the gastrointestinal effects of sulfate in

drinking water, using neonatal pigs as an animal model for human infants.

Dr. Lorraine Backer, of the National Center for Environmental Health at CDC,

presented the results of recent studies conducted by CDC of the human health effects in
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sensitive subpopulations (infants and transients) of exposure to sulfate in drinking water. The

planned study of health effects in infants from exposure to sulfate in drinking water was not

completed because very few mothers of newborns in the areas where there were high levels of

sulfate in the drinking water provided by public water systems gave or were planning to give

infant formula mixed with tap water to their babies. The study of transients involved

analyzing the frequency of self-reported diarrhea in adults exposed to varying levels of sulfate

in drinking water provided to them. In the adult study, there was no statistically significant

association between the concentration of sulfate in the drinking water and the frequency of

diarrhea. Esteban et al. (1997) found no significant association between sulfate intake and

diarrhea in infants in South Dakota.

After the presentations, Dr. Carl Shy of the University of North Carolina lead the

workshop participants in a discussion of four issues:

Issue 1 Do reported studies suggest that a certain sulfate level would not be likely to

cause adverse effects (e.g., diarrhea in infants and travelers)?

Existing data do not identify the level of sulfate in drinking water that would

be unlikely to cause adverse human health effects. The panel members noted

that the available published literature included reports that piglets in

experimental feeding trials and some people experience a laxative effect when

consuming tap water containing from 1,000 to 1,200 mg/L of sulfate (as

sodium sulfate). However, none of the studies found an increase in diarrhea,

dehydration, or weight loss.

Issue 2 Does the literature support acclimatization or adaptation (what process and

time frame does it take)?

Based on biologic plausibility and anecdotal reports, evidence indicates that

people acclimate to the presence of sulfate in drinking water. In addition,

serum sulfate levels are high (compared to adults) in human fetuses and

neonates (to support rapid growth and development). However, data

describing acclimation and the changes in sulfate metabolism during growth

and development are limited.

Issue 3 Can an infant study be done for dose-response anywhere in the U.S. or

Canada?

The difficulty of locating a population of women feeding their infants formula

mixed with unfiltered tap water containing high levels of sulfate hinders the

completion of a dose-response study in infants. A study using neonatal pigs

could assess a dose response for both magnesium and sodium sulfates.
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Issue 4 Is there enough scientific evidence that there are adverse health effects from

sulfate in drinking water to support regulation? [Congress directed EPA to use

the best available science to set drinking water goals and regulations.] 

There is not enough scientific evidence on which to base a regulation, but

panelists favored a health advisory in places where drinking water has sulfate

levels of $ 500 mg/L.
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Introduction

In the 1996 amendments to the Safe Drinking Water Act, Congress mandated that the

U.S. Environmental Protection Agency (EPA) determine by August 2001 whether to regulate

sulfate levels in drinking water. If EPA decides to regulate sulfate, the agency must propose

the Maximum Contaminant Level (MCL) by August 2003 and issue a final standard by

February 2005. Congress also directed EPA to conduct a study with the Centers for Disease

Control and Prevention (CDC) to establish a reliable dose-response relationship for sulfate

and examine effects in sensitive subpopulations (infants and transients). The directive

indicated that the study must “be based on the best available, peer-reviewed science and

supporting studies conducted in accordance with sound and objective scientific practices,” “be

conducted in consultation with interested States,” and be completed by February 1999.

CDC researchers had to cancel a planned community-based study of the frequency of

diarrhea in infants exposed to varying levels of sulfate in drinking water because they could

not identify a sufficiently large group of exposed infants. A study of adults exposed to varying

levels of sulfate in drinking water provided to them did not find an association between

exposure to sulfate and the frequency of self-reported diarrhea. Because these studies were

not able to establish a dose-response or a level of sulfate in drinking water that would not be

expected to cause adverse human health effects, CDC and EPA organized a workshop of

scientific experts to present and discuss the most relevant scientific studies conducted on the

health effects of sulfate.

Prior to the workshop, the panel members received a document reviewing the relevant

scientific literature on the health effects of sulfate. At the workshop, each panelist presented

the most current information in his or her field of expertise. The panelists and other workshop

participants discussed the information presented in the literature review and presentations,

focusing on the four key issues listed below:

Issue 1 Do the studies suggest that a certain contaminant level would not be likely to

cause adverse effects (e.g., diarrhea in infants and travelers)?

Issue 2 Does the literature support acclimatization or resistance (what process and

time frame does it take)?

Issue 3 Can an infant study be done for dose-response anywhere in the U.S. or

Canada?

Issue 4 Is there enough scientific evidence that there are adverse health effects from

sulfate in drinking water to warrant regulation? [Congress directed EPA to

use the best available science to set drinking water goals and standards.]
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Speakers

Opening/Welcome

Michael McGeehin, Ph.D., M.S.P.H., Chief, Health Studies Branch

National Center for Environmental Health, Centers for Disease Control and Prevention

Dr. Mike McGeehin, Chief of the Health Studies Branch in the National Center for

Environmental Health (NCEH) at the Centers for Disease Control and Prevention (CDC)

welcomed the participants, provided a brief background and introduction to the meeting, and

introduced Dr. Carl Shy, the facilitator for the workshop. Dr. Shy, from the Department of

Epidemiology in the School of Public Health at University of North Carolina at Chapel Hill,

gave a brief background on his experience in environmental health. He asked participants to

state their names and identify their area of expertise and its relationship to the issue of sulfate

in drinking water. Workshop presenters and their areas of expertise regarding sulfate were 

Dr. Charles Abernathy, sulfate toxicology; Dr. Lorrie Backer, principal investigator for the

CDC studies; Dr. Marie Cassidy, interaction between sulfate and the gastrointestinal tract; 

Dr. David Cole, sulfate biochemistry; Dr. Guillermo Gomez, the effects of sulfate on the

gastrointestinal system of piglets; Dr. Marilyn Morris, regulation of sulfates in the body. 

Other workshop participants were Larry Posey, CDC; Bob Benson, EPA’s Denver office;

Dale Fronenberger and Bonita Johnson, EPA’s Atlanta office; Kimberly Harris and Dorothy

Wormbly, EPA’s Chicago office; Dr. Fred Hauchman, EPA Office of Research and

Development; Irene Dooley and Jennifer Wu, EPA’s Office of Ground Water and Drinking

Water; Buck Grissom, Agency for Toxic Substances and Disease Registry (ATSDR); Mike

Baker, South Dakota Department of Environment and Natural Resources (there are110 public

water systems in South Dakota that have high levels of sulfate); Bill Hiatt, representative for a

company that manufactures ammonium sulfate; Krishna Parameswaran, involvement with

nonferrous mining drinking water supply and site cleanups; Joyce Tsuji, involvement with

mining sites; and Stefano Tervi, representative for a mineral water bottling company in Italy. 

Following the self- introductions, the panelists made their presentations.
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EPA's Scientific Work and Regulatory Background

Charles Abernathy, Ph.D., Toxicologist

Office of Water, U.S. Environmental Protection Agency

 Sulfur has many roles in the human body (e.g., as a part of amino acids). Some

sulfates have been employed as medicines in both human and veterinary medicine. For

example, the sodium and magnesium salts of sulfate have been employed as laxatives and the

zinc salt has been used as an emetic. The water solubility of these sulfate salts probably

contributes to the laxative and emetic effects, because the barium and calcium salts are less

soluble and generally not effective. The sulfate salts are not usually employed as laxatives or

emetics, but MgSO4 (magnesium sulfate, or Epsom salt) is still used as a cathartic.

As mentioned above, sulfate is a natural and necessary constituent in the bodies of

humans and other animals. In humans, serum sulfate levels range from 0.25 to 0.38 mmol/L. 

Sulfate is involved in a number of biochemical activities including the production of

chondroitin sulfate and sulfation of exogenous chemicals.

Animal toxicity studies have found acute LD50s of MgS04 to be 6 g/kg (oral exposure)

and 1.2 g/kg (intravenous exposure). There are few data on the chronic effects of exposure

to high doses of this substance. Since its potential for carcinogenicity at high doses has not

been studied, sulfate would be classified as a Group D carcinogen under EPA’s 1996

proposed guidelines (i.e., sulfate would be placed in the “carcinogenicity cannot be

determined” group).

There have been a number of studies conducted to determine the toxicity of sulfate in

humans. Chien et al. (1968) presented case reports of diarrhea in three infants exposed to

water containing sulfate (ranging from 630 to 1,150 mg/L). However, there were other

potential causes of the diarrhea in these infants (i.e., consuming infant formula with high

osmolarity or the presence of microbial pathogens) that were not thoroughly addressed by the

investigators. A survey conducted in North Dakota found a slight increase in the percentage

of people (28%) who reported that their drinking water had a laxative effect when the

drinking water contained 500 to 1,000 mg/L sulfate compared to the percentage of people

(21%) who reported a laxative effect from drinking water that contained <500 mg/L. Sixtyeight percent of people who consumed water with 1,000 to 1,500 mg/L reported a laxative

effect. Peterson (1951) analyzed the data from North Dakota and concluded that drinking

water containing $ 750 mg/L sulfate was associated with a self-reported laxative effect

whereas drinking water containing # 600 mg/L was not. Moore (1952) reanalyzed the data

reported by Peterson and found that most people experienced a laxative effect when they

drank water that contained >1,000 mg/L sulfate. In 1977, the National Academy of Science

(NAS) reported no ill effects in people who ingested water containing # 500 mg/L sulfate.

Children, transients, and the elderly are the sensitive sub-populations of interest to

EPA because of the potentially high risk of dehydration from diarrhea that might be caused by

high levels of sulfate in drinking water.

In the 1970 Community Water Supply Study, the U.S. Public Health Service (USPHS)
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measured the sulfate levels in the drinking water sources of nine geographic areas. Sulfate

was present in 645 of 658 groundwater supplies and in all 106 surface water supplies sampled. 

Sulfate levels ranged from <1 to 770 mg/L (with a median of 4.6 mg/L). Only three percent

of the water supplies sampled had sulfate levels greater than 250 mg/L.

The Safe Drinking Water Act (SDWA) of 1974 amended the Public Health Service

Act and specified that EPA set primary ( based on health effects) and secondary (based on

aesthetic and organoleptic qualities) drinking water standards.

In a 1975 survey of 625 Interstate Carrier Water Supply Systems, 3.4 percent of the

systems had sulfate levels >250 mg/L. The maximum sulfate level found was 978 mg/L. In a

survey of Rural Water Supply in the late 1970s, sulfate was found in groundwater at levels

from 10 to 1,000 mg/L, (mean = 98 mg/L), and in surface water at levels from 15 to 321

mg/L (mean = 53 mg/L).

Dr. Abernathy presented the following time line of EPA actions regarding sulfate in

drinking water:

March 31, 1977 EPA proposed the Secondary Maximum Contaminant Level

SMCL of 250 mg/L based on taste (the World Health

Organization (WHO) guideline for sulfate is 400 mg/L, based

on taste; people’s threshold for tasting sulfate ranges from 250-

350 mg/L). The Secondary MCL serves as a guideline, not a

federally enforceable standard.

July 19, 1979 The final 250 mg/L sulfate Secondary MCL was

published and became effective January 19, 1981.

November 13, 1985 EPA proposed a Health Advisory (HA) for sulfate (400 mg/L)

to protect infants. As data became available, EPA would

reconsider the need for an enforceable standard to protect

transients.

1989 A citizen suit was filed against EPA that led to a consent order

establishing a deadline for the publication of an MCL for

sulfate.

June 25, 1990 EPA proposed an enforceable MCL of 400/500 mg/L for

sulfate to protect infants. (the Canadian guideline [not

regulation] is 500 mg/L). EPA retained the Secondary MCL of

250 mg/L.
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December 20, 1994 EPA proposed an MCL and health effects goal (maximum

contaminant level goal [MCLG]) of 500 mg/L, as agreed under

the consent order.

The 1996 Amendments to the SDWA established the following deadlines:

February 1999 CDC and EPA must provide a report of jointly conducted

studies to establish a reliable dose-response relationship for

sulfate, including sensitive sub-populations (i.e., infants and

transients).

August 2001 EPA must determine whether or not to regulate sulfate.

February 2005 If the determination is to regulate, EPA must propose the MCL

by August 2003 and issue a final rule by February 2005.

In 1994 EPA estimated that approximately 2,000 of the 54,000 public water systems

in the U.S. would have sulfate levels higher than 500 mg/L. These systems include 1,241

serving 25-100 people, 493 serving 101-500 people, 194 serving 501 to 3300 people, 27

serving 3301 to 10,000 people, 10 serving 10,000 to 100,000 people, and none serving over

100,000 people. [Although public water systems serve 249 million people, 95% of the

systems serve less than 10,000 people].

Discussion

Dr. David Cole asked if pure sulfate solutions have an odor. Dr. Abernathy responded

that taste is more evident than odor, but that there is some odor. Dr. Marie Cassidy asked Dr.

Abernathy if EPA’s mandate is only for sulfate. Dr. Abernathy said that sulfate is one of

several substances that EPA is in the process of determining whether or not to regulate. Buck

Grissom, ATSDR, asked if pH affected sulfate in water. Dr. Abernathy answered that he was

not aware of any effect that pH has on water and sulfate.
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Sulfate Biochemistry

David Cole, MD, Ph.D., F.R.C.P.C., Associate Professor

Departments of Laboratory Medicine, Medicine and Genetics, University of Toronto

Sulfate (SO4

2-) is a divalent anion. There may be up to one percent sulfate present in

gastric fluids. The human body distinguishes sulfate ( 5.7 angstroms) from phosphate (6

angstroms) and thiosulfate (S2O3

2-) by the distinctive stereospecific molecular configurations

of each ion. The body maintains a homeostasis between absorbed inorganic sulfate, sulfate

compounds, and renal excretion; membrane transport and regulation contribute to this

homeostasis. Inorganic sulfate represents a small fraction of total sulfate in the body, which

includes muccopolysaccharides, chondroitin sulfate, glycolipids, steroids, thyroid hormones,

peptide hormones (gastrin), oligosaccharides, and xenobiotics (e.g., drugs). As much as 5 to

10 percent of excreted sulfate is excreted as sulfyl esters. 

Dr. Cole and his colleagues conducted studies on the shift in homeostasis between

pregnant and non-pregnant women. They found that pregnant women reabsorb more sulfate

and retain an extracellular pool for placental transfer to the fetus. There are detectable levels

of sulfate in amniotic fluid. Toward the third term, the fetus swallows amniotic fluid, which

passes through the gastrointestinal tract and is eliminated in urine. The fetus also has higher

circulating levels of sulfate than adults do. 

A study looking for a gene responsible for diastrophic dysplasia identified the genetic

sequence for one of the four known transporters of sulfate. Apparently, a sulfate deficiency

arises if this transporter does not function properly. During fetal development, sulfate

deficiencies can lead to diastrophic dyplasia (deformed tissues) of the hands and feet,

cognitive and behavioral changes, membrane structural deficiencies, early lethality, and

malformed cartilage. 
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Intestinal Physiology of Sulfate

Marie Cassidy, Ph.D., D.S.C., Associate Professor

Department of Physiology and Experimental Medicine, George Washington University

Diarrhea affects more people world-wide than any other illness. Diarrhea caused by

parasites or infections need not be life-threatening if fluids and electrolytes are replenished in a

timely manner because the intestinal lining is replaced every three to four days, thereby

washing out parasites or pathogenic microorganisms. At the apical membrane in the

intestines, cation and anion transport occurs through the cell wall. The World Health

Organization found that introducing solutions of sodium with glucose and amino acids aids in

repairing damage to the apical membrane, allowing water to flow through and between the

cells and restoring ion transport.

In the small intestine, plasma has the same osmolarity as the lumen. In the large

intestine, differences in osmolality between the plasma and the lumen allow water absorption

from the lumen into the large intestinal villi. 

Normally there is a balance between absorption and secretion in the intestinal villi. 

The presence of substances that increase the rate at which materials move through the

intestine reduces the amount of time available for reabsorption of water and may cause

diarrhea. Diarrhea can also result from an increased secretion of water into the intestinal

lumen, which may be caused by bacterial toxins (Vibrio cholerae, Esherichia coli,

Staphylococcus aureus, Pseudomonas aeruginosa [seen in AIDS patients], Bacillus areus,

Clostridium perfringens, Kiebsiella, Shigella dysenteriae, and Pnueamoniaea ), bile salts,

hormones, or high levels of osmotically active solutes such as sulfate. Congenital diarrhea can

be caused by defective sodium chloride absorption.

In addition to the mechanisms discussed above, increased intestinal hydrostatic

pressure, luminal distention, high luminal osmolarity, plasma dilution, increased mucosal

permeability, increased interstitial hydrostatic pressure, and underlying infections or

impairments (e.g., ulcerative colitis) may cause diarrhea.

Osmotic diarrhea results when there is an excess of unabsorbed osmotically active

particles (e.g., magnesium hydroxide in antacids) present in the intestinal lumen. For example,

magnesium salts, castor oil, and undigested lactose (i.e., in lactose-intolerant individuals) are

osmotically active compounds that can produce laxative effects or cause diarrhea. 

Cholesterol-binding drugs increase the concentration of bile salts in the colon, and may cause

diarrhea. 

There are antidiarrheal therapies other than sodium, glucose, amino acids, and fluid

replacement. Opiates prolong transit time (the amount of time substances are retained in the

intestines) and promote more efficient absorption, and alpha-2-adrenergic medications inhibit

anion secretion. High concentrations of steroids increase sodium absorption. 

In summary, clinical diarrhea is caused by 1) a lack of capacity to absorb fluids or

electrolytes, 2) the presence of osmotically active agents in the intestinal lumen, 3) increased

propulsion causing decreased contact time, or 4) bacterial toxins that stimulate secretion of
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water into the intestinal lumen. The presence of high levels of sulfate in the intestinal lumen

would not typically affect normal healthy adults or infants. However, people with

pathophysiology, older people taking certain medications (e.g, to treat diabetes, hypertension,

high cholesterol), people with underlying intestinal diseases, and infants in tourist areas may

be more susceptible to the effects (i.e., diarrhea) of a sudden exposure to high levels of

sulfate.

Discussion

Dr. Shy asked whether drugs to inhibit cholesterol interact with sulfate in water to

make it more hyper-osmotic. Dr. Cassidy said that she believes they would because anything

that will increase the levels of bile salts in the intestines would be likely to cause loose stools. 

Another concern is that older people may be more susceptible to high sulfate levels if they are

taking cholesterol-lowering drugs or if they have underlying health problems.
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Effects of High Sulfate Exposures

Marilyn Morris, Ph.D., Associate Professor

Department of Pharmaceuticals, State University of New York at Buffalo

Elimination of sulfate occurs through urinary excretion. In the proximal tubule of the

kidney, sulfate is reabsorbed across the brush border membrane into the cells and exits via the

basolateral membrane. Sulfate and sodium are reabsorbed into renal proximal tubular cells

through a part of the membrane sequence known as NaSi-1. The cells comprising the

intestinal ileum also contain the genetic sequence for the NaSi-1 transporter. Another

transport mechanism, the sodium-independent sulfate anion exchange transport (SAT-1), is

present in muscle and brain. Exposure to certain drugs, such as nonsteroidal antinflammatory

drug treatments or hormone therapy; changes in dietary levels of sulfate, age, pregnancy; and

disease states, such as hypothyroidism, can affect sulfate transport mechanisms.

Bauer (1976) found 85-90% absorption of sulfate at high concentrations; most of the

absorption occurred in the ileum. In a recent study, Dr. Morris and her colleagues gave diets

containing different amounts of methionine, an amino acid and sulfate-precursor, to rats. A

diet containing three times more methionine than the control diet decreased reabsorption of

sulfate from the intestine but produced little difference in serum sulfate levels. The

researchers concluded that the body can compensate for different levels of sulfate. Compared

to the levels of NaSi-1 messenger RNA (mRNA) in control animals, the levels of NaSi-1

mRNA were increased in animals that were fed the low sulfate diets, and decreased in animals

that were fed higher levels of methionine in their diets.

In an experiment using neonatal, young, and adult Guinea pigs, the younger animals

reabsorbed sulfate and sodium at higher rates than the adult animals did. Peña and Neiberger

(1997) reported that young guinea pigs fed diets high in sulfate maintained serum sulfate

concentrations within the normal range by increasing urinary excretion of sulfate. 

Diastrophic Dysplasia Sulfate Transport (DDST) is an anion exchanger present in the

intestine and in many other tissues. The Down Regulated in Adenoma (DRA) gene encodes

an intestine-specific membrane sodium-independent sulfate transport protein. This gene is

expressed in the normal colon and also in the small intestine of mice and humans. There is a

59% overlap between the genetic sequences for DRA and SAT-1 and a 60% overlap between

DRA and DTDST. 

At least one series of sulfate anion exchangers is known to be present in the intestine,

and there may be others. At this point little is known about the function of these exchangers

or about how sulfate absorption is regulated in the intestine.

Cocchett and Levy (1981) reported that, in human research subjects, a single dose of

8g of anhydrous sodium sulfate caused diarrhea. However, 8g of anhydrous sodium, sulfate

divided into four 2-gram doses, given at hourly intervals, did not cause diarrhea. In another

study (Morris and Levy, 1983), the same millimolar dose of sulfate provided from magnesium

sulfate caused adverse effects ranging from upset stomach to diarrhea. Sixty percent of the
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sodium sulfate given in divided doses was absorbed, whereas only 35% of the magnesium

sulfate was absorbed. These results indicate that the source of the sulfate (e.g., from the

magnesium or sodium salt) is important in determining the extent and nature of any potential

adverse effects.

The potential adverse effects of high sulfate ingestion include: 1) diarrhea, 2)

alterations in sulfation (e.g., metabolism of hormones, catecholamines, and bile acids), and 3)

changes in calcium and magnesium metabolism that increase urinary excretion (e.g., increased

concentrations of calcium sulfate complexes are found in renal disease patients).

Galinsky and Levy (1981) studied the concentration of acetaminophen in plasma and

found that sulfate depletion decreased sulfation, thereby increasing the amount of

acetaminophen that remained in plasma. They also found that, in infants, the sulfonation of 

acetaminophen occurs more efficiently than it does in adults. Freeman and Richards (1979)

found that sulfate and creatinine are not removed by dialysis. Patients with acute renal failure

tend to have the highest serum sulfate concentrations, but there have been no acute toxic

effects noted from sulfate retention in this circumstance.

Discussion

Dr. Cassidy asked about the connection with renal disease. Dr. Morris answered that

the connection between the two is related to the failure of reabsorption, that is, decreases in

filtration cause serum sulfate concentrations to increase. Dr. Cole said that in a study of

premature infants, he found a relationship between increased sulfate loading and the amount

of total sulfoester, but no toxic effects. Dr. Shy asked Dr. Morris to clarify her point about

how one of the potential adverse effects of high sulfate is a possible alteration in sulfation, and

asked if this alteration could influence metabolism. Dr. Morris suggested that altered sulfation

could have an impact on metabolism, but stated that this possibility has not been directly

examined. However, research has indicated that metabolism may be affected if sulfate

concentrations are too low.
1

 Although the research described in this presentation has been supported by the U.S. EPA, it has

not been subjected to agency review and, therefore, does not necessarily reflect the views of the agency.

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1Gastrointestinal Effects of Sulfate in Drinking Water: Baby Pig Study

Guillermo Gomez, Ph.D, M.S., Senior Scientist

Director, NCSU Piglet Core, Department of Animal Science, North Carolina State

University

The study reported herein was conducted at the North Carolina State University

(NCSU) Piglet Core through the Center for Gastrointestinal Biology and Disease with a grant

from the EPA .1 This study used artificially-reared neonatal piglets as a model to evaluate the

effect of inorganic sulfate on bowel function in human infants. Two experiments were

conducted to evaluate the effect of high levels of sulfate on the growth, feed intake, and feces

consistency of artificially-reared piglets and to determine the dose at which at least 50% of the

pigs developed nonpathogenic diarrhea. The effect of dietary sulfate level on kidney weight

and the concentration of sulfate in urine was also assessed.

Newborn piglets were left with their dams for approximately 48 hours and then

transferred to an isolated room containing an automated feeding device (Autosow). Piglets

were fed a basal diet with no added sulfate and were allowed to adapt to the new environment

for a 3- to 4-day period. The Autosow is a machine containing individual cages that regularly

aseptically dispenses small volumes of liquid diet according to the weight of each piglet. 

Piglets were fed liquid diets only and did not have access to drinking water. The diet reservoir

was refrigerated; therefore, bacterial growth in the diets was minimal. In each experiment, at

the end of the adaptation period (at an average age of 5 days), 40 piglets were weighed and

distributed according to body weight, sex, and litter origin into four groups. Ten individually

reared piglets per dietary treatment were fed one of four diets containing the following levels

of added inorganic sulfate (mg/L of diet), as anhydrous sodium sulfate (USP): 0, 1200, 1600,

and 2000 for Experiment 1 (18-day study), and 0, 1800, 2000, and 2200 for Experiment 2

(16-day study). Inorganic sulfate was dissolved in deionized, distilled water before the other

dietary ingredients were added. The deionized, distilled water contained <1 mg inorganic

sulfate/L; the basal diets of Experiments 1 and 2 contained 277 and 261 mg inorganic

sulfate/L, respectively. Details of the experimental protocol have been published elsewhere

(Gomez et al., 1995).

The levels of added sulfate did not affect (p < 0.05) the growth of the piglets or their

feed intake. Whereas 1200 mg added sulfate/L had essentially no effect on feces consistency,

levels >1800 mg/L of diet resulted in a persistent, nonpathogenic diarrhea in neonatal piglets. 

Added sulfate did not affect relative kidney weight (p < 0.05). Inorganic sulfate in urine

reached maximum concentration in pigs fed diets with 1600 and 1800 mg added sulfate/L in

Experiments 1 and 2, respectively (p < 0.05), but declined at higher levels. The changes in

feces consistency suggest that the level of added dietary inorganic sulfate at which 50% of

piglets develop nonpathogenic diarrhea is between 1600 and 1800 mg/L.
Page 18

Discussion

Dr. Morris clarified that the basal amount of sulfate in Dr. Gomez’s study was 270

mg/L, that the actual amount of added sulfate was 1,600 mg/L, resulting in a total amount of 

1,870 mg/L given to the piglets. Dr. Shy asked if fifty percent of the animals got diarrhea at

1,600-1,800. Dr. Gomez answered that, at 1,600 mg/L 50% of the piglets got diarrhea, but

that at 2,000 and 2,200 mg/L, all piglets had diarrhea. 

Dr. Shy asked if there was a difference between animals fed 0 mg/L and those fed

1,200 mg/L. Dr. Gomez responded that there was no effect at 1,200 mg/L, so that level was

a safe limit for piglets. Dr. Cole pointed out that the definition of “no effect” is subjective. 

For example, a pediatrician may have a different definition of “no effect” than a mother who

observes changes in the number, frequency, and volume of her infant’s stools. 

Dr. Gomez noted that studying neonatal piglets for three weeks before weaning is

comparable to following a baby for six to nine months. While the study measured sulfate in the

urine, the equipment did not allow measurement of urine or feces volume. Dr. Cole asked

whether the piglets could have shown adaptation at all but the highest sulfate levels. Dr.

Gomez said that he did not measure adaptation, but did find that all piglets grew at the same

rate, so there was no effect on growth. 

Ms. Joyce Tsuji, of Wheeler Environmental Corporation, was surprised that the piglets

showed no dehydration or weight loss. Dr. Gomez responded that his group was also

surprised by this outcome. He noted that piglets with rotovirus do become dehydrated and

eat less. 
Page 19

Health Effects from Exposure to High Levels of Sulfate in Drinking Water

Lorraine Backer, Ph.D., M.P.H., Epidemiologist

National Center for Environmental Health, Centers for Disease Control and Prevention

Sulfate is a substance that is occurs naturally in drinking water. Health concerns

regarding sulfate in drinking water have been raised because of reports of diarrhea associated

with the ingestion of water containing high levels of sulfate. Of particular concern are groups

within the general population that may be at greater risk from the laxative effects of sulfate

when they experience an abrupt change from drinking water with low sulfate concentrations

to drinking water with high sulfate concentrations. 

There are very few scientific reports describing the health effects of exposure to sulfate

in drinking water, and the concerns regarding sensitive populations are based on case studies

and anecdotal reports. One such potentially sensitive population is infants receiving their first

bottles containing tap water, either as water alone or as formula mixed with water. Another

group of people who could potentially be adversely affected by water with high sulfate

concentrations are transient populations (i.e., tourists, hunters, students, and other temporary

visitors) and people moving into areas with high sulfate concentrations in the drinking water

from areas with low sulfate concentrations in drinking water. 

The objective of the CDC/EPA studies on the health effects of exposure to sulfate was

to provide additional information regarding whether sensitive populations (infants and

transients) may be adversely affected by sudden exposure to drinking water containing high

levels of sulfate. Specifically, the researchers involved designed a field investigation of infants

exposed to naturally occurring high levels of sulfate in the drinking water provided by public

water systems and an experimental trial of exposure in adults.

In collaboration with the State Health Departments of New Mexico, South Dakota,

and Texas, we planned a prospective cohort study of infants who would be exposed to tap

water used to mix infant formula. We planned to recruit women in their third trimester of

pregnancy. Infants were to be enrolled at birth and followed for 4 weeks to determine if there

was an association between exposure to drinking water containing varying levels of sulfate

and reported cases of diarrhea. 

For a woman to be included in our study, she had to be: (1) accessible through a clinic

that offers prenatal care, (2) 35 to 36 weeks pregnant (to exclude severely premature infants

and to be able to interact with the woman at her next prenatal visit), (3) not planning to breast

feed her baby, (4) planning to feed her infant concentrated formula mixed with her home tap

water (can be boiled), (5) planning to be at home with her infant for at least one month, (6)

living in a home (private house, apartment, mobile home, etc.) that is served by a public water

supply and that does not have a water filtration system, and (7) able to read the study

instruments in either English or Spanish.

Using historic water quality data for secondary drinking water constituents (including

concentrations of sulfate) provided by the states and Geographic Information System (GIS)

techniques, we generated maps of the geographic distribution of each water system that
Page 20

simultaneously identified the level of sulfate in the water and the size of the population each

system serves. Based on the GIS maps, the number of expected births in the participating

states, the inclusion criteria we have described, and the assumption that 25% of infants are not

breast-fed, we planned a six-month recruiting period. We planned to enroll a maximum of

880 infants, 110 each from water systems within the following ranges of sulfate: < 250 mg/L

(baseline or comparison group), 251-500 mg/L, 501-700 mg/L ,and a maximum of 550 infants

from water systems with sulfate levels greater than 701 mg/L.

We conducted a pilot study of the planned recruitment methods and study instruments

in four counties in South Dakota. Local Public Health Nurses, who already had rapport with

clinic patients, were hired and trained to recruit study participants and conduct the activities

associated with the study. In the 4 counties (served by 3 Community Health Clinics), 72

women were approached about participating in the study during their prenatal visit to the

public health clinics. Of these 72 women, 30 were ineligible because they planned to breastfeed their infant, 23 were ineligible because they planned to use water other than tap water to

mix infant formula, and 11 were ineligible because they did not meet other eligibility criteria.

Eight women were eligible to participate in the study; three refused, five women

agreed to participate, and one woman completed all the study activities. Of the four women

who did not complete the study activities, two switched to bottled water as the source of

water to mix with infant formula, one chose to use ready-to-feed formula after two weeks of

using the powdered formula, and the fourth moved out of the area.

Because we experienced recruiting problems during the pilot study, we developed a

self-administered questionnaire (SAQ) to examine tap water use. The questionnaires were

developed in both English and Spanish and were provided to all women who came to one of

32 clinics in the previously identified geographic areas of New Mexico, South Dakota, and

Texas. The SAQ asked questions about the source of their home tap water, what mothers of

infants #3 months old were currently feeding their babies, and how currently-pregnant women

planned to feed their infants. 

Overall, the results from the SAQ indicate that more than half (61%) of pregnant

women report planning to breast-feed their infants. In addition, of those who plan to use

infant formula mixed with water, most (84%) plan to use water other than tap water. These

results are consistent with our experiences during the pilot study and indicate that only a very

small percentage of women who live in areas with high levels of sulfate in the tap water

provided by public water systems plan to give this water to their infants.

To examine how many of the women who completed the SAQ would have been

eligible to participate in our study, we examined the responses of women who received their

tap water from public water systems and who did not have filters on their home taps and

found that 403 women with infants # 3 months of age and 761 pregnant women met these

eligibility criteria. The highest proportions of women who had used or were planning to use

tap water to mix infant formula were in the four counties with average sulfate levels # 250

mg/L. Of the 365 pregnant women in areas with sulfate levels > 250 mg/L, 226 (62%)

planned to use infant formula. However, only 39 (11%) planned to use infant formula mixed
Page 21

with their tap water. Of the 183 women with infants #3 months old in areas with sulfate

levels > 250 mg/L, 151 (83%) used infant formula, but only 35 (19%) reported having used

infant formula mixed with their tap water.

The other population potentially sensitive to abrupt exposure to high levels of sulfate

in drinking water is transient adults (students, visitors, hunters, etc.). To study the effects on

adults of suddenly changing drinking water sources from one that has little or no sulfate to

one that is high in sulfate, we conducted an experimental study involving volunteers from

Atlanta, Georgia, including CDC employees and employees at the U.S. EPA Region IV office.

 Volunteers were randomly assigned to one of five sulfate exposure groups (i.e., 0, 250, 500,

800, or 1200 mg/L sulfate from sodium sulfate in bottled drinking water) and were provided

with bottled drinking water for six days. The bottled water for days 1, 2, and 6 contained

plain water, the bottles for days 3 through 5 contained added sulfate. The unfinished or empty

bottles were returned and weighed to determine how much water was consumed each day. 

Volunteers were blinded to the level of sulfate in their drinking water.

One hundred five study participants were divided among the dose groups as follows: 

24 received 0 mg/L sulfate; 10 received 250 mg/L sulfate; 10 received 500 mg/L sulfate; 33

received 800 mg/L sulfate; and 28 received 1200 mg/L sulfate. We analyzed the number of

bowel movements recorded each day by study participants. There were no statistically

significant differences in the mean number of bowel movements among the groups on days 3,

4, 5, or 6. There were also no statistically significant differences in the mean number of bowel

movements reported when comparing days 1 and 2 (the days when there was no sulfate in the

water) with days 3, 4, and 5 within each dose group.

The frequencies of diarrhea reported by individuals exposed to varying levels of sulfate

in their drinking water are presented in the table. Three different definitions of diarrhea were

used: increase in stool volume compared to normal, change in stool consistency to liquid or

paste, and increase in volume/change in consistency. Because the effect of sulfate is

dependent on both the weight of the participant and the amount of water each consumed 

(dose/kg of body weight), we used logistic regression to examine the reported frequency of

diarrhea (using the three different definitions described above) by sulfate dose ([concentration

of sulfate in water x volume of water consumed on days 3, 4, and 5]/body weight) in

individuals who reported normal stool volume on days 1 and 2 and who did not have family

members who experienced vomiting or diarrhea on days 3, 4, or 5). Sulfate dose was not a

statistically significant predictor of diarrhea in any of the models (p $ 0.80 for all models).
Page 22

___________________________________________________________________________

__

Sulfate Dose Osmotic Diarrhea1 Diarrhea2 Diarrhea3

 (mg/L) n No.4 (%) No.4 (%) No.4 (%)

___________________________________________________________________________

___

0 24 2/18 (11) 6/16 (38) 5/14 (36)

250 10 0/9 1/7 (14) 1/6 (17)

500 10 1/8 (12) 4/9 (44) 3/8 (38)

800 33 4/26 (15) 7/20 (35) 8/17 (47)

1200 28 5/27 (18) 6/17 (35) 6/17 (35)

___________________________________________________________________________

__

1

 Reported as an increase in stool volume on days 3, 4, or 5 and limited to those who reported normal stool

volume on days 1 and 2.

2

 Reported as paste-like or liquid stools on days 3, 4, or 5 and limited to those who reported normal stool

consistency on days 1 and 2.

3

 Reported as a change in stool bulk or consistency on days 3, 4, or 5 and limited to those who reported normal

stools on days 1 and 2.

4

 (Number of people reporting diarrhea on days 3, 4, or 5)/(Number of people who reported normal stools on

days 1 and 2 and who did not report a family member ill with vomiting or diarrhea).

To examine the data for a trend toward increased frequency of reports of diarrhea with

increasing dose, we included the dose as an ordinal variable in a logistic regression model of

osmotic diarrhea. Again, there was no statistically significant increase in reports of diarrhea

with increasing dose (one-sided p = 0.099).

The over-all purpose of these studies was to examine the association between

consumption of tap water containing high levels of sulfate and reports of osmotic diarrhea in

susceptible populations (infants and transients, i.e., those acutely exposed). We had to cancel

a planned study of infants because we could not identify enough exposed individuals from

which to draw a study population. The results of our SAQ examining tap water use indicated

that most pregnant women who completed the survey plan to breast-feed their infants. Of

those who plan to use formula mixed with water, most do not plan to use tap water to mix the

formula. In our experimental trials with adult volunteers, we did not find an association

between acute exposure to sodium sulfate in tap water (up to 1200 mg/L) and reports of

diarrhea.
Page 23

The report describing this study, “Health Effects from Exposure to High Levels of

Sulfate in Drinking Water,” accompanies this workshop summary.

Evaluation of The Association Between Infant Diarrhea and Elevated Levels of Sulfate

in Drinking Water: A Case-Control Investigation in South Dakota

Lorraine Backer, Ph.D., M.P.H., Epidemiologist

National Center for Environmental Health, Centers for Disease Control and Prevention

Dr. Emilio Esteban, et al. conducted an investigation of diarrhea in infants in South

Dakota who ingest water containing various levels of naturally-occurring sulfate. In that

state, 110,000 people live in areas (19 counties) with elevated sulfate levels. In these

counties, there were 366 births between January and March 1995, and 264 new mothers were

interviewed using a telephone questionnaire. The infants were 6.5- to 30-months-old at the

time of the interviews. Interviewers asked the mothers report the number and consistency of

their infants’ bowel movements, whether their infant had diarrhea (defined as 3 or more loose

stools in a 24-hour period), and the quantities of water consumed by their infants in the

previous seven days. Mothers were also asked to provide a sample of the water they used in

the baby’s diet. The water samples were analyzed for sulfate levels.

Cases were defined as infants with diarrhea (as reported by the mother) and control

subjects were defined as infants who did not develop diarrhea. The mean concentration of

sulfate in the water in the homes of cases was 392 mg/L, and in the homes of control subjects

was 358 mg/L. Sulfate intake was 31 mg/kg body weight for both groups. Mothers reported

diarrhea in nineteen percent of the infants living in households with sulfate levels in tap water

> 500 mg/L h, and in 14 percent of infants living in households with sulfate levels < 500 mg/L. 

This study revealed no association between exposure to sulfate from tap water and subsequent

diarrhea.

Discussion

Dr. Cassidy asked if higher sulfate levels match higher calcium or magnesium levels. 

Dr. Backer said that geographic areas with high sulfate levels in drinking water sources also

tend to have high levels of other salts and minerals, but the association is not consistent. Dr.

Cassidy asked whether, in the areas of Dr. Backer’s study, there is any sort of folklore

pertaining to why women are not choosing tap water for formula. Dr. Backer responded that

she did not hear any folklore but that the women probably tended not to use tap water for

drinking because it smelled and/or tasted bad. Dr. Backer also noted that the areas that have

very high sulfate levels tend to be rural and poor. Potential study participants were identified

through Women, Infants, and Children (WIC) clinics and it is possible that women reported

breast-feeding, even if they had or were planning to bottle-feed their babies, because WIC

clinics encourage breast-feeding.

Dr. Morris stated that she thinks researchers might be more successful in getting

women to use a certain infant formula if the women were provided, free-of-charge, with a prediluted, ready-to-use formula, with known amounts of sulfate. Dr. Abernathy responded to
Page 24

this proposal by saying that adding sulfate to infant formula poses an ethical problem. The

study would only be acceptable to CDC’s Institutional Review Board (IRB) if women

planning to use tap water to mix infant formula for their newborn infants could be identified in

geographic areas with varying levels of sulfate naturally occurring in the tap water. Diane

Burkom, from Battelle, added that even trying to influence a mother to use a certain brand of

formula that is naturally high in sulfate would be ethically questionable. Also, in the rural

areas where the sulfate levels are high, most women were already provided with free infant

formula by WIC clinics, leaving little with which to entice the mothers. Dr Cole pointed out

that with a large study sample, some diarrhea will inevitably occur that is unrelated to the

study, but which might be attributed to the study.

Dr. Cassidy asked Dr. Backer how long the adult study lasted. Dr. Backer responded

that it lasted six days, with exposure for three days, in an effort to mimic the effect of transient

exposure.

Dr. Cole commented that, in Europe, mineral water (containing up to 250 mg/L

sulfate) is considered soothing, indicating that there is a public perception that small amounts

of sulfate may be beneficial and that this perception may be supported by the results from the

adult study (the lower frequency diarrhea among study participants who consumed water

containing 250 mg/L sulfate compared to the group who consumed plain bottled water. 

However, as Ms. Tsuji mentioned, the 250 mg/L exposure group did have a small sample size

(n = 10), and the differences in diarrhea frequency between the two groups was not

statistically significant.

Dr. Gomez asked if microbial analysis was performed on the bottled water used in the

adult study. Dr. Backer indicated that she received a full report of the chemical and microbial

analyses done on the lots of water used for the adult study. Dr. Abernathy stated that the

American Academy of Pediatrics has guidelines for sulfate levels in drinking water because it

has not seen a problem with sulfate ingestion.

Dorothy Wombly, from EPA Region 5, said that most mothers are told not to use tap

water for their infants or to boil it before use. Diane Burkom made the point that boiling

water for the amount recommended by formula manufacturers (1 minute) would have no

effect on the sulfate concentration. Dr. Backer said that people in the study sites were using

water from many sources, including kiosks that provided filtered water (from public water

systems). Bonita Johnson, from EPA Region 4, asked if the types of food people eat have an

effect on diarrhea. Dr. Backer responded that some types of food could have an effect, but

that they did not ask about food consumption in the study.
Page 25

Discussion of Key Issues

Dr. Shy introduced the issues to be discussed by the participants. He stated that the

goal of the workshop was not to reach a consensus, and that the discussion should include all

points of view. The purpose of the workshop was to discuss the scientific evidence regarding

human health effects from exposure to sulfate in drinking water and whether there is sufficient

scientific evidence of a dose-response.

Issue 1 Do reported studies suggest that a certain sulfate level would not be

likely to cause adverse effects (e.g., diarrhea in infants and travelers)?

Existing data do not identify the level of sulfate in drinking water that 

would be unlikely to cause adverse human health effects. The panel

members noted that the available published literature included reports

that piglets in experimental feeding trials and some people experience a

laxative effect when consuming diets (piglets) or tap water (humans)

containing from 1,000 to 1,200 mg/L of sulfate (as sodium sulfate). 

However, none of the studies found an increase in diarrhea,

dehydration, or weight loss.

Dr. Abernathy clarified that EPA wanted to base any possible sulfate regulation on

people who had no specific diseases or underlying conditions. Dr. Cole asked whether this

category of people would be separate from the category including infants, elderly, and

travelers. Dr. Abernathy said that EPA wants to focus on infants and travelers, and that

people who are taking certain medications or have certain diseases would be considered a

separate category. Dr. Cassidy stated that it makes a difference whether the exposure is to

magnesium or sodium sulfate, and asked if either of these salts had an odor. Dr. Abernathy

responded that the regulation, if one were developed, would likely be written for total sulfate

level, and would be based on EPA’s current interpretation of the statute (SDWA).

Dr. Shy began the discussion by looking at the Heizer et al. (1997) study on the

intestinal effects of sulfate in drinking water on normal human subjects. He mentioned that, in

the dose-response study, the only effect was decreased transit (mouth-to-anus) time. In the

single dose study, 1,200 mg/L caused a significant, but mild, increase in mean stool mass. Dr.

Shy said that this study is the most important when considering effects on normal adults. Dr.

Morris commented that there is no indication from either the literature or the new data 

presented at the workshop that 500 mg/L is associated with any toxicity. Dr. Shy asked again

about the findings regarding 1,200 mg/L in the Heizer et al. (1997) study. Dr. Cassidy

responded that the level seems to be mildly cathartic but not toxic. Dr. Abernathy said that it

was important to note that the study only had 10 subjects, so it would be difficult to make a

definitive statement based on such a limited study.

Dr. Cole reiterated Dr. Cassidy’s point that, in adults with no other health issues, 500

mg/L seems to be a safe level to ingest in drinking water. Dr. Morris echoed this point by

stating that 500 mg/L is shown to be safe in all studies. Dr. Shy asked if the findings in the

Chien et al. (1968) paper were consistent with the other studies in reporting that exposure to

drinking water containing 500 mg/L sulfate had no effect. Dr. Morris noted that in the Chien
Page 26

et al. (1968) study, the sulfate levels that caused diarrhea in the three infants were 630, 720,

and 1,150 mg/L. Dr. Abernathy pointed out that case reports, such as Chien et al. (1968), are

notoriously difficult to interpret. He observed that there were many uncontrolled variables in

that study, such as the osmolarity of the infant formula and the concentrating effect of boiling

the water. Dr. Cole added that infant formula in Canada in 1968 was not controlled at all. 

Even if the formula was dry cows’ milk, cows in that area could have ingested high levels of

sulfate from their drinking water.

Dr. Shy then asked the panel to consider table of results from the study by Moore

(1952), and asked, if they could say there was no laxative effect at different levels of sulfate. 

Dr. Cole said that the Moore (1952) study was a bivariate analysis, and that it was possible

that, if one conducted a multivariate analysis of the data (considering, for example, the

relationship of iron in some of the waters), there might be different results. Dr. Abernathy

said that he was not able to get the original data from that study to do a multivariate analysis. 

In response to Dr. Cole’s mention of iron as a possible variable in a multivariate analysis, Dr.

Cassidy added that iron causes a constipation effect, not a laxative effect. Dr. Gomez pointed

out that the Moore (1952) paper does not look at how persistent the effects were. Dr.

Abernathy also added that it was a questionnaire with subjective answers to the question

about diarrhea.

Dr. Shy cautioned participants to remember that they were trying to determine the

level of sulfate at which there is no human health effect. Irene Dooley reiterated that the

results from the studies conducted by CDC and EPA did not find a dose-response association

between exposure to sulfate in drinking water and diarrhea; therefore, the literature and this

workshop will be key sources of information when the agency makes a regulatory

determination. Adding to this clarification, Dr. Abernathy said that the workshop panelists

do not have to agree on a definitive value. The EPA would like to know whether anyone

would be comfortable saying that “at X mg/L of sulfate in drinking water a healthy human is

unlikely to have an adverse health effect, but the likelihood of experiencing an adverse health

effect may increase with increasing sulfate levels.”

Dr. Backer asked if the panelists, in defining the health outcome, are looking for a

laxative effect or diarrhea specifically. She pointed out that the distinction is not made clear in

the different studies. Dr. Cassidy clarified that a laxative effect can be beneficial, but constant

diarrhea can cause problems. Dr. Cassidy stated that clinical diarrhea must be chronic to be

considered a problem for an individual. Dr. Abernathy said a doctor told him that

gastrointestinal distress lasting a week is not a problem for a healthy tourist. Dr. Cole said

that diarrhea can be defined as 1) what a mother perceives as diarrhea, or 2) a situation that

actually warrants an emergency room visit for intervention because of dehydration, based on

stool volume and frequency. He noted that since the American Pediatric Association issues

nothing about sulfate, it doesn’t perceive a correlation between sulfate and diarrhea. 

Dr. Shy pointed out that Moore (1952) looked at a “laxative effect,” which is not

necessarily an adverse human health effect. Dr. Morris suggested that we can take 0-200

mg/L as a baseline. At 500-1,000 mg/L there is only a 10 percent increase in laxative effect,

and at 1,000 mg/L 62% of respondents report experiencing a laxative effect. 
Page 27

Dr. Shy brought the discussion back to the Heizer et al. (1997) study. In this study,

six people drank plain water (containing no added sulfate) for six days, followed by six more

days in which they drank water containing 1,200 mg/L added sulfate. Study participants did

not report having diarrhea (no increase in stool frequency or consistency), but did report an

increase in stool bulk. This study was controlled (although small) and did not show adverse

health effects in adults from exposure to sulfate in drinking water. The second study reported

by Heizer et al. (1997) involved a gradual increase in sulfate level. There were no reported

health effects from this exposure. Dr. Morris noted that the Heizer et al. (1997) study used

sodium sulfate. Dr. Gomez stated that, in his study of baby pigs exposed to 1,200 mg/L

sulfate (as sodium sulfate), the pigs did not get diarrhea.

Dr. Shy then raised the question of special populations, such as neonates. He

reiterated that the Esteban et al. (1997) study included infants (6.5 to 30 months of age), but

found no association between the level of sulfate exposure and diarrhea reported by the

mothers. Dr. Cassidy pointed out that the Chien et al. (1968) study involved only three

infants. Dr. Shy repeated that we do not know the total amount of sulfate (including formula

and tap water) that the infants received in the Chien et al. (1968) report. They received at

least 630 mg/L, but the amount could have been higher. Dr. Cassidy said that Chien et al.

(1968) proposed 400 mg/L as a tentative acceptable level for infants. She added that there is

no evidence in the literature that sulfate causes problems for the elderly. 

Bob Benson, from EPA Region 8, referring to Dr. Cole’s comment that water with

sulfate levels of $ 1,000 mg/L are hyper-osmolar, asked at what point the osmotic pressure in

the lumen would equal the osmotic pressure in the intercellular fluid. Dr. Cole responded

that, for sodium sulfate, the concentration would be close to 40,000 Fosmoles of sulfate. The

study by Gomez et al. (1995) shows that even though sulfate anions are not enough to draw

intracellular fluid into the lumen, sulfate interaction with the cellular structure affects the

transfer of water. Also, there is some biological evidence to suggest that sulfate does interact

to change cellular physiology in the gut. However, the Gomez et al. (1995) study showed

that the diarrhea observed in the piglets is not purely an osmotic diarrhea because that would

be expected produce weight loss and dehydration, and the piglets did not experience either.

Dr. Cassidy reported that there is also a physiological mechanism that balances the

effects of changes in osmolarity and maintains ion and water transport across the lumen. Even

with hyper-osmolar diarrhea, the body eventually will adjust the osmolarity of the lumen to

balance water absorption and loss.

Issue #2 Does the literature support acclimatization or adaptation (what process

and time frame does it take)?

Based on biologic plausibility and anecdotal reports, evidence indicates

that people acclimate to the presence of sulfate in drinking water. In

addition, serum sulfate levels are high (compared to adults) in human

fetuses and neonates (to support rapid growth and development). 

However, data describing acclimation and the changes in sulfate

metabolism during growth and development are limited.
Page 28

Dr. Cassidy responded that there is very little information on acclimatization, but,

based on pathogenic responses, evidence indicates that sulfate acclimatization would probably

occur within 3-4 cell cycles, over the course of one to two weeks. Dr. Cole indicated that his

opinion, based on kidney changes, Gomez’s study, clinical results, and anecdotal evidences, is

that acclimation is a theoretically possible biologic process. Dr Cole suggested, however, that

the evidence that acclimation occurs is not fully convincing. Dr. Gomez said that in his

relatively long, 18-day study, the piglets did seem to acclimate to sulfate.

Dr. Shy asked the participants to consider the issue of travelers versus residents and

Dr. Morris asked if EPA would consider setting levels for all people living in an area or just

for infants starting on formula and travelers? Dr. Abernathy mentioned that EPA has

considered, in the previous proposal, posting signs for travelers. He added that providing

bottled water for infants in certain areas is also an option.

Ms. Tsuji asked if neonates acclimate faster because they are growing. She also asked

if the data presented by Dr. Cole regarding high sulfate levels in amniotic fluid suggested that

infants suffer fewer adverse health effects from exposure to high levels of sulfate because they

acclimate more quickly. Dr. Cole responded that both intra-cellular sulfate and intervascular

sulfate are elevated before birth and during some period after birth to support growth and

development. But the infant gastrointestinal tract is somewhat more permeable to salts and is

more sensitive than that of an adult. If powdered milk (which has high osmolarity) is pushing

the infant gastrointestinal tract to its limit, high levels of sulfate from another source (such as

tap water) could cause diarrhea. Dr. Cassidy added that the configuration and shape of the

infant’s intestinal cells depend on the diet. Dr. Morris stated that sulfate transport

mechanisms develop over time, and that the process has not been studied. Bat (1969) found

that, in adult rats, transport and absorption occurred in the ileum. Neonatal rats had a

different distribution of sulfate in tissues, suggesting changes in the mechanisms of sulfate

absorption during different stages of development.

Bill Hiatt, from BASF Corporation, suggested that a developmental effect would

justify a higher level of concern for establishing a primary drinking water standard than would

a transitory effect among travelers. Dr. Cole noted that people may be likely to protect their

infants by using bottled water.

Issue #3 Can an infant study be done for dose-response anywhere in the U.S. or

Canada?

The difficulty in locating a population of women feeding their infants

formula mixed with unfiltered tap water containing high levels of

sulfate hinders the completion of an infant study of the dose-response to

sulfate exposure. A study using neonatal pigs could assess a dose

response for both magnesium and sodium sulfates.

Dr. Backer began by stating her opinion, based on recruitment efforts for the study she

attempted to conduct, that it is not possible to do a population-based study in the United

States that includes infants naturally exposed to varying levels of sulfate from tap water

provided by public water systems. Dr. Cassidy said that such a study could be done only as an
Page 29

animal study, and that piglets are the best model to use. She added that such a study could

include intestinal biopsies to establish the mechanism by which sulfate exerts its effects. She

also suggested looking at other parameters as well, such as renal function.

Irene Dooley said that EPA traditionally uses a safety factor of 10 for transfer of

animal to human results, which, for the Gomez et al. (1995) study, would suggest limiting

levels of sulfate to 160-220 mg/L. Dr. Cole responded that, while there perhaps should be a

factor, in this case he does not think a factor of 10 makes sense because there is no

biotransformation (e.g. activation) of the compound. Mr. Benson asked panelists if they agree

that a safety factor of 10 was not needed when extrapolating from piglets to humans. Dr.

Cassidy said that researchers do not use pigs often because they are very expensive, but they

are much better models for human intestinal physiology than other animals such as rodents

(i.e., studies have shown that the tissue in the gut of piglets and infant humans is very similar).

Dr. Abernathy explained that FDA, in 1954, derived a safety factor of 100 for “noobserved effect levels” (NOEL) of animal studies. Since that time, the safety factor has been

split into two 10-fold multipliers (a 10-fold safety factor when extrapolating from normal to

sensitive humans and a 10-fold safety factor when extrapolating from animals to humans). 

Empirical data compiled by Dourson and Stara (1983) has shown that the variation among

various factors, e.g., subchronic to chronic effects, could often be accounted for by using a 3-

fold factor, indicating that the usual 10-fold factors are sufficient. The World Health

Organization referred to these factors an acceptable daily intake (ADI) and safety factor (SF),

but EPA now uses the terms Reference Dose (RfD) and Uncertainty Factors (UF). However,

depending on the completeness of the data base, the 10-fold UF does not have to be

employed. For example, the data base on nitrate/nitrite and fluoride contained a lot of data on

human exposures, and EPA used an UF of one.

Dr. Cole stated that results using the piglet model of human intestinal physiology

would require a safety factor less of than 10. He mentioned that Stephanie Atkinson studied

the tolerance of phosphate in infant formula by neonates, particularly low-birth weight and

premature infants. Data on the effects in neonatal piglets was directly comparable to that on

the effects in human infants (i.e., no safety factors were applied). Dr. Cole suggested a safety

factor between 1.5 and 2 for neonatal piglets and human infants.

Dr. Gomez added that an important component of this kind of research is that work

with baby pigs is done in departments of animal veterinary sciences, but should be done in

connection with medical schools (especially by pediatricians).

Dr. Shy summarized the panelists’ discussion, including the need for a dose-response

study using an animal model and the determination of an appropriate safety factor for

extrapolation of results from animals to humans. Dr. Cassidy added that it would be

important to also look at magnesium sulfate, as well as sodium sulfate.

Dr. Shy said that we can assume that other countries have areas where the sulfate

levels in drinking water are high, but asked if an infant study be ethically acceptable. Dr.

Cassidy repeated Dr. Cole’s observation that said it would be unlikely that researchers could

identify an exposed infant population, partly because if infants get diarrhea, mothers will find
Page 30

an alternate source of water. Dr. Shy wondered whether it would be possible to identify

exposed infants if a study were to start with new mothers. Dr. Cassidy brought up the

possibility of doing a pediatric survey in Europe where sulfate levels are high. Dr. Cole

cautioned that those surveys cannot always eliminate the effects of other constituents of

drinking water. He suggested that such a survey could be done in the developing world, but

that doing so may be logistically difficult. He added that women everywhere use the cleanest

water for their infants. Diane Burkom, from Battelle, said that in considering other possible

sources of the diarrhea, the researchers limited their study to public water supplies because

private wells have a higher risk for bacterial contamination than public water supplies do. Dr.

Cassidy added that pathologic bacterial diarrhea would be an issue in the developing world.

Dr. Shy asked about conducting a randomized trial in a place that had a natural sulfate

level of 1,000 mg/L and no alternative water sources. Study participants could be provided

with water containing either 0 or 500 mg/L added sulfate, and the health outcome would be

diarrhea. He asked panelists whether such a trial would be ethically acceptable, pointing out

that if the trial is conducted at a site which has a normal sulfate level of 1,000 mg/L, and no

other water supply choices, the study would provide study subjects with water that contained

less sulfate than they normally would be exposed to. Dr. Gomez said that Peru uses

rainwater, which is easy to collect, as a source of drinking water and that hygiene and viruses

are more difficult to control in a developing country. Dr. Cole said a study would be

theoretically possible, but that an Institutional Review Board (IRB) would not sanction the

protocol, since the researchers would, after determining that the high levels of sulfate caused

illness, possibly leave the community and not provide a permanent source of improved water. 

Dr. Cassidy added that she did not know of a population in which diarrhea is not

bacteriologic.

Dr. Morris said that maybe one could do such a study in the U.S. or Canada, but that

there is a need for more animal studies. Dr. Shy said a randomized trial would take care of

the uncertainty of the baseline diarrhea level, and Dr. Backer replied that she could not locate

1000 babies in the U.S. to do such a study. Dr. Gomez asked if it is possible to lower sulfate

levels in areas where it is high. Irene Dooley responded that treatments such as reverse

osmosis and ion exchange are possible, but it could be costly to require that all public water

systems meet a level of 500 mg/L. Michael Baker, from the South Dakota Department of

Environment and Natural Resources, Drinking Water Program, said that South Dakota did an

analysis of the water systems that exceed 500 mg/L and estimated that it would cost $60

million to lower the sulfate levels the 110 systems in the state to 500 mg/L. The average

household cost for public water in South Dakota is approximately $9 per month for water, but

would increase to approximately $28 per month to compensate for the cost of treatment to

remove sulfate (reverse osmosis and ion exchange). South Dakota systems would likely chose

to convert to using surface water sources for drinking water rather than to remove sulfate

from ground water. Removing sulfate from drinking water would also be a financial burden

on the water treatment facilities. All but 27 systems with $ 500 mg/L sulfate are in lowincome areas. The rest serve cloistered religious communities. Dr. Cassidy asked if there are

public health reports of increased physician visits in areas with high sulfate? Mr. Baker said

that his department did a non-scientific polling of 27 pediatricians and several family
Page 31

practitioners, and none reported ever treating diarrhea caused by exposure to sulfate.

Dr. Abernathy stated that the 1977 National Academy of Sciences (NAS) report

concluded that there are no adverse human health effects associated with exposure to 500

mg/L sulfate or less, but EPA would need to study the data used to support that conclusion.

Dr. Cole asked Mr. Baker if there is a relationship between sulfate content and the

population’s use of water for cooking, drinking, coffee, etc. Mr. Baker that sulfates come

from wells that are dug into the geologic formation called the Dakota Formation, and there

has always been an objection to the taste of this water; it makes terrible coffee. The levels of

dissolved solids are also high; however, before 1965, people used the water because they had

no choice. Using Rural Water Assistance grants, 39 systems switched to surface water for

aesthetic reasons. Now people can choose to purchase bottled water or install reverse

osmosis filtration systems in their homes. When Mr. Baker looked for health effects from

drinking water that contained high levels of sulfate, he found only one physician’s assistant

who treated three youths from a combine crew who reported diarrhea after drinking

community water that contained 1,200 mg/L sulfate. However, these individuals were

drinking very large quantities of water (5 to 10 liters per day per person). Dr. Backer added

that in their infants sulfate study areas, people also used filters and bottled water for aesthetic

purposes.

Dr. Shy repeated that Dr. Abernathy’s statement that by 2001 EPA must decide

whether or not to regulate sulfate, and asked whether EPA can regulate substances for

reasons other than health risk.. Dr. Abernathy said that EPA regulations can be based only on

the need to reduce the frequency of adverse health effects, but that States can issue

regulations for aesthetic reasons, such as taste.

Dr. Shy asked if there exists adequate scientific evidence that there are adverse health

effects associated with high levels of sulfate in drinking water. Dr. Abernathy asked whether

the workshop might consider making this question Issue 4. Dr. Backer wanted to know what

EPA’s non-regulatory options are. Irene Dooley responded that if EPA decides not to

regulate the levels of sulfate in drinking water, EPA could keep the current secondary

guideline of 250 mg/L, which is based on taste and odor. EPA can also put out health

advisories or consumer advisories in localized areas.
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Issue #4 Is there adequate scientific evidence that there are adverse health effects

from sulfate in drinking water to support regulation?

While there is not enough scientific evidence on which to base a

regulation, a health advisory in places that have sulfate levels of 500

mg/L or higher would acknowledge the needs of sensitive

subpopulations.

Dr. Shy briefly summarized the studies by Moore (1952), Heizer et al. (1997),

Esteban et al. (1997), and Gomez et al. (1995). The Moore (1952) study found a laxative

effect in water with high levels of sulfate. The Heizer et al. (1997) study found that adults

who ingested 1,200 mg/L sulfate had no diarrhea but reported increased stool bulk. Esteban

et al. (1997) found no increases in diarrhea in infants who ingested water containing up to

1350 mg/L sulfate, but the study had a small sample size and thus limited power to detect an

association. Gomez et al. (1995), found no effect in the frequency of diarrhea in piglets fed a

diet that contained 1,200 mg/L sulfate. Fifty percent of the piglets given 1,600-1,800 mg/L

sulfate had; however, the diarrhea did not affect weight of the piglets.

Dr. Cassidy wanted to know the range of sulfate levels currently found in tap water. 

Dr. Abernathy said that surveys indicated about 3% of the tap water in the U.S. exceeds 250

mg/L, and levels up to 770 to 1,000 mg/L have been measured. For the 1994 proposal to

regulate sulfate, EPA estimated about 1965 public water supplies would exceed 500 mg/L. 

Mr. Baker said that community systems in South Dakota may have sulfate levels as high as

1,350 mg/L, and some private wells are higher (up to 2,000 mg/L sulfate). Dr. Morris stated

that healthy adults would have no problem with 1500 mg/L. However, she cautioned that

mothers of infants, the elderly, and people with certain health problems may need to be

cautious when using for drinking water containing high levels of sulfate.

Dr. Abernathy informed the panelists that even if EPA decides that scientific evidence

cannot support issuing a federal regulation, states may still choose to regulate the amount of

sulfate in drinking water. Kim Harris, from EPA Region 5, told participants that if EPA

decides not to regulate sulfate, the potential health risks for susceptible populations will still

be addressed (e.g., with health advisories similar to those created for cryptosporidium). 

Dr. Cassidy asked if there are surveillance or reporting data describing sulfate levels in

public water systems. Irene Dooley answered that there is a requirement to report sulfate

levels based on the unregulated contaminant monitoring requirements of 1992. EPA is in the

process of analyzing this data from the states. Dr. Cassidy asked if this data contains reports

of diarrhea or other adverse health effects. Dr. Backer responded that CDC and EPA are

developing a study to establish a national baseline for gastrointestinal illness. One challenge

associated with collecting this type of data is that when people have diarrhea, they usually go

to the drug store, not a doctor. Dr. Backer pointed out that monitoring the purchases of

over-the-counter medications in geographically defined areas can be an alternative approach

for evaluating localized gastrointestinal distress. 

Dr. Shy directly asked the panelists if there is an answer to Issue 4. Dr. Cole answered

that there is nothing in the literature regarding effects in healthy adults from exposure to high
Page 33

levels of sulfate in drinking water, but that he believes that a health advisory would be in the

best interest for infants. He also said that an advisory for elderly people and for travelers

would be appropriate. Dr. Cassidy agreed with Dr. Cole that there is not enough scientific

evidence to indicate that exposure to high levels of sulfate causes adverse human health

effects.

Dr. Abernathy stated that EPA needs to specify a safe level, even in a health advisory. 

He suggested that EPA could, for example, set a health advisory at 500 mg/L.

Dr. Morris answered that there is not enough evidence to support a health-based

regulation for sulfate levels for healthy adults. The populations of concern are infants, the

elderly, and people with health problems. Dr. Morris said that, in her opinion, information

from the available literature is that, 500 mg/L may be protective, but additional studies need to

be done to identify the appropriate concentration. 

Dr. Gomez noted that special attention should be given to states that have a potential

problem. Ms. Tsuji added that it appears that while 3% of 200 million (6 million), people are

exposed, it is hard to find them, and we cannot be sure what else is in their water, so it may be

better to manage through pediatricians, the health department, and WIC clinics, and on an

individual level instead of trying to regulate at a national level. She noted that sulfate does

not cause irreversible damage, and that regulating other water contaminants is more urgent. 

Mr. Baker gave his opinion that he is not in favor of regulating sulfate at this point, because

people are resolving the problem.

Dr. Shy summarized by saying no one study can provide a dose-response relationship

for sulfate, and that other studies are necessary. The existing literature supports issuing health

advisories, especially for infants, that sulfate levels > 500 mg/L may have negative health

effects. Dr. Cole reiterated his belief that it would not be possible to conduct an infant study

in the U.S. or Canada and that he does not believe the literature indicates acclimitization. 

Krishna Parameswaran stated that his company has three mining sites in the west in areas with

sulfates in the drinking water, and the workers there do not experience diarrhea. 
Page 34

Literature Cited

Bauer JH. Oral administration of radioactive sulfate to measure extracellular fluid space in

man. J Appl Physiol. 1976;40(No.4):648-650.

Chien L, Robertson H, Gerrard JW. Infantile gastroenteritis due to water with high sulfate

content. Can Med Assoc J. 1968; 99: 102-104.

Cocchetto DM, Levy G. Absorption of orally administered sodium sulfate in humans. J

Pharm Sci. 1981;7(No. 3):331-333.

Dourson ML, Stara JF. Regulatory history and experimental support of uncertainty (safety)

factors. Regul Toxicol Pharmacol. 1983;3:224-238.

Esteban, E, Rubin CH, McGeehin MA, Flanders WD, Baker MJ, and Sinks TH. Evaluation of

infant diarrhea associated with elevated levels of sulfate in drinking water: a case-control

investigation in South Dakota. Int J Occup Med Environ Health. 1997; 3(3): 171-176.

Freeman RM, Richards CJ. Studies on sulfate in end-stage renal disease. Kidney Int

1979;15(2):167-75.

Galinsky RE, Levy G. Dose- and time-dependent elimination of acetaminophen in rats:

pharmacokinetic implications of cosubstrate depletion. J Pharmacol Exp Ther 1981;219(No.

1):14-20.

Gomez GG, Sandler RS, Seal, E Jr. High levels of inorganic sulfate cause diarrhea in neonatal

piglets. J Nutr. 1995;125: 2325-2332.

Heizer WD, Sandler RS, Seal E Jr, Murray SC, Busby MG, Schliebe BG, and Pusek SN. 

Intestinal effects of sulfate in drinking water on normal human subjects. Dig Dis Sci 42(5):

1055-1061.

Moore EW. Physiological effects of the consumption of saline drinking water. A progress

report to the 16th meeting of the Subcommittee on Sanitary Engineering and Environment. 

Appendix B. January 1952. Washington, DC: National Academy of Sciences. 1952.
Page 35

Morris ME, Levy G. Absorption of sulfate from orally administered magnesium sulfate in

man. J Toxicol Clin Toxicol. 1983;20(2): 107-114.

Peña DR, Neiberger RE. Renal brush border sodium-sulfate cotransport in guinea pig: effect

of age and diet. Pediatr Nephrol 1997;11(No. 6):724-727

Peterson NL. Sulfates in drinking water. Official Bulletin: North Dakota Water and Sewage

Works Conference 1951;18(10&11): 6-11.
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Appendix A: Workshop Agenda

The Health Effects from Exposure to Sulfate

in Drinking Water Workshop

Agenda

8:30-8:50 Registration

8:50-9:00 Welcome & Purpose of Meeting

 Michael A. McGeehin, Ph.D., M.S.P.H., NCEH, CDC

9:00-9:10 Introduction of Workshop Facilitator

 Carl Shy, MD, University of North Carolina at Chapel Hill

9:10-9:25 EPA’s Scientific Work, Safe Drinking Water Statute & Regulatory

Background 

 Charles Abernathy, Ph.D., Office of Science and Technology, EPA 

9:25-9:40 Sulfate Biochemistry

 David Cole, MD, University of Toronto

9:40-9:55 Intestinal Physiology

 Marie Cassidy, Ph.D., D.S.C., George Washington University

9:59:55-10:10 Effects of High Sulfate Exposures

 Marilyn Morris, Ph.D., School of Pharmacy, SUNY-Buffalo, NY.

10:10-10:25 BREAK

10:25-10:55 Health Effects from Exposure to High Levels of Sulfate in Drinking Water
Page 37

 Lorraine Backer, Ph.D., M.P.H., NCEH,

10:55-11:10 Animal Studies

 Guillermo Gomez, Ph.D., North Carolina State University

11:10-11:15 Presentation of Issues

 Carl Shy, M.D., M.S.P.H., University of North Carolina

11:15-12:00 Facilitated Panel Discussion of Issue 1

 Carl Shy, M.D., M.S.P.H., University of North Carolina

12:00-1:00 LUNCH

1:00-1:45 Facilitated Panel Discussion of Issue 2

 Carl Shy, M.D., M.S.P.H., University of North Carolina

1:45-3:00 Facilitated Panel Discussion of Issue 3

 Carl Shy, M.D., M.S.P.H., University of North Carolina

3:00-3:15 BREAK

3:15-3:45 Facilitated Panel Discussion of Issue 4

 Carl Shy, M.D., M.S.P.H., University of North Carolina

3:45-4:15 Facilitated Discussion: comments from the public

 Carl Shy, M.D., M.S.P.H., University of North Carolina

4:15-4:30 Next Steps and Adjourn

 Carl Shy, M.D., M.S.P.H., University of North Carolina
Page 38

Appendix B: List of Participants

Health Effects from Exposure to High Levels of Sulfate in Drinking Water Workshop

September 28, 1998

Atlanta, Georgia

Facilitator:

Carl Shy, M.D., Dr.P.H.

University of North Carolina at Chapel Hill

School of Public Health

Department of Epidemiology

CB #7400, McGavran-Greenberg Hall

Chapel Hill, NC 27599-7400

(919) 966-7446

(919) 966-2089 (fax)

E-mail: carl_shy@unc.edu

Speakers:

Charles Abernathy, Ph.D.

US EPA, Office of Water

401 M Street, SW

Washington, DC 20460

(202) 260-5374

(202) 260-1036 (fax)

E-mail: abernathy.charles@epa.gov

Lorraine C. Backer, Ph.D., MPH
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Centers for Disease Control and Prevention

National Center for Environmental Health

Health Studies Branch

4770 Buford Highway NEMS F-46

Atlanta, GA 30341

770-488-7603

770-488-3506 (fax)

E-mail: lfb9@cdc.gov

Marie Cassidy, Ph.D., DSC

George Washington University Medical Center

Department of Physiology and Experimental Medicine

Ross Hall

2300 I Street, NW

Washington, DC 20037

(202) 994-3552

(202) 994-3553 (fax)

David Cole, MD

University of Toronto

Department of Laboratory Medicine and Pathobiology

Room 415, Banting Building

100 College Street

Toronto, Ontario M5G 1L5, Canada

(416) 978-6720

(416) 978-5650 (fax)

E-Mail: davidec.cole@utoronto.ca

Guillermo G. Gomez, Ph.D.

North Carolina State University

Environmental Science
Page 40

Box 7626; Grinnells Lab

Raleigh, NC 27695-7626

(919) 515-2019

(919) 515-7780 (fax)

E-Mail: guillermo_gomez@ncsu.edu

Michael A. McGeehin, Ph.D., M.S.P.H.

Chief, Health Studies Branch

Centers for Disease Control and Prevention

National Center for Environmental Health

4770 Buford Highway NE; MS F-46

Atlanta, GA 30341-3724

770-488-7351

770-488-3506 (fax)

E-mail: mam7@cdc.gov

Marilyn Morris, Ph.D.

SUNY - Buffalo

Department of Pharmaceuticals

517 Hochstetter Hall

Amherst, NY 14260

(716) 645-2440 x 230

(716) 645-3693 (fax)

Other participants:

Michael Baker

South Dakota Department of Environment and Natural Resources

Drinking Water Program

Joe Foss Building

523 East Capital Avenue
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Pierre, SD 57501 

(605) 773-3779 (or 3754)

(605) 773-5286 (fax)

Robert Benson

EPA Region 8 (8P-W-MS)

999 18th Street Suite 500

Denver, CO 80202

(303) 312-7070

(303) 312-6131 (fax)

Email: benson.bob@epamail.epa.gov

Diane Burkom

Battelle Memorial Institute

Centers for Public Health Research and Evaluation

6115 Falls Road

Baltimore, MD

(410) 372-2702

(410) 377-6802 (fax)

E-mail: burkom@battelle.org

Irene Dooley

US EPA (Mailcode 4607)

Office of Ground Water and Drinking Water

401 M St. SW

Washington, D.C. 21046

(202) 260-9531

(202) 260-3762 (fax)

E-mail: dooley.irene@epamail.epa.gov

Dale Froneberger
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US EPA, Drinking Water Section

61 Forsyth St.

Atlanta, GA 30303

(404) 562-9446

(404) 562-9439 (fax)

E-mail: froneberger.dale@epa.mail.epa.gov

Kenneth Goodman, M.A.

Battelle Memorial Institute

Centers for Public Health Research and Evaluation

2101 Wilson Blvd., Suite 800

Arlington, VA 22201

(703) 875-2101

(703) 527-5640 (fax)

E-mail: goodmanj@battelle.org

Bob Grissom

Centers for Disease Control and Prevention

ATSDR

1600 Clifton Road

Mail Stop E-32

Atlanta, GA 30333

(404) 639-0661

(404) 639-0655 (fax)

E-mail: reg3@cdc.gov

Lisa Harbin

Battelle Memorial Institute

Centers for Public Health Research and Evaluation

6115 Falls Road

Baltimore, MD
Page 43

(410) 372-2749

(410) 377-6802 (fax)

E-mail: harbin@battelle.org

Kimberly Harris

EPA Region 5

77 West Jackson (WD15J)

Chicago IL 60604

312-886-4239

312-886-6171 (fax)

Bill Hiatt

BASF Corporation

Sand Hill Road

Enka, NC 28728

828-667-7519

828-667-7718 (fax)

E-mail: hiattw@basf.com

Bonita Johnson

EPA Region 4

61 Forsyth Street, SW

Atlanta GA 30303-3104

404-562-9442

404-562-9439 (Fax)

E-mail: johnson.bonita@epamail.epa.gov
Page 44

Luke Naeher

Centers for Disease Control and Prevention

National Center for Environmental Health

Health Studies Branch

4770 Buford Highway NE; MS F-46

Atlanta, GA 30341-3724

(770) 488-7350

(770) 488-3506 (fax)

E-mail: lcn6@cdc.gov

Krishna Parameswaran

Asarco Incorporated

180 Maiden Lane

New York, NY 10038

(212) 510-2121

(212) 510-1951 (fax)

E-mail: kparameswaran@asarco.com

Stefano Terzi

San Pellegrino

Quality Assurance Manager

Localitá Ruspino

24016 San Pellegrino Termo

Milan, Italy

3334523256

3334523230 (fax)

E-mail: terzi@spm.it

Joyce Tsuji

Foster Wheeler Environmental Corp.

17319—159th Ave., SE
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Renton, WA 98058

425-271-6215

425-271-6116 (fax)

E-mail: jtsuji@fwenc.com

Dorothy Wormbly

EPA Region 5

77 West Jackson (WD15J)

Chicago IL 60604

312-886-9736

312-886-6171 (fax)

Jennifer Wu

US EPA (Mailcode 4607)

Office of Ground Water and Drinking Water

401 M St. SW

Washington, D.C. 20460

(202) 260-0425

(202) 260-3762 (fax)

E-mail: wu.jennifer@epa.gov

Stenographer:

Jewel Davis

Davis Stenotype Reporting

703 Buchanan St., NE

Washington, DC 20017

(202) 526-1115