Document ID: EPA-HQ-OW-2002-0021-0138
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2003-05-15T04:00Z

Drinking
Water
Advisory:
Consumer
Acceptability
Advice
and
Health
Effects
Analysis
on
Sulfate
Printed
on
Recycled
Paper
Drinking
Water
Advisory:
Consumer
Acceptability
Advice
and
Health
Effects
Analysis
on
Sulfate
U.
S.
Environmental
Protection
Agency
Office
of
Water
(
4304T)
Health
and
Ecological
Criteria
Division
Washington,
DC
20460
www.
epa.
gov/
safewater/
ccl/
pdf/
sulfate.
pdf
EPA
822­
R­
03­
007
February
2003
iii
Sulfate
 
February
2003
FOREWORD
The
Drinking
Water
Advisory
Program,
sponsored
by
the
Health
and
Ecological
Criteria
Division
of
the
Office
of
Science
and
Technology
(
OST),
Office
of
Water
(
OW),
provides
information
on
the
health
and
organoleptic
(
taste,
odor,
etc.)
effects
of
contaminants
in
drinking
water.
The
Drinking
Water
Advisory
documents
are
a
component
of
the
OW
Health
Advisory
Program.
Drinking
Water
Advisories
differ
from
Health
Advisories
because
of
their
focus
on
aesthetic
properties
(
e.
g.,
taste,
odor,
color)
of
drinking
water.
A
Drinking
Water
Advisory
is
prepared
when
contaminants
cause
adverse
taste
and
odor
influences
at
concentrations
lower
than
those
for
adverse
health
effects.

A
Drinking
Water
Advisory
is
not
an
enforceable
standard
for
action.
It
describes
nonregulatory
concentrations
of
the
contaminant
in
water
that
are
expected
to
be
without
adverse
effects
on
both
health
and
aesthetics.
Both
Health
Advisories
and
Drinking
Water
Advisories
serve
as
technical
guidance
to
assist
Federal,
State,
and
local
officials
responsible
for
protecting
public
health
when
emergency
spills
or
contamination
situations
occur.
They
are
not
to
be
construed
as
legally
enforceable
Federal
standards.
They
are
subject
to
change
as
new
information
becomes
available.
This
draft
supersedes
any
previous
draft
advisories
for
this
chemical.

The
Advisory
discusses
the
limitations
of
the
current
database
for
estimating
a
risk
level
for
sulfate
in
drinking
water
and
characterizes
the
hazards
associated
with
exposure.
The
Drinking
Water
Health
Advisory
value
was
developed
by
a
panel
of
experts
through
a
workshop
held
on
September
28,
1998,
and
sponsored
by
the
Centers
for
Disease
Control
(
CDC)
and
the
United
States
Environmental
Protection
Agency
(
U.
S.
EPA).
The
experts
who
participated
in
the
workshop
were:

Charles
Abernathy,
Ph.
D.
­
U.
S.
EPA
David
Cole,
M.
D.,
Ph.
D.
­
University
of
Toronto
Marie
Cassidy,
Ph.
D.
­
George
Washington
University
Marilyn
Morris,
Ph.
D.
­
State
University
of
New
York:
Buffalo
Guillermo
Gomez,
Ph.
D.
­
North
Carolina
State
University
Lorraine
Backer,
Ph.
D.
­
National
Center
for
Environmental
Health
at
CDC
A
workshop
report
was
prepared
that
summarized
the
data
considered
at
the
workshop
and
its
findings.
This
report
was
published
by
EPA
as
Document
Number
815­
R­
99­
002
in
January
1999
(
EPA,
1999b).
The
workshop
report
was
externally
peer
reviewed
by
the
following
scientists
(
EPA,
1999c):

Laurence
L.
Brunton,
Ph.
D.
­
University
of
California
San
Diego
Paul
E.
Brubaker,
Ph.
D.
­
Brubaker
Associates,
New
Jersey.
Michael
L.
Dourson,
Ph.
D.
­
Toxicology
Excellence
for
Risk
Assessment,
Ohio
iv
Sulfate
 
February
2003
CONTENTS
FOREWORD
...............................................................................................................................
iii
ABBREVIATIONS
........................................................................................................................
v
EXECUTIVE
SUMMARY
............................................................................................................
1
1.0
INTRODUCTION
.................................................................................................................
4
2.0
SULFATE
IN
THE
ENVIRONMENT
..................................................................................
4
2.1
Water
.............................................................................................................................
4
2.2
Soil
................................................................................................................................
6
2.3
Air
.................................................................................................................................
6
2.4
Food
...............................................................................................................................
7
2.5
Summary
.......................................................................................................................
7
3.0
CHEMICAL
AND
PHYSICAL
PROPERTIES
....................................................................
7
4.0
TOXICOKINETICS
..............................................................................................................
9
4.1
Absorption
.....................................................................................................................
9
4.2
Distribution
...................................................................................................................
9
4.3
Metabolism
..................................................................................................................
11
4.4
Excretion
.....................................................................................................................
11
5.0
HEALTH
EFFECTS
DATA
................................................................................................
12
5.1
Human
.........................................................................................................................
13
5.1.1
Short­
Term
Exposure
Studies
..............................................................................
13
5.1.2
Long­
Term
Exposure
Studies
..............................................................................
15
5.2
Animal
.........................................................................................................................
16
5.2.1
Short­
Term
Exposure
Studies
................................................................................
16
5.2.2
Long­
Term
Exposure
Studies
................................................................................
17
5.2.3
Reproductive
and
Developmental
Studies
.............................................................
18
5.2.4
Cancer
Studies
.......................................................................................................
18
6.0
ORGANOLEPTIC
PROPERTIES
......................................................................................
19
7.0
CHARACTERIZATION
OF
HAZARD
AND
DOSE­
RESPONSE
...................................
20
7.1
Hazard
Characterization
..............................................................................................
20
7.2
Characterization
of
Organoleptic
Effects
....................................................................
21
7.3
Dose­
Response
Characterization
................................................................................
21
8.0
REFERENCES
....................................................................................................................
24
v
Sulfate
 
February
2003
ABBREVIATIONS
CDC
Centers
for
Disease
Control
and
Prevention
CSF
cerebrospinal
fluid
g
gram
kg
kilogram
L
liter
m3
cubic
meters
mg
milligram
min
minute
mM
millimolar
mmol
millimole
NTP
National
Toxicology
Program
OST
Office
of
Science
and
Technology
OW
Office
of
Water
PAPS
3N­
phosphoadenosine­
5N­
phosphosulfate
ppm
parts
per
million
PWS
public
water
system
RfD
Reference
Dose
SDWA
Safe
Drinking
Water
Act
SDWIS/
FED
Safe
Drinking
Water
Information
System/
Federal
SO
4
2­
sulfate
SMCL
secondary
maximum
contaminant
level
UCM
unregulated
contaminant
monitoring
µ
g
microgram
µ
mol
micromole
1
Sulfate
 
February
2003
EXECUTIVE
SUMMARY
The
EPA
Office
of
Water
is
issuing
this
advisory
to
provide
guidance
to
communities
that
may
be
exposed
to
drinking
water
contaminated
with
high
sulfate
concentrations.
The
advisory
provides
an
analysis
of
the
current
health
hazard
information
and
an
evaluation
of
available
data
on
the
organoleptic
(
i.
e.,
taste
and
odor)
problems
associated
with
sulfate­
contaminated
water,
because
organoleptic
problems
will
affect
consumer
acceptance
of
water
resources.
This
advisory
does
not
recommend
a
Reference
Dose
(
RfD)
because
of
limitations
of
available
data
for
assessing
risks.
However,
the
advisory
does
provide
guidance
on
the
concentrations
above
which
health
and
organoleptic
problems
would
likely
occur.
This
Drinking
Water
Advisory
does
not
mandate
a
standard
for
action;
rather
it
provides
practical
guidelines
for
addressing
sulfate
contamination
problems
and
supersedes
previous
draft
advisories
for
sulfate
Conclusion
and
Recommendation
In
order
to
enhance
consumer
acceptance
of
water
resources,
this
advisory
recommends
reducing
sulfate
concentrations
to
or
below
250
mg/
L,
the
EPA
=
s
Secondary
Maximum
Contaminant
Level
(
SMCL)
for
sulfate.
The
SMCL
is
based
on
taste
considerations.
It
is
not
a
federally
enforceable
regulation,
but
is
intended
as
a
guideline
for
States.
States
may
establish
higher
or
lower
levels
depending
on
the
local
conditions,
such
as
unavailability
of
alternate
source
waters
or
other
compelling
factors,
provided
that
public
health
and
welfare
are
not
adversely
affected.

A
health­
based
advisory
for
acute
effects
(
absence
of
laxative
effects)
of
500
mg
of
sulfate/
L
is
recommended.
This
value
depends
on
the
absence
of
other
osmotically
active
materials
in
drinking
water,
which
could
lower
the
sulfate
level
associated
with
a
laxative
effect.
Where
the
water
contains
high
concentrations
of
total
dissolved
solids
and/
or
other
osmotically
active
ions,
laxative­
like
effects
may
occur
if
the
water
is
mixed
with
concentrated
infant
formula
or
a
powdered
nutritional
supplement.
In
such
situations,
an
alternate
low­
mineral­
content
water
source
is
advised.
Infants
are
more
susceptible
than
adults
to
diarrheal
water
loss
because
of
differences
in
gastrointestinal
structure
and
function.

The
soft
stool
or
diarrhea
that
results
from
sulfate
is
an
osmotic
diarrhea;
that
is,
it
happens
when
the
osmolality
(
number
of
dissolved
particles)
in
the
intestinal
contents
exceeds
that
of
the
body
fluids.
When
this
occurs,
water
is
drawn
from
the
body
fluids
into
the
intestines,
increasing
the
moisture
content
and
volume
of
the
fecal
matter.
Whether
or
not
diarrhea
or
soft
stools
occur
depends
on
the
amount
of
sulfate
and
other
osmotically
active
materials
that
are
present
in
the
intestines;
these
materials
include
magnesium,
sodium,
and
some
sugars.
An
osmotic­
induced
diarrhea
ceases
once
the
osmotically
active
gastrointestinal
contents
are
excreted.
In
the
case
of
sulfate,
adults
appear
to
adapt
within
1
or
2
weeks
and
are
no
longer
affected
by
the
sulfate
in
their
drinking
water
supply.
Infants,
however,
may
be
more
sensitive.

Sulfate
in
the
Environment
Sulfates
are
naturally
occurring
substances
that
are
found
in
minerals,
soil,
and
rocks.
They
are
present
in
ambient
air,
groundwater,
plants,
and
food.
The
principal
commercial
use
of
sulfate
is
in
the
chemical
industry.
Sulfates
are
discharged
into
water
in
industrial
wastes
and
through
atmospheric
deposition.
Sulfate
concentration
in
seawater
is
about
2,700
milligrams
per
liter
2
Sulfate
 
February
2003
(
mg/
L).
It
ranges
from
3
to
30
mg/
L
in
most
freshwater
supplies,
although
much
higher
concentrations
($
1000
mg/
L)
are
found
in
some
geographic
locations.
In
the
United
States,
the
median
concentration
for
a
20­
State
cross­
section
was
24
mg/
L;
the
99th
percentile
value
was
560
mg/
L.
In
general,
food
is
the
principal
source
of
exposure.
However,
in
areas
with
high
sulfate
concentrations,
exposure
from
water
can
exceed
that
from
food.

Studies
of
Sulfate
Effects
Long­
term
and
short­
term
exposure
studies
to
determine
a
hazard
assessment
for
sulfate
are
currently
available
in
humans
and
animals.
The
findings
from
cancer,
noncancer,
and
taste
and
odor
studies
are
discussed
below.

Cancer
Studies.
There
has
been
no
traditional
NTP
oral
cancer
bioassay
for
inorganic
sulfate
as
the
ion
of
interest.
In
an
8­
month
preliminary
study,
no
tumors
were
observed
in
Wistar
rats
after
intramuscular
injection
of
0.7
mg
sodium
sulfate
every
other
day
for
4
weeks.
However,
in
this
study
the
sodium
sulfate
treatment
was
used
as
a
control
against
which
to
evaluate
the
effects
of
nickel
sulfate
and
nickel
hydroxide.
Accordingly,
the
present
database
is
of
limited
value
for
evaluating
the
tumorigenicity
of
sulfate.
After
reviewing
toxicity
data
on
sulfates
food
additives,
the
Select
Committee
of
the
Life
Sciences
Research
Office
concluded
that
there
was
no
evidence
that
sulfuric
acid
or
ammonium,
calcium,
potassium,
and
sodium
sulfates
present
a
hazard
to
the
public
health
when
they
are
used
at
levels
that
are
current
or
that
might
reasonably
be
expected
in
the
future.

Noncancer
Studies.
The
collective
evaluation
of
the
noncancer
data
in
humans
and
animals
suggests
that
acute
exposures
to
sulfate
exert
a
laxative
effect
(
loose
stool)
and
sometimes
diarrhea
(
unusually
frequent
or
unusually
liquid
bowel
movements)
following
acute
exposures
to
high
concentrations.
However,
these
effects
are
not
observed
for
longer
term
exposures.
This
may
be
because
of
acclimation
to
sulfate
over
time.

No
adverse
developmental
effects
were
observed
following
the
administration
of
2,800
mg/
kg/
day
of
sulfate
to
pregnant
ICR/
SIM
mice
on
gestation
days
8
to
12.
No
reproductive
effects
were
observed
following
the
ingestion
of
drinking
water
containing
up
to
5,000
mg/
L
of
sulfates
by
ICR/
SIM
mice
and
3,298
mg/
L
of
sulfates
by
Hampshire
×
Yorkshire
×
Duroc
pigs
.
On
the
basis
of
these
studies,
sulfate
does
not
appear
to
be
a
reproductive
or
a
developmental
toxicant.

Studies
on
Taste
and
Odor.
Few
studies
are
available
that
report
on
the
organoleptic
properties
(
i.
e.,
taste
and
odor)
of
sulfate.
None
of
the
studies
reported
an
odor
threshold;
therefore,
all
of
the
reported
values
are
based
on
taste
thresholds.
It
is
not
possible
to
precisely
identify
a
specific
taste
threshold
for
sulfates
in
drinking
water
because
the
taste
threshold
concentration
varies
among
individuals.
In
addition,
the
associated
cations,
different
water
matrices,
and
temperatures
also
influence
taste.
On
the
basis
of
the
available
data,
no
significant
taste
effects
have
been
found
to
occur
at
sulfate
concentrations
of
about
200
B
300
mg/
L.
3
Sulfate
 
February
2003
Characterization
Summary
The
data
from
short­
term
studies
suggest
that
a
mild
laxative
response
can
occur
at
sulfate
concentrations
greater
than
500
mg/
L,
especially
if
there
are
other
osmotically
active
substances
present
in
the
water.
In
the
absence
of
other
osmotically
active
materials,
the
laxative
effects
are
unlikely
to
be
observed
at
concentrations
up
to
about
1,000
mg/
L
sulfate.
These
effects
are
exhibited
as
an
increase
in
stool
volume,
moisture,
and/
or
increased
intestinal
transit
time
rather
than
frank
diarrhea.

Where
drinking
water
contains
high
levels
of
sulfate
or
total
dissolved
solids,
it
should
not
be
used
in
the
preparation
of
powdered
infant
formula
or
nutritional
supplements.
An
alternate
lowmineral
water
source
should
be
used.
Because
laxative
effects
have
not
been
observed
with
long­
term
exposures
to
sulfate­
containing
water,
the
data
suggest
that
acclimatization
occurs
as
exposures
continue.

The
available
database
does
not
permit
EPA
to
construct
a
quantitative
dose­
response
assessment
for
the
laxative
effects
of
sulfate.
The
current
SMCL
of
250
mg/
L
should
protect
almost
all
consumers
from
the
esthetic
effects
of
sulfate,
and
the
health­
based
advisory
value
of
500
mg/
L
will
protect
against
sulfate's
laxative
effects
in
the
absence
of
high
concentrations
of
other
osmotically
active
chemicals
in
the
water.
4
Sulfate
 
February
2003
1.0
INTRODUCTION
This
advisory
provides
information
to
Tribes,
States,
local
drinking
water
facilities,
and
public
health
personnel
on
the
health
and
taste
effects
resulting
from
sulfate
contamination
of
potable
water.
There
are
limited
scientific
data
on
the
health
effects
of
sulfate,
but
adequate
data
are
available
on
the
range
of
exposure
concentrations
that
may
pose
a
concern.

2.0
SULFATE
IN
THE
ENVIRONMENT
Sulfates
occur
naturally
and
are
abundant
in
the
environment,
generally
originating
from
mineral
deposits,
soil,
and
rocks,
or
the
combustion
of
sulfur­
containing
fuels.
Sulfate,
a
soluble,
divalent
anion
(
SO
4
2­),
results
from
the
oxidation
of
elemental
sulfur,
sulfide
minerals,
or
organic
sulfur
(
Alley
1993,
Field
1972,
Wetzel
1983).
The
anion
is
often
associated
with
alkali,
alkaline
earth,
or
transition
metals
through
ionic
bonds
(
Field
1972).

Sulfates
are
used
in
mining,
pulping,
metal
and
plating
industries,
water
and
sewage
treatment,
and
leather
processing,
and
in
the
manufacture
of
numerous
chemicals,
dyes,
glass,
paper,
soaps,
textiles,
fungicides,
insecticides,
astringents,
and
emetics
(
Greenwood
et
al.
1984).
Various
sulfate
salts
are
used
in
foods
(
FDA
1999),
and
ammonium
sulfate
is
used
in
the
fertilizer
industry.

Sulfur
is
the
14th
most
abundant
element
in
the
earth's
crust,
and
the
8th
or
9th
most
abundant
in
sediments
(
Kaplan
1972).
It
is
constantly
transferred
among
compartments
by
the
sulfur
cycle
and
is
ubiquitous
in
the
environment.
Anthropogenic
sulfur
emissions
have
a
significant
impact
on
the
sulfur
cycle,
with
at
least
80%
of
global
sulfur
dioxide
(
SO
2)
emissions
and
more
than
45%
of
river­
borne
sulfates
traceable
to
human
activity
(
Moore
1991).

2.1
Water
Sulfate
is
found
almost
universally
in
natural
waters
at
concentrations
ranging
from
a
few
tenths
to
several
thousand
milligrams/
liter
(
mg/
L).
The
highest
concentrations
are
usually
found
in
groundwater
and
are
considered
to
be
a
mixture
of
sulfates
from
atmospheric,
geochemical,
and
biological
sources.
Approximately
30%
of
sulfate
in
groundwater
may
be
of
atmospheric
origin,
and
the
remainder
from
geologic
and
biological
processes.
Sulfates
are
discharged
into
surface
water
through
industrial
wastes
and
atmospheric
deposition
of
sulfur
dioxide.

The
sulfate
concentration
in
seawater
is
about
2,700
mg/
L
(
Hitchcock
1975)
and
ranges
from
3
to
30
mg/
L
in
freshwater
lakes
(
Katz
1977).
Sulfate
content
in
drinking
water
ranges
from
0
to
1,000
mg/
L
in
the
United
States
(
Trembaczowski
1991).
In
a
survey
of
rivers
in
western
Canada,
sulfate
concentrations
ranged
from
1
to
3,040
mg/
L,
with
concentrations
generally
in
the
range
of
1
to
580
mg/
L
(
Environment
Canada
1984).

Sulfate
has
been
monitored
under
the
Safe
Drinking
Water
Act
(
SDWA)
Unregulated
Contaminant
Monitoring
(
UCM)
program
since
1993
(
57
FR
31776).
Monitoring
ceased
for
small
public
water
systems
(
PWSs)
under
a
direct
final
rule
published
January
8,
1999
(
64
FR
5
Sulfate
 
February
2003
1494),
and
ended
for
large
PWSs
with
promulgation
of
the
new
Unregulated
Contaminant
Monitoring
Regulation
(
UCMR)
issued
September
17,
1999
(
64
FR
50556)
and
effective
January
1,
2001.

The
Safe
Drinking
Water
Information
System
(
SDWIS/
FED)
is
a
database
of
analytical
data
on
the
concentrations
of
contaminants
in
drinking
water.
Sulfate
levels
reported
in
the
SDWIS/
FED
database
were
analyzed
from
a
20­
State
cross­
section
(
U.
S.
EPA
2001).
The
median
concentration
of
all
PWS
samples
was
24
mg/
L
and
the
99th
percentile
concentration
of
all
PWS
samples
was
560
mg/
L.
Minimum
reporting
levels
varied
from
system
to
system
and
State
to
State.
The
99th
percentile
concentration
is
a
summary
statistic
to
indicate
the
upper
bound
of
occurrence
values
because
maximum
values
can
be
extreme
values
(
outliers)
that
sometimes
result
from
sampling
or
reporting
error.

Additional
sulfate
occurrence
data
submitted
for
EPA's
Chemical
Monitoring
Reform
(
CMR)
evaluation
by
the
States
of
Alabama,
California,
Illinois,
Montana,
New
Jersey,
and
Oregon
augment
the
SDWIS/
FED
20­
State
cross­
section
analysis
(
U.
S.
EPA
2001).
Five
of
these
CMR
States
are
not
represented
in
the
cross­
section.
Data
from
the
CMR
States
show
that
concentrations
are
generally
similar
to
those
found
in
the
20­
State
cross­
section
(
Table
1).
Even
in
states
such
as
Montana,
where
the
99th
percentile
concentration
is
substantially
greater
than
that
of
the
20­
State
cross­
section,
the
median
concentration
is
still
quite
similar
to
the
median
of
the
cross­
section
States
(
U.
S.
EPA
2001).

Table
1.
Median
and
99th
percentile
concentrations
for
sulfate
in
CMR
States
State
Median
concentration
99th
percentile
concentration
Alabama
8.1
mg/
L
72
mg/
L
California
33
mg/
L
523
mg/
L
Illinois
60
mg/
L
760
mg/
L
Montana
22
mg/
L
1,200
mg/
L
New
Jersey
15.9
mg/
L
260
mg/
L
Oregon
5.1
mg/
L
79
mg/
L
Although
88%
of
the
16,495
systems
included
in
the
20­
State
cross­
section
reported
sulfate
at
concentrations
greater
than
the
minimum
reporting
level,
only
about
5%
exceeded
the
250
mg/
L
SMCL.
Within
the
twenty
individual
States,
the
number
of
systems
that
exceeded
the
SMCL
ranged
from
0
to
approximately
11%.
A
greater
percentage
of
surface
water
systems
exceeded
the
250
mg/
L
threshold;
however,
groundwater
systems
do
generally
show
the
highest
sulfate
concentrations
(
U.
S.
EPA
2001).
6
Sulfate
 
February
2003
A
survey
of
more
than
900
community
water
supplies
found
that
25
(­
3%)
had
sulfate
concentrations
above
250
mg/
L
(
McCabe
et
al.
1970).
Another
survey
of
approximately
650
rural
water
systems
reported
sulfate
present
in
271
of
495
groundwater
supplies
(
55%),
with
a
mean
sulfate
concentration
of
98
mg/
L
(
a
range
of
10
to
1,000
mg/
L).
Sulfate
was
found
in
101
of
154
surface
water
supplies
at
a
mean
concentration
of
53
mg/
L
for
those
systems
that
detected
sulfate
(
a
range
of
15
to
321
mg/
L)
(
U.
S.
EPA
1994).

Several
surveys
have
been
conducted
in
Canada
on
the
occurrence
of
sulfates
in
drinking
water.
A
study
of
17
drinking
water
supplies
in
Ontario
from
1985
through
1986
found
mean
sulfate
concentrations
of
22.5
and
12.5
mg/
L
in
treated
and
untreated
water,
respectively
(
Ontario
Ministry
of
the
Environment
1987).
A
study
of
78
municipal
drinking
water
supplies
in
Nova
Scotia
between
1987
and
1988
found
mean
sulfate
concentrations
of
14.2
mg/
L
in
treated
water
(
Nova
Scotia
Department
of
Public
Health
1988).
Sulfate
concentrations
were
significantly
higher
in
Saskatchewan,
with
median
concentrations
of
368
and
97
mg/
L
(
range
of
3
to
2,170
mg/
L)
reported
for
treated
ground
and
surface
waters,
respectively
(
Saskatchewan
Environment
and
Public
Safety
1989).
Based
on
the
mean
sulfate
concentration
measured
in
Ontario
(
22.5
mg/
L)
and
an
average
daily
water
consumption
of
2
L
per
day
for
an
adult,
the
average
daily
intake
from
this
source
would
be
45
mg.
However,
in
areas
with
high
sulfate
levels
in
drinking
water,
such
as
Saskatchewan,
daily
sulfate
intake
could
be
more
than
4,000
mg
(
WHO
1996).

2.2
Soil
Sulfate
can
be
formed
from
the
oxidation
of
elemental
sulfur,
sulfide
minerals,
or
organic
sulfur
(
Alley
1993,
Field
1972,
Wetzel
1983).
It
is
one
of
the
predominant
anions
in
soil
but
is
not
highly
mobile.
Sulfate
anion
is
often
associated
through
ionic
bonds
with
alkali,
alkaline
earth,
or
transition
metals
(
Field
1972).
Sulfur
can
be
retained
in
soil
through
biochemical
processes,
such
as
incorporation
into
the
soil
organic
pool
as
sulfate
esters
of
humic
material
or
other
complex
organic
molecules.
Sulfur
can
also
be
retained
by
adsorption
onto
soil
particles,
such
as
hydrous
iron
and
aluminum
sesquioxides.
The
average
sulfur
(
total)
concentration
in
soils
in
the
United
States
is
1,600
parts
per
million
(
ppm
or
mg/
kg;
a
range
of
<
800
to
48,000
mg/
kg)
(
Shacklette
and
Boerngen
1984).
The
determinant
in
soil
for
the
adsorption
of
sulfate
is
the
content
of
hydrous
sesquioxides
and
organic
matter.
A
strong
correlation
was
found
between
pH
and
the
ability
to
remove
sulfates
from
soil
solutions;
therefore,
factors
affecting
soil
acidity
would
also
affect
sulfate
retention
(
Patil
et
al.
1989).

2.3
Air
The
main
sources
of
atmospheric
sulfate
are
sulfur
oxides,
which
are
primarily
emitted
to
the
atmosphere
from
sulfur­
containing
fuel
combustion.
Total
global
sulfur
dioxide
production
continually
increased
from
1930
to
1980
(
the
years
when
data
are
available;
Moore
1991).
Global
production
of
sulfur
dioxide
increased
from
49
×
106
metric
tons
per
year
to
126
×
106
metric
tons
per
year
between
1930
and
1980.

Sulfur
dioxide
(
SO
2)
emissions
have
become
a
major
concern
for
industrialized
nations.
Sulfur
dioxide
interacts
with
atmospheric
water
and
oxygen
to
produce
sulfuric
acid
(
H
2
SO
4),
causing
acid
rain
(
Moore
1991,
Wetzel
1983).
In
addition,
SO
2
is
converted
to
sulfate
in
the
atmosphere
7
Sulfate
 
February
2003
and
deposited
on
soils.
This
can
lead
to
the
acidification
of
soil
solutions
and
elevate
sulfate
concentrations
in
terrestrial
waters
(
Drever
1988).

Limited
information
is
available
on
the
concentration
of
sulfates
in
ambient
air.
In
a
study
consisting
of
23,000
samples
from
405
sites
in
49
States,
sulfate
concentration
was
estimated
to
range
from
0.5
to
228.4
µ
g/
m3.
The
median
exposure
concentrations
(
0.7
to
19.5
µ
g/
m3)
were
considered
to
be
more
representative
of
exposures
than
were
the
mean
values.
Using
the
upper
median
exposure
concentration
(
19.5
µ
g/
m3)
and
assuming
an
inhalation
rate
of
20
m3/
day
for
a
70­
kg
adult,
the
daily
dose
due
to
sulfate
in
ambient
air
would
be
6
µ
g/
kg/
day
(
Abernathy
et
al.
2000).

2.4
Food
In
foods,
sulfate
is
present
as
the
salts
of
sodium,
calcium,
iron,
magnesium,
manganese,
zinc,
copper,
ammonium,
and
potassium
(
FDA
1999).
Sulfate
salts
are
used
in
the
food
industry
in
a
wide
variety
of
products,
such
as
dietary
supplements,
breads,
preserved
fruits
and
vegetables,
gelatins,
and
puddings.
The
average
daily
intake
of
sulfate
in
food
in
the
United
States
has
been
estimated
to
be
453
mg,
based
on
data
on
food
consumption
and
the
reported
usage
of
sulfates
as
additives
(
FASEB
1975).
Many
sulfate
compounds
in
food
are
"
Generally
Regarded
as
Safe"
(
GRAS)
by
the
U.
S.
Food
and
Drug
Administration
(
FDA
1999).

2.5
Summary
Average
daily
intake
of
sulfate
from
drinking
water,
air,
and
food
is
approximately
500
mg,
with
food
being
the
major
source.
However,
in
areas
with
high
sulfate
concentrations
in
the
drinking
water
supplies,
drinking
water
may
constitute
the
principal
intake
source
(
WHO
1996).

3.0
CHEMICAL
AND
PHYSICAL
PROPERTIES
Sulfate
(
SO
4
2­)
is
a
soluble,
divalent
anion;
common
salts
include
sodium,
potassium,
magnesium,
calcium,
and
barium
sulfate.
The
majority
of
sulfate
salts
are
soluble
in
water,
the
exceptions
being
the
sulfates
of
lead,
barium,
and
strontium.
The
chemical
and
physical
properties
for
the
common
sulfate
salts
are
detailed
in
Table
2
(
NIOSH
1981,
Budavari
1996,
Scofield
and
Hsieh
1983).
Sulfate
 
February
2003
8
Table
2.
Chemical
and
physical
properties
of
sulfates
Chemical
Name
Sulfuric
acid
Sodium
sulfate
Potassium
sulfate
Magnesium
sulfate
Calcium
sulfate
Barium
sulfate
Chemical
formula
H
2
SO
4
Na
2
SO
4
K
2
SO
4
MgSO
4
CaSO
4
BaSO
4
CAS
No.
7664­
93­
9
7757­
82­
6
7778­
80­
5
7487­
88­
9
7778­
18­
9
7727­
43­
7
Synonym
Oil
of
vitriol;
Hydrogen
sulfate
Thenardite
(
decahydrate
is
Glauber's
salt)
Tartarus
vitriolatus;

Arcanum
duplicatum
Bitter
salts;
heptahydrate;
epsom
salts
Anhydrite;
Anhydrous
gypsum;

Anhydrous
calcium
sulfate
Barite;
Blanc
fixe;

Raybar
Molecular
weight
98.08
142.06
174.26
120.38
136.14
233.39
Physical
state
Colorless
to
dark
brown,
oily,
odorless
liquid
White
powder
or
orthorhombic
bipyramidal
crystals
Colorless
or
white
rhombic
or
hexagonal
crystals
Colorless
rhombic
bitter
crystal
Orthorhomic
crystal
of
variable
color
Fine,
heavy,
odorless
powder
or
polymorphous
crystals
Boiling
point
(
oC)
315
­
338
NA
1,689
NA
1,193
1,149
Melting
point
(
oC)
10.4
888
1,067
NA
1,450
1,580
Density
(
g/
mL)
1.84
2.68
2.66
2.66
2.96
4.2
­
4.5
Vapor
pressure
(
mmHg)
<
0.001
NA
NA
NA
NA
NA
Specific
gravity
1.84
2.68
2.66
1.67
2.96
4.2
­
4.5
Water
solubility
(
g/
100
mL)
Miscible
29l
12
71
at
20
°
C
and
91
at
40
°
C
0.2
Practically
insoluble,

0.00025
Taste
threshold
in
water
(
mg/
L)
NA
180
­
550
NA
400
­
600
250
­
900
NA
Odor
threshold
(
air)

(
mg/
m3)
>
1
NA
NA
NA
NA
NA
NA
­
Not
available.
9
Sulfate
 
February
2003
4.0
TOXICOKINETICS
4.1
Absorption
Estimates
of
sulfate
absorption
are
derived
indirectly
from
reported
excretion
data.
Absorption
of
sulfate
from
the
intestine
depends
upon
the
amount
of
sulfate
ingested.
For
example,
Bauer
(
1976)
reported
that
when
radiotracer
doses
of
60­
80
µ
Ci
35S­
sodium
sulfate
were
administered
orally
to
humans
(
eight
adults),
80%
or
more
of
the
radioactivity
was
recovered
in
the
urine
at
24
hours,
suggesting
that
at
least
80%
of
sulfate
must
have
been
absorbed.
However,
the
high
doses
of
sulfate
that
induced
catharsis
exceeded
intestinal
absorption
capacity,
and
thus
were
excreted
in
the
feces.

The
type
of
cation
associated
with
sulfate
may
also
influence
absorption.
Morris
and
Levy
(
1983b)
reported
30.2
±
17.2%
of
the
dose
was
excreted
in
24­
hour
urine
after
oral
administration
of
magnesium
sulfate
(
5.4
g
sulfate)
to
seven
healthy
individuals,
as
compared
to
43.5
±
12.0%
excreted
after
oral
administration
of
sodium
sulfate
(
5.4
g
sulfate)
in
five
healthy
men
(
Cocchetto
and
Levy
1981).
This
finding
suggests
that
magnesium
sulfate
is
absorbed
to
a
lesser
extent
than
sodium
sulfate.
Morris
and
Levy
(
1983b)
indicated
that
the
comparison
of
these
two
salts
is
limited
in
that
data
were
obtained
in
separate
experiments
from
a
small
number
of
subjects
rather
than
from
parallel
experiments
with
the
same
pool
of
subjects.

Florin
et
al.
(
1991)
performed
sulfate
balance
studies
in
normal
subjects
and
subjects
with
ileostomies
(
subjects
with
ileum
removed
surgically).
The
study
authors
wanted
to
determine
how
much
sulfate
reached
the
colon
and
the
extent
to
which
diet
and
endogenous
sources
contributed
to
colonic
sulfate
concentration.
All
subjects
were
fed
diets
containing
between
1.6
and
16.6
mmol
SO
4/
day
(
0.15­
1.6
g/
day).
Sulfate
was
measured
in
the
diet,
urine,
and
feces
to
determine
sulfate
balance
(
using
anion
exchange
chromatography).
There
was
a
net
absorption
of
sulfate
with
a
plateau
at
0.48
g/
day
in
the
ileostomy
patients.
Sulfate
absorption
in
normal
subjects
did
not
plateau
even
at
the
highest
dietary
concentration
examined.
The
dietary
contribution
to
the
colonic
sulfate
pool
was
determined
to
be
up
to
0.86
g/
day
because
linearity
was
observed
between
diet
and
upper
gastrointestinal
loss
for
intakes
greater
than
0.67
g/
day.
The
study
authors
concluded
that
diet
and
intestinal
absorption
were
the
principal
factors
affecting
the
amount
of
sulfate
reaching
the
colon.
This
study
also
suggests
that
the
upper
digestive
tract
is
primarily
responsible
for
sulfate
absorption.

4.2
Distribution
Inorganic
sulfate
is
freely
distributed
in
blood
and
does
not
accumulate
in
tissues.
Most
sulfate
found
in
human
tissues
is
biosynthetically
incorporated
into
macromolecules
and
is
organic.
The
normal
serum
level
of
sulfate
found
in
humans
(
0.3
mmol/
L
or
29
mg/
L)
is
lower
than
that
in
rodents
(
1
mmol/
L
or
96
mg/
L)
or
in
other
animal
species
(
Krijgsheld
et
al.
1980,
Cole
and
Scriver
1980).

A
circadian
variation
of
serum
inorganic
sulfate
levels
has
been
demonstrated
in
humans.
Hoffman
et
al.
(
1990)
fed
seven
male
volunteers
an
identical
diet,
including
fluids,
a
parameter
that
is
not
typically
included
in
dietary
studies.
Blood
samples
were
collected
in
a
total
of
10
intervals
over
a
24­
hour
period.
Average
serum
inorganic
sulfate
levels
were
lowest
in
the
10
Sulfate
 
February
2003
morning
(
302
µ
mol/
L
or
29
mg/
L)
and
highest
in
the
early
evening
(
408
µ
mol/
L
or
39
mg/
L).
This
difference
is
statistically
significant
(
p
<
0.005).
The
average
24­
hour
level
was
360
µ
mol/
L,
or
35
mg/
L.
There
was
considerable
variability
among
subjects.
The
authors
speculated
that
a
portion
of
the
variation
in
serum
sulfate
could
be
due
to
variation
in
the
dietary
sulfate
content.

It
is
reported
that
dietary
protein
could
have
major
influence
on
the
serum
sulfate
levels.
For
example,
Cole
et
al.
(
1991)
studied
12
fasting
subjects
who
were
randomly
fed
an
isocaloric
meal
containing
either
high
or
low
protein
content
and
monitored
their
serum
sulfate
levels
up
to
3.5
hours
after
feeding.
Serum
sulfate
levels
increased
from
a
baseline
value
of
276
to
314
µ
mol/
L
(
27
to
30
mg/
L)
at
2.5
hours
after
the
low­
protein
meal
and
returned
to
the
baseline
by
3.5
hours.
Serum
sulfate
levels
increased
from
baseline
values
of
253
to
382
µ
mol/
L
(
24
to
37
mg/
L)
at
3
hours
and
remained
significantly
elevated
at
3.5
hours
after
the
high­
protein
meal.
The
increase
in
inorganic
sulfate
was
attributed
to
the
oxidation
of
sulfur
containing
amino
acids.
The
reason
for
the
differences
in
the
time
to
reach
peak
sulfate
levels
between
the
low­
and
highprotein
groups
is
not
clear.
The
inorganic
sulfate
excreted
in
the
urine
was
not
measured
in
this
study.

Ingesting
drinking
water
containing
high
sulfate
concentrations
has
only
slight
effects
on
serum
sulfate
levels.
Hindmarsh
et
al.
(
1991)
compared
serum
levels
of
inorganic
sulfate
in
14
healthy
volunteers
at
2
locations
(
Saskatoon:
8
men;
Rosetown:
4
men
and
2
women)
using
municipal
drinking
water
with
varying
sulfate
concentrations.
In
Saskatoon
the
sulfate
concentration
was
77
ppm
(
mg/
L)
and
in
Rosetown
the
sulfate
concentration
was
1,157
ppm
(
mg/
L).
The
cations
associated
with
the
sulfate
were
not
reported.
Baseline
serum
levels
of
inorganic
sulfate
were
0.35
±
0.06
mmol/
L
(
34
mg/
L)
in
the
Saskatoon
subjects
and
0.50
±
0.11
mmol/
L
(
48
mg/
L)
in
the
Rosetown
subjects.
These
findings
suggest
that
a
15­
fold
increase
in
sulfate
concentration
in
drinking
water
will
result
in
only
a
1.4­
fold
increase
in
serum
sulfate.
The
reasons
for
observing
only
a
slight
increase
in
serum
sulfate
in
Rosetown
subjects
could
be
homoeostatic
control
mechanisms
and
dietary
differences.

Serum
inorganic
sulfate
concentrations
are
reported
to
be
higher
in
infants
and
young
children
than
in
adults.
For
example,
Cole
and
Scriver
(
1980)
compared
serum
inorganic
sulfate
concentrations
in
subjects
under
3
years
old
(
n
=
46),
children
between
3
and
4
years
old
(
n
=
27),
adolescents
in
a
hospitalized
population
(
10
to
18
years
old)
(
n
=
12),
and
healthy
adults
(
n
=
10).
On
the
first
day
of
life,
mean
sulfate
concentrations
were
0.47
mmol/
L
(
45
mg/
L)
(
95%
confidence
limits
of
0.29
to
0.95
mmol/
L),
and
by
3
years
of
age,
concentrations
dropped
to
0.33
mmol/
L
or
32
mg/
L,
(
95%
confidence
limits
of
0.22
to
0.67
mmol/
L),
which
was
comparable
to
the
adult
levels
0.33
mmol/
L
or
32
mg/
L
(
95%
confidence
limits
of
0.22
B
0.43
mmol/
L).
The
study
authors
state
that
the
increased
concentration
in
newborns
might
be
a
result
of
lower
glomerular
filtration
rates,
increased
resorption,
and/
or
developmental
needs.

Serum
levels
of
inorganic
sulfate
were
found
to
be
increased
in
pregnant
women
in
the
third
trimester
(
0.434
±
0.006
mmol/
L
[
42
mg/
L]
compared
to
a
nonpregnant
control
value
of
0.328
±
0.010
mmol/
L
[
31
mg/
L])
(
Cole
et
al.
1985).
It
was
suggested
that
the
fetus
may
need
to
concentrate
inorganic
sulfate
to
support
its
development.
Similarly,
Cole
et
al.
(
1992)
reported
that
inorganic
sulfate
levels
in
amniotic
fluid
were
increased
in
the
third
trimester
compared
with
the
second
trimester.
Levels
in
amniotic
fluid
were
0.317
±
0.022
mmol/
L
(
30
mg/
L)
in
the
11
Sulfate
 
February
2003
second
trimester,
but
were
0.693
±
0.042
mmol/
L
(
66
mg/
L)
in
the
third
trimester.
The
sulfate
levels
correlated
with
the
creatinine
and
uric
acid
levels
in
the
amniotic
fluid,
suggesting
that
renal
excretion
by
the
fetus
may
be
the
major
source
of
the
inorganic
sulfate
in
the
amniotic
fluid
in
the
late
stages
of
gestation.

Levels
of
inorganic
sulfate
in
the
cerebrospinal
fluid
(
CSF)
were
reportedly
lower
than
those
in
serum.
Cole
et
al.
(
1982)
measured
inorganic
sulfate
in
CSF
from
25
infants
and
children.
Mean
CSF
sulfate
was
0.170
mmol/
L
(
16.3
mg/
L)
in
children
less
than
3
years
of
age
and
0.095
mmol/
L
(
9.1
mg/
L;
range
0.059
to
0.165
mmol/
L)
in
children
older
than
3
years
of
age.
Similar
to
CSF
concentrations,
the
serum
sulfate
concentration
decreased
from
0.5
mmol/
L
(
48
mg/
L)
in
the
newborn
to
0.3
mmol/
L
(
29
mg/
L)
in
children
older
than
3
years
of
age.
Because
both
CSF
and
serum
sulfate
levels
decrease
in
a
similar
fashion,
the
ratio
of
sulfate
CSF/
serum
remains
constant
at
0.33
in
infants
and
children.

The
levels
of
inorganic
sulfate
in
human
colostrum
and
milk
were
0.066
±
0.021
mmol/
L
(
6.3
mg/
L)
and
0.029
±
0.006
mmol/
L
(
2.8
mg/
L),
respectively
(
McNally
et
al.
1991).
The
mean
sulfate
level
in
the
saliva
in
fasting
adults
(
n
=
17)
was
0.072
±
0.004
mmol/
L,
or
6.9
mg/
L
(
Cole
and
Landry
1985).

4.3
Metabolism
Inorganic
sulfate
is
incorporated
into
several
types
of
biomolecules,
such
as
glycoproteins,
glycosaminoglycans,
and
glycolipids
(
Brown
et
al.
1965,
Daughaday
1971,
Morris
and
Sagawa
2000).
Inorganic
sulfate
enters
a
metabolic
pathway
as
an
activated
nucleotide
intermediate,
3Nphosphoadenosine
5N­
phosphosulfate
(
PAPS),
which
serves
as
a
substrate
for
a
number
of
relatively
specific
sulfotransferases.
Sulfotransferases
are
enzymes
that
catalyze
the
sulfation
process
(
or
sulfamation
in
the
case
of
aromatic
amines).
They
are
found
in
the
intestinal
mucosa,
liver,
and
kidney
(
Bostrom
1965,
Mulder
and
Keulemans
1978)
and
in
human
platelets
(
Rein
et
al.
1981).
Sulfate
plays
an
important
role
in
the
detoxification
and
catabolism
of
various
endogenous
(
catecholamines,
steroids,
bile
acids)
and
exogenous
(
acetaminophen
and
other
drugs)
compounds.
Sulfate
combines
with
several
of
these
compounds
to
form
soluble
sulfate
esters
(
Mulder
and
Keulemans
1978,
Weitering
et
al.
1979,
Sipes
and
Gandolfi
1991).

Because
inorganic
sulfate
is
used
in
the
metabolism
of
several
compounds,
sulfate
levels
could
be
affected
by
the
presence
of
drugs
in
the
body.
In
humans,
the
effect
of
acetaminophen
administration
on
the
serum
sulfate
pool
has
been
studied
(
Morris
and
Levy
1983a).
In
eight
human
volunteers
orally
administered
1.5
g
of
acetaminophen,
the
mean
serum
concentration
of
inorganic
sulfate
was
significantly
(
p
<
0.001)
reduced
from
0.410
to
0.311
mmol/
L
(
39
to
30
mg/
L)
within
2
hours.
Similar
findings
were
observed
in
other
human
studies
(
Hendrix­
Treacy
et
al.
1986),
as
well
as
in
animals
(
Morris
et
al.
1984),
after
acetaminophen
administration.

4.4
Excretion
Sulfates
are
usually
eliminated
by
renal
excretion
in
free
unbound
form
or
as
conjugates
of
various
chemicals.
At
high
sulfate
doses
that
exceed
intestinal
absorption,
sulfate
is
excreted
in
feces.
12
Sulfate
 
February
2003
Cocchetto
and
Levy
(
1981)
conducted
a
study
with
five
male
volunteers
who
were
orally
administered
18.1
g
Na
2
SO
4A10H
2
O
(
5.4
g
sulfate)
in
50
mL
of
water
as
a
single
bolus
dose
or
as
four
equally
divided
hourly
doses.
Urinary
excretion
of
inorganic
sulfate
was
measured
at
24,
48,
and
72
hours.
Prior
to
dosing,
the
baseline
excretion
of
inorganic
sulfate
(
free
form)
was
measured
several
times
for
each
individual.
The
normal
baseline
excretion
of
inorganic
sulfate
ranged
from
13
to
25
mmol/
24
hours
(
1.3
to
2.4
g/
24
hours).
To
calculate
the
amount
of
the
exogenous
dose
that
was
excreted,
the
individual
baseline
values
were
subtracted
from
the
total
urinary
inorganic
sulfate.
Over
72
hours,
a
mean
of
53.4%
of
the
single
dose
or
61.8%
of
the
divided
dose
was
recovered
in
the
urine.
In
general,
at
least
two­
thirds
of
the
72­
hour
sulfate
excreted
appeared
in
the
urine
in
24
hours.
The
divided
dose
was
fairly
well
tolerated,
but
the
single
dose
caused
severe
diarrhea.

The
excretion
of
inorganic
sulfate
in
humans
is
dependent
on
the
cation.
Morris
and
Levy
(
1983b)
reported
that
orally
administered
magnesium
sulfate
in
humans
was
absorbed
less
completely
and
more
variably
than
sodium
sulfate.
Seven
male
volunteers
received
13.9
g
of
MgSO
4A7H
2
O
(
5.4
g
sulfate)
in
four
1.4­
g
portions
in
100
mL
of
water
over
a
4­
hour
period.
Based
on
the
concentration
of
free
sulfate
in
72­
hour
urine,
at
least
37%
of
the
dose
was
excreted.
An
average
of
30.2%
±
17%
of
the
sulfate
was
excreted
in
urine
over
24
hours
for
magnesium
sulfate
as
compared
with
43.5%
±
12%
for
sodium
sulfate.
There
was
high
intersubject
variation.
Compared
to
sodium
sulfate
administered
in
an
identical
fashion,
the
magnesium
salt
was
less
bioavailable.

Bauer
(
1976)
reported
that
when
doses
between
60
and
80
µ
Ci
35S
(
as
sodium
sulfate)
were
administered
orally
to
eight
humans,
80%
was
recovered
in
the
urine
at
24
hours.
For
comparison,
86%
of
the
same
dose
given
intravenously
was
excreted
in
the
urine
in
24
hours.

The
kidney
regulates
and
maintains
serum
sulfate
levels
through
a
capacity­
limited
reabsorption
mechanism.
In
humans,
the
maximum
rate
of
transport
is
0.11
mM/
min.
If
intestinal
absorption
is
slow
or
saturated,
sulfates
are
eliminated
in
the
feces.
As
a
result,
sulfates
do
not
accumulate
in
the
body
even
after
consumption
of
high
levels
(
Morris
and
Levy
1983a,
Cole
and
Scriver
1980).

5.0
HEALTH
EFFECTS
DATA
Data
are
available
on
the
short­
and
long­
term
effects
of
sulfate
in
humans
and
animals.
In
general,
a
laxative
effect
is
the
most
common
manifestation
of
exposure
to
high
concentrations
of
sulfate.
The
soft
stool
or
diarrhea
that
results
from
sulfate
is
an
osmotic
diarrhea,
i.
e.,
one
that
results
when
the
osmolality
of
the
intestinal
contents
exceeds
that
of
the
interstitial
fluids.
When
this
occurs,
water
is
drawn
across
the
intestinal
membrane
into
the
lumen,
increasing
the
moisture
content
and
volume
of
the
fecal
matter.
This
leads
to
an
increased
intestinal
peristalsis
and
evacuation
of
the
intestinal
contents.
Poorly
absorbed
dissolved
materials
such
as
magnesium
sulfate,
sorbitol,
or
lactulose
are
often
associated
with
osmotic­
induced
diarrheas.
An
osmotic­
induced
diarrhea
ceases
once
the
osmotically
active
gastrointestinal
contents
are
excreted
(
Stipanuk
2000).

The
osmotic
diarrheal
response
to
sulfate
is
influenced
by
the
total
temporal
osmolyte
load,
as
13
Sulfate
 
February
2003
well
as
the
sulfate
concentration.
For
example,
if
water
contains
magnesium
ion
as
well
as
sulfate
ion,
the
diarrheal
response
will
be
increased
because
both
ions
are
osmotically
active.
This
complicates
interpretations
of
some
of
the
ecological
sulfate
studies
where
data
are
reported
for
sulfate
concentrations
but
not
for
the
presence
of
other
drinking
water
constituents
that
may
be
osmotically
active.

5.1
Human
5.1.1
Short­
Term
Exposure
Studies
Sulfate
salts
are
known
to
have
laxative
properties
in
humans
(
Schofield
and
Hsieh
1983).
A
dose
of
15
g
of
magnesium
or
sodium
sulfate
will
produce
catharsis
within
3
hours,
but
lower
doses
can
also
produce
this
effect.
For
example,
approximately
5
g
of
magnesium
sulfate
was
reported
to
cause
significant
laxative
effects
when
administered
in
a
dilute
solution
to
a
fasting
man
(
Fingl
1980).
Cocchetto
and
Levy
(
1981)
reported
that
a
single
dose
of
8
g
of
anhydrous
sodium
sulfate
induced
severe
diarrhea
lasting
up
to
24
hours
in
five
human
subjects.
However,
the
same
amount
of
sodium
sulfate
taken
at
four
equal
hourly
doses
produced
either
no
diarrhea
or
mild
diarrhea
of
short
duration.

Humans
appear
to
develop
a
tolerance
to
water
containing
high
sulfate
concentrations
(
Schofield
and
Hsieh
1983).
Although
the
rate
at
which
acclimation
occurs
has
not
been
determined,
it
is
generally
considered
to
occur
in
adults
within
one
to
two
weeks
(
U.
S.
EPA
1999b).
No
specific
data
on
the
length
of
time
necessary
for
humans
to
acclimatize
to
the
cathartic
effects
of
sulfates
were
identified.

The
sulfate
salt
is
important
in
determining
the
extent
and
nature
of
any
laxative
effect.
Morris
and
Levy
(
1983b)
reported
that
when
humans
were
given
the
same
millimolar
dose
of
sulfate
as
either
magnesium
or
sodium
sulfate,
the
magnesium
sulfate
induced
more
adverse
effects,
ranging
from
upset
stomach
to
diarrhea,
than
did
sodium
sulfate.

Chien
et
al.
(
1968)
reported
three
cases
of
diarrhea
in
infants
in
Saskatchewan,
Canada,
attributable
to
exposure
to
high
sulfate
concentrations
in
the
water
supply.
In
each
case,
local
well
water
with
sulfate
concentrations
between
630
and
1,150
mg/
L
and
a
high
total
dissolved
solid
concentration
of
2,424
to
3,123
mg/
L
was
used
to
prepare
infant
formulas.
The
total
dissolved
solid
concentrations
reported
in
this
study
greatly
exceeded
the
United
States'
secondary
standard
for
total
dissolved
solids
of
500
mg/
L.

When
milk
or
water
with
low
sulfate
content,
and
presumably
lower
total
dissolved
solids,
replaced
the
local
well
water,
recovery
occurred
(
Chien
et
al.
1968).
Diarrhea
returned
when
the
original
well
water
was
re­
introduced.
The
study
authors
concluded
that
waters
with
a
sulfate
content
higher
than
400
mg/
L
were
unsuitable
for
consumption
by
infants.
Interpretation
of
this
study
is
limited
by
the
number
of
the
study
subjects
(
n
=
3)
and
by
the
lack
of
data
on
sulfate
concentration
in
and
osmolarity
of
the
infant
formula.

In
a
case­
control
investigation
to
assess
the
association
between
infant
diarrhea
and
ingestion
of
water
containing
elevated
sulfate
levels,
Esteban
et
al.
(
1997)
reported
that
no
significant
association
existed
between
exposure
to
sulfate
from
tap
water
and
subsequent
diarrhea
in
14
Sulfate
 
February
2003
infants.
A
total
of
274
mothers
of
infants
born
in
19
South
Dakota
counties
with
high
sulfate
concentrations
in
tap
water
were
identified
and
interviewed
using
a
telephone
questionnaire
(
n
=
262)
or
in
person
(
n
=
12).
The
mothers
were
questioned
on
the
frequency
and
consistency
of
the
infant
=
s
bowel
movements
and
on
the
amount
of
water
that
the
infant
drank
in
the
previous
7
days.
Diarrhea
was
defined
as
three
or
more
loose
stools
in
a
24­
hour
period.
A
sample
of
the
water
used
in
the
infant
=
s
diet
was
also
submitted
by
the
mother
and
analyzed
for
sulfate.
Two
hundred
seventy­
four
infants
were
included
in
the
study.
Cases
were
defined
as
infants
that
developed
diarrhea
(
as
identified
by
the
mothers);
controls
were
defined
as
infants
that
did
not
develop
diarrhea.

The
average
sulfate
concentration
in
drinking
water
for
cases
was
416
mg/
L
versus
353
mg/
L
for
controls.
The
corresponding
median
sulfate
concentration
for
cases
was
289
mg/
L
(
range
0!
1,271
mg/
L);
the
median
concentration
for
controls
was
258
mg/
L
(
range
0!
2,787
mg/
L).
The
median
water
intake
for
the
controls
was
lower
than
for
the
cases
(
0.2
vs.
0.5
L/
day).
Mean
and
median
daily
sulfate
intake
from
water
for
all
infants
in
the
study
was
29
and
17
mg/
kg/
day,
respectively.
Mothers
reported
diarrhea
in
19%
of
the
infants
living
in
households
with
sulfate
levels
in
tap
water
>
500
mg/
L
and
in
14%
of
infants
living
in
households
with
sulfate
levels
<
500
mg/
L.
There
was
no
significant
correlation
(
OR
=
1.4;
95%
CI
=
0.5!
4.0)
between
the
incidence
of
diarrhea
and
the
level
of
sulfate
in
water
samples
.

Heizer
et
al.
(
1997)
examined
bowel
function
in
healthy
adults
following
exposure
to
various
sodium
sulfate
concentrations
in
drinking
water.
In
a
single­
dose
study
of
six
adults
(
three
men
and
three
women),
each
subject
received
drinking
water
with
sulfate
concentrations
of
0
or
1,200
mg/
L
for
two
consecutive
6­
day
periods.
A
fluid
intake
of
36
mL/
kg/
day
was
maintained
in
these
subjects.
Stool
mass,
frequency,
consistency,
and
mouth­
to­
anus
appearance
time
for
colored
markers
were
measured.
When
subjects
received
sulfate
at
1,200
mg/
L,
mean
stool
mass
per
6­
day
pool
period
increased
from
621
g
to
922
g
(
p
=
0.03).
Mean
stool
mass
per
hour
increased
from
4.8
g
to
6.6
g
(
p
=
0.03)
with
a
change
in
sulfate
concentration
from
0
to
1,200
mg/
L.
However,
stool
frequency,
consistency,
and
mouth­
to­
anus
appearance
time
were
not
significantly
different
for
the
high­
sulfate
water.

Heizer
et
al.
(
1997)
also
reported
data
from
a
multiple
dose
study
in
four
subjects
(
two
men
and
two
women).
Each
subject
received
drinking
water
with
increasing
sulfate
concentrations
of
0,
400,
600,
800,
1,000,
and
1,200
mg/
L
over
six
consecutive
2­
day
periods.
In
this
study,
there
was
a
significant
linear
trend
for
decreasing
mouth­
to­
anus
marker
appearance
time
with
increasing
sulfate
concentrations
(
p
=
0.03).
When
the
10
subjects
(
4
subjects
from
the
multipledose
study
and
6
subjects
from
the
single­
dose
study
reported
above)
were
used
to
compare
effects
of
0
mg/
L
and
1,200
mg/
L
sulfate,
significant
differences
in
stool
consistency
(
p
=
0.02)
and
transit
time
(
p
=
0.03)
were
observed.
However,
none
of
the
subjects
reported
diarrhea
or
passed
more
than
three
stools
per
day.

In
order
to
determine
the
effects
of
high
sulfate
concentrations
in
transient
populations
(
students,
visitors,
hunters,
etc.),
the
Centers
for
Disease
Control
(
CDC),
with
funding
from
EPA
(
1999a),
conducted
a
study
in
adult
human
volunteers.
The
study
was
designed
to
determine
if
any
adverse
effects
would
occur
in
persons
suddenly
changing
drinking
water
sources
from
one
with
little
or
no
sulfate
to
one
with
high
sulfate
concentrations.
A
total
of
105
participants
were
randomly
assigned
to
five
sulfate­
exposure
groups
and
were
exposed
to
sulfate
in
bottled
water
15
Sulfate
 
February
2003
over
a
period
of
6
days.
The
participants
received
water
containing
sulfate
only
for
days
3
through
5
and
were
given
sulfate­
free
bottled
water
for
days
1,
2,
and
6.
Subjects
were
blinded
to
the
level
of
sulfate
in
the
drinking
water.
The
number
of
participants
in
each
exposure
category
varied:
0
mg/
L
(
n
=
24),
250
mg/
L
(
n
=
10),
500
mg/
L
(
n
=
10),
800
mg/
L
(
n
=
33),
or
1,200
mg/
L
(
n
=
28).

Several
criteria
were
used
to
monitor
whether
the
sulfate
had
a
laxative
effect.
The
subjects
kept
track
of
the
number
of
bowel
movements
they
had
on
each
day
of
the
study.
They
were
also
asked
to
rate
the
quality
of
their
stools
according
to
three
definitions
of
diarrhea.
Osmotic
diarrhea
was
defined
as
an
increase
in
stool
volume,
diarrhea
1
was
defined
as
paste­
like
or
liquid
stools,
and
diarrhea
2
was
defined
as
change
in
stool
bulk
and
consistency.
There
were
no
statistically
significant
differences
in
the
mean
number
of
bowel
movements
among
the
groups
on
days
3,
4,
5,
or
6;
or
in
the
mean
number
of
bowel
movements
when
days
3,
4,
and
5
were
compared
with
days
1
and
2.
There
was
also
no
apparent
trend
in
the
percentage
of
subjects
that
reported
diarrhea
during
the
exposure
period
as
opposed
to
the
control
period
(
days
1
and
2)
using
any
of
the
definitions
of
diarrhea.

The
data
were
also
evaluated
using
logistic
regression
analysis
to
determine
the
effects
of
sulfate
based
on
dose.
The
dose
was
calculated
for
each
subject
from
the
amount
of
water
consumed,
the
amount
of
sulfate
in
drinking
water,
and
the
body
weight
of
the
participant.
Using
this
method,
there
were
no
statistically
significant
dose­
response
associations
between
sulfate
dose
and
reports
of
diarrhea
(
one­
sided
p
=
0.099)
using
any
of
the
three
definitions.

The
authors
also
combined
the
incidence
for
diarrhea
under
any
of
the
three
definitions
for
the
lowest
three
dose
groups
(
0,
250,
and
500
mg/
L)
and
compared
it
with
the
incidences
of
the
800
mg/
L
and
1,200
mg/
L
dose
groups.
There
were
no
statistically
significant
differences
between
groups
for
any
of
the
three
diarrhea
categories.
However,
there
was
a
dose­
related
trend
for
increased
stool
volume
(
osmotic
diarrhea)
with
increasing
sulfate
exposure
when
the
three
groups
were
compared
(
9%,
15%,
and
18%,
respectively).

5.1.2
Long­
Term
Exposure
Studies
Peterson
(
1951)
analyzed
the
data
from
about
300
questionnaires
that
had
been
collected
by
the
North
Dakota
Department
of
Health
as
part
of
its
routine
monitoring
of
the
mineral
content
of
groundwater
supplies.
The
questionnaires
had
been
distributed
to
private
well
owners
along
with
requests
for
samples
of
well
water
for
analysis.
The
questionnaires
solicited
information
on
odor,
taste,
effects
on
cooking,
and
laxative
effects
from
the
water.
The
questionnaires
analyzed
by
Peterson
(
1951)
were
a
subset
of
about
2,500
submitted
to
the
Department
of
Health.
They
were
selected
because
analytical
data
for
the
water
were
available
and
the
questionnaire
was
complete
enough
to
be
used
for
data
analysis.
Peterson
(
1951)
plotted
the
concentration
of
sodium
sulfate
and
magnesium
sulfate
in
the
water
against
whether
water
use
was
associated
with
a
laxative
effect.
Both
sodium
and
magnesium
ions
were
present
in
most
of
the
water
samples.
He
concluded
that
sulfate
was
likely
to
have
a
laxative
effect
when
the
concentrations
exceed
750
mg/
L,
but
was
unlikely
to
have
such
an
effect
at
concentrations
less
than
600
mg/
L.
As
the
concentration
of
the
magnesium
in
the
water
increased,
the
sulfate
concentration
that
was
associated
with
a
laxative
response
decreased.
16
Sulfate
 
February
2003
Moore
(
1952)
analyzed
data
from
248
wells
from
the
North
Dakota
Department
of
Health
survey
(
Peterson
1951
data).
Questionnaires
completed
by
the
users
of
the
wells
provided
a
YES
or
NO
response
for
laxative
effects
for
176
of
248
wells.
For
69
wells
with
positive
responses
for
laxative
effects,
the
mean
sulfate
level
was
1,250
mg/
L
and
the
median
was
1,090
mg/
L.
For
107
wells
with
negative
responses,
the
mean
and
median
sulfate
levels
were
500
mg/
L
and
403
mg/
L,
respectively.
When
the
data
were
separated
into
specific
ranges,
the
percent
of
YES
responses
for
laxative
effects
was
22%
(
10/
46)
for
wells
with
levels
between
0
and
200
mg/
L;
24%
(
9/
37)
for
wells
with
levels
between
200
and
500
mg/
L;
33%
(
13/
39)
for
wells
with
levels
between
500
and
1,000
mg/
L;
and
69%
(
37/
54)
for
levels
>
1,000
mg/
L.
Moore
(
1952)
concluded
that
sulfate
ion
concentration
is
critical
at
1,000
mg/
L
and
at
more
than
2,000
mg/
L
is
almost
certain
to
produce
discernible
physiological
effects.
For
a
combination
of
magnesium
and
sulfate,
effects
are
likely
to
occur
when
the
total
concentration
exceeds
1,000
mg/
L.
Many
of
the
wells
in
this
data
set
also
contained
high
levels
of
total
dissolved
solids
and
magnesium.
Similar
results
were
obtained
when
Cass
(
1953)
analyzed
the
data
provided
in
the
North
Dakota
survey.

5.2
Animal
5.2.1
Short­
Term
Exposure
Studies
The
oral
LD
50
s
of
ammonium
sulfate,
sulfuric
acid,
and
potassium
sulfate
in
the
rat
are
3,000
B
4,000
mg/
kg,
2,140
mg/
kg
(
FASEB
1975),
and
6,600
mg/
kg
(
RTECS
2000),
respectively.
The
oral
LD
50
of
sodium
sulfate
in
the
mouse
is
5,989
mg/
kg
(
RTECS
2000).

Adams
et
al.
(
1975)
supplied
groups
of
three
White
Leghorn
hens
with
drinking
water
containing
250
to
16,000
mg
sulfate/
L
(
as
sodium
or
magnesium
sulfate).
At
16,000
mg/
L,
the
hens
exhibited
decreased
body
weight,
decreased
feed
consumption,
decreased
egg
production,
and
increased
water
consumption.
At
this
dose,
mortality
(
100%)
occurred
by
day
7
for
hens
drinking
water
with
magnesium
sulfate,
and
by
day
12
for
hens
drinking
water
with
sodium
sulfate.
Necropsy
revealed
focal
necrosis
of
individual
renal
glomeruli,
with
uric
acid
accumulation
in
both
the
kidney
and
gut.
Similar,
but
less
severe,
histologic
changes
were
seen
in
hens
receiving
water
at
4,000
mg/
L
for
up
to
3
weeks.

Paterson
et
al.
(
1979)
administered
drinking
water
containing
3,000
mg/
L
of
added
sulfate
(
as
either
sodium
sulfate
or
a
1:
1
combination
of
both
sodium
and
magnesium
sulfate)
for
28
days
to
groups
of
17
or
18
weanling
pigs
(
7.7
to
8
kg).
The
control
group
(
n
=
16)
received
water
containing
320
mg/
L
sulfate.
No
significant
changes
(
p
>
0.05)
in
average
daily
weight
gain
or
feed/
gain
ratio
were
observed
when
the
treated
group
was
compared
to
controls.
Fluid
consumption
increased
for
both
groups
receiving
the
high
concentration
of
sulfate
in
their
water,
and
stools
were
soft
for
these
animals
compared
with
controls.

Sulfate
(
sodium
and
magnesium
sulfate
in
combination
or
independently)
was
administered
to
young
pigs
at
concentrations
ranging
from
600
to
1,800
mg/
L
in
drinking
water
for
28
days.
Weight
gain,
feed
consumption,
water
consumption,
feed
conversion,
prevalence
of
diarrhea,
and
evidence
of
common
postweaning
enteric
pathogens
were
determined.
Sulfate
did
not
impair
performance
or
health
of
pigs.
However,
loose
and
watery
stools
appeared
to
be
more
prevalent
in
the
groups
receiving
1,800
mg/
L
sulfate
(
both
salts
independently
and
in
combination)
17
Sulfate
 
February
2003
compared
to
control,
600
mg/
L,
and
1,200
mg/
L
groups
(
Veenhuizen
et
al.
1992).
Similar
results
were
observed
in
an
earlier
study
by
Anderson
and
Stothers
(
1978)
in
which
groups
of
nine
young
pigs
given
water
containing
600
mg/
L
total
solids
as
sodium
sulfate
displayed
scouring
(
soft
stools),
primarily
during
the
first
week
of
a
6­
week
experimental
period.

Gomez
et
al.
(
1995)
used
neonatal
piglets
to
study
the
effect
of
inorganic
sulfate
on
bowel
function.
Two
experiments
were
conducted
to
evaluate
the
effect
of
high
levels
of
inorganic
sulfate
on
the
growth,
feed
intake,
and
feces
consistency
of
piglets,
and
to
determine
the
dose
at
which
at
least
50%
of
piglets
develop
an
osmotic
diarrhea.
In
each
experiment,
40
pigs
with
an
average
age
of
5
days
were
individually
caged
and
reared
with
an
automatic
feeding
device.
Groups
of
10
pigs
were
fed
1
of
4
liquid
diets
containing
inorganic
sulfate
(
anhydrous
sodium
sulfate)
at
0,
1,200,
1,600,
or
2,000
mg/
L
(
of
diet)
for
an
18­
day
study,
or
0,
1,800,
2,000,
or
2,200
mg/
L
for
a
16­
day
study.
The
levels
of
added
sulfate
did
not
affect
(
p
>
0.05)
the
growth
of
piglets
or
their
feed
intake.
Whereas
1,200
mg
sulfate/
L
had
essentially
no
effect
on
feces
consistency,
concentrations
greater
than
1,200
mg/
L
increased
the
prevalence
of
diarrhea.
Concentrations
greater
than
1,800
mg/
L
resulted
in
a
persistent
diarrhea.
The
changes
in
feces
consistency
suggest
that
the
level
of
added
dietary
inorganic
sulfate
at
which
50%
of
piglets
develop
diarrhea
is
between
1,600
and
1,800
mg/
L.
Analysis
of
rectal
swabs
showed
no
evidence
of
E.
coli
or
rotavirus
infection.

5.2.2
Long­
Term
Exposure
Studies
In
a
90­
day
subchronic
study,
Wurzner
(
1979)
examined
the
effects
of
sulfate
in
drinking
water
in
Sprague­
Dawley
rats
(
25/
sex/
group).
Treated
animals
received
mineral
waters
containing
low
(<
10
mg/
L),
intermediate
(
280
mg/
L),
or
high
(
1,595
mg/
L)
concentrations
of
sulfate.
Control
animals
were
provided
with
tap
water
containing
9
to
10
mg/
L
sulfate.
No
information
was
provided
on
the
concentrations
of
minerals
other
than
sulfate
in
the
three
different
mineral
waters.
No
mortalities
or
effects
on
body
weight,
food
consumption,
food
efficiency
(
a
measure
of
food
intake
versus
body
weight
change),
or
water
consumption
were
observed.
No
soft
feces
or
diarrhea
were
observed.
No
effects
on
hematology
or
serum
chemistry
(
blood
urea
nitrogen,
glucose,
triglycerides,
cholesterol,
total
protein,
and
alkaline
phosphatase
activity)
were
observed
after
90
days.
Organ
weights
were
not
affected,
and
no
histologic
changes
were
observed
at
any
tissue
site.
Five
rats/
sex/
group
continued
treatment
beyond
the
90
days.
Blood
urea
nitrogen
in
the
high­
dose
group
tended
to
be
decreased
in
both
sexes,
but
this
occurred
only
after
6
months
of
treatment.

Digesti
and
Weeth
(
1976)
supplied
groups
of
four
weanling
Hereford­
Angus
heifers
with
drinking
water
containing
110
to
2,500
mg/
L
sodium
sulfate.
After
90
days
of
dosing,
no
overt
toxicity
was
observed
in
any
animals;
feed
consumption,
water
consumption,
and
growth
were
not
affected.
Increased
levels
of
methemoglobin
and
sulfhemoglobin
were
observed
in
the
animals
consuming
1,250
and
2,500
mg/
L
sodium
sulfate;
this
was
attributed
to
the
bacterial
reduction
of
sulfate
to
sulfide
in
the
rumen.
At
2,500
mg/
L,
renal
filtration
of
sulfate
was
increased
by
37.7%
and
renal
reabsorption
was
decreased
by
23.7%.
18
Sulfate
 
February
2003
5.2.3
Reproductive
and
Developmental
Studies
Three
oral
studies
on
reproductive
and
developmental
effects
were
identified
for
sulfate.
On
the
basis
of
these
studies,
it
appears
that
sulfate
does
not
induce
adverse
reproductive
or
developmental
effects.

Sodium
sulfate
was
administered
by
gavage
at
a
concentration
of
2,800
mg/
kg/
day
to
pregnant
ICR/
SIM
mice
on
gestation
days
8
to
12
(
Seidenberg
et
al.
1986).
There
was
no
evidence
of
maternal
toxicity
or
increased
resorption
rate.
Pup
survival
was
100%,
and
no
adverse
developmental
effects
were
observed.
Neonatal
birth
weight
was
significantly
increased
in
the
treated
group
compared
with
controls.

Six
groups
of
10
female,
randomly
bred
albino
ICR
mice
were
administered
sodium
sulfate
in
drinking
water
at
dose
levels
of
0
(
distilled
water
control),
0
(
sodium
control),
625,
1,250,
2,500,
or
5,000
mg/
L
beginning
1
week
prior
to
breeding
(
Andres
and
Cline
1989).
The
amount
of
sodium
in
all
groups,
except
the
distilled
water
control,
was
kept
constant
by
administering
sodium
bicarbonate.
Control
mice,
receiving
only
distilled
water,
consumed
significantly
less
(
p
<
0.05)
than
mice
receiving
sulfate
treatments,
and
sodium­
control
mice
drank
significantly
more
water
(
p
<
0.05)
than
mice
treated
with
sulfate.
All
mice
were
carried
to
term.
No
differences
were
found
in
litter
size,
litter
weaning
weights,
or
gestational
or
lactational
weight
gain
of
the
dams
among
sulfate
treatments.
Histopathology
evaluations
were
not
performed.
The
authors
concluded
that
water
containing
up
to
5,000
mg/
L
sulfate
is
not
toxic
to
the
gestating
mouse.

Paterson
et
al.
(
1979)
investigated
the
effects
of
water
with
a
high
sulfate
content
on
swine
and
their
offspring.
The
pigs,
31
sows
and
27
gilts
of
Hampshire
×
Yorkshire
×
Duroc
breeding,
were
randomly
divided
into
three
groups
that
received
either
tap
water
(
320
mg
sulfate/
L)
or
water
with
sodium
sulfate
added
at
1,790
mg/
L
or
3,298
mg/
L.
The
animals
were
given
access
to
these
waters
from
prebreeding
day
30
through
lactation
day
28.
No
significant
differences
in
gestation
or
lactation
weight
gain,
number
of
pigs
delivered,
or
average
pig
and
litter
birth
weights
were
reported.

5.2.4
Cancer
Studies
In
a
study
of
the
toxicity
and
carcinogenicity
of
nickel
compounds
(
nickel
hydroxide
and
nickel
sulfate)
in
Wistar
rats,
sodium
sulfate
(
used
as
a
control)
did
not
appear
to
be
tumorigenic
(
Kasprazak
et
al.
1980).
In
this
study,
Wistar
rats
(
100
males
and
10
females)
were
injected
intramuscularly
every
other
day
for
4
weeks
with
0.7
mg
sodium
sulfate/
rat
(
approximately
2
mg
SO
4
2­/
kg
in
aqueous
solution
at
pH
5.6).
After
8
months,
no
tumors
were
observed
in
either
the
sodium
sulfate
or
nickel
sulfate
treated
rats.
However,
the
value
of
this
study
in
assessing
the
carcinogenic
effects
of
sulfate
ingestion
is
limited
because
of
the
route
of
exposure,
the
duration
of
the
study,
and
the
nonstandard
protocol.
19
Sulfate
 
February
2003
6.0
ORGANOLEPTIC
PROPERTIES
Water
contaminated
with
sulfates
may
have
an
unpleasant
taste.
Characteristics
such
as
taste,
odor,
and
color,
often
referred
to
as
organoleptic
properties,
are
not
used
by
EPA
for
developing
primary
water
standards.
Organoleptic
properties,
however,
can
be
used
in
the
establishment
of
secondary
drinking
water
standards.

EPA
established
a
secondary
drinking
water
standard
of
250
mg/
L
for
sulfate
in
1984
based
on
taste
properties
(
U.
S.
EPA
1984).
This
value
was
adopted
from
the
Public
Health
Service
Drinking
Water
Standards
(
PHS
1962).
Secondary
standards
are
not
enforceable
by
the
Federal
Government;
they
are
recommended
to
States
as
reasonable
goals
for
contaminants,
but
there
is
no
obligation
for
the
States
to
reach
these
goals.

There
is
a
paucity
of
actual
experimental
data
available
on
the
taste
threshold
for
sulfate.
Taste
threshold
concentrations
for
several
common
sulfate
salts
have
been
reported.
The
taste
thresholds
varied
depending
on
the
type
of
salt:
170­
370
mg/
L
sulfate
as
sodium
sulfate,
180­
640
mg/
L
as
calcium
sulfate,
and
320­
480
mg/
L
as
magnesium
sulfate
(
Lockhart
et
al.
1955,
as
cited
in
PHS
1962).

The
detection
of
taste
differs
from
the
perception
of
a
taste
as
unpleasant.
Accordingly,
the
results
reported
by
Heizer
et
al.
(
1997)
on
the
response
of
10
subjects
to
sulfate
in
drinking
water
are
of
interest.
After
completion
of
the
exposure
component
of
this
study,
8
of
the
10
subjects
rated
the
taste
of
1,200
mg/
L
sulfate,
as
sodium
sulfate,
as
neutral
to
slightly
unpleasant.
One
subject
rated
the
water
as
moderately
unpleasant
and
another
as
very
unpleasant.
This
study
indicates
there
is
variability
in
the
response
to
the
taste
of
sulfate,
and
the
threshold
for
detecting
an
unpleasant
taste
is
apparently
above
the
threshold
of
taste.

In
the
study
of
the
laxative
effects
of
sulfate
that
was
conducted
for
EPA
by
CDC
(
U.
S.
EPA
1999a),
the
subjects
were
asked
if
the
smell
or
taste
of
the
water
was
different
from
that
which
they
usually
consumed.
All
subjects
received
sulfate­
free
control
water
on
days
1,
2,
and
6
of
the
study
and
either
the
sulfate­
free
water
(
controls)
or
a
sulfate­
containing
water
on
days
3,
4,
and
5
of
the
study.
There
was
a
definite
increase
in
the
number
of
subjects
who
thought
that
the
water
tasted
differently
on
days
3,
4,
and
5
for
the
800
and
1,200
mg/
L
concentrations,
with
79%
and
82%
reporting
a
difference
in
taste,
respectively.
Average
daily
water
consumption
also
decreased
in
these
same
groups
on
days
3,
4,
and
5
when
compared
with
intakes
on
days
1,
2,
and
6.
About
half
of
the
participants
receiving
the
250
and
500
mg/
L
concentrations
reported
a
difference
in
taste
(
57%
and
50%
respectively)
on
the
days
when
they
were
exposed
to
sulfate.
Water
consumption
showed
a
downward
trend
over
this
same
period
as
well.
Twenty­
five
percent
of
the
control
group
also
reported
that
there
was
a
difference
in
the
taste
of
the
water.
For
this
group,
there
was
no
downward
trend
in
water
consumption
across
the
3­
day
exposure
period.

The
ability
to
taste
differs
among
individuals,
as
well
as
in
the
same
individual
at
different
times.
Temperature
and
the
presence
of
other
dissolved
solids
in
the
water
also
influence
taste.
Given
the
expected
variability
in
taste,
as
well
as
the
results
in
Heizer
et
al.
(
1997),
the
U.
S.
EPA
secondary
maximum
contaminant
level
(
SCML)
of
250
mg/
L
should
be
adequately
protective
for
adverse
sulfate
taste
effects.
20
Sulfate
 
February
2003
7.0
CHARACTERIZATION
OF
HAZARD
AND
DOSE­
RESPONSE
7.1
Hazard
Characterization
Some
data
are
available
that
report
human
responses
to
sulfate.
Data
include
those
from
controlled
settings
(
i.
e.,
studies
and
experimental
trials)
and
uncontrolled
settings
(
i.
e.,
case
studies
from
areas
with
high
sulfate
concentrations
in
the
drinking
water).
Most
of
the
available
data
are
based
on
short­
term
exposure
and
were
obtained
from
controlled
studies.
Reports
on
long­
term
exposure
are
based
on
responses
to
questionnaires
in
North
Dakota
and
South
Dakota,
States
with
high
sulfate
concentrations
in
their
drinking
water
supply.
In
animals,
data
on
reproductive
and
developmental
effects
are
available
for
short­
term
and
long­
term
exposures
to
sulfate.
There
are
limited
data
on
the
potential
carcinogenic
effects
of
sulfate.

The
available
data
demonstrate
that
sulfate
induces
a
laxative
effect
following
acute
exposures
to
relatively
high
concentrations
(
Anderson
and
Stothers
1978,
Fingl
1980,
Schofield
and
Hsieh
1983,
Stephen
et
al.
1991,
Cochetto
and
Levy
1981,
U.
S.
EPA
1999a,
Gomez
et
al.
1995,
Heizer
et
al.
1997).
The
concentrations
of
sulfate
that
induced
these
effects
varied,
but
all
occurred
at
concentrations
>
500
mg/
L.
However,
the
severity
of
the
laxative
effect
that
occurs
from
acute
sulfate
exposures
may
be
dependent
on
the
sulfate
salt,
as
well
as
how
the
dose
is
administered.
For
example,
magnesium
sulfate
exerts
a
stronger
laxative
effect
than
sodium
sulfate.
This
likely
occurs
because
magnesium
sulfate
is
absorbed
less
completely
than
sodium
sulfate
and
has
a
more
pronounced
effect
on
the
osmolarity
of
the
intestinal
contents
(
Morris
and
Levy
1983b).
Additionally,
a
single
dose
of
sulfate
that
produces
a
laxative
effect
does
not
have
the
same
effect
when
divided
and
administered
in
intervals,
i.
e.,
a
single
dose
produced
severe
diarrhea,
whereas
divided
doses
produced
only
mild
or
no
diarrhea
(
Cochetto
and
Levy
1981).

Chronic
and
subchronic
exposures
to
high
concentrations
of
sulfate
do
not
appear
to
produce
the
same
laxative
effect
as
seen
in
acute
exposures.
In
a
90­
day
study
using
Sprague­
Dawley
rats,
Wurzner
(
1979)
did
not
observe
soft
feces
or
diarrhea
in
rats
administered
mineral
waters
containing
up
to
1,595
mg/
L
of
sulfate.
However,
earlier
reports
indicate
that
chronic
exposure
to
high
sulfate
concentrations
in
drinking
water
resulted
in
laxative
effects
in
humans
(
Peterson
1951,
Moore
1952,
Cass
1953).
These
reports
used
data
that
were
based
on
questionnaires,
which
may
be
subject
to
bias.
For
example,
the
questionnaire
included
an
inquiry
about
the
laxative
effect
that
requested
a
YES
or
NO
response.
This
type
of
question
is
subject
to
the
respondent
=
s
interpretation
of
what
constitutes
a
laxative
effect.
In
addition,
sulfate
was
probably
not
the
only
contaminant
found
in
the
drinking
water.
Chronic
exposure
to
sulfate
may
not
have
the
same
laxative
effect
as
an
acute
exposure
because
humans
appear
to
develop
a
tolerance
to
drinking
water
with
high
sulfate
concentrations
(
Schofield
and
Hsieh
1983).
It
is
not
really
known
when
this
acclimation
occurs;
however,
in
adults,
acclimation
is
thought
to
occur
between
one
to
two
weeks
(
U.
S.
EPA
1999b).

No
adverse
developmental
effects
were
observed
following
the
administration
of
2,800
mg/
kg/
day
of
sulfate
to
pregnant
ICR/
SIM
mice
on
gestation
days
8
to
12
(
Seidenberg
et
al.
1986).
No
reproductive
effects
were
observed
following
the
ingestion
of
drinking
water
containing
up
to
5,000
mg/
L
of
sulfates
by
ICR/
SIM
mice
(
Andres
and
Cline
1989)
or
3,298
mg/
L
of
sulfates
by
Hampshire
×
Yorkshire
×
Duroc
pigs
(
Paterson
et
al.
1979).
Based
on
these
studies,
sulfate
does
not
appear
to
be
a
reproductive
or
a
developmental
toxicant.
21
Sulfate
 
February
2003
No
tumors
were
observed
after
8
months
in
a
study
using
Wistar
rats
injected
intramuscularly
with
sodium
sulfate
every
other
day
for
4
weeks
(
Kasprazak
et
al.
1980).
Because
of
the
shortterm
observation
period,
the
route
of
exposure,
and
the
experimental
protocol,
it
is
not
possible
to
draw
conclusions
on
the
potential
carcinogenicity
of
sulfate.
Because
of
the
limited
data,
U.
S.
EPA/
Office
of
Water
(
1993)
has
classified
sulfate
as
Group
D
 
not
classified
as
to
human
carcinogenicity.
This
category
is
reserved
for
contaminants
with
inadequate
evidence
to
support
a
determination
on
carcinogenicity.

7.2
Characterization
of
Organoleptic
Effects
The
ability
to
taste
differs
among
individuals,
as
well
as
for
the
same
individual
at
different
times.
The
temperature
of
the
water,
the
companion
ion,
and
the
presence
of
other
dissolved
solids
impact
the
taste
sensation.
There
is
also
a
difference
between
the
concentrations
that
impart
a
taste
to
water
and
those
that
are
classified
as
causing
an
unpleasant
taste.
Each
of
these
factors
makes
it
difficult
to
define
a
taste
threshold
for
sulfate.

The
experimental
data
on
the
organoleptic
properties
of
sulfate
in
drinking
water
are
limited.
No
studies
were
identified
that
were
conducted
using
standard
taste­
testing
procedures.
In
the
study
by
Heizer
et
al.
(
1997),
8
of
10
subjects
rated
the
taste
of
drinking
water
containing
1,200
mg/
L
sulfate
as
neutral
to
only
slightly
unpleasant.
Two
subjects
classified
the
taste
as
moderately
to
extremely
unpleasant.
In
the
study
conducted
by
CDC
for
EPA
(
1999a),
about
50%
of
the
participants
could
not
distinguish
between
the
taste
of
sulfate­
free
water
and
water
containing
either
250
mg/
L
sulfate
or
500
mg/
L
sulfate.
Even
when
the
water
contained
1,200
mg/
L
sulfate,
20%
of
the
participants
could
not
detect
the
taste.

Given
the
variability
in
the
ability
of
consumers
to
identify
a
taste
in
water
that
contains
sulfate,
the
present
SMCL
of
250
mg/
L
appears
to
be
adequately
protective
of
the
aesthetic
taste
properties
of
drinking
water
containing
sulfate.

7.3
Dose­
Response
Characterization
Although
several
studies
(
Peterson
1951,
Moore
1952,
Cass
1953)
have
examined
the
effects
of
long­
term
exposure
of
humans
to
sulfate
in
drinking
water,
none
of
them
can
be
used
to
derive
a
dose­
response
characterization.
These
studies
utilized
data
collected
from
the
North
Dakota
Department
of
Health
Survey
(
Moore
1952).
An
increasing
trend
was
observed
in
persons
reporting
laxative
effects
as
sulfate
concentrations
increased
(
i.
e.,
22%,
24%,
33%,
and
69%
for
sulfate
concentrations
of
0­
200,
200­
500,
500­
1,000,
and
>
1,000
mg/
L,
respectively).
However,
the
results
of
these
studies
cannot
be
used
to
derive
a
dose­
response
characterization
for
the
following
reasons:
(
1)
the
results
are
based
on
recall
with
little
scientific
weight
(
i.
e.,
sulfate
may
have
induced
the
laxative
effects,
but
it
cannot
be
proven);
and
(
2)
the
water
samples
had
varying
concentrations
of
magnesium
and
total
dissolved
solids
in
addition
to
sulfate.

No
laxative
effects
were
observed
in
rats
(
Wurzner
1979)
or
heifers
(
Digesti
and
Weeth
1976)
following
long­
term
exposure
to
sulfate
in
drinking
water.
Consequently,
these
studies
cannot
be
used
for
a
dose­
response
characterization.
22
Sulfate
 
February
2003
Because
sulfate
appears
to
exert
its
laxative
effect
with
short­
term
exposures
rather
than
longterm
exposures,
several
short­
term
exposure
studies
were
reviewed.
Three
short­
term
studies
were
identified
that
evaluated
the
effect
of
various
sulfate
concentrations
on
bowel
function
in
a
controlled
environment:
two
in
humans
and
one
in
animals.
In
the
multiple­
dose
study
by
Heizer
et
al.
(
1997),
sulfate
concentrations
of
0,
400,
600,
800,
1,000,
or
1,200
mg/
L
were
given
to
four
subjects
(
two
men
and
two
women)
for
six
consecutive
2­
day
periods
(
2
days
per
concentration).
A
significant
trend
was
observed
for
a
decreasing
mouth­
to­
anus
markerappearance
time
of
chemical
markers
with
increasing
sulfate
concentration.
For
a
single­
dose
study
by
the
same
researchers,
six
adults
(
three
men
and
three
women)
received
drinking
water
with
sulfate
concentrations
of
0
or
1,200­
mg/
L
for
two
consecutive
6­
day
periods.
Statistically
significant
increases
in
mean
stool
mass
per
6­
day
pool
and
in
mean
stool
mass
per
hour
were
observed
in
the
1,200­
mg/
L
dose
group.
However,
none
of
the
subjects
reported
frank
diarrhea.

CDC
conducted
a
study
for
EPA
(
1999a)
that
examined
the
effect
of
sudden
changes
in
sulfate
levels
in
drinking
water
in
105
subjects.
The
participants
received
water
containing
sulfate
at
0,
250,
500,
800,
or
1,200
mg/
L
from
day
3
through
day
5,
and
were
given
sulfate­
free
bottled
water
for
days
1,
2,
and
6.
There
were
no
statistically
significant
differences
in
the
mean
number
of
bowel
movements
in
any
group
or
a
dose­
response
relationship
between
sulfate
dose
and
reports
of
diarrhea
(
one­
sided
p
=
0.099).
However,
when
the
diarrhea
incidence
data
for
the
lowest
three
dose
groups
were
compared
to
the
incidence
for
the
800
mg/
L
and
1,200
mg/
L
dose
groups,
there
was
a
dose­
related
trend
for
increased
stool
volume
(
osmotic
diarrhea)
when
the
three
groups
were
compared
(
9%,
15%,
and
18%).
The
dose­
related
trend,
however,
was
not
statistically
significant.

Neonatal
piglets
were
exposed
to
various
concentrations
of
sulfate
to
simulate
the
effect
of
inorganic
sulfate
on
the
bowel
function
in
infants
(
Gomez
et
al.
1995).
No
diarrhea
was
observed
in
any
of
the
piglets
at
0
and
1,200
mg/
L
concentrations;
however,
concentrations
greater
than
1,200
mg/
L
resulted
in
an
increased
prevalence
of
diarrhea,
and
concentrations
greater
than
1,800
mg/
L
resulted
in
persistent,
nonpathogenic
diarrhea.

These
studies
as
a
group
suggest
that
there
is
a
risk
for
a
laxative­
type
response
to
sulfate
in
drinking
water
at
concentrations
greater
than
1,000
mg/
L
(
U.
S.
EPA
1999a,
Heizer
et
al.
1997,
Moore
1952).
The
observed
effect
is
a
response
to
the
net
osmolarity
of
the
intestinal
contents,
and
thus
is
influenced
not
only
by
sulfate
intake,
but
also
by
the
presence
of
other
osmotically
active
materials
in
the
drinking
water
or
diet,
and
by
the
temporal
pattern
of
sulfate
ingestion.
The
laxative
effect
of
sulfate
can
be
manifest
as
an
increase
in
stool
mass,
increased
stool
volume,
increased
stool
moisture,
decreased
intestinal
transit
time,
and/
or
frank
diarrhea.
Frank
diarrhea
did
not
occur
in
either
of
the
controlled
human
studies
of
sulfate
exposure
(
U.
S.
EPA
1999a,
Heizer
et
al.
1997).
There
was
merely
a
slight
increase
in
stool
mass
or
stool
volume
with
sulfate
concentrations
of
800
to
1,200
mg/
L.

At
this
time,
it
is
not
possible
to
characterize
a
dose­
response
relationship
for
laxative
effects
due
to
short­
or
long­
term
exposure
to
sulfate.
A
Centers
for
Disease
Control
and
Prevention
(
CDC)
panel
favored
a
health
advisory
for
situations
where
sulfate
levels
in
drinking
water
are
greater
than
500
mg/
L
(
U.
S.
EPA
1999b).
The
most
sensitive
endpoint
was
considered
by
the
panelists
to
be
osmotic
diarrhea.
The
panelists
concluded
that
the
existing
literature
supports
restricting
sulfate
exposure,
especially
for
infants,
when
the
advisory
value
of
500
mg/
L
is
exceeded.
The
23
Sulfate
 
February
2003
panelists
referred
to
the
study
by
Chien
et
al.
(
1968),
which
found
that
sulfate
levels
$
630
mg/
L
caused
diarrhea
in
infants.
It
should
be
noted
that
this
effect
was
observed
after
the
infants
had
ingested
formula
made
with
water
containing
sulfate
and
other
osmotically
active
agents.
In
fact,
the
total
dissolved
solid
concentration
of
the
water
used
to
prepare
infant
formulas
was
high
(
2,424
to
3,123
mg/
L)
and
in
two
cases
contained
substantial
quantities
of
magnesium
(
124
and
130
mg/
L).
The
CDC
panel
concluded
that
500
mg/
L
seemed
to
be
a
safe
level
for
sulfate
ingestion,
as
500
mg/
L
was
shown
to
be
safe
in
all
studies.
For
comparison,
the
osmolarity
of
500
mg/
L
sulfate
as
sodium
sulfate
is
15.6
mOsmol/
L
whereas
the
osmolarity
of
the
ions
(
Na,
K,
Cl,
and
citrate)
in
Pedialyte,
a
preparation
used
to
treat
diarrhea
and
replenish
electrolytes
in
infants,
is
110
mOsmol/
L.
When
the
dissolved
sugars
in
Pedialyte
are
included
the
osmolarity
increases
to
250
mOsmol/
L.

The
experimental
data
on
the
organoleptic
properties
of
sulfate
in
drinking
water
are
limited.
In
a
study
by
Heizer
et
al.
(
1997),
8
of
10
subjects
rated
the
taste
of
drinking
water
containing
1,200
mg/
L
sulfate
as
neutral
to
slightly
unpleasant.
Only
two
classified
the
taste
as
moderately
to
extremely
unpleasant.
In
the
study
conducted
by
CDC
for
EPA
(
1999a),
approximately
50%
of
the
participants
stated
that
water
containing
250
mg/
L
sulfate
and
500
mg/
L
sulfate
tasted
different
from
the
sulfate­
free
control
water.

Given
the
apparent
variability
in
consumers'
ability
to
identify
a
taste
in
water
that
contains
sulfate,
the
present
SMCL
of
250
mg/
L
appears
to
be
adequately
protective
of
the
esthetic
taste
properties
of
drinking
water
containing
sulfate.
The
health­
based
advisory
value
of
500
mg/
L
will
protect
against
sulfate's
laxative
effects
in
the
absence
of
high
concentrations
of
other
osmotically
active
chemicals
in
the
water.
In
situations
where
the
water
contains
high
concentrations
of
total
dissolved
solids
and/
or
other
osmotically
active
ions,
laxative­
like
effects
may
occur
if
the
water
is
mixed
with
concentrated
infant
formula
or
powdered
nutritional
supplements.
In
such
situations,
an
alternate
low­
mineral­
content
water
source
is
advised.
Infants
are
more
susceptible
to
diarrheal
water
loss
than
adults
because
of
differences
in
gastrointestinal
structure
and
function.
24
Sulfate
 
February
2003
8.0
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