Page
1
of
18
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
24,
2002
MEMORANDUM
SUBJECT:
Tolerance
Reassessment
Decisions
Completed
by
the
Inert
Ingredient
Focus
Group
FROM:
Peter
Caulkins,
Associate
Director
Registration
Division
TO:
Betty
Shackleford,
Acting
Associate
Director
Special
Review
and
Reregistration
Division
The
purpose
of
this
document
is
to
provide
the
Special
Review
and
Reregistration
Division
(
SRRD)
with
an
update
on
tolerance
reassessment
decisions.

Please
find
attached
the
five
Decision
Documents
that
represent
the
Mineral
Acids
Grouping.
In
total
these
documents
represent
52
tolerance
reassessments.

If
you
have
any
comments
or
questions,
please
contact
Kathryn
Boyle
at
703­
305­
6304.

Attachments
Page
2
of
18
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
24,
2002
MEMORANDUM
FROM:
Kathryn
Boyle,
CoChair
IIFG
and
Kerry
Leifer,
CoChair
IIFG
TO:
Robert
Forrest,
Chief
Minor
Use,
Inerts,
and
Emergency
Response
Branch
SUBJECT:
IIFG
Decision
Documents
on
Reassessing
Exemptions
from
the
Requirement
of
a
Tolerance
for
the
Mineral
Acids
(
Hydrochloric,
Carbonic,
Phosphoric,
and
Sulfuric)
and
their
Ammonium,
Calcium,
Ferrous,
Ferric,
Magnesium,
Potassium,
Sodium,
and/
or
Zinc
Salts
Collectively
these
Decision
Documents
cover
four
mineral
acids
and
the
salts
of
these
acids.
The
individual
Decision
Documents
are:
(
1)
Hydrochloric
Acid
and
Salts,
(
2)
Salts
of
Carbonic
Acid,
(
3)
Phosphoric
Acid
and
Salts,
and
(
4)
Sulfuric
Acid
and
Salts.
The
Inert
Ingredient
Focus
Group
reassessment
is
based
on
various
conclusions
of
the
FAO/
WHO
Joint
Expert
Committee
on
Food
Additives,
conclusions
of
various
FDA
GRAS
(
Generally
Recognized
As
Safe)
Assessments,
information
previously
used
by
OPP
as
part
of
the
reregistration
process,
and
other
information
available
on
government
websites.

In
total
46
exemptions
from
the
requirement
of
a
tolerance
in
40
CFR
180
are
reassessed.
This
total
consists
of
18
in
the
phosphoric
acid
document,
nine
in
the
hydrochloric
acid
document,
six
in
the
carbonic
acid
document,
and
13
in
the
sulfuric
acid
document.
Page
3
of
18
INERT
INGREDIENT
FOCUS
GROUP
DECISION
DOCUMENT
for
Salts
of
Carbonic
Acid
Petition
No.:
no
Tolerance
Reassessments?:
yes
Chemical
Category/
Group:
mineral
acid
and
salts
The
following
describes
the
various
ways
that
salts
of
carbonic
acid
are
used.

Table
1:
Use
Pattern
(
pesticidal
­
inert
ingredient)

Chemical
Name
PC
Code
40
CFR
180.1001
Inert
Use
Pattern
(
Pesticidal)
Current
Inert
List
ammonium
bicarbonate
873401
(
c)
surfactant,
suspending
agent,
dispersing
agent
4B
magnesium
carbonate
873503
(
c),
(
e)
anticaking
agent,
conditioning
agent
4B
potassium
carbonate
873504
(
d)
buffering
agent
4B
sodium
bicarbonate
873505
(
c)
neutralizer
4A
There
is
also
a
tolerance
exemption
for
sodium
carbonate
40
CFR
180.2.

The
tolerance
exemptions
for
calcium
carbonate
were
reassessed
in
the
IIFG
Decision
Document
"
Weathered
Materials",
dated
January
31,
2002.
Calcium
carbonate
is
a
List
4A
Potassium
bicarbonate
(
40
CFR
180.1177)
and
sodium
bicarbonate
(
40
CFR
180.1176)
are
used
as
active
ingredients.
(
Note
that
both
tolerance
exemptions
were
established
post­
FQPA.)
Potassium
bicarbonate
is
used
in
six
products
at
204
use
sites,
which
includes
many
food
crops,
as
well
as
ornamentals
and
turf.
It
is
used
against
45
pests
including
mildew
and
leaf
spot.
Sodium
bicarbonate
is
in
one
product
which
is
a
product
used
only
to
formulate
other
pesticides.
There
are
no
longer
any
EPA­
registered
active
ingredient
uses
for
any
of
the
other
above­
listed
Page
4
of
18
carbonate
salts.

It
is
noted
that
there
is
information
in
this
document
on
other
carbonate
salts
for
which
tolerance
exemptions
do
not
currently
exist.
These
data
are
being
used
as
surrogate
data.

Table
2:
Use
Pattern
(
FDA
GRAS)

Chemical
GRAS
Citation
GRAS
Uses
ammonium
bicarbonate
21
CFR
184.1135
dough
strengthener,
leavening
agent,
pH
control
agent,
texturizer
ammonium
carbonate
21
CFR
184.1137
leavening
agent,
pH
control
agent
magnesium
carbonate
21
CFR
184.1425
anticaking
and
free­
flow
agent,
flour
treating
agent,
lubricant
and
release,
nutrient
supplement,
pH
control
agent,
processing
aid,
synergist
potassium
bicarbonate
21
CFR
184.1613
formulation
aid,
nutrient
supplement,
pH
control
agent,
processing
aid
potassium
carbonate
21
CFR
184.1619
flavoring
agent
and
adjuvant,
nutrient
supplement,
pH
control
agent,
processing
aid
sodium
bicarbonate
21
CFR
184.1736
(
no
limitations
specified)

sodium
carbonate
21
CFR
184.1742
antioxidant,
curing
and
pickling
agent,
flavoring
agent
and
adjuvant,
pH
control
agent,
processing
aid
Sodium
bicarbonate
also
is
used
in
food
contact
surface
sanitizing
solutions
under
21
CFR
178.1010.
Page
5
of
18
Table
3:
Use
Pattern
(
non­
pesticidal)

Chemical
Uses
ammonium
bicarbonate
in
baking
powder
formulations;
in
cooling
baths;
fire
extinguishers;
manufacture
of
porous
plastics,
ceramics;
manufacture
of
dyes
and
pigments;
in
compost
heaps
to
accelerate
decomposition;
as
fertilizer;
for
defatting
textiles;
in
cold
wave
solutions;
in
chrome
leather
tanning;
to
remove
gypsum
from
heat
exchangers
and
other
processing
equipment.
magnesium
carbonate
used
to
prepare
high
purity
magnesium
compounds
in
the
paint
and
printing
inks
industries;
manufacture
of
fireproofing,
fire­
extinguishing,
flooring,
and
polishing
compounds;
fillers
and
smoke
suppressants
in
the
plastics
and
rubber
industries;
USP
grade
is
used
as
an
additive
to
table
salt
to
keep
it
free
flowing;
a
bulking
compound
in
powder
formulations;
an
antacid.
potassium
carbonate
manufacture
of
soap,
glass,
pottery,
smalts
and
many
potassium
salts;
in
analytical
chemistry;
Television
glass
accounts
for
a
substantial
portion
of
the
consumption
of
potassium
carbonate
because
the
potassium
salt
is
more
compatible
with
the
lead,
barium,
and
strontium
oxides
contained
in
these
glasses
than
is
sodium
carbonate.
sodium
bicarbonate
Leavening
agent
in
baking
powder
and
food
ingredients;
component
of
soaps,
detergents
and
pharmaceuticals;
agent
in
leather
tanning;
textile
manufacturing;
paper
manufacturing;
fire
extinguishers;
in
industrial
and
household
chemicals
It
should
be
noted
that
ammonium
bicarbonate
can
be
used
as
a
fertilizer.
Plants
need
various
elements
(
metals
and
non­
metals)
for
proper
growth.
Especially
for
agricultural
crops,
plants
are
supplied
these
elements
as
part
of
chemical
fertilizers.
The
most
important
elements
for
plant
growth
are
nitrogen,
phosphorus,
and
potassium.
Other
metals
needed
in
the
soil
for
plant
up­
take
are
calcium,
magnesium,
iron,
and
trace
elements
such
as
zinc.
Ammonium
bicarbonate
can
be
intentionally
added
to
growing
agricultural
crops
as
needed
to
promote
plant
growth.

Assessment
of
the
Salts
of
Carbonic
Acid
The
ammonium,
sodium,
potassium,
and
magnesium
salts
of
carbonic
acid
are
being
assessed
as
a
group
due
to
their
chemical
similarities.
However,
these
salts
all
contain
either
the
bicarbonate
ion
(
HCO
3
­
1
)
or
the
carbonate
ion
(
CO
3
­
2
),
and
thus
share
some
common
chemistries.
A
major
focus
of
this
assessment
is
the
work
previously
performed
by
FDA
in
assessing
the
safety
of
these
chemicals
as
food
additives.

1.
Physical/
Chemical
Properties:

The
physical
and
chemical
properties
of
the
salts
of
carbonic
acid
are
described
in
the
May
7,
2002
EFED
Assessment.
See
attached.

2.
Information
Sources:
Page
6
of
18
The
following
information
was
used
in
performing
this
assessment:
The
available
information
consisted
of
information
retrieved
from
various
websites,
such
as,
°
EPA
(
www.
epa.
gov),
°
NIOSH,
(
www.
cdc.
gov/
niosh/
ipcsneng/
neng1333.
html),
(
www.
cdc.
gov/
niosh/
ipcsneng/
neng0969.
html),
°
TOXNET
(
www.
toxnet.
nlm.
nih.
gov.),
°
WHO
(
www.
inchem.
org/
documents/
jecfa/
jecmono/
v17je02.
htm)

Various
FDA
GRAS
Assessments
were
also
used.

3.
NIOSH
(
National
Institute
for
Occupational
Safety
and
Health)

The
NIOSH
International
Chemical
Safety
Card
for
ammonium
hydrogen
carbonate
indicates
that
a
TLV
(
Threshold
Limit
Value)
has
not
been
established.
The
chemical
can
irritate
the
skin
and
the
respiratory
tract.

The
NIOSH
International
Chemical
Safety
Card
for
magnesium
carbonate
indicates
a
TLV
(
Threshold
Limit
Value)
of
10
mg/
m3.
The
chemical
may
have
effects
on
the
lungs
if
the
magnesite
(
the
naturally
occurring
form
of
magnesium
carbonate)
contains
more
than
1%
crystalline
silica.

4.
Acid
Characteristics
An
acid
is
a
substance
that
when
dissolved
in
water
yields
H+
ions.
The
increase
of
the
concentration
of
the
H+
ions
lowers
the
pH.
Mineral
acids
contain
a
non­
metal
such
as
phosphorus,
nitrogen,
sulfur,
or
chlorine
which
may
or
may
not
be
combined
with
oxygen.
When
combined
with
oxygen,
these
anions
can
be
referred
to
as
oxyanions.
Strong
acids
are
those
acids
that
when
dissolved
completely
transfer
their
H+
ions
to
water.
Others
acids
such
as
carbonic
are
referred
to
as
weak
acids:
they
exist
in
solution
as
a
mixture
of
acid
molecules
and
various
ions
formed
by
the
dissociation
of
the
acid
molecule.
The
predominant
anions
for
carbonic
acid
are
bicarbonate
(
HCO
3
­
1
)
at
pHs
below
8
and
carbonate
(
CO
3
­
2
)
at
pHs
above
10.

5.
Cations:
Sodium,
Potassium,
and
Magnesium
Generally,
when
any
salt
of
an
acid,
such
as
carbonic
acid,
is
dissolved
in
water,
dissociation
yields
the
anions,
which
are
negatively
charged,
and
a
positively
charged
cation.
In
the
human
body,
these
salts
tend
to
dissociate
and
thus,
for
the
most
part,
react
in
the
body
as
the
anion
and
the
cation.

Metals
such
as
sodium,
magnesium,
and
potassium
are
required
for
proper
functioning
of
human
biological
systems.
For
risk
assessment
purposes
an
important
feature
of
these
metals
is
that
overall
the
body
does
have
an
effective
means
of
processing
them.
The
primary
means
of
exposure
to
these
cations
is
ingestion.
Four
of
the
most
common
cations
required
for
functioning
Page
7
of
18
of
human
biology
are:
sodium,
potassium,
calcium
and
magnesium.
Chemically,
sodium
and
potassium
belong
to
the
same
chemical
family:
calcium
and
magnesium
belong
to
a
different
chemical
family.

Sodium:

The
average
human
body
burden
of
sodium
is
approximately
20
grams
(
g)
for
a
70
kilogram
(
kg)
adult.
The
sodium
cation
is
necessary
for
the
nerves
and
muscles
to
function
properly.
It
is
the
principal
cation
of
extracellular
fluid,
and
helps
to
maintain
the
body's
water
balance.
These
electrolytes,
the
electrically
charged
ions
in
the
body
fluids,
consist
to
a
great
extent
of
sodium
and
potassium.
There
is
no
Recommended
Dietary
Allowance
(
RDA)
for
sodium.

Potassium:

The
average
human
body
burden
of
potassium
is
approximately
140
g
for
a
70
kg
adult.
The
potassium
cation
is
important
in
regulating
blood
pressure,
regulating
cellular
water
content,
maintaining
proper
pH
balance,
and
transmission
of
nerve
impulses.
It
helps
to
regulate
the
electrical
activity
of
the
heart
and
muscles.
The
potassium
RDA
is
900
mg/
day.

Magnesium:

The
average
human
body
burden
of
magnesium
is
approximately
20
g
for
a
70
kg
adult.
The
magnesium
cation
is
also
used
in
building
bones.
It
plays
a
role
in
releasing
energy
from
muscles
and
regulating
body
temperature.
The
RDA
for
magnesium
is
310
to
320
mg/
day
for
adult
females
and
400
to
420
mg/
day
for
adult
males
with
the
RDA
increasing
with
increasing
age.

6.
Ammonium
Salt:

Ammonium
carbonate
salts
dissociate
to
form
the
positively
charged
ammonium
cation
(
NH
4
+).
Humans
cannot
convert
atmospheric
nitrogen
to
any
form
that
can
be
used
as
part
of
any
of
the
various
metabolic
cycles.
Therefore,
reduced
nitrogen
(
NH
4
+)
has
to
enter
the
body
from
an
outside
source.
These
sources
are
the
nitrogen­
containing
amino
acids
in
protein
which
are
consumed
daily
as
part
of
the
diet.
Although
the
human
body
can
produce
some
amino
acids,
ten
amino
acids
are
considered
"
essential"
amino
acids,
i.
e.,
they
must
be
consumed
in
the
diet.

Generally
the
body
works
to
maintain
a
balance
of
nitrogen
intake
and
nitrogen
excretion.
The
estimated
daily
ammonia
intake
through
food
and
drinking
water
is
18
mg.
In
contrast,
4000
mg
of
ammonia
per
day
are
produced
endogenously
in
the
human
intestine.

Ammonia
and
the
ammonium
ion
are
integral
components
of
normal
human
metabolic
processes.
Ammonia
is
released
following
deamination
that
occurs
when
protein
is
used
by
the
body
for
energy
production.
The
liver
converts
ammonia
via
the
urea
cycle
into
urea.
According
Page
8
of
18
to
FDA
in
the
"
Evaluation
of
the
Health
Aspects
of
Certain
Ammonium
Salts
as
Food
Ingredients"
(
1974),
"
the
normal
liver
so
readily
detoxifies
ammonium
ion
from
alimentary
sources
that
blood
concentrations
of
ammonium
salts
do
not
rise
to
the
levels
necessary
to
evoke
toxic
response."
Approximately
80%
of
the
body's
excess
nitrogen
is
eliminated
through
the
kidneys
as
urea,
approximately
25
to
30
grams
per
day.
Page
9
of
18
7.
Toxicological
Profile
Table
The
Agency
has
not
reviewed
any
of
the
toxicological
studies
in
the
following
table
for
any
of
the
salts
of
carbonic
acid.
The
reviews
of
these
studies
were
obtained
from
Toxnet,
as
well
as
other
government
websites.

Table
4:
Toxicological
Profile
Chemical
Toxicity
Other
Information
Ammonium
carbonate
Contact
with
eyes
or
skin
causes
irritation,
if
inhaled
will
cause
difficulty
in
breathing;
Ammonium
compounds
used
as
fertilizers
are
a
toxicological
hazard
when
livestock
have
access
to
residues
or
pools
of
solution
on
a
pasture
CERCLA
Reportable
Quantity:
greater
than
5000
lb
(
2270
kg);

Designated
as
a
hazardous
substance
under
section
311(
b)(
2)(
A)
of
the
Federal
Water
Pollution
Control
Act
and
further
regulated
by
the
Clean
Water
Act
Ammonium
bicarbonate
Inhalation
may
cause
respiratory
irritation;

Contact
with
eyes
or
skin
causes
irritation;

There
appears
to
be
a
more
rapid
excretion
of
ammonia
following
ammonium
bicarbonate
infusions,
which
result
in
higher
unionized
ammonia
levels
in
blood
compared
with
those
following
ammonium
chloride
infusions;
Mutagenicity:
Ames
assays
strains
TA
97
and
TA102
with
and
without
rat
liver
activation:
Negative.
CERCLA
Reportable
Quantity:
greater
than
5000
lb
(
2270
kg);

Designated
as
a
hazardous
substance
under
section
311(
b)(
2)(
A)
of
the
Federal
Water
Pollution
Control
Act
and
further
regulated
by
the
Clean
Water
Act
Page
10
of
18
Magnesium
Carbonate
Repeated
doses
may
cause
diarrhea,
which
may
cause
fluid
and
electrolyte
imbalance;

Can
cause
hypermagnesemia
in
those
with
severely
impaired
renal
function;

Can
alkalinize
the
urine;

Magnesium
salts
are
poorly
absorbed
from
the
intestine;

Normal
range
of
magnesium
serum
concentrations
1.5
to
2.5
mEq/
L
1974
Production
in
US:
5.4
x
106
kg
(
1227
tons),

with
another
2%
of
that
amount
imported
that
year.

Potassium
Carbonate
Oral
LD50:
Rat
1870
mg/
kg;
Mouse
2570
mg/
kg;

Inhalation
LC50:
Rat
>
500
mg/
m3;

Irritating
to
skin
,
mucous
membrane
of
eyes
and
upper
respiratory
tract;

Irritant
and
caustic
action
similar
to
that
of
potassium
hydroxide,
but
less
severe;
Negative
in
the
Ames
assays
with
two
strains
of
Salmonella
typhimurium
(
TA
97
and
TA102)
with
and
without
activation
Common
Name:
Potash.

Sodium
Bicarbonate
Developmental
Toxicity:
No
effects
found
up
to
580
mg/
kg
in
mice,
340
mg/
kg
in
rats,
and
330
mg/
kg
in
rabbits;

Negative
in
the
Ames
assays
with
two
strains
of
Salmonella
typhimurium
(
TA
97
and
TA102)
with
and
without
activation;

Daily
doses
up
to
25
mEq/
kg
were
administered
to
patients
for
3
weeks,

changes
in
plasma
electrolyte
concentration
were
not
remarkable,
plasma
total
carbon
dioxide
increased
by
only
5
mEq/
L
with
largest
dose,

considerable
weight
gain
was
most
prominent
effect;

No
reports
of
toxicity
caused
by
the
ingestion
of
baking
soda;

Daily
dose
limited
to
200
mEq
in
persons
under
60
year
age
and
100
in
those
older;
Adults
with
normal
renal
function
can
tolerate
up
to
1700
mEq
daily
with
minimal
symptoms;

Contra
indicated
for
alkalosis
(
metabolic
or
respiratory),
chloride
loss
due
to
vomiting
or
continuous
GI
suction,
or
hypocalcemia;

Eliminated
principally
in
the
urine,
alkalizes
it
Common
Name:
Baking
soda.

1984
Production
in
US:
3.2
x
108
kg
(
72727
tons),
with
another
5%
of
that
amount
imported
same
year.
Page
11
of
18
Sodium
Carbonate
Oral
LD50:
rat
2880
to
4090
mg/
kg;

Inhalation
LC50:
rat
2300
mg/
m3
(
2
hour);

Inhalation
LC50:
mouse
1200
mg/
m3
(
2
hour);

Skin
irritation:
mild;

Eye
irritation
:
mild­
moderate;

Aqueous
solutions
are
strongly
alkaline;

Concentrated
solutions
tend
to
produce
local
necrosis
of
mucous
membranes;

Sensitivity
reactions
may
occur
from
repeated
topical
use;

Ingestion
of
large
quantities
may
produce
corrosion
of
GI
tract,
vomiting,

diarrhea,
circulatory
collapse,
death;

Dusts
of
vapors
of
sodium
carbonate
may
cause
irritation
of
mucous
membranes
with
subsequent
coughing
and
shortness
of
breath;

A
primary
irritant
at
concentrations
below
15%
and
caustic
at
concentrations
above
approximately
15%,
depending
on
contact
time,
areas
of
exposure,
and
other
factors;
Developmental
toxicity
test
on
gestation
days
6
to
15
in
rats,
mice
and
rabbits
at
levels
of
3.4
to
340
mg/
kg:
no
effects
on
nidation
or
survival
of
the
dams
or
fetuses.
Common
name:
washing
soda
Page
12
of
18
8.
Agency
Review
of
Toxicity
Data
for
Potassium
Bicarbonate
and
Sodium
Bicarbonate
Sodium
bicarbonate
has
an
acute
oral
LD
50
greater
than
5000
mg/
kg
in
rats,
an
acute
dermal
LD
50
greater
than
2000
mg/
kg
in
rabbits,
and
an
acute
inhalation
LC
50
greater
than
4.74
mg/
L
in
rats.
It
causes
minimal
eye
irritation
and
slight
dermal
irritation
in
rabbits,
and
is
a
dermal
non­
sensitizer
in
guinea
pigs.

Potassium
bicarbonate
has
an
acute
oral
LD
50
greater
than
2825
mg/
kg
in
rats,
an
acute
dermal
LD
50
greater
than
2000
mg/
kg
in
rabbits,
and
an
acute
inhalation
LC
50
greater
than
4.96
mg/
L
in
rats.
It
causes
slight
eye
irritation
and
slight
dermal
irritation
in
rabbits,
and
is
a
dermal
non­
sensitizer
in
guinea
pigs.

9.
FDA
GRAS
(
Generally
Recognized
As
Safe)
Assessments
The
FDA
Assessment
is
titled
"
Evaluation
of
the
Health
Aspects
of
Carbonates
and
Bicarbonates
as
Food
Ingredients"
(
1975).
"
Carbonates
and
bicarbonates
are
used
in
foods
as
neutralizers
and
leavening
agents.
These
anions
occur
in
body
fluids
and
tissues
as
the
result
of
normal
metabolic
processes
and
are
important
in
the
control
of
acid­
base
balance.
Except
for
calcium,
most....
are
fairly
soluble
in
water."
The
possible
average
daily
intake
of
added
carbonates
(
i.
e.,
those
used
as
food
additives)
at
that
time
were:

Table
5:
Daily
Intake
Chemical
Name
0
to
5
Months
(
mg/
kg)
6
to
11
Months
(
mg/
kg)
12
to
23
Months
(
mg/
kg)
2
to
65+
Years
(
mg/
kg)

ammonium
bicarbonate
3
12
18
8
ammonium
carbonate
8
34
35
12
magnesium
carbonate
2
8
12
6
potassium
bicarbonate
11
2
<
1
­­­

potassium
carbonate
3
15
22
10
sodium
bicarbonate
29
171
251
80
sodium
carbonate
1
6
6
2
Potassium
and
Sodium
Carbonate
and
Bicarbonate
Page
13
of
18
In
the
FDA
Assessment
acute,
short­
term,
and
developmental
toxicity
studies
and
mutagenicity
studies
were
evaluated
for
potassium
carbonate
and
bicarbonate.
For
sodium
carbonate
and
bicarbonate
acute,
short­
term,
and
developmental
toxicity
studies,
and
mutagenicity
and
metabolism
studies
were
evaluated.
There
was
also
some
human
data.
No
chronic
studies
were
identified.

"
The
results
of
acute
toxicity
and
short­
term
feeding
experiments
are
not
readily
extrapolated
in
determining
toxic
levels
for
carbonate
salts
consumed
by
humans.
Treatment
of
gastric
or
peptic
ulcers
in
patients
with
large
amounts
of
carbonate
salts
in
various
forms
has
been
utilized
for
many
years
and
only
rarely
have
deleterious
results
of
changes
of
acid­
base
balance
been
reported.
When
the
human
respiratory
and
renal
functions
are
normal,
the
mechanisms
for
disposing
of
bicarbonate
intake
in
large
amounts
through
excretion
appear
to
be
highly
efficient."

"
There
is
no
evidence
in
the
available
information
on
...
potassium
carbonate,
potassium
bicarbonate,
sodium
carbonate,
[
or]
sodium
bicarbonate
...
that
demonstrates
or
suggests
reasonable
grounds
to
suspect
a
hazard
to
the
public
when
used
at
levels
that
are
now
current
or
that
might
reasonably
be
expected
in
the
future."

Ammonium
Carbonate
and
Bicarbonate
The
FDA
Assessment
is
titled
"
Evaluation
of
the
Health
Aspects
of
Certain
Ammonium
Salts
as
Food
Ingredients"
(
1974).

"
Ammonia
and
ammonium
ion
are
integral
components
of
normal
metabolic
processes
and
play
an
essential
role
in
the
physiology
of
man.
Although
there
have
been
no
significant
feeding
studies
specifically
designed
to
ascertain
the
safety
threshold
of
ammonium
compounds
as
food
ingredients,
numerous
metabolic
studies
have
been
reported
in
the
scientific
literature.
Extrapolation
of
these
finding
to
the
concentrations
of
ammonium
compounds
normally
present
in
foods
does
not
suggest
that
there
would
be
untoward
effects
at
such
levels."

Magnesium
Carbonate
The
FDA
Assessment
is
titled
"
Evaluation
of
the
Health
Aspects
of
Magnesium
Salts
as
Food
Ingredients"
(
1976).
Magnesium
is
(
1)
a
dietary
essential,
(
2)
involved
in
many
metabolic
reactions,
(
3)
important
in
electrolyte
balance,
and
(
4)
present
in
fruits,
vegetables,
grains,
milk,
meat
and
fish.
No
chronic
toxicity
data
were
available.
The
"
status
of
magnesium
as
a
ubiquitous
and
essential
dietary
ingredient
for
the
maintenance
of
homeostatic
and
bioenergetic
mechanisms
leads
to
the
opinion
that
none
of
the
available
evidence
suggests
any
probable
hazard
when
any
of
the
GRAS
compounds
of
magnesium
is
used
as
a
food
ingredient."
The
conclusion
was
reached
that
there
was
no
available
information
on
magnesium
chloride
to
demonstrate,
or
suggest
Page
14
of
18
"
reasonable
grounds
to
suspect,
a
hazard
to
the
public
when
...
used
at
levels
that
are
now
current
and
in
the
manner
now
practiced,
or
which
might
reasonably
be
expected
in
the
future."

10.
FAO/
WHO
Expert
Committee
on
Food
Additives
Ammonium
carbonate
and
ammonium
hydrogen
carbonate
(
previously
known
as
ammonium
bicarbonate)
were
evaluated
previously
in
1966.
The
evaluation
was
performed
using
the
available
data
on
ammonium
carbonate
and
ammonium
bicarbonate
as
well
as
surrogate
data
on
ammonium
chloride
and
various
carbonate
salts.
Acute,
short­
term,
and
developmental
toxicity
studies,
mutagenicity
studies,
and
human
studies
were
used.

"
These
compounds
(
ammonium
ion
and
bicarbonate
ion
)
are
normal
metabolites
in
man.
Although
specific
toxicological
data
for
ammonium
carbonate
and
ammonium
bicarbonate
are
limited,
extrapolation
of
results
from
studies
with
ammonium
compounds
(
primarily
ammonium
chloride)
and
with
sodium
or
potassium
carbonate
provide
a
basis
for
evaluation.
Clinical
studies
in
man
show
that
administration
of
high
doses
of
ammonium
chloride
or
of
sodium
bicarbonate
results
in
changes
in
the
acid­
base
balance.
This
is
the
normal
physiological
response.
The
levels
of
ammonium
carbonate
and
bicarbonate
in
the
diet
from
food
additive
use
are
extremely
small
compared
to
the
levels
required
to
cause
physiological
changes
and
pose
no
toxicological
hazard."

The
estimate
of
acceptable
daily
intake
for
man
is
"
not
specified."
"
The
statement
`
ADI
not
specified'
means
that,
on
the
basis
of
the
available
data
(
toxicological,
biochemical,
and
other),
the
total
daily
intake
of
the
substance,
arising
from
its
use
or
uses
at
the
levels
necessary
to
achieve
the
desired
effect
and
from
its
acceptable
background
in
food,
does
not,
in
the
opinion
of
the
Committee,
represent
a
hazard
to
health.
For
this
reason,
and
for
the
reasons
stated
in
individual
evaluations,
the
establishment
of
an
acceptable
daily
intake
(
ADI)
in
mg/
kg
bw
is
not
deemed
necessary."

11.
Human
Health
Hazard
Characterization:

When
dissolved
in
water,
salts
of
carbonic
acids
form
basic
solutions.
The
toxicity
(
the
irritation
and
caustic
effects)
of
these
chemicals
tend
to
resemble
those
of
the
hydroxides,
although
to
a
lesser
extent.
In
solution
these
chemicals
could
effectively
perform
as
buffering
agents,
pH
adjusters,
or
neutralizers
in
pesticide
products.
This
is
indicative
of
the
use
of
small
amounts
of
the
chemical
that
are
incorporated
in
a
pesticide
product
to
modify
and/
or
control
the
pH.
After
the
pH
adjustment
is
performed,
the
aqueous
solution
of
carbonate
salts
would
be
neutralized.
If
used
as
an
active
ingredient
the
chemical
is
subject
to
FIFRA
registration
requirements
and
various
labeling
language.
These
chemicals
must
be
used
and
applied
according
to
good
manufacturing
or
good
agricultural
practices.
However,
there
are
no
significant
adverse
effects,
to
the
general
public
or
any
population
subgroup
from
consumption
of
residues
of
the
ammonium,
potassium,
magnesium,
and
sodium
salts
of
carbonic
acid
resulting
from
pesticide
Page
15
of
18
product
uses.

As
a
group
these
salts
of
carbonic
acid
constitute
a
group
of
chemicals
with
many
uses
including
direct
use
in
the
food
supply.
Various
ammonium,
magnesium,
potassium,
and
sodium
salts
of
carbonic
acid
have
been
reviewed
by
both
FDA
and
WHO.
These
chemicals
have
been
used
in
the
food
supply
for
a
number
of
years.

The
available
toxicity
data
indicates
that
the
human
body
metabolizes
carbonates,
ammonium,
magnesium,
potassium,
and
sodium
ions
through
well­
understood
pathways.
In
fact,
the
metals
are
necessary
human
nutrients.
Given
the
long
history
of
safe
use,
the
available
toxicity
data,
and
an
understanding
of
the
human
body's
ability
to
metabolize
these
chemicals,
and
the
evaluations
by
FDA
and
WHO,
the
IIFG
believes
that
ammonium,
potassium,
sodium
and
magnesium
carbonate
salts
are
of
low
oral
toxicity.

12.
Type
of
Risk
Assessment/
Risk
Characterization:

The
toxicity
of
these
chemicals
derives
from
the
irritation
and
caustic
effects;
therefore,
a
qualitative
assessment
for
all
pathways
of
human
exposure
(
food,
drinking
water,
and
residential)
is
appropriate.

Given
the
widespread
occurrence
of
these
chemicals
in
the
existing
food
supply,
the
amounts
that
can
be
applied
to
food
as
a
result
of
a
use
in
a
pesticide
product
would
not
be
expected
to
significantly
increase
the
existing
amounts
in
the
food
supply.
There
is
no
available
information
on
any
of
the
chemicals
considered
in
this
document
indicative
of
a
human
health
hazard
resulting
from
the
EPA­
regulated
uses
as
well
as
the
FDA
GRAS
uses
to
the
general
public
or
any
population
subgroup.
No
additional
information
is
needed
to
assess
their
safety.

13.
Sensitivity
of
Infants
and
Children:

Overall,
when
considering
the
oral
pathway
(
ingestion),
these
chemicals
have
low
toxic
potential.
At
this
time,
there
is
no
concern
for
potential
sensitivity
to
infants
and
children.
A
safety
factor
analysis
has
not
been
used
to
assess
the
risk.
For
the
same
reasons
the
additional
tenfold
safety
factor
is
unnecessary.

14.
Environmental
Fate
and
Ecotoxicity
Assessment/
Characterization:

In
general,
the
constituents
of
the
salts
of
carbonic
acid
are
commonly
found
in
soil
and
water
in
the
environment
suggesting
that
releasing
low
levels
of
these
chemicals
would
not
normally
be
expected
to
adversely
effect
wildlife
or
water
resources.
Large
releases
may
adversely
affect
wildlife
and
water
resources
either
directly
or
indirectly.
Direct
effects
may
result
from
exceeding
toxicity
thresholds
of
specific
chemicals.
Indirect
effects
may
be
manifested
through
disrupting
ecosystems
through
altering
pH
or
increasing
availability
of
algal
nutrients.

The
magnitude
of
the
pH
changes,
and
thus
the
magnitude
of
effects,
would
depend
on
a
Page
16
of
18
number
of
factors
including
the
amount
of
material
released
and
the
buffering
capacity
of
the
exposed
soil
or
water.
Normal
aquatic
pHs
range
from
5
to
9.
EPA's
Office
of
Water
recommended
water
quality
criteria
for
pH
are
6.5
to
9
for
freshwater
and
6.5
to
8.5
for
saltwater.
At
higher
or
lower
pH
aquatic
life
is
expected
to
be
adversely
impacted.
In
addition,
rapid
changes
in
pH
can
also
be
detrimental
to
aquatic
life.

The
magnesium,
potassium
and
sodium
salts
of
carbonic
acid
should
dissociate
in
water
resulting
in
a
positively
charged
(
cation)
metal
in
solution.
Dissociation
is
frequently
dependent
on
pH,
with
lower
(
more
acidic)
pHs
resulting
in
higher
levels
of
dissociation
and
greater
solubility.
Aquatic
toxicity
of
metals
varies
with
the
species
of
metal
and
its
concentration.
Metals
do
not
degrade
and
thus
are
permanent
in
the
environment.
They
are
likely
to
dissipate
by
being
sequestered
in
soil,
sediment,
and
plants.

15.
Cumulative
Exposure:

Section
408(
b)(
2)(
D)(
v)
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide
chemical's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
The
chemicals
considered
in
this
document
are
structurally
related;
however,
these
salts
of
carbonic
acid
are
low
toxicity
chemicals.
Therefore,
the
resultant
risks
separately
and/
or
combined
should
also
be
low.
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
these
pesticide
chemicals
have
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
these
pesticide
chemicals
in
a
cumulative
risk
assessment.

16.
Determination
of
Safety:

Based
on
its
review
and
evaluation
of
the
available
information,
EPA
concludes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
the
general
population,
and
to
infants
and
children
from
aggregate
exposure
to
residues
of
ammonium,
sodium,
potassium,
and
magnesium
salts.
Therefore,
the
following
exemptions
from
the
requirement
of
a
tolerance
are
reassessed:
In
40
CFR
180.2
sodium
carbonate.
In
40
CFR
180.1001
(
c)
ammonium
bicarbonate,
magnesium
carbonate,
and
sodium
bicarbonate.
In
40
CFR
180.1001
(
d)
potassium
carbonate.
In
40
CFR
180.1001
(
e)
magnesium
carbonate.

17.
List
Reclassifications:

The
following
List
reclassifications
are
made
or
confirmed:

Ammonium
bicarbonate:
List
4B
Ammonium
carbonate:
List
4B
Magnesium
carbonate
(
less
than
1%
crystalline
silica):
List
4A
given
its
similarities
to
calcium
carbonate
Potassium
Bicarbonate:
List
4A
given
its
similarities
to
sodium
bicarbonate
Potassium
Carbonate:
List
4B
given
its
similarities
to
potassium
hydroxide
Page
17
of
18
Sodium
Bicarbonate:
List
4A
considering
its
use
as
baking
soda
Sodium
Carbonate:
List
4B
given
its
similarities
to
potassium
carbonate
Given
the
chemical
similarities,
and
that
data/
information
on
the
following
chemicals
was
used
as
surrogate
data
for
tolerance
reassessment,
exemptions
from
the
requirement
of
a
tolerance
may
be
established
for
ammonium
carbonate,
potassium
bicarbonate,
and
sodium
carbonate.

The
following
table
lists
the
various
chemical
names,
CAS
Reg.
No.,
and
CAS
Index
Names
that
will
be
used
for
listing
in
40
CFR.
180.
Note
that
both
the
anhydrous
and
the
hydrated
forms
are
included.
The
Agency
sees
no
reason
to
distinguish
between
these
chemicals
given
that
the
only
difference
is
the
attachment
of
the
water
molecules.

Chemical
Name
CAS.
Reg.
No.
Chemical
Abstacts
Index
Name
ammonium
bicarbonate
1066­
33­
7
Carbonic
acid,
monoammonium
salt
(
8CI,
9CI)

ammonium
carbonate
10361­
29­
2
Carbonic
acid,
ammonium
salt
(
8CI,
9CI)

ammonium
carbonate
506­
87­
6
Carbonic
acid,
diammonium
salt
(
8CI,
9CI)

magnesium
carbonate
546­
93­
0
Carbonic
acid,
magnesium
salt
(
1:
1)
(
8CI,
9CI)

potassium
carbonate
584­
08­
7
Carbonic
acid,
dipotassium
salt
(
8CI,
9CI)

potassium
hydrogen
carbonate
{
KHCO3}
298­
14­
6
Carbonic
acid,
monopotassium
salt
(
8CI,
9CI)

potassium
carbonate
trihydrate
{
2K2CO3
.3H2O}
18662­
52­
7
Carbonic
acid,
dipotassium
salt,
trihydrate
(
8CI)

sodium
bicarbonate
{
NaHC03}
144­
55­
8
Carbonic
acid
monosodium
salt
(
8CI,
9CI)

sodium
carbonate
{
Na2CO3}
497­
19­
8
Carbonic
acid
disodium
salt
(
8CI,
9CI)

sodium
carbonate
decahydrate
{
Na2CO3
.
10H2O}
6132­
02­
1
Carbonic
acid
disodium
salt,
decahydrate
(
8CI,
9CI)

sodium
carbonate
heptahydrate
{
Na2CO3
.
7H2O}
56399­
31­
6
Carbonic
acid
disodium
salt,
heptahydrate
(
9CI)

sodium
carbonate
monohydrate
{
Na2CO3
.
H2O}
5968­
11­
6
Carbonic
acid
disodium
salt,
monohydrate
(
8CI,
9CI)

sodium
sesquicarbonate
{
Na2CO3
.
NaHCO3
.
2H2O}
533­
96­
0
Carbonic
acid,
sodium
salt
(
2:
3)
(
8CI,
9CI)

Attachment:
Page
18
of
18
EFED
Review
of
Mineral
Acids
(
Birchfield;
May
7,
2002)
