Document ID: EPA-HQ-OPP-2003-0230-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-08-05T04:00Z

Page
1
of
8
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
29,
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
Document
on
Reassessing
Tolerance
Exemptions
for
Lactic
Acid
The
Inert
Ingredient
Focus
Group
reassessment
of
lactic
acid
is
based
on
the
conclusions
of
the
FAO/
WHO
Joint
Expert
Committee
on
Food
Additives,
the
FDA
Assessment
of
lactic
acid,
and
the
information
submitted
to
EPA's
High
Production
Volume
Challenge
Program.

The
three
tolerance
exemptions
in
40
CFR
180
are
reassessed.
Page
2
of
8
INERT
INGREDIENT
FOCUS
GROUP
DECISION
DOCUMENT
Lactic
Acid
Petition
No.:
no
Tolerance
Reassessments?:
yes
Common
Chemical
Name:
lactic
acid
CAS
Index
Name:
propanoic
acid,
2­
hydroxy­
(
2S)­

Chemical
Category/
Group:
organic
acid
CAS.
Reg.
No.:
50­
21­
5
(
racemic
mixture);
79­
33­
4
(
L­
isomer)

inert
PC
Code:
800159
(
only
the
racemic
mixture)

active
PC
Code:
128929
(
only
the
L­
isomer)

HPV
Chemical?
yes
Data
Posted?
yes
There
are
two
isomers
of
lactic
acid.
The
L­
isomer
occurs
during
normal
mammalian
metabolism.
Commercially
available
lactic
acid
can
be
the
L­
isomer
or
a
mixture
of
the
D­
and
the
L­
isomers,
which
is
also
referred
to
as
racemic.
FDA
believes
that
most
of
the
lactic
acid
added
directly
to
food
is
racemic.
The
D­
isomer
can
be
formed
by
selective
fermentation
using
certain
Lactobacilli.

Use
Pattern
(
pesticidal):
As
an
active
ingredient,
lactic
acid
is
used
as
a
plant
growth
regulator
(
40
CFR
180.1090).
Lactic
acid
is
used
in
food­
contact
surface
sanitizing
solutions.
As
an
inert
ingredient,
lactic
acid
has
tolerance
exemptions
in
40
CFR
180.1001
(
c)
and
(
e)
as
a
solvent.

Use
Pattern
(
non­
pesticidal):
Lactic
acid
can
be
produced
commercially
either
by
fermentation
of
carbohydrates
such
as
glucose,
sucrose,
or
lactose.
It
is
used
in
food
processing
as
an
acidulant,
to
impart
a
characteristic
sourness
to
foods,
and
to
control
pH.
It
can
be
found
in
fruit
juices,
dairy
products,
tomato
products,
products
such
as
pickles
and
sauerkraut,
and
in
beer
and
wine.
In
the
meat
processing
industry
lactic
acid
is
used
as
part
of
a
sanitizing
solution
that
is
applied
to
carcasses
(
approximately
2%
lactic
acid)
.
Page
2
of
8
Lactic
acid
is
GRAS
(
generally
recognized
as
safe)
with
limitations
but
allowing
for
use
of
all
three
forms
(
L­
isomer,
D­
isomer
and
racemic
mixture)
as
a
direct
food
additive.
21
CFR
184.1061
(
c)(
1)
specifies
that
lactic
acid
can
be
used
as
an
antimicrobial
agent,
a
curing
and
pickling
agent,
a
flavor
enhancer,
a
flavoring
agent
and
adjuvant,
a
pH
control
agent,
and
a
solvent
and
vehicle.
21
CFR
184.1061
(
c)(
2)
is
very
specific
that
lactic
acid
cannot
be
used
in
infant
foods
and
infant
formulas.

Lactic
acid
is
GRAS
when
used
in
accordance
with
good
manufacturing
or
feeding
practices
(
21
CFR
582.1061).
Lactic
acid
is
also
used
in
cosmetics
and
skin
care
products,
and
in
the
leather
tanning,
textile
finishing,
plastics
and
adhesives
industries.

Assessment
of
Lactic
Acid
1.
Physical/
Chemical
Properties:

Chemical
Properties
Chemical
Property
Lactic
Acid
Form
liquid
or
white
crystals,
colorless
to
slightly
yellow,
nearly
odorless
Molecular
Weight
90
Vapor
Pressure
(
mmHg)
0.0814
@
25oC
Henry's
Law
Constant
1.13
x
10­
7
@
25oC
Water
Solubility
very
highly
soluble
exceeding
1
kg/
L
(
1
x106
mg/
L)
@
20oC
Koc
(
estimated)
1
Partition
Coefficient
log
Kow
­
0.72
@
25oC
(
lactic
acid
will
be
found
in
the
water
phase
as
opposed
to
sorbed
onto
soil,
sediments
and
organic
materials)

Although
lactic
acid
has
an
experimentally
measured
vapor
pressure
of
approximately
0.0814
mmHg
at
25oC
indicating
a
high
potential
to
volatilize,
volatilization
from
water
is
not
expected
to
be
significant
due
to
its
low
Henry's
Law
Constant.

2.
Introduction:

Lactic
acid
occurs
naturally
in
meats,
fruits,
tomato
juice,
beer
wine,
molasses,
sour
milk,
yogurt,
and
cottage
cheese.
The
protein
in
the
milk
is
curdled
(
coagulated)
by
the
lactic
acid.
The
available
information
also
indicates
that
lactic
acid
and
calcium
lactate
have
been
added
to
Page
3
of
8
commercially
prepared
foods
since
the
1940
­
1950s.
FDA
estimated
per
capita
daily
intake
based
on
1960/
1970
data
as
15
mg
of
lactic
acid.
Blood
levels
of
lactic
acid
can
range
from
4.5
to
19.8
mg/
dl
(
milligrams
per
deciliter).

Lactic
acid
is
also
produced
in
the
body:
it
is
widely
distributed
as
a
metabolic
product
in
living
cells.
The
glycogen
within
the
muscles
is
split
to
form
glucose.
During
anaerobic
metabolism
(
metabolism
without
oxygen)
the
glucose
is
converted
to
energy
with
the
lactic
acid
being
an
intermediate
product
of
carbohydrate
or
glucose
metabolism.
The
presence
of
lactic
acid
in
the
muscle
tissue
causes
the
soreness
that
can
be
felt
after
exercising.

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/
neng0501.
html)
°
TOXNET
(
www.
toxnet.
nlm.
nih.
gov.),
°
WHO
(
www.
inchem.
org/
documents/
jecfa/
jecmono/
v05je86.
htm)
and
(
www.
inchem.
org/
documents/
jecfa/
jecmono/
40abcj444.
htm)

Additional
information
included
the
information
submitted
to
EPA's
High
Production
Volume
Challenge
Program
"
HPV
Data
Set,
Lactic
Acid,
CAS
#
50­
21­
5"
(
Submitted
January
3,
2002).

FDA's
(
Food
and
Drug
Administration)
"
Evaluation
of
the
Health
Aspects
of
Lactic
Acid
and
Calcium
Lactate
as
Food
Ingredients"
(
1978)
was
also
used
in
this
assessment.

The
NIOSH
International
Safety
Card
for
lactic
acid
gave
the
following
information:
It
is
a
medium
strong
acid.
The
substance
irritates
the
skin
and
the
respiratory
tract
and
is
corrosive
to
the
eyes.
Corrosive
on
ingestion.
A
TLV
(
Threshold
Limit
Value)
has
not
been
established.

3.
WHO
(
World
Health
Organization)
Assessment
WHO
evaluated
lactic
acid
in
both
1966
and
1973.
The
1966
assessment
indicated
that
metabolic
studies
on
the
utilization
of
lactic
acid
in
infants
and
adults
were
required.
The
1973
assessment
covered
lactic
acid
as
well
as
its
ammonium,
calcium,
potassium,
and
sodium
salts.
The
1973
assessment
revised
the
1966
monograph
by
incorporating
additional
data.
"
Man
has
consumed
fruits,
sour
milk
and
other
fermented
products
containing
DL­
lactic
acid
for
centuries,
apparently
without
any
adverse
effects."
Acute,
subchronic,
and
absorption
and
metabolism
studies
were
available.

The
conclusions
were
as
follows:

"
In
evaluating
lactic
acid,
emphasis
is
placed
on
its
well­
established
metabolic
Page
4
of
8
pathways
after
normal
consumption
in
man.
It
is
an
important
intermediate
in
carbohydrate
metabolism.
However,
human
studies
determining
the
maximum
load
of
lactate
are
not
available.
There
is
some
evidence
that
babies
in
their
first
three
months
of
life
have
difficulties
in
utilizing
small
amounts
of
DL
and
D(­)
lactic
acids.
No
limit
need
be
set
for
the
acceptable
daily
intake
for
man.

Estimate
of
acceptable
daily
intake:
Not
Limited
Neither
D(­)
lactic
acid
nor
(
DL)
lactic
acid
should
be
used
in
infant
foods."

It
should
be
noted
that
an
"
ADI
without
an
explicit
indication
of
the
upper
limit
of
intake
(`
ADI
not
specified')
may
be
assigned
to
substances
of
very
low
toxicity,
especially
those
that
are
food
constituents
or
that
may
be
considered
as
foods
or
normal
metabolites
in
man.
The
expression
`
ADI
not
specified'
has
been
adopted
by
the
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives
at
its
Eighteenth
session
as
a
more
suitable
expression
than
`
ADI
not
limited'
previously
used.
However,
an
additive
having
an
`
ADI
not
specified'
must
meet
the
criteria
of
good
manufacturing
practice
­
for
example
it
should
have
proven
technological
efficacy
and
be
used
at
the
minimum
level
of
efficacy,
it
should
not
conceal
inferior
food
quality
or
adulteration,
and
it
should
not
create
a
nutritional
imbalance."

4.
FDA
Assessment
In
performing
the
1978
FDA
Assessment
the
following
types
of
information
were
reviewed:
absorption,
metabolism,
and
excretion
studies,
acute
toxicity
studies,
subchronic
studies,
mutagenicity
studies,
and
human
studies.
Additionally,
a
great
deal
of
research
effort
had
been
expended
to
understand
the
effect
of
feeding
infants
formulas
acidified
with
lactic
acid.

"
Lactic
acid
is
produced
in
varying
amounts
by
most
living
tissues
as
a
normal
metabolic
intermediate.
The
lactate
turnover
rate
in
man
has
been
estimated
to
be
of
the
order
of
2
g/
kg/
day."

The
conclusions
are:

"
There
is
no
evidence
in
the
available
information
on
L(+)
lactic
acid
...
that
demonstrates
or
suggests
reasonable
grounds
to
suspect
a
hazard
to
the
public
when
they
are
used
at
levels
that
are
now
current
or
that
might
reasonably
be
expected
in
the
future.

There
is
no
evidence
in
the
available
information
on
either
of
the
isomers
of
lactic
acid
....
and
their
racemates
that
demonstrates
or
suggests
reasonable
grounds
to
suspect
a
hazard
to
individuals
beyond
infancy
when
they
are
used
at
levels
that
are
now
current
or
that
might
reasonably
be
expected
in
the
future.

The
evidence
of
D(­)­
lactic
acid,
DL
­
lactic
acid
...
is
insufficient
to
determine
Page
5
of
8
that
the
adverse
effects
reported
would
not
be
deleterious
to
infants
should
they
be
used
in
infant
formulas.
Lactic
acid
acidification
of
generally
available
infant
formulas
is
not
now
being
practiced
in
the
United
States."

5.
Agency­
Reviewed
Studies
The
Agency
has
reviewed
an
acute
oral
toxicity
study
in
the
rat
for
lactic
acid.
The
LD
50
is
4936
mg/
kg
(
male)
and
3543
mg/
kg
(
female).
Acute
oral,
dermal
and
inhalation
data
indicate
toxicity
category
III.
Results
from
a
primary
dermal
irritation
study
place
lactic
acid
in
toxicity
category
I,
based
on
severe
dermal
irritation.
Lactic
acid
is
not
a
dermal
sensitizer.
A
primary
eye
irritation
study
was
waived
since
the
pH
of
lactic
acid
is
less
than
2.
At
this
extremely
low
pH,
lactic
acid
is
automatically
placed
into
toxicity
category
I
for
potential
corrosion
and
severe
eye
irritation.

6.
Hazard
Characterization:

Lactic
acid
(
all
three
forms)
occurs
naturally.
The
L­
isomer
is
part
of
human
metabolic
activity.
Mankind
has
consumed
lactic
acid
(
much
of
it
probably
in
the
racemic
form)
for
years.
At
present,
there
are
no
available
information
on
lactic
acid
indicative
of
a
hazard,
significant
adverse
effects,
to
the
general
public
from
consumption
of
residues
of
lactic
acid.
WHO
has
not
sought
limitations
on
the
use
of
lactic
acid
or
specified
the
use
of
a
particular
isomer
for
the
general
public.
FDA
allows
the
use
of
all
three
forms
of
lactic
acid
as
a
direct
food
additive
and
has
granted
lactic
acid
GRAS
status
for
six
specified
use
patterns.

There
are
concerns
are
for
dermal
and
eye
irritation.
As
an
active
ingredient
lactic
acid
is
subject
to
FIFRA
registration
requirements
and
various
labeling
language.
Lactic
acid
must
be
used
and
applied
according
to
good
manufacturing
or
good
agricultural
practices.
No
additional
data
are
required
to
assess
the
safety
of
lactic
acid.

7.
Type
of
Human
Health
Risk
Assessment:

Qualitative
for
all
pathways
of
human
exposure:
food,
drinking
water,
and
residential.
Lactic
acid
is
not
toxic
by
the
oral,
dermal
or
inhalation
routes
of
exposure.

8.
Sensitivity
of
Infants
and
Children:

Given
the
wide
spread
occurrence
of
lactic
acid
in
the
food
supply,
the
amount
of
lactic
acid
that
can
be
applied
to
food
as
a
result
of
its
use
in
a
pesticide
product
should
not
significantly
increase
the
existing
amounts
in
the
food
supply.

However,
there
is
some
evidence
that
premature
or
very
young
infants
can
experience
adverse
effects
when
fed
D­
isomer
lactic
acid.
(
According
to
FDA
the
results
of
the
various
Page
6
of
8
studies
are
conflicting
and
difficult
to
interpret.)
The
FAO/
WHO
Assessment
noted
that
these
adverse
effects
occur
in
the
first
three
months
of
life.
In
the
1978
FDA
Assessment
these
concerns
were
expressed
(
see
section
4),
as
well
as
FDA's
belief
that
lactic
acid
was
not
used
in
infant
formulas
in
the
United
States.

EPA
believes
that
there
is
no
exposure
of
premature
or
very
young
infants
to
lactic
acid.
First,
premature
or
very
young
infants
ingest
only
formula
or
breast
milk.
(
It
is
generally
recommended
that
infants
not
consume
solid
food
until
4
to
6
months
of
age.)
Regulation
of
infant
formulas
is
under
the
purview
of
FDA.
(
www.
fda.
gov/
fdac/
features/
596_
baby.
html).
To
carry
out
their
regulation
of
infant
foods
and
infant
formulas,
FDA
published
in
21
CFR
184.1061
(
c)(
2)
a
very
specific
limitation
that
lactic
acid
cannot
be
used
in
infant
foods
and
infant
formulas.
Therefore,
infants
consuming
only
infant
formula
or
breast
milk
are
not
exposed
to
lactic
acid.
Second,
even
if
a
very
young
infant
were
to
be
fed
some
solid
food,
given
the
characteristics
of
lactic
acid,
residues
are
not
likely
to
be
present
in
food
commodities.
As
discussed
below
(
section
9)
lactic
acid
is
readily
biodegradable.
It
is
not
likely
to
be
taken
up
by
plants.

Once
past
this
several
month
time­
period,
there
is
no
longer
a
concern
for
potential
sensitivity
to
infants
and
children.
Older
infants,
like
adults,
process
lactic
acid
through
well
understood
metabolic
pathways.
A
safety
factor
analysis
has
not
been
used
to
assess
the
risk.
For
the
same
reasons
the
additional
tenfold
safety
factor
is
unnecessary.

9.
Environmental
Fate
Assessment
Lactic
acid
undergoes
rapid
aerobic
and
anaerobic
biodegradation
in
both
soil
and
water
with
an
estimated
half­
life
of
5
days
or
less.
Mineralization,
degradation
to
form
CO
2,
H
2
O
and
other
minor
constituents,
will
occur
in
days
to
weeks.
As
a
readily
available
carbon
source,
most
microorganisms
will
preferentially
degrade
substances
of
the
carboxylic
acid
group
before
utilizing
more
complex
molecules
as
an
energy
source.
Lactic
acid
is
classified
as
readily
biodegradable.

Mobility
of
lactic
acid
is
expected
to
be
high
based
on
adsorption
estimates;
however,
migration
to
ground
water
should
be
substantially
mediated
through
its
rapid
biodegradation.
Runoff
to
surface
is
expected
to
dominate
the
non­
degradation
pathways
of
dissipation.
However,
no
environmental
occurrence
data
in
ground
or
surface
water
were
available.
Partitioning
to
air
is
expected
to
be
low
from
water
sources
and
perhaps
higher
from
dryer
surfaces
such
as
in
soil
matrices
at
water
contents
less
than
the
wilting
point.
Hydrolysis
is
not
expected
to
be
a
route
of
degradation.
Photodegradation
will
play
a
minor
role
in
the
dissipation
of
the
compound.
Bioconcentration
is
not
expected
to
occur.

10.
Ecotoxicity
Data:

Fish
Acute
Toxicity
(
96h­
LC50)
(
mg/
L)
Invertebrate
Acute
Toxicity
(
48
h­
EC50)
(
mg/
L)
Algae
Toxicity
(
70
h­
EC50)
(
mg/
L)
Mammal
Acute
Oral
(
LD50);
Most
sensitive
only
Page
7
of
8
Freshwater/
M/
E:
130­
320
(
M);

Freshwater
2
x
105
(
E);

M/
E:
13156
(
E)
Freshwater:
240
(
M);

1.85
x
105
(
E);

M/
E:
3.95
x
105
(
E)
3500
(
M);

99055
(
96h­
EC50)
(
E)
3543
­
4936
mg/
kg
bw
(
M);

E:
Estimated
by
Structure
Activity
Relationship
(
SAR).
M:
Measured/
Calculated
M/
E:
Marine/
Estuarine
Ecotoxicity
data
indicate
that
these
compounds
are
practically
non­
toxic
on
an
acute
basis.
No
chronic
tests
were
available,
but
estimated
aquatic
chronic
toxicity
would
indicate
little
concern
for
adverse
effects.
Terrestrial
animal
toxicity
based
on
available
mouse,
rat,
and
hamster
data
indicate
lactic
acid
is
practically
non­
toxic
on
an
acute
basis
and
no
chronic
effects
were
observed
in
available
studies.

11.
Ecotoxicity
Data
from
Open
Literature:

The
following
data
is
from
the
Bowmer,
C.
T.,
et.
al.
"
The
Ecotoxicity
and
the
Biodegradability
of
Lactic
Acid,
Alkyl
Lactate
Esters
and
Lactate
Salts."
1998.
Chemosphere
37(
7)
1317­
1333.

Test
organism
Lactic
acid
(
ppm)

Algae1
(
72­
96
hr)
NOEC
1900
Daphnia
magna
EC
50
240
Fish2
LC
50
320
3
1
S.
capricornutm
2
zebra
fish
or
fathead
minnow
3
The
authors
propose
that
the
toxicity
in
this
test
is
a
result
lactic
acid's
acidic
properties
and
the
change
in
pH.

12.
Environmental
Fate
and
Ecotoxicity
Characterization
Environmental
loadings
of
lactic
acid
are
attributable
to
natural
and
anthropogenic
sources.
Lactic
acid
is
very
highly
soluble
in
water,
mobile
and
not
likely
to
volatilize
from
either
soil
or
water.
There
are
no
significant
toxicity,
exposure
and/
or
risk
concerns
for
lactic
acid.

13.
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's
residues
and
"
other
substances
that
have
a
common
mechanism
of
Page
8
of
8
toxicity."
EPA
does
not
have,
at
this
time,
available
data
to
determine
whether
lactic
acid
has
a
common
mechanism
of
toxicity
with
other
substances
or
how
to
include
this
pesticide
chemical
in
a
cumulative
risk
assessment.

14.
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
lactic
acid
residues.
Therefore,
the
following
three
exemptions
from
the
requirement
of
a
tolerance
for
lactic
acid
are
reassessed:
In
40
CFR
180.1001(
c),
40
CFR
180.1001(
e),
and
40
CFR
180.1090.

15.
List
Reclassification:

The
following
List
reclassification
is
made
or
confirmed:

Lactic
acid:
List
4B
given
its
toxicity
I
classification
for
eye
and
skin
irritation
Attachment:

EFED
Tolerance
Review
(
Abel;
June
3,
2002)