Document ID: EPA-HQ-OPP-2005-0524-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-12-30T05:00Z

Page
1
of
42
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
09/
27/
2005
MEMORANDUM
SUBJECT:
Aquashade:
Revised
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Code:
110301,
DP
Barcode:
321912
Regulatory
Action:
Phase
1
Reregistration
Action
FROM:
Wade
Britton,
MPH,
Industrial
Hygienist
and
Risk
Assessor
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

AND
Kim
Morgan,
PhD,
Toxicologist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THROUGH:
Catherine
Eiden,
Branch
Chief
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Kendra
Tyler,
CRM
Reregistration
Branch
1
SRRD
(
7508C)

The
HED
Chapter
has
been
revised
to
reflect
a
correction
made
in
Section
6.3.2,
Recreational
Uses.
In
the
original
document,
the
dose
and
MOE
reported
for
adult
and
child
recreational
swimmers
were
reversed.
Page
2
of
42
Table
of
Contents
1.0
Executive
Summary
........................................................................................................
4
2.0
Ingredient
Profile
............................................................................................................
8
2.1
Summary
of
Registered/
Proposed
Uses....................................................................
9
2.2
Structure
and
Nomenclature...................................................................................
10
2.3
Physical
and
Chemical
Properties
.........................................................................
10
3.0
Metabolism
Assessment
................................................................................................
11
3.1
Comparative
Metabolic
Profile
.............................................................................
11
4.0
Hazard
Characterization/
Assessment
.................................................................................
11
4.1
Hazard
Characterization........................................................................................
11
4.1.5.
Acute
Toxicity
.........................................................................................
12
4.2
FQPA
Hazard
Considerations
...............................................................................
15
4.2.1
Adequacy
of
the
Toxicity
Data
Base
..........................................................
15
4.2.2
Evidence
of
Neurotoxicity..........................................................................
15
4.2.3
Developmental
Toxicity
Studies.................................................................
15
4.2.4
Reproductive
Toxicity
Study......................................................................
16
4.2.5
Additional
Information
from
Literature
Sources
.
......................................
17
4.2.6
Pre­
and/
or
Post­
natal
Toxicity....................................................................
17
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study..................................
18
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
Study.....
18
4.3.2
Evidence
that
supports
not
requiring
Developmental
Neurotoxicity
Study
18
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
..........................................
18
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49....................................
18
4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population...................................
18
4.4.3
Chronic
Reference
Dose
(
cRfD).................................................................
18
4.4.4
Incidental
Oral
Exposure
(
Short­
and
Intermediate­
Term)
..........................
20
4.4.5
Dermal
Absorption.....................................................................................
20
4.4.6
Dermal
Exposure
(
Short,
Intermediate
­
Term)............................................
20
4.4.7
Inhalation
Exposure
(
Short,
Intermediate­
Term)........................................
21
4.4.8
Margins
of
Exposure
..................................................................................
21
4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments.....................
22
4.4.10
Classification
of
Carcinogenic
Potential....................................................
22
4.5
Special
FQPA
Safety
Factor
.................................................................................
25
5.0
Public
Health
Data
............................................................................................................
25
5.1
Incident
Reports
....................................................................................................
25
6.0
Exposure
Characterization/
Assessment
.............................................................................
26
6.1
Dietary
Exposure/
Risk
Pathway.............................................................................
26
6.2
Water
Exposure/
Risk
Pathway...............................................................................
27
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway......................................
27
6.3.1
Home
Uses.................................................................................................
28
6.3.2
Recreational
Uses.......................................................................................
30
6.3.3
Residential
Aggregated
Exposure
and
Risk
Estimates
..............................
30
6.3.4
Other
(
Spray
Drift,
etc.)
.............................................................................
31
Page
3
of
42
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization....................................................
31
7.1
Acute
Aggregate
Risk...........................................................................................
31
7.2
Short­
Term
Aggregate
Risk
...................................................................................
32
7.4
Long­
Term
Aggregate
Risk
..................................................................................
32
7.5
Cancer
Risk
...........................................................................................................
32
8.0
Cumulative
Risk
Characterization/
Assessment
..................................................................
32
9.0
Occupational
Exposure/
Risk
Pathway
...............................................................................
33
9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
.........................................................
33
9.2
Short/
Intermediate/
Long­
Term
Postapplication
Risk..............................................
36
10.0
Data
Needs
and
Label
Requirements
.............................................................................
37
10.1
Toxicology
..........................................................................................................
37
10.2
Occupational
and
Residential
Exposure
...............................................................
37
1.0
TOXICOLOGY
DATA
REQUIREMENTS......................................................................
39
2.0
NON­
CRITICAL
TOXICOLOGY
STUDIES
...............................................................
40
3.0
TOLERANCE
REASSESSMENT
................................................................................
42
Page
4
of
42
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
toxicity
and
exposure
data
bases
for
the
aquatic
algaecide/
herbicide
Aquashade,
containing
the
dyes
erioglaucine
(
Acid
Blue
9
or
FD&
C
Blue
No.
1)
and
tartrazine
(
Acid
Yellow
23
or
FD&
C
Yellow
No.
5);
and
has
conducted
a
human
health
risk
assessment
in
support
of
the
Reregistration
Eligibility
Decision
(
RED)
for
these
active
ingredients.

Erioglaucine
and
tartrazine
have
many
non­
pesticidal
uses,
including
their
use
as
inert
ingredients
(
dyes)
in
other
pesticide
formulations
and
as
approved
food
coloring
additives
in
a
variety
of
applications.
These
substances
are
each
Generally
Recognized
As
Safe
(
GRAS)
for
general
use
as
food,
drug,
and
cosmetic
color
additives
by
the
Food
and
Drug
Administration
(
FDA).

This
risk
assessment
considers
only
the
use
of
erioglaucine
and
tartrazine
as
active
ingredients
in
Aquashade
and
similar
products.
Human
health
risks
associated
with
their
use
as
inert
ingredients
were
recently
assessed
by
the
Office
of
Pesticide
Programs'
Registration
Division
(
RD)
[
Reassessment
of
the
Requirement
of
a
Tolerance
for
the
FDA­
Certified
Color
Additives
FD&
C
Blue
No.
1,
FD&
C
Red
No.
40,
and
FD&
C
Yellow
No.
5
(
Tartrazine),
K.
Liefer,
December
21,
2004).
HED
relied
heavily
on
the
information
presented
in
RD's
inert
ingredient
risk
assessment
in
this
assessment
of
the
human
health
risks
from
the
pesticidal
uses
of
Aquashade.

Use
Information
Aquashade
is
registered
for
use
as
an
aquatic
algaecide/
herbicide.
The
two
dyes
erioglaucine
and
tartrazine
work
by
blocking
penetration
of
the
portion
of
the
light
spectrum
required
for
photosynthesis,
thereby
limiting
the
growth
of
filamentous
algae
and
submerged
aquatic
vegetation.
Application
is
recommended
early
in
the
growing
season
while
growth
is
on
the
bottom
of
the
water
body
or
later
in
the
season
after
the
killing
and/
or
removal
of
any
existent
growth.
Repeated
applications
are
allowed
to
maintain
an
effective
concentration
of
product
in
the
water
body.
Aquashade
may
be
used
in
natural
or
manmade
ponds,
lakes,
fountains,
fish
farms
and
fish
hatcheries;
and
may
be
applied
by
both
professional
applicators
and
homeowners
(
Admiral
Liquid;
EPA
Reg.
No.
67064­
2
 
approved
3/
24/
05).
Water
bodies
treated
with
Aquashade
may
not
be
used
for
human
consumption.
However,
treated
water
may
be
used
for
irrigation
of
crops,
livestock
watering
and
fishing.

Toxicology
The
available
toxicity
data
on
the
two
main
ingredients
of
Aquashade,
erioglaucine
and
tartrazine,
are
adequate
to
assess
the
chemical's
hazard
potential.
A
product
containing
68%
erioglaucine
and
4.5%
tartrazine
was
used
in
the
acute
studies.
It
has
a
low
acute
toxicity
with
no
deaths
occurring
near
the
limit
dose
in
oral
studies
(
Category
IV).
It
has
a
moderate
acute
toxicity
in
dermal
studies
(
Category
III).
Based
on
the
uses,
the
requirement
for
the
acute
inhalation
study
has
been
historically
waived.
There
were
no
clinical
signs
of
systemic
toxicity
in
the
acute
oral
and
dermal
studies.
No
significant
differences
exist
between
males
and
females.
Page
5
of
42
The
tested
product
caused
slight
eye
irritation
(
Category
III).
It
was
negative
for
dermal
irritation
(
Category
IV);
however,
it
is
a
dermal
sensitizer.

Tartrazine
and
erioglaucine
each
have
very
low
toxicity
potentials.
A
definitive
target
organ
has
not
been
identified
and
clinical
signs
were
not
observed
in
any
study
performed
using
these
dyes.
Systemic
toxicity
was
observed
in
one
study
in
the
toxicity
database
and
was
limited
to
a
decrease
in
mean
body
weight
following
long­
term
dietary
exposure
to
high
doses
in
rats.
There
were
no
adverse
effects
observed
in
mice
or
dogs.
All
NOAELs
were
reported
to
be
$
500
mg/
kg/
day
with
the
exception
of
a
non­
guideline
21­
day
dermal
study
in
rats.
The
NOAEL
for
this
study
was
5
mg/
kg/
day;
however,
this
was
the
highest
dose
tested.

In
both
the
prenatal
developmental
toxicity
study
in
rats
and
the
3­
generation
reproduction
study
in
rats
with
tartrazine,
adverse
effects
were
not
observed
at
any
levels
below
the
limit
dose.
Given
the
similar
toxicity
profiles
of
the
two
dyes,
erioglaucine
is
expected
to
demonstrate
a
similar
developmental
and
reproductive
toxicity
profile.
No
adverse
effects
have
been
associated
with
exposure
resulting
from
the
FDA­
approved
uses
of
either
tartrazine
or
erioglaucine.
Based
on
the
lack
of
evidence
of
pre­
and/
or
post­
natal
susceptibility
following
exposure
to
tartrazine
or
erioglaucine,
and
considering
the
lack
of
residual
uncertainties
for
pre­
and/
or
post­
natal
toxicity,
no
special
FQPA
safety
factor
is
needed
(
1X).

There
was
no
evidence
of
neurotoxicity
reported
in
any
study.

No
evidence
of
carcinogenicity
was
observed
in
carcinogenicity
studies
in
mice
and
rats
with
erioglaucine,
(
Borzelleca
and
Hallagan,
1988a,
1988b)
and
tartrazine
(
Borzelleca
et
al,
1990).
These
substances
are
not
mutagenic
in
the
standard
Ames
assay
with
or
without
metabolic
activation
(
Brown
et
al,
1978).

Erioglaucine
and
tartrazine
are
rapidly
metabolized,
and
excreted
in
rats,
rabbits,
and
dogs.
Erioglaucine
is
poorly
absorbed;
however,
this
is
not
the
case
for
tartrazine.
The
presence
of
the
dyes
was
found
in
the
bile.
The
parent
compounds
are
excreted
unchanged
mainly
in
the
feces
with
a
small
amount
excreted
by
the
urine.

Residue
Chemistry
Water
bodies
treated
with
Aquashade
may
not
be
used
for
human
consumption.
However,
treated
water
may
be
used
for
irrigation
of
crops,
livestock
watering
and
fishing,
which
could
theoretically
result
in
residues
of
erioglaucine
and/
or
tartrazine
in
human
foods.
In
addition,
Aquashade
may
be
used
in
fish
farms/
hatcheries.
In
1982,
based
on
Aquashade's
low
toxicity
profile,
EPA
waived
residue
chemistry
data
requirements
and
established
an
exemption
from
the
requirement
of
a
tolerance
for
erioglaucine
when
used
as
an
aquatic
plant
control
agent
under
40
CFR
180.1074.
Tartrazine,
when
used
as
a
dye,
had
previously
been
exempted
from
the
requirement
of
a
tolerance
as
an
inert
(
or
occasionally
as
an
active)
ingredient
in
pesticide
formulations
applied
to
growing
crops
or
to
raw
agricultural
commodities
after
harvest
under
40
CFR
180.1001(
c)
(
currently
40
CFR
180.910).
HED
has
determined
that
the
existing
exemption
for
tartrazine
as
an
inert
ingredient
is
not
sufficient
to
satisfy
reregistration
requirements
for
the
active
ingredient
when
used
as
an
aquatic
plant
control
agent.
Therefore,
we
are
recommending
Page
6
of
42
that
the
exemption
for
erioglaucine
at
40
CFR
180.1074
be
revised
to
include
both
erioglaucine
and
tartrazine.

Environmental
Fate
The
color
additives
erioglaucine
and
tartrazine
are
water
soluble,
are
fully
dissociated
in
the
environmentally
significant
pH
range
of
5
to
9,
and
are
stable
towards
abiotic
hydrolysis.
Indirect
photolysis
in
water
is
a
major
route
of
transformation
for
these
and
other
structurally
related
dyes.
The
two
dyes
are
not
readily
biodegradable
under
aerobic
conditions,
but
biodegrade
under
anaerobic
conditions.
They
do
not
adsorb
strongly
to
soils/
sediments
and
are
predominantly
found
in
the
water
column.
Volatilization
from
soils
and
water
is
not
likely
to
be
a
transport
process
in
the
environment.
Both
dyes
are
highly
hydrophilic
and
are
not
likely
to
bioaccumulate
in
fish.

Products
containing
erioglaucine
and
tartrazine
are
applied
to
contained
water
bodies
with
little
or
no
outflow,
and
none
of
the
water
bodies
treated
with
the
products
serves
as
a
source
of
drinking
water.
Therefore,
no
drinking
water
assessment
is
needed
for
these
chemicals
when
used
as
algaecides/
herbicides
according
to
product
labeling.

Residential
Exposure
Aquashade
is
labeled
for
consumer
use
to
control
aquatic
algae
and
weeds
in
ponds
and
lakes.
The
anticipated
use
patterns
and
current
labeling
indicate
several
residential
handler
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
to
make
Aquashade
applications.
Residents
or
consumers
applying
Aquashade
products
to
ponds
or
lakes
may
be
exposed
for
short­
term
(
1
to
30
days)
duration
through
skin
contact
or
by
inhalation.
All
residential
handler
scenarios
assessed
(
dermal
and
inhalation)
resulted
in
estimated
MOEs
greater
than
100
and,
therefore,
are
not
of
concern.
Residential
short­
term
dermal
MOEs
range
from
1,930
(
Liquids
for
Pouring
Applications)
to
16,000
(
Liquids
for
LCO
Handgun),
and
shortterm
inhalation
MOEs
range
from
550,000
(
Liquids
for
Garden
Hose
End
Sprayer)
to
6,600,000
(
Liquids
for
Pouring
Applications).

Postapplication
exposures
to
children
and
adults
that
contact
Aquashade­
treated
swimming
ponds
are
anticipated.
To
address
the
risk
of
such
exposures,
a
screening
tool
called
the
Swimmer
Exposure
Assessment
Model
(
SWIMODEL)
was
applied.
The
SWIMODEL
uses
well­
accepted
screening
exposure
assessment
equations
to
calculate
the
total
worst­
case
exposure
for
swimmers
expressed
as
a
mass­
based
intake
value
(
mg/
event).
Postapplication
residential
exposure
durations
are
expected
to
be
short­
and
intermediate­
term
(
1
to
6
months)
in
duration.
All
residential
postapplication
scenarios
assessed
(
dermal,
ingestion,
aural,
buccal/
sublingual,
and
nasal/
orbital
routes
of
exposure)
resulted
in
estimated
combined
MOEs
well
above
100
and,
therefore,
are
not
of
concern.

To
better
quantify
residential
Aquashade
hazard,
results
from
residential
handler
and
residential
postapplication
(
i.
e.,
swimmer)
risk
assessments
were
aggregated.
Aggregate
calculations
of
residential
exposure
were
performed
using
worst­
case
MOEs
resulting
from
each
assessment.
Page
7
of
42
The
residential
aggregated
exposure
resulted
in
an
estimated
MOE
of
1700
and,
therefore,
is
not
a
risk
of
concern.

Aggregate
Risk
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
pesticide
exposures
and
risks
from
three
major
sources:
drinking
water,
food
and
residential
exposures.
Since
Aquashade
is
applied
to
contained
water
bodies
with
little
or
no
outflow,
and
none
of
the
treated
water
bodies
serves
as
a
source
of
drinking
water,
no
drinking
water
exposure
is
expected.
Although
water
treated
with
Aquashade
may
potentially
be
used
for
irrigation
of
food
crops
and
livestock
watering,
and
Aquashade
is
registered
for
use
in
fish
farms
and
hatcheries,
HED
has
not
quantitatively
assessed
exposures
and
risks
from
food
sources
for
several
reasons:
(
1)
Aquashade
is
used
primarily
in
ornamental
and/
or
recreational
lakes
and
ponds
with
very
little
treated
water
expected
to
be
used
for
agricultural
purposes.
(
2)
Erioglaucine
and
tartrazine
are
highly
water
soluble
compounds
and,
as
such,
not
likely
to
accumulate
in
livestock
or
fish
tissues.
The
results
of
the
rat
metabolism
study
with
erioglaucine
support
this
determination,
since
nearly
the
entire
administered
dose
was
excreted
unchanged
in
the
feces
in
less
than
2
days.
(
3)
Any
residues
of
erioglaucine
or
tartrazine
occurring
in
foods
from
the
use
of
Aquashade
as
an
aquatic
algaecide/
herbicide
would
be
negligible
compared
to
residues
in
food
from
the
common
use
of
these
dyes
as
food
coloring
additives.
(
4)
The
most
significant
route
of
exposure
to
erioglaucine
and
tartrazine
from
the
use
of
Aquashade
is
residential
exposure,
including
residential
handler
and
postapplication
(
swimming)
exposure.
HED
believes
that
the
conservative
residential
exposure
and
risk
estimates
discussed
above
are
more
than
adequate
to
cover
any
food
exposures
that
could
potentially
occur
from
the
use
of
Aquashade
as
an
aquatic
algaecide/
herbicide.

Occupational
Exposure
Exposure
of
pesticide
handlers
is
likely
during
the
occupational
use
of
Aquashade
in
a
variety
of
occupational
environments.
Since
no
chemical­
specific
handler
exposure
data
are
available
for
Aquashade,
short­
and
intermediate­
term
dermal
and
inhalation
exposures
were
assessed
using
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1
and
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).
PHED
and
ORETF
data
were
used
with
other
HED
standard
values
for
areas
treated
per
day,
body
weight
and
the
level
of
personal
protective
equipment
(
PPE)
and
engineering
controls
to
assess
handler
exposures
to
Aquashade.
Using
these
assumptions,
the
calculated
occupational
handler
exposures
for
all
scenarios
resulted
in
estimated
MOEs
greater
than
100
and,
therefore,
are
not
of
concern.
Short­
and
intermediateterm
dermal
MOEs
range
from
410
(
Liquids
for
Pouring
Applications)
to
4,300
(
Liquids
for
Garden
Hose­
End
Sprayer),
and
short­
and
intermediate­
term
inhalation
MOEs
range
from
120,000
(
Liquids
for
Garden
Hose
End
Sprayer)
to
1,600,000
(
Liquids
for
Pouring
Applications).

Since
Aquashade
is
an
algaecide/
herbicide,
HED
is
not
aware
of
any
postapplication
activities
which
may
result
in
exposure.
No
harvesting
is
required,
and
while
scouting
may
include
identifying
any
algae
or
aquatic
weed
regrowth,
these
activities
should
not
require
contact
with
the
treated
water
body.
For
these
reasons,
occupational
postapplication
exposure
of
workers
to
Page
8
of
42
previously
treated
water
bodies
is
expected
to
be
negligible
and
was
not
assessed.
Furthermore,
any
postapplication
activities
that
could
potentially
occur
would
not
be
expected
to
exceed
those
assessed
from
residential
exposures
to
Aquashade
which
are
not
of
concern.

Conclusions
Aquashade
is
a
low
toxicity
algaecide/
herbicide
whose
potential
non­
occupational
routes
of
exposure
include
residential
handler
and
postapplication
(
swimming)
exposures.
None
of
the
water
bodies
treated
serves
as
a
source
of
drinking
water;
and,
while
treated
water
may
be
used
to
irrigate
food
crops
or
for
livestock
watering,
resulting
food
residues
are
expected
to
be
negligible.
Under
the
conditions
of
its
current
use,
human
health
risks
to
workers
handling
the
pesticide
or
to
the
general
population
are
below
HED's
level
of
concern.
Aggregate
risk
estimates
from
residential
handler
and
postapplication
residential
exposures
are
well
below
HED's
level
of
concern.

2.0
Ingredient
Profile
Aquashade
is
an
aquatic
algaecide/
herbicide
which
is
composed
of
a
combination
of
the
dyes
erioglaucine
and
tartrazine.
Application
is
recommended
early
in
the
growing
season
while
growth
is
on
the
bottom
of
the
water
body
or
later
in
the
season
after
the
killing
and/
or
removal
of
any
existent
growth.
Repeated
applications
are
allowed
to
maintain
an
effective
concentration
of
product
in
the
water
body.
Aquashade
works
by
controlling
the
portion
of
the
light
spectrum
required
for
photosynthesis,
thereby
inhibiting
growth
of
filamentous
algae
and
submerged
aquatic
vegetation.

Aquashade
is
formulated
for
use
in
occupational
settings
as
either
a
liquid
or
water
soluble
packet
(
WSP)
product,
and
can
be
applied
by
pouring
or
dropping
the
WSP
in
water
body
from
the
shoreline,
or
possibly
by
boat
for
larger
water
bodies.
It
is
formulated
for
residential
use
as
a
liquid
product
only
(
67064­
2).
While
not
specified
on
product
labeling,
applications
could
be
made
by
LCO
handgun
or
garden
hose
end
sprayer.
The
combination
of
erioglaucine
and
tartrazine
are
the
active
ingredients
for
5
registered
products.
Each
product
has
a
different
ratio
of
the
dyes,
but
in
all
of
the
product
formulations
the
percent
of
Acid
Blue
9
is
higher
than
that
of
Acid
Yellow
23.
Aquashade
is
applied
at
a
rate
of
0.22
to
1.1
pounds
of
active
ingredient
per
acre­
foot.
Page
9
of
42
2.1
Summary
of
Registered/
Proposed
Uses
Table
2.1
Summary
of
Registered
Aquashade
Commercial
Uses
Liquid
Formulation
Product
Crop
Max
App
Rate
(
lb
ai/
acre­
foot)
Amount
of
Product
for
Area
To
Be
Treated
Application
Methods
Aquashade
(
33068­
1)
Ornamental
and
Recreational
Lakes
and
Ponds,
Fish
Rearing
and
Fish
Farming
Ponds,
Golf
Course
Ponds
1.1
0.5
gallon/
acre­
foot
(
2
ppm)
Pouring
Admiral
Liquid
(
67064­
2)
Fountains,
Fish
Farms,
Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
0.73
0.5
gallon/
acre­
foot
(
2ppm)
Pouring
Algae
Blocker
(
8709­
6)
Garden
Ponds,
Goldfish
Ponds,
Koi
Ponds,
Ornamental
Ponds
0.22
120
ml
/
1500
gallons
Pouring
Aquashade
OA
(
33068­
2)
Aquariums,
Fountains,
Ornamental
Ponds,
Recirculated
or
Artificial
Waterscapes
0.22
1
ounce/
1000
gallons
Pouring
Water
Soluble
Packets
(
WSP)

Admiral
WSP
(
67064­
1)
Fish
Farms,
Fish
Hatcheries,
Fountains,
Golf
Courses,
Manmade
Ponds,
Swimming
Ponds
0.73
2
WSPs/
acre­
foot
(
11
ounces)
WSP
Page
10
of
42
2.2
Structure
and
Nomenclature
Table
2.2
Aquashade
Nomenclature
Chemical
Structure
Empirical
Formula
C37H34N2Na2
O9
S3
C16H9N4O9S2Na3
Common
Name
Erioglaucine,
Acid
Blue
9
Tartrazine,
Acid
Yellow
23
CAS
Name
disodium
bis[
4­(
N­
ethyl­
N­
3­
sulfonatophenylmethyl)
aminophenyl]
phenyl
methylium
4,5­
dihydro­
5­
oxo­
1­(
4­
sulophenyl)­
4­
[(
4­
sulfophenyl)
azo]­
1H­
pyrazole­
3­
carboxylic
acid
trisodium
salt
CAS
Registry
Number
2650­
18­
2
1934­
21­
0
End
Use
Products/
EPs
33068­
1
23.63%
2.39%
33068­
2
2.36%
0.24%
67064­
1
49.72%
3.27%
67064­
2
15.31%
1.00%
8709­
6
2.36%
0.24%

2.3
Physical
and
Chemical
Properties
Table
2.3
Physicochemical
Properties
of
Aquashade
Parameter
Value
Reference
Acid
Blue
9
Acid
Yellow
23
Molecular
Weight
792.86
534.37
SRC,
2004
Melting
point
>
250
°
C
>
300
°
C
SRC,
2004
Water
solubility
at
25
°
C
160
g/
L
at
25
°
C
EPI
Suite,
2004
Page
11
of
42
Table
2.3
Physicochemical
Properties
of
Aquashade
Parameter
Value
Reference
Acid
Blue
9
Acid
Yellow
23
Vapor
pressure
2.97
x
10­
42
mmHg
at
25
°
C
7.43
x
10­
22
mmHg
at
25
°
C
EPI
Suite,
2004
Octanol/
water
partition
coefficient
(
Kow)
Kow
=
0.032
Kow
=
6.3
x
10­
11
SRC,
2004
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Erioglaucine
was
administered
orally
to
rats
as
a
2%
aqueous
solution
at
a
level
of
200
mg/
rat.
Almost
the
entire
amount
was
excreted
unchanged
in
the
feces
within
40
h
after
administration.
In
a
later
investigation,
the
presence
of
the
color
in
the
bile
was
observed
in
rats,
rabbits
and
dogs
after
oral
administration.
In
the
case
of
the
dog,
the
amount
did
not
exceed
5%
of
the
dose
administered
(
Hess
&
Fitzhugh,
1953;
1954;
1955).
Administration
of
an
aqueous
solution
of
the
color
by
stomach
tube
resulted
in
89
%
excretion
in
the
feces;
none
was
found
in
the
urine.
After
subcutaneous
injection
of
80­
100
mg
some
79%
was
excreted;
77%
appeared
in
the
feces
and
2.5%
in
the
urine
(
Imperial
Chemical
Industries,
1958).

Metabolism
studies
for
plants
and
livestock
are
not
available
for
comparison
and
have
not
been
required.

4.0
Hazard
Characterization/
Assessment
4.1
Hazard
Characterization
A
combination
of
erioglaucine
(
Acid
Blue
9
or
FD&
C
Blue
No.
1)
and
tartrazine
(
Acid
Yellow
23
or
FD&
C
Yellow
No.
5)
is
commonly
referred
to
as
Aquashade.
Five
currently
registered
pesticide
products,
which
are
used
as
aquatic
algaecides/
herbicides,
contain
a
combination
of
erioglaucine
and
tartrazine.
These
substances
are
each
Generally
Recognized
As
Safe
(
GRAS)
for
general
use
as
food,
drug,
and
cosmetic
color
additives
by
the
Food
and
Drug
Administration
(
FDA).

The
end­
use
products
each
have
a
different
ratio
of
the
dyes.
A
product
containing
68%
erioglaucine
and
4.5%
tartrazine
was
used
in
the
acute
studies.
It
has
a
low
acute
toxicity
with
no
deaths
occurring
near
the
limit
dose
in
oral
studies
(
Category
IV).
It
has
a
moderate
acute
toxicity
in
dermal
studies
(
Category
III).
Based
on
the
uses,
the
requirement
for
the
acute
inhalation
study
has
been
historically
waived.
There
were
no
clinical
signs
of
systemic
toxicity
Page
12
of
42
in
the
acute
oral
and
dermal
studies.
No
significant
differences
exist
between
males
and
females.
The
tested
product
caused
slight
eye
irritation
(
Category
III).
It
was
negative
for
dermal
irritation
(
Category
IV);
however,
it
is
a
dermal
sensitizer.

Tartrazine
and
erioglaucine
each
have
very
low
toxicity
potentials.
A
definitive
target
organ
has
not
been
identified
and
clinical
signs
were
not
observed
in
any
study
preformed
using
these
dyes.
Systemic
toxicity
was
observed
in
one
study
in
the
toxicity
database
and
was
limited
to
a
decrease
in
mean
body
weight
following
long­
term
dietary
exposure
to
high
doses
in
rats.
There
were
no
adverse
effects
observed
in
mice
or
dogs.
All
NOAELs
were
reported
to
be
$
500
mg/
kg/
day
with
the
exception
of
a
non­
guideline
21­
day
dermal
study
in
rats.
The
NOAEL
for
this
study
was
5
mg/
kg/
day;
however,
this
was
the
highest
dose
tested.

In
both
the
prenatal
developmental
toxicity
study
in
rats
and
the
3­
generation
reproduction
study
in
rats
with
tartrazine,
adverse
effects
were
not
observed
at
any
levels
below
the
limit
dose.
Given
the
similar
toxicity
profiles
of
the
two
dyes,
erioglaucine
is
unlikely
to
demonstrate
quantitative
or
qualitative
susceptibility.
No
adverse
effects
have
been
associated
with
exposure
resulting
from
the
FDA­
approved
uses
of
either
tartrazine
or
erioglaucine.

Based
on
the
lack
of
evidence
of
pre­
and/
or
post­
natal
susceptibility
following
exposure
to
tartrazine
or
erioglaucine,
and
considering
the
lack
of
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity,
no
special
FQPA
safety
factor
is
needed
(
1X).

There
was
no
evidence
of
neurotoxicity
reported
in
any
study.

No
evidence
of
carcinogenicity
was
observed
in
carcinogenicity
studies
in
mice
and
rats
with
erioglaucine,
(
Borzelleca
and
Hallagan,
1988a,
1988b)
and
tartrazine
(
Borzelleca
et
al,
1990).
These
substances
are
not
mutagenic
in
the
standard
Ames
assay
with
or
without
metabolic
activation
(
Brown
et
al,
1978).

Erioglaucine
and
tartrazine
are
rapidly
metabolized,
and
excreted
in
rats,
rabbits,
and
dogs.
Erioglaucine
is
poorly
absorbed;
however,
this
is
not
the
case
for
tartrazine.
The
presence
of
the
dyes
was
found
in
the
bile.
The
parent
compounds
are
excreted
unchanged
mainly
in
the
feces
with
a
small
amount
excreted
by
the
urine.

4.1.5.
Acute
Toxicity
Table
4.1a
Acute
Toxicity
Profile
­
Admiral
WSP
(
Erioglaucine
68.13%;
Tartrazine
4.51%)

Guideline
No.
Study
Type
MRIDs
Results
Toxicity
Category
870.1100
Acute
oral
[
rats]
45281101
LD50
>
5000
mg/
kg
IV
870.1200
Acute
dermal
[
rabbit]
45144401
LD50
>
2000
mg/
kg
III
Page
13
of
42
870.1300
Acute
inhalation
NA
data
requirement
waived
870.2400
Acute
eye
irritation
[
rabbit]
44902902
No
eye
irritation
III
870.2500
Acute
dermal
irritation
[
rabbit]
45086102
negative
IV
870.2600
Skin
sensitization
[
guinea
pig]
44902904
positive
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3200
21/
28­
Day
dermal
toxicity
(
species)
43410101
Acceptable/
Non­
Guideline
0,
0.5,
5
mg/
kg/
day
Systemic
NOAEL
 
5.0
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
870.3700a
Prenatal
developmental
(
rats)
Tartrazine
434081011
Acceptable/
Guideline
0,
100,
300,
1000
mg/
kg/
day
Maternal
NOAEL
=
1000
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
Developmental
NOAEL
=
1000
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
870.3700b
Prenatal
developmental
(
rats)
Tartrazine
No
MRID
Collins
et
al
1990
0,
60,
100,
200,
400,
600
or
1000
mg/
kg/
day
Maternal
NOAEL
=
1000
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
Developmental
NOAEL
=
1000
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
870.3800
Reproduction
and
fertility
effects
(
rats)
Tartrazine
43410901
Acceptable/
Guideline
0,
7.5,
75,
225
or
750
mg/
kg/
day
Parental/
Systemic
NOAEL
=
750
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
Reproductive
NOAEL
=
750
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
Offspring
NOAEL
=
NOAEL
=
750
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
870.4100
Chronic
toxicity
(
dog)
Tartrazine
No
MRID
FDA,
1985
NOAEL
=
500
mg/
kg/
day
LOAEL
=
not
identified
Page
14
of
42
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.4200
Carcinogencity
Satisfied
by
870.4300a­

870.4300a
Combined
chronic
toxicity/
Carcinogenicity
(
rat)
Erioglaucine
No
MRID
Borzelleca
et
al,
1990
F:
0,
63,
631,
1262
mg/
kg/
day
M:
0,
54,
536,
1072
mg/
kg/
day
NOAEL
=
631
mg/
kg/
day
LOAEL
=
1262
mg/
kg/
day
based
on
decreased
body
weight
in
females.
No
evidence
of
carcinogenicity
870.4300b
Combined
chronic
toxicity/
Carcinogenicity
(
rat)
Tartrazine
No
MRID
Borzelleca
et
al,
1988a
F:
0,
53,
1056,
2641
mg/
kg/
day
M:
0,
67,
1339,
3348
mg/
kg/
day
NOAEL
=
2641
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
No
evidence
of
carcinogenicity
870.4300c
Combined
chronic
toxicity/
Carcinogenicity
(
mice)
Erioglaucine
No
MRID
FDA,
1982
NOAEL
=
1200
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
No
evidence
of
carcinogenicity
870.4300d
Combined
chronic
toxicity/
Carcinogenicity
(
mice)
Erioglaucine
No
MRID
Borzelleca
et
al,
1990
F:
0,
897,
2690,
8966
mg/
kg/
day
M:
0,
735,
2206,
7354
mg/
kg/
day
NOAEL
=
7354
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
No
evidence
of
carcinogenicity
870.4300e
Combined
chronic
toxicity/
Carcinogenicity
(
mice)
Tartrazine
No
MRID
Borzelleca
et
al,
1988b
F:
0,
974,
2912,
9735
mg/
kg/
day
M:
0,
41,
2431,
8103
mg/
kg/
day
NOAEL
=
8103
mg/
kg/
day
(
HDT)
LOAEL
=
not
identified
No
evidence
of
carcinogenicity
870.5100
Bacterial
reverse
mutation
test
Tartrazine
No
MRID
Hansen
et
al,
1964
as
cited
in
JEFCA,
1969
Negative.

870.6200b
Subchronic
neurotoxicity
screening
battery
N/
A
870.6300
Developmental
neurotoxicity
N/
A
Page
15
of
42
Table
4.1b
Subchronic,
Chronic
and
Other
Toxicity
Profile
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.7485
Metabolism
and
pharmacokinetics
(
species)
No
MRID
Imperial
Chemical
Industries,
1958
Erioglaucine
was
administered
orally
to
rats
as
a
2%
aqueous
solution
at
a
level
of
200
mg/
rat.
Almost
the
entire
amount
was
excreted
unchanged
in
the
feces
within
40
h
after
administration.

870.7600
Dermal
penetration
(
species)
N/
A
Special
studies
N/
A
4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
This
risk
assessment
takes
a
weight
of
the
evidence
approach,
considering
the
available
data
from
a
variety
of
sources,
including
studies
submitted
and
reviewed
by
the
agency,
the
Food
and
Drug
Administration
(
FDA)
and
the
Joint
Expert
Committee
on
Food
Additives
of
the
Food
and
Agriculture
Organization/
World
Health
Organization
(
JECFA).
This
information
is
sufficient
to
evaluate
the
toxicity
of
Aquashade
and
related
compounds.
Based
on
the
information
available
from
these
sources,
the
database
is
complete
and
there
are
no
data
gaps.

4.2.2
Evidence
of
Neurotoxicity
Neurotoxicity
studies
have
not
been
conducted
on
either
erioglaucine
or
tartrazine.
However,
no
evidence
of
neurotoxicity
was
observed
in
any
study.
No
clinical
signs
indicative
of
neurotoxicity
were
noted
in
subchronic
and
chronic
studies
in
dogs
or
rats.

4.2.3
Developmental
Toxicity
Studies
In
a
developmental
toxicity
study
(
MRID
43408101),
groups
of
22­
23
Long­
Evans
female
rats
were
administered
tartrazine
(
92%,
Lot
No.
CCIC­
7)
at
dose
levels
of
0,
100,
300,
or
1000
mg/
kg/
day.
Included
were
3
control
groups
containing
22
female
rats
per
group
and
one
positive
control
group
in
which
trypan
blue
was
administered
to
22
female
rats
at
30
mg/
kg/
day
from
day
7
through
day
9
of
gestation
by
subcutaneous
injection.
All
dams
were
sacrificed
on
day
20
of
gestation.
Page
16
of
42
No
clinical
signs
of
toxicity
and
no
mortality
were
observed.
There
were
no
treatment
related
effects
on
maternal
body
weight
gain,
pregnancy
rate,
early
deliveries,
fetal
resorption,
viability,
fetal
weight
or
sex
ratio.
The
NOAEL
for
maternal
toxicity
was
1000
mg/
kg/
day
(
HDT).
The
LOAEL
could
not
be
determined.
The
NOAEL
for
developmental
toxicity
was
1000
mg/
kg/
day
(
HDT)
and
the
LOAEL
could
not
be
determined.

The
study
is
acceptable/
guideline.
It
satisfies
the
requirement
for
a
guideline
series
83­
3(
a)
developmental
toxicity
study
in
rats.
Although
the
dose
levels
chosen
for
this
study
were
insufficient
to
produce
systemic
or
developmental
toxicity,
the
limit
dose
was
reached
and
the
intent
of
the
guideline
requirement
was
met.
The
high
dose
of
1000
mg/
kg/
day
is
consistent
with
no
effects
in
rats
and
is
considered
to
adequately
address
the
issue
as
to
whether
or
not
FD&
C
Yellow
No.
5
causes
prenatal
developmental
toxicity.

In
a
second
cited
prenatal
developmental
study,
tartrazine
was
given
to
Osborne­
Mendel
rats
by
gavage
at
dose
levels
of
0,
60,
100,
200,
400,
600
or
1000
mg/
kg/
day
on
days
0­
19
of
gestation.
No
maternal
or
developmental
toxicity
was
observed
when
the
rats
were
killed
on
day
20.
The
mean
daily
food
consumption
for
the
entire
period
of
gestation
was
significantly
greater
in
the
females
given
1000
mg/
kg
body
weight/
day
than
in
the
controls,
but
maternal
body­
weight
gain
was
not
affected.
No
dose­
related
effects
were
observed
in
implantations,
fetal
viability
or
external
fetal
development.
Fetal
skeletal
and
visceral
development
was
similar
among
fetuses
from
all
groups.
At
the
doses
given,
tartrazine
was
neither
toxic
nor
teratogenic
(
Collins
et
al,
1990).

4.2.4
Reproductive
Toxicity
Study
In
a
3­
generation
reproduction
study
(
MRID
43410901),
groups
of
10
male
and
20
female
Long­
Evans
rats
were
administered
tartrazine
(
92%
ai,
Lot
No.
CC1C­
7)
at
dose
levels
of
0,
7.5,
75,
225,
or
750
mg/
kg/
day
in
the
diet.
First
generation
rats
produced
2
litters;
second
generation
rats
produced
3
litters
(
one
of
which
was
sacrificed
on
Day
19
G.
D.
for
embryologic
examination),
and
the
third
generation
produced
2
litters.

There
were
no
adverse
treatment
related
effects
on
parental
survival,
body
weight,
body
weight
gain,
food
consumption,
efficiency
of
food
utilization,
mating,
pregnancy
or
fertility
rates,
gestation
length,
offspring
viability,
weight
and
sex,
Day
19
sacrifice
data
or
necropsy
findings.
The
NOAEL
for
reproductive/
systemic
effects
is
750
mg/
kg/
day
(
HDT).
The
LOAEL
was
not
determined.

This
study
is
acceptable
and
satisfies
the
guideline
requirement
for
a
2­
generation
reproductive
study
(
OPPTS
870.3800);
OECD
416
in
rat.
Although
the
dose
levels
chosen
for
this
study
were
insufficient
to
produce
systemic
or
reproductive
toxicity,
the
intent
of
the
guideline
requirement
was
met
as
described
in
§
81
through
§
86
of
subdivision
F
of
the
Pesticide
Assessment
Guidelines.
The
high
dose
of
750
mg/
kg/
day
is
consistent
with
no
effects
in
rats
and
is
considered
to
adequately
address
the
issue
as
to
whether
or
not
FD&
C
Yellow
No.
5
causes
reproductive
toxicity.
Page
17
of
42
4.2.5
Additional
Information
from
Literature
Sources
It
should
be
noted
that
the
toxicological
database
for
erioglaucine
and
tartrazine,
including
all
subchronic
and
chronic
studies,
was
evaluated
by
the
FDA
and
an
international
peer
review
committee,
JEFCA
(
http://
www.
fao.
org/
ag/
AGP/
AGPP/
Pesticid/
Default.
html.)
The
FDA
and
JECFA
evaluations
of
erioglaucine
and
tartrazine
include
reviews
of
numerous
animal
toxicity
studies
involving
dogs,
hamsters,
guinea
pigs,
rabbits,
rats,
and
mice
as
part
of
their
toxicity
endpoint
selection
process.
In
permanently
listing
erioglaucine
and
tartrazine
as
color
additives
for
use
in
foods,
drugs
and
cosmetics,
FDA
concluded
that
these
colorants
were
safe
and
determined
a
maximum
acceptable
daily
intake
for
erioglaucine
and
tartrazine
(
FDA
1982,
1985).
Similarly,
JECFA
has
evaluated
these
compounds
for
the
purpose
of
establishing
estimates
of
acceptable
daily
intakes
(
ADIs)
(
JECFA
1964,
1969,
1980).
Table
3
lists
the
respective
FDA
and
JECFA
ADIs
for
these
substances.

Table
3.
FDA
and
JECFA
Acceptable
Daily
Intake
(
ADI)
Values
(
in
mg/
kg­
bw/
day)

Color
Additive
FDA
ADI
JECFA
ADI
Erioglaucine
12.0
0
­
12.5
Tartrazine
5.0
0
­
7.5
4.2.6
Pre­
and/
or
Post­
natal
Toxicity
4.2.6.1
Determination
of
Susceptibility
No
quantitative
or
qualitative
evidence
supports
increased
susceptibility
of
rat
or
fetuses
from
in
utero
exposure
to
tartrazine
in
the
developmental
toxicity
studies.
There
was
not
a
prenatal
developmental
study
in
rabbits
available
in
the
database.
In
both
the
prenatal
developmental
toxicity
study
in
rats
and
the
3­
generation
reproduction
study
in
rats
with
tartrazine,
adverse
effects
were
not
observed
at
any
levels
below
the
limit
dose.
Given
the
similar
toxicity
profiles
of
the
two
dyes,
erioglaucine
is
unlikely
to
demonstrate
quantitative
or
qualitative
susceptibility.
No
adverse
effects
have
been
associated
with
exposure
resulting
from
the
FDA­
approved
uses
of
either
tartrazine
or
erioglaucine.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre­
and/
or
Post­
natal
Susceptibility
There
is
no
degree
of
concern
and
there
are
no
residual
uncertainties.
No
quantitative
or
qualitative
sensitivity
was
observed
in
the
rat
and
rabbit
developmental
studies
or
in
the
3­
generation
reproduction
study
in
the
rat
when
tested
with
tartrazine.
Given
the
similar
toxicity
profiles
of
the
two
dyes,
erioglaucine
is
unlikely
to
demonstrate
quantitative
or
qualitative
susceptibility.
Based
on
the
lack
of
evidence
of
pre­
and/
or
post­
natal
susceptibility
following
exposure
to
tartrazine
or
erioglaucine,
and
considering
the
lack
of
residual
uncertainties
for
pre
Page
18
of
42
and/
or
post­
natal
toxicity,
no
special
FQPA
safety
factor
is
needed
(
1X).
There
is
no
concern
for
developmental
neurotoxicity
resulting
from
exposure
to
erioglaucine
and
tartrazine.

4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
Study
There
is
no
evidence
that
supports
requiring
a
developmental
neurotoxicity
study.

4.3.2
Evidence
that
supports
not
requiring
Developmental
Neurotoxicity
Study
The
available
data
on
the
toxicity
of
Erioglaucine
and
tartrazine
do
not
support
the
recommendation
for
a
developmental
neurotoxicity
study.
No
evidence
of
neurotoxicity
was
observed
in
any
study.

4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
There
is
no
appropriate
endpoint
for
females
age
13­
49
attributable
to
a
single
exposure
available
from
oral
studies
including
the
developmental
toxicity
studies.

4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
There
is
no
appropriate
endpoint
for
the
general
population
to
a
single
exposure
available
from
oral
studies
including
the
developmental
toxicity
studies.

4.4.3
Chronic
Reference
Dose
(
cRfD)

Studies
Selected:
Chronic
oral
toxicity
study
in
dogs
(
tartrazine)
and
chronic
oral
toxicity/
carcinogenicity
study
in
rats
(
erioglaucine;
co­
critical).

MRID
No.:
No
MRID;
listed
as
reviewed
by
the
FDA
Executive
Summary:
Chronic
oral
toxicity
study
in
dogs
(
tartrazine).
The
chronic
study
in
dogs
was
submitted
to
the
FDA
and
was
used
to
establish
their
ADI.
In
Federal
Register
Vol.
50.
No
171,
the
FDA
reported
that
there
were
a
"
large
number
of
animals
of
both
sexes".
Furthermore,
"
pilot
studies
to
determine
maximum
tolerated
dosages
and
two
control
groups
increased
the
power
of
these
tests
for
detecting
dose­
related
effects."
These
Page
19
of
42
studies
were
designed
and
conducted
in
full
compliance
with
good
laboratory
practice
regulations
and
were
subject
to
FDA
inspection
while
they
were
being
conducted.
The
study
in
dogs
showed
no
adverse
effects
at
any
level.
The
NOAEL
was
500
mg/
kg/
day
and
a
LOAEL
was
not
established.

Co­
Critical
Study
MRID
No.:
No
MRID;
listed
as
cited
by
Borzelleca
et
al,
1990
Executive
Summary:
Combined
chronic
toxicity/
carcinogenicity
study
in
rats
FD
&
C
Blue
No.
1
(
erioglaucine)
was
fed
to
Charles
River
CD
rats
as
a
dietary
mixture
in
lifetime
toxicity/
carcinogenicity
studies.
The
rat
study
was
conducted
with
an
in
utero
phase
in
which
the
compound
was
administered
to
the
F0
generation
rats
(
60/
sex/
group)
at
dietary
concentrations
of
0.0%,
0.1%,
1.0%
or
2.0%
equaling
approximately
0,
63,
631
and
1262
mg/
kg/
day
and
0,
54,
536,
and
1072
mg/
kg/
day
in
females
males,
respectively.
After
randomly
selecting
the
F1
animals,
the
lifetime
phase
was
initiated
at
the
same
levels
with
70
rats/
sex/
group,
including
two
control
groups.
The
maximum
exposure
times
were
116
and
111
weeks
for
males
and
females,
respectively.
The
no­
observed­
adverse­
effect
levels
are
dietary
concentrations
of
2.0%
for
males
(
1072
mg/
kg
body
weight/
day),
and
1.0%
for
females
(
631
mg/
kg/
day)
based
on
a
15.0%
decrease
in
terminal
body
weight
and
decreased
survival
in
the
high­
dose
(
1262
mg/
kg/
day)
females
compared
with
the
combined
control
groups
(
Borzelleca
et
al,
1990
).

Dose
and
Endpoint:
The
NOAEL
of
500
mg/
kg/
day
(
HDT)
in
the
chronic
oral
toxicity
study
in
dogs
with
tartrazine.
This
is
supported
by
a
combined
chronic
toxicity/
carcinogenicity
study
in
rats
with
erioglaucine,
which
reported
a
NOAEL
of
631
mg/
kg/
day
based
on
decreased
body
weight
at
1262
mg/
kg/
day
in
females
(
LOAEL).

Uncertainty
Factor
(
UF):
100;
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variations.

Comments
About
Study/
Endpoint/
UF:
In
1985,
the
FDA
used
the
chronic
study
in
dogs
to
derive
the
ADI
for
tartrazine.
The
risk
assessment
team
also
used
this
study
(
OPPTS
number
870.4100a)
for
the
selection
of
the
chronic
endpoint.
The
rat
combined
chronic
toxicity/
carcinogenicity
study
(
OPPTS
number
870.4300a)
using
erioglaucine
is
considered
supportive
of
the
oral
dog
study
using
tartrazine.
The
NOAEL
of
500
mg/
kg/
day
demonstrated
in
the
chronic
dog
study
with
tartrazine
is
the
most
conservative
endpoint
in
the
database.
Although
this
study
is
from
the
FDA's
register,
it
is
fully
supported
by
rat
combined
chronic
toxicity/
carcinogenicity
study
(
NOAEL
=
631
mg/
kg/
day)
with
erioglaucine
and
by
other
chronic
studies
in
the
tartrazine/
erioglaucine
database
which
all
demonstrate
extremely
high
NOAELs
(>
1000
mg/
kg/
day).
Since
the
formulated
products
used
are
often
a
combination
of
tartrazine
and
erioglaucine,
the
selection
of
an
endpoint
using
these
two
studies
allowed
the
team
to
make
the
most
conservative
and
protective
estimation
of
the
chronic
reference
dose.
Page
20
of
42
Chronic
RfD
=
500
mg/
kg/
day
=
5
mg/
kg/
day
(
tartrazine)

100
4.4.4
Incidental
Oral
Exposure
(
Short­
and
Intermediate­
Term)

Studies
Selected:
Chronic
oral
toxicity
study
in
dogs
(
tartrazine)
and
chronic
oral
toxicity/
carcinogenicity
study
in
rats
(
erioglaucine;
co­
critical).

MRID
No.:
No
MRIDs;
listed
as
reviewed
by
the
FDA
Executive
Summary:
see
section
4.4.3
Dose
and
Endpoint:
The
NOAEL
of
500
mg/
kg/
day
(
HDT)
in
the
chronic
oral
toxicity
study
in
dogs
with
tartrazine.
This
is
supported
by
a
combined
chronic
toxicity/
carcinogenicity
study
in
rats
with
erioglaucine,
which
reported
a
NOAEL
of
631
mg/
kg/
day
based
on
decreased
body
weight
at
1262
mg/
kg/
day
in
females
(
LOAEL).

Uncertainty
Factor
(
UF):
100;
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variations.

Comments
About
Study/
Endpoint/
UF:
Prenatal
developmental
studies
using
tartrazine
in
rats
are
available;
however,
the
NOAELs
are
1000
mg/
kg/
day.
For
this
reason,
the
team
selected
the
aforementioned
chronic
studies
and
acknowledges
that
these
endpoints
are
conservative
and
should
be
protective
for
any
potential
adverse
effects.
Therefore,
the
duration
and
dosing
and
the
endpoint
are
appropriate
for
this
scenario.

4.4.5
Dermal
Absorption
No
dermal
absorption
study
was
available.
Therefore,
the
default
dermal
absorption
factor
of
100%
was
used.
It
should
be
noted
that
use
of
the
default
dermal
absorption
factor
resulted
in
a
highly
conservative
estimation
of
risk
through
this
route
of
exposure.

4.4.6
Dermal
Exposure
(
Short,
Intermediate
­
Term)

Studies
Selected:
Chronic
oral
toxicity
study
in
dogs
(
tartrazine)
and
chronic
oral
toxicity/
carcinogenicity
study
in
rats
(
erioglaucine;
co­
critical).

MRID
No.:
43410101
Executive
Summary:
See
section
4.4.3
Page
21
of
42
Dose
and
Endpoint:
The
NOAEL
of
500
mg/
kg/
day
(
HDT)
in
the
chronic
oral
toxicity
study
in
dogs
with
tartrazine.
This
is
supported
by
a
combined
chronic
toxicity/
carcinogenicity
study
in
rats
with
erioglaucine,
which
reported
a
NOAEL
of
631
mg/
kg/
day
based
on
decreased
body
weight
at
1262
mg/
kg/
day
in
females
(
LOAEL).

Uncertainty
Factor
(
UF):
100;
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variations.

Comments
about
Study/
Endpoint/
UF:
An
appropriate
dermal
toxicity
study
was
not
available
for
any
exposure
scenario.
There
was
a
non­
guideline
21­
day
dermal
study
in
rabbits
in
the
database
with
a
NOAEL
of
5
mg/
kg/
day
(
HDT).
However,
given
that
all
other
guideline
studies
had
NOAELs
 
500
mg/
kg/
day
and
that
5
mg/
kg/
day
was
the
highest
dose
tested
in
the
dermal
study,
selection
of
an
endpoint
based
on
this
study
is
likely
to
give
an
extremely
conservative
endpoint
and
is
unlikely
to
be
near
the
threshold
dose.
Therefore,
we
selected
the
chronic
oral
toxicity
study
in
dogs,
assuming
100%
dermal
absorption.
This
selection
is
supported
by
the
dietary
combined
chronic
toxicity/
carcinogenicity
study
in
rats
using
erioglaucine
which
had
a
NOAEL
of
631mg/
kg/
day
(
compared
with
500
mg/
kg/
day
with
tartrazine).
The
magnitude
of
the
effect
over
this
interval
is
considered
appropriate
for
short­
and
intermediate­
term
exposures.
Since
the
end­
use
products
are
composed
of
mainly
erioglaucine,
this
endpoint
should
be
conservative
and
protective
for
any
potential
adverse
effects
via
the
dermal
route
of
exposure.

4.4.7
Inhalation
Exposure
(
Short,
Intermediate­
Term)

Studies
Selected:
Chronic
oral
toxicity
study
in
dogs
(
tartrazine)
and
chronic
oral
toxicity/
carcinogenicity
study
in
rats
(
erioglaucine;
co­
critical).

MRID
No.:
43410101
Executive
Summary:
See
Section
4.4.3
Dose
and
Endpoint:
The
NOAEL
of
500
mg/
kg/
day
(
HDT)
in
the
chronic
oral
toxicity
study
in
dogs
with
tartrazine.
This
is
supported
by
a
combined
chronic
toxicity/
carcinogenicity
study
in
rats
with
erioglaucine,
which
reported
a
NOAEL
of
631
mg/
kg/
day
based
on
decreased
body
weight
at
1262
mg/
kg/
day
in
females
(
LOAEL).

Uncertainty
Factor
(
UF):
100;
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variations.

Comments
about
Study/
Endpoint/
UF:
Appropriate
inhalation
toxicity
studies
were
not
available
for
any
exposure
scenario.
The
magnitude
of
the
effect
over
this
interval
is
considered
appropriate
for
short­
and
intermediate­
term
exposures.
100%
inhalation
absorption
is
assumed.

4.4.8
Margins
of
Exposure
The
Margins
of
Exposure
(
MOEs)
of
concern
for
occupational
exposure
risk
assessments
are
as
follows:
Page
22
of
42
Duration
of
Exposure
Route
of
Exposure
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1­
6
Months)
Long­
Term
(>
6
Months)

Occupational
(
Worker)
Exposure
Dermal
100
100
NA
Inhalation
100
100
NA
Residential
(
Non­
Dietary)
Exposure
Oral
100
100
NA
Dermal
100
100
NA
Inhalation
100
100
NA
N/
A
=
Not
applicable
For
occupational
short­
and
intermediate­
term
dermal
and
inhalation
exposure
risk
assessments,
a
MOE
of
100
is
required.
In
addition,
an
MOE
of
100
is
required
for
residential
short­
and
intermediate­
term
oral,
dermal
and
inhalation
exposure
risk
assessments.
All
MOEs
are
based
on
the
conventional
uncertainty
factor
of
100X
(
10X
for
intraspecies
variation
and
10X
for
interspecies
extrapolation).

4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
As
per
1996
FQPA,
when
there
are
potential
residential
exposures
to
the
pesticide,
aggregate
risk
assessment
must
consider
exposures
from
three
major
sources:
oral,
dermal
and
inhalation
exposures.
All
routes
of
exposure
for
all
durations
of
exposure
can
be
aggregated.
A
cancer
aggregate
risk
assessment
is
not
required
because
there
is
no
evidence
of
carcinogenicity
(
see
cancer
weight
of
evidence
below).

4.4.10
Classification
of
Carcinogenic
Potential
No
evidence
for
carcinogenicity
was
seen
in
rats.
Administration
of
tartrazine
or
erioglaucine
to
rats
for
two
years
did
not
result
in
an
increase
in
overall
tumor
incidence
or
increase
the
incidence
of
any
specific
type
of
tumor
at
doses
approaching
the
limit
dose.
The
chemical
was
negative
for
gene
mutation
in
Salmonella
typhimurium.
Page
23
of
42
Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
females
13­
49)
NA
No
appropriate
endpoint
for
females
age
13­
49
attributable
to
a
single
exposure.

Acute
Dietary
(
general
population)
NA
No
appropriate
endpoint
for
the
general
population
attributable
to
a
single
exposure.

Chronic
Dietary
(
all
populations)
NOAEL
=
500
mg/
kg/
day
(
HDT)
(
Tartrazine)

Co­
critical:
NOAEL
=
631
mg/
kg/
day
(
Erioglaucine)

UF
=
100X
Chronic
RfD
=
5
mg/
kg/
day
FQPA
SF
=
1X
cPAD
=
chronic
RfD
FQPA
SF
=
5
mg/
kg/
day
Chronic
oral
toxicity
in
dogs
LOAEL
=
not
identified
(
Tartrazine)

Co­
critical:

Combined
chronic
toxicity/
carcinogenicity
study
in
rats
(
Erioglaucine)

LOAEL
=
1262
mg/
kg/
day
based
on
decreased
body
weight
in
females.

Incidental
Oral
Short­
(
1
­
30
days)

and
Intermediate­

Term
(
1
 
6
months)
NOAEL
=
500
mg/
kg/
day
(
HDT)
(
Tartrazine)

Co­
critical:
NOAEL
=
631
mg/
kg/
day
(
Erioglaucine)
Residential
MOE
=
100
Occupational
MOE=
NA
Chronic
oral
toxicity
in
dogs
LOAEL
=
not
identified
(
Tartrazine)

Co­
critical:

Combined
chronic
toxicity/
carcinogenicity
study
in
rats
(
Erioglaucine)

LOAEL
=
1262
mg/
kg/
day
based
on
decreased
body
weight
in
females.
Page
24
of
42
Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Chemical
for
Use
in
Human
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Dermal
Short­(
1­
30
days)

and
Intermediate­

Term
(
1
 
6
months)
NOAEL
=
500
mg/
kg/
day
(
HDT)
(
Tartrazine)

Co­
critical:
NOAEL
=
631mg/
kg/
day
(
Erioglaucine)

UF
=
100X
(
dermal
absorption
rate
=
100%)
Residential
MOE
=
100
Occupational
MOE
=
100
Chronic
oral
toxicity
in
dogs
LOAEL
=
not
identified
(
Tartrazine)

Co­
critical
Combined
chronic
toxicity/
carcinogenicity
study
in
rats
(
Erioglaucine)

LOAEL
=
1262
mg/
kg/
day
based
on
decreased
body
weight
in
females.

Dermal
Long­
Term
(>
6
months)
NA
NA
Inhalation
Short­

(
1
­
30
days)
and
Intermediate­
Term
(
1
 
6
months)
NOAEL
=
500
mg/
kg/
day
(
HDT)
(
Tartrazine)

Co­
critical:
NOAEL
=
631
mg/
kg/
day
(
Erioglaucine)

UF
=
100X
(
inhalation
absorption
rate
=
100%)
Residential
MOE
=
100
Occupational
MOE
=
100
Chronic
oral
toxicity
in
dogs
LOAEL
=
not
identified
(
Tartrazine)

Co­
critical
Combined
chronic
toxicity/
carcinogenicity
study
in
rats
(
Erioglaucine)

LOAEL
=
1262
mg/
kg/
day
based
on
decreased
body
weight
in
females.

Inhalation
Long­
Term
(>
6
months)
NA
NA
Cancer
(
oral,
dermal,
inhalation)
Classification:
No
evidence
or
carcinogenicity
Page
25
of
42
4.5
Special
FQPA
Safety
Factor
Based
on
the
hazard
data,
the
risk
assessment
team
recommended
the
special
FQPA
SF
be
reduced
to
1x
because
there
are
no
concerns
and
no
residual
uncertainties
with
regard
to
preand
or
post­
natal
toxicity.
The
erioglaucine
and
tartrazine
risk
assessment
team
evaluated
the
quality
of
the
exposure
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
be
reduced
to
1x.
The
recommendation
is
based
on
the
following:

°
No
dietary
food
exposure
assessment
required.

°
The
dietary
drinking
water
assessment
is
not
required.

°
The
SWIMODEL,
an
assessment
tool
employed
to
address
the
potential
for
postapplication
residential
exposures/
risks
(
i.
e.,
swimming
ponds),
uses
screening
exposure
assessment
equations
to
calculate
the
total
worst­
case
exposure
for
swimmers.
The
SWIMODEL
was
developed
based
upon
reliable
data
and
is
unlikely
to
underestimate
exposure/
risk.

4.6
Endocrine
disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(
EDSP).
In
the
available
toxicity
studies
on
erioglaucine
and
tartrazine,
there
was
no
estrogen,
androgen,
and/
or
thyroid
mediated
toxicity.

When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
erioglaucine
and
tartrazine
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
Public
Health
Data
5.1
Incident
Reports
Reference:
Review
of
Aquashade
Incident
Reports,
Chemicals
#
110303,
#
110301,
and
#
110302,
DP
Barcode:
D302184,
Jerome
Blondell,
08/
22/
05.
Page
26
of
42
There
were
almost
no
reports
of
ill
effects
from
exposure
to
Aquashade
in
the
available
data
bases.
The
lack
of
incidents
further
supports
HED's
characterization
of
Aquashade
as
a
low
toxicity
pesticide
with
little
potential
for
acute
effects.

One
report
was
found
in
the
OPP
Incident
Data
System
(
IDS)
in
which
blue
water
was
observed
in
a
government
office
building
in
Ohio
in
1989.
An
investigation
found
that
Acid
Blue
9
(
a
component
of
Aquashade)
had
backflowed
into
the
building's
potable
water
system
apparently
causing
12
illnesses.
Ultimately,
it
was
determined
that
this
incident
is
too
poorly
documented
and
not
a
basis
for
conclusions
about
the
human
toxicity
of
the
product
in
question.

Reports
from
scientific
literature
suggest
that
there
was
concern
that
Aquashade
could
cloud
water
to
the
point
of
reducing
visibility
and
disorient
divers
into
lakes
treated
with
Aquashade
and
possibly
lead
to
drowning.
However,
further
studies
were
conducted
and
it
was
concluded
that
"
The
results
of
this
study
suggest
that
the
drownings
reported
in
North
Carolina
could
not
have
been
solely
or
primarily
due
to
the
addition
of
Aquashade
to
the
lake
water.
It
appears
more
likely
that
a
high
volume
of
plant
material
may
have
remained
in
the
lake
and
may
have
been
more
responsible
for
the
disorientation
of
swimmers
and
divers
who
drowned.
Under
the
conditions
of
this
experiment,
Aquashade
does
not
appear
to
reduce
the
visibility
of
water
significantly
in
a
manner
that
would
create
unsafe
swimming
hazards."

There
are
no
incidents
reported
by
the
Poison
Control
Center
(
PCC),
the
California
Department
of
Pesticide
Regulation
(
CDPR),
the
National
Pesticide
Information
Center
(
NPIC),
or
the
National
Institute
of
Occupational
Safety
and
Health's
Sentinel
Event
Notification
System
for
Occupational
Risks
(
NIOSH
SENSOR).

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
Since
Aquashade
is
applied
to
contained
water
bodies
with
little
or
no
outflow,
and
none
of
the
treated
water
bodies
serves
as
a
source
of
drinking
water,
no
drinking
water
exposure
is
expected.
Although
water
treated
with
Aquashade
may
potentially
be
used
for
irrigation
of
food
crops
and
livestock
watering,
and
Aquashade
is
registered
for
use
in
fish
farms
and
hatcheries,
HED
has
not
quantitatively
assessed
exposures
and
risks
from
food
sources
for
several
reasons:
(
1)
Aquashade
is
used
primarily
in
ornamental
and/
or
recreational
lakes
and
ponds
with
very
little
treated
water
expected
to
be
used
for
agricultural
purposes.
(
2)
Erioglaucine
and
tartrazine
are
highly
water
soluble
compounds
and,
as
such,
not
likely
to
accumulate
in
livestock
or
fish
tissues.
The
results
of
the
rat
metabolism
study
with
erioglaucine
support
this
determination,
since
nearly
the
entire
administered
dose
was
excreted
unchanged
in
the
feces
in
less
than
2
days.
(
3)
Any
residues
of
erioglaucine
or
tartrazine
occurring
in
foods
from
the
use
of
Aquashade
as
an
aquatic
algaecide/
herbicide
would
be
negligible
compared
to
residues
in
food
from
the
common
use
of
these
dyes
as
food
coloring
additives.
Page
27
of
42
6.2
Water
Exposure/
Risk
Pathway
Reference:
Ecological
Risk
Assessment
for
the
Re­
registration
of
Tartrazine
("
Acid
Yellow
23")
and
Erioglaucine
("
Acid
Blue
9")
Dyes
in
the
End­
use
Products
Aquashade,
Admiral,
and
Algae
Blocker,
James
Goodyear
and
Silvia
Termes,
09/
XX/
05.

The
color
additives
erioglaucine
and
tartrazine
are
water
soluble,
are
fully
dissociated
in
the
environmentally
significant
pH
range
of
5
to
9,
and
are
stable
towards
abiotic
hydrolysis.
Indirect
photolysis
in
water
is
a
major
route
of
transformation
for
these
and
other
structurally
related
dyes.
The
two
dyes
are
not
readily
biodegradable
under
aerobic
conditions,
but
biodegrade
under
anaerobic
conditions.
They
do
not
adsorb
strongly
to
soils/
sediments
and
are
predominantly
found
in
the
water
column.
Volatilization
from
soils
and
water
is
not
likely
to
be
a
transport
process
in
the
environment.
Both
dyes
are
highly
hydrophilic
and
are
not
likely
to
bioaccumulate
in
fish.

Products
containing
erioglaucine
and
tartrazine
are
applied
to
contained
water
bodies
with
little
or
no
outflow,
and
none
of
the
water
bodies
treated
with
the
products
serves
as
a
source
of
drinking
water.
Therefore,
no
drinking
water
assessment
is
needed
for
these
chemicals
when
used
as
algaecides/
herbicides
according
to
product
labeling.

6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
References:
Aquashade:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document;
DP
Barcode:
D302180;
W.
Britton;
09/
13/
05.

Aquashade:
Revised
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document;
DP
Barcode:
D321915;
W.
Britton;
09/
27/
05.

Aquashade
is
labeled
for
consumer
use
to
control
aquatic
algae
and
weeds
in
ponds
and
lakes.
The
anticipated
use
patterns
and
current
labeling
indicate
several
residential
handler
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
to
make
Aquashade
applications.
Residents
or
consumers
applying
Aquashade
products
to
ponds
or
lakes
may
be
exposed
for
short­
term
(
1
to
30
days)
duration
through
skin
contact
or
by
inhalation.
While
the
potential
for
inhalation
exposure
exists,
risks
are
assumed
to
be
negligible
based
upon
very
low
vapor
pressure
values
corresponding
to
the
dyes
erioglaucine
and
tartrazine;
2.97
x
10­
42
mmHg
and
7.43
x
10­
22
mmHg
at
25
°
C,
respectively.

Postapplication
exposures
to
children
and
adults
that
contact
Aquashade­
treated
swimming
ponds
are
anticipated.
To
address
the
risk
of
such
exposures,
a
screening
tool
called
the
Swimmer
Exposure
Assessment
Model
(
SWIMODEL)
was
applied.
The
SWIMODEL
uses
well­
accepted
screening
exposure
assessment
equations
to
calculate
the
total
worst­
case
exposure
for
swimmers
expressed
as
a
mass­
based
intake
value
(
mg/
event).
Postapplication
residential
exposure
durations
are
expected
to
be
short­
and
intermediate­
term
(
1
to
6
months)
in
duration.
Page
28
of
42
To
better
quantify
residential
Aquashade
hazard,
results
from
residential
handler
and
residential
postapplication
risk
assessments
were
aggregated.
Aggregate
calculations
of
residential
exposure
were
performed
using
worst­
case
MOEs
resulting
from
each
assessment.

6.3.1
Home
Uses
Aquashade
Residential
Handler
Exposure
Scenarios:
Aquashade
is
labeled
for
consumer
use
to
control
aquatic
algae
and
weeds
in
ponds
and
lakes;
therefore,
pesticide
handler
exposure
to
Aquashade
is
likely
to
occur
during
its
use.
The
anticipated
use
patterns
and
current
labeling
indicate
several
residential
handler
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
be
potentially
used
for
consumer
Aquashade
applications.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
the
following
scenarios.

Mixer/
Loader/
Applicators:
(
1)
Liquids
for
Pouring
Applications
(
using
PHED
mixer/
loader
data)
(
2)
Liquids
for
Garden
Hose­
End
Sprayer
(
ORETF)
(
3)
Liquids
for
LCO
Handgun
(
ORETF)

Data
and
Assumptions
for
Handler
Exposure
Scenarios:
A
series
of
assumptions
served
as
the
basis
for
completing
the
residential
handler
risk
assessments.
Each
assumption
and
factor
is
detailed
below.
In
addition
to
these
factors,
unit
exposure
values
were
used
to
calculate
risk
estimates.
Mostly,
these
unit
exposure
values
were
taken
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
studies.
Both
PHED
and
the
individual
studies
are
presented
below.
[
Note:
Several
of
the
assumptions
and
factors
used
for
the
assessment
are
similar
to
those
used
in
the
occupational
assessment
presented
in
Section
9.1.
As
such,
only
factors
that
are
unique
to
the
residential
scenarios
are
presented
below.]

C
HED
has
developed
standard
unit
exposure
values
for
many
occupational
scenarios
to
ensure
consistency
in
exposure
assessments.
These
standard
values
were
used
to
calculate
handler
exposures
for
the
associated
scenarios.
For
those
scenarios
where
standard
values
have
not
been
developed,
surrogate
values
based
on
a
similar
scenario
were
used.

C
HED
always
considers
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments.
If
additional
information
such
as
average
or
typical
rates
are
available,
these
values
also
may
be
used
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.

Risk
Summary:
A
summary
of
the
short­
term
risks
(
dermal
and
inhalation)
for
each
exposure
scenario
is
presented
below
in
Table
6.3.1.
All
residential
handler
scenarios
assessed
resulted
in
estimated
MOEs
greater
than
100
and,
therefore,
are
not
of
concern.
Short­
and
intermediateterm
MOEs
do
not
differ
because
they
share
the
same
toxicological
endpoint.
Residential
shortterm
dermal
MOEs
range
from
1,930
(
Liquids
for
Pouring
Applications)
to
16,000
(
Liquids
for
LCO
Handgun),
and
short­
term
inhalation
MOEs
range
from
550,000
(
Liquids
for
Garden
Hose
End
Sprayer)
to
6,600,000
(
Liquids
for
Pouring
Applications).
Page
29
of
42
Table
6.3.1
Short­
term
Exposures
and
Risks
for
Residential
Handlers
of
Aquashade
Exposure
Scenario
(
Scenario
#)
Crop1
Dermal
Unit
Exposure
(
mg/
lb
ai)

2
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
3
Application
Rate3
(
lb
ai
/
acre
foot)
4
Area
Treated
Daily
(
acrefeet
5
Surface
Area
(
acres)
Depth
of
Water
Body
(
feet)
Baseline
Dermal
MOE
6
Baseline
Inhalation
MOE7
Mixer/
Loader/
Applicator
Liquids
for
Pouring
Applications
(
1)
Fountains,
Fish
Farms,

Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
3.1
1.2
0.73
8
8
1
1930
5000000
Liquids
for
Pouring
Applications
(
1)
Ornamental
and
Recreational
Lakes
and
Ponds
3.1
1.2
1.1
4
1
4
2600
6600000
Liquids
for
Garden
Hose
End
Sprayer
(
ORETF)
(
2)
Fountains,
Fish
Farms,

Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
2.6
11
0.73
8
8
1
2300
550000
Liquids
for
Garden
Hose
End
Sprayer
(
ORETF)
(
2)
Ornamental
and
Recreational
Lakes
and
Ponds
2.6
11
1.1
4
1
4
3100
720000
Liquids
for
LCO
Handgun
(
ORETF)
(
3)
Fountains,
Fish
Farms,

Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
0.50
1.9
0.73
8
8
1
12000
3100000
Liquids
for
LCO
Handgun
(
ORETF)
(
3)
Ornamental
and
Recreational
Lakes
and
Ponds
0.50
1.9
1.1
4
1
4
16000
4200000
Page
30
of
42
1Crops
and
use
patterns
are
from
product
labeling.
2Baseline
dermal
unit
exposures
represent
short
pants
and
short
sleeved
shirt.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
3Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
4Application
rates
are
based
on
maximum
values
found
in
various
sources
including
LUIS
and
various
labels.
In
most
scenarios,
a
range
of
maximum
application
rates
is
used
to
represent
the
range
of
rates
for
different
crops/
sites/
uses.
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
acre­
foot.
5Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
6
Dermal
MOE
=
NOAEL
(
500
mg/
kg/
day)
/
Daily
dermal
dose
(
mg/
kg/
day).
MOEs
are
reported
to
2
significant
figures.
7Inhalation
MOE
=
NOAEL
(
500
mg/
kg/
day)
/
Daily
inhalation
dose
(
mg/
kg/
day).
MOEs
are
reported
to
2
significant
figures.

6.3.2
Recreational
Uses
Aquashade
can
be
used
in
areas
that
can
be
frequented
by
the
general
population
including
residential
areas
(
i.
e.,
swimming
ponds).
There
is
potential
for
dermal,
ingestion,
aural,
buccal/
sublingual,
and
nasal/
orbital
routes
of
exposure
to
adults
and
children
following
its
residential
application.
The
potential
for
incidental
exposures
of
short­
term
duration
exist
from
the
day
of
application
to
the
water
body.
Intermediate­
term
exposures
could
also
occur
and
were
considered
as
well.

Risks
were
calculated
for
residential
handler
and
postapplication
exposures
using
the
Margin
of
Exposure
(
MOE)
approach;
the
MOE
is
a
ratio
of
the
body
burden
to
the
toxicological
endpoint
of
concern.
All
short­
and
intermediate­
term
residential
postapplication
scenarios
assessed
(
dermal,
ingestion,
aural,
buccal/
sublingual,
and
nasal/
orbital
routes
of
exposure)
resulted
in
estimated
combined
MOEs
greater
than
100
and,
therefore,
are
not
of
concern.
A
summary
of
these
MOEs
is
presented
in
Table
6.3.2.

Table
6.3.2
Recreational
Swimmer
Aquashade
MOEs
Exposed
Person
Exposure
Duration
Water
Concentration
(
µ
g/
L)
Dose
(
mg/
kg/
day)
NOAEL
(
mg/
kg/
day)
MOE
Child
 
22
kg
2000
0.10
500
4900
Adult
 
70
kg
Short­/

Intermediateterm
2000
0.032
500
15600
6.3.3
Residential
Aggregated
Exposure
and
Risk
Estimates
To
better
quantify
residential
Aquashade
hazard,
results
from
residential
handler
and
residential
postapplication
risk
assessments
were
aggregated.
Aggregate
calculations
of
residential
exposure
were
performed
using
worst­
case
MOEs
resulting
from
each
assessment.

The
residential
aggregated
exposure
resulted
in
an
estimated
MOE
of
1700
and,
therefore,
is
not
a
risk
of
concern.
Page
31
of
42
6.3.4
Other
(
Spray
Drift,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
of
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
the
ground
application
methods
employed
for
Aquashade.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
On
a
chemical
by
chemical
basis,
the
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off
target
drift
with
specific
products
with
significant
risks
associated
with
drift.

7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
pesticide
exposures
and
risks
from
three
major
sources:
drinking
water,
food
and
residential
exposures.
Since
Aquashade
is
applied
to
contained
water
bodies
with
little
or
no
outflow,
and
none
of
the
treated
water
bodies
serves
as
a
source
of
drinking
water,
no
drinking
water
exposure
is
expected.
Although
water
treated
with
Aquashade
may
potentially
be
used
for
irrigation
of
food
crops
and
livestock
watering,
and
Aquashade
is
registered
for
use
in
fish
farms
and
hatcheries,
HED
has
not
quantitatively
assessed
exposures
and
risks
from
food
sources
for
several
reasons:
(
1)
Aquashade
is
used
primarily
in
ornamental
and/
or
recreational
lakes
and
ponds
with
very
little
treated
water
expected
to
be
used
for
agricultural
purposes.
(
2)
Erioglaucine
and
tartrazine
are
highly
water
soluble
compounds
and,
as
such,
not
likely
to
accumulate
in
livestock
or
fish
tissues.
The
results
of
the
rat
metabolism
study
with
erioglaucine
support
this
determination,
since
nearly
the
entire
administered
dose
was
excreted
unchanged
in
the
feces
in
less
than
2
days.
(
3)
Any
residues
of
erioglaucine
or
tartrazine
occurring
in
foods
from
the
use
of
Aquashade
as
an
aquatic
algaecide/
herbicide
would
be
negligible
compared
to
residues
in
food
from
the
common
use
of
these
dyes
as
food
coloring
additives.
(
4)
The
most
significant
route
of
exposure
to
erioglaucine
and
tartrazine
from
the
use
of
Aquashade
is
residential
exposure,
including
residential
handler
and
postapplication
(
swimming)
exposure.
HED
believes
that
the
conservative
residential
exposure
and
risk
estimates
discussed
above
are
more
than
adequate
to
cover
any
food
exposures
that
could
potentially
occur
from
the
use
of
Aquashade
as
an
aquatic
algaecide/
herbicide.

7.1
Acute
Aggregate
Risk
A
toxicological
endpoint
of
concern
attributable
to
a
single
dose
has
not
been
identified
for
Aquashade.
Therefore,
an
acute
aggregate
risk
assessment
has
not
been
conducted.
Page
32
of
42
7.2
Short­
Term
Aggregate
Risk
The
short­
term
aggregate
risk
assessment
considered
residential
handler
and
postapplication
(
swimming)
exposures
to
Aquashade
only,
as
there
are
no
sources
of
drinking
water
treated
with
Aquashade
and
food
exposures
are
expected
to
be
negligible.
Short­
term
residential
handler
exposure
may
result
when
Aquashade
is
used
to
control
aquatic
algae
and
weeds
in
ponds
and
lakes.
Short­
term
residential
postapplication
exposures
may
result
when
children
and
adults
contact
Aquashade­
treated
swimming
ponds.
Short­
term
risks
were
calculated
for
residential
handler
and
postapplication
exposures
using
the
Margin
of
Exposure
(
MOE)
approach;
the
MOE
is
a
ratio
of
the
body
burden
to
the
toxicological
endpoint
of
concern.

To
better
quantify
residential
Aquashade
hazard,
results
from
residential
handler
and
postapplication
risk
assessments
were
aggregated.
Calculations
of
aggregate
residential
exposures
were
performed
using
worst­
case
MOEs
from
each
assessment.

The
estimated
aggregate
residential
exposure
resulted
in
an
MOE
of
1700
and,
therefore,
is
not
of
concern.

7.3
Intermediate­
Term
Aggregate
Risk
The
use
of
Aquashade
as
an
algaecide/
herbicide
is
not
expected
to
result
in
dietary
exposure
to
erioglaucine
or
tartrazine,
either
from
drinking
water
or
food;
and
residential
handler
exposures
are
expected
to
be
short­
term
only.
Therefore,
only
intermediate­
term
postapplication
(
swimming)
exposures
are
expected
and
an
intermediate­
term
aggregate
risk
assessment
is
not
necessary.

7.4
Long­
Term
Aggregate
Risk
Long­
term
exposures
are
not
expected
based
on
current
uses;
therefore,
a
long­
term
aggregate
assessment
was
not
conducted.

7.5
Cancer
Risk
A
cancer
aggregate
risk
assessment
is
not
required,
since
there
was
no
evidence
of
carcinogenicity
in
the
toxicology
studies
submitted
for
Aquashade.

8.0
Cumulative
Risk
Characterization/
Assessment
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
erioglaucine
and
tartrazine
and
any
other
substances
and
Aquashade
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
Aquashade
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
Page
33
of
42
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

9.0
Occupational
Exposure/
Risk
Pathway
Reference:
Aquashade:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document;
DP
Barcode:
D302180;
W.
Britton;
09/
13/
05.

HED
determined
that
the
potential
for
occupational
exposure
to
Aquashade
exists
in
a
variety
of
occupational
environments.
The
anticipated
use
patterns
and
current
labeling
indicate
several
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
for
Aquashade
applications.
These
include
the
handling
of
Aquashade
during
mixing,
loading,
and
applying
processes
(
i.
e.
mixer/
loaders,
and
mixer/
loader/
applicators).
As
a
result,
a
risk
assessment
has
been
completed
for
the
occupational
handler
scenario.
Short­
term
(
1
to
30
days)
and
intermediate­
term
dermal
and
inhalation
exposures
(
1
to
6
months)
may
occur;
however,
long­
term
exposures
(
greater
than
6
months)
are
not
expected.

9.1
Short/
Intermediate/
Long­
Term
Handler
Risk
Aquashade
Handler
Exposure
Scenarios:
The
anticipated
use
patterns
and
current
labeling
indicate
several
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
be
potentially
used
for
Aquashade
applications.
The
quantitative
exposure/
risk
assessment
developed
for
occupational
handlers
is
based
on
the
following
scenarios.

Mixer/
Loaders:
(
1)
Liquids
for
Pouring
Applications
Mixer/
Loader/
Applicators:
(
2)
Liquids
for
Garden
Hose­
End
Sprayer
(
ORETF)
(
3)
Liquids
for
LCO
Handgun
(
ORETF)

Data
and
Assumptions
for
Handler
Exposure
Scenarios:
A
series
of
assumptions
served
as
the
basis
for
the
occupational
handler
risk
assessments.
The
assumptions
used
in
the
risk
assessment
calculations
are
detailed
below:

C
Occupational
handler
exposure
estimates
were
based
on
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
and
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).

C
HED
has
developed
standard
unit
exposure
values
for
many
occupational
scenarios
to
ensure
consistency
in
exposure
assessments.
These
standard
values
were
used
to
Page
34
of
42
calculate
handler
exposures
for
the
associated
scenarios.
For
those
scenarios
where
standard
values
have
not
been
developed,
surrogate
values
based
on
a
similar
scenario
were
used.

C
The
adverse
effects
for
the
short­
and
intermediate­
term
dermal
and
inhalation
endpoints
are
based
on
studies
where
the
effects
were
observed
in
males
and
females,
therefore,
the
body
weight
of
an
average
adult
(
i.
e.
70
kg)
was
used
to
estimate
exposure.

C
For
non­
cancer
assessments,
HED
assumes
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments.

C
The
average
occupational
workday
is
assumed
to
be
8
hours.

C
The
daily
areas
treated
were
defined
for
each
handler
scenario
(
in
appropriate
units)
by
determining
the
amount
that
can
be
reasonably
treated
in
a
single
day
(
e.
g.,
acres,
square
feet,
cubic
feet,
or
gallons
per
day).
When
possible,
the
assumptions
for
daily
areas
treated
are
taken
from
the
Health
Effects
Division
Science
Advisory
Committee
on
Exposure
SOP
#
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture,
which
was
completed
on
July
5,
2000.
Since
Aquashade
is
not
used
in
agriculture
the
above
source
is
not
applicable.
Therefore,
the
daily
area
treated
with
Aquashade
was
investigated
and
was
assumed
to
be
25
acre­
feet
per
day
[
Personal
Communication
per
Email
from
Dr.
Kurt
Getsinger
(
USACE)
to
J.
Carter
(
OPP,
BEAD),
8/
22/
05].
This
high­
end
estimate
is
recognized
to
be
conservative;
however,
the
value
is
assumed
to
result
in
risks
that
represent
reasonable
worst­
case
estimates
of
exposure
to
occupational
handlers
of
Aquashade.

Risk
Summary:
A
summary
of
the
short­
and
intermediate­
term
risks
(
dermal
and
inhalation)
for
each
exposure
scenario
is
presented
below
in
Table
9.1.
The
calculated
occupational
handler
exposures
for
all
scenarios
resulted
in
estimated
MOEs
greater
than
100
and,
therefore,
are
not
of
concern.
Short­
and
intermediate­
term
MOEs
do
not
differ
because
they
share
the
same
toxicological
endpoint.
Short­
and
intermediate­
term
dermal
MOEs
range
from
410
(
Liquids
for
Pouring
Applications)
to
4,300
(
Liquids
for
Garden
Hose­
End
Sprayer),
and
short­
and
intermediate­
term
inhalation
MOEs
range
from
120,000
(
Liquids
for
Garden
Hose
End
Sprayer)
to
1,600,000
(
Liquids
for
Pouring
Applications).
Page
35
of
42
Table
9.1
Short­
and
Intermediate­
term
Baseline
Exposures
and
Risks
for
Occupational
Handlers
of
Aquashade
Exposure
Scenario
(
Scenario
#)
Crop1
Dermal
Unit
Exposure
(
mg/
lb
ai)
2
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
3
Application
Rate
(
lb
ai
/
acre
foot)
4
Area
Treated
Daily
(
acrefeet
5
Baseline
Dermal
MOE
6
Baseline
Inhalation
MOE7
Mixer/
Loader
Liquids
for
Pouring
Applications
(
1)
Ornamental
and
Recreational
Lakes
and
Ponds
3.1
1.2
1.1
25
410
1100000
Liquids
for
Pouring
Applications
(
1)
Fountains,
Fish
Farms,
Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
3.1
1.2
0.73
25
620
1600000
Mixer/
Loader/
Applicator
Liquids
for
Garden
Hose
End
Sprayer
(
2)
Ornamental
and
Recreational
Lakes
and
Ponds
0.45
11
1.1
25
2800
120000
Liquids
for
Garden
Hose
End
Sprayer
(
2)
Fountains,
Fish
Farms,
Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
0.45
11
0.73
25
4300
170000
Liquids
for
LCO
Handgun
(
ORETF)
(
3)
Ornamental
and
Recreational
Lakes
and
Ponds
0.50
1.9
1.1
25
2500
670000
Liquids
for
LCO
Handgun
(
ORETF)
(
3
Fountains,
Fish
Farms,
Fish
Hatcheries,
Golf
Courses,
Lakes,
Manmade
Ponds,
Swimming
Ponds
0.50
1.9
0.73
25
3800
100000
Page
36
of
42
1
Crops
and
use
patterns
are
from
product
labeling.
2Baseline
dermal
unit
exposures
represent
long
pants,
long
sleeved
shirts,
shoes,
and
socks.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
3Baseline
inhalation
unit
exposures
represent
no
respirator.
Values
are
reported
in
the
PHED
Surrogate
Exposure
Guide
dated
August
1998
or
are
from
data
submitted
by
the
Outdoor
Residential
Exposure
Task
Force
dated
May
2000.
4Application
rates
are
based
on
maximum
values
found
in
various
sources
including
LUIS
and
various
labels.
In
most
scenarios,
a
range
of
maximum
application
rates
is
used
to
represent
the
range
of
rates
for
different
crops/
sites/
uses.
Most
application
rates
upon
which
the
analysis
is
based
are
presented
as
lb
ai/
acre­
foot.
5Amount
treated
is
based
on
the
area
or
gallons
that
can
be
reasonably
applied
in
a
single
day
for
each
exposure
scenario
of
concern
based
on
the
application
method
and
formulation/
packaging
type.
(
Standard
EPA/
OPP/
HED
values).
6
Dermal
MOE
=
NOAEL
(
500
mg/
kg/
day)
/
Daily
dermal
dose
(
mg/
kg/
day).
MOEs
are
reported
to
2
significant
figures.
7Inhalation
MOE
=
NOAEL
(
500
mg/
kg/
day)
/
Daily
inhalation
dose
(
mg/
kg/
day).
MOEs
are
reported
to
2
significant
figures.

HED
believes
that
the
risk
estimates
presented
in
this
occupational
assessment
represent
the
best
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
HED
also
believes
that
the
risks
represent
reasonable
worst­
case
estimates
of
exposure,
because
maximum
application
rates
are
coupled
with
medium­
to
high­
end
estimates
of
area
treated
daily
to
define
risk
estimates
that
likely
fall
in
the
upper
percentiles
of
the
actual
exposure
distributions.
Using
these
worst­
case
assumptions,
estimated
occupational
handler
MOEs
for
all
exposure
scenarios
are
greater
than
100
and
are,
therefore,
not
of
concern.

9.2
Short/
Intermediate/
Long­
Term
Postapplication
Risk
HED
uses
the
term
A
postapplication
@

to
describe
exposures
that
occur
when
individuals
are
present
in
an
environment
that
has
been
previously
treated
with
a
pesticide
(
also
referred
to
as
reentry
exposure).
Such
exposures
may
occur
when
workers
enter
previously
treated
areas
to
perform
job
functions,
including
activities
related
to
crop
production,
such
as
scouting
for
pests
or
harvesting.
Postapplication
exposure
levels
vary
over
time
and
depend
on
such
things
as
the
type
of
activity
(
scouting,
harvesting,
etc.),
the
nature
of
the
crop
or
target
that
was
treated,
the
type
of
pesticide
application
(
foliar,
soil­
incorporated,
banded,
etc.)
and
the
chemical
=

s
degradation
properties.
In
addition,
the
timing
of
pesticide
applications,
relative
to
harvest
activities,
can
greatly
reduce
the
potential
for
postapplication
exposure.

Aquashade
is
generally
applied
prior
to
or
early
in
the
growing
season
when
growth
is
on
the
bottom
of
the
water
body.
Applications
can
also
be
made
later
in
the
growing
season
when
growth
is
closer
to
the
surface
after
the
killing
and/
or
removal
of
any
existent
growth.
Since
Aquashade
is
an
algaecide/
herbicide,
HED
is
not
aware
of
any
postapplication
activities
which
may
result
in
exposure.
No
harvesting
is
required,
and
while
scouting
may
include
identifying
any
algae
or
aquatic
weed
regrowth,
these
activities
should
not
require
contact
with
the
treated
water
body.
For
these
reasons,
occupational
postapplication
exposure
of
workers
to
previously
treated
water
bodies
is
expected
to
be
negligible
and
was
not
assessed.
Furthermore,
any
postapplication
activities
that
could
potentially
occur
would
not
be
expected
to
exceed
those
assessed
from
residential
exposures
to
Aquashade
which
are
not
of
concern.

In
accordance
with
the
Worker
Protection
Standard
(
WPS),
a
restricted­
entry
interval
(
REI)
is
established
to
mitigate
contact
with
a
pesticide
in
treated
agricultural
areas.
However,
since
Aquashade
has
no
agricultural
applications
an
REI
was
not
required.
Page
37
of
42
10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
 
none
required
10.2
Occupational
and
Residential
Exposure
­
none
References:

Review
of
Aquashade
Incident
Reports,
Chemicals
#
110303,
#
110301,
and
#
110302,
DP
Barcode:
D302184,
Jerome
Blondell,
08/
22/
05.

Aquashade:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document;
DP
Barcode:
302180,
Wade
Britton,
09/
13/
05.

Aquashade:
Revised
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document;
DP
Barcode:
D321915;
W.
Britton;
09/
27/
05.

Toxicity
References:

BIBRA.
1999.
BIBRA
International
Ltd.
Toxicity
profile:
Brilliant
Blue
FCF,
3rd
ed.
Carshalton,
Surrey:
BIBRA
International
Ltd.,
11
pp.

Borzelleca,
J.
F.
and
J.
B.
Hallagan.
1988a.
Chronic
toxicity/
carcinogenicity
studies
of
FD&
C
Yellow
No.
5
(
tartrazine)
in
rats.
Fd.
Chem.
Toxicol.
26(
3):
179­
187.

Borzelleca,
J.
F.
and
J.
B.
Hallagan.
1988b.
A
chronic
toxicity/
carcinogenicity
study
of
FD&
C
Yellow
No.
5
(
tartrazine)
in
mice.
Fd.
Chem.
Toxicol.
26(
3):
189­
194.

Borzelleca,
J.
F.,
K.
Depukat,
and
J.
B.
Hallagan.
1990.
Lifetime
toxicity/
carcinogenicity
studies
of
FD&
C
Blue
No.
1
(
Brilliant
Blue
FCF)
in
rats
and
mice.
Fd.
Chem.
Toxicol.
28:
221­
234.

Brown,
J.
P.,
G.
W.
Roehm,
and
R.
J.
Brown.
1978.
Mutagenicity
testing
of
certified
food
colors
and
related
azo,
xanthene
and
triphenylmethane
dyes
with
the
Salmonella/
microsome
system.
Mutat.
Res.
56:
249­
271.

Collins,
T.
F.
X.,
T.
N.
Black,
L.
H.
Brown,
et
al.
1990.
Study
of
the
teratogenic
potential
of
FD&
C
Yellow
No.
5
when
given
by
gavage
to
rats.
Fd.
Chem.
Toxic.
28(
12):
821­
827.

Collins,
T.
F.
X.,
T.
N.
Black,
M.
W.
O'Connell,
Jr.,
et
al.
1992.
Study
of
the
teratogenic
potential
of
FD&
C
Yellow
No.
5
when
given
in
drinking
water.
Fd.
Chem.
Toxic.
30(
4):
263­
268.

FDA.
1982.
FD&
C
Blue
No.
1.;
Final
Rule.
47
FR
42563;
September
28,
1982
FDA.
1985.
FD&
C
Yellow
No.
5.;
Final
Rule;
Removal
of
Stay.
40
FR
35774;
September
4,
1985.
Page
38
of
42
IACM.
2004.
International
Association
of
Color
Manufacturers.
Test
Plan
and
Robust
Summaries
for
C.
I.
Acid
Yellow
23
(
FD&
C
Yellow
5).
http://
www.
epa.
gov/
chemrtk/
ciacdylo/
c15133tp.
pdf
JECFA.
1964.
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives.
Tartrazine.
WHO
Food
Additive
Series.
66.25/
NMRS
38B­
JECFA
8/
88.
http://
www.
inchem.
org/
documents/
jecfa/
jeceval/
jec_
1936.
htm
JECFA.
1969.
Joint
FAO/
WHO
Expert
Committee
on
Food
Additives.
Toxicological
Evaluation
of
Some
Food
Colours,
Emulsifiers,
Stabilizers,
Anti­
caking
Agents
and
Certain
Other
Substances.
FAO
Nutrition
Meetings
Report
Series
No.
46A
.
World
Health
Organization,
Geneva.
http://
www.
inchem.
org/
documents/
jecfa/
jecmono/
v46aje08.
htm
Leifer,
Kerry.
2004.
United
States
Environmental
Protection
Agency.
Reassessment
of
Exemptions
from
the
requirement
of
a
tolerance
for
the
FDA­
certified
color
additives
FD&
C
Blue
No.
1,
FD&
C
Red
No.
40,
and
FD&
C
Yellow
No.
5.

Sasaki,
Y.
F.,
S.
Kawaguchi,
A.
Kamaya,
et
al.
2002.
The
comet
assay
with
8
mouse
organs:
results
with
39
currently
used
food
additives.
Mutat.
Res.
519:
103­
119.

SRC.
2004.
Syracuse
Research
Corporation.
Interactive
Physical
Properties
(
PHYSPROP)
Database
Demo.
Search
terms:
FD&
C
Blue.
No.
1,
FD&
C
Red
No.
40,
FD&
C
Yellow
No.
5.
(
November
28,
2004)
http://
www.
syrres.
com/
esc/
physdemo.
htm
Page
39
of
42
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
requirements
(
40
CFR
158.340)
for
food
use
for
erioglaucine
and
tartrazine
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

Technical
Test
Required
Satisfied
870.1100
Acute
Oral
Toxicity....................................................
870.1200
Acute
Dermal
Toxicity
...............................................
870.1300
Acute
Inhalation
Toxicity
...........................................
870.2400
Primary
Eye
Irritation
.................................................
870.2500
Primary
Dermal
Irritation............................................
870.2600
Dermal
Sensitization...................................................
yes
yes
no
yes
yes
yes
yes
yes
­
yes
yes
yes
870.3100
Oral
Subchronic
(
rodent)
............................................
870.3150
Oral
Subchronic
(
nonrodent).......................................
870.3200
21­
Day
Dermal...........................................................
870.3250
90­
Day
Dermal...........................................................
870.3465
90­
Day
Inhalation.......................................................
yes
yes
yes
no
no
yes*
yes*
yes
­
­

870.3700a
Developmental
Toxicity
(
rodent)
................................
870.3700b
Developmental
Toxicity
(
nonrodent)...........................
870.3800
Reproduction..............................................................
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(
rodent)
...........................................
870.4100b
Chronic
Toxicity
(
nonrodent)......................................
870.4200a
Oncogenicity
(
rat).......................................................
870.4200b
Oncogenicity
(
mouse).................................................
870.4300
Chronic/
Oncogenicity.................................................
yes
yes
yes
yes
yes
yes
yes
yes**
yes**
yes
870.5100
Mutagenicity 
Gene
Mutation
­
bacterial....................
870.5300
Mutagenicity 
Gene
Mutation
­
mammalian...............
870.5375
Mutagenicity 
Structural
Chromosomal
Aberrations
..
870.5385
Mutagenicity 
Other
Genotoxic
Effects......................
yes
no
no
no
yes
­
­
­

870.6100a
Acute
Delayed
Neurotox.
(
hen)...................................
870.6100b
90­
Day
Neurotoxicity
(
hen)
........................................
870.6200a
Acute
Neurotox.
Screening
Battery
(
rat)......................
870.6200b
90
Day
Neuro.
Screening
Battery
(
rat)
........................
870.6300
Develop.
Neuro
..........................................................
no
no
no
no
no
­
­
­
­
­

870.7485
General
Metabolism....................................................
870.7600
Dermal
Penetration.....................................................
yes
no
yes
­

Special
Studies
for
Ocular
Effects
Acute
Oral
(
rat)
..........................................................
Subchronic
Oral
(
rat)
..................................................
Six­
month
Oral
(
dog)..................................................
no
no
no
­
­
­

*
Satisfied
by
the
chronic
(
rodent)
toxicity
study­
guideline
870.4100a
**
Satisfied
by
the
chronic
(
nonrodent)
toxicity
study­
guideline
870.4100b
**
Satisfied
by
the
chronic/
oncogenicity
study­
guideline
870.4300
Page
40
of
42
2.0
NON­
CRITICAL
TOXICOLOGY
STUDIES
Chronic
toxicity/
carcinogenicity
studies
of
FD
&
C
Yellow
No.
5
(
tartrazine)
in
rats
(
870.4300b)

FD
&
C
Yellow
No.
5
was
fed
to
Charles
River
CD
rats
as
a
dietary
mixture
in
two
long­
term
toxicity/
carcinogenicity
studies.
The
studies
were
conducted
with
an
in
utero
phase
in
which
the
compound
was
administered
to
the
F0
generation
rats
(
60/
sex/
group)
at
levels
of
0.0,
0.1,
1.0
or
2.0%
('
original
study')
equal
to
0,
53,
1056,
2641
mg/
kg/
day
and
0,
67,
670,
1339,
3348
mg/
kg/
day,
in
males
and
females,
respectively.
A
second
study
(`
high­
dose
study')
was
conducted
with
0.0
or
5.0%
tartrazine
equal
to
2641
or
3348
in
males
and
females,
respectively.
The
concurrent
control
groups
received
the
basal
diet.
After
random
selection
of
the
F1
animals,
the
long­
term
phase
was
initiated
using
the
same
dietary
levels
with
70
rats
of
each
sex/
group,
including
the
three
control
groups.
The
maximum
exposure
to
the
coloring
was
113
and
114
wk
for
males
and
females,
respectively,
in
the
'
original'
study
and
122
and
125
wk
for
males
and
females,
respectively,
in
the
'
high­
dose'
study.
No
compound­
related
effects
were
noted.
The
noadverse
effect
level
found
in
this
study
was
5.0%
in
the
diet
providing
an
average
intake
of
2641
and
3348
mg/
kg/
day
for
male
and
female
rats,
respectively
(
Borzelleca
et
al,
1988b).

Chronic
toxicity/
carcinogenicity
studies
of
FD
&
C
Blue
No.
1
(
erioglaucine)
in
mice
(
870.4300d)
Charles
River
CD­
1
mice
(
60/
sex/
group)
were
fed
FD
&
C
Blue
No.
1
as
a
dietary
admixture
at
levels
of
0.0%,
0.5%,
1.5%
or
5.0%
in
a
lifetime
toxicity/
carcinogenicity
study.
The
maximum
exposure
time
was
104
wk
for
both
males
and
females.
No
consistent,
significant
compoundrelated
adverse
effects
were
noted.
The
no­
observed­
adverse­
effect
level
established
in
this
study
is
a
dietary
concentration
of
5.0%
(
7354
mg/
kg/
day
and
8966
mg/
kg/
day
for
male
and
female
mice,
respectively
(
Borzelleca
et
al,
1990)

Chronic
toxicity/
carcinogenicity
study
of
FD
&
C
Yellow
No.
5
(
tartrazine)
in
mice
(
870.4300e)

Charles
River
CD­
1
mice
were
fed
FD
&
C
Yellow
No.
5
in
the
diet
at
levels
of
0.0,
0.5,
1.5
or
5.0%
in
a
long­
term
toxicity/
carcinogenicity
study.
Each
group
consisted
of
60
males
and
60
females.
Maximum
exposure
was
104
wk
for
both
males
and
females.
No
consistent,
significant
compound­
related
adverse
effects
were
noted.
The
no­
observed­
adverse
effect
level
established
in
this
study
was
5.0%
(
8103
mg/
kg/
day
and
9735
mg/
kg/
day
for
male
and
female
mice,
respectively
(
Borzelleca
et
al,
1988b).

http://
www.
ncbi.
nlm.
nih.
gov/
entrez/
query.
fcgi?
db=
pubmed&
cmd=
Search&
term=%
22Borzelleca
+
JF%
22%
5BAuthor%
5D
21­
Day
Dermal
(
rabbits)
In
a
subchronic
dermal
toxic:
(
MRID
43410101),
54
female
albino
rabbits
were
divided
into
6
treatment
groups
of
9
animals
each.
Three
animals
with
intact
skin
and
3
animals
with
abraded
skin
per
group
were
given
20
treatments
over
2
days.
An
additional
3
animals
with
intact
skin
per
group
received
65
doses
over
28­
days.
An
additional
3
animals
with
intact
skin
per
group
received
65
doses
over
a
91
day
period.
Treatments
were
composed
of
the
following:
1)
water,
2)
Page
41
of
42
USP
White
Ointment,
3)
0.1%
a.
i.
(
Acid
Blue
9)
in
water,
4)
1.0%
a.
i.
in
water,
5)
0.1%
a.
i.
in
USP
ointment
and
6)
1.0%
a.
i.
in
USP
White
Ointment.
Treatments
were
applied
at
a
rate
of
0.5
g
or
0.5
ml
per
kg.
of
body
weight
(
representing
approximately
0.5
and
5.0
mg/
kg/
day).
There
were
no
treatment
related
effects
on
survival,
clinical
signs,
body
weight,
hematology,
urinalysis,
organ
weight
or
pathology.
The
NOAEL
is
>
5.0
mg/
kg/
day
females
(
HDT).
The
LOAEL
was
not
determined.

The
study
is
acceptable/
non­
guideline.
It
satisfies
the
requirement
for
a
guideline
series
82­
2
subchronic
dermal
toxicity
study
in
rabbits.

Bacterial
reverse
mutation
test
(
Ames
Test)

Thirty­
seven
azo,
xanthene
and
triphenylmethane
dyes
including
FD&
C
colors
currently
approved
for
use
in
the
U.
S.
A.
and
a
number
of
de­
listed
food
colors
were
tested
in
the
Salmonella/
microsome
system.
In
addition
to
direct
plate
tests
with
five
tester
strains
(
TA1535,
TA100,
TA1537,
TA1538,
TA98),
the
azo
dyes
were
also
assayed
after
chemical
reduction
to
their
component
amines.
Also,
a
selected
group
of
azo
dyes
was
subjected
to
liquid
tests
(
both
aerobic
with
microsomes
and
anaerobic)
and
to
plate
tests
involving
initial
16
h
anaerobic
incubations
to
facilitate
microbial
reduction
of
the
azo
bond.
None
of
the
presently
listed
FD
and
C
colors
was
mutagenic
in
any
of
the
test
modifications.
Among
formerly
listed
colors
only
Butter
Yellow
(
p­
dimethylaminoazobenzene),
a
recognized
animal
carcinogen,
was
mutagenic
in
the
aerobic
liquid
test.
Several
other
azo
dyes
were
either
directly
mutagenic,
viz.
Acid
Alizarin
Yellow
R
and
Alizarin
Yellow
GG;
required
microsomal
activation,
viz.
Acid
Alizarin
Red
B
and
Methyl
Red;
or
required
chemical
reduction
and
microsomal
activation,
viz.
Acid
Alizarin
Violet
N
and
Sudan
IV.
Of
the
non­
azo
dyes
tested
only
two
xanthene
dyes
appeared
to
be
mutagenic,
viz.
9­(
2­
sulfophenyl)­
6­
hydroxy­
3­
isoxanthenone
and
its
2,4,5,7­
tetrabromo
derivative
(
Brown
et
al,
1978).

Metabolism
Erioglaucine
was
administered
orally
to
rats
as
a
2%
aqueous
solution
at
a
level
of
200
mg/
rat.
Almost
the
entire
amount
was
excreted
unchanged
in
the
feces
within
40
h
after
administration.
In
a
later
investigation,
the
presence
of
the
color
in
the
bile
was
observed
in
rats,
rabbits
and
dogs
after
oral
administration.
In
the
case
of
the
dog,
the
amount
did
not
exceed
5%
of
the
dose
administered
(
Hess
&
Fitzhugh,
1953;
1954;
1955).
Administration
of
an
aqueous
solution
of
the
color
by
stomach
tube
resulted
in
89
%
excretion
in
the
feces;
none
was
found
in
the
urine.
After
subcutaneous
injection
of
80­
100
mg
some
79%
was
excreted;
77%
appeared
in
the
feces
and
2.5%
in
the
urine
(
Imperial
Chemical
Industries,
1958).
Page
42
of
42
3.0
TOLERANCE
REASSESSMENT
Active
ingredient
Current
Tolerance
Tolerance
Reassessment
Comment
Tolerance
Exemption
Listed
Under
40
CFR
§
180.1074:

F.
D.&
C.
Blue
No.
1
Exempted
from
the
requirement
of
a
tolerance
when
used
as
an
aquatic
plant
control
agent.
Exempted
from
the
requirement
of
a
tolerance
when
used
as
an
aquatic
plant
control
agent.
In
1982,
based
on
Aquashade's
low
toxicity
profile,
EPA
waived
residue
chemistry
data
requirements
and
established
an
exemption
from
the
requirement
of
a
tolerance
for
erioglaucine
(
F.
D&
C.
Blue
No.
1)
when
used
as
an
aquatic
plant
control
agent.
Tartrazine,
when
used
as
a
dye,
had
previously
been
exempted
from
the
requirement
of
a
tolerance
as
an
inert
(
or
occasionally
as
an
active)
ingredient
in
pesticide
formulations
applied
to
growing
crops
or
to
raw
agricultural
commodities
after
harvest
under
40
CFR
180.1001(
c)
(
currently
40
CFR
180.910).
HED
has
determined
that
the
existing
exemption
for
tartrazine
as
an
inert
ingredient
is
not
sufficient
to
satisfy
reregistration
requirements
for
the
active
ingredient
when
used
as
an
aquatic
plant
control
agent.

Therefore,
HED
recommends
that
the
exemption
for
erioglaucine
at
40
CFR
180.1074
be
revised
to
include
both
erioglaucine
(
F.
D.&
C.
Blue
No.
1)
and
tartrazine
(
F.
D.&
C.
Yellow
No.
5).