Document ID: EPA-HQ-OPP-2005-0492-0024
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-16T04:00Z

i
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
PC
Code:
006304,
006308,
006321
DP
BARCODE:
315682
MEMORANDUM
May
22,
2006
SUBJECT:
Oxytetracycline:
Tier
I
Drinking
Water
Exposure
Assessment
of
Oxytetracycline
Supporting
the
Reassessment
Under
FQPA
of
Pear
and
Peach
&
Nectarine
Use
Patterns
and
the
Assessment
of
the
New
Use
Pattern,
Apple:
Cover
Memorandum
TO:
Lance
Wormell,
Chemical
Review
Manager
RB2/
SRRD
(
7508C)

Stephen
Schaible,
Product
Manager
RSB/
RD
(
7505C)

FROM:
Greg
Orrick,
Environmental
Scientist
Elizabeth
Behl,
Chief
ERB4/
EFED
(
7507C)

THROUGH:
R.
David
Jones,
Ph.
D.,
Senior
Agronomist
ERB4/
EFED
(
7507C)

The
attached
drinking
water
assessment
for
oxytetracycline
on
pear,
peach
&
nectarine,
and
apple
use
patterns
has
been
revised
to
address
phase
3
comments
received
by
the
Agency.
Oxytetracycline
equivalents
on
agricultural
end
use
product
(
EUP)
labels
have
been
confirmed
at
17%.
Clarification
of
the
molecular
weight
and
structure
of
"
oxytetracycline
calcium
complex"
is
recommended,
however,
as
the
term
appears
to
represent
oxytetracycline
calcium
salt
in
product
chemistry
studies
(
e.
g.
MRID
43262301)
and
a
complex
of
oxytetracycline
and
complexing
agent
in
Confidential
Statements
of
Formula.

The
hydroxytetracycline
monohydrochloride
technical
label
(
EPA
Reg.
No.
74596­
5;
80990­
2)
is
labeled
for
"
domestic
outdoor
use."
However,
this
use
was
not
addressed
in
this
assessment
because
it
is
for
a
technical
formulation.

Language
clarification
is
recommended
for
crop
use
directions
in
EPA
labels
(
EPA
Reg.
No.
55146­
89;
100­
900;
80990­
1).
Maximum
application
rates
per
year,
maximum
numbers
of
ii
applications
per
year,
minimum
application
intervals,
and
application
methods
are
often
suggested
rather
than
clearly
listed
as
mandatory.
For
example,
EPA
Reg.
No.
80990­
1
offers
a
"
recommended
concentration
or
rate"
for
applications
on
pear,
but
doesn't
give
an
annual
limit.
EPA
Reg.
No.
100­
900
specifies
a
use
rate
on
pear
of
up
to
150
gal/
acre
of
200
ppm
solution,
which
is
equivalent
to
1.5
lbs
product/
acre;
but
also
directs
not
to
apply
more
than
1
lb
product/
acre.
The
latter
instruction
was
followed
for
modeling,
but
the
label
should
be
rewritten
so
as
not
to
contradict
itself.
EPA
Reg.
No.
80990­
1,
100­
900,
and
55146­
89
do
not
specify
application
methods
for
pears,
although
EPA
Reg.
No.
100­
900
generally
recommends
application
by
air­
blast
sprayer.
In
contrast,
all
labels
with
peach
and
nectarine
use
patterns
specify
pressure
spray
or
air­
blast
spray
application.

All
laboratory
fate
and
degradation
studies
were
waived
for
this
chemical
12
years
ago.
Since
then,
the
use
of
this
chemical
has
expanded
significantly.
Availability
of
these
basic
environmental
fate
studies
would
greatly
decrease
the
uncertainty
associated
with
exposure
assessments.

If
the
conservative
EDWCs
in
this
memo
result
in
dietary
risk
exceedances,
contact
Greg
Orrick
(
703­
305­
6140)
of
Environmental
Risk
Branch
IV
to
request
a
refined
Tier
II
drinking
water
exposure
assessment.
Page
1
of
14
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
PC
Code:
006304,
006308,
006321
DP
BARCODE:
315682
MEMORANDUM
May
22,
2006
SUBJECT:
Oxytetracycline:
Tier
I
Drinking
Water
Exposure
Assessment
of
Oxytetracycline
Supporting
the
Reassessment
Under
FQPA
of
Pear
and
Peach
&
Nectarine
Use
Patterns
and
the
Assessment
of
the
New
Use
Pattern,
Apple.

TO:
Lance
Wormell,
Chemical
Review
Manager
RB2/
SRRD
(
7508C)

Stephen
Schaible,
Product
Manager
RSB/
RD
(
7505C)

FROM:
Greg
Orrick,
Environmental
Scientist
Elizabeth
Behl,
Chief
ERB4/
EFED
(
7507C)

THROUGH:
R.
David
Jones,
Ph.
D.,
Senior
Agronomist
ERB4/
EFED
(
7507C)

Executive
Summary
This
assessment
provides
Tier
I
estimated
drinking
water
concentrations
(
EDWC)
from
the
maximum
use
pattern
of
oxytetracycline,
hydroxytetracycline
monohydrochloride,
and
oxytetracycline
calcium
(
PC
Codes
006304,
006308,
006321;
hereafter
collectively
referred
to
as
"
oxytetracycline")
in
surface
water
and
in
groundwater
in
support
of
human
health
risk
assessment
(
Table
1).
EDWC
values
were
generated
to
compare
the
current
oxytetracycline
use
patterns
of
pear
and
peach
&
nectarine,
which
are
registered
for
three
agricultural
products,
and
the
proposed
oxytetracycline
use
on
apples
(
Table
5).

Table
1.
Tier
I
EDWCs
in
surface
water
and
groundwater
for
peaches
and
nectarines,
which
is
the
maximum
use
pattern
for
oxytetracycline.
Maximum
Use
Pattern
Surface
Water
Acute
EDWC
(
ppb)
Surface
Water
Chronic
EDWC
(
ppb)
Groundwater
EDWC
(
ppb)
Peaches
&
Nectarines
89.4
4.6
0.033
Page
2
of
13
Model
input
parameters
include
conservative
assumptions
because
all
environmental
fate
studies
for
oxytetracycline
were
waived
during
the
reregistration
process.
Label
ambiguity
contributes
to
uncertainty
in
EDWCs
as
well.
Acute
and
chronic
surface
water
EDWCs
were
calculated
with
the
screening
mechanistic
model
FIRST
v1.0
(
Aug.
1,
2001).
Groundwater
EDWCs
used
for
both
acute
and
chronic
risk
assessment
were
generated
with
the
screening
regression
model
SCI­
GROW
v2.3
(
Jul.
29,
2003).

Concentrations
of
oxytetracycline
degradates
are
not
estimated,
as
the
Health
Effects
Division
(
HED)
has
not
found
any
degradates
to
be
of
toxic
concern.
1
Monitoring
data
are
not
available
to
represent
water
quality
impacts
associated
with
the
registered
crop
uses.
Available
monitoring
data
are
described
on
page
11
to
provide
insight
into
the
prevalence
of
oxytetracycline
in
the
environment
resulting
from
nonagricultural
uses.

This
assessment
only
considers
potential
drinking
water
exposure
from
oxytetracycline
applied
to
selected
crops
in
order
to
control
fire
blight
and
bacterial
spot.
Other
uses
of
oxytetracycline,
including
pharmaceuticals,
animal
feeding
operations,
and
aquaculture,
are
regulated
by
the
FDA.
The
extent
to
which
these
nonagricultural
uses
may
result
in
environmental
and
dietary
exposure
has
not
been
assessed,
nor
has
potential
environmental
risk
from
emergence
of
antimicrobial
drug
resistance
in
bacterial
pathogens,
development
of
cross
resistance
to
other
tetracycline
compounds,
or
drug
resistance
transference
from
benign
pathogens
to
harmful
pathogens.
Available
monitoring
data,
which
may
include
water
quality
impacts
from
some
of
these
nonagricultural
uses,
is
described.

Problem
Formulation
The
purpose
of
this
screening­
level
drinking
water
risk
assessment
is
to
provide
estimated
drinking
water
concentrations
(
EDWCs)
of
oxytetracycline
in
surface
water
and
in
groundwater
in
support
of
the
human
health
chapters
of
the
Tolerance
Reregistration
Eligibility
Decision
(
TRED)
risk
assessment
and
the
registration
for
the
new
use
on
apple
(
EPA
Reg.
No.
618­
104).
The
EDWC
values
in
Table
5
were
generated
for
the
current
and
proposed
oxytetracycline
use
patterns
of
pear,
peach
&
nectarine,
and
apple,
which
are
registered
for
three
agricultural
formulated
enduse
products
[
EPA
Reg.
No.
100­
900
(
618­
104
proposed);
55146­
89;
and
80990­
1
(
74896­
4)].
Other
registered
agricultural
uses
are
tree
injection
and
marine
paint
antifoulant
additive
uses;
however,
these
uses
are
not
calculated
for
in
this
assessment
because
they
are
not
expected
to
lead
to
significant
drinking
water
exposure.
Other
non­
pesticidal
uses
of
oxytetracycline
are
also
not
considered
in
this
assessment.

A
screening­
level
assessment
is
performed
and
available
monitoring
data
is
characterized
for
this
Tier
I
drinking
water
exposure
assessment.
The
Tier
I
models
FIRST
(
surface
water)
and
SCI­
GROW
(
ground
water)
are
used
to
conservatively
estimate
concentrations
in
source
surface
and
ground
water
that
could
potentially
be
used
as
drinking
water.
These
screening
models
are
designed
not
as
explicit
predictions
of
typical
exposure,
but
as
upper­
bound
estimates
of
the
exposure
that
could
occur
in
the
environment
under
conditions
that
are
favorable
to
runoff
(
FIRST)
and
leaching
(
SCI­
GROW).
The
models
simulate
processes
that
could
affect
the
transportation
of
compounds
to
water
bodies
via
runoff,
erosion,
spray
drift,
or
leaching
in
order
to
1
Personal
communication
with
William
Donovan,
OPP/
HED,
on
July
29,
2005.
Page
3
of
13
indicate
which
chemicals
exceed
levels
of
concern,
warranting
a
more
refined
assessment.
The
models
estimate
exposure
based
on
a
few
chemical
and
use
input
parameters
and
on
the
conservative,
upper­
end
results
of
hundreds
of
runs
on
the
PRZM
and
EXAMS
models,
which
have
limitations
in
their
ability
to
represent
some
processes
and
factors,
such
as
spray
drift,
certain
runoff
factors,
within­
site
variability,
crop
growth,
soil
water
transport,
and
weather.

Oxytetracycline
calcium
complex
is
the
active
ingredient
in
two
current
registrations
(
EPA
Reg.
No.
100­
900
and
55146­
89);
hydroxytetracycline
monohydrochloride
is
the
active
ingredient
in
the
third
current
registration
(
EPA
Reg.
No.
80990­
1).
Oxytetracycline
base
is
not
an
active
ingredient
in
any
registered
end
products.
All
three
oxytetracycline
active
ingredients
are
collectively
referred
to
as
"
oxytetracycline"
in
this
assessment
because
they
all
share
the
same
biologically
active
oxytetracycline
base,
and
are
expected
to
behave
similarly
in
the
environment,
displaying
the
same
mechanisms
of
effect
in
each
formulation.
Note,
however,
that
oxytetracycline
calcium
complex
is
not
strictly
a
calcium
salt,
but
a
complex
of
oxytetracycline
and
calcium­
rich
complexing
agent.
The
percentage
of
the
biologically
active
oxytetracycline
base
(
equivalent)
for
all
end
use
formulations
is
17%.
Concentrations
of
oxytetracycline
degradates
are
not
estimated,
as
the
Health
Effects
Division
(
HED)
has
not
found
any
degradates
to
be
of
toxic
concern.
2
All
requirements
for
fate
data
on
oxytetracycline
were
waived
during
the
reregistration
process
because
oxytetracycline
had
a
limited
use
pattern
and
because
it
was
expected
to
pose
low
risk
(
Office
of
Pesticide
Programs,
1993).
Product
chemistry
studies
provide
data
on
water
solubility
(
MRID
44219401,
46109401,
43262301,
and
41602001).
A
peer­
reviewed
study
from
the
open
literature
on
the
soil
to
water
partition
coefficients
(
Kd)
of
oxytetracycline
in
30
soils
of
the
eastern
United
States
provides
the
information
on
mobility
used
in
this
assessment
to
model
exposure
(
Jones
et
al.,
2005).
However,
all
standard
environmental
degradation
data
required
for
risk
assessment
are
unavailable
Oxytetracycline
has
uses
regulated
by
the
FDA
that
may
lead
to
environmental
and
irrigation
reservoir
exposure,
such
as
concentrated
animal
feeding
operations
(
CAFO),
concentrated
aquatic
animal
production
facilities
(
CAAPF),
aquaculture,
and
silviculture
operations.
These
uses
require
an
NPDES
permit
to
discharge
listed
pollutants
[
40
CFR
pt.
122
(
2004)];
however,
oxytetracycline
is
not
currently
a
listed
pollutant
[
40
CFR
pt.
401.15
(
2004)]
under
the
Clean
Water
Act
[
33
U.
S.
C.
Sec.
1251
et
seq.
(
2003)].
Studies
have
shown
that
antibiotics
mixed
in
aquaculture
feed
tend
to
accumulate
in
and
persist
in
the
sediment
below,
where
wild
fish
and
invertebrates
can
uptake
them
into
their
tissues
to
levels
unacceptable
for
human
consumption
(
Milewski,
2001;
Capone
et
al.,
1996).

Fate
and
Transport
Characterization
Many
data
gaps
exist
for
fate
and
transport
characterization
because
no
environmental
fate
(
Subdivision
N)
studies
have
been
submitted
for
oxytetracycline.
They
were
waived
in
the
reregistration
process
(
USEPA,
1993)
on
the
basis
of
limited
use
patterns
at
the
time
and
low
estimated
risks.
The
following
are
fate
and
transport
data
from
product
chemistry
studies
and
the
2
Personal
communication
with
William
Donovan,
OPP/
HED,
on
July
29,
2005.
Page
4
of
13
open
literature.
Data
from
open
literature
do
not
fulfill
Subdivision
N
data
requirements,
but
were
used
in
this
assessment
in
the
absence
of
other
data.

Solubility
Product
chemistry
studies
indicate
that
the
water
solubility
of
hydrochloride
salt
is
1g
in
2
mL
(
500,000
mg
L­
1)
and
that
oxytetracycline
base
and
calcium
salt
are
slightly
soluble
(
MRID
41602001,
46109401,
43262301,
44219401).
They
also
report
that
the
0.1%
solution
pH
of
calcium
salt
is
7.5
to
10.0,
which
implies
that
the
water
solubility
is
somewhat
near
10
g
L­
1
(
10,000
mg
L­
1;
MRID
44219401).
Therefore,
these
compounds
are
soluble
enough
to
dissolve
in
surface
water
and
groundwater;
however,
their
exact
water
solubilities
are
not
well
defined.

Mobility
Soil
to
water
partition
coefficients
(
Kd)
for
oxytetracycline
in
30
eastern
U.
S.
soils
representing
five
soil
orders
and
28
soil
series
have
been
published
in
a
peer­
reviewed
study
(
Jones
et
al.,
2005).
The
study
concluded
that
soil
texture,
cation
exchange
capacity,
and
iron
oxide
content
appeared
to
most
influence
oxytetracycline
sorption
in
soils
with
organic
carbon
content
of
0
to
4%.
Soil
organic
carbon
content
negatively
correlated
with
compound
sorption
in
those
soils,
but
not
with
a
single
soil
of
9%
organic
carbon.
Kd
values
ranged
from
486
L
kg­
1
to
12,047
L
kg­
1
(
pH
5.5).
Data
from
this
study
were
used
to
generate
EDWCs
for
this
assessment.
Based
on
the
range
of
Kd
values
presented
in
this
literature
review,
oxytetracycline
has
relatively
low
mobility,
and
is
expected
to
preferentially
adsorb
to
soils
with
minimal
expected
transport
in
the
dissolved
phase
in
runoff
or
leachate.

Degradation
The
following
studies
from
open
literature
may
offer
insight
regarding
the
degradation
of
oxytetracycline.
The
USGS
Kansas
Water
Science
Center3
published
a
study
on
the
chemical
degradation
of
antibiotics
in
anaerobic
swine
lagoons,
which
found
that
oxytetracycline
hydrolysis
rates
generally
increase
as
pH
deviates
from
7
and
as
temperature
increases
in
synthetic
systems
(
Loftin
et
al.,
2004).
A
kinetics
study
of
oxytetracycline
found
that
high
temperatures,
light
exposure,
alkaline
conditions,
the
presence
of
a
substrate,
and
the
presence
of
organic
matter
each
led
to
decreased
concentrations
of
the
compound
in
deionized
water
as
compared
to
contrasting
conditions
(
Doi
and
Stoskopf,
2000).
An
aerobic
aquatic
dissipation
study
performed
in
diffuse
light
found
that
oxytetracycline
"
might
be
considered
as
moderately
persistent,"
displaying
firstorder
half­
lives
of
31
to
175
days
in
natural
surface
water
and
sediment
(
Ingerslev
et
al.,
2001).
These
data
are
not
acceptable
according
to
40
CFR
Pt.
158
data
requirements
and
cannot
be
used
as
inputs
to
model
environmental
exposure.

Models
Used
The
Tier
I
screening
model
FIRST
v1.0
(
Aug.
1,
2001)
simulates
the
upper­
end
exposure
of
the
standard
water
body,
the
Index
Reservoir,
to
pesticide
residues
in
runoff
and
spray
drift
from
an
application
within
the
standard
watershed.
Peak
and
annual
mean
EDWCs
are
generated
3
Online
at:
http://
ks.
water.
usgs.
gov.
Page
5
of
13
to
estimate
acute
and
chronic
exposure.
The
Index
Reservoir
covers
5.2
hectares
(
ha)
with
an
average
depth
of
2.74
meters
(
m)
in
a
standard
watershed
of
172.8
ha.
A
more
detailed
description
of
the
index
reservoir
watershed
can
be
found
in
Jones
et
al.,
1998.
The
FIRST
model
and
users
manual
may
be
downloaded
from
the
US
Environmental
Protection
Agency
Water
Models
webpage
4
The
Tier
I
screening
model
SCI­
GROW
v2.3
(
Jul.
29,
2003)
simulates
the
exposure
of
shallow
groundwater
to
pesticide
residues
from
application
to
a
field
with
highly
permeable
soil.
A
single
90­
day
running
average
EDWC
is
estimated
through
regression
as
a
screen
for
both
acute
and
chronic
exposure.
This
estimated
value
is
protective
as
a
maximum
acute
exposure
value
because
SCI­
GROW
simulates
exposure
to
shallow
wells
in
unconfined
aquifers
with
short
well
screens
overlain
by
highly
permeable
soils
that
are
conducive
to
leaching.
Many
drinking
water
wells
have
larger
well
screens
and
are
not
in
unconfined
aquifers
overlain
by
highly
permeable
soils.
The
SCI­
GROW
model
and
users
manual
may
be
downloaded
from
the
EPA
Water
Models
web­
page.
3
Both
FIRST
and
SCI­
GROW
were
run
to
estimate
screening­
level
exposure
of
drinking
water
sources
from
oxytetracycline.

Use
Characterization
Oxytetracycline
base
[
2­
naphthacenecarboxamide,
4­(
dimethylamino)­
1,4,4a,
5,5a,
6,11,
12a­
octahydro­
3,5,6,10,12,12a­
hexahydroxy­
6­
methyl­
1,11­
dioxo­,
(
4S,
4aR,
5S,
5aR,
6S,
12aS)­],
also
known
as
terramycin
(
CAS
RN
79­
57­
2),
its
salts
hydroxytetracycline
monohydrochloride
(
CAS
RN
2058­
46­
0)
and
calcium
oxytetracycline
(
CAS
RN
7179­
50­
2
and
15251­
48­
6)
are
three
active
ingredients
that
share
the
biologically
active
component
of
an
antibiotic
produced
by
the
actinomycete
Streptomyces
rimosus.
Oxytetracycline
is
a
human
and
animal
drug
and
is
used
as
a
pesticide
to
control
bacteria,
fungi,
and
mycoplasma­
like
organisms.

The
hydrochloride
salt
and
calcium
complex
formulations
of
oxytetracycline
are
currently
formulated
as
a
wettable
powder
for
agricultural
uses,
registered
to
control
fire
blight
on
pear
and
bacterial
spot
on
peaches
and
nectarines
(
EPA
Reg.
No.
55146­
89;
100­
900;
and
80990­
1
(
74896­
4)).
The
State
of
Washington
has
two
special
local
need
[
§
24(
c)]
registrations
(
WA­
010020
and
WA­
980014)
to
use
the
EPA
Reg.
No.
100­
900
product
on
pears.
Apple
uses
similar
to
EPA
Reg.
No.
100­
900
are
pending
under
EPA
Reg.
No.
618­
104.
Non­
agricultural
registrations
specify
hydroxytetracycline
monohydrochloride
and
oxytetracycline
calcium
complex
as
tree
injections
for
coconut
palm
and
pritchardia
palm
and
hydroxytetracycline
monohydrochloride
as
an
antifoulant
in
marine
paint
for
barnacle
control.

Use
pattern
values
from
active
and
proposed
labels
with
ground
spray
and
aerial
applications
are
listed
in
Table
2.

4
Online
at:
http://
www.
epa.
gov/
oppefed1/
models/
water/
index.
htm.
Page
6
of
13
Table
2.
Labeled
values
for
pear,
peach
&
nectarine,
and
apple
use
patterns.
Use
Pattern
EPA
Reg.
No.
App.
Rate1
(
lb
a.
i./
ac)
Applications
per
Year
Application
Interval
(
days)
Application
Method
Apple
618­
104
0.255
6
3
Air­
blast
Peach
&
Nectarine
55146­
89,
80990­
1,
74896­
11
0.638
9
7
Air­
blast
Peach
&
Nectarine
100­
900
0.255
8
7
Air­
blast
Pear
100­
900,
55146­
89,
80990­
1,
74896­
11
0.170
10
4
Air­
blast
Pear
100­
900
WA­
010020
0.170
6
4
Aerial
Pear
100­
900
WA­
980014
0.085
10
4
Aerial
1.
App.
rate
(
lb
a.
i./
ac)
means
application
rate
(
pounds
of
active
ingredient
per
acre),
which
was
calculated
by
multiplying
the
product
oxytetracycline
equivalent
percentage
by
the
maximum
pounds
of
product
applicable
to
an
acre,
as
specified
by
the
label.

Application
rates
in
pounds
of
active
ingredient
per
acre
(
lb
a.
i./
ac)
were
calculated
by
multiplying
oxytetracycline
active
ingredient
equivalent
percentages
specified
on
the
labels
by
the
maximum
pounds
of
product
applicable
to
an
acre
(
e.
g.
(
17%
a.
i.)
x
(
3.75
lb
/
500
gal)
x
(
500
gal
/
1
acre)
=
0.638
lb
a.
i./
acre).
The
number
of
applications
per
year
and
the
interval
between
them
are
found
in
rather
ambiguous
label
directions,
such
as,
"
Applications
are
weekly,"
and
"
This
may
involve
up
to
8
to
10
applications"
(
EPA
Reg.
No.
55146­
89
and
80990­
1).
These
instructions
were
interpreted
as
directions,
not
as
suggestions.
However,
succinctly
stated
label
directions
would
decrease
the
need
for
interpretation,
and
associated
uncertainties.

EPA
Reg.
No.
100­
900
specifies
a
use
rate
on
pear
of
200
ppm
solution
in
up
to
150
gal/
acre,
which
is
equivalent
to
1.5
lbs
product/
acre;
but
also
directs
not
to
apply
more
than
1
lb
product/
acre.
The
latter
instruction
was
followed
for
modeling,
but
the
label
is
confusing
as
written.

The
recommended
application
method
for
use
patterns
under
EPA
Reg.
No.
100­
900
is
airblast
sprayer.
Peach
and
nectarine
uses
on
other
labels
are
also
specified
for
air­
blast
spray
or
hand­
held
spray.
Pear
uses
on
EPA
Reg.
No.
55146­
89,
100­
900,
and
80990­
1
have
no
application
method
specified;
however,
air­
blast
spray
was
assumed
to
apply.
The
special
local
need
labels
for
the
State
of
Washington
are
the
only
labels
that
specifically
allow
aerial
application.

Input
Parameters
This
screening­
level
assessment
uses
maximum
application
practices
from
each
registered
and
proposed
use
to
generate
conservative
EDWCs.
Maximum
application
practices
involve
the
maximum
single
application
rate,
the
maximum
number
of
applications
per
year,
and
the
minimum
interval
between
applications
allowed
by
the
label.
All
use
patterns
on
the
labels
were
modeled
for
surface
water
and
groundwater
in
order
to
provide
estimates
of
the
range
of
concentrations
associated
with
each
crop
and
use
pattern.
The
shaded
values
in
Table
2
represent
the
maximum
use
pattern
used
to
generate
EDWCs
in
support
of
risk
assessment,
listed
in
Table
1.
Page
7
of
13
FIRST
Input
parameters.

Input
parameters,
justifications,
and
source
references
for
the
FIRST
model
appear
in
Table
3
for
oxytetracycline
use
on
apple,
peach
and
nectarine,
and
pear
orchards.

Table
3.
FIRST
input
parameters
for
oxytetracycline
applied
to
pear,
peach
&
nectarine,
and
apple.
1
Input
Parameter
Value
Justification
Source
Percent
cropped
area
0.87
Default
USEPA,
2002
Kd
(
mL/
g)
771
Represents
the
lowest
Kd
for
a
non­
sand
soil.
Jones
et
al.,
2005
Aerobic
soil
metabolism
half­
life
(
days)
Stable
Conservative
assumption
due
to
data
gap.
N/
A
Wetted
in?
No
Label
directions
Label
Solubility
in
water
(
ppm)
1000
Arbitrary
value
based
on
product
chemistry
study
values
for
each
compound.
MRID
44219401
Aerobic
aquatic
metabolism
half­
life
(
days)
Stable
Conservative
assumption
due
to
data
gap.
N/
A
Hydrolysis
half­
life
at
pH
7
(
days)
Stable
Conservative
assumption
due
to
data
gap.
N/
A
Aqueous
photolysis
half­
life
(
days)
Stable
Conservative
assumption
due
to
data
gap.
N/
A
1.
Use
pattern
parameters
are
listed
in
Table
2.

Because
suitable
environmental
fate
data
were
not
available,
degradation
rate
input
parameters
listed
were
assumed
to
be
stable.
This
approach
provides
a
highly
conservative
estimate
of
potential
exposure.

The
water
solubilities
of
oxytetracycline
salts
and
complexes
are
not
well
established.
However,
the
water
solubility
value
of
the
least
soluble
moiety
is
at
least
10
g
L­
1,
which
is
far
above
EDWCs.
Solubility
values
serve
as
upper
limits
to
EDWCs
in
the
FIRST
model.
Therefore,
an
arbitrary
water
solubility
value
of
1000
mg
L­
1
was
selected
as
a
conservative
and
consistent
upper
EDWC
limit
for
use
in
modeling
oxytetracycline
active
ingredients.

The
default
percent
cropped
area
(
PCA)
used
(
0.87)
is
the
maximum
fraction
of
any
HUC­
8
basin
in
the
United
States
that
is
agricultural
land.
It
is
a
conservative
estimate
of
actual
cropped
area
fractions
both
because
it
is
a
maximum
value
and
because
a
basin
may
contain
more
than
one
crop
(
Effland
et
al.,
1999).

The
FIRST
input
(
and
output)
file
for
the
use
pattern
of
highest
EDWCs
is
included
in
Attachment
I
of
the
Appendix.

SCI­
GROW
Input
parameters.

Input
parameters,
justifications,
and
source
references
for
the
SCI­
GROW
model
appear
in
Table
4
for
oxytetracycline
use
on
apple,
peach
and
nectarine,
and
pear
orchards.
Page
8
of
13
Table
4.
SCI­
GROW
input
parameters
for
oxytetracycline
applied
to
pear,
peach
&
nectarine,
and
apple.
1
Input
Parameter
Value
Justification
Source
KOC
(
L/
Kg)
9995
Assumption
based
on
limit
of
model
validity.
N/
A
Aerobic
soil
metabolism
half­
life
(
days)
1000
Conservative
assumption
due
to
data
gap.
N/
A
1.
Use
pattern
parameters
are
listed
in
Table
2.

The
lowest
KOC
value
calculated
for
input
into
SCI­
GROW,
based
on
Kd
values
from
a
literature
review
(
Jones
et
al.,
2005),
was
27,303
L
kg­
1,
which
is
above
9,995
L
kg­
1,
the
limit
of
the
scope
of
the
model's
regression
data.
The
KOC
is
not
a
valid
description
of
binding
for
oxytetracycline
because
of
the
negative
correlation
between
organic
carbon
content
and
sorption;
however,
a
Koc
value
is
necessary
to
yield
the
model
input.
Due
to
these
considerations,
9,995
L
kg­
1
was
used
as
the
KOC
model
input
for
oxytetracycline,
which
adds
to
the
conservativeness
of
groundwater
EDWCs
in
this
assessment
The
aerobic
soil
metabolism
half­
life
of
oxytetracycline
was
conservatively
assumed
to
be
stable
in
the
absence
of
source
data.
The
SCI­
GROW
model
does
not
accept
a
stable
input
value
for
the
aerobic
soil
metabolism
half­
life,
however.
Therefore,
1000
days
was
arbitrarily
chosen
as
a
half­
life
value
that
is
expected
to
exceed
the
true
value
in
order
to
approach
stability
without
escaping
the
scope
of
the
regression
data
used
to
develop
the
model.

The
SCI­
GROW
input
(
and
output)
file
for
the
use
pattern
of
highest
EDWC
is
included
in
Attachment
II
of
the
Appendix.

Results
EDWCs
generated
as
described
above
are
listed
in
Table
5.
All
use
patterns
on
the
labels
were
modeled
for
surface
water
and
groundwater
in
order
to
provide
estimates
of
the
range
of
concentrations
associated
with
each
crop
and
use
pattern.
The
maximum
use
pattern
of
oxytetracycline
is
on
peaches
and
nectarines
as
directed
by
EPA
Reg.
No.
55146­
89,
80990­
1,
and
74896­
4,
which
yields
maximum
EDWCs
recommended
to
represent
drinking
water
exposure
in
this
screening
level
assessment
(
Table
1
and
shaded
in
Table
5).
EDWCs
are
highly
conservative,
due
to
conservative
assumptions
about
the
environmental
fate
of
oxytetracycline.

Table
5.
Tier
I
EDWCs
in
surface
water
and
groundwater
from
use
patterns
for
oxytetracycline.
Use
Pattern
EPA
Registration
Number
Surface
Water
Acute
EDWC
(
ppb)
Surface
Water
Chronic
EDWC
(
ppb)
Groundwater
EDWC
(
ppb)

Apple
618­
104
23.9
1.3
0.009
Peaches
&
Nectarines
55146­
89,
80990­
1,
74896­
4
89.4
4.6
0.033
Peaches
&
Nectarines
100­
900
31.8
1.7
0.012
Pear
100­
900,
55146­
89,
80990­
1,
74896­
4
26.5
1.4
0.010
Pear
100­
900
WA­
010020
15.4
1.0
0.006
Pear
100­
900
WA­
980014
12.9
0.9
0.005
Page
9
of
13
The
screening
models
are
designed
not
as
explicit
predictors
of
typical
exposure,
but
as
upper
bound
estimators
of
the
exposure
that
could
occur
in
the
environment
under
conditions
which
are
highly
favorable
to
runoff
(
FIRST)
and
leaching
(
SCI­
GROW).
These
models
should
simply
indicate
which
chemicals
exceed
levels
of
concern,
warranting
more
refined
assessment.
The
models
estimate
exposure
based
on
a
few
chemical
and
use
input
parameters
and
on
the
conservative,
upper­
end
results
of
hundreds
of
runs
on
the
PRZM
and
EXAMS
models,
which
have
limitations
in
their
ability
to
represent
some
processes
and
factors,
such
as
spray
drift,
certain
runoff
factors,
within­
site
variability,
crop
growth,
soil
water
transport,
and
weather.

Surface
water
acute
EDWCs
calculated
by
FIRST
for
control
of
fire
blight
on
peach
and
nectarine
range
from
32
to
89
ppb
due
to
the
ranges
of
application
rates
and
numbers
of
applications
per
year,
as
directed
by
the
labels.
The
EDWC
for
EPA
Reg.
No.
55146­
89,
80990­
1,
and
74896­
4
(
89.4
ppb)
is
a
181%
increase
over
the
EDWC
for
EPA
Reg.
No.
100­
900
(
31.8
ppb)
due
to
the
150%
increase
in
application
rate
and
one
additional
application
per
year
between
the
labels.

Monitoring
A
USGS
monitoring
study
of
139
streams
in
30
states
was
conducted
from
1999
to
2000
to
measure
concentrations
of
95
organic
wastewater
contaminants
(
Kolpin
et
al.,
2002).
Sites
selected
for
sampling
in
this
reconnaissance
study
were
in
"
areas
considered
susceptible
to
contamination
from
human,
industrial,
and
agricultural
wastewater (
i.
e.
downstream
of
intense
urbanization
and
livestock
production)."
Sampling
sites
did
not
represent
application
of
oxytetracycline
to
crops.
Instead,
their
selection
targeted
streams
that
received
wastewater
from
treatment
facilities,
septic
systems,
animal
feeding
operations,
and
land
application
of
waste.
However,
results
do
provide
some
indication
of
the
general
prevalence
of
organic
wastewater
contaminants
in
the
environment.

Oxytetracycline
was
analyzed
using
two
methods.
One
method
analyzed
for
oxytetracycline
in
84
samples,
yielding
one
detection
at
0.34
µ
g/
L
(
detection
frequency
of
1.2%).
The
second
method
did
not
detect
oxytetracycline
in
115
samples.
The
minimum
reporting
level
for
both
methods
was
0.10
µ
g/
L.
The
authors
concluded
that
"
the
low
frequency
of
detection
for
the
tetracycline
(
chlortetracycline,
doxycycline,
oxytetracycline,
tetracycline)
and
quinolone
(
ciprofloxacin,
enrofloxacin,
norfloxacin,
sarafloxacin)
antibiotics
is
not
unexpected
given
their
apparent
affinity
for
sorption
to
sediment."

Further
monitoring
studies
of
oxytetracycline
were
not
found
in
a
brief
literature
search.
Oxytetracycline
and
related
tetracyclines
are
not
analytes
listed
in
the
U.
S.
Geological
Service
(
USGS)
National
Water
Quality
Assessment
(
NAWQA)
database,
5
National
Stream
Quality
Accounting
Network
(
NASQAN)
database,
6
or
the
California
Department
of
Pesticide
Regulation
(
DPR)
Surface
Water
Database.
7
5
Online
at:
http://
infotrek.
er.
usgs.
gov/
servlet/
page?_
pageid=
543&_
dad=
portal30&_
schema=
PORTAL30.
6
Online
at:
http://
water.
usgs.
gov/
nasqan.
7
Online
at:
http://
www.
cdpr.
ca.
gov/
docs/
sw/
surfdata.
htm.
Page
10
of
13
States
and
federal
agencies
have
no
oxytetracycline
monitoring
data
reporting
requirements
specified
by
statute,
regulation,
or
guidance.
Consequently,
oxytetracycline
is
not
listed
in
the
EPA
Safe
Drinking
Water
Information
System
(
SDWIS)
database,
8
nor
is
it
found
in
EPA
Unregulated
Contaminants
Monitoring
Regulation
(
UCMR)
chemical
monitoring
databases.
9
Groundwater
monitoring
studies
from
1971
to
1991
listed
in
the
EPA
Pesticides
in
Ground
Water
Database
(
USEPA,
1992)
did
not
include
oxytetracycline
as
an
analyte.

Drinking
Water
Treatment
The
Office
of
Pesticide
Programs
(
OPP)
does
not
have
direct
data
on
the
effects
of
drinking
water
treatment
on
oxytetracycline.
Based
on
the
soil
to
water
partitioning
data
(
Jones
et
al.,
2005),
carbon
filtering
may
reduce
oxytetracycline
concentrations,
as
other
chemicals
with
high
soil
to
water
or
octanol
to
water
partition
coefficients
tend
to
be
hydrophobic
and
are
removed
well
with
activated
carbon
filtering.
Flocculation
and
sedimentation
removal
may
be
effective
at
reducing
oxytetracycline
concentrations
as
well.
These
processes
use
the
affinity
of
the
compound
to
organic
matter
to
collect
and
remove
it
from
water.
However,
the
mobility
study
by
Jones
et
al.
(
2005)
referenced
above
found
that
oxytetracycline
sorption
to
soils
negatively
correlated
with
soil
organic
carbon
content
in
soils
with
0
to
4%
organic
carbon.
Consequently,
the
chemical
complexity
of
oxytetracycline
may
render
treatment
processes
such
as
carbon
filtering,
flocculation,
and
sedimentation
ineffective.

Hydrolysis
rates
for
oxytetracycline
may
increase
as
pH
deviates
from
7
(
Loftin
et
al.,
2004).
Therefore,
softening
may
substantially
reduce
oxytetracycline
concentrations
(
via
alkaline
hydrolysis),
as
softening
raises
the
pH
of
the
water
as
high
as
11.

The
Office
of
Pesticide
Programs
currently
does
not
have
sufficient
information
to
account
for
locations
where
activated
carbon
filtering,
flocculation,
sedimentation,
or
softening
removal
processes
are
utilized
at
public
drinking
water
treatment
facilities,
and
thus
cannot
systematically
use
this
information
to
generate
EDWCs.
In
the
absence
of
direct
data,
and
having
insufficient
ancillary
data
to
consider
hydrophobicity
or
hydrolysis,
the
effects
of
drinking
water
treatment
were
not
taken
into
account
in
this
assessment.

Uncertainties
There
are
a
number
of
factors
inherent
in
exposure
modeling
that
can
affect
the
accuracy
and
precision
of
analysis
including
the
quality
of
the
input
data,
and
the
ability
of
the
models
to
represent
real
scenarios.
In
this
assessment,
conservative
assumptions
were
made
in
the
absence
of
environmental
fate
data,
and
the
resulting
EDWCs
are
concomitantly
inflated.
These
assumptions
are
consistent
with
Tier
I
exposure
estimates.
Additional
data
on
rates
of
metabolism
would
greatly
increase
statistical
confidence,
and
likely
reduce
the
EDWCs.
Clear
label
language
regarding
maximum
application
rates
per
year,
maximum
numbers
of
applications
per
year,
minimum
application
intervals,
and
application
methods
would
increase
confidence
in
the
EDWCs
as
well.

8
Online
at:
http://
www.
epa.
gov/
safewater/
data/
getdata.
html.
9
Online
at:
http://
www.
epa.
gov/
safewater/
data/
ucmrgetdata.
html.
Page
11
of
13
Literature
Citations
Internal
EPA
Documents
MRID
41602001.
Dowd,
N.
E.,
J.
D.
DeFoe.
1990.
Oxytetracycline
Hydrochloride
and
Oxytetracycline
Calcium
Complex
 
Product
Chemistry
Data.
Performed
and
submitted
by
Pfizer
Inc.

MRID
44219401.
McKay,
Ph.
D.,
B.
M.
1997.
Determination
of
Physical­
Chemical
Characteristics
of
4%
w/
w
Propylene
Glycol
Solution
of
the
Calcium
Salt
of
Oxytetracycline.
Performed
by
Formulogics,
Inc.
Submitted
by
Tree
Tech
Microinjection
System.

MRID
43262301.
Johnson,
Ph.
D.,
N.
A.
1994.
Product
Chemistry
Data
for
the
End
Use
Product
Mycoshield
®
Brand
of
Agricultural
Terramysin
®
.
Performed
by
Merck
Research
Laboratories.
Submitted
by
Merck
&
Co.,
Inc.

MRID
46109401.
Irrig,
H.
2003.
Manufacturing
Process
Description
and
Supporting
Data
for
Oxytetracycline
Calcium
Technical
(
ASF793),
Addendum
to
MRID:
41602001.
Performed
and
submitted
by
Syngenta
Crop
Protection,
Inc.

Open
Literature
Capone,
D.
G.,
D.
P.
Weston,
V.
Miller,
C.
Shoemaker.
1996.
Antibacterial
Residues
in
Marine
Sediments
and
Invertebrates
Following
Chemotherapy
in
Aquaculture.
Aquaculture
145(
1­
4):
55­
75.

Doi,
A.
M.,
M.
K.
Stoskopf.
2000.
The
Kinetics
of
Oxytetracycline
Degradation
in
Deionized
Water
under
Varying
Temperature,
pH,
Light,
Substrate,
and
Organic
Matter.
Journal
of
Aquatic
Animal
Health
12(
3):
246­
253.

Effland,
W.
R.,
N.
C.
Thurman,
I.
Kennedy.
1999.
Proposed
Methods
for
Determining
Watershed­
derived
Percent
Crop
Areas
and
Considerations
for
Applying
Crop
Area
Adjustments
to
Surface
Water
Screening
Models.
Presentation
to
the
FIFRA
Science
Advisory
Panel,
May
27,
1999.
Online
at:
http://
www.
epa.
gov/
scipoly/
sap/
1999/
index.
htm.

Ingerslev,
F.,
L.
Torang,
M.
Loke,
B.
Halling­
Sorensen,
N.
Nyholm.
2001.
Primary
Biodegradation
of
Veterinary
Antibiotics
in
Aerobic
and
Anaerobic
Surface
Water
Simulation
Systems.
Chemosphere
44:
865­
872.

Jones,
A.
D.,
G.
L.
Bruland,
S.
G.
Agrawal,
D.
Vasudevan.
2005.
Factors
Influencing
the
Sorption
of
Oxytetracycline
to
Soils.
Environmental
Toxicology
and
Chemistry
24(
4):
761­
770.
Page
12
of
13
Jones,
R.
D.,
S.
Abel,
W.
R.
Effland,
R.
Matzner,
R.
Parker.
1998.
An
Index
Reservoir
for
Use
in
Assessing
Drinking
Water
Exposure.
Proposed
Methods
for
Basin­
scale
Estimation
of
Pesticide
Concentrations
in
Flowing
Water
and
Reservoirs
for
Tolerance
Reassessment.
Presentation
to
FIFRA
Science
Advisory
Panel,
June
29­
30,
1998.
Online
at:
http://
www.
epa.
gov/
scipoly/
sap/
1998/
index.
htm.

Kolpin,
D.,
E.
Furlong,
M.
Meyer,
E.
Thurman,
S.
Zaugg,
L.
Barber,
H.
Buxton.
2002.
Pharmaceuticals,
Hormones,
and
Other
Organic
Wastewater
Contaminants
in
U.
S.
Streams,
1999­
2000:
A
National
Reconnaissance.
Environmental
Science
&
Technology
36(
6):
1202­
1211.

Loftin,
K.,
C.
Adams,
M.
Meyer,
R.
Surampali.
2004.
Hydrolysis
of
Selected
Veterinary
Antibiotics
and
Their
Chemical
Degradation
in
Anaerobic
Swine
Lagoons.
The
Ninth
Symposium
on
the
Chemistry
&
Fate
of
Modern
Pesticides,
Vail,
Colorado.
August
16­
19,
2004.
Abstract
online
at:
http://
ks.
water.
usgs.
gov/
Kansas/
pubs/
abstracts/
chemfate.
kl.
2004.
htm.

Milewski,
I;
Tlusty,
M.
F.,
D.
A.
Bengston,
H.
O.
Halvorson,
S.
D.
Oktay,
J.
B.
Pearce,
R.
B.
Rheault,
Jr.
(
eds.).
2001.
Impacts
of
Salmon
Aquaculture
on
the
Coastal
Environment:
A
Review.
Marine
Aquaculture
and
the
Environment;
A
meeting
for
Stakeholders
in
the
Northeast.
166
­
197
pp.
Cape
Cod
Press,
Falmouth,
Massachusetts.
324
p.

USEPA.
1992.
Pesticides
in
Ground
Water
Database:
A
Compilation
of
Monitoring
Studies:
1971­
1991:
National
Summary.
U.
S.
Environmental
Protection
Agency.
Washington
DC.

USEPA.
1993.
Reregistration
Eligibility
Document
for
Hydroxytetracycline
Monohydrochloride
and
Calcium
Oxytetracycline,
List
A,
Case
0020.
U.
S.
Environmental
Protection
Agency,
Office
of
Pesticide
Programs.
March,
1993.

USEPA.
2002.
Guidance
for
Selecting
Input
Parameters
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides.
U.
S.
Environmental
Protection
Agency,
Office
of
Prevention,
Pesticides
and
Toxic
Substances,
Office
of
Pesticide
Programs,
Environmental
Fate
and
Effects
Division.
Feb.
28,
2002.
Online
at:
http://
www.
epa.
gov/
oppefed1/
models/
water/
input_
guidance2_
28_
02.
htm.
Page
13
of
13
Appendix
Attachment
I:
FIRST
Input/
Output
File
(
Mar.
24,
2006
09:
02)

RUN
No.
3
FOR
OTC
ON
P
&
N
*
INPUT
VALUES
*
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
%
CROPPED
INCORP
ONE(
MULT)
INTERVAL
Koc
(
PPM
)
(%
DRIFT)
AREA
(
IN)
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
.637(
5.737)
9
7
771.0
1000.0
ABLAST(
6.3)
87.0
.0
FIELD
AND
RESERVOIR
HALFLIFE
VALUES
(
DAYS)
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(
FIELD)
RAIN/
RUNOFF
(
RESERVOIR)
(
RES.­
EFF)
(
RESER.)
(
RESER.)
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
.00
2
N/
A
.00­
.00
.00
.00
UNTREATED
WATER
CONC
(
MICROGRAMS/
LITER
(
PPB))
Ver
1.0
AUG
1,
2001
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
PEAK
DAY
(
ACUTE)
ANNUAL
AVERAGE
(
CHRONIC)
CONCENTRATION
CONCENTRATION
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
89.347
4.536
Attachment
II:
SCI­
GROW
Input/
Output
File
(
Mar.
24,
2006
09:
06)

SciGrow
version
2.3
chemical:
OTC
time
is
3/
24/
2006
9:
6:
59
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
Application
Number
of
Total
Use
Koc
Soil
Aerobic
rate
(
lb/
acre)
applications
(
lb/
acre/
yr)
(
ml/
g)
metabolism
(
days)
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
0.637
9.0
5.737
1.00E+
04
1000.0
­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­­
groundwater
screening
cond
(
ppb)
=
3.29E­
02
************************************************************************