UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
October
15,
2002
MEMORANDUM
SUBJECT:
EFED
response
to
Syngenta's
errors­
only
comments
on
the
Agency
document
"
Comparative
Risks
of
Nine
Rodenticides
to
Birds
and
Nontarget
Mammals"

TO:
John
Pates,
Chemical
Review
Manager
Susan
Lewis,
Branch
Chief
FROM:
William
Erickson,
Biologist
Douglas
Urban,
Senior
Biologist
Environmental
Risk
Branch
III,
Environmental
Fate
and
Effects
Division
THRU:
Stephanie
Irene,
Acting
Chief
Environmental
Risk
Branch
III,
Environmental
Fate
and
Effects
Division
The
Environmental
Fate
and
Effects
Division
(
EFED)
has
reviewed
Syngenta's
30­
day
errorsonly
response
to
the
Agency
document
"
Comparative
Risks
of
Nine
Rodenticides
to
Birds
and
Nontarget
Mammals"
dated
October
3,
2001.
Syngenta's
comments
of
December
5,
2001
were
prepared
by
J.
Hott,
Regulatory
Product
Manager,
with
support
from
J.
Akins,
Toxicologist;
D.
Kaukeinen,
Technical
Specialist;
and
J.
Shaw,
Environmental,
Stewardship
and
Policy
Leader.
As
stated
in
the
Agency's
October
23,
2001
cover
letter
sent
for
the
assessment,
the
registrants'
30­
day
response
should
address
only
mathematical,
computational,
typographic,
or
other
similar
errors.
Matters
of
policy,
interpretation,
or
applicability
of
data
will
be
addressed
after
the
public
comment
period
in
accordance
with
the
Agency's
reregistration
process
for
pesticides.

In
response
to
error
comments
by
Syngenta,
other
rodenticide
registrants,
and
the
Rodenticide
Registrants
Task
Force,
EFED
has
made
necessary
computational
and/
or
typographical
corrections.
However,
EFED
notes
that
many
comments
relate
to
policy,
interpretation,
or
applicability
of
data,
and
those
comments
will
be
addressed
along
with
public
comments
after
the
60­
day
public­
comment
period.
2
"
Comparative
Risks
of
Nine
Rodenticides
to
Birds
and
Nontarget
Mammals":

Syngenta
Response
GENERAL
COMMENTS
Document
is
not
a
"
Risk
Assessment".
The
EPA
document
"
Comparative
Risks
of
Nine
Rodenticides
to
Birds
and
Nontarget
Mammals"
reviews
hazard
studies
and
incidents
and
develops
hazard
indices,
but
does
not
adequately
address
the
important
exposure
portion
to
establish
"
Risk".
There
is
a
clear
difference
between
the
term
and
meaning
of
"
Risk"
as
compared
to
"
Hazard".
Risk
is
a
function
of
the
Hazard
(
toxicity
characteristics)
and
exposure
(
product
use
and
associated
exposure
potential).
Given
that
the
remit
of
EFED
biologists
was
to
produce
a
Rodenticide
Risk
Assessment,
we
maintain
that
this
goal
has
not
yet
been
achieved
because
no
exposure
analysis
has
been
provided.
In
fact,
the
resulting
"
Hazard
Study"
is
preliminary
to
a
Problem
Formulation
stage,
which
would
normally
precede
a
Risk
Assessment.

EFED
response:
This
has
been
addressed
in
the
revised
document.
As
Syngenta
knows,
rodenticide
baits
are
formulated
to
be
lethal
to
rodents
and
a
few
other
small
mammals,
and
they
are
not
selective
to
the
target
species.
Although
many
factors
influence
which
nontarget
animals
might
be
exposed
to
baits,
many
nontarget
organisms
are
attracted
to
and
consume
grain­
based
baits.
Predators
and
scavengers
also
feed
on
rats
and
mice
or
other
target
species,
and
they
are
not
likely
to
avoid
feeding
on
those
that
have
eaten
rodenticide
bait.
Thus,
rodenticide
baits
also
pose
potential
secondary
risks.
EFED
believes
that
the
potential
for
risks
to
birds
and
nontarget
mammals
is
well
established
for
some
of
these
rodenticides.

The
risk
assessment
is
based
on
the
available
data.
Registrants,
including
Syngenta,
have
not
submitted
the
data
that
would
be
needed
to
assess
the
probability
of
exposure.
These
data
have
been
outlined
in
a
section
on
Uncertainty
and
Data
Needs
in
the
revised
assessment.
The
methodology
used
is
similar
to
that
used
in
the
Agency's
"
Comparative
Analysis
of
Acute
Risk
From
Granular
Pesticides"
(
EPA
1992)
and
"
A
Comparative
Analysis
of
Ecological
Risks
from
Pesticides
and
Their
Use:
Background,
Methodology,
Case
Study"
(
EPA
1998);
both
were
reviewed
by
a
FIFRA
Scientific
Review
Panel.
Concerning
the
latter
analysis,
the
Panel
noted
the
many
scientific
uncertainties
in
the
method,
yet
agreed
that
it
was
a
useful
screening
tool
that
provides
a
rough
estimate
of
relative
risk.
The
Panel
made
a
number
of
helpful
suggestions
to
improve
the
utility
of
the
method,
most
of
which
are
included
here.

Risk
conclusions
are
presented
in
tabular
and
graphical
form
based
on
two
analyses
of
the
available
data.
The
first
is
a
comparative
ranking
of
the
potential
risk
based
on
a
comparative­
analysis
model,
and
the
second
is
a
tabular
comparative
rating
of
potential
risk
based
on
a
qualitative
"
weight­
of­
evidence"
assessment.
Quantitative
estimates
of
3
risk
are
used
in
both;
however,
the
"
weight­
of
evidence"
assessment
includes
qualitative
assessments
of
secondary
risk
based
on
mortality
and
other
adverse
effects
reported
in
laboratory
and
field
studies,
operational
control
programs,
and
incident
reports,
as
well
as
toxicokinetic
data
and
residue
levels
reported
in
primary
consumers.
This
approach
is
in
concert
with
EPA's
risk­
assessment
guidelines
(
EPA
1998),
where
professional
judgement
or
other
qualitative
evaluation
techniques
may
be
used
to
rank
risks
using
categories
such
as
low,
medium,
and
high
when
exposure
and
effects
data
Document
does
not
provide
for
"
Risk/
Benefit"
Considerations.
The
benefit
analysis
and
regulatory
history
sections
are
completely
absent
in
the
EPA
Comparative
Assessment
document
as
compared
with
the
EPA
RED
in
1998
(
page
102­
103,
7­
8).
This
is
an
error
based
on
the
FIFRA
law,
which
is
a
Risk­
Benefit
law.
These
are
especially
important
sections,
since
the
target
species
and
non­
target
species
(
mammals)
are
nearly
identical
physiologically.
It
is
impossible
to
identify
a
rodenticide
that
poses
no
risk
to
mammals,
and
the
EPA
"
recognizes
that
new
technologies
do
not
exist"
for
rodent
control
(
EPA
RED
Rodenticide
Cluster).

In
other
Reregistration
Eligibility
Decision
and
Reduced
Risk
assessments
with
which
we
are
familiar,
the
Agency
systematically
addresses
the
products'
use
in
accordance
with
benefits,
including
Resistance
Management.
The
second­
generation
rodenticides
were
designed
to
control
populations
of
rodents
that
are
resistant
to
the
first
generation
rodenticides
and
to
eliminate
the
need
for
refeeding
to
ingest
lethal
doses.
The
ecological
risk
posed
by
second­
generation
rodenticides
should
be
analyzed
separately
from
the
first
generation.
First
generation
rodenticides
should
not
be
used
to
replace
the
second­
generation
rodenticides
unless
one
is
willing
to
further
increase
the
range
of
resistant
rodent
populations
and
return
to
the
greater
exposure
represented
by
refeeding
requirements.

The
benefits
of
rodenticides
in
general
in
combating
harmful
pest
rodents
need
to
be
considered.
Acceptable
risk
levels
for
rodenticides
cannot
be
set
without
establishing
some
measure
of
the
economic
and
public
health
detriments
that
pest
rodent
cause.

EFED
response:
The
Agency
will
be
considering
benefits
of
rodenticides
in
a
later
phase
of
the
reregistration
process.
The
current
document
is
EFED's
assessment
of
risks.

Exposure
considered
comparable
for
all
rodenticides.

The
Review's
assumption
that
exposure
of
non­
target
organisms
is
equivalent
for
the
various
rodenticides
(
pages
1­
2
and
elsewhere)
ignores
very
significant
differences
in
activity
and
action,
market
share,
label
uses,
and
formulation
differences.
Risks
will
not
increase
or
decrease
equally
if
one
rodenticide
is
used
instead
of
another.
In
fact,
some
rodenticides
have
singular
utility.
Brodifacoum,
for
example,
is
the
only
anticoagulant
documented
and
labeled
to
control
both
warfarin­
resistant
rats
and
warfarin­
resistant
4
mice.
Brodifacoum
can
be
used
outside
of
structures
in
non­
urban
areas,
whereas
bromadiolone
and
difethialone
cannot.
Bromadiolone
and
brodifacoum
can
be
used
outside
in
burrows,
but
difethialone
cannot.
So
there
cannot
be
an
equal
substitution
of
one
second­
generation
anticoagulant
for
another.
The
brodifacoum
label
is
broader
than
the
other
products
in
recognition
of
its
superior
efficacy
and
the
additional
data
that
was
provided
by
Syngenta
and
its
heritage
companies.

EFED
response:
EFED's
previous
comment
addresses
exposure.
EFED
also
notes
that
the
Agency
requested
use
information
from
registrants
prior
to
issuance
of
the
Rodenticide
Cluster
Reregistration
Eligibility
Document
(
RED),
but
that
information
was
not
provided.
Differences
is
uses
among
the
rodenticides
will
be
considered
and
reevaluated
during
the
reregistration
process.

Toxicological
and
hazard
findings
taken
out
of
context.

Rodenticides
are
by
their
nature,
vertebrate
pesticides.
No
"
perfect
rodenticide"
has
yet
been
developed
that
is
specific
to
rodents.
It
is
hardly
surprising
that
non­
target
animals
can
be
poisoned
under
controlled
conditions
in
the
laboratory
or
through
misuse
in
the
field.
However,
such
findings
are
often
irrelevant
or
insignificant
in
regard
to
the
commercialized,
intended
use
pattern.
Yet
this
review
presents
an
exhaustive
summary
of
such
disparate
information
as
a
basis
for
Agency
concern.
Likewise,
a
review
of
incident
data
is
not
a
substitute
for
an
exposure
assessment.
Incidents
are
a
function
of
the
prevalence
of
use
and
how
the
product
is
used
or
misused.
Incident
data
would
more
properly
be
useful
in
the
development
of
a
Problem
Formulation
stage
of
a
risk
assessment,
prior
to
an
exposure
analysis.

Highly
different
studies
and
incident
situations
are
grouped
together
in
this
document
for
comparison.
No
consideration
is
given
to
the
quality
of
studies,
the
purposes
for
which
they
were
conducted,
and
their
appropriateness
for
a
risk
evaluation.
The
abbreviated
nature
and
wide
data
spread
of
many
studies
make
their
utility
limited.
In
many
cases
in
conclusions
and
calculations,
specific
non­
target
animal
feeding
behaviors
and
diet
preferences
are
ignored
in
making
assumptions
of
amounts
of
rodenticides
consumed
directly
(
primary
exposure)
or
indirectly
(
secondary
exposure).
Many
incidents
appear
to
have
no
confirmed
cause
of
death,
or
have
multiple
causative
factors.

The
use
patterns
and
practices
that
have
been
developed
and
formalized
into
labeling
statements
and
the
products
allowed
by
the
Agency
to
be
marketed
have
resulted
from
extensive
studies
that
registrants
have
conducted
to
meet
Agency
requirements.
The
efficacy
studies
required
for
the
advanced
anticoagulants
(
single­
feed)
in
particular
have
selected
for
highly
active
products.
It
now
seems
the
Agency
is
concerned
about
the
very
product
qualities
that
directly
resulted
from
the
very
test
requirements
that
registrants
were
required
to
meet
from
the
EPA.
Evaluations
with
compounds
such
as
brodifacoum
have
been
extensive.
5
Advanced
non­
target
risk
evaluations
involving
radio
telemetry
studies
were
conducted
at
the
request
of
the
Agency
under
an
EUP
program,
in
full
consultation
with
Agency
biologists.
The
resulting
barn
owl
field
study
evaluated
commensal
rodent
baiting
hazards
for
brodifacoum
to
the
raptor
most
at
risk,
and
the
Agency
accepted
both
the
protocol
for
this
work
as
well
the
independent
study
directors'
findings
(
Hegdal
and
Blaskiewicz,
1984).
These
findings
were
that
commensal
baiting
did
not
pose
a
significant
risk
to
populations
of
barn
owls.
Too
little
has
been
made
of
this
study
in
the
Agency
"
Comparative
Risk"
document
which,
at
its
core,
is
about
raptor
hazard
with
an
emphasis
on
brodifacoum.
In
fact,
the
barn
owl
study
met
the
Tier
3
requirements
that
addressed
these
non­
target
concerns
back
in
the
early
1980s.
It
is
entirely
proper
to
question
older
data,
but
no
information
is
presented
to
refute
the
earlier
findings,
and
they
should
not
be
ignored.
The
barn
owl
findings
resulted
in
the
Agency
allowing
brodifacoum
products
to
be
used
outside
of
structures
in
non­
urban
areas,
unlike
the
other
advanced
anticoagulants.

Furthermore,
the
EPA
stated
in
the
1998
RED
that:
"
The
U.
S.
Environmental
Protection
Agency
(
EPA)
has
completed
its
reregistration
eligibility
decision
of
the
pesticides
brodifacoum,
bromadiolone,
chlorophacinone,
diphacinone
and
its
sodium
salt,
bromethalin,
and
pival
and
its
sodium
salt.
This
decision
includes
a
comprehensive
reassessment
of
the
required
target
data
and
the
use
patterns
of
currently
registered
products.
These
chemicals
are
rodenticides
used
in
urban,
suburban,
and
rural
areas
for
the
control
of
commensal
rodents.
 .
With
the
exception
of
pival
and
its
sodium
salt,
the
Agency
has
concluded
that
the
uses,
as
prescribed
in
this
document,
with
additional
labeling
requirements
and
a
number
of
risk
mitigation
measures,
will
not
cause
unreasonable
risks
to
humans
or
the
environment 
The
Agency
has
determined
that
all
uses
of
brodifacoum,
bromethalin,
and
bromadiolone
are
eligible
for
reregistration."

EFED
response:
This
is
not
an
errors
response.
These
issues
will
be
addressed
along
with
other
responses
after
the
public­
comment
period.

Pooling
of
Wildlife
Incident
Data.

In
other
Reregistration
Eligibility
Decision
and
Reduced
Risk
assessments
that
have
been
addressed
by
the
Agency
over
the
last
ten
years
or
more,
the
Agency
systematically
addresses
the
product's
use
and
resulting
exposure
and
risk
potential
to
nontarget
wildlife.
The
current
document
mentions
the
use
site
areas,
but
it
does
not
separate
the
uses
regarding
risk.
Three
critical
issues,
pertaining
to
incident
data,
that
need
to
be
addressed
are
listed
below:

1)
The
EPA
over­
interprets
the
impacts
of
residue
analysis
to
the
causation
of
mortality.
Low
levels
of
persistent
compounds
such
as
brodifacoum
cannot
be
directly
related
to
cause
of
death,
particularly
when
case
study
information
indicate
other
lethal
or
potentially
lethal
effects
such
as
vehicle
impact.
The
Agency
should
break
out
6
incident
data
where
causation
cannot
be
determined
or
where
multiple
potential
causative
factors
were
identified.

2)
When
comparing
the
incident
or
study
data
between
active
ingredients,
the
EPA
should
take
into
account
how
and
where
the
product
was
used,
and
the
total
amount
of
product
that
is
being
used.
In
order
to
allow
for
comparisons
to
be
made,
the
Agency
should,
at
a
minimum,
divide
incidents
into
the
following
groups:

a)
Incident
occurred
by
intentional
poisoning;

b)
Incident
resulting
from
the
experimental
application
of
a
rodenticide
(
e.
g.,
for
control
of
orchard
voles)
in
efficacy
or
hazard
studies
involving
a
use
pattern
that
is
different
from
the
commensal
rodent
use
pattern.

c)
Incident
occurred
by
off­
label
use
in
the
United
States
(
e.
g.,
misapplications
or
uses
in
other
countries
that
are
different
that
US);

d)
Incident
occurred
by
currently
labeled
use.

3)
Establish
the
total
sales
of
the
product
compared
to
the
total
number
of
incidents.

i)
It
is
important
to
take
into
account
the
total
sales
of
a
product
and
use
of
a
product
before
comparing
risk.
In
the
case
of
brodifacoum,
the
Agency
indicates
that
the
product
has
180
incidents,
which
the
Agency
alleges
is
far
more
than
the
other
rodenticides.
However,
earlier
in
the
document,
the
Agency
states
that
brodifacoum
makes
up
for
more
than
93%
of
the
total
sales
of
rodenticides
in
the
United
Sates.
When
the
ratio
of
incidents
to
containers
sold
for
brodifacoum
in
1997
is
compared
with
four
other
rodenticides
incidents
to
sales
ratio
in
1997,
brodifacoum
is
determined
to
pose
the
least
risk
(
Table
1).
Based
on
this
analysis,
if
bromodiolone
were
to
replace
brodifacoum,
one
would
expect
a
31­
fold
increase
in
wildlife
incidents
with
bromodiolone.

ii)
This
analysis
should
be
conducted
once
the
above
steps
are
completed
to
take
into
account
the
product
use
and
confidence
in
the
causation.
7
Table
1.
Incident
Risk
Based
on
Total
Product
Sold.

Rodenticide
Total
incident
#
*
Total
incident
#
in
1997
Total
Container
Sales
in
1997
#
Incidents
/
Total
Containers
Sales
in
1997
#
Incidents
in
1997/
Total
Container
Sales
in
1997***

Brodifacoum
180
**
44,144,456
0.0000041
<<
0.0000041
Bromadiolone
37
**
294,706
0.00013
<
0.00013
Diphacinone
18
**
2,860,419
0.0000063
<<
0.0000063
Chlorophacinone
10
**
18,360
0.00054
<
0.00054
*
The
number
of
incidents
is
captured
from
many
years.
**
This
number
needs
to
be
calculated.
***
This
number
needs
to
be
calculated
taking
into
account
the
total
number
of
containers
sold
over
the
same
period
of
time
that
the
incidents
were
recorded.

EFED
response:
EFED
believes
it
is
highly
misleading
to
refer
to
"
total"
incidents,
rather
than
"
reported"
incidents,
because
most
incidents
are
not
reported.
The
Agency
does
not
know
the
amount
of
brodifacoum
or
other
rodenticides
sold
and
applied
in
the
U.
S.,
although
we
have
repeatedly
requested
this
information
from
rodenticide
registrants.
The
statement
that
brodifacoum
accounts
for
93%
of
the
over­
the­
counter
sales
(
not
total
sales)
was
attributed
to
an
RRTF
article
(
Kaukeinen
et
al.
2000)
in
a
conference
proceedings.
However,
the
only
information
provided
is
container
sales
for
four
of
the
nine
rodenticides.
No
information
is
provided
regarding
container
sizes,
regional
or
state
use,
or
other
important
use
information.

In
a
meeting
with
the
Agency
on
October
9,
2002,
the
RRTF
provided
a
handout
on
"
Estimates
of
%
Chance
of
Incidents
Occurring
Based
on
Total
Number
of
OTC
Placements".
The
chance
of
an
incident
occurring
was
based
solely
on
an
estimate
of
total
placements
compared
to
the
total
number
of
incidents
reported.
However,
such
estimates
are
of
little
value
without
factoring
in
the
probability
that
an
incident
occurs
but
is
not
discovered,
the
probability
that
an
incident
is
discovered
but
not
reported
to
the
proper
authorities,
and
the
probability
that
an
incident
is
reported
but
no
residue
analysis
is
conducted.
Moreover,
simply
considering
over­
the­
counter
sales
completely
ignores
incidents
that
might
occur
from
use
by
Certified
Applicators.

Statistical
Methodology
The
EFED
has
not
utilized
standard
and
conventional
methodologies
that
allow
for
a
true
risk
assessment
on
rodenticidal
baits
and
thus,
this
document
falls
short
of
the
standard
EFED
Tier
1
Agency
assessments
that
we
are
familiar
with
for
other
products.
No
scientific
rationale
is
provided
to
support
the
methodology
and
approach
used
by
EFED.
The
HD5
method,
for
example,
is
utilized
in
the
document
for
rodenticides;
will
all
8
pesticides
now
be
analyzed
by
the
HD5
method?
Is
this
method
recommended
by
the
EFED
Probabilistic
Risk
Assessment
team
as
more
appropriate
than
other
methods?
Summary
values
produced
by
the
analyses
do
not
provide
a
comparison
of
risk,
but
rather
reflect
the
particular
`
measures
of
effect'
selected
by
EFED
and
the
weighing
that
EFED
gave
them.
Parameters
such
as
body
retention
times
are
only
one
component
and
do
not
necessarily
relate
to
risk
determination.

A
decision­
making
analysis
does
not
appear
to
be
appropriate
for
an
ecological
risk
assessment,
nor
is
it
an
adequate
substitute
for
the
scientific
evaluation
of
exposure
and
risk.
Such
a
decision­
making
analysis
might
more
properly
be
used
following
completion
of
a
risk
assessment,
such
as
in
a
`
reduced
risk
rationale'.
Based
upon
our
exposure
to
the
science
of
risk
assessment,
we
believe
there
are
better
and
more
appropriate
approaches
to
develop
probabilistic
methods
with
better
application
to
rodenticides
than
those
chosen
by
EFED
in
this
review.

EFED
response:
This
is
not
an
errors
response,
but
EFED
notes
that
EFED's
Probabilistic
Risk
Assessment
team
and
Division
Director
were
consulted.
They,
as
well
as
numerous
internal
and
external
reviewers,
concurred
that
the
approach
used
in
the
assessment
is
appropriate
for
the
available
data.
See
also
previous
comments.

Specific
Errors
and
Comments:

The
references
to
2­
gram
pellets
(
pages
45,
46,
57
and
91)
are
incorrect.
Talon
pellets
of
3/
16
inch
weigh,
on
average,
0.2
grams
each,
not
2
grams.
Therefore,
an
animal
eating
2
grams
of
Talon
would
need
to
be
ingesting
10
pellets,
not
one.
Only
for
mice
or
mouse­
sized
animals
does
an
LD50
allow
for
one
brodifacoum
pellet
to
approximate
a
lethal
dose.
Likewise,
calculations
such
as
in
Table
31
equating
LD50
to
dose
in
numbers
of
pellets
are
off
by
an
order
of
magnitude
because
of
this
error.

EFED
response:
The
size
of
the
bait
pellet
has
been
corrected
in
the
revised
assessment.

The
"
Bird
LD50"
(
page
i
and
elsewhere)
of
0.26
mg/
kg
is
actually
the
mallard
LD50.
Other
birds
including
raptors
have
LD50s
of
10
to
40
times
this
amount
(
Godfrey,
1985).
It
is
misleading
to
choose
the
lowest
LD50
figure
to
represent
all
bird
species.
The
mallard
study
utilized
a
vitamin
K­
deficient
diet,
causing
an
abnormally
low
value;
a
normal
diet
produced
a
mallard
LD50
of
2.0
mg/
kg.

EFED
response:
EFED
reports
an
LD50
of
0.26
mg/
kg
for
the
mallard
in
Table
3
of
the
risk
assessment.
That
value
is
based
on
a
"
core"
study
submitted
to
the
Agency.
Syngenta
has
provided
no
documentation
that
the
mallard
acute­
oral
study
was
based
on
a
vitamin
K­
deficient
diet.
In
fact,
a
previous
acute
oral
study
was
invalidated
because
vitamin
K
(
an
antidote)
had
been
added
to
the
test
diet.
The
value
of
2.0
mg/
kg
cited
by
Syngenta
is
actually
an
LC50
from
a
dietary
study,
and
it
is
reported
as
an
LC50
value
in
Table
3
and
is
used
in
the
RQ
calculations
for
dietary
risk.
Syngenta
should
also
note
9
that
Table
3
lists
LD50
values
of
<
0.75
mg/
kg
for
both
the
Canada
goose
and
the
southern
black­
backed
gull,
neither
of
which
is
"
10
to
40
times"
greater
than
the
value
of
the
mallard.

It
is
inappropriate
to
group
end­
point
results
of
different
toxicology
studies
from
the
standpoint
of
risk
assessment
(
pages
i,
ii,
19,
151
and
elsewhere).
Many
of
these
studies
were
designed
to
reach
an
endpoint.
The
greater
number
of
studies
on
brodifacoum
are
a
result
of
its
popularity
as
a
rodenticide.
Fewer
studies
were
done
on
other
anticoagulants
so
fewer
poisoned
birds
were
produced.
These
studies
cannot
thus
be
compared.
The
statement
that
brodifacoum
exhibits
much
more
secondary
toxicity
risk
to
birds
than
other
anticoagulants,
while
not
adequately
determined,
is
followed
by
a
statement
that
difethialone
secondary
risks
are
likely
comparable
to
those
posed
by
brodifacoum
(
page
i).

EFED
response:
This
is
not
an
errors
response.
Policy
and
procedural
matters
will
be
addressed
along
with
other
responses
after
the
public­
comment
period.

Comments
on
sublethal
effects
of
anticoagulants
are
speculative
and
contrary
to
all
research
findings
from
over
20
years
of
intensive
study
of
these
compounds
by
researchers
(
pages
74,
96
and
elsewhere).
The
only
effect
of
these
products
is
on
the
clotting
ability
of
the
blood.
Similar
products
are
utilized
as
human
medications
to
prevent
blood
clots
and
behavioral
side­
effects
are
not
noted.

EFED
response:
Syngenta
has
provided
no
supporting
documentation
for
this
assertion.
The
issue
of
sublethal
effects
will
be
addressed
through
a
data
call­
in.

Likewise,
the
argument
for
individual
susceptibility
is
speculative
(
page
45).
Scientific
procedures
establish
median
values
(
such
LD
or
LC
values)
on
which
to
base
regulatory
and
developmental
decisions.
Regulatory
law
cannot
be
developed
based
upon
an
undemonstrated
fear
of
outlying
values.

Why
is
persistence
equated
with
toxicity
(
pages
60,
61,
66
and
elsewhere)?
The
livers
of
birds
and
mammals
are
designed
to
sequester
and
breakdown
foreign
substances
so
that
they
can
be
excreted
from
the
body.
Only
circulating
levels
of
anticoagulants
in
blood
that
are
high
enough
to
affect
coagulation
are
of
concern.
Low
levels
of
anticoagulant
in
the
liver
are
biomarkers
of
some
prior
exposure
but
cannot
be
demonstrated
to
be
causative
in
deleterious
behavioral
or
health
effects.

EFED
response:
While
the
retention
time
is
not
a
direct
measure
of
effect
for
secondary
risk
to
birds
and
mammals,
it
is
an
important
contributing
factor.
The
combination
of
mean
%
mortality
from
secondary
laboratory
toxicity
studies
which
characterizes
the
secondary
toxicity
from
short­
term
exposures,
and
available
data
on
retention
time
in
both
blood
and
liver
which
indicates
how
long
toxic
levels
can
persist
in
target
animal
tissues,
can
characterize
the
secondary
risk
to
birds
and
mammals.
The
relationship
10
between
liver
residues
and
toxicity
is
discussed
in
the
document.
Methods
to
determine
what
liver
concentration
might
corroborate
death
from
anticoagulant
exposure,
or
even
if
such
a
cause­
effect
relationship
is
appropriate,
e.
g.,
the
"
threshold
of
toxicity"
concentration
in
liver
tissue
are
requested
in
the
section
on
Uncertainty
and
Data
Needs
in
the
comparative
risk
assessment.

Because
of
the
commensal
rodent
use
pattern,
it
is
generally
recognized
that
dogs
are
the
non­
target
animals
most
at
risk,
and
certainly
more
dog
incident
and
treatment
data
is
available
than,
for
example,
with
birds.
Syngenta
believes
the
Agency
could
have
made
more
use
of
companion
animal
hazard
and
risk
information
in
ranking
rodenticides
or
for
application
to
determinations
for
other
animals.
However,
dog
toxicity
information
(
pages
56­
60)
is
poorly
presented
in
the
Agency
review
document.

An
adequate
review
of
the
published
literature
has
not
been
carried
out
by
the
Agency
and
a
table
of
accurate
dog
LD50
values
for
rodenticides
is
not
presented,
only
a
commentary
citing
a
mixture
of
tolerated
dose
studies
of
limited
utility.
Difethialone
has
a
published
LD50
value
of
4.0
mg/
kg
(
Liphatech
Tech
Bulletin).
Bromadiolone
has
an
LD50
to
dogs
of
8.1
as
reported
in
Poche
(
1988).
This
data
supercedes
that
in
Marsh,
1985
as
quoted
by
the
Agency.
We
note
that
only
the
lower
LD50
values
in
Marsh,
1985
were
chosen
for
the
Agency's
example,
rather
than
the
middle
or
upper
values
within
the
range
of
published
LD50s
that
Marsh
cites.

The
definitive
brodifacoum
dog
study
was
published
by
Godfrey,
M.
E.
R.,
Reid,
T.
C.,
and
McAllum,
H.
J.
F.
(
1981).
The
Acute
Toxicity
of
the
Anticoagulant
Brodifacoum
to
Dogs".
N.
Z.
Journal
of
Experimental
Agriculture.
9,
147­
149.
This
article
notes
a
3.56
mg/
kg
value
based
on
a
test
involving
59
adult
mixed­
breed
dogs.
The
dose
that
resulted
in
no
adult
mortalities
was
0.5
mg/
kg
(
59
dogs).
Brodifacoum,
while
highly
toxic
to
rodents,
may
not
possess
a
significantly
greater
toxicity
to
mammals
such
as
dogs
than
other
advanced
anticoagulants.
The
following
table
derived
from
the
1990
National
Animal
Poison
Control
Center
Annual
Report
supports
the
contention
that
non­
target
poisonings
seen
with
brodifacoum
result
in
no
greater
percentage
of
symptoms
or
death
than
other
commonly­
available
anticoagulant
and
non­
anticoagulant
rodenticides.
11
Table
2.
Call
Incidence
from
National
Animal
Poison
Control
Center,
1990*

Rodenticide
%
Dog
%
Cat
%
Symptoms**
%
Deaths**

Brodifacoum
81.3
5.9
15.1
6.0
Bromadiolone
78.1
5.3
26.8
9.8
Diphacinone
80.3
2.6
36.8
7.0
Warfarin
79.1
6.7
12.7
13.2
Bromethalin
74.9
9.1
22.9
2.5
Cholecalciferol
81.5
6.5
40.8
12.4
*
Percent
incidence
calculated
from
total
number
of
calls
for
each
compound
**
Totals
for
combined
dog
and
cat
calls
EFED
response:
EFED
believes
that
the
toxicity
data
presented
for
the
nine
rodenticides
is
comprehensive.
Data
having
more
recent
dates
do
not
`
supercede'
older
data;
they
are
simply
additional
data
to
consider.
As
Syngenta
knows,
EFED
assesses
risks
to
nontarget
wildlife,
not
pets.
The
Agency
considers
dogs
to
be
domestic
pets,
and
risks
to
domestic
pets
are
addressed
by
the
Agency's
Health
Effects
Division.
Moreover,
the
Godfrey
et
al.
(
1981)
study
was
an
antidote
study,
not
an
acute­
oral
toxicity
study.
