United
States
Office
of
Prevention,
Pesticides
July
7,
2005
Environmental
Protection
and
Toxic
Substances
Agency
(
7508C)

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Procymidone
1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
Dear
Reader:

This
is
the
Environmental
Protection
Agency's
(
hereafter
referred
to
as
EPA
or
the
Agency)
"
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
for
Procymidone,"
which
was
approved
on
July
6,
2005.
This
document
is
also
known
as
a
Tolerance
Reassessment
Decision,
or
TRED.
A
Notice
of
Availability
of
this
tolerance
reassessment
decision
will
be
published
shortly.

The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
enactment
of
the
FQPA
on
August
3,
1996.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
Once
a
safety
finding
has
been
made,
the
tolerances
are
considered
reassessed.
Existing
tolerances
and
exemptions
associated
with
procymidone
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.

Procymidone
is
a
fungicide
used
to
treat
wine
grapes
outside
of
the
United
States.
A
tolerance
of
5
ppm
for
wine
grapes
has
been
established,
with
no
U.
S.
registrations,
to
permit
the
import
of
wine
produced
from
procymidone
treated
grapes.
Currently,
procymidone
exposures
to
the
U.
S.
general
population
exist
only
through
drinking
imported
wine
made
from
procymidone
treated
grapes.
Since
there
are
no
registered
uses
of
procymidone
in
the
U.
S.,
no
occupational,
residential,
or
drinking
water
exposures
are
expected.

The
Agency
has
completed
the
human
health
risk
assessment
for
procymidone.
These
findings
are
presented
fully
in
the
human
health
risk
assessment
document,
"
Procymidone:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
Document,"
dated
June
13,
2005.
The
procymidone
toxicological
database
is
adequate
for
hazard
characterization
and
sufficient
data
are
available
to
assess
potential
susceptibility
to
the
young.
Therefore,
the
FQPA
Safety
Factor
(
SF)
was
reduced
to
1X.
Acute
and
cancer
dietary
assessments
were
performed
for
procymidone.
A
chronic
dietary
2
assessment
was
not
performed
since
the
same
NOAEL
and
endpoint
(
developmental
effect,
NOAEL
=
3.5
mg/
kg/
day)
were
chosen
for
both
chronic
and
acute
assessments.
The
dietary
exposure
analysis
for
food
resulted
in
risk
estimates
below
the
Agency's
level
of
concern.
A
Tier
I
acute
dietary
assessment
was
performed
for
procymidone.
At
the
95th
percentile,
acute
dietary
risk
were
1.7%
of
the
acute
Population
Adjusted
Dose
(
aPAD)
for
females
13­
49.
The
Agency
classified
procymidone
as
a
probable
human
carcinogen.
Cancer
risk
was
estimated
to
be
1.8
x
10­
6.
Conservative
assumptions
were
used
in
conducting
the
cancer
analysis.
Thus,
actual
exposure
is
likely
to
be
substantially
lower
than
the
estimated
exposure
and
consequently
not
of
concern.

3,5­
Dichloroaniline
(
3,5­
DCA)
is
a
common
metabolite
to
iprodione,
vinclozolin,
and
procymidone.
The
3,5­
DCA
metabolite
was
not
detected
in
grapes,
but
occurs
during
fermentation.
Based
on
modeling
from
drinking
water
residues
of
3,5­
DCA,
cancer
risk
estimates
from
iprodione
and
vinclozolin
exceeded
the
Agency's
level
of
concern.
Mitigation
and
monitoring
were
imposed
for
iprodione
and
vinclozolin
to
deal
with
these
exceedences.

A
cancer
assessment
was
performed
for
3,5­
DCA
as
a
result
of
all
three
chemical
uses
in
food
and
wine
only.
The
aggregate
carcinogenic
risk
estimate
for
consumption
of
food
and
wine
containing
residues
of
3,5­
DCA
as
a
result
of
use
of
iprodione,
vinclozolin,
and
procymidone
is
1.3
x
10­
6.
To
obtain
the
carcinogenic
risk
estimate
for
3,5­
DCA,
the
established
Q
1*
for
p­
chloroaniline
(
PCA)
was
used
as
a
surrogate
Q
1*
in
this
assessment
because
of
the
structural
similarities
between
3,5­
DCA
and
PCA.
EPA
believes
that
the
use
of
the
PCA
Q
1*
represents
a
reasonable
risk
estimate.

There
are
no
data
gaps
for
procymidone.
Based
on
the
human
health
assessment,
risks
associated
with
procymidone
are
considered
to
be
minimal
in
the
United
States
due
to
its
low
acute
toxicity
and
its
low
dietary
exposure.
Therefore,
no
mitigation
measures
are
needed,
and
the
current
tolerance
for
wine
grapes
at
40
CFR
180.455
for
residues
of
procymidone
is
now
considered
reassessed
under
section
408(
q)
of
the
FFDCA.

FQPA
requires
that
EPA
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
The
Agency
considers
other
substances
because
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect,
as
would
a
higher
level
of
exposure
to
any
of
the
substances
individually.

EPA
has
not
made
a
common
mechanism
of
toxicity
finding
and
therefore,
has
not
assumed
that
procymidone
has
a
common
mechanism
of
toxicity
with
other
substances
for
the
purposes
of
this
tolerance
action.
However,
procymidone
is
structurally
related
to
vinclozolin
and
iprodione,
and
the
metabolite
3,5­
DCA
is
produced
by
each
of
these
chemicals.

EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
"
may
have
an
effect
in
humans
that
is
similar
to
endocrine
effects."
Procymidone
is
known
to
interfere
with
the
endocrine
system
related
to
its
anti­
androgenic
activity
ultimately
resulting
in
reproductive
effects.
In
several
studies,
a
number
of
testicular
effects
were
observed
at
one
or
more
dose
levels
in
the
developmental,
multigeneration,
and
chronic
toxicity
studies
in
rats.
When
additional
appropriate
screening
and/
or
testing
protocols
currently
being
3
considered
under
the
Agency's
Endocrine
Disruptor
Screening
Program
(
EDSP)
have
been
developed,
procymidone
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

This
document
summarizes
the
Agency's
decision
on
the
tolerance
reassessment
for
procymidone.
Please
contact
Demson
Fuller
of
my
staff
with
any
questions
regarding
this
decision.
He
may
be
reached
by
phone
at
(
703­
308­
8062)
or
via
e­
mail
at
fuller.
demson@
epa.
gov.

Sincerely,

Debra
Edwards,
Ph.
D.
Director
Special
Review
and
Reregistration
Division
