Document ID: EPA-HQ-OPP-2004-0202-0052
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-08-02T04:00Z

1
  
73
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
February
3,
2005
MEMORANDUM
SUBJECT:
PENTACHLORONITROBENZENE
(
PCNB):
2nd
Revised
HED
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(
RED).
PC
Code:
056502.
Case#
0128
List
A.
DP
Barcode
D312691.

FROM:
Diana
Locke,
Ph.
D.
Risk
Assessor/
Toxicologist
Reregistration
Branch
II
Health
Effects
Division
(
7509C)

THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(
7509C)

TO:
Margaret
Rice,
Chief
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(
7508W)

Attached
is
the
revised
Human
Health
Assessment
for
PCNB.
The
assessment
has
been
revised
according
to
public
comments
submitted
jointly
by
the
registrants
(
Amvac
Chemical
Corporation,
Crompton
Corporation,
and
Gustafson
LLC)
of
PCNB
manufacturing
use
and
end
use
products,
and
the
Golf
Course
Superintendents
Association
of
America
(
GCSAA).
The
Agency
solicited
these
comments
from
the
public
as
part
of
the
procedures
to
ensure
transparency
and
public
participation
in
reregistration
eligibility
decision­
making.
The
Agency
solicited
comments
from
all
stakeholders
and
interested
parties
during
Phase
3
of
the
Interim
Public
Participation
Process.
Where
appropriate,
this
risk
assessment
document
and
the
supporting
discipline
chapters
have
been
revised
to
reflect
added
clarification
and
pertinent
changes.
The
Health
Effects
Division's
(
HED)
responses
to
submitted
comments
can
be
found
in
RESPONSE
TO
PUBLIC
COMMENTS.
The
Health
Effects
Division's
Response
to
Comments
on
EPA's
HED
Chapter
of
the
PCNB
Reregistration
Eligibility
Document
(
07/
27/
04).
PC
Code:
056502,
DP
Barcode
D312692.
Diana
Locke.
February
3,
2005.
We
believe
that
this
revised
assessment
provides
as
realistic,
as
well
as
protective,
characterization
of
the
potential
risks
associated
with
the
use
of
PCNB,
based
on
the
available
data
and
models.
Fulfillment
of
the
data
gaps,
or
changes
in
use
patterns,
could
alter
the
assessment.

The
revised
Human
Health
Assessment
for
the
PCNB
RED
document
was
generated
as
part
of
Phase
4
of
the
Interim
Public
Participation
Process.
The
Health
Effects
Division's
(
HED)
chapter
reflects
the
Agency's
current
guidelines
concerning
the
retention
of
the
Food
Quality
Protection
Act
(
FQPA)
factor
and
risk
assessment.
This
chapter
includes
a
summary
of
the
product
and
residue
chemistry,
and
dietary
risk
assessment
from
Sherrie
Kinard,
toxicology
review
from
Laurence
Chitlik,
occupational
and
residential
exposure
assessment
from
Seyed
Tadayon,
incidence
review
from
Ruth
Allen,
drinking
water
exposures
from
Cheryl
Sutton
[
Environmental
Fate
and
Effects
Division
(
EFED)],
as
well
as
risk
assessment
and
characterization
from
Diana
Locke.

This
assessment
provides
information
to
support
the
issuance
of
a
risk
management
decision
document
known
as
a
Reregistration
Eligibility
Decision
(
RED)
Document
for
PCNB.
EPA's
pesticide
reregistration
process
provides
for
the
review
of
older
pesticides
(
those
initially
registered
prior
to
November
1984)
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
to
ensure
that
they
meet
current
scientific
and
regulatory
standards.
The
process
considers
the
human
health
and
ecological
effects
of
pesticides
and
incorporates
a
reassessment
of
tolerances
(
pesticide
residue
limits
in
food)
to
ensure
that
they
meet
the
safety
standard
established
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996.

cc:
Tina
Levine
Debbie
Edwards
William
Hazel
Jill
Bloom
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY................................................................................
Page
5
of
72
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
...................
Page
9
of
72
3.0
HAZARD
CHARACTERIZATION...................................................................
Page
9
of
72
3.1
Hazard
Profile.........................................................................................
Page
9
of
72
3.2
FQPA
Considerations
............................................................................
Page
14
of
72
3.3
Dose
Response
Assessment....................................................................
Page
14
of
72
3.4
Endocrine
Disruption.............................................................................
Page
17
of
72
3.5
Potential
Hexachlorobenzene
and
Pentachlorobenzene
Contamination....
Page
18
of
72
3.6
Residues
of
Pentachlorophenol...............................................................
Page
18
of
72
4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION...........................
Page
19
of
72
4.1
Summary
of
Registered
Uses
.................................................................
Page
19
of
72
4.2
Tolerance
Reassessment.........................................................................
Page
22
of
72
4.3
Dietary
Exposure/
Risk
Pathway.............................................................
Page
24
of
72
4.3.1
Residue
Profile
........................................................................
Page
24
of
72
4.3.2
Dietary
Exposure
Assessment..................................................
Page
26
of
72
4.3.2.1
Acute
Dietary
...........................................................
Page
27
of
72
4.3.2.2
Chronic
Dietary
........................................................
Page
27
of
72
4.3.2.3
Cancer
Dietary..........................................................
Page
29
of
72
4.4
Water
Exposure/
Risk
Pathway...............................................................
Page
29
of
72
4.4.1
Environmental
Fate
.................................................................
Page
29
of
72
4.4.2
Estimated
Drinking
Water
Concentrations
(
EDWCs)...............
Page
29
of
72
4.4.3
Monitoring
Data......................................................................
Page
30
of
72
4.5
Residential
and
Other
Non­
occupational
Exposure/
Risk
Pathways
.........
Page
30
of
72
4.5.1
Home
Uses..............................................................................
Page
31
of
72
4.5.1.1
Handler.....................................................................
Page
31
of
72
4.5.1.2
Residential
Postapplication........................................
Page
32
of
72
4.5.2
Recreational
............................................................................
Page
33
of
72
4.6
Other
(
Spray
Drift;
Farm
Worker
Children,
etc.)
....................................
Page
35
of
72
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONSPage
35
of
72
5.1
Overview...............................................................................................
Page
35
of
72
5.2
Acute
Aggregate
Risk............................................................................
Page
36
of
72
5.3
Short­
Term
Aggregate
Risk...................................................................
Page
36
of
72
5.4
Intermediate­
Term
Aggregate
Risk
........................................................
Page
37
of
72
5.5
Chronic
Aggregate
Risk.........................................................................
Page
37
of
72
5.6
Cancer
Aggregate
Risk
..........................................................................
Page
37
of
72
6.0
CUMULATIVE................................................................................................
Page
38
of
72
7.0
OCCUPATIONAL
EXPOSURE.......................................................................
Page
39
of
72
7.1
Agricultural,
Seed
Treatment,
and
Non­
crop/
Utility
Uses.......................
Page
39
of
72
7.1.1
Handler
...................................................................................
Page
39
of
72
7.1.1.1
Exposure
and
Risk
Estimates
for
Agricultural
Uses
...
Page
40
of
72
7.1.1.2
Exposure
and
Risk
Estimates
for
Seed
Handlers........
Page
41
of
72
7.1.2
Postapplication
Exposures.......................................................
Page
43
of
72
7.1.2.1
Noncancer
Postapplication
Exposure
and
Risk
EstimatesPage
44
of
72
7.2
Incident
Data
.........................................................................................
Page
44
of
72
8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
.....................................................
Page
44
of
72
8.1
Toxicology
............................................................................................
Page
44
of
72
8.2
Product
Chemistry.................................................................................
Page
45
of
72
8.3
Residue
Chemistry.................................................................................
Page
45
of
72
REFERENCES.......................................................................................................
Page
45
of
72
ATTACHMENTS...................................................................................................
Page
46
of
72
APPENDIX
1
.........................................................................................................
Page
47
of
72
APPENDIX
2
.........................................................................................................
Page
56
of
72
    
5
  
73
PENTACHLORONITROBENZENE
1.0
EXECUTIVE
SUMMARY
PCNB
is
an
organochlorine
used
mainly
as
a
soil
applied,
contact
(
non­
systemic),
fungicide
for
soil
treatment
around
vegetables,
field
crops,
turf,
and
ornamentals.
PCNB
has
agricultural,
nonfood
feed,
and
residential
uses.
As
a
fungicide,
PCNB
is
effective
in
retarding
germination
and
colony
growth,
and
suppressing
sporulation.
PCNB
is
also
used
as
a
seed
treatment
for
the
control
of
soil
and
seed
borne
diseases
of
root,
leafy,
and
row
crops,
as
well
as
turf.
It
is
primarily
applied
as
a
spray,
through
sprinkler
irrigation
systems
or
granular
preparations
to
soil,
though
it
has
many
other
methods
of
application.
It
is
formulated
as
a
flowable
concentrate
(
FlC),
water
dispersible
granular
(
WDG),
wettable
powder
(
WP),
emulsifiable
concentrate
(
EC),
granular
(
G),
dust
(
D),
and
ready­
to­
use
(
RTU)
formulations.
These
products
may
be
applied
as
pre­
plant
incorporated
applications,
in­
furrow
applications,
broadcast
applications,
or
banded
applications
using
ground
equipment,
or
as
seed
treatments.

Hazard
Summary
Generally,
PCNB
has
low
acute
toxicity,
with
most
study
results
in
Toxicity
Categories
III
or
IV.
Several
studies
indicate
that
PCNB
is
a
sensitizer
while
other
available
data
provide
conflicting
information
that
it
is
not
a
sensitizer.
These
differences
might
relate
to
differences
in
impurities
associated
with
variations
in
production
batches
and
manufacturing
sites,
and/
or
differences
in
testing
methodology.
Subchronic
and
chronic
studies
indicate
that
the
thyroid
and
liver
are
the
target
organs
for
PCNB.
Limited
evidence,
such
as
increased
thyroid
stimulating
hormone
(
TSH),
and
thyroid
and
liver
hypertrophy,
suggest
that
the
thyroid
effects
may
be
due,
at
least
in
part,
to
a
disturbance
of
thyroid
homeostasis.
Aminotransferase
activities
(
AST/
ALT,
particularly
ALT)
decrease
in
a
dose­
dependent
manner
by
as
much
as
30­
80%
in
rats
and
dogs.
However,
there
are
no
data
to
evaluate
the
toxicological
significance
of
the
these
findings.
The
Agency
has
requested
that
the
registrants
address
these
issues
of
thyroid
activity
and
transaminase
enzymatic
activity.
National
Toxicology
Program
(
NTP)
genetic
toxicology
testing
indicates
that
PCNB
is
not
mutagenic
in
bacteria
or
in
cultured
mammalian
cells.
PCNB
was
negative
for
the
induction
of
Sister
Chromatid
Exchanges
(
SCE)
in
vitro.
PCNB
is
classified
as
a
Group
C­
possible
human
carcinogen
and
the
HED
management
recommended
that
for
risk
assessment
purposes,
the
Reference
Dose
(
RfD)
approach
should
be
used
for
quantification
of
human
risk.

There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
after
in
utero
exposure
(
relative
to
structural
alteration
or
developmental
delays),
or
after
pre­
or
postnatal
exposure
to
rats
in
multi­
generation
reproduction
studies.
There
are
no
findings
of
significant
toxicological
concern
identified
in
the
submitted
developmental
or
reproductive
toxicity
data.
Also,
no
neurobehavioral
alterations
nor
evidence
of
neuropathological
effects
were
observed
in
the
available
data.
Based
on
the
weight
of
evidence,
HED
management
concluded
that
a
developmental
neurotoxicity
(
DNT)
study
is
not
required
for
PCNB.
However,
HED
determined
that
the
thyroid
is
a
target
organ
of
PCNB
toxicity
and
thyroid
hormones
are
    
6
  
73
adversely
affected,
although
the
database
is
incomplete
relative
to
this
specific
assessment.
In
addition,
data
gaps
for
metabolism/
kinetic
data
further
contribute
to
the
uncertainty
of
the
risk
assessment.
Together,
these
findings
constitute
a
trigger
for
requesting
additional
data
to
allow
for
assessment
of
thyroid
function
in
adults
and
developing
offspring
for
PCNB
and
its
metabolites.
Since
adverse
effects
on
thyroid
homeostasis
at
critical
development
periods
can
affect
development
in
children,
HED
has
determined
that
the
FQPA
safety
factor
will
be
retained
at
10X
(
FQPA
SF
of
10X),
which
was
applied
to
the
dietary,
as
well
as
all
residential/
recreational
exposure
(
incidental
oral,
dermal
and
inhalation)
scenarios.

Residue
Chemistry
The
tolerance
expression
for
PCNB
includes
parent
and
the
metabolites,
pentachloroaniline
(
PCA)
and
pentachlorothioisole
(
PCTA).
However,
neither
of
the
two
major
food
monitoring
programs
analyzes
for
both
metabolites
in
every
sample
consistently
or
the
number
of
samples
that
are
analyzed
for
more
than
one
metabolite
is
generally
insufficient
(<
100)
for
use
in
the
risk
assessment
according
to
HED
guidelines.
Eighty­
four
polychlorinated
phenyl
metabolites
of
concern
have
been
identified
in
animal
and
plant
metabolism,
and
environmental
degradate
data.
The
Agency
maintains
that
due
to
insufficient
toxicity
data
on
the
metabolites
of
PCNB,
and
due
to
the
polychlorinated
nature
of
the
PCNB
metabolites,
these
metabolites
cannot
be
comfortably
ruled
out
as
being
toxic
unless
proven
otherwise
through
suitable
toxicity
data,
which
may
be
generated
by
the
registrant.
All
these
metabolites
are
included
in
the
dietary
risk
assessment.
In
order
to
estimate
the
total
residues
of
concern
(
i.
e.,
include
residues
of
all
84
metabolites),
it
was
assumed
that
the
Total
Toxic
Residue
(
TTR)
would
be
equal
to
or
less
than
the
estimated
Total
Radioactive
Residues
(
TRR)
in
each
crop,
which
includes
extractable
as
well
as
unextractable
residues.
To
estimate
the
TTR
for
each
crop,
the
monitoring
data
for
that
crop
and
the
ratio
of
TRR
to
PCNB
observed
in
the
metabolism
studies
were
used.
The
available
monitoring
data
also
showed
detected
residues
of
PCNB
and/
or
its
metabolites
in/
on
a
number
of
crops
for
which
there
is
no
registration.
Additional
data
are
required
for
a
number
of
crops.
Data
on
plant
and
animal
metabolism
studies
are
required.
Tolerances
on
livestock
commodities
need
to
be
established.

Dietary
Exposure
and
Risk
Estimates
No
adverse
effects
attributed
to
a
single
exposure
(
dose)
were
identified.
Therefore,
no
acute
dietary
risk
assessment
was
conducted.

The
chronic
dietary
risk
assessment
is
considered
to
be
a
highly
refined
assessment
using
all
available
monitoring
data,
%
crop
treated
(%
CT)
information,
and
processing
factors.
However,
because
monitoring
data
did
not
analyze
for
all
PCNB
metabolites
of
concern
(
84),
the
ratio
of
TRR
to
PCNB
from
available
metabolism
studies
in
combination
with
monitoring
residue
data
on
PCNB,
or
TRR
values
directly,
were
used
to
estimate
the
total
residues
of
concern.
Since
residues
of
PCNB
and/
or
its
metabolites
were
detected
in
monitoring
data
for
some
unsupported
(
not
registered/
without
tolerances)
food
uses,
assessments
using
the
Dietary
Exposure
Evaluation
Model­
Food
Consumption
Intake
Database
(
DEEM­
FCID)
and
Lifeline,
with
and
without
    
7
  
73
unsupported
food
uses,
were
performed.
The
chronic
dietary
risk
assessment,
for
food
alone,
shows
that
the
risks
for
all
population
subgroups
are
below
the
level
of
concern;
i.
e.,
100%
chronic
Population
Adjusted
Dose
(
cPAD),
with
and
without
nonregistered
crops.
The
highest
estimated
risks
are
for
children
1­
2
years
of
age
(
34%
cPAD),
based
on
food
consumption
alone.
The
major
contribution
to
the
risk
came
from
milk
fat,
followed
by
brassica
vegetables.

Residential/
Recreational
Exposure
and
Risk
Estimates
­
Handlers
and
Postapplication
In
residential
settings,
the
Agency
does
not
use
personal
protective
equipment
(
PPE)
to
limit
exposures,
because
they
are
viewed
as
impractical
and
not
enforceable.
Risk
estimates
are
based
on
handlers
wearing
short­
sleeved
shirts,
short
pants,
shoes,
and
socks.
No
chemical­
specific
data
are
available
for
residential/
recreational
scenarios
so,
estimates
from
available
databases
and
standard
assumptions
were
used
to
calculated
potential
exposures
along
with
using
maximum
application
rates
and
a
dermal
absorption
factor
selected
from
a
submitted
dermal
toxicity
study.
The
residential
scenarios
where
Margins
of
Exposure
(
MOEs)
do
not
meet
the
Agency's
target
MOE
of
1000,
and
therefore
are
of
concern,
include
dermal
risk
for
mixing/
loading/
applying
liquids
with
low
pressure
handwand
(
280)
and
dermal
and
inhalation
risks
for
garden
hose­
end
sprayer
and
belly
grinder
(
12).

Short­
term
postapplication
risk
estimates
resulting
from
dermal
contact
with
treated
turf
during
high
contact
lawn
activities
at
application
rates
of
32.67
lbs
active
ingredient
per
acre
(
ai/
A)
and
43.56
lbs
ai/
A
exceeded
the
level
of
concern
for
adults
(
MOE
30­
40)
and
for
children
(
MOE
82­
110).
Activities
such
as
golfing
and
mowing
lawns
treated
with
PCNB
at
application
rates
of
32.67
and
43.56
lbs
ai/
A
resulted
in
MOEs
of
430­
575
for
golfing
and
860­
1145
for
mowing,
and
exceed
HED's
level
of
concern.
Aggregating,
or
adding
residential
handler
exposure
and
postapplication
exposure
also
results
in
MOEs
below
1000.
The
risk
estimates
for
toddler's
nondietary
ingestion
of
PCNB
on
treated
turf
indicate
that
risks
exceed
HED's
level
of
concern
for
hand­
to­
mouth
transfer
(
MOE
2),
incidental
turfgrass
mouthing
(
MOE
6­
8),
and
incidental
ingestion
of
soil
(
MOE
460­
612).

Aggregate
Risk
Estimates
For
PCNB
and
its
metabolites,
quantitative
aggregate
exposure
assessments
that
include
food
+
drinking
water
+
incidental
oral/
dermal/
inhalation
exposures
were
not
performed
since
potential
exposures
and
their
associated
risks
from
individual
sources
of
exposures
were
already
of
concern,
particularly
for
children.
However,
chronic
dietary
aggregate
exposures
were
estimated
by
combining
food
and
estimated
drinking
water
exposures
(
provided
by
EFED)
directly
in
the
DEEM­
FCID
program.
They
showed
chronic
aggregate
risks
of
concern
for
all
exposed
population
subgroups,
particularly
infants
(
460%
cPAD)
and
children
1­
2
years
old
(
240%
cPAD).

Occupational
Exposure
and
Risk
Estimates
­
Handlers
and
Postapplication
    
8
  
73
No
chemical­
specific
data
are
available
for
occupational
exposure
scenarios
so,
estimates
from
available
databases
and
standard
assumptions
were
used
to
calculated
potential
exposures.
The
results
of
the
short­
and
intermediate­
term
occupational
handler
assessments
indicate
that
for
the
dry
flowable
formulation,
the
majority
of
the
potential
exposure
scenarios
result
in
total
MOE(
s)
>
the
target
MOE
of
100
at
the
baseline
clothing
attire
of
long
pants,
long
sleeved
shirts,
no
gloves,
and
no
respirator
while
using
open
systems.
For
the
liquid
formulation,
the
risk
estimates
indicate
that
in
order
for
the
mixer/
loaders
to
achieve
MOEs
of
100
for
all
uses
at
both
the
shortand
intermediate­
term
exposure
durations
that
minimum
PPE
clothing
attire
be
required
(
i.
e.,
long
pants,
long
sleeved
shirts,
chemical
resistant
gloves,
and
a
dust/
mist
respirator
while
using
open
systems).
This
is
consistent
with
the
current
label
except
for
the
need,
in
some
scenarios,
to
add
an
organic
vapor
respirator.
The
risk
estimates
for
the
majority
of
uses
with
the
wettable
powder
formulation
are
not
of
concern
(
clothing
attire
of
long
pants,
long
sleeved
shirts,
chemical
resistant
gloves,
and
no
respirator).
However,
the
risk
estimates
indicate
that
in
order
for
the
mixer/
loaders
of
wettable
powders
to
achieve
MOEs
of
100
for
all
uses
at
both
the
short­
and
intermediate­
term
durations
that,
for
some
uses,
PCNB
should
be
packaged
in
water
soluble
packets.
The
dust
formulation
was
only
used
for
seed
treatment
and
has
acceptable
risks.

The
results
of
the
short­
and
intermediate­
term
seed
handler
assessments
indicate
that,
for
all
formulations,
the
majority
of
the
potential
exposure
scenarios
result
in
total
MOEs
>
100
with
long
pants,
long
sleeved
shirts,
gloves,
and
no
respirator
while
using
open
systems.
Seed
handlers
working
in
a
smaller
facility,
performing
multiple
activities,
might
require
a
respirator
to
reduce
exposures
so
that
potential
risks
(
MOEs)
would
be
>
100
and
not
of
concern.

There
is
a
low
potential
for
occupational
postapplication
exposure
when
used
as
a
pre­
plant
or
at
planting
fungicide.
Therefore,
HED
does
not
require
a
postapplication
assessment
for
seed
treatment
or
agricultural
uses.
However,
the
Agency
has
determined
that
there
are
potential
postapplication
exposures
to
individuals
re­
entering
PCNB
treated
areas
for
the
purpose
of
golf
course
and
turf
maintenance.
Available
databases,
standard
assumptions,
and
submitted
transferable
residue
values
were
used,
and
adjusted
when
needed,
to
estimate
potential
postapplication
exposures.
The
short­
and
intermediate­
term
estimated
risks
to
golf
course
workers
or
sod
growers
doing
hand
harvesting
on
day
zero
result
in
MOEs
>
the
target
MOE
of
100
and
do
not
exceed
HED's
level
of
concern
at
the
32.67
and
43.56
lb
ai/
A
application
rates.

A
number
of
accidental
human
poisonings
from
exposure
to
PCNB
in
both
occupational
and
residential
settings
have
been
reported.
Though
the
data
from
these
sources
often
lacked
specific
information
on
the
extent
of
exposure
and
the
circumstances
of
exposure,
the
incidence
information
indicate
definite
poisoning
risks
from
misuse
of
products
that
contain
PCNB,
e.
g.
from
not
wearing
PPE.
    
9
  
73
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.

Kinard.
December
14,
2004.

Chemical
Name:
Pentachloronitrobenzene,
PCNB
CAS
Number:
82­
68­
8
Empirical
Formula:
C6Cl5NO2
Molecular
Weight:
295.3
Specific
Gravity:
1.718
Boiling
Point:
328
°
C
Melting
Point:
142­
145
°
C
Vapor
Pressure:
1.13
x
10­
4
mmHg
Water
solubility:
440
ppb
3.0
HAZARD
CHARACTERIZATION
PCNB
(
PC
Code
056502)­
Revised
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
(
RED).
Laurence
D.
Chitlik,
January
7,
2005;
Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
Briefing
Memorandum
to
Metabolism
Assessment
Review
Committee
to
discuss
PCNB
residues
of
concern
for
inclusion
in
dietary
risk
assessment.
Chemical
056502.
Mohsen
Sahafeyan
&
Laurence
Chitlik.
April
8th,
2003.

3.1
Hazard
Profile
Generally,
PCNB
has
low
acute
toxicity,
with
most
study
results
in
Toxicity
Categories
III
or
IV.
Several
studies
indicate
that
PCNB
is
a
sensitizer
while
other
available
data
provide
conflicting
information
that
it
is
not
a
sensitizer.
These
differences
might
relate
to
differences
in
impurities
associated
with
variations
in
production
batches
and
manufacturing
sites,
and/
or
differences
in
testing
methodology.
Though
information
in
the
published
literature
indicates
that
PCNB
undergoes
extensive
biotransformation
in
mammals,
there
is
uncertainty
as
to
its
biological
halflife
and
thus,
as
to
its
potential
for
bioaccumulation.
Data
in
the
literature
suggest
that
its
half­
life
might
be
relatively
short
at
low
doses
and
higher
at
higher
doses.
The
registrants
have
been
asked
to
address
the
issue
of
biological
half­
life
and
therefore,
the
potential
for
bioaccumulation.
    
10
  
73
Table
1a.
Acute
Toxicity
(
Uniroyal/
Crompton)

Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
870.1100
Acute
Oral
43198201
LD50
=
>
5000
mg/
kg
IV
870.1200
Acute
Dermal
43198202
LD50
=
>
5000
mg/
kg
IV
870.1300
Acute
Inhalation
43118201
LC50
=
>
1.7
mg/
L
III
870.2400
Primary
Eye
Irritation
43198203
Slight
irritant
III
870.2500
Primary
Skin
Irritation
43198204
Non
irritant
IV
870.2600
Dermal
Sensitization
40609001
Weak
sensitizer
870.6200
Acute
Neurotoxicity
NA
Table
1b.
Acute
Toxicity
(
Amvac)

Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
870.1100
Acute
Oral
41443101
LD50
=
>
5050
mg/
kg
IV
870.1200
Acute
Dermal
41443102
LD50
=
>
2020
mg/
kg
III
870.1300
Acute
Inhalation
41443103
LC50
=
>
6.49
mg/
L
III
870.2400
Primary
Eye
Irritation
41443104
Slight
irritant
III
870.2500
Primary
Skin
Irritation
41443105
Non
irritant
IV
870.2600
Dermal
Sensitization
45236401
40734001
Sensitizer
Non­
sensitizer
870.6200
Acute
Neurotoxicity
NA
Subchronic
and
chronic
studies
indicate
that
the
thyroid
and
liver
are
target
organs
for
PCNB.
Limited
evidence
(
increased
TSH,
and
thyroid
and
liver
hypertrophy)
suggest
that
the
thyroid
effects
may
be
due,
at
least
in
part,
to
a
disturbance
of
thyroid
homeostasis.
Aminotransferase
activities
(
AST/
ALT,
particularly
ALT)
decrease
in
a
dose­
dependent
manner
by
as
much
as
30­
80%
in
rats
and
dogs.
However,
the
available
data
are
inadequate
to
evaluate
the
toxicological
significance
of
these
findings.
The
registrants
are
requested
to
address
these
issues
of
thyroid
activity
and
aminotransferase
enzymatic
activity.
    
11
  
73
TABLE
2.
SUBCHRONIC/
CHRONIC
TOXICITY
PROFILE
DER#
MRID/
SPONSOR
Study
Type
&
Dose
Levels
*
NOAEL
(
mg/
kg/
day)
**
LOAEL
(
mg/
kg/
day)

1
41987301
UNIROYAL
2­
Yr.
Chronic
Toxicity/
Carcinogenicity
Feeding
­
Rat
(
1991)
0,
1,
150,
300
mg/
kg/
day
(_/_)
Systemic:
1
Systemic:
150
Based
on
an
increase
in
hepatocellular
hypertrophy,
hepatocellular
hyperplasia
(_)
&
thyroid
hypertrophy
&
hyperplasia
Increase
in
thyroid
follicular
cell
adenomas
&
carcinomas
in
_
at
150
&
300
(
p<
0.05)
&
_
trend
only.

2
43015801
AMVAC
2­
Yr.
Chronic
Toxicity/
Carcinogenicity
Gavage
­
Rat
(
1993)
0,
3.6,
36,
357,
714
mg/
kg/
day
(_/_)
3.6
_
36
_
36
_,
357
_
Hepatocellular
hypertrophy
&
the
thyroid
follicular
cell
hypertrophy/
hyperplasia.
Negative
for
neoplasia.

3
45609101
NTP
TR325
2­
Yr.
Carcinogenicity
in
Mice
(
1987).
0,
400,
&
1000
mg/
kg/
day
_
0,
600
&
1400
mg/
kg/
day
_
No
increased
neoplasia
but
reduced
survival
decreased
sensitivity
of
study.

4
41718600
&
41718601
UNIROYAL
1
Yr.
Chronic
Toxicity
Feeding
­
Dog
(
1993).
0,
0.375,
3.75,
&
37.5
mg/
kg/
day
(
used
dog
conversion
factor)
(_/_)
3.75
37.5
based
on
increased
serum
ALP
and
cholesterol,
increased
liver
weight
and
hepatocellular
hypertrophy.

5
43469301,
43469302,
43469303
AMVAC
2­
Generation
Reproduction
­
Rat
(
1994)
0,
10,
100,
1000
mg/
kg/
day
10
_
100
_
100
_,
1000_
based
on
increases
in
hepatocellular
hypertrophy
&
thyroid
follicular
cell
hypertrophy/
hyperplasia.

6
41918701
UNIROYAL
2­
Generation
Reproduction
­
Rat
(
1991).
0,
1.2,
169,
344
(_)
&
0,
1.5,
218,
455
(_)
Parental:
1.2
_,
1.5
_
Repro/
Dev:
1.2
Parental:
169_,
218_
based
on
decreased
body
weight
and
weight
gain.
Repro/
Dev:
169
based
on
decreased
mean
pup
weights.

7
40588601
UNIROYAL
Developmental
Tox
Gavage
­
Rat
(
1988).
0,
30,
600,
1200
mg/
kg/
day
Maternal:
>
1200
Develop:
>
1200
Maternal
>
1200
(
HDT)
Develop
>
1200
(
HDT)

8
41361301
AMVAC
Developmental
Tox
Gavage
­
Rabbit
(
1989).
0,
100,
300,
&
900
mg/
kg/
day
Maternal:
300
Develop:
>
900
Maternal:
900
based
on
clinical
signs
of
toxicity,
decreased
body
weight
gain
&
food
consumption,
abortions
&
premature
delivery
Develop:
>
900
(
HDT)

9
40717102
UNIROYAL
Developmental
Tox
Gavage
­
Rabbit
(
1988).
0,
6.25,
12.5,
125,
&
250
mg/
kg/
day
Maternal:
12.5
Develop:
125
Maternal:
125
based
on
decreased
maternal
body
weight
&
body
weight
gain.
Develop:
250
based
on
decreased
fetal
weights.
    
12
  
73
10
41361201
AMVAC
Developmental
Tox
Gavage
­
Rat
(
1989).
0,
250,
750,
&
1500
mg/
kg/
day
Maternal:
>
1500
Develop:
>
1500
Maternal:
>
1500
Develop:
>
1500
Small
increases
in
incidences
of
thoracic
vertebrae/
fetus
seen
at
750
but,
no
dose­
response,
not
considered
biologically
significant
&
not
seen
in
any
other
study.

11
42630801
UNIROYAL
7,
14,
30
or
90­
Day
Subchronic
­
Male
Rat
(
1993).
Non­
guideline
0,
1.0,
&
333
mg/
kg/
day
<
1.0
(
90
days)
1.0
(
90
days)
based
on
liver
&
thyroid
hypertrophy.
After
14
&
30
days:
thyroid
follicular
epithelial
hypertrophy
observed
at
333
(
HDT).

12
42416001
AMVAC
13­
Week
Subchronic
Gavage
­
Rat
(
1992).
0,
5,
10,
100,
or
1000
mg/
kg/
day
_/_
100
(_/_)
1000
(_/_)
based
on
increased
relative
(
to
body)
liver
wt.
&
histopathological
changes
in
the
liver
&
thyroid.

13
42413901,
42713401
&
42713402
UNIROYAL
21­
Day
Dermal
­
Rat
(
1992).
0,
30,
300,
or
1000
mg/
kg/
day
(_/_)
Systemic:
>
1000
Systemic:
>
1000
(
HDT)

14
42416002
AMVAC
21­
Day
Dermal
­
Rat
(
1992).
0,
100,
300
&
1000
(_/_)
300
1000
based
on
the
increased
incidences
of
dilatation
of
the
thyroid
follicles
&
hypertrophy
of
the
thyroid
follicular
epithelium
in
_.
No
reported
treatment
related
effects
in
_.

15
255226/
250698
SYNGENTA/
SYNGENTA
TECHNICAL
Skin
Penetration
Study
of
Olin's
Terraclor
Formulations
(
1983).
(
20%
Dust
&
75%
WP)
Approx.
30%
recovery
after
5
days
&
only
1­
2%
after
4
hr.
exposure
N/
A
16
44096601
UNIROYAL
Metabolism
­
Special
Non­
Guideline
­
Rat
(
1996).
N/
A
N/
A
17
44096602
UNIROYAL
Metabolism
­
Special
Non­
Guideline
­
Rat
(
1996).
N/
A
N/
A
*
NOAEL
=
No
Observable
Adverse
Effect
**
LOAEL
=
Lowest
Observable
Adverse
Effect
HDT
=
Highest
Dose
Tested
In
a
21­
day
dermal
toxicity
study
in
rats,
dilation
of
the
thyroid
follicles
and
hypertrophy
of
the
thyroid
follicular
epithelium
were
observed
at
the
highest
dose
tested
(
1000
mg/
kg/
day)
in
males
only.
These
changes
were
not
observed
in
any
of
the
other
dose
groups,
including
controls,
or
in
any
females,
nor
were
any
other
treatment­
related
effects
observed.
The
NOAEL
is
300
mg/
kg/
day.

No
inhalation
toxicity
studies
are
available.
Absorption
by
the
inhalation
route
is
considered
to
be
    
13
  
73
equivalent
to
absorption
by
the
oral
route.

No
findings
of
significant
toxicological
concern
were
identified
in
the
submitted
developmental
or
reproductive
toxicity
data.
No
neurobehavioral
alterations
nor
evidence
of
neuropathological
effects
were
observed
in
the
available
data.
There
was
no
indication
of
increased
susceptibility
in
these
studies.
Due
to
concerns
for
the
potential
impact
of
PCNB
exposure
on
the
function
of
the
thyroid
as
evidenced
by
the
increases
in
thyroid
weights
and
the
changes
noted
in
TSH,
T3,
and
T4,
noted
in
the
PCNB
database,
a
comparative
thyroid
assay
in
young
and
adult
rats
which
includes
hormonal
measurements
for
thyroid
function
is
required.
This
request
stems
from
concerns
regarding
the
possible
impact
of
perturbations
of
thyroid
function
on
the
development
of
the
young.

There
is
no
indication
of
immunotoxicity
at
this
time.
However,
effects
on
thyroid
function
have
been
reported
in
a
number
of
studies
submitted
to
the
Agency.
Data
are
required.
There
is
no
evidence
that
PCNB
is
neurotoxic.
Therefore,
acute
delayed
neurotoxicity,
acute
and
subchronic
neurotoxicity
studies,
and
a
DNT
study
are
not
required
(
at
this
time).

Although
data
are
available
to
demonstrate
a
hormonal
mechanism
of
action
for
PCNB,
data
are
insufficient
to
fully
characterize
the
hazards
at
this
time.
Results
from
the
NTP
genetic
toxicology
testing
(
NTP
TR
325,
1987
submitted
as
MRID#
45609101),
indicate
that
PCNB
(
lot
and
%
ai
not
specified)
is
not
mutagenic
in
bacteria
or
in
cultured
mammalian
cells.
There
is
suggestive
in
vitro
evidence
showing
that
PCNB
is
clastogenic
in
the
absence
of
S9
activation
and
equivocal
in
the
presence
of
S9
activation.
However,
in
a
more
definitive
erythrocyte
mouse
micronucleus
assay
(
MRID#
45539601),
PCNB
was
not
shown
to
be
clastogenic.
PCNB
was
also
negative
for
the
induction
of
SCEs
in
vitro.
The
carcinogenicity
of
PCNB
was
assessed
in
reviews
of
1977
(
special
review),
and
in
1986
and
1992
(
Second
Carcinogenicity
Peer
Review
of
PCNB.
Pamela
Hurley
and
Esther
Rinde.
December
18,
1992).
In
1992,
the
Cancer
Peer
Review
Committee
(
CPRC)
classified
PCNB
as
a
Group
C­
possible
human
carcinogen
and
recommended
that
for
the
purpose
of
risk
characterization,
the
RfD
approach
should
be
used
for
quantification
of
human
risk.

Although
a
rat
metabolism
study
has
been
identified
as
a
significant
data
gap,
several
nonguideline
and
unacceptable
(
but
potentially
upgradable)
rat
metabolism
studies
have
been
submitted
to
the
Agency.
Both
the
guideline
metabolism,
and
special
biological
half­
life
and
bioaccumulation
studies,
are
required
and
are
considered
data
gaps.
Data
from
a
series
of
limited
single­
and
repeated­
dose
Rhesus
monkey
studies
suggest
that
PCNB
bioaccumulates
in
mammals.
In
this
same
series,
it
was
noted
that
both
the
biliary­
fecal
and
renal­
urinary
routes
were
utilized
for
the
excretion
of
PCNB
and
its
metabolites,
with
a
slight
preference
for
the
fecal
route.
The
limited
data
in
rats,
monkeys,
and
dogs
that
are
available
suggest
that
generally
it
is
the
metabolites
that
are
accumulated
within
tissues
to
a
greater
extent
than
parent
PCNB
itself.
    
14
  
73
3.2
FQPA
Considerations
There
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
after
in
utero
exposure
(
relative
to
structural
abnormalities
and
developmental
delays),
or
after
pre­
or
postnatal
exposure
to
rats
in
multigeneration
reproduction
studies.
Acceptable
developmental
toxicity
studies
in
rats
and
rabbits,
and
reproductive
toxicity
studies
are
available
and
adequate
for
FQPA
considerations.
Based
on
the
weight
of
evidence,
a
DNT
study
is
not
required
for
PCNB.
However,
due
to
adverse
effects
on
the
thyroid
observed
in
adults
[
organ
weights,
neoplastic
and
non­
neoplastic
histopathology
and
hormonal
effects
(
TSH,
T3
and
T4)]
a
trigger
has
been
exceeded
requiring
an
assessment
for
potential
functional
deficit
associated
with
the
development
of
offspring.
In
addition,
a
data
gap
for
metabolism/
kinetic
data
creates
further
uncertainty
relative
to
this
issue
since
the
potential
for
bioaccummulation
of
PCNB
and
metabolites
exists.
Specifically,
a
comparative
thyroid
assay
in
young
and
adult
rats
which
includes
hormonal
measurements
for
thyroid
function,
is
required
supported
by
adequate
metabolism
and
kinetic
data
including
half­
life
and
steady
state
data.

The
absence
of
these
data
(
specifically
comparative
thyroid
and
pharmacokinetic
data),
the
adverse
effects
on
thyroid
function
observed
in
the
current
data
base,
and
the
concern
for
adverse
effects
on
thyroid
function
and
the
potential
for
associated
adverse
effects
during
critical
periods
of
development,
resulted
in
the
Agency
retaining
the
FQPA
safety
factor
of
10X
(
FQPA
SF
of
10X),
which
was
applied
to
the
dietary,
as
well
as
all
residential/
recreational
exposure
(
incidental
oral,
dermal
and
inhalation)
scenarios.
The
10X
FQPA
SF
is
required
since
the
available
data
provide
no
basis
to
support
reduction
or
removal
of
the
default
10X
factor.

3.3
Dose
Response
Assessment
No
adverse
effects
attributed
to
a
single
exposure
(
dose)
were
identified,
including
in
the
rat
or
rabbit
developmental
toxicity
studies.
Therefore,
no
acute
dietary
endpoint
was
selected.
Subchronic
and
chronic
studies
indicate
that
the
thyroid
and
liver
are
target
organs
for
PCNB.

The
chronic
dietary,
long­
term
dermal,
and
long­
term
inhalation
endpoints
were
selected
from
the
chronic/
oncogenicity
feeding
study
in
rats
based
on
hepatocellular
hypertrophy,
hepatocellular
hyperplasia,
and
thyroid
hypertrophy
observed
at
150
mg/
kg/
day
(
NOAEL
1.0
mg/
kg/
d).
The
FQPA
SF
of
10X
was
applied,
as
well
as
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variability,
for
a
total
UF
of
1000.
Therefore,
the
chronic
reference
Dose
(
RfD)
is
1
mg/
kg/
day
÷
1000
=
0.001
mg/
kg/
day.

The
short­
term
(
1­
30
days)
incidental
oral
and
inhalation
endpoints
were
selected
from
the
90­
day
subchronic
feeding
study
in
male
rats
based
on
thyroid
follicular
epithelial
hypertrophy
observed
at
333
(
HDT)
mg/
kg/
day
after
14
and
30
days
(
NOAEL
=
1.0
mg/
kg/
day).
The
residential/
recreational
Level
of
Concern
(
LOC)
is
1000
based
on
FQPA
SF
of
10X,
10X
for
interspecies
extrapolation,
and
10X
for
intraspecies
variability.
An
LOC
of
100,
based
on
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variability,
is
adequate
for
occupational
    
15
  
73
exposures
(
see
Table
3).

The
intermediate­
term
(
1­
6
months)
incidental
oral
and
inhalation
endpoints
were
also
selected
from
the
subchronic
feeding
study
in
male
rats.
The
LOAEL
is1.0
mg/
kg/
day
based
on
liver
and
thyroid
hypertrophy
seen
at
90
days
(
NOAEL
=
<
1.0
mg/
kg/
day).
For
a
summary
of
the
LOCs,
or
target
margins
of
exposure
(
MOEs)
for
risk
assessment,
see
the
table
below.

The
short­
and
intermediate­
term
dermal
endpoints
were
selected
from
the
21­
day
dermal
toxicity
study
in
rats
based
on
hypertrophy
of
the
thyroid
follicular
epithelium
and
dilation
of
the
thyroid
follicles
in
males
only
observed
at
1000
mg/
kg/
day
(
NOAEL
=
300
mg/
kg/
day).

TABLE
3.
LEVEL
OF
CONCERN
(
LOC)

Route
D
uratio
n
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1
­
6
Months)
Long­
Term
(>
6
Months)

Occupational
(
Worker)
Exposure
Dermal
100
100
100
Inhalation
100
100
100
Residential/
Recreational
Exposure
Oral
1000
1000
N/
A
Dermal
1000
1000
1000
Inhalation
1000
1000
1000
Current
HED
policy
requires
that
FQPA
safety
factors
be
retained
for
dietary
and
nonoccupational
exposures,
when
appropriate,
not
occupational
exposures
(
Memorandum,
Special
Report
of
the
FQPA
Safety
Factor
Committee,
B.
Tarplee
and
J.
Rowland,
April
15,
1998).
Therefore,
an
MOE
of
>
100
is
needed
in
the
occupational
exposure
risk
assessment.

Though
a
dermal
penetration
study
was
available,
it
was
not
considered
acceptable
for
risk
assessment
purposes.
An
estimation
of
dermal
absorption
of
33%
was
extrapolated
using
the
systemic
LOAEL
of
333
mg/
kg/
day
from
the
subchronic
oral
toxicity
study
in
male
rats
and
the
LOAEL
of
1000
mg/
kg/
day
from
the
21­
day
dermal
toxicity
study
in
the
rat:
the
ratio
is
333/
1000
or
33%.
It
was
noted
that
thyroid
toxicity
was
the
common
toxic
effect
seen
via
both
routes
in
the
same
species.
Absorption
by
the
inhalation
route
was
considered
to
be
equivalent
to
absorption
by
the
oral
route.
    
16
  
73
Table
4.
Summary
of
Toxicology
Endpoint
Selection
EXPOSURE
SCENARIO
DOSE
(
mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
No
appropriate
endpoint
attributed
to
a
single
dose
was
identified.
Therefore,
an
acute
RfD
was
not
established.

Systemic
toxicity
LOAEL
=
150
mg/
kg/
day,
based
on
hepatocellular
hypertrophy,
hepatocellular
hyperplasia
(
females)
and
thyroid
hypertrophy
and
hyperplasia.
Combined
chronic
toxicity/
carcinogenicity
study
in
rats
MRID#
41987301
Chronic
Dietary
NOAEL
=
1.0
UF
=
100
FQPA
SF
=
10X
Chronic
RfD
=
0.01
mg/
kg/
day
cPAD1=
0.001
mg/
kg/
day
NOAEL=
1.0
UF
=
100
FQPA
SF
=
10X
Based
on
thyroid
follicular
epithelial
hypertrophy
observed
at
333
(
LOAEL)
after
14
&
30
days.
Nonguideline
90­
day
subchronic
oral
toxicity
study
in
male
rats
MRID#
42630801
Incidental
Oral,
Short
(
1­
30
days)­
Term
LOC
for
residential
MOE
=
1000
NOAEL=
<
1.0
UF
=
100
FQPA
SF
=
10X
LOAEL
is
1.0
mg/
kg/
day
based
on
liver
&
thyroid
hypertrophy
at
90
days.
Nonguideline
90­
day
subchronic
oral
toxicity
study
in
male
rats
MRID#
42630801
Incidental
Oral,
Intermediate
(
1­
6
months)­
term
LOC
for
residential
MOE
=
1000
NOAEL
=
300
UF
=
100
FQPA
SF
=
10X
LOAEL
is
1000
mg/
kg/
day
based
on
hypertrophy
of
the
thyroid
follicular
epithelium
and
dilation
of
the
thyroid
follicles
in
males
only.
21­
Day
dermal
toxicity
study
in
male
and
female
rats
MRID#
42416002
Dermal,
Short
(
1­
30
days)­
&
Intermediate
(
1­
6
months)­
Term
LOC
for
residential
MOE
=
1000
LOC
for
occupational
MOE
=
100
NOAEL
=
1.0
UF
=
100
FQPA
SF
=
10X
Systemic
toxicity
LOAEL
=
150
mg/
kg/
day,
based
on
hepatocellular
hypertrophy,
hepatocellular
hyperplasia
(
females)
and
thyroid
hypertrophy
and
hyperplasia.
Chronic
toxicity/
carcinogenicity
study
in
rats
MRID#
41987301
Dermal,
Long­
Term
(
6
months
to
life­
time)

Absorption
factor
33%
used
for
conversion
from
oral
to
dermal
route
LOC
for
residential
MOE
=
1000
LOC
for
occupational
MOE
=
100
NOAEL=
1.0
UF
=
100
FQPA
SF
=
10X
Based
on
thyroid
follicular
epithelial
hypertrophy
observed
at
333
(
LOAEL)
after
14
&
30
days.
Nonguideline
90­
day
subchronic
oral
toxicity
study
in
male
rats
MRID#
42630801
Inhalation,
Short
(
1­
30
days)­
Term
LOC
for
residential
MOE
=
1000
LOC
for
occupational
MOE
=
100
Inhalation,
NOAEL=
<
1.0
LOAEL
is
1.0
mg/
kg/
day
based
on
liver
&
Nonguideline
90­
day
subchronic
    
17
  
73
UF
=
100
FQPA
SF
=
10X
thyroid
hypertrophy
at
90
days.
oral
toxicity
study
in
male
rats
MRID#
42630801
Intermediate
(
1­
6
months)­
Term
LOC
for
residential
MOE
=
1000
LOC
for
occupational
MOE
=
100
NOAEL
=
1.0
UF
=
100
FQPA
SF
=
10X
Systemic
toxicity
LOAEL
=
150
mg/
kg/
day,
based
on
hepatocellular
hypertrophy,
hepatocellular
hyperplasia
(
females)
and
thyroid
hypertrophy
and
hyperplasia.
Chronic
toxicity/
carcinogenicity
study
in
rats
MRID#
41987301
Inhalation,
Long­
Term
(
6
months
to
life­
time)

LOC
for
residential
MOE
=
1000
LOC
for
occupational
MOE
=
100
Group
C
­
Possible
human
carcinogen
Combined
incidence
of
thyroid
follicular
cell
adenomas
&
carcinomas
significantly
increased
in
males
but
not
females,
with
a
significant
trend
in
both
sexes.
Chronic
toxicity/
carcinogenicity
study
in
rats
MRID#
41987301
Cancer
Q1*
not
calculated
(
not
required)

1
PAD
=
acute
or
chronic
RfD
FQPA
safety
factor
3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
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
scientific
bases
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
PCNB,
the
data
are
inadequate
to
fully
appropriately
assess
the
thyroid
effects
observed
in
animal
studies.
Comparative
thyroid
data
are
requested.
When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
PCNB
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
    
18
  
73
3.5
Potential
Hexachlorobenzene
and
Pentachlorobenzene
Contamination
Hexachlorobenzene
(
HCB)
and
pentachlorobenzene
(
PCB)
are
manufacturing
impurities
in
technical
pentachloronitrobenzene
(
PCNB).
During
a
special
review
in
the
1980s
of
PCNB,
it
was
concluded
that
the
most
likely
cause
of
any
adverse
effects
of
PCNB
was
due
to
the
presence
of
the
impurities.
The
Agency
entered
into
an
agreement
with
the
manufacturers
to
reduce
the
amount
of
one
of
these
impurities,
HCB,
in
the
technical
grade
PCNB
to
0.5%
by
April
1983,
and
to
0.1%
by
April
1988
(
47
FR
18177).

Both
HCB
and
PCB
are
considered
by
the
Agency
to
be
possible
human
carcinogens
(
B2
carcinogens).
In
1994,
the
Agency
expressed
its
concern
to
Amvac
and
Uniroyal
[
Letters
dated
October
4,
1994.
Jack
Housenger
to
Jeannie
K.
Smith
(
Amvac),
Jack
Housenger
to
W.
F.
Cummings
(
Uniroyal)]
about
cancer
risks
from
the
manufacturing
impurities,
HCB
and
PCB.
The
Agency
sought
to
establish
a
maximum
allowable
level
of
HCB
at
0.05%
and
0.01%
for
PCB.
Both
registrants
complied
with
the
changes
and
subsequent
formulations
of
PCNB
contained
HCB
and
PCB
contamination
levels
at
or
below
the
new
allowable
limits.

Based
on
these
limits,
and
the
registrants'
efforts
to
keep
contamination
levels
below
these
levels,
HED
has
determined
that
the
potential
for
HCB
or
PCB
contamination
should
not
result
in
risks
of
concern.
However,
the
toxicological
hazards/
risks
relative
to
other
contaminants
in
PCNB
are
not
well
understood
and
their
presence
should
also
be
reduced
to
a
minimum.

3.6
Residues
of
Pentachlorophenol
Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.
Kinard.
December
14,
2004;
Pentachloronitrobenzene,
Second
Revised
Drinking
Water
Assessment:
New
Tier
2
Drinking
Water
EDWCs
for
Use
in
the
Human
Health
Risk
Assessment.
D291286.
Cheryl
A.
Sutton.
July
15,
2004;
Pentachlorophenol
­
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
Jess
Rowland.
December
8,

1997.

Residues
of
free
pentachlorophenol
(
PCP),
a
known
carcinogen,
and
conjugated
PCP
were
found
in
some
crops,
and
were
detected
in
a
submitted
anaerobic
soil
metabolism
study
and
a
submitted
terrestrial
field
dissipation
study.
With
one
exception,
the
conjugated
PCP
residues
in
crops
were
thiol
compounds
that
are
not
expected
to
form
the
phenol
during
metabolism/
degradation.
Of
potential
concern,
because
it
may
cleave
to
form
PCP,
is
PCP­
glycoside
(
PCP­
Gly)
that
was
found
in
potato
callus
and
peels
in
an
early,
inadequate,
metabolism
study
(
MRID#
41562903).
In
a
more
recent,
adequate,
potato
metabolism
study,
callus
and
peels
were
not
sampled
separately,
but
no
PCP­
Gly
was
found
in
any
potato
samples.
Although,
PCP­
Gly
was
not
found
in
the
later,
submitted
adequate
potato
metabolism
study,
the
first
study
can
not
be
dismissed
since
the
inadequacy
of
the
study
was
decided
on
based
on
other
aspects
of
that
study,
and
the
second
study
did
not
sample
callus
or
peels
separately.
Free
PCP
was
detected
in
a
rotational
crop
study
on
turnip
one
year
following
soil
treatment
at
10
or
2
lbs
ai/
A.
The
concentrations
were
<
0.001
ppm
in
tops
and
<
0.004
ppm
in
roots.
In
the
case
of
the
rotational
crop
study,
PCNB
is
not
registered
for
use
on
turnips,
but
turnips
were
rotated
into
a
field
where
crops
were
    
19
  
73
treated
with
PCNB.
Free
PCP
was
not
found
in
any
other
crop
studies
nor
in
any
other
environmental
fate
studies.
Its
source
is
unknown.

PCP
is
a
general
biocide
which
is
used
extensively
in
the
United
States
as
a
wood
preservative.
While
it
appears
from
the
published
literature
that
PCP
can
be
formed
from
PCNB
during
microbial
degradation
in
soil
(
see
revised
EFED
chapter),
the
weight
of
evidence
is
not
substantial
and
conclusions
on
when
(
i.
e.,
under
what
environmental
conditions)
PCP
can
be
expected
to
form
in
the
environment
cannot
be
validly
drawn.
Based
on
the
currently
available
information,
EFED
believes
that
there
is
not
sufficient
evidence
that
PCP
will
routinely
be
formed
from
PCNB
in
the
environment.
Information
on
the
microbial
metabolism
of
PCNB
in
both
aerobic
and
anaerobic
soil/
water
systems
is
necessary
for
a
more
complete
evaluation
of
the
potential
for
the
formation
of
PCP
resulting
from
the
use
of
PCNB.
Also
of
potential
use
would
be
additional
field
dissipation
studies
in
which
PCP
is
actually
monitored
as
a
potential
degradate.
Though
it
has
been
suggested
that
detection
of
PCP
in
field
studies
is
due
to
historical
use,
this
theory
is
not
supported
by
the
data.
In
a
terrestrial
field
dissipation
study
(
MRID
43061501)
submitted
to
EFED,
a
clear
pattern
of
increasing
and
decreasing
levels
of
PCP
was
seen,
which
does
not
support
the
notion
that
residues
were
present
prior
to
the
time
the
study
was
conducted.
Based
on
both
HED's
and
EFED's
analysis
of
the
PCP­
related
data,
there
is
insufficient
information
or
cause
to
conduct
a
robust
quantitative
risk
assessment
for
PCP
at
this
time.
However,
a
"
worst
case"
analysis
was
conducted
assuming
potential
residues
of
PCP
in
all
tuber
crops
and
using
the
recently
revised
Q1*
(
3/
4
scaling
factor)
of
0.07
x
10­
1
mg/
kg­
day.
Under
these
circumstances,
the
potential
risk
may
be
5
x
10­
8
(
general
population),
which
is
not
of
concern.

4.0
EXPOSURE
ASSESSMENT
AND
CHARACTERIZATION
4.1
Summary
of
Registered
Uses
Pentachloronitrobenzene
(
PCNB):
Revised
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document.
D291283.
Seyed
Tadayon.
November
15,
2004;
Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.
Kinard.
December
14,
2004.

PCNB
is
an
organochlorine
fungicide
used
for
seed
and
soil
treatments
at
planting.
Products
containing
PCNB
are
used
in
both
occupational
and
residential/
recreational
settings.
Registered
use
sites
include,
beans,
brassica
crops,
cotton,
garlic,
hot
pepper,
peanut,
pepper,
potato,
tomatoes,
seed
treatment,
ornamental
plants,
cut
flowers,
dormant
roses
and
bulbs,
magnolia
tree,
southern
pine
seedlings
and
turf.

PCNB,
has
trade
names
including
Terraclor,
Terraclor
Super
X,
Quintozene,
and
Turfcide.
The
common
fungi
controlled
by
PCNB
are;
black
root
(
Corticium
solani),
black
rot
of
bulbs
(
Sclerotinia),
Camellia
flower
blight
(
Sclerotinia),
club
root
(
Plasmodiophora),
common
bunt/
stinking
smut
(
Tilletia
foetida/
T.
caries)
of
wheat,
leaf
spots,
loose
smut
of
oat
(
Ustilago
avenae),
melting
out
(
Drechslera
poae),
melting­
out
(
Helminthosporium),
neck
rot
(
Stromatinia/
sclerotinia),
and
needle
blight
(
Dothistroma).
    
20
  
73
Table
5:
Use
Patterns,
Application
Rate,
and
Frequency
of
Application
for
PCNB
Crops
Application
Rate
lb
ai/
acre
Frequency
of
Timing
of
Application
Agricultural
Usage
Patterns
Beans:
Bush
Beans
Dry/
green
+
bush/
pole
Dry/
succulent/
snap
Not
specified
Pole
Beans
Snap/
Dry
+
Bush
Snap/
Dry
+
Pole
1.5
to
2.1
lbs
ai/
A
1.1
1.1
to
1.5
1.36
to
1.5
1.5
to
2.1
1.5
to
2.1
1.7
to
2.1
At
planting
Brassica
Crops:
Broccoli,
Brussels
Sprouts,
Cabbage,
Cauliflower,
Chinese
Broccoli,
Chinese
Cabbage,
Collards,
Kale,
Mustard
Greens
30
lbs
ai/
A
(
Transplant
solutions:
4.5
lbs
ai/
A)
Pre
planting
or
at
planting
Cotton
Cotton
Seedling
0.93
to
2.1
lbs
ai/
A
0.3
to
1.5
At
planting
Garlic
(
in
furrow
and
clove
mist
spray)
20
to
20.6
lbs
ai/
A
at
planting
Hot
peppers
1.3
to
1.5
lbs
ai/
A
At
planting
Peanuts
2
to
10
lbs
ai/
A
(
plus:
aircraft
­
10
lb
ai/
A)
At
planting
and
early
pegging
Peppers
7.2
to
7.5
lbs
ai/
A
Transplant
Solution:
3.5
lbs
ai/
100
gal
At
planting
Potatoes
10
to
25
lbs
ai/
A
Preplant
Tomatoes
7.2
to
21.78
lbs
ai/
A
Preplanting
or
at
planting
Seed
Treatment
0.0375
to
0.253
lb
ai/
100
lbs
seed
Preplant
Ornamental
Usage
Patterns
Azalea/
Camellia
Plants
217.8
to
290.4
lbs
ai/
A
Preplanting
or
at
planting
Bulbs
Dutch
Iris
Easter
Lily,
Hyacinth,
Iris,
Narcissus,
Tulip
Gladiolus
Lily
­
various
147
to
150
lbs
ai/
A
196
to
212.4
98
to
185.1
212.4
[
Transplant
solutions:
1.5
lb
ai/
100
gallons
to
1.5
lb
ai/
3.2
gal]
[
Bulb
soak:
4.5
lb
ai/
100
gal]
At
planting
Cut
Flowers:
spray/
dip
1.5
lb
ai/
100
gal
Prior
to
storage
Dormant
Roses
&
Bulbs:
spray/
dip
4.5
lb
ai/
100
gal
to
1.5
lbs
ai/
3.2
gal
Pre
plant
or
pre
storage
Magnolia
Tree:
Foliar
spray
1.5
lb
ai/
100
gal/
or
6
lb
ai/
A
At
least
4
sprays
at
2
weeks
intervals
Southern
Pine
Seedlings
36.8
to
38.1
lbs
ai/
A
(
37.5
typical)
Pre
plant
Ornamental
Plants:
Pre
planting
or
at
planting
    
21
  
73
Bedding
Plants
Calendula/
Larkspur/
Snapdragon/
Sweet
Peas
Dutch
Iris
Easter
Lily
Flowering
Bedding
­
broadcast
­
soil
drench
­
bench
soil
Flower
&
Foliage
Flower,
Foliage,
Shrub,
Tree
Flower/
Foliage/
Woody&
Bedding
Foliage
Gladiolus
Hyacinth/
Iris/
Narcissus/
Tulip
Lilies
Tropical
Foliage
Vegetable
Bedding
Woody
&
Herbaceous
40.8
lbs
ai/
A
100
to
119.6
to
375
(
1/
10)
16.4
to
200
200
10.2
to
87.12
10.2
to
102.1
65.3
196.0
130.7
7.14
to
114.3
87.12
(
growing
media
mix)
120
212
212.4
40.8
40.84
40.8
to
87.1
Turf:
Turf
Home
Lawns
Commercial
Turf:
Commercial
&
Home
32.7
to
43.1
lbs
ai/
A
21.7
to
32.7
21.3
32.7
to
43.6
More
reapplication
at
lower
rate
Reapplication
at
3
to
4
weeks
interval
Table
6
represents
information
on
registered
use
sites
and
application
rates
for
seed
treatment
uses.
Application
rates
cover
various
types
of
commercial
seed
treaters
and
seed
planters.

Table
6.
Application
Rate
for
seed,
seed
piece,
and
cloves
Application
Rate
lbs
ai/
100
lbs
seed
(
Commercial)
Application
Rate
lbs
ai/
100
lbs
seed
(
On­
Farm)

crop
minimum
typical
maximum
minimum
typical
maximum
barley
0.0394
0.1045
0.1307
0.0390
­­­
0.0878
bean
0.0256­
0.0523
0.0347
 
0.0750
corn
0.0523
0.0372
­­­
0.0558
cotton
0.0656
0.2526
0.0788
0.0750
0.0750­
0.1250
0.0150
garlic
 
 
­­­
 
 
­­­

oats
0.0394
0.0977­
0.1045
0.1957
0.0302
 
0.0604
pea
0.0523
0.1045
0.0521
 
0.1042
peanut
0.0305
0.0375­
0.0523
0.0610
0.0375
0.0375­
0.0417
0.0750
potato
 
 
­­­
 
 
­­­

rice
 
 
­­­
0.0417
 
0.0926
safflower
 
 
­­­
 
 
­­­

sorghum
 
0.0305
­­­
 
 
­­­

soybean
0.0256
0.0256­
0.0525
0.1045
0.0695
 
0.1044
    
22
  
73
sugar
beet
0.0958
 
0.1873
0.0313
 
0.0625
wheat
0.0256
0.0256­
0.0523
0.0525
0.0347
 
0.0521
4.2
Tolerance
Reassessment
Permanent
tolerances
for
PCNB
residues
in/
on
plant
commodities
are
currently
expressed
as
residues
of
PCNB
per
se
[
40
CFR
§
180.291(
a)]
or
as
the
combined
residues
of
PCNB,
and
its
metabolites,
PCA
and
methyl
pentachlorophenyl
sulfide
(
MPCPS)
[
40
CFR
§
180.291(
b)].
There
are
also
interim
tolerances,
which
are
also
expressed
as
PCNB
per
se
[
40
CFR
§
180.319].
There
are
presently
no
tolerances
for
PCNB
in
animal
commodities.

On
April
16,
2003,
the
MARC
decided
that
for
risk
assessment
purposes,
PCNB
and
all
its
metabolites
(
including
minor
metabolites)
are
of
concern
in
plant
and
animal
commodities.
However,
the
residues
of
concern
for
tolerance
setting
purposes
in
primary
and
rotational
crops
and
livestock
are
PCNB,
PCA,
and
PCTA
(
also
abbreviated
as
MPCPS).
A
summary
of
the
PCNB
tolerance
reassessment
and
recommended
modifications
in
commodity
definitions
are
presented
below.

Table
7.
Tolerance
Reassessment
Summary
for
PCNB.

Commodity
Current
Tolerance
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment/
Correct
Commodity
Definition
Tolerances
listed
under
40
CFR
§
180.291(
a):

Cottonseed
0.1
TBD
a
Residue
data
are
required
from
both
Uniroyal
and
Amvac.

Tolerances
listed
under
40
CFR
§
180.291(
b):

Collards
0.2
0.2
Kale
0.2
0.2
Mustard
Greens
0.2
0.2
Residue
data
from
IR­
4
support
the
current
regional
tolerance
in
state
of
Georgia.

Tolerances
listed
under
40
CFR
§
180.319
b:

Beans
0.1
TBD
Residue
data
are
required
from
both
Uniroyal
and
Amvac.

Broccoli
0.1
Brussels
Sprouts
0.1
Cabbage
0.1
Cauliflower
0.1
0.1
The
available
residue
data
from
Uniroyal
and
Amvac
on
broccoli
and
cabbage
would
support
a
permanent
0.1
ppm
tolerance
for
the
Head
and
Stem
Brassica
Vegetable
Crop
Subgroup.
Additional
residue
data
for
broccoli
from
Amvac
are
required.
    
23
  
73
Commodity
Current
Tolerance
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment/
Correct
Commodity
Definition
Garlic
0.1
0.05
Residue
data
from
Uniroyal
indicate
that
the
tolerance
could
be
lowered.
Residue
data
must
be
submitted
by
Amvac.

Peanuts
1.0
TBD
Additional
residue
data
are
required
from
both
Uniroyal
and
Amvac.

Potatoes
0.1
1.0
Additional
residue
data
are
required
from
both
Uniroyal
and
Amvac.

Peppers
0.1
Tomatoes
0.1
0.2
Residue
data
from
Uniroyal
on
peppers
and
tomatoes
would
support
a
permanent
0.2
ppm
tolerance
for
the
Fruiting
Vegetables
(
except
Cucurbits)
Crop
Group.
Additional
residue
data
from
Amvac
are
required.

Tolerances
That
Need
To
Be
Proposed
under
40
CFR
§
180.291(
a)

Cotton
gin
byproducts
­­
TBD
New
field
trial
data
are
required.

Potato,
wet
peel
­­
7.0
Based
on
a
7x
concentration
factor
and
the
HAFT
residues
(
0.95
ppm)
from
Amvac's
potato
field
trials
Barley,
grain,
hay
and
straw
­­

Corn,
grain,
forage
and
fodder
­­

Oat,
forage,
grain,
hay
and
straw
­­

Peas
­­

Rice,
grain
and
straw
­­

Safflower,
seed
­­

Sorghum
forage,
grain,
and
stover
­­
TBD
Data
are
required
from
Amvac
depicting
PCNB
residues
in/
on
RACs
derived
from
seed
treated
with
PCNB
at
the
maximum
labeled
rate.

Soybean,
forage,
hay
and
seeds
­­
0.02
The
available
data
from
Amvac
would
support
separate
tolerances
on
soybean
forage,
hay,
and
seeds
at
0.02
ppm
Sugar
beet,
roots
and
tops
­­

Wheat,
forage,
grain,
hay
and
straw
­­
TBD
Residue
data
are
required.

milk
­­
0.05
Based
on
data
from
the
cattle
feeding
study
and
assuming
a
dietary
burden
of
32.3
ppm
for
dairy
cattle.

Cattle
fat,
meat,
and
mbyp
­­
1.0
Goat
fat,
meat,
and
mbyp
­­
1.0
Horse
fat,
meat,
and
mbyp
­­
1.0
Sheep
fat,
meat,
and
mbyp
­­
1.0
Based
on
data
from
the
cattle
feeding
study
and
assuming
a
dietary
burden
of
32.3
ppm
for
beef
cattle.
    
24
  
73
Commodity
Current
Tolerance
(
ppm)
Tolerance
Reassessment
(
ppm)
Comment/
Correct
Commodity
Definition
Hog
fat,
meat,
and
mbyp
­­
TBD
Tolerances
of
hog
commodities
should
be
established
at
the
method
LOQ;
however,
a
enforcement
method
has
not
yet
been
submitted
for
livestock
commodities.

Eggs
­­
0.05
Poultry,
fat
­­
0.5
Poultry,
mbyp
 
0.05
Tolerances
are
based
on
the
available
feeding
study
and
assuming
a
dietary
burden
of
0.38
ppm
for
poultry
a
TBD
=
To
be
determined.
Tolerance
cannot
be
determined
at
this
time
because
additional
data
are
required
or
are
currently
under
review.
b
CFR
reports
these
as
"
interim"
tolerances.
Tolerances
listed
under
§
180.319
should
be
reassigned
to
§
180.291(
a)
as
time­
limited
or
permanent
tolerances.
Furthermore,
all
the
current
tolerance
expressions
which
include
PCNB
per
se
should
be
changed
to
include
PCNB,
PCA,
and
PCTA
per
the
MARC
decision
on
4/
16/
2003.

4.3
Dietary
Exposure/
Risk
Pathway
Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
Briefing
Memorandum
to
Metabolism
Assessment
Review
Committee
to
discuss
PCNB
residues
of
concern
for
inclusion
in
dietary
risk
assessment.
Chemical
056502.
Mohsen
Sahafeyan
&
Laurence
Chitlik.
April
8th,
2003;
Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Held
on
April
16th,
2003
to
discuss
residues
of
concern
in
risk
assessment
and
tolerance
expression
of
PCNB.
Chemical
056502.
Mohsen
Sahafeyan
&
Laurence
Chitlik.
May
8th,
2003;
Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.
Kinard.
December
14,
2004;
Pentachloronitrobenzene,
Second
Revised
Drinking
Water
Assessment:
New
Tier
2
Drinking
Water
EDWCs
for
Use
in
the
Human
Health
Risk
Assessment.
D291286.
Cheryl
A.
Sutton.
July
15,
2004.

4.3.1
Residue
Profile
The
nature
of
the
residue
in
plants
and
animals
is
adequately
understood.
A
submitted
metabolism
study
in
lactating
goats
identified
the
major
metabolites
in
ruminant
tissues
to
be
PCA,
PCTA,
Nglucuronide
of
PCA
(
PCA­
Gluc),
and
N­
hydroxypentachloroaniline
(
NOHPCA)­
Gluc.
The
major
identified
residues
in
poultry
tissues
included
PCNB,
PCA,
PCTA
sulfoxide,
tetrachloroaniline
methyl
sulfoxide,
and
tetrachlorophenyl
methyl
sulfone.
The
nitro
group
of
PCNB
provides
a
reactive
center
which
allows
rapid
metabolism
via
three
primary
routes:
reduction
of
the
nitro
group,
displacement
of
the
nitro
group
by
the
sulfhydryl
group
of
reduced
glutathione
to
give
a
glutathione
adduct
which
is
metabolized
further,
and
dechlorination.
PCNB
is
relatively
stable
in
soil
in
comparison
with
plants
and
animals.

For
the
primary
crops,
plant
metabolism
studies
on
peanuts,
potato,
and
cabbage
(
cabbage
study
unacceptable)
indicated
that
the
major
identified
radioactive
residues
(
i.
e.
 
10%
total
radioactive
residue
or
TRR)
were
PCNB,
S­(
pentachlorophenyl)
malonycysteine,
N­
malonyl­
S­
(
tetrachloroaminophenyl)­
cysteine,
tetrachlorophenyl
sulfoxide,
and
tetrachlorophenyl
methyl
sulfone.
Numerous
other
polychlorinated
phenyl
compounds
were
identified
in
both
the
primary
crop
and
rotational
crop
(
lettuce,
turnip
roots
and
tops,
and
wheat)
studies.
    
25
  
73
A
total
of
84
polychlorinated
phenyl
metabolites
of
PCNB
have
been
identified
in
animal
and
plant
metabolism,
and
environmental
degradate
data.
For
identification
and
structures
of
each,
see
APPENDIX
2.
The
limited
data
that
are
available
suggest
that
generally,
it
is
the
metabolites
that
are
accumulated
within
plant
and
animal
tissues
to
a
greater
extent
than
the
parent
PCNB
itself.
The
Agency
maintains
that
due
to
insufficient
toxicity
data
on
the
metabolites
of
PCNB,
and
due
to
the
polychlorinated
nature
of
the
PCNB
metabolites,
these
metabolites
cannot
be
comfortably
ruled
out
as
being
toxic
unless
proven
otherwise
through
suitable
toxicity
data,
which
may
be
generated
by
the
registrant.
The
Agency
also
maintains
that
the
general
non­
toxic
nature
of
polar
metabolites
can
not
extended
to
include
each
and
every
instance,
particularly
when
1)
data
on
non­
toxicity
or
reduced
toxicity
of
those
metabolites
are
lacking,
and
2)
the
uncertainty
of
such
a
generalization
may
potentially
put
the
health
of
the
general
public
at
risk.
As
there
is
a
likelihood
of
release
of
conjugated
and
bound
metabolites,
such
compounds
can
not
also
be
dismissed
unless
proven
otherwise
through
suitable
toxicity
data.
Therefore,
at
this
time,
PCNB
and
all
its
polychlorinated
phenyl
metabolites
are
of
toxicological
concern
and
will
be
included
in
the
risk
assessment.
The
metabolites
are
considered
to
be
toxicologically
equivalent
to
the
parent,
PCNB.

Though
no
residues
of
PCP,
a
known
carcinogen,
have
been
found
in
ruminant
and
poultry
data,
PCP
was
found
in
one
plant
rotational
crop
study
(
turnip),
but
not
in
any
other
plant
study.
PCP
was
detected
in
an
anaerobic
soil
metabolism
study
and
a
terrestrial
field
dissipation
study.
The
circumstances
under
which
PCP
might
be
present
are
uncertain
and
the
submitted
data
in
which
PCP
was
detected
are
limited.
Therefore,
a
robust
quantitative
exposure
assessment
of
PCP
in
food
or
drinking
water
cannot
be
conducted
at
this
time,
but
a
screening
level
assessment
was
conducted
for
tubers
(
see
section
3.6).
Additional
data
are
requested.
    
26
  
73
TABLE
8
Chemical:
PCNB
(
pentachloronitrobenzene)

Date:
16­
April­
2003
MARC
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Plants
­
Primary
crops
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Plants
­
Rotational
crops
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Livestock
­
Ruminant
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Livestock­
Poultry
Parent
plus
all
identified
metabolites
Parent,
PCA,
PCTA
Fish
and
Shellfish
N/
A
N/
A
Water
Parent,
PCA,
and
PCP
N/
A
PCA
=
pentachloraniline.
PCTA
=
pentachlorothioanisole
or
methyl
pentachlorophenyl
sulfide.
PCP
=
pentachlorophenol
4.3.2
Dietary
Exposure
Assessment
The
tolerance
expression
for
PCNB
includes
the
metabolites,
PCA
and
PCTA.
Of
the
two
major
food
monitoring
programs,
however,
only
Food
and
Drug
Administration
(
FDA)
analyzes
for
the
combined
residues
of
PCNB,
PCA,
and
PCTA,
while
United
States
Department
of
Agriculture's
(
USDA)
Pesticide
Data
Program
(
PDP)
only
randomly
analyzes
for
PCA
or
PCTA.
Furthermore,
in
the
monitoring
data,
the
number
of
samples
that
are
analyzed
for
more
than
one
metabolite
is
generally
insufficient
(<
100)
for
use
in
the
risk
assessment
according
to
HED
guidelines.
This
is
particularly
true
for
FDA
data
on
all
PCNB
registered
crops;
therefore,
all
the
monitoring
data
that
were
used
in
this
dietary
risk
assessment
were
PDP
data.
In
particular,
PDP
data
from
the
two
most
recent
years
for
each
crop
were
utilized
(
spanning
1997­
2002).
In
order
to
estimate
the
total
residues
of
PCNB
and
all
its
metabolites
of
concern,
it
was
assumed
that
the
TTR,
or
total
residues
of
concern,
would
be
equal
to
or
less
than
the
estimated
TRR
in
each
crop,
which
includes
extractable
as
well
as
unextractable
residues.
Since
the
metabolites
of
concern
are
all
polychlorinated
phenyls
and
the
likelihood
of
any
unextractable
residue
of
PCNB
containing
a
polychlorinated
phenyl
structure
is
high;
using
TRR
values
to
represent
TTR
does
not
result
in
underestimation
of
the
risk.
To
estimate
the
TTR
for
each
crop,
the
monitoring
data
for
that
crop
and
the
ratio
of
TRR
to
PCNB
observed
in
the
metabolism
studies
were
used.
    
27
  
73
The
available
monitoring
data
(
1994­
2002
PDP
and
FDA)
show
detected
residues
of
PCNB
and/
or
its
metabolites
in/
on
a
number
of
unregistered
crops.
The
1994­
2002
PDP
data
show
detected
residues
of
PCNB
and/
or
PCA
on
winter
squash­
fresh,
carrots,
spinach,
cucumbers,
asparagus,
pears
and
celery.
The
1998­
2001
FDA
data
on
crops
of
domestic
origin
show
detected
residues
of
"
Quintozene
(
total),"
which
includes
PCNB,
PCA,
and
PCTA,
on
domestic
head
lettuce,
farm­
raised
tilapia,
squash,
carrot,
and
ginseng.
The
1998­
2001
FDA
data
on
imported
commodities
also
show
a
number
of
unregistered
commodities
with
detected
residues
of
"
Quintozene
(
total)"
in/
on
squash,
carrots,
spinach,
ginger
root,
and
ginseng,
with
73%
of
ginseng
samples
in
all
FDA
data
(
and
58%
in
FDA
surveillance
data)
from
different
countries
having
detected
residues
of
"
Quintozene
(
total)"
with
a
range
from
trace
to
17.44
ppm.
Detected
residues
of
PCNB
and/
or
its
metabolites
on
domestic
and
imported
commodities
can
be
attributed
to
its
long
half
life
in
soil,
as
the
available
studies
and
literature
suggest.
Therefore,
those
crops
which
have
a
considerable
number
of
detects
in
both
PDP
and
FDA
(
carrots,
spinach,
cucumber,
ginseng)
were
incorporated
into
the
chronic
dietary
risk
assessment.

4.3.2.1
Acute
Dietary
No
adverse
effects
attributed
to
a
single
exposure
(
dose)
were
identified
including
in
the
rat
or
rabbit
developmental
toxicity
studies.
Therefore,
no
acute
dietary
endpoint
was
selected
so,
no
acute
dietary
risk
assessment
was
conducted.

4.3.2.2
Chronic
Dietary
The
chronic
dietary
risk
assessment
is
considered
to
be
a
highly
refined
assessment
using
all
available
monitoring
data,
%
CT
information,
and
processing
factors
(
submitted
data
and
default
factors).
However,
because
monitoring
data
did
not
analyze
for
all
PCNB
metabolites
of
concern
(
84),
the
ratio
of
TRR
to
PCNB
from
available
metabolism
studies
in
combination
with
monitoring
residue
data
on
PCNB,
or
TRR
values
directly,
were
used
to
estimate
the
total
residues
of
concern.

The
chronic
risk
assessment
was
performed
with
both
the
DEEM­
FCID
 
(
Version
1.30)
and
Lifeline
 
(
Version
2.0)
models.
The
1994­
1996
and
1998
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(
CSFII)
were
used
in
both
models
for
the
consumption
database.
Since
residues
of
PCNB
and/
or
its
metabolites
were
detected
in
monitoring
data
for
some
unsupported
(
not
registered/
without
tolerances)
food
uses,
assessments
using
DEEM­
FCID
and
Lifeline,
with
and
without
unsupported
food
uses,
were
performed.
One
assessment
includes
all
the
residues
associated
with
the
registered
foods/
commodities,
while
the
other
also
includes
residues
detected
on
crops/
commodities
for
which
there
are
no
registrations/
tolerances.

It
is
believed
that
the
wide
presence
of
PCNB
and/
or
its
metabolites
on
unsupported
crops
is
due
to
its
uptake
from
soil
by
rotated
crops
(
rather
than
illegal
use),
which
in
turn
is
due
to
a
very
long
half
life
(
aerobic
soil
t1/
2
>
1000
days
PCNB
+
PCA)
of
PCNB
and/
or
its
metabolites
in
soil.
Though
a
rotational
crop
restriction
would
normally
be
addressed
during
the
mitigation
phase
of
this
review,
the
length
of
the
restriction
is
unlikely
to
be
feasible
for
the
growers.
Based
on
the
    
28
  
73
available
rotational
crop
data,
ChemSAC
(
June
2003)
decided
that
only
registered
crops
should
be
rotated
to
PCNB­
treated
fields.
Due
to
the
persistence
of
the
PCNB
and/
or
its
metabolites
in
soil
for
more
than
two
years,
ChemSAC
expressed
a
concern
even
with
imposing
restriction
of
rotation
only
to
the
labeled
crops.
ChemSAC
decided
that
the
extension
of
plant
back
interval
(
PBI)
restriction
to
3
or
4
years
or
a
restriction
of
rotation
to
the
labeled
crops
for
3­
4
years
could
not
be
enforced.

The
chronic
dietary
risk
assessment
shows
that
the
risks
for
all
population
subgroups
are
below
the
level
of
concern;
i.
e.
<
100%
cPAD,
with
and
without
unregistered
crops.
The
highest
estimated
risks
are
for
children
1­
2
years
of
age.
The
major
contribution
to
the
risk
came
from
milk
fat,
followed
by
brassica
vegetables.
The
high
contribution
of
the
milk
to
the
risk
is
due
to
high
consumption
of
this
food,
particularly
in
children,
combined
with
the
high
levels
of
TRR
found
in
milk
in
the
goat
metabolism
study.

The
major
source
of
uncertainty
in
this
chronic
dietary
risk
assessment
is
in
the
residue
estimates.
In
particular,
using
TRR:
PCNB
ratios
from
the
metabolism
study
in
combination
with
PCNB
residues
from
the
monitoring
data
and
use
of
absolute
TRR
values
from
the
cabbage
metabolism
study
to
estimate
TTR
for
brassica
vegetables
can
be
significant
determinants
of
uncertainty.
In
addition,
uncertainties
in
the
calculation
of
secondary
residues
can
be
considerable.
Despite
the
lack
of
monitoring
residue
data
on
all
PCNB
metabolites
and
an
incomplete
metabolism
study
on
cabbage,
this
assessment
is
considered
highly
refined
because
it
includes
all
available
residue
information,
%
CT,
and
processing
factor
information.
Future
refinement
of
this
assessment
would
be
aided
if
monitoring
programs
used
validated
common­
moiety
methods
for
detection
of
PCNB
and
all
its
metabolites
in
registered
and
nonregistered
commodities.

Table
9.
Result
of
Chronic
Dietary
(
food
only)
Exposure
and
Risk
Estimates
for
PCNB.

Risk
from
all
crops
a
Risk
from
registered
crops
only
DEEM­
FCID
Lifeline
DEEM­
FCID
Lifeline
Population
Subgroup
cPAD
mg/
kg/
day
Exposure
mg/
kg/
d
%
cPAD
b
Exposure
mg/
kg/
d
%
cPAD
Exposure
mg/
kg/
d
%
cPAD
Exposure
mg/
kg/
d
%
cPAD
U.
S.
Population
0.001
0.000121
12%
0.000252
25%
0.000102
10%
0.000229
23%

All
infants
(<
1
yr)
0.001
0.000072
7%
0.00002
2%
0.000057
6%
0.000014
1%

Children
1­
2
yrs
0.001
0.000345
34%
0.000331
33%
0.000269
27%
0.000276
28%

Children
3­
5
yrs
0.001
0.000254
25%
0.000199
20%
0.000199
20%
0.000145
14%

Children
6­
12
yrs
0.001
0.000161
16%
0.00013
13%
0.000128
13%
0.000093
9%

Youth
13­
19
yrs
0.001
0.000104
10%
0.000092
9%
0.000086
9%
0.000066
7%

Adults
20­
49
yrs
0.001
0.000097
10%
0.000263
26%
0.000084
8%
0.000244
24%

Adults
50+
yrs
0.001
0.000104
10%
0.000303
30%
0.000094
9%
0.000286
29%

Females
13­
49
yrs
0.001
0.000096
10%
0.000261
26%
0.000083
8%
0.000236
24%

a
Registered
crop
uses
plus
measured
PCNB
residues
on
food
crops/
commodities
without
tolerances
    
29
  
73
b
%
cPAD
=
(
exposure
mg/
kg/
d
÷
cPAD
mg/
kg/
d)
x
100
4.3.2.3
Cancer
Dietary
PCNB
is
classified
as
a
Group
C­
possible
human
carcinogen
and
the
HED
team
recommended
that
for
risk
assessment
purposes,
the
RfD
approach
should
be
used
for
quantification
of
human
risk.
Consistent
with
the
weak
evidence
of
carcinogenic
effects
in
one
of
the
3
lifetime
bioassays,
the
HED
team
indicated
that
a
dose­
response
assessment
for
cancer
(
either
linear
low­
dose
extrapolation
or
margin
of
exposure
calculation)
was
not
needed.

4.4
Water
Exposure/
Risk
Pathway
Pentachloronitrobenzene,
Second
Revised
Drinking
Water
Assessment:
New
Tier
2
Drinking
Water
EDWCs
for
Use
in
the
Human
Health
Risk
Assessment.
D291286.
Cheryl
A.
Sutton.
July
15,
2004.

4.4.1
Environmental
Fate
In
general,
PCNB
is
a
persistent,
volatile
compound
that
will
be
immobile
in
most
soils,
but
may
have
slight
or
even
moderate
mobility
in
coarser
(
sandy)
soils,
particularly
those
that
are
low
in
organic
matter.
While
PCNB
is
expected
to
be
persistent
in
aerobic
environments,
it
is
microbially
degraded
more
rapidly
in
anaerobic
environments.
It
is
stable
to
hydrolysis
and
is
effectively
stable
to
photodegradation
on
soil,
but
appears
(
based
on
two
submitted
studies)
to
photodegrade
fairly
rapidly
in
water,
with
half­
lives
on
the
order
of
a
few
days
or
less.
While
evidence
of
aqueous
photodegradation
of
PCNB
was
not
found
in
the
literature,
EFED
found
the
submitted
studies
acceptable
and,
therefore,
used
the
half­
life
values
determined
in
those
studies.
The
major
degradates
of
PCNB
in
the
environment
are
PCA
and
PCTA;
minor
degradates
are
pentachlorothioanisole
sulfoxide
(
PCTASO),
pentachlorothioanisole
sulfone
(
PCTASO2),
and
PCB,
which
is
also
present
as
an
impurity
along
with
HCB.
While
PCP
was
detected
in
two
of
the
submitted
studies,
there
is
not
sufficient
evidence
(
either
from
the
submitted
data
or
from
published
literature)
that
the
compound
will
routinely
be
formed
from
PCNB
in
the
environment.

Aerobic
Soil
Metabolism
Half­
life
t1/
2
=
77,
189
days
(
parent
only);
t1/
2
=
489,
1012
days
(
parent
plus
PCA)
1;
t1/
2
=
983,
1052
days
(
total
residues)

Anaerobic
Soil
Metabolism
Half­
life
t1/
2
=
9
days,
<
30
(
DT50
2;
parent
only);
t1/
2
=
210,
410
days
(
parent
plus
PCA,
PCP);
t1/
2
=
268,
334
days
(
total
residues)

1For
the
purposes
of
the
drinking
water
assessment,
half­
lives
were
recalculated
to
account
for
the
parent
plus
the
degradates
PCA
and
PCP,
when
monitored
and
detected.
2
DT50
=
time
to
disappearance
or
dissipation
of
50%
of
the
initial
concentration
of
the
parent
compound.
*
More
than
one
half­
life
is
listed
when
more
than
one
study
was
submitted.

4.4.2
Estimated
Drinking
Water
Concentrations
(
EDWCs)

Some
chemical­
specific
water
monitoring
data
are
available
but
they
are
limited
and
not
at­
the­
tap
data.
Therefore,
EDWCs
were
calculated
by
EFED
to
estimate
the
potential
contribution
to
the
acute
and
chronic
exposure
from
drinking
water.
The
chronic
EDWC
(
point
estimate)
was
then
incorporated
directly
into
DEEM­
FCID
(
see
Aggregate
Risk
section).
The
drinking
water
exposure
assessment
is
based
on
maximum
application
rates
and
use
patterns.
Lacking
environmental
fate
    
30
  
73
data
on
the
metabolites,
it
was
assumed
that
their
mobility
into
sources
of
drinking
water
is
the
same
as
the
parent.

Table
10.
Tier
2
EDWCs
for
Drinking
Water
Risk
Assessment.

Surface
water
drinking
water
sources
acute:
440
ug/
L
(
ppb)
1
1­
in­
10­
years
(
chronic):
65.5
ug/
L
(
ppb)
30­
year
average:
33.7
ug/
L
(
ppb)

Groundwater
drinking
water
sources
30.6
ug/
L
(
ppb)
2
1Surface
water
EDWC
values
(
Tier
II
screening
level)
were
generated
using
the
PRZM/
EXAMS
model
with
a
foliar/
ground
spray
to
turf
in
Pennsylvania
application
scenario
(
two
applications
of
33.67
lb
a.
i./
A,
at
a
21­
day
interval).
The
actual
output
value
from
PRZM/
EXAMS
was
587.7
ppb
for
the
turf
use
acute
concentration.
However,
as
this
is
greater
than
the
aqueous
solubility
of
440
ppb
for
PCNB,
the
solubility
limit
should
be
used
instead.
2Groundwater
EDWC's
(
Tier
I
screening
level)
are
based
on
PCNB
use
on
bulb
crops
at
213.4
lb
a.
i./
A/
application
in
a
single
application.

Though
EFED
has
made
a
preliminary
assessment
of
the
potential
EDWCs
for
the
soil
drench
use
of
PCNB,
prior
to
a
final
determination
of
EDWC's
associated
with
a
soil
drench
use,
it
is
necessary
that
EFED
obtain
additional
information
from
the
registrants
on
this
use
pattern,
particularly
with
regard
to
drenching
practices,
time
between
drench
and
transplant,
number
of
treatments,
estimated
amount
of
pesticide/
formulated
product
not
retained
in
the
drenched
container,
and
planting
densities
for
transplants
in
the
field.

4.4.3
Monitoring
Data
NAWQA
monitoring
data
are
not
available.
Updated
monitoring
data
from
STORET
are
also
not
available.
To
supplement
the
limited
monitoring
data
that
are
available,
EFED
conducted
a
literature
search
to
obtain
published
information
(
generally
post­
1990
only).
PCNB
and
its
major
degradates
PCA
and
PCTA
have
not
been
detected
frequently
in
North
America.
The
presence
of
PCA
and
PCTA
in
the
environment
are
most
likely
a
result
of
the
use
of
PCNB.
Detections
of
the
potential
degradate
PCP
in
the
environment
cannot
necessarily
be
attributed
to
its
existence
as
a
degradate
of
PCNB,
but
can
be
the
result
of
its
use
as
a
pesticide
itself
(
wood
preservative).
PCP
was
not
found
in
any
surface
water
samples.
Similarly,
detections
of
the
degradate
(
and
impurity
in
PCNB)
PCB
in
the
environment
are
most
likely
a
result
of
its
existence
as
a
byproduct
in
the
manufacture
of
other
compounds,
its
existence
as
a
degradate
of
HCB,
and
its
industrial
uses.
There
are
no
drinking
water
standards
or
health
advisories
for
PCNB.

4.5
Residential
and
Other
Non­
occupational
Exposure/
Risk
Pathways
Pentachloronitrobenzene
(
PCNB):
Revised
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document.
D291283.
Seyed
Tadayon.
November
15,
2004.

There
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
products
containing
PCNB.
There
is
also
a
potential
for
exposure
from
entering
areas
treated
with
PCNB,
such
as
entering
treated
lawns,
including
golf
courses,
that
could
lead
to
exposures
for
both
adults
and
children.
Risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.
For
residential
handler
exposure
assessments,
HED
used
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
study
data
and
the
Residential
Standard
Operating
Procedures
(
SOPs).
4.5.1
Home
Uses
    
31
  
73
PCNB
is
registered
for
use
on
residential
lawns.
It
is
not
a
restricted
use
chemical.
Therefore,
homeowners
may
obtain
and
apply
PCNB
to
the
lawn
to
deter
fungal
growth.
The
labels
recommend
no
more
than
2
applications
per
year.
Following
application
to
the
lawn,
adults
may
be
exposed
to
PCNB
through
dermal
contact
with
the
lawn
and
mowing
activities.
Children
(
primarily
toddlers)
may
have
dermal
contact
with
the
treated
lawn,
as
well
as
hand
to
mouth,
object
to
mouth,
and
incidental
ingestion
exposures.
Screening­
level
assumptions
are
incorporated
into
residential
exposure
assessments
and
are
therefore,
high­
end.

4.5.1.1
Handler
The
Agency
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
Residential
handlers
are
assumed
to
complete
all
elements
of
an
application,
including
mixing/
loading,
with
little
use
of
any
protective
equipment.
Residential
handler
exposure
scenarios
are
only
considered
to
be
short­
term
in
nature
due
to
the
episodic
uses
associated
with
homeowner
products.
Area/
volumes
of
spray
or
chemical
used
in
the
risk
assessment
are
based
on
HED
guidance
specific
to
residential
use
patterns.
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
handler
risk
assessments.
HED
based
its
calculations
on
what
would
reasonably
be
treated
by
homeowners
such
as
the
size
of
a
lawn,
or
the
size
of
a
garden.
This
information
was
used
by
the
HED
to
define
chemical
use
values
for
handlers
which
in
turn
were
coupled
with
unit
exposure
values
to
calculate
risks.
The
factors
used
for
the
PCNB
assessment
were
those
presented
in
the
HED
Science
Advisory
Committee
Policy
12:
Recommended
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
which
was
completed
on
February
22,
2001.
In
addition
to
these
factors,
unit
exposure
values
were
used
to
calculate
risk
estimates.
These
unit
exposure
values
were
taken
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
or
from
ORETF
data.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
scenarios:

1.
Applying
Granulars
for
Hand
application
2.
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
3.
Mixing/
Loading/
Applying
Liquids
for
Backpack
sprayer
application
4.
Mixing/
Loading/
Applying
Liquids
for
Garden
hose­
end
sprayer
(
ORETF
­
RTU)
application
5.
Mixing/
Loading/
Applying
Liquids
for
Garden
hose­
end
sprayer
(
ORETF
­
conventional)
application
6.
Loading/
Applying
Granulars
for
Belly
Grinder
application
7.
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
8.
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
In
residential
settings,
the
Agency
does
not
use
PPE
to
limit
exposures,
because
they
are
viewed
as
impractical
and
not
enforceable.
Risk
estimates
are
based
on
handlers
wearing
short­
sleeve
shirts,
short
pants,
shoes,
and
socks.
The
overall
uncertainty
factor
applied
to
residential
handler
risk
assessments
is
1000.
Residential
risks
are
of
concern
for
a
few
scenarios,
(
i.
e.,
MOE
<
1000),
including
dermal
risk
for
mixing/
loading/
applying
liquids
with
a
low
pressure
handwand
and
dermal
and
inhalation
risk
for
the
garden
hose­
end
sprayer
and
belly
grinder.
    
32
  
73
Table
11:
Summery
Short
Term
Residential
Handler
Risk
for
PCNB
Exposure
Scenario
(
Scenario
#)
Use1
Application
Rate2
Daily
Area
Treated/
day3
Dermal
MOE4
Inhalation
MOE5
Applicator
Applying
Granulars
for
Hand
application
(
1)
Turf
32.67
lb
ai
/
A
0.023
A
65
200
Mixer/
Loader/
App
Mixing/
Loading/
Applying
Liquids
for
Low
Pressure
Handwand
application
(
2)
0.15
lb
ai
/
gal
5
gal
280
3100
Mixing/
Loading/
Applying
Liquids
for
Backpack
sprayer
application
(
3)
0.15
lb
ai
/
gal
5
gal
5500
3100
Mixing/
Loading/
Applying
Liquids
for
Garden
hose­
end
sprayer
(
ORETF
­
RTU)
application
(
4)
32.67
lb
ai
/
A
0.5
A
490
390
Mixing/
Loading/
Applying
Liquids
for
Garden
hose­
end
sprayer
(
ORETF
­
conventional)
application
(
5)
32.67
lb
ai
/
A
0.5
A
120
250
Loading/
Applying
Granulars
for
Belly
Grinder
application
(
6)
32.67
lb
ai
/
A
0.5
A
12
69
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
(
7)
32.67
lb
ai
/
A
0.5
A
1900
4900
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
(
8)
Turf
43.56
lb
ai
/
A
0.5
A
1400
3700
1Crops
and
use
patterns
are
from
PCNB
labels
and
LUIS
report
2Application
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/
A.
In
some
cases,
the
application
rate
is
based
on
applying
a
solution
at
concentrations
specified
by
the
label
(
i.
e.,
presented
as
lb
ai/
gallon).
3Amount
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).
4Dermal
MOE
=
short­
term
endpoint
for
dermal,
such
as
oral
NOAEL
(
300
mg/
kg/
day)
/
Daily
Dermal
Dose.
Target
Dermal
MOE
is
1000.
5Inhalation
MOE
=
oral
NOAEL
(
1
mg/
kg/
day)
/
Daily
Inhalation
Dose.
Target
Inhalation
MOE
is
1000.

4.5.1.2
Residential
Postapplication
Adults
and
children,
are
potentially
exposed
to
residues
after
application
of
PCNB
products
in
residential
settings.
After
application
to
turf,
short­
to
intermediate­
term
dermal
exposures
are
anticipated
for
adults
and
children.
Incidental
oral
exposure
is
also
expected
to
occur
for
small
children
and
is
combined
with
their
dermal
exposures,
where
applicable
(
i.
e.,
playing
on
turf).
The
physical
and
behavioral
differences
between
adults
and
children
are
continuously
being
studied
by
the
Agency,
and
the
current
standard
assumptions
set
forth
by
the
HED
and
the
Science
Advisory
Panel
(
SAP)
are
contained
in
the
Residential
SOPs
(
revised
February,
2001).

Though
the
label
prohibits
application
more
than
2
times
per
year,
even
with
the
slow
dissipation
rates,
it
is
not
expected
that
individual
residential
exposure
duration
would
exceed
30
days
in
duration
since
exposure
on
a
residential
lawn
would
diminish
continuously
with
time.
However,
short­
and
intermediate­
term
risks
were
assessed
using
maximum
application
rates
for
each
scenario
to
be
protective
of
any
longer
exposures/
risks.
Residential
postapplication
exposure
assessments
    
33
  
73
assume
residents
wear
the
following
attire:
short
sleeved
shirt,
short
pants,
shoes
and
socks,
and
no
gloves
or
respirator.
Negligible
PCNB
inhalation
exposure
is
anticipated
for
non­
handlers
due
to
the
low
chemical
vapor
pressure
and
dilution
of
vapor
outdoors.
The
scenarios
likely
to
result
in
postapplication
exposures
are
as
follows:

·
dermal
contact
of
adults
and
toddlers
to
treated
turf
and
lawns;
and
·
oral
exposure
to
toddlers
from
ingestion
of
grass,
soil,
or
hand­
to­
mouth
contact
Representative
turf/
lawn
reentry
activities
include,
but
are
not
limited
to:

·
Adults
involved
in
a
low
exposure
activity,
such
as
golfing
or
walking
on
treated
turf;
·
Toddlers
involved
in
a
low
exposure
activity,
such
as
walking
on
treated
turf;
·
Adults
mowing
or
other
moderate
contact
activity,
for
1­
2
hours;
·
Adults
involved
in
a
high
exposure
activity,
such
as
heavy
yard
work;
and
·
Toddlers
involved
in
high
exposure
activities
on
turf.

Although
a
Turf
Transferable
Residue
(
TTR)
study
(
MRID#
44687101)
was
submitted
in
support
of
the
reregistration
of
PCNB,
it
was
not
acceptable
for
this
assessment.

4.5.2
Recreational
PCNB
has
recreational
uses
on
golf
courses.
According
to
a
1992
report
from
The
Center
For
Golf
Course
Management,
12.2
%
of
the
population
were
golfers
(
i.
e.,
28.5
million
people).
Golf
is
considered
a
lifetime
sport
so
individuals
of
all
ages,
excluding
very
small
children,
routinely
play.
Potential
risks
to
young
children
are
difficult
to
assess
because
of
the
uncertainties
associated
with
any
extrapolations
using
adult
dermal
exposure
data
and
because
of
the
increased
likelihood
that
other
behaviors
might
contribute
to
exposure
such
as
mouthing
contaminated
hands
or
golf
balls.

The
exposure
duration
was
assumed
to
be
4
hours
since
this
is
the
estimate
of
the
average
time
it
takes
to
play
a
round
of
golf,
which
is
based
on
the
report
completed
by
the
Center
For
Golf
Course
Management
[
1992
Golf
Course
Operations:
Cost
of
Doing
Business/
Profitability.
Library
of
Congress
GV975.
G56
1992].
The
dose
levels
calculated
for
adult
golfers
can
be
considered
upper
level
estimates
of
exposure
for
several
reasons
including;
the
clothing
scenario
considered
(
i.
e.,
shorts
and
short­
sleeved
shirts
are
not
worn
by
all
golfers),
and
because
combining
average
values
across
several
input
parameters
mathematically
results
in
an
upper
percentile
calculated
value.
    
34
  
73
Table
12
:
Summary
of
Risk
for
Residential/
Recreational
Postapplication
Activities
on
Treated
Turf
with
PCNB
Activity
Application
Rate
(
lb
ai/
acre)
TTR
5%
of
application
ratea
Transfer
Coefficient
(
cm2/
hr)
b
Dermal
Dose
(
mg/
kg/
day)
c
MOEd
(
day
0)

32.67
7.09
2.856
40
high
contact
lawn
activities:
adults
43.56
6.89
14500
2.939
30
32.67
18.3
2.720
110
high
contact
lawn
activities:
toddler
43.56
19.77
5200
2.938
80
32.67
18.3
0.262
1145
mowing
turf:
adults
43.56
24.4
500
0.349
860
32.67
18.3
0.523
575
golf
course
reentry:
adult
43.57
24.4
500
0.698
430
a
TTR
source:
5%
of
application
rate,
"
Residential
SOP
Revised
February
2001
"
was
used
for
determination
of
MOE's.
b
Transfer
coefficient
from
the
Residential
SOP's
(
02/
01).
c
Dermal
dose
=
normalized
TTR
(
µ
g/
cm2)
x
TC
(
cm2/
hr)
x
conversion
factor
(
1
mg/
1,000
µ
g)
x
exposure
time
(
2
hrs/
day
playing
or
mowing;
4
hrs
golfing)
/
body
weight
(
70
kg
adult
or
15
kg
child
1­
6
yrs).
d
MOE
=
NOAEL
(
300
mg/
kg/
day;
based
on
a
dermal
study)
/
dermal
dose
Note:
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
The
oral
non­
dietary
risk
estimates
for
small
children
from
hand­
to­
mouth
and
ingestion
exposure
while
playing
on
PCNB
treated
turf
are
contained
in
Table
13.
Risk
estimates
were
combined
where
applicable
for
PCNB
T
able
13:
Residential
Oral
Non­
dietary
Short­
and
Intermediate­
term
Postapplication
Risks
for
PCNB
Exposure
Scenario
Route
of
Exposure
Population
Application
Ratea
MOEb
Short­
term
Postapplication
Exposures
32.67
2
Hand
to
Mouth
Activity
on
Turf
Oral
Toddler
43.56
2
32.67
8
Object
to
Mouth
Activity
on
Turf
Oral
Toddler
43.56
6
32.67
612
Incidental
Soil
Ingestion
Oral
Toddler
43.56
460
Intermediate­
term
Postapplication
Exposures
32.67
1
Hand
to
Mouth
Activity
on
Turf
Oral
Toddler
43.56
1
32.67
8
Object
to
Mouth
Activity
on
Turf
Oral
Toddler
43.56
6
32.67
612
Incidental
Soil
Ingestion
Oral
Toddler
43.56
460
a
Application
rates
represent
a
range
of
label
rates
of
32.67­
43.56
lb
ai/
acre
for
all
liquid
and
granular
products
which
may
be
applied
to
residential
and
recreational
lawns
either
professionally
or
by
a
consumer.
Incidental
oral
doses
were
calculated
using
formulas
presented
in
the
Residential
SOPs
(
updated
1999­
2000).
Short­
term
doses
were
calculated
using
the
following
formulas:
(
1)
Hand­
to­
mouth
oral
dose
to
children
on
the
day
of
treatment
(
mg/
kg/
day)
=
[
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
    
35
  
73
dislodgeable
from
potentially
wet
hands
(
5%)
x
11.2
(
conversion
factor
to
convert
lb
ai/
acre
to
µ
g/
cm2)]
x
median
surface
area
for
1­
3
fingers
(
20
cm
2
/
event)
x
hand­
to­
mouth
rate
(
20
events/
hour)
x
exposure
time
(
2
hr/
day)
x
0.001
mg/
µ
g]
x
50%
extraction
by
saliva
/
bw
(
15
kg
child
1­
6
yrs).
This
formula
is
based
on
proposed
changes
to
the
December
1999
Residential
SOPs.
(
2)
Turf
mouthing
oral
dose
to
child
on
the
day
of
treatment
(
mg/
kg/
day)
=
[
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
dislodgeable
from
potentially
wet
hands
(
20%)
x
11.2
(
conversion
factor
to
convert
lb
ai/
acre
to
µ
g/
cm2)
x
ingestion
rate
of
grass
(
25
cm
2
/
day)
x
.001
mg/
µ
g]
/
bw
(
15
kg
child
1­
6
yrs).
Soil
ingestion
oral
dose
to
child
on
the
day
of
treatment
(
mg/
kg/
day)
=
[(
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
retained
on
uppermost
1
cm
of
soil
(
100%
or
1.0/
cm)
x
4.54e+
08
µ
g/
lb
conversion
factor
x
2.47e­
08
acre/
cm2
conversion
factor
x
0.67
cm3/
g
soil
conversion
factor)
x
100
mg/
day
ingestion
rate
x
1.0e­
06
g/
µ
g
conversion
factor]
/
bw
(
15
kg;
child
1­
6
yrs).
Short
term
dose
based
residue
on
the
soil
on
day
of
application.
b
MOE
=
NOAEL
(
1
mg/
kg/
day
for
both
short­
and
intermediate­
term
assessments)
/
Oral
Dose
(
mg/
kg/
day).
Aggregate
MOEs
=
NOAEL
/
[
sum
of
incidental
oral
doses]
with
an
target
MOE
of
1000.

4.6
Other
(
Spray
Drift;
Farm
Worker
Children,
etc.)

Spray
drift
is
always
a
potential
source
of
exposure
to
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
ground
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies,
and
other
parties,
for
pesticide
regulation
to
develop
the
best
spray
drift
management
practices.
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
composed
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
air­
blast,
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
and
risks
associated
with
aerial
as
well
as
other
application
types,
where
appropriate.
This
will
include
expanding
the
scope
of
the
residential
exposure
assessments
by
developing
guidance
for
characterizing
exposures
from
other
sources
not
already
addressed,
such
as
from
spray
drift,
residential
residue
track­
in,
exposures
to
farm
worker
children,
and
exposures
to
children
in
schools.

Of
note,
measurable
levels
of
PCNB
were
detected
in
an
ambient
air
monitoring
study
conducted
by
CalEPA's
Department
of
Pesticide
Regulation
(
CDPR)
in
Lompoc,
California
(
Santa
Barbara
County)
in
2000
(
http://
www.
cdpr.
ca.
gov/
docs/
dprdocs/
lompoc/
vol3_
multiple_
pest/
volume3_
march2003.
pdf).
PCNB
was
detected
in
72%
of
the
air
samples
taken
between
May­
August
2000.
Since
this
information
raised
concerns
for
potential
risks
to
by­
standers
and
workers
in
adjacent
fields,
a
screening
level
assessment
was
conducted
by
the
USEPA
and
determined
that
these
potential
exposures
resulted
in
risks
below
HED's
level
of
concern
(
i.
e.
>
MOE
1000).

5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATIONS
5.1
Overview
Due
to
the
availability
of
acceptable
oral
and
dermal
studies
using
PCNB,
the
dietary,
incidental
oral,
and
dermal
risk
assessments
were
conducted
using
route­
specific
endpoints.
There
are
no
subchronic
inhalation
toxicity
data
on
PCNB.
Due
to
the
greenhouse
use
of
PCNB,
a
90­
day
    
36
  
73
inhalation
toxicity
study
of
PCNB
is
requested.
To
fully
characterize
the
hazard
and
potential
risk
from
exposures
to
PCNB
additional
studies
are
requested:
study
to
assess
thyroid
toxicity
in
adults
vs.
offspring
development;
study
to
address
the
toxicological
significance
of
alterations
in
AST/
ALT
activities;
and
a
metabolism
study
that
includes
blood
kinetics
and
half­
life
of
PCNB.
No
acute
dietary
endpoint
was
selected
since
no
adverse
effects
attributed
to
a
single
exposure
(
dose)
were
identified,
including
in
the
rat
or
rabbit
developmental
toxicity
studies.
The
chronic
dietary,
and
short­,
intermediate­,
and
long­
term
dermal,
inhalation,
and
incidental
oral
endpoints
are
all
based
on
a
common
the
toxic
effect,
thyroid
toxicity,
observed
in
animals
following
subchronic
or
chronic
exposure.
Some
production
lots
of
PCNB
have
been
determined
to
be
positive
for
dermal
sensitization,
while
others
have
tested
negative,
perhaps
associated
with
variations
of
production
methods
and
levels
of
impurities.
PCNB
is
not
mutagenic
in
bacteria
or
in
cultured
mammalian
cells.
There
is
suggestive
in
vitro
evidence
showing
that
PCNB
is
clastogenic
in
the
absence
of
S9
activation
and
equivocal
in
the
presence
of
S9
activation.
However,
in
a
more
definitive
erythrocyte
mouse
micronucleus
study,
PCNB
was
shown
not
to
be
clastogenic.
PCNB
was
also
negative
for
induction
of
SCEs
in
vitro.
PCNB
is
classified
as
a
Group
C
carcinogen
("
Possible"
human
carcinogen).

In
assessing
aggregate
risks,
HED
has
considered
exposures
from
dietary
(
food
and
drinking
water)
and
non­
dietary
(
dermal
and
inhalation)
pathways.
For
residential
and
other
non­
dietary
exposure
pathways
relevant
incidental
oral,
dermal,
and
inhalation
(
if
applicable)
exposures
are
included
to
calculate
short­,
intermediate,
and
long­
term
aggregate
risks.
For
the
dietary
pathway,
food
exposure
estimates
come
from
the
dietary
exposure
analysis
discussed
above
(
Section
4.3.2).
Generally,
when
there
are
insufficient
water
monitoring
data
available
to
quantitatively
include
in
the
aggregate
risk
assessment
as
a
means
of
assessing
whether
or
not
aggregate
exposures
to
a
chemical
and
its
metabolites
are
likely
to
exceed
levels
of
concern.
EFED
has
provided
estimated
drinking
water
concentrations.

For
PCNB
and
its
metabolites,
quantitative
aggregate
exposure
assessments
that
include
dietary
(
food
+
drinking
water)
+
incidental/
dermal/
inhalation
exposures
were
not
performed,
since
potential
exposures
and
their
associated
risks
from
individual
sources
of
exposures
were
already
of
concern,
particularly
for
children.
However,
chronic
aggregate
exposures
were
estimated
by
combining
food
and
estimated
drinking
water
exposures
directly
in
the
DEEM­
FCID
program.

5.2
Acute
Aggregate
Risk
No
adverse
effects
attributed
to
a
single
exposure
(
dose)
were
identified,
no
acute
dietary
risk
assessment
was
conducted
and
therefore,
no
acute
aggregate
risk
assessment
was
conducted.

5.3
Short­
Term
Aggregate
Risk
Short­
term
(
1­
30
days)
aggregate
risk
includes
the
chronic
estimated
dietary
exposure
plus,
when
applicable,
estimated
residential/
recreational
incidental
oral,
dermal,
and
inhalation
exposures
resulting
from
the
registered
uses
of
the
chemical.
In
the
case
of
PCNB,
dietary
exposures
from
food
plus
water
are
already
of
concern
for
all
populations,
especially
infants
(
460%
cPAD),
children
1­
2
years
(
240%
cPAD),
children
3­
5
years
(
217%
cPAD),
and
the
general
population
    
37
  
73
(
150%
cPAD).
Add
to
that,
potential
risks
of
concern
from
dermal
contact
with
treated
lawns
(
MOE
40
for
adults),
and
ingestion
of
granulars
(
MOE
<
1
for
toddlers),
and
aggregate
risks
would
clearly
be
of
even
greater
concern.
Though
dietary
exposures
to
adult
homeowners
from
food
alone,
may
be
acceptable
(
25%
cPAD
or
less
for
general
population),
when
potential
drinking
water
(
total
150%
cPAD),
and
dermal
(
MOE
65)
and
inhalation
(
MOE
200)
risks
from
applying
granulars
by
hand,
and
postapplication
dermal
risks
(
MOE
30)
from
high
contact
lawn
activities
on
turf
are
considered,
aggregate
risks
are
of
concern
(
target
MOE
>
1000).
When
potential
dietary
(
food
+
water)
risks
to
infants
(
460%
cPAD)
and
children
(
240%
cPAD
for
1­
2
yr.
olds)
are
considered
with
potential
residential
postapplication
incidental
oral
(
MOE
460)
and
hand­
to­
mouth
(
MOE
1)
risks,
estimated
aggregate
risks
are
even
greater.

5.4
Intermediate­
Term
Aggregate
Risk
Intermediate­
term
(
1­
6
months)
aggregate
risk
includes
the
chronic
estimated
dietary
exposure
plus,
when
applicable,
estimated
intermediate­
term
residential/
recreational
incidental
oral,
dermal,
and
inhalation
exposures
resulting
from
the
registered
uses
of
the
chemical.
Residential
handler
exposures
are
generally
considered
to
be
short­
term
only
due
to
the
episodic
uses
associated
with
the
product.
Though
the
label
prohibits
application
more
than
2
times
per
year,
even
with
the
slow
dissipation
rates,
it
is
not
expected
that
the
individual
postapplication
residential
exposure
duration
would
exceed
30
days
in
duration
since
exposure
on
a
residential
lawn
would
diminish
continuously
with
time.
However,
short­
and
intermediate­
term
risks
were
assessed
using
maximum
application
rates
for
each
scenario
to
be
protective
of
any
longer
exposures/
risks.
The
potential
exposures
and
risks
from
the
separate
sources
of
exposure,
alone,
are
of
concern,
particularly
for
children.
As
above
(
section
5.3),
when
these
potential
exposures
and
associated
risks
are
layered
upon
each
other,
risk
concerns
are
increased.

5.5
Chronic
Aggregate
Risk
Chronic
aggregate
risk
estimates
include
only
dietary
pathways
of
exposure
(
food
+
water).
Chronic
aggregate
exposures
were
estimated
by
combining
food
and
estimated
drinking
water
exposures
directly
in
the
DEEM­
FCID
program.
The
chronic
dietary
risk
without
the
inclusion
of
water
is
below
the
Agency's
level
of
concern;
i.
e.,
<
100%
cPAD.
When
exposures
from
drinking
water
are
added,
chronic
aggregate
risks
for
all
exposed
population
subgroups,
particularly
infants
(
460%
cPAD)
and
children
1­
2
years
old
(
240%
cPAD)
are
above
HED's
level
of
concern.

5.6
Cancer
Aggregate
Risk
PCNB
is
classified
as
a
Group
C­
possible
human
carcinogen
and
the
HED
team
recommended
that
for
risk
assessment
purposes,
the
RfD
approach
should
be
used
for
quantification
of
human
risk.
Therefore,
a
separate
assessment
of
aggregate
cancer
risk
is
not
required.
    
38
  
73
Table
14.
Result
of
Chronic
Dietary
Exposure
and
Risk
Estimates
for
PCNB.

Risk
from
all
crops
(
no
water)
Risk
from
all
crops
Including
risk
from
water
DEEM­
FCID
Lifeline
DEEM­
FCID
Population
Subgroup
cPAD
mg/
kg/
day
Exposure,
mg/
kg/
day
%
cPAD
Exposure,
mg/
kg/
day
%
cPAD
Exposure,
mg/
kg/
day
%
cPAD
U.
S.
Population
0.001
0.000121
12%
0.000252
25%
0.001051
150%

All
infants
(<
1
yr)
0.001
0.000072
7%
.00002
2%
0.004598
460%

Children
1­
2
yrs
0.001
0.000345
34%
0.000331
33%
0.002395
240%

Children
3­
5
yrs
0.001
0.000254
25%
0.000199
20%
0.002173
217%

Children
6­
12
yrs
0.001
0.000161
16%
0.00013
13%
0.001485
149%

Youth
13­
19
yrs
0.001
0.000104
10%
0.000092
9%
0.001102
110%

Adults
20­
49
yrs
0.001
0.000097
10%
0.000263
26%
0.001386
139%

Adults
50+
yrs
0.001
0.000104
10%
0.000303
30%
0.001460
146%

Females
13­
49
yrs
0.001
0.000096
10%
0.000261
26%
0.001379
138%

·
 
Risk
from
all
crops 
indicates
the
risk
from
oral
consumption
of
residues
found
in
the
food
chain
at
present
time,
whether
from
registered
or
unregistered
crops
(
for
details
see
discussion
under
residue
section).

6.0
CUMULATIVE
The
Food
Quality
Protection
Act
(
1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
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
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

Guidance
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity
is
available
from
the
OPP
Website
(
http://
www.
epa.
gov/
pesticides).
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
each
substance
has
been
completed.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"
Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(
64
FR
5795­
5796,
February
5,
1999).

PCNB
is
a
member
of
the
substituted
aromatics
class
of
pesticides
(
George
W.
Ware,
The
Pesticide
Book,
Fourth
ed.,
1994).
Other
members
of
this
class
include
2,6­
dichloro­
4­
    
39
  
73
nitroaniline
(
dichloran,
DCNA)
and
chlorothalonil.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
risk
assessment
for
PCNB
because
HED
has
not
yet
initiated
a
review
to
determine
if
these
or
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
in
humans
in
common
with
it.

7.0
OCCUPATIONAL
EXPOSURE
Pentachloronitrobenzene
(
PCNB):
Revised
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document.
D291283.
Seyed
Tadayon.
November
15,
2004.

7.1
Agricultural,
Seed
Treatment,
and
Non­
crop/
Utility
Uses
For
agricultural
uses,
HED
relied
almost
completely
on
surrogate
data
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)
Version
1.1.
Chemical
specific
postapplication
exposure
data
have
not
been
submitted
by
the
registrant
in
support
of
reregistration
of
PCNB.
However
there
is
a
low
potential
for
occupational
postapplication
exposure
when
a
pre­
plant
or
at
planting
fungicide
is
used.
Many
agricultural
operations
mechanically
plant
seeds
early
in
the
season,
which
minimizes
the
potential
for
contact.
Significant
exposure
during
harvesting
or
any
other
late
season
activities,
is
not
likely
since
the
chemical
is
applied
pre­
plant
or
at
planting.
However
the
Agency
has
determined
that
there
are
potential
postapplication
exposures
to
individuals
reentering
PCNB
treated
areas
for
the
purpose
of
mowing
(
roadsides,
rights­
of­
way,
golf
course)
and
harvesting
(
sod
farms).

7.1.1
Handler
HED
determined
potential
exposures
to
handlers
by
identifying
exposure
scenarios
from
the
various
application
equipment­
types
that
are
recommended
on
PCNB
labels.
Based
on
reviewing
pesticide
labels
and
a
use
meeting
with
the
registrants,
agricultural
use
patterns
specific
to
PCNB
are
associated
with
the
following
application
methods/
equipment:

Agricultural
Uses:
 
Chemigation
 
Ground
boom
sprayer
 
Airblast
sprayer
 
Push
type
spreader
 
Tractor
drawn
spreader
 
Aerial
application
Seed
Treatment
Uses:
 
Commercial
seed
treater
 
On
farm
seed
treatment
 
Planter/
seed
box
    
40
  
73
7.1.1.1
Exposure
and
Risk
Estimates
for
Agricultural
Uses
HED
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
the
usual
use­
patterns
associated
with
PCNB.
The
potential
handler
exposures
to
the
103
identified
exposure
scenarios
were
assessed
using
the
toxicological
endpoints
and
uncertainty
factors
associated
with
the
a.
i.
Therefore,
the
level
of
PPE
was
determined
by
the
assessment
of
the
a.
i.
independently
from
the
currently
required
risk
mitigation
measures
on
PCNB
labels.
This
distinction
of
determining
risk
mitigation
measures
based
on
the
a.
i.
instead
of
the
label
required
PPE
is
important
because
of
the
nature
of
the
end­
use
products.
For
example,
some
end­
use
products
require
additional
PPE
because
of
the
end­
use
product's
potential
for
eye
and/
or
skin
irritation.
Conversely,
HED
does
not
want
to
mandate
additional
PPE
(
e.
g.,
heat
stress
issues)
if
it
is
not
required
based
on
the
endpoint
and
uncertainty
factors.
There
are
some
PPE,
such
as
chemical­
resistant
aprons
and/
or
head
gear,
that
the
HED
uses
as
qualitative
measures
because
there
are
no
recognized
protection
factors
(
PF)
to
assess
their
effectiveness.

The
risks
are
presented
separately
for
some
scenarios
and
combined
for
others.
Most
of
the
hand­
held
equipment
such
as
push
type
granular
spreaders
are
assessed
as
mixer/
loader/
applicators,
a
combined
function.
With
these
types
of
small
operations
the
mixing,
loading,
and
applying
are
almost
always
carried
out
by
the
same
individual.
There
are
data
available
to
estimate
exposure
from
these
small
area
activities.
For
equipment
such
as
groundboom
tractors,
or
airblast
sprayers,
the
tasks
are
assessed
separately
for
mixer/
loaders
and
applicators.
By
separating
the
two
job
functions,
HED
can
determine
the
most
appropriate
PPE
or
engineering
controls
without
requiring
the
handler
to
wear
PPE
throughout
the
entire
workday
or
engineering
controls
that
are
not
needed.

MOEs
were
calculated
for
handlers
for
short­
(
1­
30
days)
and
intermediate­
term
(
1­
6
months)
durations.
The
assessment
includes
MOE
calculations
for
various
levels
of
PPE
using
the
surrogate
data
from
PHED
(
V1.1).
The
short­
term
duration
is
believed
to
be
most
representative
of
private
growers
and
the
intermediate­
term
duration
represents
commercial
applicators
who
may
repeatedly
apply
PCNB
for
1
to
6
months.
PCNB
was
classified
as
a
category
C
possible
human
carcinogen
and
not
requiring
any
type
of
quantitative
cancer
risk
assessment.

The
risk
estimates
for
short­
and
intermediate­
term
dermal
exposures
resulted
largely
in
MOEs
greater
than
or
equal
to
the
target
MOE
of
100,
with
use
of
PPE
or
engineering
controls.
The
following
scenarios
did
not
have
MOEs
>
100
at
any
mitigation
level
and
therefore,
are
of
concern
(
bracketed
numbers
correspond
to
those
in
Table
15;
Appendix
1):

(
6)
mixing/
loading
dry
flowable
for
chemigation
application
(
sod
farms),
(
58)
sprays
for
high
pressure
handwand
application
(
ornamentals),
(
94)
mixing/
loading/
applying
liquid
for
handgun
(
lawn)
sprayer
(
ORETF)
application,
(
98)
mixing/
loading/
applying
granular
for
belly
grinder
application
(
ornamentals)
(
100)
mixing/
loading/
applying
wettable
powders
for
low
pressure
handwand
application
(
ornamentals
­
woody
shrubs
and
vines,
and
herbaceous
plants),
    
41
  
73
(
101)
mixing/
loading/
applying
wettable
powders
for
low
pressure
handwand
application
(
ornamentals
­
shade
trees)

The
results
of
the
inhalation
handler
risk
assessment
for
both
the
short­
and
intermediate­
term
exposure
durations
are
summarized
in
Table
15
(
Appendix
1).
All
inhalation
scenarios
had
MOEs
>
100,
though
some
required
the
addition
of
PPE
or
engineering
controls
including:

(
6)
mixing/
loading
dry
flowable
for
chemigation
application
(
sod
farms),
(
16)
mixing/
loading
liquids
for
chemigation
application,
(
24)
mixing/
loading
liquids
for
chemigation
application,
(
25)
mixing/
loading
liquids
for
aerial
application,
(
42)
mixing/
loading
wettable
powder
for
chemigation
application
(
cole
crops),
(
50)
mixing/
loading
wettable
powder
chemigation
application
(
sod
farms),
(
51)
mixing/
loading
wettable
powders
for
groundboom
application,
(
58)
sprays
for
high
pressure
handwand
application
(
ornamentals),
(
87)
sprays
for
high­
pressure
handwand
application,
(
100)
mixing/
loading/
applying
wettable
powders
for
low
pressure
handwand,
application
(
ornamentals
­
woody
shrubs
and
vines,
and
herbaceous
plants),
(
101)
mixing/
loading/
applying
wettable
powders
for
low
pressure
handwand,
application
(
ornamentals
­
shade
trees).

The
results
of
the
short­
and
intermediate­
term
occupational
handler
assessments
indicate
that
for
the
dry
flowable
formulation,
the
majority
of
the
potential
exposure
scenarios
result
in
total
MOE(
s)
>
100
at
the
baseline
clothing
attire
of
long
pants,
long
sleeved
shirts,
no
gloves,
and
no
respirator
while
using
open
systems.
For
the
liquid
formulation,
the
risk
estimates
indicate
that
in
order
for
the
mixer/
loaders
to
achieve
MOEs
of
100
for
all
uses
at
both
the
short­
and
intermediate­
term
exposure
durations,
minimum
PPE
clothing
attire
should
be
required
(
i.
e.,
long
pants,
long
sleeved
shirts,
chemical
resistant
gloves,
and
a
dust/
mist
respirator
while
using
open
systems).
This
is
consistent
with
the
current
label
except
for
the
need,
in
some
scenarios,
to
add
an
organic
vapor
respirator.
The
risk
estimates
for
the
majority
of
uses
with
the
wettable
powder
formulation
are
acceptable
(
clothing
attire
of
long
pants,
long
sleeved
shirts,
chemical
resistant
gloves,
and
no
respirator).
However,
the
risk
estimates
indicate
that
in
order
for
the
mixer/
loaders
of
wettable
powders
to
achieve
MOEs
of
100
for
all
uses
at
both
the
short­
and
intermediate­
term
durations
that,
for
some
uses,
PCNB
should
be
packaged
in
water
soluble
packets.

7.1.1.2
Exposure
and
Risk
Estimates
for
Seed
Handlers
There
are
a
number
of
methods
that
can
be
used
to
treat
seeds
both
commercially
and
on­
farm.
On­
farm
seed
treatment
methods
include
concrete
tumbler,
drill
box,
duster,
in­
furrow,
mist­
type
seed
treater,
planter/
seed
box,
seed
treater
and
slurry­
type
seed
treater.
Commercial
seed
treatment
equipment
produced
by
Gustafson
include
Computerized
Seed
and
Chemical
Proportioner,
Gustafson
Accu­
Treat
Treater,
Gustafson
S­
Series
and
SS­
Series,
Gustafson
SSAMP
Treater,
and
Triple
Treat
Seed
Treater.
    
42
  
73
On­
farm
seed
treatment
is
considered,
by
most
sources,
to
represent
a
relatively
small
proportion
of
the
total
use
of
treated
seed
in
the
U.
S.
This
may
be
due,
in
large
part,
to
the
greater
time
investment,
labor,
and
equipment
commitment
required
for
on­
farm
seed
treatment
compared
to
buying
the
treated
seed.
However,
some
seed
crops
record
a
sizable
percentage
of
on­
farm
seed
treatment.
A
risk
assessment
for
on­
farm
seed
treatment
(
planter
box)
was
completed
using
a
submitted
dust
formulation
study.
The
dust
formulation
study
is
the
only
on­
farm
seed
treatment
study
available,
and
is
used
as
a
surrogate
for
planter
box
seed
treatment
with
a
liquid
formulation.
The
planter
box
seed
treatment
liquid
formulation
risk
assessment
is
considered
conservative
since
treatments
with
dust
formulations
usually
present
higher
risks
than
liquids.
There
are
no
data
for
other
seed
treatments
done
on­
farm.

An
exposure
assessment
was
conducted
for
workers
loading
treated
seed
into
plant
hoppers
and
driving
a
closed
cab
tractor
to
pull
the
planter
around
the
field.
Commercial,
on­
farm
seed
treatment,
and
planter
exposures
were
addressed
using
the
Science
Advisory
Council
Exposure
Policy
14
(
May,
2003),
seed
treatment
SOP.
This
database
was
created
by
USEPA,
and
measures
exposure
values
for
seed
treaters
and
planters
under
actual
field
conditions.
There
are
potential
exposures
to
loader/
applicators,
baggers,
sewers,
workers
performing
multiple
activities
and
on­
farm
treatment
with
planter
boxes,
and
seed
planters
during
the
usual
use­
patterns
associated
with
PCNB.
Six
exposure
scenarios
were
identified
to
represent
the
extent
of
PCNB
seed
treatment
uses.
PCNB
labels
include
a
multitude
of
uses
and
a
wide
range
of
application
rates.
Though
the
seed
treatment
risk
assessment
is
not
all
inclusive,
an
attempt
has
been
made
to
assess
a
range
of
application
rates
to
capture
the
exposures
associated
within
each
scenario.
MOEs
were
calculated
for
handlers
for
short­
and
intermediate­
term
durations.
The
short­
term
duration
is
believed
to
be
the
most
representative
of
on­
farm
seed
treaters
and
the
intermediateterm
duration
represents
commercial
seed
treaters
who
may
repeatedly
apply
PCNB
for
1
to
6
months.
The
assessment
includes
MOE
calculations
for
various
feasible
levels
of
PPE
using
the
surrogate
data
from
the
seed
treatment
SOP.

The
results
of
the
short­
and
intermediate­
term
seed
handler
assessments
indicate
that,
for
all
formulations,
the
majority
of
the
potential
exposure
scenarios
result
in
total
MOEs
>
100
with
long
pants,
long
sleeved
shirts,
gloves,
and
no
respirator
while
using
open
systems.
Seed
handlers
working
in
a
smaller
facility,
performing
multiple
activities,
might
require
a
respirator
to
reduce
exposures
so
that
potential
risks
(
MOEs)
would
be
>
100
and
not
of
concern.

Table
16:
Summary
of
Short
and
Intermediate­
term
Dermal
and
Inhalation
Risk
from
Seed
Treatment
for
PCNB
(
MOEs
)

Loader/
applicat
or
Bagger
Sewer
Multiple
activities
On­
Farm
(
planter
box)
Planters
Crops
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Barley
1000
200
2500
500
3600
350
550
50
300
9000
3600
900
    
43
  
73
T
able
16:
Summary
of
Short
and
Intermediate­
term
Dermal
and
Inhalation
Risk
from
Seed
Treatment
for
PCNB
(
MOEs
)

Loader/
applicat
or
Bagger
Sewer
Multiple
activities
On­
Farm
(
planter
box)
Planters
Crops
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Derm
al
Inh
Bean
3000
700
8000
1500
1100
0
100
0
1500
150
550
2000
0
1600
0
4000
Corn
3200
700
8000
1500
1200
0
110
0
1800
150
2100
7300
0
4500
0
11000
2300
500
5700
1100
8400
750
1200
100
930
3300
0
3600
870
Cotton
NA
NA
NA
NA
NA
NA
NA
NA
3500
1200
0
1300
330
Oats
650
150
1700
300
2400
200
360
300
400
1300
0
2400
600
Pea
1500
350
4000
730
5700
500
800
75
250
9000
1300
0
3000
Peanut
1250
0
2800
3150
0
6000
4600
0
420
0
6800
600
240
8400
1450
00
3600
Rice
900
200
2300
400
3400
300
500
50
150
5300
2000
500
Safflower
2100
470
5300
1000
7700
700
1100
100
NA
NA
5700
0
14000
Sorghum
4200
940
1100
0
2000
1500
0
140
0
2300
200
NA
NA
4300
00
11000
0
Soybeans
1500
350
3900
700
5700
500
800
75
3300
1200
00
7000
1600
Sugar
beet
4100
900
1000
0
2000
1500
0
130
0
2000
200
7000
2300
00
1100
00
27000
Wheat
2400
600
6000
1100
9000
800
1300
120
340
1200
0
7000
1600
7.1.2
Postapplication
Exposures
There
is
a
low
potential
for
occupational
postapplication
exposure
when
used
as
a
pre­
plant
or
at
planting
fungicide.
PCNB
is
applied
to
the
soil
directly
and
is
soil
incorporated
well
before
the
plants
are
mature.
Further,
the
timing
of
the
application
greatly
reduces
the
potential
for
postapplication
exposure
to
treated
foliage
and/
or
soil.
Also,
many
agricultural
operations
    
44
  
73
mechanically
plant
seeds
early
in
the
season,
which
minimizes
the
potential
for
contact.
Significant
exposure
during
harvesting
or
any
other
late
season
activities,
is
not
likely
since
the
chemical
is
applied
pre­
plant.
Therefore,
HED
does
not
require
a
postapplication
assessment
for
seed
treatment
or
agricultural
uses.
However,
the
Agency
has
determined
that
there
are
potential
postapplication
exposures
to
individuals
re­
entering
PCNB
treated
areas
for
the
purpose
of:

Roadsides:
mowing;
Bermuda
grass
rights­
of­
way:
mowing;
Sod
farms:
mowing
and
harvesting;
Golf­
course
turfgrass:
mowing.
    
45
  
73
7.1.2.1
Noncancer
Postapplication
Exposure
and
Risk
Estimates
For
golf
course
maintenance
or
sod
harvesting,
transfer
coefficients
of
3400
and
6800
cm2/
hr
were
used,
based
on
the
Agricultural
Re­
entry
Task
Force
(
ARTF)
data
(
see
HED
Exposure
SAC
Policy
guidance
3.1,
8/
00).
Transferable
residue
values
from
the
submitted
TTR
study
(
MRID#
446871­
01)
were
used
and
adjusted
when
needed.
The
short­
and
intermediate­
term
estimated
risks
to
golf
course
workers
or
sod
growers
doing
hand
harvesting
on
day
zero
result
in
MOEs
>
100
and
do
not
exceed
HED's
level
of
concern
at
the
32.67
and
43.56
lb
ai/
A
application
rates.

Table
17:
Days
After
Treatment
Target
MOE
Achieved
(
Target
MOE
=
100)

Crop/
Use
Pattern
Application
Rate
(
lb
ai/
acre)
Postapplication
Activity
TTR
(
sites)
µ
g/
cm2
DAT
0a
Transfer
Coefficientb
MOEc
REI
(
days)

32.67
0.366
2100
0
Golf
Course
Turf
43.56
Mow,
seed,
mechanical
weed,
aerate,
fertilize,
prune
0.488
3400
1580
0
32.67
0.366
1120
0
Sod
Farms
43.56
Mow,
scout,
mechanical
weed,
irrigate
0.488
6800
790
0
a
TTR
source:
MRID
#
446871­
01
turf
transferable
residue
study.
DAT
0
residue
values
were
used
for
the
short­
term
assessments
and
DAT
7
residue
values
were
used
for
the
intermediate­
term
assessments.
The
study
was
conducted
in
CA,
OR,
MO
using
an
average
application
rate
of
32.67lb
ai/
acre
for
each
sites.
When
assessing
activities
involving
a
different
application
rate
than
was
used
in
the
study,
the
TTR
values
were
adjusted
proportionately
to
reflect
the
different
application
rates.
For
example
for
an
application
rate
of
43.56
lb
ai/
acre
:
normalized
(
adjusted)
TTR
=
Turf
study
TTR
x
43.56
lb
ai/
A
assessed
rate
/
32.67
lb
ai/
A
study
rate.
b
Transfer
coefficient
from
:
Policy
Memo
#
003
.1
"
Agricultural
Transfer
Coefficients,"
Revised
­
August
7,
2000.
C
MOE
=
NOAEL
(
300
mg/
kg/
day;
based
on
a
dermal
study)
/
dermal
dose
Note:
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
7.2
Incident
Data
Review
of
PCNB
Poisoning
Incident
Data
Chemical:
#
056502.
Ruth
H.
Allen.
February
4,
2003.

The
Agency
has
reviewed
the
Incident
Data
System
(
IDS),
the
Poison
Control
Center,
the
California
Department
of
Food
and
Agriculture
(
Department
of
Pesticide
Regulation),
and
the
National
Pesticide
Telecommunications
Network
(
NPTN)
databases
for
reported
human
incident
information
for
PCNB.
A
number
of
accidental
human
poisonings
from
exposure
to
PCNB
in
both
occupational
and
residential
settings
have
been
reported.
The
data
from
these
sources
often
lacked
specific
information
on
the
extent
of
exposure
and
the
circumstances
of
exposure.
Collectively,
however,
the
incidence
information
indicate
definite
poisoning
risks
from
misuse
of
products
that
contain
PCNB,
or
from
not
wearing
PPE,
especially
eye
protection.
Most
of
the
incidents
reported
were
of
eye
and
skin
irritation.

8.0
DATA
NEEDS/
LABEL
REQUIREMENTS
8.1
Toxicology
1.
Although
the
thyroid
is
a
target
organ
for
PCNB,
thyroid
hormone
and
TSH
determinations
have
been
performed
only
in
one
nonguideline
study
(
90­
day
study
in
male
rats)
using
    
46
  
73
inappropriate
dose
spacing
(
0,
1,
&
333
mg/
kg/
day),
which
precludes
a
meaningful
assessment
of
dose­
response
and
time­
course
features
of
the
effect.
A
study
to
assess
thyroid
toxicity
in
adults
vs.
offspring
development
is
requested.
The
study
should
include;
a)
assays
of
appropriate
hormones;
b)
organ
weights;
and
c)
histopathology.
The
study
should
be
conducted
at
adequate
doses.
The
registrants
are
requested
to
consult
the
Agency
concerning
protocol
development.

2.
Aminotransferase
activities
(
AST/
ALT,
particularly
ALT)
decrease
in
dose­
dependent
manner
by
as
much
as
30­
80%
in
rats
and
dogs.
Although
the
literature
indicates
that
aminotransferase
inhibition
may
result
in
increases
in
Gamma­
aminobutyrate
(
GABA),
hepatocellular
tyrosine,
and
other
amino
acid­
related
compounds,
there
are
insufficient
data
to
evaluate
the
toxicological
significance
of
the
inhibition
findings
for
PCNB.
The
registrants
are
requested
to
address
the
toxicological
significance
of
these
alterations
in
AST/
ALT
activities.

3.
Although
information
in
the
published
literature
indicates
that
PCNB
undergoes
extensive
biotransformation
in
mammals,
there
is
an
uncertainty
as
to
its
biological
half­
life
and
thus,
as
to
its
potential
for
bioaccumulation.
Data
in
the
literature
suggest
that
its
half­
life
might
be
relatively
short
at
low
doses
and
higher
at
higher
doses.
It
is
therefore
requested
that
the
registrants
perform
a
guideline
metabolism
study
of
PCNB
(
including
a
mass
balance
of
radioactivity
in
excreta,
tissues,
and
carcass),
including
a
Tier
II
study
of
blood
kinetics,
to
determine
a
half­
life
of
PCNB.
The
registrants
should
consult
the
Agency
as
to
the
details
of
the
protocol.

4.
There
are
no
subchronic
inhalation
toxicity
data
on
PCNB.
Due
to
the
greenhouse
use
of
PCNB,
a
90­
day
inhalation
toxicity
study
of
PCNB
is
requested.
It
is
recommended
that
interim
thyroid
hormone
analyses
be
made
at
7,
14,
30,
and
90
days.

8.2
Product
Chemistry
1.
Additional
data
are
required
for
the
Amvac
95%
T
concerning
preliminary
analysis
(
OPPTS
830.1700).
For
specifics
see
Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.
Kinard.
December
14,
2004.

8.3
Residue
Chemistry
See
Residue
Chemistry
chapter
(
12/
14/
04).

REFERENCES
National
Toxicology
Program.
1987.
NTP
Technical
Report
on
the
Toxicology
and
Carcinogenesis
Studies
of
Pentachloronitrobenzene
in
B6C3
F1
Mice.
U.
S.
Department
of
Health
and
Human
Services.
Public
Health
Service.
National
Institutes
of
Health
(
NIH)
Publication
No.
87­
2581.
NTP
TR
325.
    
47
  
73
ATTACHMENTS
PCNB
(
PC
Code
056502)­
Revised
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
(
RED).
Laurence
D.
Chitlik.
January
7,
2005.

Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
Briefing
Memorandum
to
Metabolism
Assessment
Review
Committee
to
discuss
PCNB
residues
of
concern
for
inclusion
in
dietary
risk
assessment.
Chemical
056502.
Mohsen
Sahafeyan
&
Laurence
Chitlik.
April
8th,
2003;

Pentachloronitrobenzene
(
PCNB).
(
List
A,
Case
No.
0128)
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Held
on
April
16th,
2003
to
discuss
residues
of
concern
in
risk
assessment
and
tolerance
expression
of
PCNB.
Chemical
056502.
Mohsen
Sahafeyan
&
Laurence
Chitlik.
May
27th,
2003
Pentachloronitrobenzene,
Second
Revised
Drinking
Water
Assessment:
New
Tier
2
Drinking
Water
EDWCs
for
Use
in
the
Human
Health
Risk
Assessment.
D291286.
Cheryl
A.
Sutton.
July
15,
2004.

Pentachloronitrobenzene
(
PCNB):
Revised
Occupational
and
Residential
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision
Document.
D291283.
Seyed
Tadayon.
November
15,
2004.

Pentachloronitrobenzene
(
PCNB).
Revised
Reregistration
Eligibility
Decision
Document
(
RED):
Product
and
Residue
Chemistry
Considerations.
PC
Code
056502.
Reregistration
Case
0128.
DP
Barcode.
D291280.
Sherrie
L.
Kinard.
December
14,
2004.

Pentachlorophenol:­
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
Jess
Rowland.
December
8,
1997.

Review
of
PCNB
Poisoning
Incident
Data
Chemical:
#
056502.
Ruth
H.
Allen.
February
4,
2003.

Second
Carcinogenicity
Peer
Review
of
PCNB.
Pamela
Hurley
and
Esther
Rinde.
December
18,
1992.
    
48
  
73
APPENDIX
1
T
able
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Mixer/
Loader
Dry
Flowables
for
High­
Pressure
HandWand
application
(
1)
Containerized
nursery
stock,
soil
drench
(
beans,
brussels
sprouts,
cabbage,

cauliflower)
0.0038
1000
gals
85000
85000
120000
No
Data
24000
120000
240000
No
Data
Dry
Flowables
for
Chemigation
application
(
2)
Commercial/

industrial
lawns
32.67
10
970
970
1400
No
Data
280
1400
2800
No
Data
Dry
Flowables
for
High­
Pressure
HandWand
application
(
3)
Commercial/

industrial
lawns,

residential
lawn
0.04
1000
gals
8500
8500
12000
No
Data
2400
12000
24000
No
Data
Dry
Flowables
for
Chemigation
application
(
4)
Golf
course
turf
(
tees/
greens)
32.67
10
970
970
1400
No
Data
280
1400
2800
No
Data
Dry
Flowables
for
Chemigation
application
(
5)
Golf
course
turf
(
fairways)
32.67
40
240
240
340
No
Data
70
360
700
No
Data
Dry
Flowables
for
Chemigation
application
(
6)
Sod
farms
32.67
350
28
28
39
No
Data
8
41
80
No
Data
Dry
Flowables
for
High­
Pressure
HandWand
application
(
7)
Ornamentals
(
herbaceous
plants,

woody
shrubs
and
vines)
1.50
1000gals
210
210
300
No
Data
61
310
610
No
Data
Dry
Flowables
for
High­
Pressure
HandWand
application
(
8)
Containerized
nursery
stock,
soil
drench
(
pepper,
tomato)
0.0038
1000
gals
85000
85000
120000
No
Data
24000
120000
240000
No
Data
Dry
Flowables
for
Groundboom
application
(
9)
Soil
band
treatment
(
broccoli,
brussels
sprouts,
cabbage,

cauliflower)
30
80
130
130
190
No
Data
38
190
380
No
Data
Dry
Flowables
for
Groundboom
application
(
10)
Cotton
2
200
800
800
1100
No
Data
230
1200
2300
No
Data
No
    
49
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Dry
Flowables
for
Groundboom
application
(
11)
Peanuts
11.59
80
340
340
480
No
Data
98
500
980
Data
Mixing/
Loading
Liquids
for
Groundboom
application
(
12)
Band
treatment
(
dried
beans,
succulent
beans,

lima)
2
80
45
5700
7700
15000
360
1800
3600
5300
Mixing/
Loading
Liquids
for
Groundboom
application
(
13)
Band
treatment,
soil
treatment
(
garlic)
20
80
4.5
570
770
1500
36
180
360
530
Mixing/
Loading
Liquids
for
Chemigation
application
(
14)
Ornamental
lawn
and
turf
32.67
5
44
5600
7600
15000
360
1800
3600
5200
Mixing/
Loading
Liquids
for
Chemigation
application
(
15)
Commercial/
industrial
lawns
32.67
10
22
2800
3800
7500
180
890
1800
2600
Mixing/
Loading
Liquids
for
Chemigation
application
(
16)
Sod
farms
32.67
350
0.63
80
110
210
5.1
26
51
74
Mixing/
Loading
Liquids
for
Grounfboom
application
(
16a)
Sod
farms
32.67
80
2.8
350
470
930
22
110
220
320
Mixing/
Loading
Liquids
for
Chemigation
application
(
17)
Golf
course
turf
32.67
10
22
2800
3800
7500
180
890
1800
2600
Mixing/
Loading
Liquids
for
Chemigation
application
(
18)
Golf
course
turf
(
fairways)
32.67
40
5.5
700
950
1900
45
220
450
650
Mixing/
Loading
Liquids
for
High­
Pressure
HandWand
application
(
19)
Commercial
industrial
lawn
0.15
1000
gals
48
6100
8200
16000
390
1900
3900
5600
Mixing/
Loading
Liquids
for
Groundboom
application
(
20)
Cotton
2
200
18
2300
3100
6100
150
730
1500
2100
Mixing/
Loading
Liquids
for
Groundboom
application
(
21)
Garlic
20
80
4.5
570
770
1500
36
180
360
530
Mixing/
Loading
Liquids
for
Groundboom
application
(
22)
Peanuts
10
80
9.1
1100
1500
3100
73
360
730
1100
Mixing/
Loading
Liquids
for
Groundboom
application
(
23)
Potato
25
80
3.6
460
620
1200
29
150
290
420
Mixing/
Loading
Liquids
for
Chemigation
Potato
25
350
0.83
100
140
280
6.7
33
67
96
    
50
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
application
(
24)

Mixing/
Loading
Liquids
for
Aerial
application
(
25)
Potato
25
350
0.83
100
140
280
6.7
33
67
96
Mixing/
Loading
Liquids
for
Groundboom
application
(
26)
Soil
band
treatment
(
broccoli,
Chinese
broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
30
80
3
380
510
1000
24
120
240
350
Mixing/
Loading
Liquids
for
High­
Pressure
HandWand
application
(
27)
Containerized
stock
(
broccoli,
Chinese
broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
0.02
1000
gals
480
6100
82000
160000
3900
19000
39000
56000
Mixing/
Loading
Liquids
for
Airblast
application
(
28)
Foliar
spray
(
magnolia
tree)
6
20
60
7600
10000
20000
490
2400
4900
7000
Mixing/
Loading
Liquids
for
Groundboom
application
(
29)
Tomato,
pepper
7.50
80
12
1500
2100
4100
97
490
970
1400
Mixing/
Loading
Liquids
for
Groundboom
application
(
30)
Southern
pine
(
seed
orchard)
42.50
10
17
2100
2900
5700
140
690
1400
2000
Mixing/
Loading
Liquids
for
Dip
tank
application
(
31)
Ornamental
bulb
soak
and
cut
flowers
0.02
100
gals
4800
61000
0
820000
1600000
39000
190000
390000
560000
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
32)
Beans
1.50
80
21000
25000
51000
1000000
340
1700
3400
17000
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
33)
Soil
band
treatment
(
broccoli,
brussels
sprouts,
cabbage,

cauliflower,
collards,

kale,
mustard)
30
80
1000
1300
2600
51000
17
86
170
860
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
34)
Golf
course
turf
(
tees/
greens)
43.56
10
5700
7000
14000
280000
95
470
950
4700
    
51
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
35)
Golf
course
turf
(
fairways)
43.56
40
1400
1700
3500
71000
24
120
240
1200
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
36)
Sod
farms
43.56
80
720
870
1800
35000
12
59
120
590
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
37)
Cotton
2
200
6300
7600
15000
310000
100
510
1000
5100
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
38)
Pepper
1.35
80
23000
28000
57000
1100000
380
1900
3800
19000
Loading
Granulars
for
Tractor­
Drawn
Spreaders
application
(
39)
Potato
25
80
1300
1500
3100
62000
21
100
210
1000
Wettable
Powders
for
Groundboom
application
(
40)
beans(
lima,
snap,

dried)
1.50
80
47
1000
1300
18000
14
68
140
2400
Wettable
Powders
for
Chemigation
application
(
41)
beans(
lima,
snap,

dried)
1.50
350
11
240
310
4100
3.1
16
31
560
Wettable
Powders
for
Chemigation
application
(
42)
soil
band
treatment
(
broccoli,
Chinese,

broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
30
350
0.54
12
15
200
0.16
0.78
1.6
28
Wettable
Powders
for
Groundboom
application
(
43)
soil
band
treatment
(
broccoli,
Chinese,

broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
30
80
2.4
51
67
890
0.68
3.4
6.8
120
Wettable
Powders
for
Chemigation
application
(
44)
commercial/
industrial
lawns
40.80
10
14
300
400
5300
4
20
40
710
Wettable
Powders
for
High­
Pressure
HandWand
application
(
45)
commercial/
industrial
lawns
0.50
1000
gals
11
250
320
4300
3.3
16
33
580
Wettable
Powders
for
Groundboom
application
(
46)
cotton
2
200
14
310
400
5400
4.1
20
41
730
    
52
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Wettable
Powders
for
Chemigation
application
(
47)
cotton
2
350
8.1
180
230
3100
2.3
12
23
420
Wettable
Powders
for
Chemigation
application
(
48)
golf
course
turf
(
tees
and
greens)
40.80
10
14
300
400
5300
4
20
40
710
Wettable
Powders
for
Chemigation
application
(
49)
golf
course
turf
(
fairways)
40.80
40
3.5
76
99
1300
0.100
5
1.00
180
Wettable
Powders
for
Chemigation
application
(
50)
sod
farms
40.80
350
0.4
8.7
11
150
0.11
0.57
1.1
20
Wettable
Powders
for
Groundboom
application
(
51)
sod
farms
40.80
80
1.7
38
49
660
0.50
2.5
5
89
Wettable
Powders
for
Groundboom
application
(
52)
Peanuts
2
80
35
770
1000
13000
10
51
100
1800
Wettable
Powders
for
Chemigation
application
(
53)
peanuts
2
350
8.1
180
230
3100
2.3
12
23
420
Wettable
Powders
for
Groundboom
application
(
54)
pepper,
tomato
7.50
80
9.5
210
270
3600
2.7
14
27
490
Wettable
Powders
for
Groundboom
application
(
55)
pine
(
seed
orchard)
37.50
10
15
330
430
5700
4.3
22
43
780
Applicator
Sprays
for
High­
Pressure
HandWand
application
(
56)
containerized
nursery
stock,
soil
drench
(
beans,
brussels
sprouts,
cabbage,

cauliflower)
0.0038
1000
gals
3100
8800
16000
No
Data
240
1200
2400
No
Data
Sprays
for
High­
Pressure
HandWand
application
(
57)
commercial/
industrial
lawns,
residential
lawn
0.04
1000
gals
310
880
1600
No
Data
24
120
240
No
Data
Sprays
for
High­
Pressure
HandWand
application
(
58)
ornamentals
(
foliar
application
only)
1.50
1000
gals
7.8
22
39
No
Data
0.59
2.9
5.9
No
Data
Sprays
for
High­
Pressure
HandWand
application
(
59)
containerized
nursery
stock,
soil
drench
(
pepper,
tomato)
0.0038
1000
gals
3100
8800
16000
No
Data
240
1200
2400
No
Data
Sprays
for
Groundboom
application
(
60)
Soil
band
treatment
(
broccoli,
brussels
sprouts,
cabbage,

cauliflower)
30
80
630
630
800
1800
39
190
390
680
    
53
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Sprays
for
Groundboom
application
(
61)
Cotton
2
200
3800
3800
4800
11000
240
1200
2400
4100
Sprays
for
Groundboom
application
(
62)
Peanuts
11.59
80
1600
1600
2100
4500
100
500
1000
1800
Sprays
for
Groundboom
application
(
63)
Band
treatment
(
dried
beans,
succulent
beans,

lima)
2
80
9400
9400
12000
26000
590
2900
5900
10000
Sprays
for
Groundboom
application
(
64)
Band
treatment,
soil
treatment
(
garlic)
20
80
940
940
1200
2600
59
290
590
1000
Sprays
for
High­
Pressure
HandWand
application
(
65)
commercial
industrial
lawn
0.15
1000
gals
78
220
390
No
Data
5.9
29
59
No
Data
Sprays
for
Groundboom
application
(
66)
Cotton
2
200
3800
3800
4800
11000
240
1200
2400
4100
Sprays
for
Groundboom
application
(
67)
Garlic
20
80
940
940
1200
2600
59
290
590
1000
Sprays
for
Groundboom
application
(
68)
Peanuts
10
80
1900
1900
2400
5300
120
580
1200
2000
Sprays
for
Groundboom
application
(
69)
Potato
25
80
750
750
950
2100
47
230
470
810
Sprays
for
Aerial
application
(
70)
potato
25
350
No
Data
No
Data
No
Data
480
No
Data
No
Data
No
Data
120
Sprays
for
Groundboom
application
(
71)
Soil
band
treatment
(
broccoli,
Chinese
broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
30
80
630
630
800
1800
39
190
390
680
Sprays
for
High­
Pressure
HandWand
application
(
72)
containerized
stock
(
broccoli,
Chinese
broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,

cauliflower,
collards,

kale,
mustard)
0.02
1000
gals
780
2200
3900
No
Data
59
290
590
No
Data
Sprays
for
Airblast
application
(
73)
Foliar
spray
(
magnolia
tree)
6
20
490
730
800
9200
130
650
1300
1300
    
54
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Sprays
for
Groundboom
application
(
74)
Tomato,
pepper
7.50
80
2500
2500
3200
7000
160
780
1600
2700
Sprays
for
Groundboom
application
(
75)
Southern
pine
(
seed
orchard)
42.50
10
3500
3500
4500
9900
220
1100
2200
3800
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
76)
Beans
1.50
80
18000
24000
42000
83000
490
2400
4900
2700
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
77)
Soil
band
treatment
(
broccoli,
brussels
sprouts,
cabbage,

cauliflower,
collards,

kale,
mustard)
30
80
880
1200
2100
4200
24
120
240
130
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
78)
Golf
course
turf
(
tees/
greens)
43.56
10
4900
6700
11000
23000
130
670
1300
730
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
79)
Golf
course
turf
(
fairways)
43.56
40
1200
1700
2900
5700
33
170
330
180
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
80)
Sod
farms
43.56
80
610
840
1400
2900
17
84
170
91
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
81)
Cotton
2
200
5300
7300
13000
25000
150
730
1500
800
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
82)
Peanuts
2
80
13000
18000
31000
63000
360
1800
3600
2000
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
83)
Pepper
1.35
80
20000
27000
46000
93000
540
2700
5400
2900
Applying
Granulars
for
Tractor­
Drawn
Spreaders
application
(
84)
Potato
25
80
1100
1500
2500
5000
29
150
290
160
Sprays
for
Groundboom
application
(
85)
Beans(
lima,
snap,

dried)
1.50
80
13000
13000
16000
35000
790
3900
7900
14000
Sprays
for
Groundboom
application
(
86)
Soil
band
treatment
(
broccoli,
Chinese,

broccoli,
brussels
sprouts,
cabbage,

Chinese
cabbage,
30
80
630
630
800
1800
39
190
390
680
    
55
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
cauliflower,
collards,

kale,
mustard)

Sprays
for
High­
Pressure
HandWand
application
(
87)
commercial/
industrial
lawns
0.50
1000
gals
23
66
120
No
Data
1.8
8.8
18
No
Data
Sprays
for
Groundboom
application
(
88)
Cotton
2
200
3800
3800
4800
11000
240
1200
2400
4100
Sprays
for
Groundboom
application
(
89)
Sod
farms
40.80
80
460
460
580
1300
29
140
290
500
Sprays
for
Groundboom
application
(
89a)
Sod
farms
32.67
80
570
570
730
1600
36
180
360
620
Sprays
for
Groundboom
application
(
90)
Peanuts
2
80
9400
9400
12000
26000
590
2900
5900
10000
Sprays
for
Groundboom
application
(
91)
Pepper,
tomato
7.50
80
2500
2500
3200
7000
160
780
1600
2700
Sprays
for
Groundboom
application
(
92)
Pine
(
seed
orchard)
37.50
10
4000
4000
5100
11000
250
1200
2500
4300
Flagger
Flagging
for
Sprays
application
(
93)
Potato
25
350
220
240
240
11000
23
110
230
1100
Mixer/
Loader/
App
Mixing/
Loading/
Applying
Liquids
for
Handgun
(
lawn)
Sprayer
(
ORETF)
application
(
94)
Ornamentals
(
herbaceous
plants,

woody
shrubs
and
vines)
218
5
No
Data
No
Data
77
No
Data
36
No
Data
No
Data
No
Data
Mixing/
Loading/
Applying
Liquids
for
Handgun
(
lawn)
Sprayer
(
ORETF)
application
(
95)
Ornamental
and
Lawn
turf
32.67
5
No
Data
No
Data
510
No
Data
240
No
Data
No
Data
No
Data
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
(
96)
Commercial
industrial
lawns
43.56
5
280
440
880
No
Data
44
No
Data
No
Data
No
Data
Loading/
Applying
Granulars
for
Belly
Grinder
application
(
97)
ornamental
lawns
and
turf
43.56
0.5
96
100
No
Data
No
Data
52
270
520
No
Data
Loading/
Applying
Granulars
for
Belly
Grinder
application
(
98)
ornamentals
(
shade
trees,
herbaceous,

woody
shrubs
and
vines)
217.80
0.5
19
21
No
Data
No
Data
10
54
100
No
Data
    
56
  
73
Table
15:
Summery
of
Short
and
Intermediate­
Term
Occupational
Risk
for
PCNB
Dermal
MOE
Inhalation
MOE9
Exposure
Scenario
(
Scenario
#)
Crop
App
Rate4
lbai/
A
or
lb
ai/
gal
Daily
Area
Treated
A
or
gals
Baseline
PPE1
PPE2
PPE3
PPE4
PPE5
PPE6
Eng.
C
Baseline
PPE1
PPE4
PPE2
PPE5
PPE3
PPE6
Eng.
C
Loading/
Applying
Granulars
for
Push­
type
spreader
(
ORETF)
application
(
99)
Ornamentals
(
shade
trees,
herbaceous,

woody
shrubs
and
vines)
217.80
0.5
550
880
1800
No
Data
88
No
Data
No
Data
No
Data
Mixing/
Loading/
Applying
Wet
Powders
for
Low
Pressure
Handwand
application
(
100)
ornamental
(
woody
shrubs
and
vines,

herbaceous
plants)
217.80
5
2.2
2.2
3.1
No
Data
0.058
0.29
0.58
No
Data
Mixing/
Loading/
Applying
Wet
Powders
for
Low
Pressure
Handwand
application
(
101)
ornamental
(
shade
trees)
37.50
5
13
13
18
No
Data
0.34
1.7
3.4
No
Data
Baseline
:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
long­
sleeved
shirts,
long
pants,
no
gloves,
and
no
respirator.

PPE1:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
a
no
respirator.

PPE2:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
a
dust/
mist
(
5
fold
PF)
respirator.

PPE3:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
an
air
purifying
(
10
fold
PF)
respirator.

PPE4:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
coveralls
over
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
no
respirator.

PPE5:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
coveralls
over
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
a
dust/
mist
(
5
fold
PF)
respirator.

PPE6:
Occupational
handlers
using
open
mixing
techniques
and
open
cab
tractors
are
wearing
coveralls
over
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
an
air
purifying
(
10
fold
PF)

respirator.
Engineering
Controls:
Occupational
handlers
using
closed
mixing
techniques
and
enclosed
cab
tractors
or
cockpits
while
wearing
long­
sleeved
shirts,
long
pants,
chemical
resistant
gloves,
and
no
respiratory
protection.
    
57
  
73
APPENDIX
2
A
compiled
list
of
all
metabolites
of
PCNB
found
in
plant
metabolism,
animal
metabolism,
rotational
crops,
water,
and
rat
(
toxic)
studies.

#
Matrices
(
MRID
in
parentheses)
Chemical
Name
(
other
names
in
parenthesis)
Structure
1
Potato
(
45307303)
peanut
(
45307302)
peanut
roots
(
41562902)
whole
potato,
callus,
and
peel
(
41562903)
cabbage
leaves
(
41562904)
chicken
fat
(
41692801)
Rotational
crops:
lettuce,
wheat
forage,
wheat
straw
(
44577501)
pentachloronitrobenzene
(
PCNB)

2
Potato
(
45307303)
peanut
(
45307302)
whole
potato
and
peel
(
41562903)
goat
liver
(
41692805)
goat
kidney
(
41692805)
goat
omental
fat
(
41692805)
goat
renal
fat
(
41692805)
goat
milk
(
41692805)
chicken
fat
(
41692801)
egg
yolk
(
41692801)
Rotational
crops:
turnip
top,
turnip
root,
lettuce,
wheat
forage,
wheat
straw
(
44577501)
pentachloroaniline
(
PCA)

3
Potato
(
45307303)
whole
potato
and
peel
(
41562903)
cabbage
leaves
(
41562904)
chicken
thigh
(
41692801)
egg
yolk
(
41692801)
Rotational
crops:
turnip
root,
lettuce,
wheat
forage,
wheat
straw
(
44577501)
pentachlorothioanisole
(
PCTA)

or,

(
methyl
pentachlorophenyl
sulfide,
MPCPS)

4
Potato
(
45307303)
peanut
(
45307302)
Rotational
crops:
lettuce
(
44577501)
S­(
pentachlorophenyl)
malonylcysteine
(
PCP­
MalCys)

(
C5MaCy)

5
Potato
(
45307303)
peanut
(
45307302)
Rotational
crops:
wheat
forage,
aminotetrachlorobenzene
sulfonic
acid
(
AM
TCB
sulfonic
acid)
    
58
  
73
wheat
straw
(
44577501)
(
C4SANH)

(
tetrachlorosulfanilic
acid)

6
Potato
(
45307303)
pentachloroanisole
(
PCAN)

7
Potato
(
45307303)
egg
yolks
(
41692801)
Rotational
crops:
lettuce,
wheat
forage,
wheat
straw
(
44577501)
pentachlorobenzene
(
PCB)

8
Potato
(
45307303)
peanut
root
(
41562902)
whole
potato,
callus,
and
peel
(
41562903)
cabbage
leaves
(
41562904)
goat
liver
(
41692805)
goat
urine
(
41692805)
chicken
kidney
(
41692801)
N­
hydroxypentachloroaniline
(
NOHPCA)

9
Potato
(
45307303)
potato
callus
and
peel
(
41562903)
S­(
pentachlorophenyl)­
 ­
glutamyl
cysteine
(
PCP­
GluCys)

10
Potato
(
45307303)
Rotational
crops:
wheat
forage
(
44577501)
S­(
pentachlorophenyl)
glutathione
(
PCP­
GSH)
    
59
  
73
11
Potato
(
45307303)
peanut
roots
(
41562902)
whole
potato
callus,
and
peel
(
41592903)
chicken
excreta
(
41692801)
S­(
pentachlorophenyl)
malonylcysteine
monomethyl
ester
(
PCP­
MalCys
ester)

12
Potato
(
45307303)
chicken
fat
(
41692801)
goat
kidney
(
41692805)
tetrachloroaniline
methyl
sulfoxide
(
TCA
sulfoxide
isomers)

13
Potato
(
45307303)
tetrachloro­
methylthio­
aniline
sulfamate
(
TC­
MET­
A
sulfamate)

14
Potato
(
45307303)
potato
peel
(
41562903)
tetrachloronitrobenzene
(
TCNB
isomers)

15
Potato
(
45307303)
tetrachloronitrobenzene
sulfonic
acid
(
TCNB
sulfonic
acid
isomers)
    
60
  
73
16
Potato
(
45307303)
tetrachloronitrothioanisole
(
TCNTA
isomers)

17
Potato
(
45307303)
tetrachlorophenol
methyl
sulfoxide
(
TCP
sulfoxide)

18
Potato
(
45307303)
tetrachlorothiophenol
methyl
sulfoxide
(
TCTP
sulfoxide)

19
Potato
(
45307303)
tetrachlorothiophenol
sulfonic
acid
(
TCTP
sulfonic
acid)

20
Potato
(
45307303)
aminotetrachloroaniline
(
AM
TCA
isomers)
    
61
  
73
21
Potato
(
45307303)
aminotetrachloroaniline
sulfamate
(
AM
TCA
sulfamate)

22
Potato
(
45307303)
hydroxytetrachloroaniline
(
OH
TCA)

23
Potato
(
45307303)
N­
hydroxyamino­
tetrachloroaniline
(
NOHAM
TCA)

24
Potato
(
45307303)
N­
hydroxyamino­
tetrachlorophenol
(
NOHAM
TCP)

25
Potato
(
45307303)
N­
hydroxyaminotetrachlorothioanisole
(
NOHAM
TCTA
isomers)

26
Potato
(
45307303)
S­(
tetrachloro­
methyl
sulfoxy­
phenyl)
glutathione
(
TC­
MES­
P­
GSH)
    
62
  
73
27
Potato
(
45307303)
S­(
tetrachloro­
methyl
sulfoxy­
phenyl)
malonylcysteine
(
TC­
MES­
P­
MalCys)

28
Potato
(
45307303)
peanut
(
45307302)
S­(
tetrachloronitrophenyl)
glutathione
(
TCNP­
GSH)

29
Potato
(
45307303)
Peanut
(
45307302)
S­(
tetrachloronitrophenyl)
malonylcysteine
(
TCNP­
MalCys)

30
Potato
(
45307303)
S,
S ­(
tetrachlorophenyl)
diglutathione
(
TCP­
diGSH)

31
Potato
(
45307303)
S,
S ­(
tetrachlorophenyl)
dithioacetate
(
TCP­
dithioacetate)

32
Potato
(
45307303)
S,
S ­(
tetrachlorophenyl)­
 ­
glutamyl
cysteine­
cysteine
(
TCP­
GluCys­
Cys)
    
63
  
73
33
Potato
(
45307303)
acetyl
S,
S ­(
tetrachlorophenyl)
cysteine­
cysteinyl
 ­
hydroxyglutarate
(
AC
TCP­
Cys­
CysHOG)

34
Potato
(
45307303)
trichloronitroaniline
methyl
sulfoxide
(
RCNA
sulfoxide)

35
Potato
(
45307303)
N­
hydroxy­
trichloro­
dimethylthioaniline
(
NOH
RC­
diMET­
A)

36
Potato
(
45307303)
N­
hydroxyamino­
trichloro­
methoxyaniline
(
NOHAM
RC­
OME­
A)

37
Potato
(
45307303)
S,
S ­(
trichloroanilino)­
 ­
glutamylcysteine­
cysteine
(
RCAGluCys
Cys)
    
64
  
73
38
peanut
(
45307302)
N­
malonyl­
S­
(
tetrachloroaminophenyl)­
cysteine
39
Potato
(
45307303)
S,
S ­(
trichloronitrophenyl)
malonyl
cysteine­
thioacetate
(
RCNP­
MalCysthioacetate

40
Potato
(
45307303)
S,
S ­(
trichlorothioanisole)­
 ­
glutamyl
cysteine­
cysteine
(
RCTA­
GluCys­
Cys)

41
Potato
(
45307303)
diacetyl
S,
S ­(
trichloro­
anisole)
glutathione­
cysteine
(
diAC
RCANGSH
Cys)
    
65
  
73
42
Potato
(
45307303)
diacetyl
S,
S ­(
trichloro­
thioanisole)
diglutathione
(
diAC
RCTA­
diGluCys)

43
Potato
peel
(
41562903)
Tetrachloronitrophenol
(
TCNP)

44
potato
peel
(
41562903)
Tetrachlorophenol
(
TCP)

45
peanut
roots
(
41562902)
Tetrachloroaniline
(
TCA)

46
goat
urine
(
41692805)
Pentachloroaniline
sulfamate
    
66
  
73
47
Rotational
crops:
turnip
top,
turnip
root,
lettuce,
wheat
forage,
wheat
straw
(
44577501)
C5SA
pentachlorobenzenesulfonic
acid
48
goat
liver
(
41692805)
goat
kidney
(
41692805)
chicken
excreta
(
41692801)
chicken
liver
(
41692801)
egg
yolk
(
41692801)
Pentachlorothiophenol
(
PCTP)

49
cabbage
leaves
(
41562904)
chicken
liver
(
41692801)
Rotational
crops:
turnip
top,
turnip
root,
wheat
forage,
wheat
straw
(
44577501)
Pentachlorothioanisole
sulfoxide
(
PCTA
sulfoxide)
(
PCTASO)
(
C5MX)

50
goat
kidney
(
41692805)
chicken
fat
(
41692801)
Tetrachlorothioanisole
(
TCTA)

51
cabbage
leaves
(
41562904)
Rotational
crops:
wheat
straw
(
44577501)
Tetrachlorophenyl
methyl
sulfoxide
(
TCPM
sulfoxide)
(
C4MX)
    
67
  
73
52
cabbage
leaves
(
41562904)
chicken
kidney
(
41692801)
chicken
thigh
(
41692801)
Rotational
Crops:
turnip
top,
turnip
root,
lettuce
(
44577501)
Tetrachlorophenyl
methyl
sulfone
(
TCPM
sulfone)
(
TCTASOO)
(
C4MS)
(
TCP
methyl
sulfone)

53
cabbage
(
41562904)
Rotational
crops:
turnip
top,
turnip
root,
lettuce,
wheat
forage,
wheat
straw
(
44577501)
Trichlorophenyl
methyl
sulfone
(
RCPM
sulfone)
(
C3MS)

54
cabbage
leaves
(
41562904)
Trichlorophenol
methyl
sulfone
(
RCHM
sulfone)

55
goat
liver
(
41692805)
goat
kidney
(
41692805)
goat
urine
(
41692805)
Tetrachloro
(
methylthio)
thiophenol
(
TCTP
S­
Met)

56
goat
liver
(
41692805)
Pentachlorothiophenol
dimer
(
PCTP
dimer)
    
68
  
73
57
potato
callus
and
peel
(
41562903)
goat
urine
(
41692805)
Pentachlorothiophenyl
conjugate
(
PCTP­
X)

58
chicken
excreta
(
41692801)
chicken
kidney
(
41692801)
chicken
liver
(
41692801)
chicken
thigh
(
41692801)
S­(
pentachlorophenyl)
thioacetate
59
chicken
excreta
(
41692801)
S­(
pentachlorophenyl)
thiopyruvate
60
whole
potato,
callus,
and
peel
(
41562903)
chicken
kidney
(
41692801)
S­(
pentachlorophenyl)
cysteine
(
PCPCys

61
peanut
roots
(
41562902)
S­[(
methylthio)
tetrachlorophenyl]­
2­
thioacetic
acid
(
MTCP­
TAA)

62
potato
callus
and
peel
(
41562903)
Pentachlorothiophenyl
glycoside
(
PCTP­
Gly)
    
69
  
73
63
potato
callus
and
peel
(
41562903)
Pentachlorophenol
glycoside
(
PCPGly

64
goat
liver
(
41692805)
goat
kidney
(
41692805)
N­(
pentachloroaniline)
glucuronide
(
PCA­
Gluc)

65
Rotational
Crops:
turnip
top,
turnip
root
(
44577501)
Pentachlorophenol
(
PCP)

66
Rotational
crops:
turnip
top,
turnip
root,
lettuce,
wheat
forage,
wheat
straw
(
44577501)
tetrachlorobenzenesulfonic
acid
(
C4SA)

67
Rotational
crops:
turnip
top,
turnip
root,
wheat
forage,
wheat
straw
(
44577501)
C3SA
trichlorobenzenesulfonic
acid
    
70
  
73
68
Rotational
crops:
turnip
top,
turnip
root,
wheat
forage
(
44577501)
C2SA
dichlorobenzenesulfonic
acid
69
Rotational
crops:
wheat
forage,
wheat
straw
(
44577501)
C4MXSA
tetrachlorosulfophenyl
methyl
sulfoxide
(
tetrachlorothioanisole
sulfoxide,
sulfonic
acid)

70
Rotational
crops:
wheat
straw
(
44577501)
C3MXSA
trichlorosulfophenyl
methyl
sulfoxide
(
trichlorothioanisole
sulfoxide,
sulfonic
acid)

71
Rotational
crops:
wheat
straw
(
44577501)
C4MSSA
tetrachlorosulfophenyl
methyl
sulfone
(
tetrachlorothioanisole
sulfone,
sulfonic
acid)

72
Rotational
crops:
turnip
top,
turnip
root,
wheat
forage,
wheat
straw
(
44577501)
C3MSSA
trichlorosulfophenyl
methyl
sulfone
(
trichlorothioanisole
sulfone,
sulfonic
acid)
    
71
  
73
73
Rotational
crops:
wheat
straw
(
44577501)
C2MSSA
dichlorosulfophenyl
methyl
sulfone
(
dichlorothioanisole,
sulfonic
acid)

74
Rotational
crops:
wheat
forage,
wheat
straw
(
44577501)
C3SANH
trichlorosulfanilic
acid
75
Rotational
crops:
wheat
forage
(
44577501)
C3SAOH
hydroxy­
trichlorobenzene
sulfonic
acid
(
trichloro­
hydroxybenzene
sulfonic
acid)

76
Rotational
crops:
lettuce,
wheat
forage,
wheat
straw
(
44577501)
C4MeAcCy
N­{
1­
methyl­
2[(
tetrachlorophenyl)­
thio]
ethyl}
acetamide
(
tetrachlorophenyl
methyl
cysteine)
    
72
  
73
77
Rotational
crops:
lettuce,
wheat
forage
(
44577501)
C4MaCyFCy
S­(
tetrachlorophenyl)­
Nmalonylcysteine
S'­
formylcysteine
78
Rotational
crops:
wheat
forage
(
44577501)
C5SAHx
b
pentachlorobenzenesulfonic
acid
hexose
ester
79
Rotational
crops:
wheat
forage
(
44577501)
C4CyCy
S,
S'­
tetrachlorophenyl
dicysteine
80
Rotational
crops:
lettuce
(
44577501)
C4CyFCy
S­(
tetrachlorophenyl)­
cysteine­
S'­
formylcysteine
81
Rotational
crops:
turnip
root,
lettuce
(
44577501)
C3MSMaCy
N­
malonyl­
S­
trichloro­
(
methylsulfonophenyl)­
L­
cysteine
S­(
trichlorophenyl
methyl
sulfone)­
malonyl
cysteine
82
Rotational
crops:
turnip
top,
turnip
root
(
44577501)
C2MSMaCy
    
73
  
73
N­
malonyl­
S­
dichloro­
(
methylsulfonophenyl)­
L­
cysteine
S­(
dichlorophenyl
methyl
sulfone)­
malonyl
cysteine
83
Goat
liver
(
41692805)
glucuronide
of
NOHPCA
(
NOHPCAGluc

84
Water
(
minor
degradate)
pentachlorothioanisole
sulfone
(
PCTASO2)