Document ID: EPA-HQ-ORD-2006-0187-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-03-14T05:00Z

1
Risk
Assessment
Overview
­
or­

A
Risk
Assessment
is
Not
a
Number
Michael
S.
Metzger
HED
Risk
Assessment
Training
and
Certification
Program
2
Objectives
­
To
Understand:

°
The
risk
assessment
paradigm
°
Required
toxicity
studies
°
Route/
duration
effects
on
toxicity
°
Standard
HED
risk
assessments
°
Endpoint
selection
°
Dietary
assessment
°
Occupational/
residential
assessment
3
Objectives
 
To
Understand:

°
Drinking
water
assessments
°
Aggregate
assessment
°
Cumulative
assessment
°
A
risk
assessment
is
not
a
number!
4
The
Risk
Assessment
Paradigm:

The
"
Red
Book"

Hazard
Identification
Dose
Response
Assessment
Exposure
Assessment
Risk
Characterization
*
From
the
National
Research
Council's
Risk
Assessment
in
the
Federal
Government:
Managing
the
Process,
1983.
http://
books.
nap.
edu/
books/
030904894X/
html/
1.
html
5
Hazard
Assessment:
Typically
Required
Guideline
Studies
°
Acute
toxicity
battery
°
Subchronic
oral
toxicity
study
in
rats
°
Subchronic
dermal
toxicity
study
in
rats
and
rabbits
°
Subchronic
inhalation
toxicity
study
in
rats
°
Developmental
toxicity
studies
in
rats
and
rabbits
°
2­
Generation
reproduction
study
in
rats
6
Hazard
Assessment:
Required
Studies
°
Chronic
/
carcinogenicity
studies
in
rats,
dogs,

and
mice
°
Acute
(
ACN)
and
subchronic
(
SCN)
neurotoxicity
studies
in
rats
°
Delayed
neurotoxicity
study
in
hens
°
Mutagenicity
testing
battery
(
in
vitro)

°
Developmental
neurotoxicity
study
(
DNT)
in
rats
°
Dermal
absorption
study
°
Rat
metabolism
study
7
Hazard
Characterization
°
Important
toxicological
effects
observed
including
developmental
/
fetal,
reproductive,
endocrine,

carcinogenic,
and
other
effects
°
Any
critical
exposure
periods
and
routes
°
Metabolism
and
potential
for
bioaccumulation
°
Quality
of
the
data
and
uncertainties
°
Studies
which
provide
conflicting
results,
and
why
a
particular
study
might
be
deemed
to
be
the
most
appropriate
to
rely
on
8
Hazard
Characterization
°
Toxicity
data
available
for
related
chemicals
°
Pertinence
of
the
toxicity
observed
to
humans
°
Availability
of
epidemiological
data
which
supports
or
does
not
support
other
hazard
information
°
Adverse
effects
on
wildlife
that
may
be
pertinent
to
human
health
risk
assessment
°
Toxic
mode
of
action
information
°
Confidence
in
the
conclusions,
alternative
conclusions
which
could
be
drawn,
significant
data
gaps,
and
highlights
of
major
assumptions
9
Hazard
Characterization
°
Each
characterization
factor
describes
our
confidence
in
the
hazard
assessment,
and
therefore
our
confidence
in
the
risk
assessment

without
transparent,
clear,
consistent,

and
reasonable
characterization,
the
assessment
has
little
meaning
A
risk
assessment
is
not
a
number!
10
Dose­
Response
Assessment
and
Endpoint
Selection
°
Provides
a
quantitative
description
of
the
hazard
potential
which
can
be
used
to
assess
the
concern
for
effects
to
people
who
may
be
exposed.
11
Dose­
response
Assessment
and
Endpoint
Selection:
Definitions
°
Endpoint:
Toxic
Effect
upon
which
the
risk
assessment
is
based
°
Lowest
Observed
Adverse
Effect
Level
(
LOAEL):
Lowest
dose
from
a
study
at
which
adverse
toxic
effects
were
observed
°
No
Observed
Adverse
Effects
Level
(
NOAEL):
The
dose
below
the
LOAEL
at
which
no
adverse
toxic
effects
are
observed
°
Point
of
Departure
(
POD):
Any
dose
level
used
to
quantify
risk
(
generic)
12
*
NOAEL
/
LOAEL
Dose
Spacing
°
NOAEL
/
LOAEL
dose
spacing
usually
ranges
between
2X
and
10X.

°
True
NOAEL
will
be
somewhere
between
the
NOAEL
and
LOAEL
Will
always
lead
to
a
conservative
(
protective)
hazard
estimate
A
risk
assessment
is
not
a
number!
13
Dose­
response
Assessment
and
Endpoint
Selection:
Adverse
LOAEL
=
Lowest
Observed
Adverse
Effect
Level
LOEL
=
Lowest
Observed
Effect
Level
°
Effects
are
of
concern
only
if
they
are
"
adverse"
=
"
harmful"

Very
minimal
or
adaptive
effects
may
not
be
considered
adverse,
so
would
not
be
suitable
endpoints
for
risk
assessment
14
Dose­
response
Assessment
and
Endpoint
Selection:
Dose
"
All
substances
are
poisons;
there
is
none
which
is
not
a
poison.
The
right
dose
differentiates
a
poison
from
a
remedy."

Paracelsus
(
1493­
1541)

°
Lower
dose
 
lower
toxicity
°
Higher
dose
 
Higher
toxicity
°
No
exposure
 
No
risk
15
Hazard
Assessment:
Hazard
vs.
Risk
°
Hazard
=
toxicity
°
Risk
=
toxicity
x
exposure
16
Dose­
response
Assessment
and
Endpoint
Selection:
Duration
Longer
duration
exposure
 
more
severe
toxicity
 
toxicity
seen
at
lower
doses
Range
of
potential
exposure
durations
must
be
considered
in
risk
assessments
 
One
dose
to
lifetime
17
Dose­
response
Assessment
and
Endpoint
Selection:
Route
°
3
major
routes:
oral,
dermal,
inhalation
°
Toxic
effects
seen
 
and­
severity
of
toxic
effects
can
vary
by
route
°
Of
particular
concern
for
portal­
of­
entry
effects
°
Must
assure
that
route
of
dosing
in
animal
study
matches
human
exposure
route
 
or
characterize
any
mismatch
18
Dose­
response
Assessment
and
Endpoint
Selection
Endpoints
selected
for
risk
assessment
must
be
the
most
sensitive
endpoint
for
each
population,
and
relevant
to
humans.

°
Most
sensitive
(
protective)
 
Most
protective
POD
(
e.
g.
lowest
NOAEL,
highest
q*)

°
Relevant
 
Toxicity
seen
in
animal
studies
could
also
occur
in
humans
19
Dose­
response
Assessment
and
Endpoint
Selection:
Exposure
Scenarios
°
Dietary
°
Oral
food
and
water
(
all
ages)

°
Residential
°
Incidental
oral
ingestion
(
children,
adult
swimmers)

°
Dermal
exposure
(
all
ages)

°
Inhalation
exposure
(
adults,
children
indoors)

°
Occupational
°
Dermal
and
inhalation
exposure
(
adults)
20
Major
Risk
Assessments
Chemical­
specific
Cancer
6
months
­
lifetime
Chronic
1­
6
months
Intermediate­
term
(
IT)
1­
30
days
Short­
term
(
ST)
1­
day
Acute
Duration
of
Continuous
Exposure
Assessment
21
Major
Risk
Assessments:

"
Continuous"
Exposure
"
Continuous
Exposure"

Exposure
sufficiently
often
that
cumulative
toxicity
from
the
chemical
is
expected
to
occur
­
or­

Exposure
sufficiently
often
that
recovery
from
the
toxic
effects
is
unlikely
to
occur
between
doses
22
Major
Risk
Assessments:
Acute
°
One­
day
dietary
(
oral)
exposure
°
Food
and
water
°
One­
day
occupational
or
residential
assessments
(
oral,
dermal,
and
inhalation)

°
Used
to
refine
ST
assessments
23
Major
Risk
Assessments:
Acute
Endpoints
typically
used:

°
Developmental
(
teratogenic)
effects
°
Applicable
to
females
of
child­
bearing
age
only
°
Neurotoxicity
°
Applicable
to
everyone
24
Major
Risk
Assessments:
Acute
1
Reproduction,
rat
<
1
Subchronic,
mouse
<
1
Chronic,
monkey
<
1
Chronic,
rat
<
1
Developmental,
mouse
<
1
Developmental
neurotoxicity,
rat
1
Subchronic
neurotoxicity,
rat
1
Subchronic,
rat
4
Special
studies
7
Subchronic,
dog
22
Developmental,
rabbit
30
Developmental,
rat
30
Acute
neurotoxicity,
rat
Approximate
Percent
of
time
used
Study
Type
25
Major
Risk
Assessments:
Short
Term
(
ST)

°
Duration:
1­
30
days
continuous
exposure
°
Scenarios:

°
Single­
source
occupational
and
residential
assessments
°
When
residential
assessments
are
needed,

aggregate
assessments
for
food,
water
and
residential
°
Routes:
Oral,
dermal,
and
inhalation
26
Major
Risk
Assessments:
Short
Term
(
ST)
­
Typical
Endpoints
Incidental
oral
(
children,
adult
swimmers)

°
Maternal
effects
from
developmental
studies
(
14­
days
dosing)

°
Neurotoxicity
and
other
effects
from
subchronic
studies
Fetal
developmental
effects
not
appropriate
for
children
27
Major
Risk
Assessments:
Short
Term
(
ST)
­
Typical
Endpoints
Dermal
°
Toxicity
seen
in
21­
day
dermal
toxicity
study
 
Dermal
studies
not
always
available
 
Only
a
limited
range
of
endpoints
is
measured
in
21­
day
dermal
studies
28
Major
Risk
Assessments:
Short
Term
(
ST)
­
Typical
Endpoints
Dermal
°
From
oral
studies:

°
Developmental
endpoints
(
adult
females
only)

°
Same
as
incidental
oral
(
adults
and
children)

 
Must
be
corrected
for
%
dermal
absorption
29
Major
Risk
Assessments:
Short
Term
(
ST)
­
Typical
Endpoints
Inhalation
°
Toxicity
seen
in
28­
or
90­
day
inhalation
studies
 
Inhalation
studies
not
always
available
 
Only
a
limited
range
of
endpoints
is
measured
in
most
inhalation
studies
30
Major
Risk
Assessments:
Short
Term
(
ST)
­
Typical
Endpoints
Inhalation
°
From
oral
studies:

°
Developmental
endpoints
(
female
adults
only)

°
Same
as
incidental
oral
(
adults
and
children)

 
Must
be
corrected
for
%
inhalation
absorption
31
Major
Risk
Assessments:

Intermediate
Term
(
IT)

°
Duration:
1­
6
months
continuous
exposure
°
Scenarios:

°
Single­
source
occupational
and
residential
assessments
°
Aggregate
assessments
for
food,
water
and
residential
°
Routes:
Oral,
dermal,
and
inhalation
32
Major
Risk
Assessments:
Intermediate
Term
(
IT)
­
Typical
Endpoints
Incidental
oral
(
children,
adult
swimmers)

°
Toxic
effects
from
subchronic
or
chronic
studies
33
Major
Risk
Assessments:
Intermediate
Term
(
IT)
­
Typical
Endpoints
Dermal
°
Toxicity
effects
from
21­
day
dermal
studies
°
Matches
exposure
route
°
Toxic
effects
from
subchronic
and
chronic
oral
studies
°
Matches
exposure
duration
°
Developmental
°
If
most
sensitive

Must
determine
whether
using
route­
specific
or
duration­
appropriate
study
is
best
for
each
chemical
34
Major
Risk
Assessments:
Intermediate
Term
(
IT)
­
Typical
Endpoints
Inhalation
°
Toxic
effects
from
90­
day
inhalation
study
°
Correct
route
and
duration
°
Toxic
effects
from
subchronic
and
chronic
oral
studies
°
Matches
exposure
duration
°
Developmental
°
If
most
sensitive
35
Major
Risk
Assessments:
Chronic
°
Long­
term
dietary
(
oral)
exposure
°
Food
and
water
°
Long­
term
occupational
assessments
°
dermal
and
inhalation
°
Long­
term
residential
assessments
°
inhalation
36
Major
Risk
Assessments:

Chronic
 
Typical
Endpoints
Oral
and
Dermal
°
Toxic
effects
from
chronic
studies
°
Reproductive
effects
 
%
dermal
absorption
correction
required
for
dermal
37
Major
Risk
Assessments:
Chronic
 
Typical
Studies
Used
for
cPAD
1
Special
studies
<
1
Developmental,
rabbit
<
1
Subchronic,
mouse
<
1
Subchronic,
rabbit
<
1
Developmental,
rat
<
1
Acute
neurotoxicity,
rat
1
Chronic,
monkey
5
Subchronic,
rat
5
Chronic,
mouse
6
Subchronic,
dog
7
Reproduction,
rat
36
Chronic,
rat
36
Chronic,
dog
Approximate
Percent
of
time
used
Study
Type
38
Major
Risk
Assessments:

Chronic
 
Typical
Endpoints
Inhalation
°
Toxic
effects
seen
in
90­
day
inhalation
study
°
Toxic
effects
from
chronic
and
reproduction
studies
(
corrected
for
%
inhalation
absorption)
39
Major
Risk
Assessments:
Cancer
°
Non­
threshold
(
default)

°
Any
exposure
leads
to
some
probability
of
risk
°
Regulated
with
a
q
1
*

°
Threshold
(
only
when
Mode
of
Toxic
Action
is
known)

°
Risk
only
when
exposure
exceeds
threshold
°
Regulated
with
an
MOE,
RfD,
or
PAD
2
major
types:
40
Expressing
Risk
Risks
in
OPP
are
generally
expressed
in
the
following
ways:

°
%
Reference
Dose
(%
RfD)

°
%
Population
Adjusted
Dose
(%
PAD)

°
Margin
of
Exposure
(
MOE)

°
Cancer
Probability
Units
used
in
all
assessments
are
mg/
kg
body
weight/
day
41
Expressing
Risk:
%
Reference
Dose
(%
RfD)

Used
to
express
risks
in
acute
(
aRfD)
and
chronic
(
cRfD)
dietary
assessments
RfD
=
Point
of
Departure
(
e.
g.
NOAEL)

Uncertainty
Factors
(
except
Special
FQPA)

%
RfD
=
exposure
x
100
RfD

Because
the
Special
FQPA
SF
must
be
applied
in
HED
assessments,
the
RfD
is
now
used
in
OPP
primarily
in
calculating
a
Population
Adjusted
Dose
(
PAD)
42
Expressing
Risk:
%
Population
Adjusted
Dose
(%
PAD)

Used
to
express
risks
in
acute
(
aPAD)
and
chronic
(
cPAD)
dietary
assessments
PAD
=
Point
of
Departure
(
e.
g.
NOAEL)

Uncertainty
Factors
(
inc.
Special
FQPA)

%
PAD
=
exposure
x
100
PAD
43
Expressing
Risk:
Margin
of
Exposure
(
MOE)

Used
to
express
risk
for
ORE
assessments,

any
aggregate
assessment
which
includes
an
ORE
component,
and
some
cancer
risks
°
MOE
=
Point
of
Departure
(
e.
g.
NOAEL)

exposure
44
Expressing
Risk:
RfD/
PAD
vs.
MOE
RfD/
PAD
Risk
=
exposure
POD

As
exposure
increases,

%
RfD/%
PAD
increases
MOE
Risk
=
POD
Exposure

As
exposure
increases,

MOE
decreases
45
Expressing
Risk:
Cancer
Probability
Used
to
express
cancer
risks
when
a
nonthreshold
mechanism
is
assumed
(
q
1
*)

°
q
1
*
=
a
measure
of
dose
response
seen
in
cancer
studies
°
Risk
=
q
1
*
x
exposure
46
Dermal
Absorption
°
"
Route­
to­
route
extrapolation"
 
oral
to
dermal
°
Use
of
an
endpoint
from
an
oral
study
for
dermal
risk
assessment
°
Must
correct
dermal
exposure
to
account
for
less
than
100%
of
the
pesticide
being
absorbed
through
the
skin
into
the
body
Multiply
dermal
exposure
x
%
dermal
absorption
(
expressed
as
a
fraction)
47
Inhalation
Absorption
°
"
Route­
to­
route
extrapolation"
 
oral
to
inhalation
°
Math
is
identical
to
that
used
for
dermal
absorption
°
However,
since
always
assume
100%

inhalation
absorption,
use
of
an
oral
endpoint
is
mathematically
the
same
as
using
an
inhalation
endpoint
48
Uncertainty
and
Safety
Factors
°
"
One
of
several,
generally
10­
fold
factors,

used
in
operationally
deriving
the
RfD
and
RfC
from
experimental
data"

(
http://
www.
epa.
gov/
iris/
gloss8.
htm)

°
Intraspecies
 
variability
among
humans
°
Interspecies
 
extrapolating
animal
data
to
humans
°
Extrapolating
from
less­
than­
lifetime
to
lifetime
exposures
°
LOAEL
to
NOAEL
°
Incomplete
data
base
49
Uncertainty
and
Safety
Factors
°
Generally
10X
unless:

°
A
smaller
factor
can
be
shown
to
be
protective,
or
°
A
larger
factor
is
clearly
needed
°
Maximum
=
3000
50
Uncertainty
Factors
RfD
FQPA
SFs
Population
Adjusted
D
os
e
(
PAD)

Traditional
U
Fs
Intraspecies
Factor
In
tersp
ecies
Factor
LOAEL
to
NOAEL
Subchronic
to
C
hronic
In
com
ple
te
to
C
om
p
lete
Database
Special
FQPA
Concerns
Modifying
Factor
Specia
l
FQPA
Safety
Factor
Concerns:

°
Residual
concerns
w
ith
respect
to
e
xposure
data
°
Residual
concern
for
p
re­
and
pos
tnatal
toxic
ity
Areas
o
f
o
verlap
w
ith
T
raditional
UFs
which
d
eal
with
d
ata
problems
51
Special
FQPA
Safety
Factor
Used
when:

°
There
is
concern
that
the
NOAEL
used
in
the
risk
assessment
may
cause
risks
to
be
underestimated
because
of:

°
Poor
dose­
response
°
Small
difference
between
NOAEL
and
LOAEL
°
Concern
that
exposure
may
be
underestimated
52
Uncertainty
Factors
What
if:

°
No
interspecies
differences
°
Minimal
intra­
species
variability

Risk
estimates
will
significantly
exaggerate
real
risks!

A
risk
assessment
is
not
a
number!
53
Exposure
Assessment:
Chemistry
and
Dietary
Exposure
Assessment
Three
major
Areas:

°
Product
Chemistry
°
Residue
Chemistry
°
Dietary
Exposure
Assessment
54
Product
Chemistry
°
Manufacturing
and
Impurities
°
Identifies
important
contaminants
in
pesticide
products
which
could
be
of
risk
concern
°
Physical
/
chemical
property
data
°
Water
solubility
°
Octanol­
water
partition
coefficient
°
Vapor
pressure
55
Residue
Chemistry
Major
areas
include:

°
Metabolism
(
plant
and
livestock)

°
Residue
analytical
methods
°
Residue
Field
Trials
°
Rotational
crop
studies
°
Livestock
feeding
studies
°
Food
processing
studies
°
Residue
monitoring
studies
56
Metabolism
in
Plants
and
Livestock
Nature
of
the
Residue
(
NOR)
studies
°
Purpose:
Used
to
identify
metabolites
or
degradates
which
might
occur
in
foods
as
a
result
of
the
pesticide
use,
specifically:

°
Which
metabolites
must
be
included
in
dietary
risk
assessment
°
Which
metabolites
must
be
included
in
tolerance
expression
57
Metabolism
in
Plants
and
Livestock
Study
design:

°
Radiolabel
the
pesticide
°
Apply
to
plant
or
livestock
(
in
feed
or
directly)

consistent
with
how
pesticide
will
be
used
°
Harvest
crop
or
livestock
consistent
with
how
pesticide
will
be
used
°
Identify
and
quantify
radioactive
products
in
foods
58
Metabolism
in
Plants
and
Livestock
°
Include
metabolites
in
risk
assessment
if:

°
They
are
likely
to
be
of
risk
concern
(
i.
e.,
both
toxic
and
likely
to
result
in
significant
exposure)

°
Separate
assessments
may
be
required
for
metabolites
likely
to
have
significant
toxicity
which
is
different
from
parent
compound
°
Include
metabolites
in
tolerance
expression
if:

°
They
are
present
in
significant
amounts
and
will
be
a
good
measure
of
misuse
of
pesticide
59
Residue
Analytical
Methods
Designed
for
3
purposes:

°
Data
collection
in
field
trials
(
less
validation
required)

°
Tolerance
enforcement
(
ease
of
use
and
robustness
are
important;
may
be
MRMs)

°
Monitoring:
Multi­
Residue
Methods
(
MRMs)
for
use
in
generating
monitoring
data
for
dietary
risk
assessment
(
measure
many
pesticides
in
one
analysis)
60
Residue
Field
Trials
°
Purpose:
To
quantify
residues
in
crops
under
a
range
of
field
conditions
°
While
typically
1­
3
plant
metabolism
studies
would
be
required
to
represent
all
crops
for
a
chemical,
3­
20
field
trials
will
be
required
for
each
crop.
61
Residue
Field
Trials
Study
design:

°
Prepare
representative
formulated
products
°
Apply
each
product
to
the
crops
in
the
field
per
label
directions
(
generally
3­
20
diverse
fields
for
each
formulation)

°
Harvest
the
plants
per
label
directions
°
Measure
residues
(
those
required
for
both
the
tolerance
and
risk
assessment)
in
all
plant
parts
used
for
food
or
feed
62
Rotational
Crop
Studies
°
A
rotational
crop
is
one
which
is
planted
in
a
field
following
harvest
of
the
primary
crop.

°
Rotational
crops
can
contain
residues
resulting
from
pesticide
applications
made
to
the
primary
crop
°
Both
confined
(
radiolabeled)
and
field
(
cold)

rotational
crop
studies
may
be
required
to
identify
and
measure
these
residues
63
Livestock
Feeding
Studies
°
Purpose:
To
quantify
residues
in
meat,
milk,

poultry
and
eggs
resulting
from
livestock
consumption
of
treated
feed,
or
direct
application
to
livestock
°
While
1
livestock
metabolism
study
is
required
for
each
type
of
livestock
(
typically
chickens
and
ruminants),
several
feeding
studies
are
required
for
each
64
Livestock
Feeding
Studies
Study
design:

°
Apply
formulated
pesticide
to
livestock
either
directly
or
in
feed,
in
a
manner
similar
to
which
the
livestock
will
actually
be
exposed
(
multiple
animals)

°
Analyze
samples
of
meat,
milk,
poultry,
and
eggs
for
residues
(
both
those
required
for
risk
assessment
and
tolerance
enforcement)
65
Food
Processing
Studies
°
Purpose:
To
estimate
a
processing
factor
which
describes
the
concentration
or
reduction
in
residue
level
going
from
the
raw
to
processed
commodity
°
Required
for
all
major
processed
foods
66
Food
Processing
Studies
Study
design:

°
Obtain
sample
of
raw
commodity
containing
residues,
measure
residues
°
Process
using
methods
simulating
commercial
processing
methods
°
Measure
residues
in
processed
foods
Processing
Factor
(
PF)
=
Residue
in
proc.
Food
Residue
in
raw
food
67
Residue
Monitoring
Studies
°
Not
generally
required,
but
frequently
used
in
risk
assessment
°
Purposes:

°
Enforcement
(
targeted,
less
useful
for
risk
assessment)

°
Risk
assessment
°
Usually
generated
by
government
agencies
and
pesticide
registrants
68
Residue
Monitoring
Studies
°
Samples
collected
at
various
points
in
commerce
°
Farm
gate,
warehouses
and
food
distribution
points,

grocery
stores
°
Sample
collection
closer
to
consumer

More
accurate
risk
estimates
°
Monitoring
data
most
frequently
used:

°
USDA
PDP
data
°
FDA
Surveillance
Monitoring
°
Registrant­
generated
special
studies
69
Dietary
Exposure
Assessment
°
Two
components
°
Food
residues
°
Food
consumption
70
Dietary
Exposure:
Food
Residues
°
Residue
estimates
obtained
from
°
Field
trials
(
plants)

°
Livestock
feeding
studies
(
MMPE)

°
Monitoring
data
(
various
foods)

°
Processing
factors
(
factors
used
in
combination
with
field
trial
or
monitoring
data)
71
Dietary
Exposure:
Food
Consumption
°
Food
consumption
data
obtained
from
the
USDA's
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)(
1994­
96,

1998
supplemental
data)

°
Consumption
data
may
be
grouped
by
various
factors
including
age,
sex,

region,
ethnicity,
others
72
Dietary
Exposure:
Food
Consumption
°
CSFII
Survey
data
represent
2
nonconsecutive
days
for
each
respondent
°
Used
to
calculate
long­
term
averages
for
each
population
subgroup
°
Longitudinal
(
long­
term)
consumption
data
for
individuals
not
available
73
Dietary
Exposure:
Calculations
Exposure
=
Residue
x
Consumption
Body
Weight
mg
pest
=
mg
pest
x
g
food
x
kg
food
x
1
kgbw­
day
kg
food
day
1000
g
food
kgbw
Correction
factor
74
Dietary
Risk:
Calculations
Risk
(%
PAD)
=
Exposure
x
100
PAD
°
Equation
applies
to
both
acute
and
chronic
dietary
risk
assessments
75
Dietary
Risk:
Acute
Acute
Dietary
Risk:

 
Risk
resulting
from
1­
day
dietary
exposure
°
Residue
level,
food
consumption,
and
endpoint
all
must
represent
1­
day
exposure
or
dosing
76
Acute
Dietary
Risks:

Two
Assessment
Methods
°
Deterministic
 
less
refined
(
lower
tier)

°
Entire
range
of
food
consumption
with
only
single,
high­
end
residue
estimate
°
Screening­
level,
high­
end
risk
estimate
°
Probabilistic
 
more
refined
(
higher
tier)

°
Entire
range
of
both
food
consumption
and
residue
levels
°
More
accurate
risk
estimate
77
Acute
Dietary
Risk
Assessment
°
Outputs
for
both
deterministic
and
probabilistic
assessments
include
exposure
and
risk
estimates
for
different
exposure
percentiles
for
each
population
°
Deterministic
assessments:
Regulatory
target
is
risk
associated
with
95th
percentile
exposure
°
Probabilistic
assessment:
Regulate
target
is
risk
associated
with
99.9th
percentile
exposure
78
Acute
Dietary
Risk
Assessment:

Percentiles
Everyone
95'
th
percentile
99.9'
th
percentile
79
Chronic
Dietary
Risk
Assessment
°
Risks
resulting
from
6
months
to
lifetime
exposure
°
Residue
levels,
food
consumption:
must
be
average
values
°
Only
deterministic
assessments
are
done
since
longitudinal
consumption
data
are
not
available
°
Output:
Average
exposure
and
risk
for
each
population
subgroup
80
Dietary
Risk
Assessment:
Models
Two
models
routinely
used:

°
Dietary
Exposure
Evaluation
Model
­
Food
Commodity
Intake
Database
(
DEEM­
FCID)

°
Models
entire
range
of
single
day
exposures
or
population
averages
°
Lifeline
°
Models
longitudinal
exposures
to
individuals
(
single
day,
seasonal,
and
lifetime)
81
Dietary
Risk
Characterization
What
factors
determine
how
closely
the
risk
estimates
approximate
real
population
risks?


Estimated
risks
can
differ
by
orders
of
magnitude
when
different
data
or
methods
are
used.
82
Dietary
Risk
Characterization
°
Were
field
trial
or
monitoring
data
used
for
risk
drivers
(
foods
with
highest
risks)?
Source
of
monitoring
data?

°
Were
residues
detectable
or
based
on
limits
of
detection?

°
Were
residues
surface
of
systemic?

°
What
processing
data
were
used
(
commercial/
washing/
cooking/
peeling,
or
highend
defaults)?
83
Dietary
Risk
Characterization
°
Were
high­
end
or
a
distribution
of
residues
used?

°
Are
residues
primarily
parent
or
more/
less
toxic
metabolites?

°
Was
percent
crop
treated
used?
84
Dietary
Risk
Characterization:

Example
Assume
risk
at
99.9'
th
percentile
exposure
=
125%

aPAD
Does
this
mean
that
0.1%
of
the
population
will
get
sick
from
exposure
to
pesticide
residues?
85
Dietary
Risk
Characterization:

Example
More
potential
concern
exists
if:

°
Monitoring
data
rather
than
FT
or
feeding
study
data
used
°
A
distributional
rather
than
deterministic
assessment
was
done
°
Refined
processing,
cooking,
washing
or
other
data
were
used
NO!

It
means
that
our
regulatory
target
has
been
exceeded.


Even
with
the
most
refined
exposure
data,
hazard
conservatisms
lead
to
protective
assessments.
86
Dietary
Risk
Characterization:

Example
Does
this
mean
that
we're
never
concerned
with
risks
at
125%
aPAD?

No!

It
means
that:

°
Our
regulatory
target,
designed
to
be
protective
in
virtually
all
situations,
has
been
exceeded
°
We
must
consider
the
elements
of
the
hazard
and
exposure
characterizations
to
determine
our
degree
of
concern
87
Occupational
and
Residential
Exposure
°
Occupational
­
job­
related
exposures
°
Handler:
Mix,
load
and
apply
pesticide
(
agricultural,
professional
residential,

others)

°
Post­
application:
Reentry
after
application
(
e.
g.,
pickers,
thinners)

°
Dermal
and
inhalation
routes
88
°
Residential
­
non­
job­
related
exposures
°
Handler:
Mix,
load,
and
apply
by
homeowner
°
Post­
application:
Reentry
after
application
(
e.
g.,
playing
on
lawns,

playing
golf,
rolling
on
rug)

°
Dermal,
inhalation,
and
oral
routes
Occupational
and
Residential
Exposure
89
Occupational
Handlers
°
Application
Rate:
Label
or
usage
information
(
lbs.
A.
I./
A)

°
Acres
treated:
Standard
values
from
data
and
surveys
°
Unit
exposure:
exposure
per
pound
of
active
ingredient
handled
from
the
Pesticide
Handlers
Exposure
Database
(
PHED)

Three
Major
Inputs:
90
Pesticide
Handlers
Exposure
Database
(
PHED)

°
PHED
aggregates
data
for
different
chemicals
into
scenarios
representative
of
each
activity
/

formulation
type
/
PPE
/
etc

unit
exposures
°
e.
g.,
mix/
load
dry
flowables,
apply
granules

Concept:
Handler
exposure
is
less
dependent
on
chemical
structure,
more
dependent
on
the
physical
processes
of
mixing
and
loading,
the
type
of
formulation,
Personal
Protective
Equipment
(
PPE),

packaging,
application
equipment,
etc.
91
Occupational
Handlers:

Calculations
exposure
=
unit
x
app
x
acres
x
1
exposure
rate
day
BW
mg
=
mg
x
lbs
a.
i.
x
A
x
1
kgbw
day
lb
a.
i
applied
A
day
kgBW
°
Correction
may
be
needed
for
%
dermal
absorption
92
Occupational
Post­
Application
Workers
Three
major
inputs:

°
Dislodgable
Foliar
Residue
(
DFR):
Residue
on
foliage
which
can
rub
off
onto
worker's
skin
°
Transfer
Coefficient
(
TC):
Measure
of
contact
with
foliage
while
performing
a
specific
activity
°
Time
spent
working
93
Occupational
Post­
Application
Workers
°
The
amount
of
contact
with
foliage
while
working
(
TC)
is
not
dependent
on
the
chemical
structure,
but
depends
on
the
type
of
work,
and
the
type
and
growth
stage
of
the
crop
­
a
table
of
standard
TCs
is
available
for
specific
activities
and
crop
types/
growth
stages
°
Over
4000
activity/
growth
stage
combinations
°
The
amount
of
residue
which
can
rub
off
onto
skin
(
DFR)
is
chemical­
specific
­
DFRs
must
be
generated
for
each
chemical
Concept:
94
Occupational
Post­
Application:

Calculations
Exposure
=
DFR
x
TC
x
hours
x
correction
x
1
factor
BW
mg
=
ug
x
cm
2
x
hours
x
mg
x
1
Kgbw
day
cm
2
hour
day
1000
ug
kgbw
°
DFRs
decline
over
time

exposure
declines
over
time:
Used
to
establish
reentry
intervals
(
REIs)
95
Residential
Risk
Assessments

Standard
Operating
Procedures
for
Residential
Exposure
Assessment
("
Residential
SOPs")

 
Residential
lawns
 
Gardens
(
vegetable,

ornamental)

 
Trees
(
fruit,
nut,

ornamental)

 
Swimming
pools
 
Painting
/
wood
preserv.

 
Fogging
 
Crack
and
crevice
tx
 
Pet
uses
 
Detergents/
hand
soap
 
Impregnated
mat.

 
Termiticides
 
Indoor
inhalation
 
Rodenticides
 
U­
pick
96
Occupational
and
Residential
Exposure
°
All
data
conditionally
required
°
40
CFR
180.390,
180.440
°
May
change
in
next
revision
of
Part
158
°
Less
robust
data
than
for
dietary
exposure
°
Much
of
data
is
not
chemical­
specific,
so
generated
by
task
forces
97
Occupational
and
Residential
Exposure:
Task
Forces
°
ARTF
(
Agricultural
Reentry
TF):

°
Occupational
TCs
°
ORETF
(
Outdoor
Residential
Exposure
TF):

°
Lawn
use
exposure
data
°
NDETF
(
Non­
dietary
Exposure
TF):

°
Indoor
exposure
and
residue
data
°
REJV
(
Residential
Exposure
Joint
Venture):

°
Use
and
usage
information
°
AHETF
(
Agricultural
Handlers
Exposure
TF):

°
PHED
replacement
data
98
Occupational
and
Residential
Exposure:
Data
Call­
Ins
(
DCIs)

°
1984:
Field
worker
DCI
°
1995:
Generic
Post­
app
DCI
(
TCs)

°
No
generic
request
for
DFR
data
°
1995:
Lawn
uses
DCI
(
TCs,
activity
pattern,
etc.)

°
Handlers
 
No
DCI
ever
issued
99
Drinking
Water
°
Two
sources:

°
Surface
water:
lakes,
reservoirs,
rivers
°
Ground
water:
underground
sources
100
Surface
Water
(
SW)
Sources
of
Drinking
Water:
Monitoring
°
Preferred
data
source
­
directly
measures
what
people
could
be
exposed
to
°
Rarely
sufficient
because
of
inadequate
sampling,
particularly
for
acute
assessments
°
Geographical
representation
°
Frequency
of
sampling
°
NAWQA,
STORET,
registrant­
generated
studies
101
Surface
Water
(
SW)
Sources
of
Drinking
Water:
Models
°
Used
for
most
risk
assessments
°
Input:
phys/
chem
properties,
1/
2­
lives
°
Tier
1:
FQPA
Index
Reservoir
Screening
Tool
(
FIRST)

°
high
end
values
for
DWLOC
calculations
°
Tier
2:
Pesticide
Root
Zone
Model
­
Exposure
Analysis
Modeling
System
(
PRZM­
EXAMS)

°
high
end
values
for
DWLOC
calculations
°
direct
use
in
distributional
and
chronic
assessments
102
Ground
Water
(
GW)
Sources
Of
Drinking
Water:
Monitoring
°
Useful
for
risk
assessment
more
often
than
SW
monitoring
°
Prospective
GW
monitoring
studies
°
controlled
studies
at
vulnerable
sites
°
National
Water
Quality
Assessment
(
NAWQA)
program,
STORET
103
Ground
Water
Sources
of
Drinking
Water:
Models
°
Model
(
SCIGROW)

°
Often
used
for
risk
assessment
°
Screening
Concentration
In
GROund
Water
(
SCIGROW)

°
Input:
p­
chem
properties,
1/
2­
lives,

chemicalspecific
data
°
regression
model
°
Can
be
used
in
DWLOC
calculations,
or
directly
as
a
single
input
value
104
Aggregate
Exposure
/
Risk
Assessment
FQPA
defines
"
safe"
as:

"
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
the
pesticide
chemical
residue,
including
all
anticipated
dietary
exposure
and
all
other
exposure
for
which
there
is
reliable
information."
105
Aggregate
Exposure
/
Risk
Assessment
Aggregate
typically
includes:

°
Food
°
Drinking
water
°
Other
non­
occupational
exposures
(
e.
g.

residential,
playing
golf)

Oral,
dermal,
and
inhalation
routes
106
Five
Standard
Aggregate
Durations
/
Scenarios:

°
Acute
(<
1­
day)

 
usually
dietary
food
and
DW,
occasionally
includes
refined
residential
exposures
°
Short
(
1­
30
days)
and
Int.­
term
(
1­
6
months)

 
food,
DW,
residential
­
only
done
when
residential
scenarios
exist
°
Chronic
(
6
months
­
lifetime)

 
usually
dietary
food
and
DW,
occasionally
includes
residential
exposures
°
Cancer:

 
food,
DW,
residential
107
Aggregate
Risk
Calculations:

Population
Adjusted
Doses
°
Used
when
only
dietary
(
oral)
components
are
included:

%
PAD
agg
=
%
PAD
food
+
%
PAD
DW
108
Aggregate
Risk
Calculations:

MOE
Approach
°
Used
when
residential
scenarios
are
included,
and
target
MOEs
are
the
same
for
all
routes
of
exposure
(
or
for
cancer
assessment
using
MOE
approach)

MOE
agg
=
1
1
+
1
+
1
MOE
oral
MOE
derm
MOE
inhal
109
Aggregate
Risk
Calculations:

ARI
Approach
°
Aggregate
Risk
Index
(
ARI):
Used
when
residential
scenarios
are
included,
and
target
MOEs
are
NOT
the
same
for
all
routes
of
exposure
ARI
=
MOE
Target
MOE
ARI
agg
=
1
1
+
1
+
1
ARI
oral
ARI
derm
ARI
inhal
110
Aggregate
Risk
Calculations:

Cancer
(
q1*)
Assessment
°
When
cancer
is
quantified
using
a
q
1
*,

aggregate
by
adding
the
cancer
risk
probabilities
for
all
scenarios
°
When
using
a
q
1
*,
risks
quantified
for
general
population
only
111
Cumulative
Risk
°
Combined
aggregate
risks
from
all
chemicals
which
have
a
common
mode
of
action
­
or­

°
Combined
risks
from
food,
drinking
water,
and
residential
exposure,
for
all
pesticides
which
have
common
toxic
effects
produced
in
the
same
way
112
Risk
Characterization
/

Risk
Management
°
Risk
management
is
the
decision­
making
process
involving
considerations
of
political,

social,
economic
and
engineering
factors
with
relevant
risk
assessments
relating
to
a
potential
hazard
so
as
to
develop,
analyze
and
compare
regulatory
options
and
to
select
the
optimal
regulatory
response
for
safety
from
that
hazard.

°
A
major
purpose
of
risk
assessment
is
to
inform
risk
management
decisions
113
The
Risk
Characterization
Handbook
°
Transparency
°
Clarity
°
Consistency
°
Reasonableness
°
http://
www.
epa.
gov/
osp/
spc/
rchandbk.
pdf
114
Risk
Characterization:
Transparency
°
Clearly
understood
assumptions
and
extrapolations,
impact
on
risk
assessment
°
Use
of
modeled
vs.
measured
data,
data
gaps
°
Confidence
in
major
conclusions
°
Uncertainties
115
Risk
Characterization:
Clarity
The
final
product
should:

°
Be
as
brief
as
possible
°
Use
plain
language
°
Be
understandable
to
the
target
audience
116
Risk
Characterization:
Consistency
°
Follow
statutory
requirements
°
Follow
Agency
guidance
and
policies
°
Puts
the
risk
assessment
in
context
with
other
assessments
Necessary
in
a
regulatory
context
to
assure
a
level
playing
field
117
Risk
Characterization:
Reasonableness
°
Is
deemed
to
be
sound
by
interested
parties,

using
generally­
accepted
scientific
knowledge
°
Based
on
best
available
science
°
Provides
plausible
alternative
estimates
of
risk
°
Consistent
with
common
sense
118
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Risk
Assessment
Training
and
Certification
Program
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