Overview
of
Human
Health
Risk
Assessment
Process
Bill
Burnam
Health
Effects
Division
Office
of
Pesticide
Programs
2
Mission
of
Health
Effects
Division

Assess
the
risks
of
pesticide
use
to
humans
and
domestic
animals

We
have
both
the
Subdivision
F
Guidelines
and
the
40CFR
Toxicology
Data
Requirements
to
get
the
data
we
need
for
risk
assessment
3
Data
Needs

HED
needs
both
exposure
data
and
toxicity
data
to
assess
the
risks

The
basis
for
the
toxicity
data
requirements
and
the
dietary
exposure
data
are
from
the
old
FDA
days

Non­
dietary
exposure
data
come
later

FQPA
has
brought
about
the
need
for
other
data
4
Exposure
Data

Exposure
data
is
for
both
dietary
(
including
water)
and
non­
dietary
sources
(
including
applicators,
mixer­
loaders,
residential
and
reentry
into
treated
fields)


Jeff
Evans
will
discuss
non­
dietary
sources

Rick
Loranger
will
discuss
dietary
exposure
5
Toxicity
Data

Toxicity
data
requirements
are
meant
to
provide
data
and
endpoints
that
can
be
used
to:


Assess
the
hazards
of
pesticides
over
various
routes
(
oral,
dermal
and
inhalation)
durations
of
time
(
short,
intermediate
and
long
term)


Assess
hazards
during
critical
periods
of
life
stages
6
Durations
of
Exposure

These
durations
of
times
for
any
route
of
exposure
are
as
follows:


Acute
o
Single
day
o
May
use
toxicity
endpoints
of
concern
from
acute
neurotoxicity,

developmental
toxicity,
developmental
neurotoxicity
studies

Short
term
o
1­
30
days
o
May
use
toxicity
endpoints
of
concerns
from
the
studies
mentioned
above
plus
subchronic
studies
in
mice,
rats
and/
or
dogs

Intermediate
o
1­
180
days
o
All
the
above
plus
subchronic
and
multi­
generation
reproduction
studies

Chronic
or
long
term
o
Greater
than
180
days
o
May
use
toxicity
endpoints
of
concern
from
chronic
toxicity/
cancer
(
rat),

cancer
(
mouse),
chronic
(
dog),
multi­
generation
reproduction
(
rat)
studies
7
Critical
Testing
Period

Examples
of
the
critical
period
testing
would
be
as
follows:


Developmental
toxicity
o
During
critical
periods
of
gestation
examines
growth
and
development
of
fetuses

Reproduction
o
Through
reproductive
cycle
of
2
generations
examines
reproductive
changes
in
parents
and
toxicity
to
offspring

Developmental
neurotoxicity
o
Prenatal
and
postnatal,
examines
functional
and
morphological
hazard
in
the
offspring
8
Proposed
Changes
to
Part
158

The
proposed
2005
draft
of
Part
158
is
similar
in
format
&
design
to
the
1984
version

Food/
Non­
food

Required/
Conditionally
required

Many
footnotes

Options
for
toxicity
data
requirements
for
non­
food
uses

The
key
is
exposure
o
Magnitude,
duration
and
frequency
9
Character
of
Changes

There
are
no
sweeping
changes
but
some
evolution
of
data
requirements

But
what
has
changed?


Better
explanation
of
why
we
need
the
data

Explanation
of
why
the
data
requirements
have
changed
o
Re­
registration
process
(
1988
FIFRA
Amendments)

o
The
1983
National
Academy
Science
report
o
The
proposed
changes
in
1994
o
The
1996
FQPA
Mandate
with
emphasis
on
children's
health
risk
10
Toxicology
Data
Requirements:

Acute
Testing
870.2500
870.2400
870.1300
870.1200
870.1100
Guideline
Primary
dermal
irritation
Primary
eye
irritation
­
rabbit
Acute
inhalation
toxicity
­
rat
Acute
dermal
toxicity
Acute
oral
toxicity
­
rat
Current
requirement
Primary
dermal
irritation
Primary
eye
irritation
­

rabbit
Acute
inhalation
toxicity
­

rat
Acute
dermal
toxicity
Acute
oral
toxicity
­
rat
Proposed
requirement
Added
testing
using
the
TGAI
to
support
end­
use
products
81­
5
Added
testing
using
the
TGAI
to
support
end­
use
products
81­
4
No
changes
81­
3
Modified
test
substance
81­
2
Modified
test
substance
81­
1
Change
Guide
­
line
11
Toxicology
Data
Requirements:

Acute
Testing
870.6200
870.6100
870.2600
Guide­
line
None
Acute
delayed
neurotoxicity
­
hen
Dermal
sensitization
Current
requirement
Acute
neurotoxicity
­
rat
Delayed
neurotoxicity
(
acute)
­
hen
Dermal
sensitization
Proposed
requirement
New
requirement
­­
No
changes
81­
7
Added
testing
using
the
TGAI
to
support
end­
use
products
81­
6
Change
Guideline
12
Toxicology
Data
Requirements:

Subchronic
Testing
No
changes
90­
day
Inhalation
­

rat
870.3465
90­
day
Inhalation
­
rat
82­
4
Changed
from
CR
to
R
for
all
nonfood
uses.

90­
day
Dermal
870.3250
90­
day
Dermal
82­
3
870.3200
870.3150
870.3100
Guide­
line
21­
day
Dermal
90­
day
Feeding
 
non­
rodent
90­
day
Feeding
­

rodent
Current
requirement
21­
day
Dermal
90­
day
Feeding
 
non­
rodent
90­
day
Feeding
­

rodent
Proposed
requirement
Changed
from
CR
to
R
for
all
food
uses.
Not
required
for
nonfood
uses.

82­
2
No
changes
82­
1
Requirement
modified
to
include
2
rodent
species
82­
1
Change
Guideline
13
Toxicology
Data
Requirements:

Subchronic
Testing
870.6100
870.6200
Guideline
90­
day
Neurotoxicity
­
hen
90­
day
Neurotoxicity
­
mammal
Current
requirement
28­
day
Neurotoxicity
­
hen
90­
day
Neurotoxicity
­
rat
Proposed
requirement
New
­
conditional
requirement.

Replaces
90­
day
neurotoxicity
hen
study
82­
5
Changed
from
CR
to
R
82­
5
Change
Guideline
14
Toxicology
Data
Requirements:

Chronic
Testing
870.6100
870.4100
Guideline
Oncogenicity
 
rat
and
mouse,

preferred
Chronic
feeding
 
rodent
and
nonrodent
Current
requirement
Carcinogenicity
 
rat
and
mouse,

preferred
Chronic
feeding
 
rodent
and
nonrodent
Proposed
requirement
Changed
name.

Proposed
requirement
to
perform
range­
finding
studies
83­
2
No
changes
83­
1
Change
Guideline
15
Toxicology
Data
Requirements:

Developmental
Toxicity
&
Reproduction
New
 
conditional
requirement
science­
based
approach
to
testing.

Developmental
neurotoxicity
870.6300
None
870.3800
870.3700
Guideline
Reproduction
 
2
generation
Teratogenicity
 
2
species
Current
requirement
Reproduction
Prenatal
developmental
toxicity
 
rat
and
rabbit,
preferred
Proposed
requirement
Changed
from
CR
to
R
for
nonfood
uses
based
on
potential
exposure.

83­
4
Changed
name.

Testing
required
on
a
second
species
for
food
and
nonfood
uses
83­
3
Change
Guideline
16
Toxicology
Data
Requirements:

Mutagenicity
Testing
No
changes
Other
mutagenicity
studies
Replaces
current
mutagenicity
battery
In
vivo
cytogenetics
870.5385
870.5395
Other
genotoxic
effects
84­
4
870.5300
870.5375
870.5100
Guideline
Structural
chromosome
aberration
Gene
mutation
Current
requirement
In
vitro
mammalian
cell
assay
Bacterial
reverse
mutation
assay
Proposed
requirement
Replaces
current
mutagenicity
battery
84­
2
Replaces
current
mutagenicity
battery
84­
2
Change
Guideline
17
Toxicology
Data
Requirements:

Special
Testing
Replaces
current
neurotoxicity
battery
Peripheral
nerve
function
870.6850
None
Replaces
current
neurotoxicity
battery.

Scheduled
controlled
operant
behavior
870.6500
None
No
changes
Companion
animal
safety
870.7200
Domestic
animal
safety
85­
1
870.7600
870.7485
Guideline
Dermal
penetration
General
metabolism
Current
requirement
Dermal
penetration
General
metabolism
Proposed
requirement
No
changes
85­
2
No
changes
85­
1
Change
Guideline
18
Toxicology
Data
Requirements:

Special
Testing
870.7800
870.6855
Guideline
None
None
Current
requirement
Immunotoxicity
Neurophysiology:

Sensory
evoked
potentials
Proposed
requirement
New
requirement.

Required
for
food
uses
and
nonfood
uses.

Replaces
current
neurotoxicity
battery
Change
Guideline
