Document ID: EPA-HQ-ORD-2006-0187-0103
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-05T04:00Z

Types
of
Human
Studies
and
the
Types
of
Human
Studies
and
the
Role
of
Human
Studies
in
Pesticide
Role
of
Human
Studies
in
Pesticide
Risk
Assessment
Risk
Assessment
Ray
Kent,
Ph.
D.

Ray
Kent,
Ph.
D.

U.
S.
EPA
U.
S.
EPA
Office
of
Pesticide
Programs
Office
of
Pesticide
Programs
April
4,
2006
April
4,
2006
2
Scope
of
Human
Studies
in
OPP
Scope
of
Human
Studies
in
OPP

Toxicity
studies

Absorption,
distribution,
metabolism
and
excretion
Studies

Exposure
studies

Special
studies
3
Toxicity
Studies
Reviewed
in
OPP
Toxicity
Studies
Reviewed
in
OPP

Systemic
toxicity
studies

Dermal
irritation
or
sensitization

Eye
irritation
and
other
sensory
threshold
studies

Epidemiology,
incident
data,
case
reports

In
vitro
studies
4
Systemic
Toxicity
Studies
Systemic
Toxicity
Studies

Defined
as
studies
to
identify
or
quantify
an
adverse
response

Never
common,
these
studies
have
increased
since
passage
of
FQPA

OPP
has
no
guidelines
for
conducting
such
studies
5
Dermal
Irritation
&
Sensitization
Studies
Dermal
Irritation
&
Sensitization
Studies

Infrequently
submitted
in
support
of
conventional
pesticides

Used
for
warnings
and
other
label
language

Sometimes
submitted
in
support
of
home
uses
for
antimicrobial
pesticides

No
guidelines
for
performing
irritation
or
sensitization
studies
6
Eye
Irritation
Studies
Eye
Irritation
Studies

Studies
on
fumigant
gasses
recently
submitted

May
be
used
for
quantitative
risk
assessment

No
guidelines
in
OPP
for
human
eye
irritation
studies
7
Epidemiology
Epidemiology
&
Incident
Data
&
Incident
Data

Full
epidemiology
studies
are
infrequently
submitted

Poisoning
incidents
or
case
reports
are
considered
in
all
HED
risk
assessments

Epidemiologic
studies
and
incident
data
are
not
considered
to
involve
intentional
exposure
of
human
subjects
8
In
Vitro
Studies
In
Vitro
Studies

Usually
genotoxicity
studies
with
human
cell
lines,
or
dermal
absorption
studies
with
human
skin

Likely
to
increase
in
frequency
as
in
vitro
methods
are
perfected

Not
considered
to
be
intentional
exposure
of
human
subjects
9
Which
Toxicity
Studies
Go
to
the
HSRB?

Which
Toxicity
Studies
Go
to
the
HSRB?

Need
HSRB
review

Systemic
toxicity

Dermal
irritation
or
sensitization

Eye
irritation
No
HSRB
review

Epidemiology

Poisoning
or
incident
data

In
vitro
studies
10
ADME
Studies
ADME
Studies

Dermal
absorption
studies
are
often
submitted

Used
to
relate
exposure
data
and
toxicity
data

No
guidelines
for
human
ADME
studies

Future
ADME
studies
are
subject
to
HSRB
review
11
Exposure
Studies
in
OPP
Exposure
Studies
in
OPP

Surveys
of
food
consumption
and
human
activity
patterns

Pesticide
handler
studies

Post­
application
studies

Biomonitoring
studies
12
Dietary
and
human
activity
surveys
Dietary
and
human
activity
surveys

Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)
used
in
dietary
exposure
assessment

Consolidated
Human
Activity
Database
used
in
the
OP
and
NMC
cumulative
assessments

Surveys
are
not
considered
intentional
exposure
studies
subject
to
HSRB
review
13
Pesticide
Handler
Studies
Pesticide
Handler
Studies

Most
common
human
study

The
Pesticide
Handlers
Exposure
Database
(
PHED)
is
a
database
of
handler
studies

Guidelines
published
for
proper
conduct
of
handler
studies

Handler
studies
may
be
subject
to
HSRB
review
14
Post
Post­
application
Studies
application
Studies

Commonly
submitted
study
for
conventional
pesticides

Guidelines
published
for
proper
conduct
of
post­
application
studies

Post­
application
studies
may
be
subject
to
HSRB
review
15
Biomonitoring
Biomonitoring
Studies
Studies

Blood
or
urinary
marker
of
exposure
to
determine
delivered
dose

Requires
coordination
of
exposure
assessor
and
toxicologist
for
proper
interpretation
of
results

Future
biomonitoring
studies
will
likely
require
HSRB
review
16
Special
Human
Studies
Special
Human
Studies

Insect
Repellent
Efficacy
Studies
 

studies
are
considered
intentional
exposure
studies
for
purposes
of
HSRB
review

Mechanistic
Studies
 
requires
HSRB
review
if
human
subjects
are
involved
17
Toxicity
Reviews
in
HED
Toxicity
Reviews
in
HED

In
HED
a
human
toxicity
study
is
assigned
to
a
toxicologist
familiar
with
the
toxicology
of
an
active
ingredient

The
HED
toxicologist
evaluates
the
scientific
quality
of
a
human
study
and
how
the
study
fits
in
to
the
overall
toxicity
profile
of
an
a.
i.
18
Roles
of
Human
Toxicity
Studies
Roles
of
Human
Toxicity
Studies

Provide
endpoint
and
PoD
for
risk
assessment

Inform
the
interspecies
uncertainty
factor

Inform
the
intraspecies
uncertainty
factor
19
Roles
(
continued)

Roles
(
continued)

Mode
or
mechanism
studies
to
establish
human
relevance
of
animal
data

In
vitro
or
in
vivo
Studies
to
develop
PBPK
or
PBBR
models
20
Conclusions
Conclusions

All
human
toxicity
studies
are
considered
for
their
relevance
to
the
risk
assessment

Relevant
studies
are
reviewed
for
scientific
quality
and
ethics

The
role
of
a
study
in
a
risk
assessment
is
determined
in
a
weight
of
evidence
analysis
encompassing
the
whole
toxicity
database