1
Carbofuran
Human
Studies
EPA
Human
Studies
Review
Board
Meeting
Alexandria,
VA
May
2­
3,
2006
Donald
B.
Carlson,
PhD
Jane
D.
McCarty,
M.
S.
DABT
FMC
Corporation
©
FMC
Corporation
2006
2
Conclusions:

Carbofuran
Human
Studies
°
Met
ethical
standards
°
Have
been
judged
scientifically
valid
°
Useful
for
risk
assessment
purposes
including:

 
Determining
points
of
departure
for
dietary
and
worker
risk
assessments
 
As
basis
for
reduction
of
uncertainty
factors
°
Consistent
with
prior
external
peer
reviews
and
EPA
internal
review
comments
(
EPA,
1997)
3
FMC
Conducted
Three
Carbofuran
Studies
Involving
Humans
°
One
oral
study
(
technical
material
in
capsule)

°
Two
dermal
studies
 
75
Base
Manufacturing
Use
Product
 
Furadan
4F
(
44%
ai/
gal.)

°
Conducted
1976­
1977
 
Quincy
Research
Center,
Midwest
Research
Institute,
Kansas
City,
MO
°
Independent,
not­
for­
profit
research
institute
4
Purpose
of
Carbofuran
Human
Studies
was
to:

°
Further
understand
compound's
effects
in
pesticide
formulation
workplace
environment
°
Implement
improved
occupational
health
and
industrial
hygiene
programs
°
Enhance
the
protection
of
manufacturing
plant
employee's
safety
and
health
5
Specific
Study
Objectives
Were
Set
°
Oral
Study
 
Determine
minimum
dose
to
induce
cholinergic
effects
 
Establish
RBC
level
at
which
symptoms
occur
°
Dermal
Studies
 
Determine
threshold
toxicity
level
to
single
&
multiple
doses
of
carbofuran
under:

°
Elevated
temperature
and
humidity
conditions
°
Milder
temperature
and
humidity
conditions
°
With
physical
exercise
6
Carbofuran
Human
Studies
Met
Ethical
Standards
of
the
Time
°
Protocols
reviewed
by
Community
Review
Committee,

Inc.

 
Existing
external
non­
profit
corporation
for
the
protection
of
subjects
in
human
research
°
Subjects
gave
informed
consent;
could
withdraw
at
any
time
°
Subjects
monitored
by
qualified
medical
professionals
°
Purposes
of
studies
clearly
explained
to
subjects
 
"
Better
than
average
for
mid­
70'
s
studies"
(
EPA,
2005)

 
"
Frank
identification
of
pesticide
as
test
material"
(
EPA,
2005)

 
"
No
expected
benefit
to
volunteers
explicitly
stated"
(
EPA,
2005)
7
Oral
Study
Reviewed
by
Three
Independent
Peer
Reviewers
and
EPA
in
1997
°
Concluded:

 
Study
had
some
limitations
 
Study
judged
to
be
scientifically
relevant
 
Agreed
on
NOAEL
of
0.05
mg/
kg
 
Accepted
for
regulatory
purposes
°
Agreed
study
should
be
used
to
set
RfD
°
Agreed
study
should
be
used
to
inform
on
uncertainty
factors
8
Environmental
Conditions
Affect
75%
Base
Dermal
Studies
Results
°
High
Heat
and
Humidity
(
85­
95
°
F,
68­
89%
RH)

 
0.5­
1.0
mg/
kg:
No
symptoms,
22­
24%
RBC
ChEI
 
2.0
mg/
kg:
Severe
symptoms
of
cholinesterase
inhibition,
56%
RBC
ChEI
°
Moderate
Heat
and
Humidity
(
70­
75
°
F,
35­
40%

RH)

 
No
symptoms
up
to
and
including
32
mg/
kg
 
RBC
Cholinesterase
inhibition
15,
12,
12
and
20%
for
2,
4,
8
and
32
mg/
kg
doses
respectively
9
Furadan
4F
Results
also
complicated
by
extreme
environmental
conditions
°
High
temperature
and
humidity
(
90­
95
°
F,
70­

88%
RH)

 
Well
known
that
symptoms
of
both
ChEI
and
heat
exhaustion
include:
sweating,
fatigue,
headache,

confusion,
loss
of
muscle
coordination
and
nausea
°
At
higher
doses
of
1.0
and
2.0
mg/
kg:
No
symptoms,
25%
RBC
ChEI
°
Therefore,
symptom
of
nausea
seen
at
lowest
dose,
0.5
mg/
kg,
with
ave.
15%
RBC
ChEI,
is
unlikely
to
be
due
to
carbofuran.

 
Supported
by
lack
of
symptoms
seen
at
0.5
and
1.0
mg/
kg
in
75
base
study
10
Carbofuran
Dermal
Studies
­
Conclusions
°
High
heat
and
Humidity
Studies
­
Conducted
under
artificially
created
environment:

 
Heat
indices
up
to
140oF
 
Survey
of
major
U.
S.
cities
indicates
average
heat
index
for
July
is
100oF
and
maximum
120oF
 
Unlikely
to
encounter
comparable
extremes
under
field
conditions
°
Results
from
high
temperature
humidity
conditions
should
not
be
used
to
regulate
carbofuran
°
Moderate
conditions
are
more
relevant
for
setting
uncertainty
factors
11
Conclusions:

Carbofuran
Human
Studies
°
Met
ethical
standards
°
Have
been
judged
scientifically
valid
°
Useful
for
risk
assessment
purposes
including:

 
Determining
points
of
departure
for
dietary
and
worker
risk
assessments
 
As
basis
for
reduction
of
uncertainty
factors
°
Consistent
with
prior
external
peer
reviews
and
EPA
internal
review
comments
(
EPA,
1997)
