Document ID: EPA-HQ-ORD-2006-0187-0080
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-05T04:00Z

1
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
Aldicarb
is
a
N­
methyl
carbamate
(
NMC)
pesticide
whose
primary
toxic
effect
is
neurotoxicity
caused
by
the
inhibition
of
the
enzyme,
acetylcholinesterase,

via
carbamylation
followed
by
rapid
recovery.

Aldicarb
can,
at
sufficiently
high
doses,
lead
to
a
variety
of
clinical
signs.
The
Agency
is
conducting
an
acute,
aggregate
(
single
chemical,
multi­
route)
risk
assessment
of
aldicarb.
In
addition,
aldicarb
is
a
member
of
the
N­
methyl
carbamate
common
mechanism
group
and
is
thus
included
in
the
cumulative
(
multi­
chemical,
multi­
route)
risk
assessment
for
the
NMCs.
2
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
1.
Scientific
considerations:

The
Agency's
"
Weight
of
the
Evidence"
(
WOE)
document
and
Data
Evaluation
Records
(
DERs)
for
aldicarb
describe
the
study
design
and
results
of
the
aldicarb
acute
oral,
human
toxicity
study.
The
WOE
document
also
discusses
the
Agency's
conclusions
regarding
the
usefulness
of
the
human
study
in
the
acute,
aggregate,
single
chemical
risk
assessment
and
in
the
cumulative
risk
assessment
for
the
NMCs.
Regarding
the
aldicarb
human
study,
the
Agency
has
concluded
that
the
study
is
sufficiently
robust
for
reducing
the
inter­
species
(
i.
e.,
animal
to
human)
uncertainty
factor
in
the
aggregate
and
the
cumulative
risk
assessments.
3
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
1.
Scientific
considerations,
cont'd:

Please
comment
on
the
scientific
evidence
that
supports
whether
the
aldicarb
human
study
is
sufficiently
robust
for
reducing
the
inter­
species
(
i.
e.,
animal
to
human)

uncertainty
factor
in:

a.
single
chemical,
aggregate
risk
assessment
and
b.
cumulative
risk
assessment.
4
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
2.
Ethical
considerations:

a.
The
Agency
requests
that
the
Board
provide
comment
on
the
following:


In
light
of
the
ethics
committee's
instruction
that
the
lay
summary
be
"
greatly
expanded,"
and
the
fact
that
the
materials
used
to
obtain
informed
consent
listed
a
limited
range
of
symptoms
of
carbamate
toxicity
(
excluding
some
reported
as
adverse
effects
in
the
study),
included
multiple
references
to
the
test
material
as
a
drug,
and
failed
to
identify
dose
levels
to
be
administered
to
male
subjects,
whether,
the
materials
used
to
obtain
informed
consent
should
be
considered
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted
5
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
2.
Ethical
considerations,
cont'd:

a.
cont'd.
The
Agency
requests
that
the
Board
provide
comment
on
the
following:


Whether
the
absence
from
the
protocol
of
discussion
of
the
potential
risks
to
subjects
or
benefits
to
society
of
conducting
the
proposed
research
(
as
required
by
the
1989
Declaration
of
Helsinki,
Principle
#
4,
with
which
the
research
asserted
compliance)
should
be
considered
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted;
and
6
Aldicarb
Aldicarb
Charge
to
the
HSRB
Charge
to
the
HSRB
2.
Ethical
considerations,
cont'd:

b.
The
Agency
asks
that
the
Board
provide
comment
on
the
following,
taking
into
account
all
that
is
known
about
the
ethical
conduct
of
this
study:


OPP's
conclusion
that
there
is
not
clear
and
convincing
evidence
that
the
conduct
of
the
research
was
fundamentally
unethical.


Whether
there
is
clear
and
convincing
evidence
that
the
conduct
of
the
study
was
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted