Document ID: EPA-HQ-ORD-2006-0187-0087
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-05T04:00Z

1
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
Azinphos
methyl
(
AZM)
is
an
organophosphate
pesticide
(
OP).
Consistent
with
other
OPs,
AZM
elicits
neurotoxicity
through
the
inhibition
of
the
enzyme,
acetylcholinesterase,
via
phosphorylation
of
the
active
site.
At
sufficiently
high
doses,
exposure
to
AZM
can
lead
to
a
variety
of
clinical
signs.
The
Agency
is
developing
an
assessment
to
estimate
risk
to
workers
from
exposure
to
AZM.
In
addition,
AZM
is
a
member
of
the
OP
common
mechanism
group
and
is
thus
included
in
the
cumulative
risk
assessment
for
the
OPs.
2
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
1.
Scientific
considerations:

The
Agency's
WOE
document
and
DER
for
AZM
describe
the
study
design
and
results
of
the
AZM
repeat
dose,
oral,
human
toxicity
study.
The
WOE
document
also
discusses
the
Agency's
conclusions
regarding
the
usefulness
of
the
human
study
in
the
worker
risk
assessment
and
in
the
cumulative
risk
assessment
for
the
OPs.

For
AZM,
the
Agency
has
concluded
that
the
human
toxicity
study
is
appropriate
for
developing
a
point
of
departure
for
extrapolation
of
risk
to
workers
exposed
to
AZM
via
the
dermal
and
inhalation
routes.
3
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
1.
Scientific
considerations,
cont'd:

For
the
cumulative
risk
assessment,
the
Agency
has
determined
that
because
no
cholinesterase
inhibition
was
seen
in
the
human
toxicity
study,
it
is
not
possible
to
evaluate
whether
steady
state
had
been
reached
in
humans
at
28
days
of
exposure.
Thus,
the
Agency
has
concluded
that
the
AZM
repeat
dose,
oral,
toxicity
study
is
not
sufficiently
robust
for
informing
the
inter­
species
factor
in
the
cumulative
risk
assessment
of
the
OPs.
4
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
1.
Scientific
considerations,
cont'd:

Please
comment
on
the
scientific
evidence
that
supports
the
Agency's
conclusions
for:

a.
the
use
of
the
human
toxicity
study
to
develop
a
point
of
departure
for
extrapolation
of
risk
to
workers
in
the
worker
risk
assessment,
and
b.
the
determination
that
the
human
toxicity
study
cannot
be
used
to
inform
the
inter­
species
factor
in
the
cumulative
risk
assessment.
5
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
2.
Ethical
considerations:

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


Whether
the
informed
consent
materials
 

which
refer
to
"
the
company"
and
"
supervising
doctor",
without
further
identification,
and
contain
no
discussion
of
who
would
benefit
from
the
research
 
should
be
considered
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted;
and,
6
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
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
any
discussion
of
the
potential
risks
to
subjects
or
benefits
to
society
of
conducting
the
proposed
research
(
as
required
by
the
1996
Declaration
of
Helsinki,
Principle
#
5,
with
which
the
research
asserted
compliance)
should
be
considered
significantly
deficient
relative
to
the
ethical
standards
prevailing
when
the
study
was
conducted;
and
7
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
2.
Ethical
considerations:

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/
each]
study:
provide
comment
on
the
following:


OPP's
conclusion
that
there
is
not
clear
and
convincing
evidence
that
the
conduct
of
the
research
was
fundamentally
unethical.
8
Azinphos
Azinphos
Methyl
Charge
to
the
HSRB
Methyl
Charge
to
the
HSRB
2.
Ethical
considerations:

b,
cont'd.
The
Agency
asks
that
the
Board
provide
comment
on
the
following,
taking
into
account
all
that
is
known
about
the
ethical
conduct
of
[
this/
each]
study:
provide
comment
on
the
following:


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.