UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
January
18,
2002
MEMORANDUM
SUBJECT:
RESPONSE
TO
COMMENTS.
Response
to
Comments
on
EPA's
Human
Health
Risk
Assessment
of
Endosulfan
01/
31/
01.
PC
Code:
079401,
Case
#
819236,
DP
Barcode
D279252.

FROM:
Diana
Locke,
Ph.
D.
Toxicologist
Reregistration
Branch
II
Health
Effects
Division
(7509C)

THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)

TO:
Dan
Helfgott,
Acting
Chief
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7508W)

The
attached
document
titled,
"HED's
Response
to
Comments
for
Endosulfan,"
was
generated
in
Phase
4
of
the
Proposed
Public
Participation
Process
(FR
Notice
03/
15/
00)
to
address
comments
submitted
by
the
Endosulfan
Task
Force
(Aventis
CropScience
USA
LP,
FMC
Corporation,
and
Makhteshim­
Agan
of
North
America,
Inc.),
the
Natural
Resources
Defense
Council
(NRDC),
the
Farmworker
Justice
Fund,
Inc.,
the
Institute
for
Agriculture
and
Trade
Policy,
the
Pesticide
Action
Network
North
America
(PANNA)
and
their
affiliate,
the
Pesticide
Action
Network
Asia
and
Pacific
(PANAP),
Respiratory
and
Environmental
Disabilities
Association
of
Hawaii,
and
the
Rural
Action
Safe
Pest
Control
Program
(RASPCP)
to
the
Agency
during
Phase
3
concerning
the
Agency's
Human
Health
Risk
Assessment
of
Endosulfan
01/
31/
01.
The
attached
document
is
the
Agency's
response
to
those
comments.
This
response
includes
input
from
John
Punzi
(Residue
Chemistry),
Sherrie
Kinard
(Dietary
Assessment)
Robert
Fricke
(Toxicology),
Elizabeth
Mendez
(Toxicology),
Renee
Sandvig
(Occupational
and
Residential
Exposure),
Ruth
Allen
(Incident
Data),
and
Diana
Locke
(Risk
Assessment).

cc:
Stacey
Milan
Margaret
Stasikowski
Lois
Rossi
Pauline
Wagner
TABLE
OF
CONTENTS
I.
Introduction
.............................................................
1
II.
ResidueChemistry........................................................
1
III.
Dietary
(Food)
Assessment
.................................................
4
IV.
DrinkingWater..........................................................
4
V.
Toxicology
.............................................................
4
VI.
OccupationalExposure....................................................
7
VII.
IncidentData
.........................................................
10
1
January
18,
2002
HED'S
RESPONSE
TO
COMMENTS
FOR
ENDOSULFAN
I.
Introduction
The
following
is
the
Health
Effects
Division's
(HED)
response
to
comments
(Phase
4)
for
endosulfan,
generated
in
response
to
the
comments
submitted
to
the
public
docket
by
the
Endosulfan
Task
Force
(ETF),
environmental
interests,
and
consumer
concerns
groups
in
Phase
3
of
the
Proposed
Public
Participation
Process.
Some
of
the
responses
serve
as
clarification
or
a
restatement
of
Agency
policies
and
guidance
and
it
is
hoped
that
this
will
provide
a
greater
understanding
of
the
Agency's
position
and
procedures
on
these
matters.
During
Phase
3,
HED's
endosulfan
risk
assessment
document
was
placed
in
the
public
docket
and
all
interested
parties
were
given
60
days
to
comment
to
the
Agency
in
writing.
Comments
concerning
the
rationale
behind
Agency
decisions,
endpoints
selected,
exposure
assessment,
and
interpretation
of
available
data,
were
submitted.
Since
there
were
a
number
of
comments
submitted
from
very
differing
sources,
HED's
responses
will
be
directed
to
the
issues
raised
and
not
to
each
of
the
commentors.
In
many
cases,
the
same
subject
matter
was
raised
by
several
of
the
commentors
but
with
very
different
view
points.

Several
issues
related
to
the
quantitative
risk
assessment
and
characterization
cannot
be
dealt
with
in
the
Phase
4
timeframe.
Emerging
Agency
policy
on
these
issues
is
expected
to
impact
the
risk
assessment
and
will
be
incorporated
into
a
revised
risk
assessment
document
in
the
Spring
of
2002.
During
Phase
3,
the
ETF
submitted
new
data
and
information
that
may
also
impact
the
quantitative
risk
assessment.
These
data/
information
are
being
reviewed
and
will
be
included,
where
appropriate,
in
the
revised
risk
assessment
(Spring
2002).

II.
Residue
Chemistry
The
reregistration
requirements
for
magnitude
of
the
residue
studies
in
grains
and
processed
grains
are
fulfilled
according
to
an
HED
memo
dated
January
10,
2001
(DP
Barcode,
D268415).

This
conclusion
will
be
incorporated
into
a
revised
chapter.

Existing
labels
carry
a
Lima
bean
use
restriction.
The
Agency
agreed
to
remove
this
restriction
(July
2001,
J.
Punzi
written
reply
to
Nang­
Ly
Chow).

This
restriction
will
be
removed
in
the
revised
chapter.

The
ETF
is
proposing
a
tolerance
of
1.
0
ppm
for
crop
group
9.
2
As
noted
in
the
January
3,
2001
Residue
Chemistry
Chapter,
the
available
residue
data
are
adequate
to
support
this
use.

The
existing
tolerance
for
mustard
seed
will
be
maintained.

The
Agency
will
review
MRID#
00003724
for
this
use
and
examine
application
rates
and
use
parameters.

The
ETF
and
IR­
4
are
asking
the
Agency
to
review
MRID#
s
00138256,
00003587,
and
00003843,
as
well
as
available
raspberry
data
for
adequacy
in
supporting
a
crop
group
tolerance
for
cane
berry.

The
Agency
will
review
the
appropriate
studies
for
this
use
and
examine
application
rates
and
use
parameters.

The
ETF
are
asking
the
Agency
to
consider
available
data
to
support
a
crop
group
tolerance
for
fruiting
vegetables
(Crop
Group
8).

The
Agency
will
review
the
available
data.

The
ETF
is
proposing
that
the
Agency
translate
existing
residue
data
from
potatoes
and
carrots
(root
portion)
and
turnip
greens,
sugarbeet
tops,
kale
and
spinach
(leafy
portion)
to
rutabaga
and
radish.
The
ETF
notes
that
radish
and
rutabaga
use
is
permitted
on
Canadian
labels
and
for
harmonization
reasons
under
NAFTA,
the
data
translation
described
above
is
appropriate.

The
Agency
will
review
the
appropriate
data.

The
ETF
is
requesting
a
tolerance
for
pistachio
nuts
by
translation
of
the
available
data
for
almonds
(MRID#
s
00003713
and
00004254).

The
Agency
will
review
the
available
data.

The
ETF
is
proposing
to
retain
current
labeled
Post
Harvest
Intervals
for
celery
and
leaf
lettuce
and
to
raise
the
tolerances
to
8
ppm
(celery)
and
6
ppm
(leaf
lettuce).
The
proposal
is
supported
by
residue
chemistry
studies
MRID#
s
44346904,
44346906
performed
in
1995.

The
Agency
will
review
all
available
data
for
endosulfan
in/
on
lettuce
and
celery
and
determine
the
adequacy
of
the
data.

The
ETF
notes
that
the
Agency
used
a
pineapple
processing
study
(MRID#
00157147)
to
determine
the
concentration
factors
in
pineapple
peel
and
pineapple
wet
bran.
The
Agency
did
not
review
MRID#
44617402
for
tolerance
reassessment.
Therefore,
the
ETF
requests
that
the
data
be
reviewed
to
determine
processing
factors
for
pineapple
juice
and
pineapple
processed
3
residue/
wet
bran.

The
Agency
will
review
all
available
data
for
endosulfan
in/
on
pineapple
and
determine
the
adequacy
of
the
data.

The
ETF
does
not
agree
with
the
Agency's
calculation
of
a
maximum
dietary
burden
(MDB)
using
pineapple
processed
residues
as
20­
30
%
of
the
total
diet.
The
ETF
correctly
states
this
would
be
very
localized
since
Hawaii
is
the
only
state
where
pineapples
are
grown.
Furthermore,
since
the
MDB
is
based
on
the
pineapple
residues
from
the
processing
study,
inappropriate
values
were
used
in
the
computation.

The
MDB
reflects
very
conservative
diets
based
on
worst
case
scenarios.
Livestock
used
for
meat
and
milk
in
Hawaii
and
subsequent
exposure
to
residues
of
endosulfan
is
not
unrealistic
in
acute
assessments.
While
the
animal
diet
may
be
inappropriate
to
use
for
an
exposure
assessment,
the
dietary
risks
are
small.

Based
on
a
revised
MDB,
reassessed
tolerances
for
fat,
meat
byproducts,
liver,
meat
and
milk
need
to
be
revised.

We
will
review
the
appropriate
pineapple
study
and
make
a
recommendation.

The
ETF
identified
one
error
in
the
end­
use
labels;
The
maximum
application
rate
for
the
emulsifiable
concentrate
(EC)
formulation
used
on
walnuts
reads
2.5
lb
ai/
A
in
the
text.
The
ETF
believes
this
is
an
error
as
the
labels
read
2.0
lb
ai/
A.

The
Agency
has
indeed
verified
that
there
is
a
label
(reg.#
10163­
110)
for
an
EC
formulation
to
be
used
at
2.
5
lbs
ai/
A.
As
a
point
of
reference,
2
lbs
ai/
A
was
used
for
the
wettable
powder
(reg.#
279­
2659).
The
Agency
assesses
exposures
up
to
the
highest
application
rate
for
which
there
is
a
current
registration.
The
Agency
is
reviewing
whether
the
submitted
residue
data
support
these
application
rates.

The
ETF
has
noted
possible
errors
and
requests
correction
for
revisions
to
the
chapter:

Errors
in
Table
8:
Almonds
reassessed
to
0.
2
ppm
vs
0.3
ppm
as
listed
in
the
text.

Cotton
gin
byproducts
reassessed
to
30
ppm
vs
28
ppm
listed
in
the
text.

The
Agency
will
revise
the
appropriate
sections
as
identified
in
this
response
before
the
RED
for
endosulfan
is
finalized.
4
III.
Dietary
(Food)
Assessment
99.9
th
Percentile
Policy
Not
Consistently
Applied
In
HED's
dietary
assessment,
exposure
to
all
populations
was
assessed
at
the
99.
9
th
percentile,
not
just
children
1­
6
years
of
age.
Regulating
at
the
99.9
th
percentile
is
HED's
current
approach
when
the
assessment
includes
such
refinements
as
the
use
of
monitoring
data,
percent
crop
treated,
and
processing
data.
The
endosulfan
assessment
includes
all
of
these
refinements.

Percent
of
Food
Treated
in
Acute
Risk
Assessment
The
current
approach
for
the
application
of
percent
crop
treated
estimates
was
used
in
the
endosulfan
dietary
assessment.
The
maximum
percent
crop
treated
estimates
were
used
in
the
acute
dietary
assessment,
and
the
weighted
average
estimates
were
used
in
the
chronic
dietary
assessment.
The
acute
dietary
assessment
was
also
done
in
accordance
with
HED
SOP
99.6:
Classification
of
Food
Forms
With
Respect
to
Level
of
Blending
(8/
20/
99).

IV.
Drinking
Water
Drinking
Water
Levels
of
Comparison,
derived
from
dietary
(food)
exposures
estimated
at
the
99.9
th
percentile,
were
compared
to
drinking
water
exposures
calculated
at
the
90
th
percentile.
This
underestimates
risk.

The
Environmental
Fate
and
Effects
Division
(EFED),
which
conducts
the
drinking
water
assessment,
uses
the
90
th
percentile
in
its
calculations
to
provide
HED
with
a
somewhat
conservative
estimate
in
which
it
is
assumed
that
one
high/
maximum
concentration
event
will
occur
once
every
ten
years
for
just
one
day
during
that
year.
It
is
EFED's
standard
policy
to
use
this
1­
in­
10
year
storm
event.
With
additional
data,
further
refinements
could
be
made.

V.
Toxicology
Endocrine
disruption
As
part
of
the
hazard
characterization
required
for
risk
assessment,
the
toxicological
database
for
endosulfan
was
reviewed
and
evaluated,
and
is
suggestive
of
endocrine­
related
effects
due
to
endosulfan
exposure.
The
concern
that
endosulfan
may
be
an
endocrine
disruptor
is
based
on
reports
in
the
open
literature
and
in
studies
submitted
to
the
Agency.
The
Agency's
weight­
of­
evidence
that
endosulfan
may
be
an
endocrine
disruptor
is
presented
in
Appendix
A
of
the
HED
Toxicology
Chapter
(HED
DOC
Number:
014049,
dated
November
12,
1999).
The
ETF
submitted
its
own
weight­
of­
evidence
report
(MRID
44939102)
in
evaluating
the
potential
endocrine
effects
of
endosulfan;
which
was
reviewed
by
the
Agency
(ENDOSULFAN:
1
Crisp,
T.
M.
et
al.
Environmental
Endocrine
Disruption:
An
Effects
Assessment
and
Analysis.
Environmental
Health
Perpectives
106
pp.
11­
56.

2
ATSDR
Toxicity
Profile
for
Endosulfan.
September,
2000.

5
Evaluation
of
Registrant
Submission
Endosulfan:
Evaluation
of
Possible
Endocrine
Effects
in
Mammalian
Species.
Elizabeth
Méndez.
December
11,
2000).
After
reviewing
several
published
articles,
the
ETF
concluded
that
"endosulfan
does
not
meet
the
criteria
of
an
endocrine
disruptor."
The
registrant
stated
that
in
vitro
studies
show
that
endosulfan
has
a
low
binding
potency
to
the
human
estrogen
receptors
and
that
"no
effects
were
found
on
endocrine,
reproductive
or
sexually
regulated
systems
in
vivo
at
doses
causing
clear
toxicity."

The
Agency
identifies
an
environmental
endocrine
disruptor
as
an
exogenous
agent
that
interferes
with
the
synthesis,
secretion,
transport,
binding
action,
or
elimination
of
natural
hormones
in
the
body
that
are
responsible
for
the
maintenance
of
homeostasis,
reproduction,
development,
and/
or
behavior.
1
Based
on
these
criteria,
the
Agency
disagrees
with
the
conclusion
by
the
registrant
that
endosulfan
does
not
meet
the
definition
of
an
endocrine
disruptor.
Binding
to
the
estrogen
receptor
is
only
one
potential
mode
of
action
for
endocrine
disruptors,
namely
direct
interaction
with
a
receptor
in
the
target
cells.
Substances
that
act
as
endocrine
disruptors
may
perturb
the
endocrine
system
in
a
variety
of
ways
including
but
not
limited
to
interfering
with
the
synthesis,
secretion,
or
transport
of
hormones
in
the
organism.
Some
examples
of
endocrine
disruption
that
do
not
involve
receptor
binding
are:
1)
depression
of
the
steroidogenic
enzymes
and
cytochrome
P450­
dependent
monooxygenases,
which
suggests
that
conversion
of
cholesterol
to
testosterone
may
be
affected
by
endosulfan;
2)
decreases
in
luteinizing
hormone
(LH)
activity
that
may
result
in
decreases
in
the
activity
of
Steroidogenic
Acute
Regulatory
Protein
responsible
for
translocation
of
cholesterol
from
the
cytosol
to
the
inner
mitochondria
[transport
and
synthesis
affected];
and
3)
effects
on
the
sex­
hormone
binding
globulin
(SHBG)
as
indicated
by
decreases
in
plasma
and
testicular
testosterone
in
conjunction
with
serum
testosterone
[effect
on
hormone
transport].
2
Consequently,
the
absence
of
high
binding
affinity
to
the
estrogen
receptor
should
not
be
interpreted
as
lack
of
endocrine
disruption
potential.
The
Agency
notes
that
other
organochlorines
(i.
e.
DDT,
DDE,
dieldrin,
and
methoxychlor)
have
been
demonstrated
to
interact
with
the
endocrine
system
in
spite
of
differing
binding
affinities
to
the
estrogen
receptor.

Finally,
the
registrant
states
that
no
effects
were
reported
after
administration
of
endosulfan
on
the
endocrine,
reproductive
or
sexually
regulated
systems
at
doses
causing
clear
toxicity.
However,
it
is
noteworthy
that
testicular
atrophy
was
reported
during
a
Chronic
Oral
Toxicity
Study
in
Rats
(MRID#
00004256)
submitted
to
the
Agency.
Additionally,
increased
pituitary
and
uterine
weights
were
also
observed
during
a
Multi­
Generation
Reproduction
Study
(MRID#
00148264).
Furthermore,
an
increase
in
the
incidence
of
parathyroid
hyperplasia
was
also
reported
during
the
Chronic
Oral
Toxicity
study
in
Rats.
The
Agency
emphasizes
the
fact
that
the
endocrine
system
integrates
a
variety
of
CNS­
pituitary­
target
organ
pathways
that
not
only
affect
reproductive
or
sexually
regulated
parameters
but
also
regulates
a
wide
array
of
bodily
3
R.
L.
Cooper
and
R.
J.
Kavlock.
Endocrine
Disruptors
and
Reproductive
Development:
a
Weight­
of
Evidence
Overview.
J.
Endocrinology
152
pp.
159.­
166
6
functions
and
homeostasis.
3
Though
this
is
not
the
case
for
endosulfan,
it
is
important
to
note
that
a
lack
of
overt
toxicity
to
the
reproductive
system
should
not
be
interpreted
as
conclusive
evidence
of
a
lack
of
endocrine
disruption.
Given
the
effects
noted
in
the
Chronic
Oral
Toxicity
Study
in
Rats
and
the
Multi­
Generation
Reproduction
Study
submitted
to
the
Agency,
the
potential
of
endosulfan
to
act
as
an
endocrine
disruptor
can
not
be
discounted.
The
Agency
has
requested
that
a
Developmental
Neurotoxicity
Study
be
conducted;
the
Agency
believes
that
this
study
will
provide
additional
data
that
may
help
elucidate
this
matter.

Selection
of
toxicology
endpoints
for
dermal
and
inhalation
NOAELs
A
re­
review
of
the
of
the
study
(MRID#
00146841,
00147744)
selected
for
establishing
the
dermal
NOAEL
and
LOAEL
indicates
that
9
mg/
kg/
day
is
not
an
effect
level.
In
this
study,
rats
were
treated
dermally
for
21
days
at
dose
levels
of
0,
1,
3,
9,
27
or
81
(males
only)
mg/
kg/
day.
At
9
mg/
kg/
day,
2/
6
males
died;
at
27
mg/
kg/
day
no
mortalities
were
observed
in
males
and
3/
6
females
died,
and
at
81
mg/
kg/
day
3/
6
males
died.
The
two
males
which
died
at
9
mg/
kg/
day
may
have
been
a
result
of
non­
treatment
related
causes
(very
small
immature
testes
and
livers).
It
is
biologically
improbable
to
have
lethality
at
one
dose,
no
lethality
at
a
three­
fold
higher
dose
and
lethality
again
at
a
nine­
fold
higher
dose
The
histopathological
findings
were
also
reexamined.
The
study
pathology
report
states
that
the
two
males
in
the
9
mg/
kg/
day
group
and
the
5
females
in
the
27
mg/
kg/
day
group
"showed
signs
of
incipient
and
in
some
cases
advanced,
autolysis."
Further,
there
was
no
apparent
dose­
response
for
the
incidence
of
histopathological
findings
in
the
liver.

In
another
dermal
toxicity
study,
animals
were
dosed
at
0,
3,
6,
12,
48,
96
(males
only)
or
192
(males
only)
mg/
kg/
day.
The
NOAEL
for
this
study
was
established
at
12
mg/
kg/
day
in
females
and
96
mg/
kg/
day
in
males,
based
on
increased
mortalities
at
48
mg/
kg/
day
in
females
and
at
192
mg/
kg/
day
in
males.

The
selection
of
the
appropriate
NOAEL
for
dermal
toxicity
will
be
deferred
to
HED's
Hazard
Identification
Assessment
Review
Committee
(HIARC).

Endosulfan
is
not
likely
to
bioaccumulate
The
most
compelling
evidence
to
support
the
ETF
claim
that
endosulfan
does
not
bioaccumulate
was
presented
in
a
recently
submitted
toxicokinetic
study
(MRID#
45546201).
In
this
study,
14
C­
endosulfan
(1
mg/
kg/
day)
was
administered
to
male
and
female
rats
for
up
to
28
days.
A
steady
state
concentration
in
blood
and
tissues
was
achieved
by
day
23.
At
day
28,
7
treatment
was
stopped
and
blood
and
tissue
levels
of
labeled
residues
were
measured
for
5
days.
At
the
end
of
the
treatment­
free
period,
there
was
no
evidence
that
indicated
that
endosulfan
bioaccumulates.
Only
9.253%
of
the
total
administered
dose
remained
in
males
and
9.
794%,
in
females
at
the
end
of
the
treatment­
free
period
(i.
e.
over
90%
of
the
radioactivity
was
eliminated).

The
use
of
a
3­
fold
factor
to
account
for
lack
of
long­
term
dermal
study
In
the
absence
of
dermal
toxicity
studies
beyond
30
days
exposure,
the
HIARC
concluded
(HED
Doc
No:
014024)
that
an
additional
3X
factor
is
needed
to
address
the
uncertainty
in
extrapolating
data
from
greater
than
30
days
up
to
several
months
and/
or
years.
This
factor
was
added
based
on
concerns
that
endosulfan
bioaccumulates.
A
recently
submitted
toxicokinetic
study
(MRID#
45546201)
provides
evidence
that
endosulfan
does
not
bioaccumulate.
However,
the
decision
to
retain
or
remove
the
3­
fold
safety
factor
will
be
made
by
the
HIARC.

The
NOAEL
from
the
oral
study
for
assessing
worker
inhalation
risks
While
there
appears
to
be
merit
to
the
ETF
evaluation
of
the
inhalation
data,
the
action
requested
by
the
ETF
is
global
in
nature
and
effects
not
only
endosulfan,
but
other
chemicals
as
well.
The
use
of
oral
toxicity
data
to
establish
an
inhalation
NOAEL
will
have
to
be
deferred
until
management
review.

VI.
Occupational
Exposure
Spray
Drift
and
Take­
home
Exposures,
and
Exposures
to
Farmworker
Children
Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
regional
offices
and
state
lead
agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
of
which
U.
S.
pesticide
registrants
are
members,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off­
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types,
where
appropriate.

In
addition,
the
Agency
is
currently
in
the
process
of
revising
its
guidance
for
completing
other
types
of
assessments,
such
as
exposure
to
farmworker
children.
Modifications
to
this
assessment
shall
be
incorporated
as
updated
guidance
becomes
available.
This
will
include
8
expanding
the
scope
of
the
residential
exposure
assessments
by
developing
guidance
for
characterizing
exposures
from
other
sources
already
not
addressed,
such
as
from
spray
drift;
residential
residue
track­
in;
exposures
to
farmworker
children;
and
exposures
to
children
in
schools.

Assessing
baseline
clothing
for
occupational
mixing/
loading
activities
using
endosulfan
is
inconsistent
with
the
product
labels
and
US
EPA's
Worker
Protection
standard
and
should
be
dropped
from
the
assessment.

Baseline
clothing
attire
is
always
assessed
in
reregistration
assessments.
This
is
done
for
informational
purposes
in
order
to
determine
at
which
mitigation
level
the
risks
to
the
workers
are
no
longer
of
concern.
Also,
personal
protective
equipment
(PPE)
and
engineering
control
requirements
often
differ
on
currently
registered
labels
for
older
chemicals,
because
many
older
chemicals,
including
endosulfan,
have
a
large
number
of
registered
products
held
by
several
different
manufactures
and
the
registration
approval
dates
can
often
vary
widely.
The
Agency
does
take
the
present
PPE
and
engineering
controls
on
the
product
labels
into
consideration
during
the
risk
mitigation
process.

Many
of
the
occupational
handler
scenarios
presented
in
the
RED
represent
uses
that
are
not
supported
by
ETF
labels
and
should
be
removed
from
the
assessment.
These
are:
(1e)
mixing/
loading
of
liquids
for
rights
of
way
application;
(2d)
mixing/
loading
of
wettable
powders
for
rights
of
way
applications;
(6)
rights
of
way
spray
application;
(8)
mixing/
loading/
applying
of
liquids
with
a
low
pressure
handwand;
(9)
mixing/
loading/
applying
of
wettable
powders
with
a
low
pressure
handwand;
(10)
mixing/
loading/
applying
of
liquids
with
a
high
pressure
handwand.

The
rights
of
way
sprayer,
the
low
pressure
handwand,
and
the
high
pressure
handwand
are
considered
the
application
techniques
used
to
apply
liquids
and
wettable
powders
in
tree
bark
treatments.
The
low
and
the
high
pressure
handwands
are
also
known
to
be
commonly
used
in
greenhouses
and
in
drench
treatments.
Since
uses
in
greenhouses,
bark
and
drench
treatments
are
all
currently
registered
for
endosulfan,
the
above
occupational
scenarios
will
continue
to
be
assessed
by
the
Agency
and
included
in
the
risk
assessment.

The
use
of
a
50
percent
protection
factor
for
a
second
layer
of
clothing
is
conservative
and
overestimates
exposure.
This
is
in
conflict
with
the
90%
protection
factor
used
by
the
California
Department
of
Pesticide
Regulation.

According
to
Agency
data,
there
is
a
range
of
protection
levels
provided
by
a
second
layer
of
clothing.
While
the
90%
protection
factor
is
included
in
this
range,
the
Agency
uses
the
50
percent
protection
factor
in
order
to
provide
the
maximum
protection
to
the
worker.
This
number
takes
into
account
the
variations
in
the
types
of
clothing
that
could
be
used
and
any
possible
rips
or
holes
in
the
second
layer
of
clothing.

In
the
case
of
endosulfan,
it
is
more
appropriate
to
use
the
NOEL
from
the
oral
study
for
9
assessing
worker
inhalation
risks
than
the
NOEL
from
the
inhalation
study.

The
Agency
is
currently
considering
this
matter,
since
this
is
an
issue
that
has
arisen
for
several
other
pesticides
and
will
affect
the
overall
regulation
of
all
pesticides.
When
there
is
a
decision
on
this
issue
in
the
Agency,
the
occupational
risk
assessment
will
be
revised
as
appropriate.
Until
then,
the
inhalation
endpoint
will
be
used
as
it
currently
stands
and
this
issue
will
be
considered
when
characterizing
the
inhalation
risk
during
the
risk
mitigation
phase.
Also
see
Section
V
above.

Use
of
biphasic
kinetics
to
calculate
predicted
dislodgeable
foliar
residue
(DFR)
values
better
represents
the
data
and
provides
higher
R
squared
values
for
the
critical
phase
1
period
than
a
linear
assumption.

HED
will
reanalyze
the
distribution
of
the
DFR
data
using
the
biphasic
method
and
will
determine
which
method,
linear
or
biphasic,
best
represents
the
distribution
of
the
data
and
produces
the
highest
R
squared
value.
Any
changes
in
the
analysis
of
the
DFR
data
will
be
reflected
in
the
next
revision
of
the
occupational
exposure
assessment.

ETF
believes
that
a
50%
protection
factor
is
a
reasonable
default
for
the
use
of
protective
headgear.

HED
agrees
that
a
chemical
resistant
headgear
may
reduce
pesticide
exposure.
A
protection
factor
has
not
been
established
by
the
Agency
for
the
use
of
headgear;
therefore,
occupational
exposure
risk
estimates
are
not
quantitatively
reduced
to
take
this
protective
clothing
into
account.
One
problem
in
setting
a
generic
protection
factor
for
chemical
resistant
headgear
is
that
headgear
can
come
in
a
wide
range
of
styles,
materials,
etc.
This
causes
the
amount
of
protection
that
headgear
can
provide
to
vary
widely.
Even
so,
the
MOEs
for
airblast
applicators
presently
range
from
3.
2
to
24
at
the
additional
PPE
mitigation
level
for
dermal
risk.
The
use
of
a
50%
protection
factor
for
head/
neck
exposure
would
not
increase
the
highest
MOE
to
more
than
36,
which
is
still
far
below
the
target
MOE
of
100.
HED
will
take
into
consideration
any
data
submitted
to
support
the
ETF's
assumption
that
chemical
resistant
headgear
reduces
head/
neck
exposure
by
50%.

600
acres/
day
should
be
used
for
applications
to
small
grains
instead
of
1200
acres/
day,
based
on
California
Department
of
Pesticide
Regulation
defaults.
Due
to
the
small
size
of
ornamental
operations,
40
acres
per
day
is
not
realistic,
and
10
acres
per
day
should
be
used.

The
small
grains
treated
with
endosulfan;
rye,
oats,
barley
and
wheat;
were
considered
to
have
a
1,
200
acre
per
day
amount
treated
rate
based
on
the
values
for
wheat
in
the
National
Agricultural
Aviation
Association's
1998
Industrial
Survey
for
Agricultural
Aviation,
Timber
Mill
Research,
Inc.,
June
1998
(values
for
acres
treated
per
day
range
from
970
to
1,625
for
wheat
).
Barley,
rye,
oats
and
wheat
all
have
the
same
maximum
application
rate
of
0.
75
lbs
ai/
acre.
HED
considers
1,
200
acres
per
day
to
be
a
reasonable
assumption
for
small
grains
treated
with
10
endosulfan.
HED
now
considers
10
acres
treated
per
day
to
be
a
realistic
assumption
for
ornamentals
and
future
revisions
of
the
occupational
assessment
will
reflect
this.

Some
of
the
MOEs
are
calculated
assuming
that
PPE
or
engineering
controls
will
be
in
use.
EPA
must
remember
that
in
many
instances
PPE
is
not
provided,
does
not
fit
properly
or
is
uncomfortable
to
wear.

Occupational
risks
are
assessed
with
PPE
or
engineering
controls
in
order
to
determine
what
risk
mitigation
can
be
employed.
If
PPE
or
engineering
controls
are
determined
to
be
necessary
to
reduce
the
risk
to
a
pesticide,
then
that
condition/
restriction
will
be
placed
on
the
label
(if
not
already
present).
Any
deviations
from
the
use
of
required
label
PPE
or
engineering
controls
is
considered
by
the
EPA
to
be
a
misuse
of
the
pesticide
product.
HED
does
not
assess
risks
resulting
from
the
misuse
of
a
pesticide
product.

VII.
Incident
Data
The
Agency
has
not
included
a
number
of
important
incident
reports
in
its
evaluation
of
the
incident
data.

The
Agency's
Incident
Report
was
written
in
the
year
2000
and
the
Agency
is
aware
that
a
great
deal
more
information
is
now
available.
A
quick
MEDLINE/
PubMed
search
at
the
National
Library
of
Medicine
web
site,
revealed
560
entries
for
endosulfan.
Many
recent
entries
use
new
multiresidue
analytical
chemistry
measurement
methods.
Some
poisonings
date
back
to
1970
in
Germany.
The
literature
entries
reflect
mostly
international
pesticide
poisoning
incident
case
reports
referred
to
by
PAN
Asia
and
the
Pacific/
PAN
North
America
{Docket
#34242}
and
Ohio
based
Rural
Action
Safe
Pest
Control
Program
{Docket
#34242},
and
some
studies
appear
to
be
consistent
with
the
thrust
of
their
concerns.

Specifically,
endosulfan
is
a
wide­
spread
and
commonly
measured
contaminant
of
the
human
environment.
Evidence
from
various
places
and
test
systems
is
beginning
to
suggest
internal
enzyme,
endocrine,
and
neuronal
regulation
changes
at
the
cellular
and
sub­
cellular
levels.
Of
particular
concern
are
the
neuronal
gap
junction
and
MAP
K
(kinase)
nerve
to
nerve
cell
communication
disturbances
in
test
cell
systems
and
other
evidence
of
endocrine
disruption.
A
further
concern
is
that
persistent
organochlorine
pesticides
(POPS)
tend
to
co­
occur
in
fatty
foods
like
fish,
thus
necessitating
more
complex
analysis
on
the
implications
of
aggregate
and
cumulative
exposure.
The
number
and
diversity
of
recent
publications
that
include
endosulfan,
suggest
the
need
for
a
more
careful
literature
review
during
the
upcoming
risk
assessment
revision
process.
