Document ID: EPA-HQ-OPP-2002-0202-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2002-08-14T04:00Z

UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
31,
2002
MEMORANDUM
SUBJECT:
Revised
HED
Risk
Assessment
for
Lindane.
DP
Barcode
D284581
Reregistration
Case
#
0315;
PC
code
009001
FROM:
Becky
Daiss,
Environmental
Health
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)

THRU:
Susan
V.
Hummel,
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)

TO:
Mark
T
Howard,
Chemical
Review
Manager
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)

Attached
is
HED's
revised
risk
assessment
of
the
insecticide,
lindane
for
purposes
of
issuing
a
Reregistration
Eligibility
Decision
(RED)
Document
for
this
active
ingredient.
This
document
revises
the
June
13,
2002
version
of
the
risk
assessment
to
incorporate
changes
to
the
residue
chemistry
and
occupational
exposure
sections
based
on
updated
information.
It
also
includes
technical
corrections
to
the
documentation
for
the
worker
exporsure
assessment.
This
assessment
incorporates
information
from
the
toxicology
assessment
conducted
by
Suhair
Shallal,
the
residue
chemistry
and
dietary
exposure
and
risk
assessments
conducted
by
Thurston
Morton,
and
the
occupational
and
residential
exposure
assessment
conducted
by
Dave
Jaquith.
The
disciplinary
science
chapters
and
other
supporting
documents
have
also
been
revised
in
response
to
public
comment
where
necessary
and
are
included
as
appendices
as
follows:

Revised
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
Suhair
Shallal
(6/
18/
01,
014595)
Report
of
the
FQPA
Safety
Factor
Committee.
Brenda
Tarplee
(8/
2/
00;
014272)
Revised
Product
and
Residue
Chemistry
Chapter.
Thurston
Morton
(12/
11/
01,
D279259)
Toxicology
Chapter.
Suhair
Shallal
(9/
28/
00,
D269338)
Occupational
and
Residential
Exposure
Assessment.
David
Jaquith
(6/
4/
02,
D283397,
4/
23/
02,
D282419,
4/
24/
02,
D282418)
Revised
Dietary
Exposure
and
Risk
Estimates
for
Reregistration.
Thurston
Morton
(12/
13/
01,
D279260)
Dietary
Risk
and
Exposure
Estimate
for
Lindane
through
Subsistence
Diets
for
Indigenous
People
of
Alaska.
Thurston
Morton
(4/
17/
02,
D282455)
Environmental
Fate
and
Effects
Chapter.
Nicholas
Federoff
(12/
20/
01,
D254764;
5/
20/
02,
D281832)
2
Table
of
Contents
I.
EXECUTIVESUMMARY
..............................................
1A
UseandMajorFormulations
..........................................
1B
RegulatoryHistory
..................................................
1C
HazardIdentificationandDose­
ResponseAssessment
.....................
2D
ExposureAssessment
................................................
4E
RiskAssessment/
Characterization
......................................

6II
PhysicalandChemicalProperties
.........................................

9III
Hazard
assessment
....................................................
9A
ToxicologyAssessment...............................................
9B
DoseResponseAssessment
...........................................
14i
DeterminationofSusceptibility.....................................
14ii
CancerClassification............................................
15iii
Toxicology
Endpoint
Selection
....................................
15iv
EndocrineDisruptorEffects
......................................
19v
IncidentReports
................................................

19IV
ExposureandRiskAssessment
.........................................
20A
DietaryExposure(
FoodSources)......................................
20i
Background.....................................................
20ii
SourcesofLindaneResiduesonFoods...............................
22iii
Residue
Chemistry
Studies
for
Lindane
.............................
22B
DietaryExposureEstimates
..........................................
27C
DietaryRiskEstimates(
FoodSources).................................
29i
AcuteDietaryExposureandRiskEstimates
..........................
29ii
ChronicDietaryExposureandRiskEstimates
........................
29iii
Chronic
Dietary
Exposure
and
Risk
Estimates
for
Indigenous
People
.....
30iv
CancerDietaryExposureandRiskEstimates
........................
30D
UncertaintiesinDietaryExposureAssessment
.............................
30E
DrinkingWaterExposure
...........................................
31i
MonitoringData
................................................
32ii
GroundWater
.................................................
32iii
Surface
Water
.................................................
33iv
DrinkingWaterEstimatedEnvironmentalconcentrations
..............
33F
DrinkingWaterRiskEstimates.......................................
34i
DWLOCsforChronicExposure
....................................
34ii
DWLOCforAcuteExposure......................................
35iii
Non­
Dietary
Exposure
...........................................
­36­
3
G.
OccupationalExposureandRiskEstimates
.............................
36i
CommercialSeedTreatment.......................................
37ii
OnFarmSeedTreatment.........................................
38iiiOccupationalExposureandRisk
...................................

38V
AggregateandCumulativeExposureandRiskCharacterization...............
40A
AcuteAggregateRisk...............................................
41B
Short­
andIntermediate­
TermAggregateRisk...........................
41C
ChronicAggregateRisk
.............................................
41D
CumulativeExposureandRisk
.......................................

42VI
RiskCharacterization.................................................

43VII
DataNeeds
........................................................
46A
ToxicologyDataRequirements
.......................................
46B
Product
andResidueChemistryDataRequirements
......................
­47­
1
I.
EXECUTIVE
SUMMARY
A.
Use
and
Major
Formulations
Lindane
(gamma
isomer
of
hexachlorocyclohexane,
 
­HCH)
is
a
broad­
spectrum
organochlorine
insecticide/
acaricide
which
has
been
used
on
a
wide
range
of
soil­
dwelling
and
plant­
eating
(phytophagous)
insects.
Worldwide,
it
is
commonly
used
on
a
wide
variety
of
crops,
in
warehouses,
in
public
health
to
control
insect­
borne
diseases,
and
(with
fungicides)
as
a
seed
treatment.
Lindane
is
also
presently
used
in
lotions,
creams,
and
shampoos
for
the
control
of
lice
and
mites
(scabies)
in
humans;
these
pharmaceutical
uses
are
regulated
by
FDA.
In
the
U.
S.,
the
only
registered
food/
feed
use
is
seed
treatment
for
field
and
vegetable
crops.

Lindane
may
be
found
in
formulations
with
a
host
of
fungicides
and
insecticides.
Labels
for
products
containing
it
must
bear
the
Signal
Word
WARNING.
Some
formulations
of
lindane
are
classified
as
Restricted
Use
Pesticides
(RUP),
and
as
such
may
only
be
purchased
and
used
by
certified
pesticide
applicators.
Lindane
is
no
longer
manufactured
in
the
U.
S.
According
to
a
REFS
search,
conducted
on
5/
29/
01,
there
are
approximately
34
federally
registered
end­
use
products
(EPs)
containing
lindane
as
the
active
ingredient
and
three
Section
24
C
registrations.
Lindane
end­
use
products
are
formulated
as
dust
(D),
wettable
powder
(WP),
emulsifiable
concentrate
(EC),
flowable
concentrate
(FlC),
and
ready­
to­
use
(RTU)
solution.

The
reregistration
of
lindane
is
being
supported
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
and
its
member
company
holding
U.
S.
registrations,
Inquinosa,
S.
A.
Currently,
Inquinosa
does
not
have
any
registered
lindane
end­
use
products.
In
1993,
CIEL
offered
to
voluntarily
cancel
all
crop
uses
of
lindane
except
seed
treatment
and
certain
non­
food
uses.
The
Agency
considers
lindane
seed
treatment
as
a
food
use
requiring
tolerances
based
on
existing
data
from
radiolabeled
studies
indicating
uptake
of
residues
from
the
treated
seeds
into
the
aerial
portion
of
the
growing
crop.

B.
Regulatory
History
Lindane
is
a
List
A
reregistration
pesticide.
A
Reregistration
Standard
for
Lindane
was
issued
9/
85.
The
Residue
Chemistry
Chapter
to
the
Reregistration
Standard
was
issued
on
6/
7/
85,
an
addendum
on
9/
5/
85,
and
an
Update
on
1/
31/
91.
The
Reregistration
Standard
along
with
its
Science
Chapters
summarized
the
available
data
for
each
residue
chemistry
guideline
and
specified
what
additional
data
are
required
for
reregistration
purposes.
Data
Call­
In
(DCI)
Notices
for
lindane
were
issued
by
the
Agency
on
9/
30/
91,
3/
3/
95,
10/
13/
95,
and
3/
31/
97.
The
information
contained
in
this
document
outlines
the
current
Residue
Chemistry
Science
Assessments
with
respect
to
supporting
seed
treatment
uses
of
lindane,
as
well
as
the
reregistration
of
the
pesticide.

In
1983,
EPA
concluded
a
major
Special
Review
effort
of
lindane
based
on
carcinogenicity,
fetotoxicity/
teratogenicity,
reproductive
effects,
and
acute
effects
on
aquatic
2
organisms.
This
effort
resulted
in
the
cancellation
of
indoor
uses
of
smoke
fumigation
devices
and
greatly
limited
the
use
of
pet
dips
on
dogs.
In
addition,
there
were
uses
that
were
allowed
to
continue
only
if
certain
imposed
restrictions
were
implemented.
The
restrictions
were
based
on
the
degree
of
associated
hazards,
and
included
changes
in
warning
labels,
the
wearing
of
protective
clothing,
and
restrictions
to
limit
uses
to
certified
pest
control
operators.

In
1995,
EPA
announced
(FR
Vol.
60,
No.
143,
38329­
38331,
7/
26/
95)
its
decision
not
to
initiate
a
Special
Review
of
lindane
based
on
worker
health
concerns
arising
from
studies
showing
irreversible
renal
effects
in
the
rat.
The
Agency
has
determined
that
these
effects
occur
only
in
the
kidneys
of
male
rat
and
are
not
relevant
for
human
risk
assessment.

Tolerances
are
currently
established
under
40
CFR
§180.133
for
residues
of
lindane
per
se
in/
on
various
raw
agricultural
commodities
at
0.01
ppm
(pecans)
to
3
ppm
(cucumbers,
lettuce,
melons,
mushrooms,
pumpkins,
squash,
summer
squash,
and
tomatoes).
Lindane
tolerances
are
also
established
at
4
ppm
in
the
fat
of
meat
from
hogs
and
at
7
ppm
in
the
fat
of
meat
from
cattle,
goats,
horses,
and
sheep.
No
tolerances
have
been
established
for
processed
food/
feed
commodities.
Adequate
methods
are
available
for
the
enforcement
of
tolerances
for
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.

The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
In
addition,
the
established
tolerances
for
the
following
commodities
will
be
revoked
because
no
registrants
have
committed
to
support
the
foreign
or
domestic
uses
for:
apples,
apricots,
asparagus,
avocados,
celery,
cherry,
collards,
cucumbers,
eggplants,
grapes,
guavas,
kale,
kohlrabi,
mangoes,
melons,
mushrooms,
mustard
greens,
nectarines,
okra,
onions
(dry
bulb
only),
peaches,
pears,
pecans,
peppers,
pineapple,
plums
(fresh
prunes),
pumpkins,
quinces,
squash,
strawberries,
summer
squash,
swiss
chard
and
tomatoes.

C.
Hazard
Identification
and
Dose­
Response
Assessment
The
toxicology
database
for
lindane
is
complete
with
respect
to
the
OPPTS
Guideline
requirements.
In
acute
toxicity
studies,
lindane
is
a
moderately
toxic
compound,
EPA
toxicity
class
II.
It
is
neither
an
eye
irritant
nor
dermal
sensitizer.

The
toxicity
endpoints
used
in
this
document
to
assess
hazards
include
acute
dietary
and
chronic
dietary
reference
doses
(RfDs),
and
short­,
intermediate­
and
long­
term
dermal
and
inhalation
no
observable
adverse
affect
levels
(NOAELs).
In
light
of
the
developing
Agency
policy
on
use
of
toxicology
studies
employing
human
subjects,
HED
selected
doses
and
endpoints
for
risk
assessment
based
solely
on
animal
studies.

The
primary
effect
of
lindane
is
on
the
nervous
system;
in
acute,
subchronic,
and
developmental
neurotoxicity
studies
and
chronic
toxicity/
oncogenicity
studies,
lindane
appears
to
3
cause
neurotoxic
effects
including
tremors,
convulsions
and
hypersensitivity
to
touch.
This
is
further
corroborated
by
the
published
literature
in
which
human
exposure
has
been
seen
to
produce
neurologic
effects.
Lindane
also
causes
renal
and
hepatic
toxicity
via
the
oral,
dermal
and
inhalation
routes
of
exposure
as
seen
in
subchronic,
2­
generation
reproduction
and
chronic
toxicity
studies
in
the
rat,
as
well
as
in
studies
in
the
open
literature
(S.
Shallal,
D274510).

In
developmental
toxicity
studies,
developmental
effects
were
only
seen
at
levels
where
maternal
toxicity
was
also
evident.
In
the
rat
developmental
study,
the
developmental
effects
(extra
rib
and
total
skeletal
variations)
were
seen
at
dose
levels
(20
mg/
kg/
day)
greater
than
maternal
toxicity
(10
mg/
kg/
day).
In
the
reproductive
toxicity
study,
both
systemic
and
developmental
LOAELs
are
13
mg/
kg;
however
a
qualitative
difference
in
maternal
and
offspring
effects
(reduced
body
weight
of
maternal
animals
and
reduced
viability
and
delayed
maturation
in
pups)
indicates
an
increased
susceptibility
to
exposure.
This
is
further
corroborated
by
a
developmental
neurotoxicity
study
in
which
a
qualitative
and
quantitative
increase
in
susceptibility
is
seen.
At
the
high
dose
(13.7
mg/
kg/
day)
,
animals
in
the
F0
generation
have
a
reduced
body
weight
and
body
weight
gain
while
at
the
mid­
dose
(5.6
mg/
kg/
day),
F1
animals
have
a
reduced
survival
rate,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
as
compared
to
controls.

The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD­
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
(S.
Diwan,
11/
29/
01,
TXR
NO.
0050297)

The
International
Programme
on
Chemical
Safety
(IPCS,
1991)
states
that
lindane
does
not
appear
to
have
mutagenic
potential.
The
available
mutagenicity
studies
are
negative;
they
include
a
dominant
lethal
mutation
assay,
sister
chromatid
exchange
assay
and
mammalian
cell
culture
gene
mutation
in
V79
cells.
However,
these
studies
have
been
classified
as
unacceptable
by
EPA.

The
Food
Quality
Protection
Act
(FQPA)
Safety
Factor
Committee
evaluated
the
hazard
and
exposure
data
to
determine
if
the
10x
safety
factor
should
be
retained.
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3X
due
to
the
following
considerations:
1)
the
toxicology
data
base
is
complete;
2)
the
available
data
provide
no
indication
of
quantitative
or
qualitative
increased
susceptibility
in
rats
from
in
utero
exposure
to
lindane
in
the
prenatal
developmental
study;
3)
the
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two­
generation
reproduction
study
(no
additional
functional
or
morphological
hazards
to
the
nervous
system
were
noted);
4)
adequate
actual
data,
surrogate
data,
and/
or
modeling
outputs
are
available
to
satisfactorily
assess
food
exposure
and
to
provide
a
screening
level
drinking
water
exposure
assessment;
5)
although
the
developmental
4
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required;
and
6)
there
are
currently
no
residential
uses.
A
new
developmental
study
is
not
required
because:
a)
the
developmental
toxicity
study
in
rabbits
and
rats
using
a
subcutaneous
route
of
administration
shows
no
developmental
effects
at
the
maternally
toxic
dose;
b)
the
skeletal
effects
observed
in
the
developmental
toxicity
study
in
rats,
with
gavage
as
the
route
of
administration,
are
within
historical
controls;
c)
more
severe
maternal
effects
are
seen
in
the
rabbit
study
with
subcutaneous
administration;
d)
the
rat
appears
to
be
the
more
sensitive
species
for
developmental
effects;
and
e)
a
developmental
neurotoxicity
study
has
already
been
submitted.

D.
Exposure
Assessment
The
HED
Metabolism
Assessment
Review
Committee
(MARC)
concluded
that
the
total
radioactive
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
8/
30/
00,
D267069).
The
ChemSAC
recommended
comparing
the
results
from
the
dietary
analysis
using
the
TRRs
with
the
results
from
a
dietary
analysis
based
on
feeding
studies.
Exposure
to
lindane
was
determined
by
using
the
ratio
(ppm
TRR/
ppm
lindane
parent).
The
results
from
the
dietary
analysis
using
the
feeding
study
results
and
adjusting
the
lindane
residues
by
the
above
ratio
are
summarized
in
this
assessment.
The
Biological
and
Economic
Analysis
Division
(OPP/
BEAD)
verified
the
registrant's
percent
market
share
estimate
for
lindane
(I.
Yusuf
email,
7/
17/
00).
A
canola
processing
study
for
lindane
was
recently
reviewed
(T.
Morton,
D269388,
5/
10/
01).
Lindane
was
not
detected
in
bleached/
deodorized
canola
oil
(<
0.005
ppm).
Therefore,
½
LOQ
(0.
0025
ppm)
was
used
as
the
residue
estimate
in
DEEM
and
the
DEEM™
adjustment
factor
was
set
to
1.
DEEM™
default
concentration
factors
(adjustment
factor
1)
were
used
for
all
other
commodities.

The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Therefore,
it
is
considered
appropriate
for
the
Agency
to
perform
a
supplementary
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
the
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane.
The
dietary
risk
assessment
for
Indigenous
People
of
Alaska
for
Lindane
has
been
revised
to
incorporate
new
information
pertaining
to
subsistence
meat
intake
by
children.
(T.
Morton,
D282455,
4/
17/
02).
Using
the
limited
data
available,
we
have
extrapolated
from
this
information
and
knowledge
of
the
standard
diet
of
the
indigenous
people
of
Alaska
to
arrive
at
a
conservative
estimate.
The
data
used
in
this
assessment
is
based
on
actual
residues
found
in
animal
tissues
in
conjunction
with
typical
subsistence
diet
consumption
rates.
Because
factors
such
as
bioaccumulation
of
lindane
and
the
cumulative
effects
of
combinations
of
chemicals
which
act
through
a
common
mode
of
action
have
not
been
incorporated
into
this
assessment,
it
is
therefore
difficult
to
know
the
full
range
of
residue
to
which
indigenous
populations
may
be
exposed.

Lindane
does
not
occur
naturally
in
the
environment.
Once
released
it
can
partition
into
all
environmental
media.
Lindane
has
been
detected
in
air,
surface
water,
groundwater,
sediment,
soil,
ice,
snowpack,
fish
and
other
aquatic
organisms,
wildlife,
and
humans.
Lindane
has
been
5
found
in
pristine
environments;
the
pathway
for
contamination
is
varied
and
complex
depending
on
atmospheric
and
oceanic
circulation,
gas/
particle
partitioning,
and
solubility
of
the
substance
and
the
food
chain.
Monitoring
data
has
shown
that
Lindane
is
detectable
across
the
entire
North
American
continent,
from
Washington
D.
C.,
Denver,
Colorado,
and
the
Niagra
River
water
samples
to
air
samples
over
the
Adirondack
Mountains
in
New
York,
Newport
News,
Virginia
and
Ontario,
Canada,
as
well
as,
soil
samples
from
around
the
Great
Lakes
and
the
Gulf
of
Mexico.

The
Environmental
Fate
and
Effects
Division
(EFED)
evaluated
the
potential
for
lindane
to
contaminate
water.
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.
13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.
07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.032
µ
g/
L).

EFED
models
were
used
to
calculate
estimated
environmental
concentrations
(EECs)
in
drinking
water
from
surface
water
and
groundwater
contaminated
with
lindane
as
a
result
of
seed
treatment
uses.
Wheat
and
canola,
which
have
the
highest
application
rate
in
terms
of
lbs
a.
i
per
acre
were
used
as
the
model
crop
scenarios.
The
Screening
Concentration
in
Ground
Water
(SCI­
GROW)
model
was
used
to
estimate
concentrations
of
lindane
in
groundwater.
The
screening
model,
FQPA
Index
Reservoir
Screening
Tool
(FIRST),
was
used
to
estimate
surface
water
concentrations.

Occupational
exposure
scenarios
can
be
described
as
short
term
(1­
7
days),
intermediate
term
(7
days
to
several
months),
and
long
term
or
chronic
(several
months
to
a
lifetime).
All
of
the
lindane
exposure
scenarios
are
appropriately
described
as
short
and
intermediate
term.
HED
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
usual
use­
patterns
associated
with
lindane.
Based
on
the
use
patterns
and
potential
exposures
described
above,
6
major
exposure
scenarios
were
identified
to
represent
the
extent
of
lindane
uses:
(1)
on­
farm
seed
treatment
with
dry
formulation­
open
system,
(2)
on­
farm
seed
treatment
with
liquid
formulation
­
closed
system,
(3)
mixing/
loading
and
applying
liquid
with
commercial
seed­
treatment
equipment,
(4)
bagging
and
otherwise
handling
treated
seeds,
(5)
cleaning/
maintaining
seed
treatment
equipment,
and
(6)
loading/
planting
treated
seeds.
Worker
exposure
data
for
lindane
were
required
since
one
or
more
toxicological
criteria
had
been
triggered.
Requirements
for
applicator
exposure
studies
are
addressed
by
Series
875
Group
A
(formerly
Subdivision
U
of
the
Pesticide
Assessment
Guidelines).
Three
lindane
specific
6
exposure
studies
have
been
used
to
estimate
exposure,
one
addressing
on­
farm
treatment,
one
addressing
commercial
seed
treatment,
and
one
addressing
planting
of
treated
seed.

E.
Risk
Assessment/
Characterization
Dietary
(food
source)­
Anticipated
residues
were
provided
for
all
commodities
and
used
when
calculating
the
dietary
risk
associated
with
lindane
for
the
RED
(DP
Barcode
D279260,
T.
Morton,
12/
13/
01).
Although
the
database
for
lindane
is
substantially
complete,
additional
data
are
needed
to
eliminate
the
uncertainties
associated
with
the
exposure/
risk
assessment.
The
anticipated
residue
values
are
the
best
estimates
HED
can
provide
using
the
residue
data
available
at
this
time.
These
values
have
an
inherent
uncertainty
associated
with
variations
in
analytical
methods,
geographical
representation
of
field
trials,
seasonal
variation
of
residue
levels,
use
of
TRR
from
metabolism
studies,
etc.

The
acute
dietary
exposure
analysis
was
a
tier
3
probabilistic
assessment.
In
both
acute
and
chronic
risk
assessments,
exposure
was
compared
to
a
population
adjusted
dose,
(PAD),
which
is
the
reference
dose
(RfD)
reflecting
application
of
the
FQPA
3X
safety
factor.
HED
considers
dietary
residue
contributions
greater
than
100%
of
the
PAD
to
be
of
concern.
The
dietary
assessment
was
conducted
using
percent
crop
treated
(%
CT)
and
total
radioactive
residues
(TRRs)
from
plant
metabolism
studies
and
from
poultry
and
ruminant
metabolism
studies.
A
second
dietary
assessment
was
conducted
which
incorporated
data
generated
from
poultry
and
ruminant
feeding
studies
which
provided
lindane
only
residue
values.
In
this
assessment,
an
average
lindane
only
residue
value
was
calculated
from
three
dose
levels
and
multiplied
by
the
ratio
of
TRR:
lindane
derived
from
the
corresponding
poultry
or
ruminant
metabolism
studies.
(Average
lindane
residue
from
feeding
study
X
TRR
from
metabolism
study/
lindane
residue
from
metabolism
study).
The
following
assessments
yielded
higher
percent
aPAD
and
cPAD
values
which
were
used
to
calculate
drinking
water
levels
of
comparison
(DWLOCs).

Acute
Dietary
(Food).
The
acute
dietary
analysis
for
lindane
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software.
Results
are
reported
as
a
percentage
of
the
acute
Population
Adjusted
Dose
(aPAD)
for
the
99.9
th
percentile
of
the
population.
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
acute
PAD
(%
aPAD)
for
the
population
subgroup
all
infants
and
7
%
of
the
aPAD
for
the
U.
S.
Population
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.

Chronic
Dietary
(Food).
The
chronic
dietary
analysis
for
lindane
was
conducted
using
the
DEEM™
software.
Results
are
reported
as
a
percentage
of
the
chronic
Population
Adjusted
Dose
(cPAD).
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
population
and
11
%
of
the
cPAD
for
children
1­
6
years
of
age
(the
most
highly
exposed
population
subgroup.
The
remaining
7
population
subgroups
were
<6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.

Acute
Drinking
Water.
Acute
DWLOCs
were
calculated
based
on
the
acute
dietary
exposure
and
default
body
weights
and
water
consumption
figures.
The
EECs
for
surface
water
and
the
EECs
for
groundwater
were
less
than
the
acute
DWLOCs
for
all
sub­
populations
indicating
that
acute
aggregate
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.

Chronic
Drinking
Water.
Chronic
DWLOCs
were
calculated
based
on
the
chronic
dietary
(food)
exposure
and
default
body
weights
and
water
consumption
figures.
The
EECs
for
surface
water
and
groundwater
were
less
than
the
chronic
DWLOCs,
indicating
that
chronic
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.

Special
Populations.
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Therefore,
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D282455,
4/
17/
02).
Because
the
annual
harvest
rates
were
divided
by
365
to
obtain
daily
harvest
rates,
and
the
daily
intake
rates
were
used
in
the
assessment,
no
acute
dietary
exposure
analysis
was
conducted.
The
chronic
dietary
exposure
analysis
used
subsistence
food
harvest
amounts
and
total
HCH
residues
in
traditional
foods,
and
adjusted
the
HCH
exposure
to
obtain
lindane
exposure.
To
estimate
subsistence
food
intake
rates,
EPA
used
data
from
the
Alaska
Department
of
Fish
and
Game
Division
of
Subsistence
data
base.
This
data
base
provides
subsistence
food
harvest
amounts
for
nearly
180
Alaskan
communities
from
1990­
2001.
Since
marine
mammals
represents
the
largest
portion
of
the
subsistence
harvest,
HED
used
the
community
with
the
highest
representative
seal
harvest,
the
community
with
the
highest
walrus
harvest,
and
the
community
with
the
highest
whale
harvest
to
estimate
subsistence
intake
rates.
Other
subsistence
food
sources
(e.
g.,
land
mammals,
other
marine
mammals,
fish,
and
birds)
from
the
corresponding
Alaskan
community
were
also
included
in
estimating
subsistence
intake.

The
combined
subsistence
food
source
exposures
from
Community
1
(the
community
with
highest
total
intake
of
the
three
communities)
amounts
to
0.282065
mg/
day
HCH.
Adjusting
total
HCH
to
obtain
lindane
only
exposure
yields
a
lindane
exposure
for
Community
1
of
0.
04231
mg/
day.
(Total
HCH
is
adjusted
by
factors
of
0.
15
and
0.03
since
lindane
represents
between
3
and
15%
of
total
HCH
residues).
Based
on
revised
exposure
estimates
and
assuming
a
male
adult
body
weight
of
70
kg,
the
chronic
dietary
risk
to
adult
male
Indigenous
People
ranges
from
0.000055
­
0.
0006
mg/
kg
body
weight/
day
which
is
between
3
and
38
%
of
the
cPAD.
This
is
below
HED's
level
of
concern
(cPAD
=
0.
0016
mg/
kg
bw/
day).
The
revised
estimate
of
chronic
dietary
risk
to
adult
female
Indigenous
People
(body
weight
of
60
kg)
ranges
from
0.000064
0.0007
mg/
kg
bw/
day
or
from
4
to
44
%
of
the
cPAD,
also
below
HED's
level
of
concern.
Assuming
a
child
body
weight
of
10
kg
and
adjusting
adult
intake
by
a
factor
of
0.53
to
account
for
adult
versus
child
subsistence
meat
intake,
the
revised
lindane
dietary
risk
estimates
for
8
children
1­
6
years
from
subsistence
food
consumption
range
from
0.0002
­
0.
0022
mg/
kg
bw/
day
or
from
13
to
138%
of
the
cPAD.
For
children
7­
12
years
old,
the
lindane
residue
amount
was
divided
by
29
kg
(7­
12
year
body
weight)
to
obtain
the
%
cPAD
from
subsistence
foods.
The
resulting
range
of
lindane
dietary
risk
estimates
from
subsistence
food
consumption
for
children
712
is
4
to
48%
of
the
cPAD,
which
is
below
HED's
level
of
concern.

Residential
Risk
Estimates.
No
residential
exposure
scenarios
have
been
identified
for
pesticide
uses
of
lindane
and
therefore
no
risk
estimates
will
be
presented
in
this
document
for
non­
occupational
exposure
to
lindane.

Occupational
Risk
Estimates.
The
Agency
has
refined
occupational
estimates
using
the
toxicological
endpoints
chosen
by
OPP's
Hazard
Identification
Assessment
Committee
(HIARC)
and
two
recent
worker
exposure
studies,
one
on
commercial
seed
treatment
and
one
on
handling
and
planting
of
treated
seeds,
and
The
FQPA
uncertainty
factor
of
3X
is
not
applicable
to
occupational
risk
assessments.
Resulting
risk
estimates
are
reported
as
Margins
of
Exposure
(MOEs),
and
compared
to
the
target
MOE,
which
is
100
for
all
lindane
occupational
exposure
scenarios.

The
Agency
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
usual
use­
patterns
associated
with
lindane.
The
exposure
scenario
descriptions
based
on
the
use
pattern
of
lindane
are
presented
in
Table
12.
The
daily
exposures,
as
well
as
the
resulting
short
and
intermediate
term
MOEs
are
presented
in
Table
13.
Short
and
intermediate
(if
applicable)
term
MOEs
were
calculated
for
dermal
and
inhalation
exposure
routes
for
a
total
of
6
worker
exposure
scenarios.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low­
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
seed
treated
at
the
high­
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.
Dermal
MOEs
for
all
scenarios
range
between
9
and
119000.
Inhalation
MOEs
range
from
30
to
16000.

Aggregate
Exposure
and
Risk.
The
Agency
considered
aggregate
exposure
and
risk
estimates
for
residents
who
might
be
exposed
to
lindane
from
multiple
sources,
such
as
residential
use,
food,
and
water.
Since
no
residential
exposure
is
expected,
an
aggregate
risk
estimate
was
not
calculated.
9
Cl
Cl
Cl
Cl
Cl
Cl
II.
Physical
and
Chemical
Properties
The
chemical
structure
and
physical
properties
of
Lindane
are
given
below.

Empirical
Formula:
C6
H6
Cl6
Molecular
Weight:
290.9
CAS
Registry
No.:
58­
89­
9
PC
Code:
009001
Lindane
is
a
white
crystalline
solid
with
a
melting
point
of
112­
113

C,
specific
gravity
of
1.85,
octanol/
water
partition
coefficient
(Kow
)
of
3135,
and
vapor
pressure
of
9.4
x
10
­6
mm
Hg
at
20
C.
Lindane
is
slightly
soluble
in
water
(10
ppm
at
20
C)
and
in
most
organic
solvents,
including
acetone
and
aromatic
and
chlorinated
hydrocarbons.
Lindane
is
only
slightly
soluble
in
mineral
oils.
Lindane
is
stable
to
light,
heat,
air,
and
strong
acids,
but
decomposes
in
alkali
solutions
to
trichlorobenzenes
and
HCl.

Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
highly
persistent
(soil
half
life
of
2.
6
years).
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions.
Degradates
are
predominantly
pentachlorocyclohexane,
1,2,4,­
trichlorobenzene,
and
1,
2,
3­
trichlorobenzene.
Also,
lindane
can
possibly
transform
to
the
alpha
and
beta
isomers
of
hexachlorocyclohexane
by
biological
and
phototransformation,
although
this
issue
remains
to
be
conclusively
resolved.
Metabolites
are
not
quantified
since
they
comprise
less
than
10%
of
the
total
residue;
they
are
also
found
in
rat
metabolism
studies
and
have
therefore
been
indirectly
evaluated
for
their
toxicologic
effects.

III.
Hazard
assessment
A.
Toxicology
Assessment
Based
on
available
information
to
date,
the
Agency
has
determined
that
the
adverse
effects
of
primary
concern
for
lindane
are
those
related
to
neurotoxicity.

Organochlorine
pesticides,
such
as
lindane,
are
known
to
cause
delayed
neurotoxic
effects.
Symptoms
include
a
number
of
clinical
signs
and
symptoms,
including
headaches,
dizziness,
nausea,
vomiting,
diarrhea
and
increased
urination,
blurred
vision,
labored
breathing,
muscle
paralysis,
slow
heart
rate,
respiratory
depression,
convulsions,
coma
and
even
death.
Numerous
toxicological
studies
using
laboratory
animals
are
available
addressing
most
of
these
toxicological
endpoints
for
lindane.
In
acute,
subchronic
and
developmental
neurotoxicity
studies,
it
was
found
to
cause
neurotoxic
effects
including
tremors,
convulsions,
decreased
motor
activity,
increased
10
forelimb
grip
strength,
hypersensitivity
to
touch,
hunched
posture
and
decreased
motor
activity
habituation.
There
also
appears
to
be
a
greater
susceptibility
to
exposure
by
offspring
compared
to
parental
animals
in
the
developmental
neurotoxicity
study.
Lindane
has
also
been
implicated
as
a
possible
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
Further
studies
to
ascertain
the
validity
of
such
evidence
is
necessary
to
make
informed
risk
assessment
decisions.

Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
several
pathways:
Dehydrogenation
leading
to

HCB,
dehydrochlorination
leading
to
formation
of

pentachlorocyclohexene,
dechlorination
leading
to
formation
of

tetrachlorohexene,
or
hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolism
leads
to
a
large
number
of
metabolites.
Lindane
is
converted
by
enzymatic
reactions,
mainly
in
the
liver.

Lindane
appears
to
affect
the
liver
and
kidney
in
male
rats
when
administered
through
the
oral,
dermal
or
inhalation
routes
of
exposure.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with

10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment
The
liver
effects
include:
incidence
of
periacinar
hepatocytic
hypertrophy
which
was
significantly
(p

0.01)
increased
in
male
and
female
rats
dosed
at
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively).
In
addition,
increased
liver
and
spleen
weights,
and
decreased
platelets
were
also
noted.

Lindane
is
not
considered
teratogenic
when
administered
orally
or
subcutaneously.
Developmental
toxicity
NOAELs
were
found
to
be
at
levels
equal
to
or
greater
than
maternal
NOAELs,
except
in
the
developmental
neurotoxicity
study.
The
developmental
neurotoxicity
LOAEL
was
5.6
mg/
kg/
day
(NOAEL
is
1.2
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
maternal
toxicity
LOAEL
of
13.7
mg/
kg/
day
(NOAEL
is
5.6
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.

The
data
base
for
reproductive
toxicity
is
considered
complete.
Both
parental
and
offspring
LOAELs
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.

The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD­
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
11
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.

In
a
mammalian
cell
gene
mutation
assay
and
an
in
vivo
sister
chromatid
exchange
assay,
no
mutagenic
response
was
detected.
These
studies
were
classified
as
unacceptable
by
EPA.
The
open
literature
suggests,
however,
that
technical
grade
HCH
(hexachlorohexane;
6.
5%

HCH)
may
induce
some
mutagenic
activity
as
evidenced
in
a
dominant
lethal
mutation
assay
and
sister
chromatid
exchanges.
It
has
been
noted,
however,
by
the
IPCS
that
lindane
does
not
appear
to
have
a
mutagenic
potential.

The
acute
toxicity
studies
for
lindane
are
summarized
in
Table
1,
and
the
toxicology
profile
for
lindane
is
summarized
in
Table
2.
The
toxicology
database
required
to
support
the
Reregistration
of
lindane
is
essentially
complete.
All
required
toxicology
studies
have
been
submitted
and
reviewed
by
Agency
scientists.

Table
1.
Guideline
Acute
Toxicity
Studies
for
Lindane
STUDY
TYPE
MRID
CATEGORY
RESULT
81­
1Acute
oral­
rat
00049330
II
LD50
88
mg/
kg
­
males
91
mg/
kg
­
females
81­
2
Acute
dermal­
rabbit
00109141
II
LD50
1000
mg/
kg
­
males
900
mg/
kg
­
females
81­
3
Acute
inhalation­
rat
Acc.
263946
III
LC50
1.56
mg/
L
both
sexes
81­
4
Eye
irritation­
rabbit
Acc.
263946
III
PIS
=
0.6
no
corneal
involvement
irritation
cleared
after
24
hours
81­
5
Dermal
irritation­
rabbit
Acc.
262946
IV
PIS
=
0
not
an
irritant
81­
6
Dermal
sensitization­
g.
pig
Acc.
262946
NA
not
a
sensitizer
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
­year/
Classification
Results
870.3250
90­
Day
dermal
toxicity
in
rabbit
41427601
­1990
acceptable/
guideline
NOAEL
=
10
mg/
kg/
day
LOAEL
=
60
mg/
kg/
day
based
on
lesion
in
the
liver
in
males
and
females
and
adrenal
gland
weight
increases
in
males
870.3465
90­
Day
inhalation
toxicity
in
rat
00255003
­1983
acceptable/
guideline
NOAEL
=
0.
025
mg/
kg/
day
LOAEL
=
0.
13
mg/
kg/
day
based
on
transient
microscopic
lesions
in
the
kidney
and
increased
kidney
weights
in
the
males.

40873501
­1988
acceptable/
guideline
NOAEL
=
0.
08
mg/
kg/
day
LOAEL
=
0.25
mg/
kg/
day
based
on
death
of
one
male
and
one
female
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
­year/
Classification
Results
12
870.3700a
Prenatal
developmental
in
rat
00062656
­1976
(Subcutaneous)
unacceptable/
nonguideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
reduced
body
weight
Developmental
NOAEL
=
>30
mg/
kg/
day
LOAEL
=
not
identified
42808001
­1971
acceptable/
guideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
reduced
body
weight
and
food
consumption
Developmental
NOAEL
=
10
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
skeletal
variation.

870.3700b
Prenatal
developmental
in
rabbit
00062658
­1976
(Subcutaneous)
unacceptable/
nonguideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
clinical
signs,
mortality,
reduced
body
weight
Developmental
NOAEL
15
mg/
kg/
day
LOAEL
=
not
identified
42808002
­1971
unacceptable/
nonguideline
Maternal
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
Developmental
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
870.3800
Reproduction
and
fertility
effects
in
rat
42246101
­1991
acceptable/
guideline
NOAEL
=
1.
7
mg/
kg/
day

;
0.
09mg/
kg/
day

LOAEL
=
13
mg/
kg/
day

based
on
reduced
body
weight;
1.7
mg/
kg/
day

based
on
increased
kidney
weight
and
2
globulin
accumulation
(not
relevant
for
humans)
NOAEL
for
reproductive
toxicity
=1.
7
mg/
kg/
day
(20
ppm)
LOAEL
for
reproductive
toxicity
=
13
mg/
kg/
day
(150
ppm)
based
on
reduced
pup
body
weights
and
decreased
viability
in
both
generations
and
delayed
maturation
of
the
F2
pups
870.4300
Carcinogenicity
mice
special
study
­1987
see
below­
literature
studies
870.4100a
Chronic
toxicity
rodents
870.4200
Carcinogenicity
rats
41094101
41853701
42891201
­1993
acceptable/
guideline
NOAEL
=0.
6
mg/
kg/
day
LOAEL
=
4.8
mg/
kg/
day

;
6
mg/
kg/
day

based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets
no
evidence
of
carcinogenicity
870.5300
Gene
Mutation
Mammalian
Cell
00144500
­1985
unacceptable/
uideline
negative
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
­year/
Classification
Results
13
870.5915
In
Vivo
Sister
Chromatid
Exchange
00024504
­1984
unacceptable/
guideline
negative
870.5450
dominant
lethal
assay
00062657
unacceptable/
guideline
negative
870.6200a
Acute
neurotoxicity
screening
battery
in
rat
44769201
­1999
acceptable/
guideline
NOAEL
=
6
mg/
kg/
day

;
20
mg/
kg/
day

LOAEL
=
20
mg/
kg/
day
(

)
based
on
increased
grip
strength
and
decreased
motor
activity.
60
mg/
kg/
day
(

)
based
on
tremors,
convulsions,
decreased
motor
activity
and
increased
grip
strength.

870.6200b
Subchronic
neurotoxicity
screening
battery
in
rat
44781101
­1999
acceptable/
guideline
NOAEL
=
7.
9
mg/
kg/
day

;
7.
1
mg/
kg/
day

LOAEL
=
30.2
mg/
kg/
day
and
28.1
mg/
kg/
day
based
on
hypersensitivity
to
touch
and
hunched
posture.

870.6300
Developmental
neurotoxicity
in
rat
45073501
­1999
acceptable/
guideline
Maternal
NOAEL
=
5.
6
mg/
kg/
day
LOAEL
=
13.7
mg/
kg/
day
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
Offspring
NOAEL
=
1.
2
mg/
kg/
day
LOAEL
=
5.6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.

870.7600
Dermal
penetration
40056107­
1987
rat
40056108­
1987
rabbit
acceptable/
guideline
18
%
absorption
at
10
hours
literature
studies
Feldmann,
RJ
and
HI
Maibach,
Percutaneous
penetration
of
some
pesticides
and
herbicides
in
man,
Toxicology
and
Applied
Pharmacology,
28:
126­
132
(1974).
Non­
guideline
~10%
absorption
in
humans
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
­year/
Classification
Results
14
Other:
Tumorigenic
responses
to
lindane
in
mice:
potentiation
by
a
dominant
mutation.
Special
study
dietary
administration­
1987
NOAEL
=
not
identified
LOAEL
=
23
mg/
kg/
day
(160
ppm)
based
on
induction
of
tumors,
increased
liver
weights,
increased
enzyme
activity,
and
irreversible
Clara
cell
hyperplasia
in
lung
evidence
of
carcinogenicity­
induction
of
liver
and
lung
tumors
in
the
agouti,
pseudoagouti
and
black
mouse
strains—
only
females;
only
0
and
160
ppm
Other
Literature
Studies
In
addition
to
the
developmental
and
reproduction
studies
submitted
to
the
Agency
to
fulfill
the
OPPTS
Guidelines,
HED's
Hazard
Identification
Assessment
Review
Committee
(HIARC)
evaluated
a
segment
of
the
extensive
body
of
information
published
in
the
open
literature
dealing
with
lindane.
These
studies
show
that
exposure
to
lindane,
both
transplacental
and
via
mother's
milk,
is
possible
and
that
such
exposure
may
result
in
adverse
developmental
effects
on
human
offspring.
According
to
Karmaus
et
al
(1995),
females
exposed
to
lindane
risk
having
offspring
with
reduced
birthweight
and
length.
Pompa
et
al
(1994)
has
also
been
able
to
show
that
transfer
of
lindane
and
pentachlorobenzene
from
mother
to
newborn
rabbits
can
occur.
Rivera
et
al
(1990)
found
that
early
postnatal
exposure
to
lindane
may
induce
behavioral
changes
in
developing
rats.
Evidence
of
reproductive
failure
and
fetotoxicity
in
mice
has
been
compiled
by
Sircar
et
al.

B.
Dose
Response
Assessment
i.
Determination
of
Susceptibility
There
was
evidence
of
qualitative
increased
susceptibility
in
the
rat
multi­
generation
reproduction
study:
Both
parental
and
offspring
LOAELS
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.

There
is
also
quantitative
increased
susceptibility
demonstrated
in
the
rat
developmental
neurotoxicity
study:
Maternal
toxicity
observed
at
120
ppm
(13.7
mg/
kg/
day,
LOAEL)
is
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling
(maternal
NOAEL
is
50
ppm;
5.
6
mg/
kg/
day).
Offspring
toxicity
was
observed
at
50
ppm
(5.
6
mg/
kg/
day,
LOAEL)
and
is
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
(NOAEL
is
10
ppm;
1.
2
mg/
kg/
day).
15
The
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two­
generation
reproduction
study
­
no
additional
functional
or
morphological
changes
in
the
nervous
system
were
noted.
In
the
open
literature,
lindane
is
found
in
mother's
milk
and
metabolites
of
lindane
have
been
shown
to
cross
the
placental
barrier.

The
Food
Quality
Protection
Act
(FQPA)
Safety
Factor
Committee
met
on
August
2,
2000
and
evaluated
the
hazard
and
exposure
data
to
determine
if
the
10x
safety
factor
should
be
retained
(Tarplee,
DOC
#
014272).
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x
because:
1)
the
toxicology
data
base
is
complete;
2)
the
available
data
provide
no
indication
of
quantitative
or
qualitative
increased
susceptibility
in
rats
from
in
utero
exposure
to
lindane
in
the
prenatal
developmental
study;
3)
although
the
developmental
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required;
4)
the
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two­
generation
reproduction
study;
and
5)
adequate
actual
data,
surrogate
data,
and/
or
modeling
outputs
are
available
to
satisfactorily
assess
food
exposure
and
to
provide
a
screening
level
drinking
water
exposure
assessment;
and
6)
there
are
currently
no
residential
uses.

ii.
Cancer
Classification
On
May
30,
2001,
the
HED
Cancer
Assessment
Review
Committee
(CARC)
met
to
evaluate
the
carcinogenic
potential
of
lindane.
At
this
meeting,
the
CARC
could
not
make
a
determination
of
the
carcinogenic
potential
of
lindane
because
the
NTP
studies
were
of
limited
value
and
it
was
uncertain
if
the
study
on
Agouti,
Pseudoagouti
and
Black
mice
with
limited
data
could
be
used
for
regulatory
purposes.
In
addition,
the
CARC
was
informed
that
new
histopathology
data
would
be
submitted.
The
Committee
also
requested
additional
information
including
results
of
a
90­
day
subchronic
range­
finding
study
in
CD­
1
mice,
an
earlier
RfD
Committee
report
and
analyses
of
the
older
studies
on
lindane.

The
Committee
met
again
on
September
13,
2001
and
reevaluated
all
the
available
information/
data
including
the
old
and
the
newly
gathered
information
that
was
previously
not
available
for
review.
Based
on
the
most
recent
review
of
the
data
including
the
newly
submitted
carcinogenicity
study
in
CD­
1
mice
and
in
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.

iii.
Toxicology
Endpoint
Selection
The
Hazard
Identification
Committee
(HIARC)
met
on
June
13,
2000
to
evaluate
the
existing
toxicology
database
for
lindane
and
identify
toxicological
endpoints
and
dose
levels
of
concern
appropriate
for
use
in
risk
assessments
for
different
exposure
routes
and
durations,
and
assess/
reassess
the
reference
dose
(RfD).
HIARC
met
again
on
May
22,
2001
to
reconsider
the
16
endpoint
for
occupational
risk
assessment
for
the
inhalation
route
of
exposure.
Previously
the
endpoint
was
based
on
kidney
lesions
and
increased
kidney
weights
resulting
from
the
accumulation
of
alpha
2   
globulin.
These
effects
have
been
deemed
not
relevant
for
human
risk
assessment.
The
conclusions
and
toxicology
endpoints
selected
for
dietary
and
non­
dietary
risk
assessments
are
presented
in
Table
3
below.

The
critical
toxicology
study
for
acute
dietary
risk
assessment
is
the
acute
neurotoxicity
study
in
rats.
In
an
acute
oral
neurotoxicity
study,
groups
of
10
rats/
sex/
dose
were
administered
a
single
dose
of
lindane
by
gavage
at
concentrations
of
0
(control),
6,
20,
or
60
mg/
kg.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
testing
were
performed
prior
to
administration
and
within
3
hours
(time
of
peak
effect)
of
dosing
(day
0),
and
on
days
7
and
14
post­
dose.
Body
weights
were
recorded
pre­
test,
weekly
during
the
study
period
and
on
FOB
assessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion,
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
The
NOAEL
for
neurotoxic
effects
was
found
to
be
6
mg/
kg
for
females
and
the
LOAEL
was
20
mg/
kg
based
on
increased
forelimb
grip
strength
and
decreased
grooming
behavior
and
motor
activity
(MA).
The
NOAEL
for
neurotoxicity
in
males
is
20
mg/
kg
and
the
LOAEL
for
males
is
60
mg/
kg
based
on
tremors,
convulsions,
decreased
MA,
and
increased
forelimb
grip
strength.
The
Uncertainty
Factor
includes
10x
for
inter­
species
variation,
and10X
for
intra­
species
extrapolation.
The
FQPA
safety
factor
is
reduced
to
3X.
Therefore,
the
acute
Population
Adjusted
Dose
(aPAD)
is
0.02
mg/
kg/
day
(NOAEL
of
6
mg/
kg/
day
÷
300
(UF
of
100
x
FQPA
factor
of
3).

The
acute
dietary
endpoint
for
the
general
population
was
considered
sufficiently
protective
for
the
subpopulation
of
females
13­
50.
Although,
there
was
evidence
of
increased
susceptibility
in
the
DNT,
the
offspring
effects
were
not
attributable
to
a
single
dose.
A
separate
endpoint
for
this
subpopulation
was
therefore
not
identified.

The
critical
toxicology
study
for
chronic
non­
cancer
dietary
risk
assessment
is
the
chronic
toxicity/
oncogenicity
study
in
rats.
In
this
chronic
toxicity/
oncogenicity
study,
lindane
was
administered
in
the
diet
to
groups
of
115
male
and
115
female
Wistar
rats
per
dose
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
The
systemic
toxicity
LOAEL
for
male
and
female
rats
is
100
ppm
(4.
81
and
6.0
mg/
kg/
day,
respectively)
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
10
ppm
(0.
47
and
0.
59
mg/
kg/
day
for
males
and
females,
respectively).
The
Uncertainty
Factor
includes
10X
for
inter­
species
variation,
and10x
for
intra­
species
extrapolation.
The
FQPA
safety
factor
is
reduced
to
3X.
Therefore,
the
chronic
Population
Adjusted
Dose
(cPAD)
was
determined
to
be
0.0016
mg/
kg/
day
(NOAEL
of
0.
47
mg/
kg/
day
÷
300
(UF
of
100
x
FQPA
of
3).
For
occupational
assessment,
the
dermal
absorption
rate
for
lindane
was
estimated
to
be
approximately
10%
in
10
hours
of
exposure
in
humans.
The
HIARC
concurred
with
the
TES
17
committee
decision
(HED
Doc.
#
013460)
that
the
dermal
absorption
factor
is
10%
based
on
a
published
report
by
Feldman
and
Maibach
(Toxicology
and
Applied
Pharmacology
28,
126­
132,
1974).

Table
3.
Doses
and
Toxicological
Endpoints
Selected
for
Risk
Assessment
of
Lindane
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
TYPE/
MRID
Acute
Dietary­
general
population
NOAEL=
6
mg/
kg
UF
=
100
LOAELis20
mg/
kgbased
on
increasedgrip
strength,
increased
motor
activity
Acute
Neurotoxicity
in
Rats/
44769201
Acute
RfD
=
0.
06
mg/
kg/
day
aPAD
=
0.
02
mg/
kg/
day
Chronic
Dietary
NOAEL=
0.
47
mg/
kg/
day
UF
=
300
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Chronic
RfD
=
0.
0047
mg/
kg/
day
cPAD
=
0.0016
mg/
kg/
day
Short­
Term
1
(Dermal)
NOAEL=
1.
2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Intermediate­
Term
1
(Dermal)
NOAEL=
1.
2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Long­
Term
1
(Dermal)
NOAEL=
0.
47
mg/
kg/
day
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Dermal
Absorption
Factor
=
10%

Short
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.
5
mg/
m
3
)
based
on
clinical
signs
(diarrhea,
piloerection)
seen
at
day
14
and
continuing
for
20
days
90­
Day
Inhalation
Toxicity
/
00255003
Intermediate
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.
5
mg/
m
3
)
LOAEL
is
5.
0
mg/
m
3
based
on
increased
kidney
weights
of
female
rats
and
bone
marrow
effects.
90­
Day
Inhalation
Toxicity
/
00255003
Long
Term
2
(Inhalation)
N/
A
N/
A
N/
A
1
An
MOE
of
100
was
selected
2
Exposure
thru
this
route
for
this
duration
is
not
expected
18
The
Maibach
study
tested
12
pesticides
and
herbicides,
including
lindane,
on
human
subjects
(6
per
chemical)
to
quantify
their
dermal
penetration.
C
14
­labeled
chemicals
were
applied
topically
(4   
g/
cm
2
)
to
the
forearm
or
via
the
intravenous
route
(1   
Ci).
Excretion
of
the
chemicals
was
then
monitored
by
collecting
and
analyzing
urine
samples
during
the
5
day
testing
period.
All
results
were
calculated
as
percent
of
the
injected
or
applied
dose.
Data
obtained
after
IV
dosing
was
used
to
correct
the
skin
penetration
data
for
incomplete
urinary
recovery.
Lindane
was
shown
to
have
a
penetration
factor
of
9.3%
±
3.
7
(SD).

The
critical
study
selected
for
short­
and
intermediate­
term
dermal
risk
assessment
was
the
Developmental
Neurotoxicity
Study
in
rats.
A
90­
day
dermal
toxicity
study
in
rabbits
was
available;
the
NOAEL
was
10
mg/
kg/
day
and
the
LOAEL
was
60
mg/
kg/
day
based
on
hepatic
toxicity.
The
HIARC
did
not
consider
this
study
to
be
appropriate
for
risk
assessment
and
instead
selected
an
oral
endpoint
due
to:
1)
the
concern
for
developmental
effects
as
seen
in
pups
in
the
developmental
neurotoxicity
study,
2)
developmental
effects
are
not
evaluated
in
the
dermal
toxicity
study,
3)
the
dermal
toxicity
study
was
conducted
in
the
rabbit,
while
the
increased
susceptibility
was
seen
in
rat
pups
via
an
oral
route,
and
4)
this
endpoint
will
be
protective
of
dermally
exposed
workers.
For
developmental
toxicity,
the
NOAEL
was
1.
2
mg/
kg/
day
and
the
LOAEL
was
5.6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
The
target
MOE
is
100
(10X
for
interspecies
variation
and
10X
for
intraspecies
variation)
for
occupational
exposure.
Since
an
oral
endpoint
was
selected,
a
10%
dermal
absorption
factor
will
be
used
for
route
to
route
extrapolation.

The
critical
study
selected
for
risk
assessment
for
long­
term
dermal
exposure
was
the
Chronic
One­
Year
Toxicity
Study
in
rats,
which
is
discussed
above.
The
systemic
toxicity
LOAEL
for
male
and
female
rats
is
4.
81
and
6.0
mg/
kg/
day,
respectively,
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
0.47
and
0.
59
mg/
kg/
day
for
males
and
females,
respectively.
The
target
MOE
is
100
(10X
for
interspecies
variation
and
10X
for
intraspecies
variation)
for
occupational
exposure.
Since
an
oral
endpoint
was
selected,
a
10%
dermal
absorption
factor
will
be
used
for
route
to
route
extrapolation.

The
critical
study
for
inhalation
risk
assessment
for
lindane
is
an
90­
Day
Inhalation
Toxicity.
Lindane
was
administered
by
inhalation
to
groups
of
12
male
and
12
female
Wistar
rats
at
nominal
concentrations
of
0,
0.02,
0.10,
0.50,
or
5.0
mg/
m
3
,
6
h/
day
for
90
days.
Lindane
was
detected
in
the
brain,
liver,
fat,
and
serum
of
all
exposed
rats.
The
HIARC
established
a
NOAEL
of
0.5
mg/
m
3
for
this
risk
assessment
based
on
clinical
signs
(diarrhea
and
piloerection)
seen
at
day
14
after
exposure
and
continuing
for
20
days
at
the
highest
concentration
tested
(5
mg/
m
3
).
This
NOAEL
is
applicable
and
appropriate
only
for
short­
term
exposure
risk
assessment
because
the
effects
were
seen
during
this
period
of
exposure.
For
intermediate
exposures,
the
NOAEL
is
0.5
mg/
m
3
(0.
13
mg/
kg)
based
on
increased
kidney
weights
and
bone
marrow
effects.
For
inhalation
risk
assessments
for
occupational
exposure,
the
target
MOE
is
100
(10X
for
19
intraspecies
variation
and
10X
for
interspecies
variation).
Long­
term
inhalation
exposure
is
not
expected.

iv.
Endocrine
Disruptor
Effects
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).

v.
Incident
Reports
The
Agency
has
conducted
a
review
of
reported
poisoning
incidents
associated
with
human
exposure
to
lindane.
The
Agency
has
consulted
the
following
data
bases
for
the
poisoning
incident
data
on
the
active
ingredient
lindane:
Incident
Data
System,
Poison
Control
Center
Data
­
1993
through
1998,
California
Data
­
1982
through
1998,
and
the
National
Pesticide
Telecommunications
Network.

The
review
only
included
lindane
containing
products
currently
registered
for
use
as
a
seed
treatment.
Incidents
due
to
all
other
types
of
lindane
products
were
excluded.
No
incidents
were
located
related
to
seed
treatment
use
of
lindane.
None
of
the
cases
reported
to
Poison
Control
Centers
from
1993
through
1998
concerned
products
identified
as
being
used
for
seed
treatment.
However,
it
should
be
noted
that
nearly
one­
third
of
the
exposures
involving
lindane
did
not
identify
a
specific
product,
but
rather
just
exposure
to
lindane.
Detailed
descriptions
of
eight
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982­
1998)
were
reviewed.
In
three
of
these
cases,
lindane
was
deemed
the
primary
cause
of
the
illness.
All
three
incidents
occurred
in
1984.
All
three
cases
involved
driving
and
filling
planter
hoppers
with
treated
cotton
seed.
Two
of
the
cases,
apparently
involved
in
the
same
operation,
were
both
treated
in
a
hospital
and
off
work
for
7
days.
The
third
case
was
not
treated
in
a
hospital
but
was
off
work
for
2
days.
Specific
symptoms
were
not
reported
for
any
of
these
three
cases.
The
National
Pesticide
Telecommunications
Network
did
not
report
on
incidents
specifically
related
to
lindane
use
for
seed
treatment.
Relatively
few
incident
of
illness
have
been
reported
due
to
lindane
used
for
seed
treatment;
therefore,
no
recommendations
can
be
made
based
on
the
few
incident
reports
available.
20
IV.
Exposure
and
Risk
Assessment
A.
Dietary
Exposure
(Food
Sources)

i.
Background
In
1993,
CIEL
offered
to
voluntarily
cancel
all
crop
uses
of
lindane
except
seed
treatment
and
certain
non­
food
uses.
The
Agency
considers
lindane
seed
treatment
as
a
food
use
requiring
tolerances
based
on
existing
data
from
radiolabeled
studies
indicating
uptake
of
residues
from
the
treated
seeds
into
the
aerial
portion
of
the
growing
crop.

The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
In
addition,
the
established
tolerances
for
the
following
commodities
will
be
revoked
because
no
registrants
have
committed
to
support
the
foreign
or
domestic
uses
for:
apples,
apricots,
asparagus,
avocados,
celery,
cherry,
collards,
cucumbers,
eggplants,
grapes,
guavas,
kale,
kohlrabi,
mangoes,
melons,
mushrooms,
mustard
greens,
nectarines,
okra,
onions
(dry
bulb
only),
peaches,
pears,
pecans,
peppers,
pineapple,
plums
(fresh
prunes),
pumpkins,
quinces,
squash,
strawberries,
summer
squash,
swiss
chard
and
tomatoes.

Tolerances
for
residues
of
lindane
in/
on
food
and
feed
commodities
are
currently
established
under
40
CFR
§180.133
and
are
expressed
in
terms
of
lindane
per
se.
The
nature
of
the
residue
in
plants
is
not
adequately
understood.
A
new
nature
of
the
residue
study
from
seed
treatment
are
required
for
cereal
grain.
The
nature
of
the
residue
in
poultry
and
ruminants
is
adequately
understood.
The
HED
Metabolism
Assessment
Review
Committee
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radiolabeled
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data.

Table
4.
Tolerance
Reassessment
Summary
for
Lindane.

Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Tolerance
Listed
Under
40
CFR
§180.133
Apples
1
Revoke
Not
being
supported
for
reregistration.

Apricots
1
Revoke
Not
being
supported
for
reregistration.

Asparagus
1
Revoke
Not
being
supported
for
reregistration.

Avocados
1
Revoke
Not
being
supported
for
reregistration.

Broccoli
1
Revoke
Not
being
supported
for
reregistration.
Table
4.
Tolerance
Reassessment
Summary
for
Lindane.

Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
21
Brussels
sprouts
1
Revoke
Not
being
supported
for
reregistration.

Cabbage
1
Revoke
Not
being
supported
for
reregistration.

Cauliflower
1
Revoke
Not
being
supported
for
reregistration.

Lettuce
3
Revoke
Not
being
supported
for
reregistration.

Spinach
1
Revoke
Not
being
supported
for
reregistration.

Celery
1
Revoke
Not
being
supported
for
reregistration.

Collards
1
Revoke
Not
being
supported
for
reregistration.

Kale
1
Revoke
Not
being
supported
for
reregistration.

Kohlrabi
1
Revoke
Not
being
supported
for
reregistration.

Mustard
greens
1
Revoke
Not
being
supported
for
reregistration.

Swiss
chard
1
Revoke
Not
being
supported
for
reregistration.

Cherry
1
Revoke
Not
being
supported
for
reregistration.

Cucumbers
3
Revoke
Not
being
supported
for
reregistration.

Eggplants
1
Revoke
Not
being
supported
for
reregistration.

Fat
of
meat
from
cattle,
goats,
horses,
and
sheep
7
Revoke
Current
tolerances
are
based
on
direct
dermal
application.
The
need
for
livestock
tissue
tolerances
will
be
reevaluated
when
the
required
nature
of
the
residue
study
in
plants
is
submitted
Fat
ofmeat
from
hogs
4
Grapes
1
Revoke
Not
being
supported
for
reregistration.

Guavas
1
Revoke
Not
being
supported
for
reregistration.

Mangoes
1
Revoke
Not
being
supported
for
reregistration.

Melons
3
Revoke
Not
being
supported
for
reregistration.

Mushrooms
3
Revoke
Not
being
supported
for
reregistration.

Nectarines
1
Revoke
Not
being
supported
for
reregistration.

Okra
1
Revoke
Not
being
supported
for
reregistration.

Onions
(dry
bulb
only)
1
Revoke
Not
being
supported
for
reregistration.

Peaches
1
Revoke
Not
being
supported
for
reregistration.

Pears
1
Revoke
Not
being
supported
for
reregistration.

Pecans
0.01
Revoke
Not
being
supported
for
reregistration.

Peppers
1
Revoke
Not
being
supported
for
reregistration.

Pineapple
1
Revoke
Not
being
supported
for
reregistration.

Plums
(fresh
prunes)
1
Revoke
Not
being
supported
for
reregistration.

Pumpkins
3
Revoke
Not
being
supported
for
reregistration.

Quinces
1
Revoke
Not
being
supported
for
reregistration.

Squash
3
Revoke
Not
being
supported
for
reregistration.

Strawberries
1
Revoke
Not
being
supported
for
reregistration.

Summer
squash
3
Revoke
Not
being
supported
for
reregistration.
Table
4.
Tolerance
Reassessment
Summary
for
Lindane.

Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
22
Tomatoes
3
Revoke
Not
being
supported
for
reregistration.

ii.
Sources
of
Lindane
Residues
on
Foods
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration.
There
are
no
adequate
nature
of
the
residue
studies
for
plants
from
seed
treatment
application;
therefore,
a
new
metabolism
study
is
required
for
cereal
grain.
A
seed
treatment
metabolism
study
was
reviewed
by
HED;
although
it
was
deemed
inadequate
due
to
insufficient
characterization/
identification
of
the
radioactive
residues,
it
was
found
to
be
useful
in
the
determination
of
the
TRR
for
use
in
this
dietary
exposure
analysis.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
Secondary
residues
in
livestock
commodities
may
result
from
livestock
consuming
treated
food.
The
nature
of
the
residue
in
poultry
is
understood.
The
nature
of
the
residue
in
ruminants
is
adequately
understood
since
the
registrant
recently
submitted
the
required
data
(MRID
45224101,
45224102,
and
45277201)
to
upgrade
a
ruminant
metabolism
study
(MRID
44867104)
which
was
deemed
inadequate.
The
lindane
equivalent
residue
values
used
in
the
dietary
exposure
analyses
were
derived
using
a
ratio
of
total
radioactive
residue
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies
(ruminant
and
poultry).
Thiswould
be
worstcase
estimatesince
we
areassuming
thatallofthe
TRRwould
be
residues
of
concern.

The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
assessment
since
percent
crop
treated
was
used
in
the
analyses.
The
dietary
exposure
analyses
that
were
based
on
the
adjustment
of
the
lindane
residues
in
the
livestock
feeding
studies
is
a
Tier
3
assessment.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.

iii.
Residue
Chemistry
Studies
for
Lindane
A
tabular
summary
of
the
residue
chemistry
science
assessments
for
reregistration
of
lindane
is
presented
in
Table
A
of
the
Revised
Residue
Chemistry
Chapter
(T.
Morton,
D279259,
12/
11/
01).
When
end­
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
all
end­
use
product
labels
(e.
g.,
MAI
labels,
SLNs,
and
products
subject
to
the
generic
data
exemption)
should
be
amended
such
that
they
are
consistent
with
the
basic
producers'
labels.
A
30­
day
plant­
23
back
interval
for
leafy
vegetables
and
a
12­
month
plant­
back
interval
for
all
other
unregistered
crops
is
required
on
all
end­
use
product
labels
for
lindane.

Nature
of
the
Residue
­
Plants
(GLN
860.1300):
The
qualitative
nature
of
lindane
residues
in
plants
reflecting
seed
treatment
is
inadequately
understood.
For
the
purpose
of
reregistration,
the
basic
registrants
are
required
to
conduct
new
plant
metabolism
studies
on
lindane.
These
studies
should
be
conducted
on
a
representative
cereal
grain,
as
the
registrants
have
indicated
that
the
only
food
uses
they
are
supporting
are
for
seed
treatment
of
these
crops.
The
new
studies
should
be
conducted
at
rates
which
insure
that
sufficient
14
C­
residues
are
available
for
analysis.
Crop
samples
should
be
harvested
at
the
appropriate
stage.
Identification
of
14
C­
residues
should
also
be
confirmed
using
more
than
one
method,
or
by
GC/
MS.

Nature
of
the
Residue
­
Animals
(GLN
860.1300):
No
direct
livestock
treatments
remain
registered.
Residues
of
lindane
may
occur
in
livestock
as
a
result
of
feeding
of
lindane
treated
feed
(secondary
residues).
The
qualitative
nature
of
the
residue
in
ruminants
is
adequately
understood.
The
basic
registrants
have
recently
submitted
additional
data
for
the
ruminant
metabolism
study
(MRID
44867104)
which
was
deemed
inadequate
but
upgradable.
To
upgrade
the
study,
the
registrant
was
required
to
identify
the
metabolite
labeled
LiV
in
goat
liver's
aqueous
phase
which
accounted
for
25.2
%
of
the
total
radioactivity
(0.57
ppm).
In
addition,
storage
stability
data
was
required.
The
registrant
has
recently
submitted
the
required
data
(MRID
45224101,
45224102,
and
45277201)
thus,
adequately
addressing
this
deficiency.
The
total
radioactive
residues
(TRR;
expressed
as
lindane
equivalents)
in
collected
samples
were
3.
46
ppm
in
fat,
2.
25
ppm
in
liver,
0.
48
ppm
in
kidney,
0.
20
ppm
in
muscle,
and
0.
20
ppm
in
milk.
The
parent,
lindane
was
the
major
residue
identified
in
all
goat
matrices.

The
qualitative
nature
of
the
residue
in
poultry
is
adequately
understood.
A
poultry
metabolism
study
(MRIDs
40271301
and
44405404),
submitted
by
the
registrants
in
response
to
the
9/
85
Lindane
Reregistration
Guidance
Document,
has
recently
been
upgraded
to
acceptable
status.
A
brief
summary
of
the
poultry
metabolism
study
follows.
Laying
hens
were
dosed
with
[
14
C]
lindane
at
levels
equivalent
to
1.2
ppm
or
120
ppm
in
the
diet
for
four
consecutive
days.
Radioactive
residues
accumulated
to
the
greatest
extent
in
fatty
tissues.
In
high
dose
hens,
TRR
levels
were
highest
in
fat
(96.98
ppm)
and
lowest
in
breast
muscle
(1.44
ppm).
TRR
levels
were
proportionally
less
in
tissues
of
low­
dose
hens
(fat,
1.
26
ppm;
breast
muscle
0.
02
ppm).
In
eggs
of
high­
dose
hens,
14
C­
residues
peaked
on
Day
4
at
10.83
ppm
in
yolks
and
0.21
ppm
in
whites.
Lindane
was
the
major
residue
component
identified
and
accounted
for
approximately
95%
of
the
TRR
in
egg
yolks,
71­
86%
of
the
TRR
in
muscle,
skin,
and
fat,
and
52%
of
the
TRR
in
liver.
Other
metabolites
that
were
identified
included:
1,2,4­
trichlorobenzene;
1,3,5­
trichlorobenzene
and
dichlorobenzene(
s);
tetrachlorobenzene
(either
1,2,4,5­
or
1,2,3,4­);
PCCH;
1,
2,
3,
4tetrachlorobenzene
tetrachlorocyclohexene;
1,2,3,4,5­
pentachlorobenzene;
and
hexachlorocyclohexene.
The
results
of
the
ruminant
and
poultry
metabolism
studies
will
be
presented
to
HED's
MARC
for
determination
of
terminal
residue
of
concern
in
eggs,
milk,
and
animal
tissues
once
an
adequate
seed
treatment
metabolism
study
is
submitted.
If
the
Committee
determines
that
lindane
24
is
the
only
residue
of
concern
requiring
regulation,
then
the
existing
storage
stability
data
for
poultry
commodities,
the
analytical
method
used
for
data
collection,
and
the
poultry
feeding
study
will
be
upgraded
to
acceptable
status.

In
the
absence
of
acceptable
metabolism
studies,
the
HED
MARC
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radioactive
residues
should
be
used
for
risk
assessment
purposes
until
adequate
plant
metabolism
studies
are
submitted.

Residue
Analytical
Methods
(GLN
860.1340):
Adequate
methods
are
available
for
determination
of
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
The
Pesticide
Analytical
Manual
(PAM)
Vol.
II
lists
Methods
I
and
II
for
the
analysis
of
mixed
isomers
of
1,2,3,4,5,6­
hexachlorocyclohexane
in/
on
plant
and
animal
commodities.
Method
I
is
a
multiresidue
method
(see
"GLN
860.1360:
Multiresidue
Methods"
section)
for
chlorinated
compounds.
Method
II
is
based
upon
the
official
final
AOAC
method
(1990,
15th
edition
of
AOAC)
and
is
suitable
for
determining
residues
of
lindane
in/
on
AOAC
Group
I
nonfatty
foods
(vegetables
and
fruits),
dairy
products,
fish,
and
eggs.
The
stated
limit
of
detection
of
Method
II
is
0.05
ppm
for
most
commodities.

Because
the
nature
of
the
residue
in
plants
resulting
from
seed
treatment
uses
as
well
as
the
nature
of
the
residue
in
ruminants
have
not
been
delineated,
the
adequacy
of
the
available
analytical
methods
cannot
be
determined.
The
registrants
are
reminded
that
radiovalidation
of
enforcement
method(
s)
is
a
reregistration
requirement;
therefore,
representative
samples
from
the
requested
plant
and
ruminant
metabolism
studies
should
be
used
for
validation
and
analyzed
by
the
existing
or
proposed
enforcement
method(
s)
to
determine
whether
total
toxic
residues
are
extracted
from
weathered
samples.

Adequate
data­
collection
methods
have
been
submitted
for
detection
of
lindane
per
se
in/
on
cucumbers
and
spinach.
The
analytical
procedures
for
detecting
lindane
in
cucumbers
and
spinach
are
essentially
the
same.
Based
on
acceptable
method
validation
recoveries,
the
Agency
has
deemed
the
GC/
ECD
method
to
be
adequate
for
determining
residues
of
lindane
per
se
in
nonfatty
crops.

A
GC/
MS
method
(SOP#
Meth­
109)
entitled
"Determination
of
Lindane
in
Wheat
and
Canola
Matrices"
was
utilized
as
the
data­
collection
method
in
a
recently
submitted
wheat
field
study.
Following
extraction
and
purification,
detection
and
quantitation
were
conducted
using
a
gas
chromatograph
equipped
with
a
mass
selective
detector
(GC/
MS).
The
LOQ
was
0.
005
ppm.

A
data­
collection
method,
based
on
the
AOAC
method,
was
also
submitted
for
detection
of
lindane
per
se
in
eggs,
milk,
and
animal
tissues.
The
Agency
previously
required
an
EPA
method
validation
for
the
submitted
method
if
lindane
tolerances
for
lean
animal
tissues
were
to
be
established
because
the
AOAC
method
did
not
describe
techniques
which
the
registrant's
method
contained
(e.
g.,
gel
permeation
chromatography
and
rotary
evaporation).
The
FDA
method
now
utilizes
these
techniques;
therefore,
the
requirement
for
a
petition
method
validation
25
was
conditionally
waived
provided
HED's
MARC
determines
that
lindane
per
se
is
the
only
residue
of
concern
in
animal
commodities.

Multiresidue
Methods
(GLN
860.1360):
The
10/
99
PESTDATA
database
(PAM,
Vol.
I,
Appendix
I)
contains
data
concerning
the
applicability
of
multiresidue
methods
to
lindane.
Lindane
is
completely
recovered
(>
80%
recovery)
using
protocols
302
(Luke
method),
303
(Mills,
Onley,
and
Gaither
method),
and
304
(Mills
method)
for
fatty
and
non­
fatty
foods.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
multiresidue
methods
test
data
for
the
metabolites
of
concern.

Storage
Stability
Data
(GLN
860.1380):
The
specifics
of
reregistration
requirements
for
storage
stability
data
in
plants
and
animals
cannot
be
ascertained
until
an
acceptable
plant
metabolism
study
is
available,
and
the
HED
MARC
has
determined
the
terminal
residues
of
concern.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
and
provided
the
additional
temperature
information
is
submitted,
the
available
storage
stability
data
for
lindane
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials
and
livestock
feeding
studies.
A
summary
of
available
storage
stability
data
for
lindane
per
se
is
summarized
below.

Raw
agricultural
and
processed
commodities:
Residues
of
lindane
per
se
are
relatively
stable
under
frozen
(­
20

C)
storage
conditions
for
up
to
8
months
in/
on
cucumbers
and
spinach
and
for
approximately
14
months
in/
on
tomatoes
and
wheat
forage.
Lindane
residues
are
stable
in
wheat
grain,
wheat
hay,
and
wheat
straw
for
approximately
18
months
when
stored
under
frozen
conditions.
Lindane
residues
in
canola
seed
were
stable
for
up
to
6.
5
months
when
stored
under
frozen
conditions
(no
temperature
given).
Lindane
residues
were
stable
for
up
to
2
months
in
canola
oil
and
1.
5
months
in
canola
meal
when
stored
under
frozen
conditions
(no
temperature
given).
The
registrant
is
required
to
submit
additional
storage
stability
data
(temperature
logs)
specifying
the
storage
conditions
of
the
canola
storage
stability
samples.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials.

Animal
commodities:
Residues
of
lindane
per
se
are
relatively
stable
in
eggs,
milk,
and
edible
tissues
of
animals
stored
frozen
(­
18

C)
for
up
to
9
months.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
ruminant
and
poultry
feeding
studies.

Crop
Field
Trials
(GLN
860.1500):
A
translocation
study
(MRID
40431207)
formed
the
basis
for
food­
use
classification
of
lindane
when
the
pesticide
is
applied
as
a
seed
treatment.
In
this
study,
[
14
C]
lindane
was
applied
as
a
seed
treatment
to
corn
(field
and
sweet),
mustard,
radish,
spinach,
sugar
beet,
and
wheat
at
approximately
1x
the
label
rate.
The
treated
seeds
were
then
planted
outdoors
in
55
gallon
drum
halves
and
allowed
to
grow
under
simulated
normal
agricultural
practices.
Samples
of
immature
and
mature
crop
commodities
were
analyzed
for
total
14
C,
and
some
fractions
were
extracted
with
hexane
and
analyzed
by
a
GC
method
for
total
26
lindane.
The
study
failed
to
adequately
identify
radioactive
residues
in/
on
all
commodities
grown
from
treated
seed.
Nonetheless,
with
the
possible
exception
of
wheat
grain
and
foliage,
residues
were
characterized
to
be
not
associated
with
biological
molecules
(e.
g.,
amino
acid,
sugar,
etc.)
that
have
incorporated
the
radiolabel.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
crop
field
trial
data
for
all
residues
of
concern.

The
registrant
has
submitted
PP#
9F05057,
for
the
establishment
of
time­
limited
tolerances
for
residues
of
lindane
per
se
in/
on
the
RACs
of
crops
for
which
seed
treatments
are
being
proposed.
The
petition
included
a
number
of
leafy
and
brassica
vegetables,
radish,
and
corn.
The
only
crop
in
this
petition
which
is
now
being
supported
by
the
registrant
is
corn.
A
revised
Section
F
is
required
deleting
all
other
crops
from
the
petition.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
for
cereal
grain
is
submitted.
The
registrants
have
also
submitted
PP#
9F6022,
for
the
establishment
of
tolerances
on
lindane
per
se
in/
on
canola
for
which
seed
treatment
is
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
and
additional
residue
data
are
submitted.

In
addition,
the
registrants
recently
submitted
acceptable
residue
data
reflecting
seed
treatment
on
wheat
RACs.
A
representative
formulation
(lindane
30­
C
flowable)
was
applied
as
a
seed
treatment
to
wheat
at
0.52
oz.
ai/
cwt
(or
330
ppm
lindane
on
the
seed).
Following
treatment,
the
treated
seeds
were
planted
in
15
diverse
geographic
locations.
Wheat
forage
samples
were
collected
at
or
near
the
jointing
stage,
the
hay
samples
at
early
flower
to
soft
dough
stage,
and
the
grain
and
straw
samples
at
normal
harvest
maturity.
Residues
of
lindane
were
nondetectable
(<
0.005
ppm)
in/
on
all
treated
wheat
grain
and
straw
samples.
Residues
of
lindane
ranged
from
<0.005
ppm
(nondetectable)
to
0.
04
ppm
in/
on
treated
wheat
forage
and
from
<0.005
ppm
(nondetectable)
to
0.
02
ppm
in/
on
treated
wheat
hay.
Additional
residue
data
would
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.

Processed
Food/
Feed
(GLN
860.1520):
No
data
are
available
to
determine
whether
lindane
residues
of
concern
concentrate
in
the
processed
fractions
of
cereal
grains
following
seed
treatment.
A
processing
study
on
corn
is
required
for
the
purpose
of
reregistration.
A
processing
study
on
wheat
would
also
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.

At
this
time,
a
processing
study
for
wheat
processed
fractions
is
not
being
required
if
lindane
per
se
is
the
only
residue
of
concern
(S.
Funk,
10/
31/
95,
D213401).
In
1998,
the
U.
S.
Food
and
Drug
Administration
(FDA)
monitoring
program
analyzed
a
total
of
227
samples
of
milled
grain
products
for
lindane
residues
at
an
LOQ
of
0.
01
ppm.
Commodities
analyzed
included
flour
and
other
milled
products,
breakfast
foods,
and
baked
goods.
Lindane
was
not
detected
in
any
sample.
27
The
registrant
submitted
a
canola
processing
study
along
with
PP#
9F6022
where
lindane
residues
in/
on
canola
refined
oil,
canola
meal,
and
bleached/
deodorized
canola
oil
were
determined.
Lindane
in
canola
refined
oil
concentrated
by
a
factor
of
at
least
5.
2x.
Lindane
did
not
concentrate
in
canola
meal
and
bleached/
deodorized
canola
oil.

Meat,
Milk,
Poultry,
Eggs
(GLN
860.1480):
The
nature
of
the
residue
in
plants
is
not
understood.
Upon
receipt
of
the
requested
plant
metabolism
data,
the
Agency
will:
(i)
determine
the
adequacy
of
established
tolerances
for
animal
commodities;
(ii)
calculate
the
expected
dietary
intake
for
beef
cattle,
dairy
cattle,
and
swine;
and
(iii)
re­
evaluate
the
need
for
additional
feeding
studies.
It
should
be
noted
that
ruminant
(M.
Kovacs,
9/
20/
88,
CB
No.
4037)
and
poultry
feeding
(G.
Otakie,
8/
31/
88,
RCB
No.
4034)
studies
are
available
assuming
that
lindane
per
se
is
the
only
residue
of
concern
in
animals.

Confined/
Field
Accumulation
in
Rotational
Crops
(GLN
860.1850
and
860.1900):
The
basic
registrants
have
submitted
a
confined
rotational
crop
study
which
was
deemed
unacceptable
and
not
upgradable
because
of
inadequate
characterization
and
identification
of
residues
due
to
significant
losses
of
organosoluble
residues
during
analysis.
Although
the
study
is
inadequate
and
the
application
rate
used
(0.75
lb
ai/
A)
greatly
exceeds
the
level
of
soil
residues
that
are
likely
to
result
from
seed­
treatment
uses,
the
data
indicate
that
residues
of
lindane
persist
in
the
soil
and
can
be
taken
up
by
rotational
crops
at
intervals
up
to
one
year.

For
the
purpose
of
reregistration,
the
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30­
day
plantback
interval
for
leafy
vegetables
and
a
12­
month
plantback
interval
for
all
other
unregistered
crops
on
all
end­
use
product
labels
for
lindane
as
recommended
by
the
ChemSAC
(memo,
10/
5/
00).
Since
this
proposal
has
been
accepted
by
the
registrants,
then
limited
rotational
field
trial
data
will
not
be
required.

B.
Dietary
Exposure
Estimates
Lindane
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.
73,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
for
Individuals
(CSFII),
1989­
1992.
The
1989­
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
in
total
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples­
cooked/
canned
or
wheat­
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
US
population
and
within
population
subgroups
(e.
g.,
children
one
to
six
years
old)
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
items
for
acute
exposure
assessment.

For
chronic
exposure
and
risk
assessment,
estimates
of
average
residues
for
foods
(e.
g.,
orange)
or
food­
forms
(e.
g.,
orange­
juice)
of
interest
are
multiplied
by
the
averaged
consumption
estimate
of
each
food/
food­
form
of
each
population
subgroup.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
28
For
acute
exposure
assessments,
individual
one­
day
consumption
data
are
used
on
an
individual­
by­
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tiers
3&
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per­
capita
basis.
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
Therefore,
revised
acute,
chronic
dietary
exposure
and
risk
analyses
have
been
conducted
with
these
commodities
removed
(T.
Morton,
12/
13/
01,
279260).
The
HED
Metabolism
Assessment
Review
Committee
concluded
that
the
total
radiolabed
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
8/
30/
00,
D267069).
The
HED
ChemSAC
recommended
comparing
the
results
from
the
dietary
exposure
analysis
using
the
TRRs
as
the
residue
input
with
results
from
a
second
dietary
exposure
analysis
using
lindane
residues
per
se
from
the
livestock
feeding
studies.
Exposure
to
lindane
was
determined
by
using
the
ratio
(ppm
TRR/
ppm
lindane
parent)
from
the
livestock
metabolism
studies.
Only
the
commodities
being
supported
by
the
registrant
were
included
in
the
dietary
exposure
analysis;
no
import
uses
were
included
as
all
of
these
tolerances
will
be
revoked.
Additionally,
FDA
monitoring
data
show
that
residues
of
lindane
are
not
being
found
in
imported
commodities.
Some
residues
are
reported
for
gamma­
BHC
but
these
residues
are
associated
with
use
of
BHC,
not
lindane.
The
Biological
and
Economic
Analysis
Division
(OPP/
BEAD)
verified
the
registrant's
percent
market
share
estimate
for
lindane
(I.
Yusuf
email,
7/
17/
00).
A
canola
processing
study
for
lindane
was
recently
reviewed
(T.
Morton,
D269388,
5/
10/
01).
Lindane
was
not
detected
in
bleached/
deodorized
canola
oil
(<
0.005
ppm).
Therefore,
½
LOQ
(0.
0025
ppm)
will
be
used
as
the
DEEM™
adjustment
factor
1.
DEEM™
default
concentrations
factors
(adjustment
factor
1)
will
be
used
for
all
other
concentration
factors.
The
wheat
grain
and
forage
TRRs
were
translated
to
barley,
oats,
and
rye.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.

Anticipated
residues
(DP
Barcode
D279260,
T.
Morton,
12/
13/
01)
were
provided
for
all
commodities
and
have
been
used
when
calculating
the
dietary
risk.
Although
the
database
for
lindane
is
substantially
complete,
additional
data
are
needed
to
eliminate
the
uncertainties
associated
with
the
exposure/
risk
assessment.
The
anticipated
residue
values
are
the
best
estimates
the
Agency
can
provide
using
the
residue
data
available
at
this
time.
These
values
have
an
inherent
uncertainty
associated
with
variations
in
analytical
methods,
geographical
representation
of
field
trials,
seasonal
variation
of
residue
levels,
etc.
29
C.
Dietary
Risk
Estimates
(Food
Sources)

The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration.
A
revised
DEEM™
analysis
was
performed
to
estimate
acute
and
chronic
dietary
exposure
and
risk
from
lindane
from
all
commodities
supported
for
reregistration,
i.
e.,
seed
treatment
of
cereal
grains
(T.
Morton,
12/
13/
01,
D279260).
The
HED
Metabolism
Assessment
Review
Committee
concluded
that
the
TRRs
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
D267069,
8/
30/
00).
Results
of
the
dietary
exposure
analysis
are
presented
in
Table
5.

i.
Acute
Dietary
Exposure
and
Risk
Estimates
For
lindane,
the
acute
dietary
exposure
analysis
was
a
tier
3
probabilistic
assessment.
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
aPAD
for
the
subpopulation
all
infants
and
7
%
of
the
aPAD
for
the
U.
S.
population
when
the
feeding
studies
were
adjusted
to
include
all
lindane
related
residues
using
the
metabolism
studies.

ii.
Chronic
Dietary
Exposure
and
Risk
Estimates
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern.
The
resulting
risk
estimates
are
3
%
of
the
cPAD
for
the
U.
S.
population
and
11
%
of
the
cPAD
for
children
1­
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
<6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
to
include
all
lindane
related
residues
using
the
metabolism
studies.

Table
5.
Estimated
Acute
and
Chronic
Dietary
Exposure
and
Risk
Population
Subgroup
Acute
(99.
9th
%ile)
Chronic
(mean
exposure)

Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
0.
001305
7
0.
000054
3
All
infants
(<
1
yr)
0.003320
17
0.000072
5
Children
(1­
6
yrs)
0.
001973
10
0.000173.
11
Children
(7­
12
yrs)
0.001088
5
0.
000096
6
Females
(13­
50
yrs)
0.000467
2
0.
000034
2
Males
(13­
19
yrs)
0.000670
3
0.
000061
4
Males
(20+
yrs)
0.000458
2
0.
000034
2
Seniors
(55+
yrs)
0.000409
2
0.
000030
2
30
iii.
Chronic
Dietary
Exposure
and
Risk
Estimates
for
Indigenous
People
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D282455,
4/
17/
02).
Because
the
annual
harvest
rates
were
divided
by
365
to
obtain
daily
harvest
rates,
and
the
daily
intake
rates
used
in
the
assessment
no
acute
dietary
exposure
analysis
was
conducted.
The
chronic
analysis
used
subsistence
food
harvest
amounts,
total
HCH
residues
in
traditional
foods,
and
adjusting
the
HCH
exposure
to
obtain
lindane
exposure.
Based
on
revised
exposure
estimates,
the
chronic
dietary
risk
to
adult
male
Indigenous
People
ranges
from
0.000055
­
0.
0006
mg/
kg
body
weight/
day
which
is
between
3
and
38
%
of
the
cPAD.
This
is
below
HED's
level
of
concern
(cPAD
=
0.
0016
mg/
kg
bw/
day).
The
revised
estimate
of
chronic
dietary
risk
to
adult
female
Indigenous
People
ranges
from
0.000064
­
0.
0007
mg/
kg
bw/
day
or
from
4
to
44
%
of
the
cPAD,
also
below
HED's
level
of
concern.
The
revised
lindane
dietary
risk
estimates
for
children
resulting
from
subsistence
food
consumption
range
from
0.0002
­
0.
0022
mg/
kg
bw/
day
or
from
13%
to
138%
of
the
cPAD.
For
children
7­
12
years
old,
the
lindane
residue
amount
was
divided
by
29
kg
(7­
12
year
body
weight)
to
obtain
the
%
cPAD
from
subsistence
foods.
The
resulting
range
of
lindane
dietary
risk
estimates
from
subsistence
food
consumption
for
children
7­
12
is
4
to
48%
of
the
cPAD.

Table
6.
Assumed
Total
Dietary
Intake
of
Lindane
(gamma­
HCH)
and
Estimated
Chronic
Dietary
Risk
for
Indigenous
Peoples
Population
Subgroup
Body
Weight
(kg)
Lindane
Exposure
(mg/
kg/
day)
%
cPAD
Adult
male
70
0.
000055
­
0.
0006
3­
38
Adult
female
60
0.
000064
­
0.
00071
4­
44
Children
1­
6
10
0.0002
­
0.
0022
13­
138
Children
7­
12
29
0.
00007­
0.0008
4­
48
iv.
Cancer
Dietary
Risk
Estimates
No
dietary
cancer
risks
for
lindane
were
estimated.

D.
Uncertainties
in
Dietary
Exposure
Assessment
There
are
no
adequate
nature
of
the
residue
metabolism
studies
for
plants
from
seed
treatment
application.
New
metabolism
studies
are
required
for
three
crops;
however,
a
seed
treatment
metabolism
study
(which
was
classified
as
inadequate)
was
reviewed
by
the
Agency
and
used
in
the
determination
of
the
TRR
for
use
in
this
dietary
exposure
analysis.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
The
nature
of
the
residue
in
poultry
and
ruminants
is
understood.
The
magnitude
of
the
residue
studies
in
poultry
and
cattle
only
analyzed
for
lindane
per
se.
The
total
residue
equivalents
were
derived
using
a
ratio
of
total
radioactive
residue
31
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies.
This
would
be
worst
case
estimate
since
we
are
assuming
that
all
of
the
TRR
would
be
residues
of
concern.

The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
probabilistic
assessment
since
percent
crop
treated
was
used
in
the
analyses.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
values
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.

E.
Drinking
Water
Exposure
Although
the
only
current
agricultural
use
of
lindane
is
for
seed
treatment,
lindane
has
been
extensively
used
in
the
past
as
an
insecticide
on
a
variety
of
crops,
for
home
termite
control,
and
as
a
wood
preservative.
Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
highly
persistent
(soil
half
life
of
2.
6
years).
Even
considering
lindane's
very
low
use
rate
under
the
current
use
restriction
to
seed
treatment
(maximum
of
0.
05
lb
a.
i./
acre),
modeling
studies
show
that
lindane
concentrations
in
both
surface
and
ground
water
may
reach
environmentally
significant
levels
(>
MCL).
This
conclusion
is
based
solely
on
lindane's
use
as
a
seed
treatment
and
does
not
consider
past
uses
of
lindane.
However,
note
that
lindane
continues
to
persist
in
the
environment
from
past
uses.

Lindane
is
persistent
and
moderately
mobile.
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions.
Degradates
are
predominantly
isomers
of
benzene
hexachloride,
pentachlorocyclohexane,
1,2,4,­
trichlorobenzene,
and
1,
2,
3­
trichlorobenzene.
Also,
lindane
can
possibly
transform
to
the
alpha
and
beta
isomers
of
hexachlorocyclohexane
by
biological
and
phototransformation,
although
this
issue
remains
to
be
conclusively
resolved.
Metabolites
are
not
quantified
since
they
comprise
less
than
10%
of
the
total
residue;
they
are
also
found
in
rat
metabolism
studies
and
have
therefore
been
evaluated
for
their
toxicologic
effects.

Lindane
is
transported
through
the
environment
by
both
hydrologic
and
atmospheric
means.
Lindane
has
often
been
detected
in
surface
and
ground
water,
and
lindane
and
its
isomers
have
been
detected
in
areas
of
non
use
(e.
g.,
the
arctic),
indicating
global
atmospheric
transport.
Most
of
these
detections
resulted
from
a
combination
of
lindane's
past
widespread
use
and
its
extreme
persistence.
Currently,
U.
S.
agricultural
uses
of
lindane
are
restricted
to
seed
treatments,
and
application
rates
are
quite
low.
Even
under
these
restriction,
however,
lindane
may
reach
water
resources
at
levels
above
the
MCL
of
0.
2
µg/
L.
32
i.
Water
Monitoring
Data
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.032
µ
g/
L).
Mean
and
median
concentrations
from
monitoring
data
are
below
HED's
calculated
Drinking
Water
Levels
of
Comparison
(See
Tables
10
and
11).

ii.
Ground
Water
EFED
used
the
Screening
Concentration
in
Ground
Water
(SCI­
GROW)
model
to
estimate
lindane
concentrations
in
groundwater
contaminated
by
terrestrial
uses.
SCI­
GROW
is
a
regression­
based
model
that
uses
few
input
parameters:
pesticide's
organic
carbon
partition
coefficient
(Koc
),
aerobic
soil
degradation
half­
life,
and
product
label
application
rate
and
frequency
(Barrett,
1997).
It
provides
a
groundwater
screening
concentration
for
use
in
determining
potential
risk
to
human
health
from
drinking
water
contaminated
with
a
pesticide.
The
groundwater
concentration
is
estimated
based
on
the
maximum
application
rates
in
areas
where
groundwater
is
exceptionally
vulnerable
to
contamination.
These
vulnerable
areas
are
characterized
by
high
rainfall,
rapidly
permeable
soil,
and
shallow
aquifer.
Input
parameters
and
output
and
the
resulting
EEC
are
summarized
in
Table
7.

Table
7.
SCIGROW/
Groundwater
Input
Parameters
and
Results
for
Seed
Treatment
Application
Rate:
Wheat
Canola
1
@
0.
051
lb/
acre
1
@
0.
116
lb/
acre
Aerobic
Soil
Half
Life
980
days
(mean
value)

Organic
Carbon
Partitioning
Coefficient
(Koc
)
1367
mL/
g
(median
value)

Peak
EEC
0.011
µg/
L
(wheat)
0.025
µg/
L
(canola)

Annual
Average
EEC
0.011
µg/
L
(wheat)
0.025
µg/
L
(canola)
33
iii.
Surface
Water
Surface
water
concentrations
from
lindane
use
as
a
seed
treatment
were
previously
estimated
using
the
Generic
Estimated
Environmental
Concentrations
(GENEEC)
model.
The
GENEEC
model
is
no
longer
used
to
estimate
EECs
for
drinking
water,
however.
Therefore,
revised
surface
water
concentrations
were
predicted
with
the
assessment
model,
FIRST.
FIRST
is
based
upon
the
linked
Pesticide
Root
Zone
Model
(PRZM)
which
simulates
pesticides
in
field
run­
off
and
Exposure
Analysis
Modeling
System
(EXAMs)
which
simulates
pesticide
fate
and
transport
in
an
aquatic
environment.
FIRST
uses
an
Index
Reservoir
which
is
based
on
Shipman
City
Lake
in
Illinois
(13
acres
in
area,
9
feet
deep,
and
a
watershed
area
of
427
acres).
FIRST
is
designed
to
produce
more
realistic
estimates
of
pesticides
in
surface
water
that
is
used
as
a
source
of
drinking
water.
Table
8
presents
a
summary
of
FIRST
inputs
and
results.

Table
8.
FIRST/
Surface
Water
Input
Parameters
and
Results
for
Lindane
Seed
Treatment.

Parameter
Value
Application
Rate
and
Number
0.
051
lb
ai/
A
x
1
application
(Wheat)
0.
116
lb
ai/
A
x
1
application
(Canola)

Organic
Carbon
Partitioning
Coefficient
942
ml/
g
lowest
of
4
values
(MRID
00164346)

Solubility
7
ppm
Application
Type
Granular/
incorporated
to
1.2
inches
Percent
Cropped
Area
56%
for
Wheat
and
87%
for
Canola
Aerobic
Soil
Half­
life
980
days
single
value
(MRID
406225­
01)*

Aerobic
Aquatic
Half­
life
1960
days
(aerobic
soil
halflife
x
2)

Photolysis
stable
(MRIDs
0016457;
001645545;
447931)

Hydrolysis
stable
(MRID
00161630)

Peak
EEC
0.98
µg/
L
(wheat)
4.16
µg/
L
(canola)

Annual
Average
EEC
0.46
µg/
L
(wheat)
1.95
µg/
L
(canola)

*In
a
336­
day
aerobic
soil
metabolism
study,
lindane
degraded
very
slowly,
with
a
registrant­
calculated
half
life
of
980
days,
thus
the
"3x"
rule
was
not
applied.

iv.
Drinking
Water
Estimate
Environmental
Concentrations
The
concentrations
presented
in
Table
9
for
drinking
water
EECs
will
be
used
for
the
purposes
of
this
risk
assessment.
The
drinking
water
EECs
for
surface
water
were
based
on
the
FIRST
model
simulations.
Drinking
water
EECs
for
groundwater
were
based
on
SCIGROW
model
simulations.
34
Table
9.
Drinking
Water
EECs
for
Lindane
Drinking
Water
Source
Acute
Chronic
Groundwater
0.025
µ
g/
L
0.
025
µ
g/
L
Surface
Water
4.16
µ
g/
L
1.
95
µ
g/
L
F.
Drinking
Water
Risk
Estimates
Drinking
water
levels
of
comparison
(DWLOCs)
associated
with
acute
and
chronic
exposure
to
lindane
in
drinking
water
have
been
calculated.
These
DWLOCs
are
compared
with
the
EECs
of
lindane
in
ground
water
and
surface
water.
The
DWLOC
is
the
concentration
of
a
chemical
in
drinking
water
that
would
be
acceptable
as
an
upper
limit
in
light
of
total
aggregate
exposure
to
that
chemical
from
food,
water,
and
residential
sources.
The
acute
and
chronic
DWLOC
for
lindane
includes
aggregate
exposure
from
food
and
water
only.

i.
DWLOCs
for
Chronic
Exposure
Chronic
DWLOCs
were
calculated
based
on
the
chronic
dietary
(food)
exposure
estimates
using
lindane
TRR
that
had
been
adjusted
using
feeding
and
metabolism
studies,
along
with
default
body
weights
and
water
consumption
figures.
The
Agency's
default
body
weights
and
water
consumption
values
used
to
calculate
DWLOCs
are
as
follows:
70
kg/
2L
(adult
male),
60
kg/
2L
(adult
female),
and
10
kg/
1L
(infant/
children).
To
calculate
the
chronic
DWLOC,
the
chronic
dietary
food
exposure
was
subtracted
from
the
chronic
PAD
as
shown
in
the
following
equation:

DWLOCchronic
=
[chronic
water
exposure
(mg/
kg/
day)
x
(body
weight)]
[consumption
(L)
x
10
­3
mg/
g]
where,
chronic
water
exposure
(mg/
kg/
day)
=
[cPAD
­
(chronic
food
(mg/
kg/
day)]

The
EECs
for
both
surface
water
and
groundwater
were
less
than
the
chronic
DWLOCs,
indicating
that
chronic
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Calculated
chronic
DWLOCs
and
EECs
are
provided
in
Table
10.

Table
10.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCchronic
(ug/
L)
Surface
Water
Annual
Avg
EECs
(ug/
L)
Ground
Water
Annual
Avg
EECs
(ug/
L)

US
Population
0.
0016
0.000054
0.001546
54
1.95
0.025
All
infants
<
1
yr
0.0016
0.000072
0.001528
15
1.95
0.025
Children
(1­
6
yrs)
0.
0016
0.000173
0.001427
14
1.95
0.025
Children
(7­
12
yrs)
0.0016
0.000096
0.001504
15
1.95
0.025
Females
(13­
50
yrs)
0.0016
0.000034
0.001566
47
1.95
0.025
Males
(13­
19
yrs)
0.0016
0.000061
0.001539
54
1.95
0.025
Table
10.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCchronic
(ug/
L)
Surface
Water
Annual
Avg
EECs
(ug/
L)
Ground
Water
Annual
Avg
EECs
(ug/
L)

35
Males
20+
0.0016
0.000034
0.001566
55
1.95
0.025
Seniors
55+
0.0016
0.000030
0.00157
55
1.95
0.025
ii.
DWLOCs
for
Acute
Exposure
Acute
DWLOCs
were
calculated
based
on
the
acute
dietary
exposure
estimates
that
were
determined
using
lindane
TRR
adjusted
with
feeding
and
metabolism
studies,
along
with
default
body
weights
and
water
consumption
figures.

The
Agency's
default
body
weights
and
water
consumption
values
used
to
calculate
DWLOCs
are
as
follows:
70
kg/
2
L
(adult
male),
60
kg/
2
L
(adult
female),
and
10
kg/
1
L
(infant/
children).
To
calculate
the
DWLOC,
the
acute
dietary
food
exposure
was
subtracted
from
the
acute
PAD
using
the
equation:

DWLOCacute
=
[acute
water
exposure
(mg/
kg/
day)
x
(body
weight)]

[consumption
(L)
x
10
­3
mg/
g]

where,
acute
water
exposure
(mg/
kg/
day)
=
[aPAD
­
(acute
food
(mg/
kg/
day)]

The
EECs
for
both
surface
water
and
groundwater
were
less
than
the
acute
DWLOCs
for
all
sub­
populations
indicating
that
acute
aggregate
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Acute
DWLOCs
and
EECs
are
provided
in
Table
11.

Table
11.
Drinking
Water
Levels
of
Comparison
for
Acute
Dietary
Exposure
Population
Subgroup
Acute
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCacute
(ug/
L)
Surface
Water
Peak
EEC
(ug/
L)
Ground
Water
Peak
EEC
(ug/
L)

US
Population
0.
02
0.
0013
0.019
665
4.16
0.025
All
infants
<
1
yr.
0.
02
0.
0033
0.017
170
4.16
0.025
Children
1­
6
yrs.
0.02
0.002
0.018
180
4.16
0.025
Children
7­
12
yrs.
0.
02
0.
0011
0.019
190
4.16
0.025
Females
13­
50
yrs.
0.02
0.0005
0.019
570
4.16
0.025
Males
13­
19
yrs
0.
02
0.
0007
0.019
665
4.16
0.025
Males
20+
0.02
0.0005
0.019
665
4.16
0.025
Seniors
55+
0.02
0.0004
0.019
665
4.16
0.025
36
iii.
Non­
Dietary
Exposure
Occupational
lindane
exposure
via
dermal
and
inhalation
routes
can
occur
during
handling,
mixing,
loading,
and
applying
activities.
There
are
currently
no
residential
pesticidal
uses
being
supported
for
lindane
and
therefore,
there
is
no
potential
for
residential
exposure
from
pesticidal
uses
of
lindane.
Based
on
toxicological
criteria
and
potential
for
exposure,
HED
has
conducted
separate
dermal
and
inhalation
exposure
assessments
for
a
variety
of
occupational
scenarios.

G.
Occupational
Exposure
and
Risk
Estimates
There
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
associated
with
seed
treatment
uses
of
lindane.
Based
on
the
use
patterns
and
potential
exposures
described
above,
5
major
exposure
scenarios
were
identified
as
representative
of
lindane
uses:
(1)
on
farm
seed
treatment
with
dry
formulations
­
open
transfer
system,
(2)
on
farm
seed
treatment
with
liquid
formulations
­
closed
transfer
system,
(3)
mixing/
loading
and
applying
liquid
with
commercial
seed­
treatment
equipment,
(4)
bagging
and
otherwise
handling
treated
seeds,
(5)
cleaning/
maintaining
seed
treatment
equipment,
and
(6)
loading/
planting
treated
seeds.
To
assess
the
exposures
from
on­
farm
treatment
of
the
liquid
formulation
with
a
closed
transfer
system
(scenario
2)
and
commercial
seed
treatment
activities
with
lindane
(scenarios
3,
4a,
4b,
and
5),
the
Agency
considered
all
relevant
data,
including
a
study
which
was
conducted
at
three
seedtreatment
plants
in
Alberta,
Canada,
during
which
lindane
was
one
of
the
active
ingredients
being
monitored
(MRID
44731501).
To
refine
this
assessment,
the
Agency
also
used
surrogate
data
from
a
commercial
seed
treatment
facility
(Helix
study,
MRID
45200002),
from
which
median
unit
dermal
and
inhalation
exposure
measurements
were
available
to
assess
risks
to
various
commercial
seed
treatment
workers,
including
baggers,
sewers,
stackers,
forklift
operators,
and
cleaners.
Because
the
equipment
used
for
on­
farm
treatment
with
the
liquid
formulation
has
similar
performance
to
the
equipment
used
in
the
commercial
facility,
exposure
data
from
the
Helix
study
was
also
used
to
assess
workers
treating
seeds
for
this
scenario
(scenario
2).
In
addition,
the
Agency
used
surrogate
exposure
data
(Isophenfos
study,
MRID
42251901)
to
assess
loading
and
planting
treated
seeds
(scenario
6).

Table
12
presents
the
exposure
scenarios,
application
rates,
and
amount
potentially
handled
that
have
been
used
for
the
exposure
calculations.
Exposures
for
handling
treated
seed
before
planting
and
planting
treated
seed
use
parameters
for
wheat
and
canola
as
representative
crops.
Therefore,
the
rates/
seed
types
presented
in
Table
12
are
representative,
rather
than
inclusive,
and
no
attempt
has
been
made
to
assess
a
range
of
application
rates
to
ensure
that
all
use
rate/
exposure
scenarios
are
included.

Table
12:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Chemical
Specific
Monitoring
Data
Available?
PHED
Data?
Application
Rates
(lb
ai/
amount
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
(1)
on
farm
seed
treatment
with
dry
formulations
­
open
transfer
system
Yes
Fenske
Study
MRID
#44405802
No
0.023
lb
ai/
bushel
(60
lbs
seed)
for
wheat
0.056
­0.
125
lb
ai/
100
lb(
corn)
12000­
24000
lbs
seed
(wheat)
1500
2700
lbs
seed
(corn)
5.0
a
­9.
3
(wheat)

0.84­
3.
4
(corn)
Table
12:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Chemical
Specific
Monitoring
Data
Available?
PHED
Data?
Application
Rates
(lb
ai/
amount
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
37
(2)
on
farm
seed
treatment
with
liquid
formulations

closed
transfer
system
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)

0.
75
­
1.
5
lb
ai/
100
lb
seed
(canola)
30000
lbs
seed
b
(wheat)
2000
lbs
seed
(canola)
13
(wheat)

15/
30
(canola)

(3)
mixing/
loading
and
applying
liquid
with
a
commercial
seed­
treatment
equipment
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)

0.
75
­
1.
5
lb
ai/
100
lb
seed
(canola)
176000
lbs
seed
(wheat
and
canola)
76
(wheat)

1320/
2640
(canola)

(4)
handlerfor
commercial
seed­
treatment
equipment
(i.
e.
bagging
and
stacking
and
forklift
operator)
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)

0.75­
1.5
lb
ai/
100
lb
seed
(canola)
176000
lbs
seed
(wheat
and
canola)
76
(wheat)

1320/
2640
(canola)

(5)
Cleanerfor
commercial
seed
treatment
Yes
Helix
Study
MRID
#45200002
No
Cleaner
daily
inhalation
exposures
measured
in
mg/
kg/
day
were
taken
directly
from
the
HELIX
study.

(6)
Loading
and
Planting
treated
seed
Yes
Isophenphos
Study
MRID
#42251901
Yes
0.
043
lb
ai/
100
lb
seed
(wheat)

0.
75
­
1.
5
lb
ai/
100
lb
seed
(canola)
30000
lbs
seed
b
(wheat)
2000
lbs
seed
(canola)
13
(wheat)

15/
30
(canola)

a
Data
are
available
from
on
farm
treatment
study;
assumes
120
lbs
wheat
per
acre,
planting
100
­200
acres
per
day;
15
lbs
corn/
acre
planting
100180
acres
day
b
Daily
amount
treated
based
on
HEDs
estimates
of
acreage
that
would
be
reasonably
expected
to
be
planted
in
a
day
for
commercially
treated
seed
or
seed
treated
with
an
on­
farm
closed
system.
Assumes
120
lbs
wheat/
acre,
8
lbs
canola/
acre,
planting
an
average
of
250
acres/
day.

i.
Commercial
Seed
Treatment
HED
has
revised
its
assessment
of
occupational
exposure
for
commercial
seed
treatment.
The
previous
assessment
was
based
on
a
commercial
seed
treatment
study
(MRID
44731501)
which
was
of
a
lesser
quality
and
probably
did
not
address
changes
in
the
technology
that
have
occurred
since
the
study
was
conducted
.
The
revised
assessment
is
based
on
a
study
measuring
exposures
of
workers
treating
canola
seed
with
HELIX
289S
(a
mixture
of
thimethozam,
difenconazole,
metalaxyl,
and
fludioxonil).
The
study
was
reviewed
jointly
by
EPA
and
PMRA
(MRID
45200002).
The
HELIX
289S
Study
is
comprehensive
occupational
exposure
study
designed
and
conducted
to
quantify
potential
exposure
to
thiamethoxam,
formulated
as
a
flowable
liquid,
during
commercial
treatment
of
canola
seed.
Lindane
end­
use
products
for
canola
use
are
liquids
(flowable
formulation).
Lindane
products
for
grower
use
on
small
grains,
corn,
and
sorghum
are
dust
and
wettable
powders
and
liquids.
In
the
absence
of
more
formulation
specific
data,
HED
believes
the
HELIX
Study
provides
the
best
data
available
for
assessing
exposure/
risk
from
commercial
seed
treatment
with
lindane.
HED
has
reevaluated
the
estimates
of
exposure
and
risk
from
treatment
of
wheat
and
canola
seed
with
lindane
using
unit
dermal
and
inhalation
exposures
provided
in
the
HELIX
289FS
Study.
A
detailed
description
of
the
study
and
the
calculations
for
exposure
assessment
are
provided
in
an
April
23,
2002
memorandum
from
D.
Jaquith
(D282419).

ii.
On
Farm
Seed
Treatment
and
Planting
of
Treated
Seed
Based
on
seed
treatment
surveys
and
conversations
with
experts
in
the
field,
the
vast
majority
(98%)
of
lindane
seed
treatments
are
incorporated
into
the
seed
on
farm;
very
little
is
38
incorporated
into
the
seed
by
seed
processors.
Corn
and
oats
are
exclusively
treated
on
farm
(BEAD's
Impact
Analysis
of
the
Seed
Treatment
Uses
of
Lindane
on
Wheat,
Barley,
Oats,
Rye,
Corn,
Sorghum,
andCanola,
D.
Brassard,
2/
5/
00).
HED'sevaluationofonfarmseedtreatment
in
an
open
system
was
based
on
a
study
of
worker
exposure
to
lindane
during
manual
treatment
of
winter
wheat
(Fenske,
MRID
44405802;
D283397).
HED
also
evaluated
the
exposures
of
workers
using
on­
farm
seed
treatment
transfer
systems
for
liquid
formulations
which
provide
a
more
enclosed
environment.
For
the
closed
transfer
system
worker
exposure
analysis,
HED
used
median
unit
dermal
and
inhalation
exposures
provided
in
the
HELIX
289FS
commercial
seed
treatment
study
to
estimate
exposure
and
risk
from
lindane
treatment
of
wheat
and
canola
seed.

HED
has
also
reevaluated
exposures
from
the
loading
and
planting
of
seed
treated
with
lindane.
These
revisions
are
based
on
data
provided
in
a
study
measuring
exposures
of
workers
to
isophenphos
during
planting
of
oftanol­
treated
canola
seed
(MRID
No.
42251901).
A
detailed
description
of
the
study
and
the
calculations
for
exposure
assessment
are
provided
in
exposure
assessment
memoranda
from
D.
Jaquith
(D282418,
D283397).
The
revised
assessment
also
uses
a
higher
seeding
rate
of
8
lb/
seed/
acre.
The
previous
assessment
assumed
a
seeding
rate
of
4
lb/
seed/
acre.

iii.
Occupational
Exposure
and
Risk
Occupational
exposure
scenarios
assessed
are
summarized
in
Table
13.
The
daily
exposures,
as
well
as
the
resulting
short
and
intermediate
term
MOEs
are
presented
in
Table
14.
Short
and
intermediate
(if
applicable)
term
MOEs
were
calculated
for
dermal
and
inhalation
exposure
routes
for
a
total
of
five
worker
exposure
scenarios.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low­
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
treated
at
the
high­
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.

Dermal
MOEs
for
all
scenarios
range
between
9
and
190000.
Inhalation
MOEs
range
from
30
to
16000.
MOEs
are
not
of
concern
for
the
on
farm
worker
using
a
closed
system
and
wearing
protective
clothing
similar
to
that
of
commercial
seed
treatment
plant
workers.
However,
it
must
be
noted
that
the
exposure/
risk
assessments
presented
in
Table
13
for
the
on
farm
closed
transfer
system
scenario
are
valid
only
if
the
type
of
equipment
and
protective
clothing
used
in
the
surrogate
HELIX
study
are
employed.
Therefore,
this
closed
system
exposure/
risk
assessment
can
be
used
for
regulatory
purposes
only
if
the
personal
protective
measures
assumed
in
the
analysis
are
required
on
the
label.

Table
13.
Exposure
Scenario
Descriptions
for
the
Use
of
Lindane.

Exposure
Scenario
Data
Source
Standard
Assumptions
a
Comments
On­
farm
seed
treatment
with
dry
formulation
­
open
transfer
system
(1)
Rhone­
Poulenc
Data
Fenske
Study
MRID
#
444058­
02
Assumes
enough
seed
treated
and
planted
for
100
Acres
per
day
low
end,
180/
200
Acres
per
day
high­
end
All
data
were
for
gloved
hands;
(see
study,
Appendix
A,
D283397)
Table
13.
Exposure
Scenario
Descriptions
for
the
Use
of
Lindane.

Exposure
Scenario
Data
Source
Standard
Assumptions
a
Comments
39
On­
farm
seed
treatment
with
liquid
formulation
­
closed
transfer
system
(2)
HELIX
Study
Data
MRID
#
45200002
Assumes
250
acres
are
planted
per
day
at
120
lbs
of
wheat;
8
lbs
of
canola
seed
per
acre
See
study
review,
based
on
Imazilil
Assessment
and
BEAD
data
Mixing/
loading/
application
of
liquid
formulation
for
commercial
seed
treatment
(3)
HELIX
Study
Data
MRID
#
45200002
Assumes
throughput
of
seed
for
both
wheat
and
canola
is
176000
lbs
per
8
hour
day
See
study
review;
based
on
amounts
of
seed
from
study
data
Seed
Handler
for
commercial
seed
treatment
(4)
HELIX
Study
Data
MRID
#
45200002
Assumes
throughput
of
seed
for
both
wheat
and
canola
is
176000
lbs
per
8
hour
day
See
study
review;
based
on
amounts
of
seed
from
study
data
Cleaner
for
commercial
seed
treatment
(5)
HELIX
Study
Data
MRID
#
45200002
Based
on
practices
used
in
the
HELIX
Study
See
study
review;
based
on
amounts
of
seed
from
study
data
Loading
and
Planting
treated
seed
(6)
Isophenphos
Study
Data
MRID
#42251901
Assumes
250
acres
are
planted
per
day
at
120
lbs
of
wheat;
8
lbs
of
canola
seed
per
acre
See
study
review,
based
on
Imazilil
Assessment
and
BEAD
data
a
All
Standard
Assumptions
are
based
on
an
8­
hour
work
day
as
estimated
by
HED.

Table
14:
Daily
Exposures,
Short
and
Intermediate
MOEs
of
Workers
to
Lindane
During
Seed
Treatment
and
Planting
of
Treated
Seed.

Exposure
Scenario
(Scenario
#)
Crop
Application
Rates
(
lb
ai/
100
lbs
seed
or
Lb/
A)
Amount
Handled
per
Day
(lbs
a.
i.)
Unit
Exposure
(mg/
lb
ai)
a
Daily
Exposure
(mg/
kg/
day)
Short­
Term
&
Intermediate
Term
b
MOEs
Dermal
Inhalation
Dermal
c
Inhalation
e
Dermal
d
Inhalation
f
On
farm
seed
treatment
with
dry
formulation
­
open
transfer
system
(1)
wheat
0.043
5
(100A
planted)
9.4
0.
0016
0.70
0.0001
17
1100
0.043
10
(200
A
planted)
9.4
0.
0016
1.39
0.0002
9
550
corn
0.056
low­
end
0.84(
100
A
planted)
9.4
0.
0016
0.11
0.00002
92
6500
1.5
(180
A
planted)
9.4
0.
0016
0.20
0.00003
60
3700
0.125
high­
end
1.9
(100
A
planted)
9.4
0.
0016
0.25
0.00004
48
3000
3.4
(180
A
planted)
9.4
0.
0016
0.45
0.00007
26
1700
On
farm
seed
treatment
with
liquid
formulation­
closed
transfer
system
(2)
wheat
0.043
13
0.00083
0.00012
0.0002
0.000022
67000
5900
canola
1.5
high­
end
30
0.00083
0.00012
0.0004
0.00005
29000
2500
0.75
low­
end
15
0.00083
0.00012
0.0002
0.000026
57000
5000
Mixing/
loading/
application
of
liquid
formulation
for
commercial
seed
treatment

Treater
Closed
Transfer

chemical
resistant
coveralls
over
long­
sleeved
shirt,
longpants,
chemical
resistant
gloves(
3)
wheat
0.043
76
0.00083
0.00012
0.0010
0.00013
11000
1000
canola
1.5
high­
end
2640
0.00083
0.00012
0.036
0.0045
330
30
0.75
low­
end
1320
0.00083
0.00012
0.018
0.0023
660
60
Seed
Handler
for
commercial
seed
treatment

Bagger/
Sewer/
Stacker
chemical
resistant
coveralls
over
long­
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(4a)
wheat
0.043
76
0.00026
0.00006
0.00033
6.5E­
05
37000
2000
canola
1.5
high­
end
2640
0.00026
0.00006
0.011
0.0023
1000
60
0.75
low­
end
1320
0.00026
0.00006
0.0057
0.0011
2100
120
Table
14:
Daily
Exposures,
Short
and
Intermediate
MOEs
of
Workers
to
Lindane
During
Seed
Treatment
and
Planting
of
Treated
Seed.

Exposure
Scenario
(Scenario
#)
Crop
Application
Rates
(
lb
ai/
100
lbs
seed
or
Lb/
A)
Amount
Handled
per
Day
(lbs
a.
i.)
Unit
Exposure
(mg/
lb
ai)
a
Daily
Exposure
(mg/
kg/
day)
Short­
Term
&
Intermediate
Term
b
MOEs
Dermal
Inhalation
Dermal
c
Inhalation
e
Dermal
d
Inhalation
f
40
Seed
Handler
for
commercial
seed
treatment
­
Forklift
Operator
­
cotton/
polyester
coveralls
over
long­
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(4b)
wheat
0.043
76
0.00008
8E­
06
0.
00010
8.3E­
06
119000
16000
canola
1.5
high­
end
2640
0.00008
8E­
06
0.
0035
0.00029
3400
450
0.75
low­
end
1320
0.00008
8E­
06
0.
0018
0.00015
6800
900
Cleaner*
­
chemical
resistant
coveralls
over
long­
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(5)
wheat
NA
NA
NA
NA
0.0067
0.0012
1800
110
canola
NA
NA
NA
NA
0.
0067
0.0012
1800
110
Loading
and
Planting
Treated
Seed
(6)
wheat
0.043
13
0.06
0.0006
0.013
00011
920
1200
canola
1.5
high­
end
30
0.06
0.0006
0.03
0.00026
400
500
0.75
low­
end
15
0.06
0.0006
0.015
0.00013
800
1000
a
Median
unit
dermal
and
inhalation
unit
exposures
b
Intermediate
term
MOEs
are
not
applicable
for
Scenarios
(1)
On
Farm
Seed
Treatment
and
(5)
Planting
Treated
Seed.

c
Daily
Dermal
Exposure
(mg/
kg/
day)
=
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
bw
(60
kg).

d
Dermal
MOE
=
Oral
NOAEL
(1.
2
mg/
kg)
/
[daily
exposure
(mg/
kg/
day)
x
dermal
absorption
factor
(10%)].

e
Daily
Inhalation
Exposure
(mg/
kg/
day)
=
inhalation
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
body
weight
(70
kg).
*Cleaner
daily
inhalation
exposures,
measured
in
mg/
kg/
day,
were
taken
directly
from
the
HELIX
study.

f
Inhalation
MOE
=
NOAEL
(0.
13
mg/
kg/
day)
/
daily
exposure
(mg/
kg/
day).

V.
Aggregate
and
Cumulative
Exposure
and
Risk
Characterization
The
Food
Quality
Protection
Act
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA,
Section
408(
b)(
2)(
A)(
ii))
require
that
for
establishing
a
pesticide
tolerance
"that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(or
its
residues)
that
may
occur
from
dietary
(i.
e.,
food,
and
drinking
water),
residential
and
other
non­
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(oral,
dermal
and
inhalation).
Aggregate
risk
assessments
are
typically
conducted
for
acute
(1
day),
short­
term
(1­
7
days),
intermediate­
term
(7
days
to
several
months),
and
chronic
(several
months
to
lifetime)
exposure.
41
A.
Acute
Aggregate
Risk
The
acute
aggregate
risk
estimate
to
lindane
addresses
exposures
from
food
and
drinking
water
only
since
there
are
no
residential
pesticide
uses
remaining.
The
lindane
acute
dietary
risk
estimates,
including
all
sources
of
residues
of
lindane,
range
from
2%
to
17%
of
the
aPAD
at
the
99.9
th
percentile
of
the
population,
with
infants
(<
1yr)
being
the
highest
exposed
population
subgroup.
Thus,
the
acute
dietary
(food)
risk
estimate
associated
with
lindane
exposure
is
below
the
Agency's
level
of
concern.

Based
on
SCI­
GROW
model
simulations,
the
acute
estimated
concentration
(EEC)
of
lindane
in
groundwater
from
seed
treatment
uses
is
0.025
µg/
L.
The
acute
surface
water
EECs
resulting
from
the
use
of
lindane
are
4.
16
µg/
L
based
on
FIRST
modeling
results.
The
EECs
from
the
use
of
lindane
are
less
than
the
DWLOCs
for
all
populations,
indicating
that
acute
food
and
drinking
water
exposures
do
not
exceed
the
Agency's
level
of
concern.
It
should
be
noted
that
neither
the
model
nor
the
monitoring
data
reflect
concentrations
after
dilution
(from
source
to
treatment
to
tap)
or
drinking
water
treatment.
HED
concludes
that
acute
aggregate
lindane
exposure
in
food
and
water
from
the
use
of
lindane
does
not
exceed
the
Agency's
level
of
concern.

B.
Short­
and
Intermediate­
Term
Aggregate
Risk
The
short­
and
intermediate­
term
aggregate
risk
estimate
includes
chronic
dietary
(food
and
water)
from
lindane
uses,
and
intermediate­
term
non­
occupational
exposures
(i.
e.,
residential/
recreational
uses).
There
are
no
residential/
recreational
seed
treatment
uses
with
a
short
or
intermediate­
term
exposure
scenario.
Therefore,
a
short
and
intermediate­
term
aggregate
risk
estimate
were
not
evaluated.

C.
Chronic
Aggregate
Risk
Chronic
aggregate
risk
estimates
do
not
exceed
HED's
level
of
concern.
The
aggregate
chronic
dietary
risk
estimates
include
exposure
to
lindane
residues
in
food
and
water
only
since
no
chronic
residential
pesticide
use
scenarios
were
identified.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPAD
for
Children
1­
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
between
2%
and
6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.
Using
the
FIRST
model,
the
estimated
average
concentration
of
lindane
in
surface
water
resulting
from
seed
treatment
uses
is
1.95
ppb.
The
chronic
EEC
for
groundwater
based
on
the
SCI­
GROW
model
0.025.
Both
surface
and
groundwater
EECs
are
less
than
HED's
respective
drinking
water
level
of
comparison
for
exposure
to
lindane.
Mean
and
median
concentrations
from
monitoring
data
are
also
below
HED's
calculated
DWLOCs.
Based
on
the
42
available
information,
HED
concludes
with
reasonable
certainty
that
no
harm
to
any
population
will
result
from
chronic
aggregate
exposure
to
lindane.

D.
Cumulative
Exposure
and
Risk
The
Food
Quality
Protection
Act
(1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non­
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.

HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
for
lindane
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
lindane.
For
purposes
of
this
reregistration
decision
,
EPA
has
assumed
that
lindane
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.

On
this
basis,
the
registrant
must
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
lindane
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
lindane
need
to
be
modified
or
revoked.
If
HED
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
lindane,
HED
will
perform
aggregate
exposure
assessments
on
each
chemical,
and
will
begin
to
conduct
a
cumulative
risk
assessment.

HED
has
recently
developed
a
framework
that
it
proposes
to
use
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
was
issued
for
public
comment
on
January
16,
2002
(67
FR
2210­
2214)
and
is
available
fromthe
OPPWebsite
at:
http://
www.
epa.
gov/
pesticides/
trac/
science/
cumulative_
guidance.
pdf
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
each
substance
has
been
completed.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(64
FR
5795­
5796,
February
5,
1999).
43
VI.
Risk
Characterization
The
lindane
risk
assessment
contains
strengths,
weaknesses,
and
uncertainties
based
on
the
existing
toxicological
and
exposure
data,
modeling
methodologies,
data
gaps,
and
gaps
in
scientific
knowledge.
This
assessment
uses
standard
assumptions
regarding
human
body
weight,
work
life,
and
other
exposure
parameters;
and
interspecies
extrapolation
to
estimate
risks.
Additional
assumptions
were
made
regarding
route
to
route
extrapolation.
Strengths
and
uncertainties
of
the
assessment
are
described
below.

The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD­
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.

Lindane
is
a
neurotoxicant.
In
acute,
subchronic
and
developmental
neurotoxicity
studies,
it
was
found
to
cause
neurotoxic
effects
including
tremors,
convulsions,
decreased
motor
activity,
increased
forelimb
grip
strength,
hypersensitivity
to
touch,
hunched
posture
and
decreased
motor
activity
habituation.
There
also
appears
to
be
a
greater
susceptibility
to
exposure
by
offspring
compared
to
parental
animals
in
the
developmental
neurotoxicity
study.
Lindane
has
also
been
implicated
as
a
possible
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
Further
studies
to
ascertain
the
validity
of
such
evidence
is
necessary
to
make
informed
risk
assessment
decisions.

Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
several
pathways:
Dehydrogenation
leading
to
gamma
HCH,
dehydrochlorination
leading
to
formation
of
gamma
hexchlorohexene
or
hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolism
leads
to
a
large
number
of
metabolites.
Lindane
is
converted
by
enzymatic
reactions,
mainly
in
the
liver.

Lindane
appears
to
affect
the
liver
and
kidney
in
male
rats
when
administered
through
the
oral,
dermal
or
inhalation
routes
of
exposure.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with

10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment
The
liver
effects
include:
incidence
of
periacinar
hepatocytic
hypertrophy
which
was
significantly
(p

0.01)
increased
in
male
and
female
rats
dosed
at
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively).
In
addition,
increased
liver
and
spleen
weights,
and
decreased
platelets
were
also
noted.
44
Lindane
is
not
considered
teratogenic
when
administered
orally
or
subcutaneously.
Developmental
NOAELs
were
found
to
be
at
levels
equal
to
or
greater
than
maternal
NOAELs,
except
in
the
developmental
neurotoxicity
study.
The
developmental
neurotoxicity
LOAEL
was
5.6
mg/
kg/
day
(NOAEL
was
1.
2
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
maternal
toxicity
LOAEL
of
13.7
mg/
kg/
day
(NOAEL
is
5.6
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.

The
data
base
for
reproductive
toxicity
is
considered
complete.
Both
parental
and
offspring
LOAELs
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.

In
a
mammalian
cell
gene
mutation
assay
and
an
in
vivo
sister
chromatid
exchange
assay,
no
mutagenic
response
was
detected.
These
studies
were
classified
as
unacceptable.
The
open
literature
suggests,
however,
that
technical
grade
HCH
(hexachlorohexane;
6.
5%

HCH)
may
induce
some
mutagenic
activity
as
evidenced
in
a
dominant
lethal
mutation
assay
and
sister
chromatid
exchanges.
It
has
been
noted,
however,
by
the
IPCS
that
lindane
does
not
appear
to
have
a
mutagenic
potential.

There
are
no
adequate
nature
of
the
residue
studies
for
plants
from
seed
treatment
application.
A
new
metabolism
study
is
required
for
cereal
grains;
however,
a
seed
treatment
metabolism
study
(which
was
classified
as
inadequate)
was
reviewed
by
the
Agency
and
used
in
the
determination
of
the
TRR
for
use
in
the
dietary
exposure
analysis.
Additional
residue
data
would
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
The
lindane
residue
values
were
derived
using
a
ratio
of
total
radioactive
residue
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies.
This
would
be
worstcase
estimatesince
we
areassuming
thatallofthe
TRRwould
be
residues
of
concern.

The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
assessment
since
percent
crop
treated
was
used
in
the
analyses.
The
dietary
exposure
analyses
that
were
based
on
the
adjustment
of
the
lindane
residues
in
the
feeding
studies
is
a
Tier
3
assessment.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
values
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.
45
No
acute
or
chronic
residential
use
scenarios
were
identified
for
lindane;
therefore,
aggregate
risk
estimates
address
exposures
from
food
and
drinking
water
only.
The
lindane
acute
dietary
risk
estimates,
including
all
sources
of
residues
of
lindane,
range
from
7%
to
17%
of
the
aPAD
at
the
99.9
th
percentile
of
the
population,
with
infants
(<
1yr)
being
the
highest
exposed
population
subgroup.
Thus,
the
acute
dietary
(food)
risk
estimate
associated
with
lindane
exposure
is
below
the
Agency's
level
of
concern.
The
aggregate
chronic
dietary
risk
estimates
include
exposure
to
lindane
residues
in
food
and
water.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPAD
for
Children
1­
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
<6
%
of
the
cPAD
when
the
total
radioactive
residue
is
adjusted
using
the
metabolism
studies.
Chronic
aggregate
risk
estimates,
therefore,
do
not
exceed
HED's
level
of
concern.

Exposure
estimates
for
a
number
of
occupational
scenarios
were
derived
from
limited
data
from
the
submitted
studies,
scientific
literature,
and
knowledge
of
cultural
practices,
in
combination
with
models
and
literature
studies.
No
residential
exposure
assessment
was
conducted
by
the
Agency
since
pesticide
uses
have
been
limited
to
seed
treatment
only.
The
Agency
considers
the
occupational
exposure
estimates
to
be
the
best
available
with
current
methodologies.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low­
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
treated
at
the
high­
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.

Volatilization
appears
to
be
an
important
route
of
its
dissipation
under
the
high­
temperature
conditions
of
tropical
regions.
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.
032
µ
g/
L).

HCH
and
Lindane
have
been
found
in
the
tissues
and
fat
of
humans
living
in
the
Arctic.
It
appears
that
lindane
is
transported
from
regions
where
it
is
used
to
the
Arctic
and
has
been
found
at
detectable
levels
in
the
food
supply
of
the
indigenous
populations
of
Alaska
and
the
Northwest
Territories.
Detectable
levels
of
lindane
along
with
other
isomers
of
HCH
have
been
documented
in
fish,
elk,
caribou
and
other
aquatic
and
wildlife.
It
persists
in
the
air,
water,
and
46
soil
and
continues
to
show
patterns
of
long
range
atmospheric
movement
into
areas
where
it
has
been
banned
or
never
been
used.
The
continued
worldwide
use
of
lindane
may
pose
an
environmental,
as
well
as
a
human
toxicologic
risk
to
the
indigenous
peoples
of
the
Arctic.

The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Thus,
it
is
appropriate
for
the
Agency
to
perform
a
supplementary
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
the
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane.
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D222455,
4/
17/
02).
Based
on
this
revised
exposure
estimate,
the
chronic
dietary
risk
to
male
and
female
adult
Indigenous
People
is
below
HED's
level
of
concern.
Revised
estimate
of
risks
to
a
10
kg
child
results
in
an
estimated
chronic
dietary
risk
to
an
Indigenous
child
(1­
6
years)
of
0.0002
­
0.
0022
mg/
kg/
day
(13
to
138%
cPAD).
Revised
estimate
of
chronic
dietary
risk
to
a
7­
12
year
old
indigenous
child
(29
kg
body
weight)
is
0.
00007
­0.
0008
mg/
kg/
day
or
4­
48%
of
the
cPAD
which
is
below
HED's
level
of
concern.
It
should
be
noted
that
factors
such
as
bioaccumulation
of
lindane
and
the
cumulative
effects
of
combinations
of
chemicals
which
act
through
a
common
mode
of
action
have
not
been
incorporated
into
this
assessment.
As
the
Agency
develops
its
cumulative
risk
assessment
policies,
if
lindane
is
found
to
share
a
common
mode
of
action
with
other
chemicals,
a
more
comprehensive
evaluation
of
the
contribution
to
public
risk
will
be
initiated.

This
risk
assessment
does
not
at
this
time
include
an
assessment
of
risks
from
exposure
to
lindane
from
uses
other
than
seed
treatment
(e.
g.,
use
of
lindane
to
treat
head
lice
or
scabies).

VII.
Data
Needs
Most
of
the
Reregistration
data
requirements
for
Lindane
have
been
fulfilled.
The
few
remaining
data
requirements
are
described
below.

A.
Toxicology
Data
Requirements
870.3700b
Prenatal
developmental
in
rabbit
870.5300
Gene
Mutation
Mammalian
Cell
870.5450
Dominant
Lethal
Assay
870.5915
In
Vivo
Sister
Chromatid
Exchange
Although
the
prenatal
developmental
study
in
rabbits
was
found
unacceptable,
a
new
study
is
not
being
required
at
this
time.
The
rationale
for
this
decision
is
contained
in
the
body
of
this
document.
No
further
genetic
toxicity
testing
are
required
at
this
time.
The
mutagenic
potential
of
lindane
will
be
reevaluated
in
conjunction
with
the
carcinogenicity
review
and
a
determination
as
to
the
need
for
further
studies
will
occur
at
that
time.
47
B.
Product
and
Residue
Chemistry
Data
Requirements
Product
Chemistry

All
pertinent
product
chemistry
data
are
satisfied
for
the
Kanoria
99.5%
T/
TGAIs
except
additional
data
are
required
concerning
UV/
visible
absorption
(OPPTS
830.7050).
Pertinent
product
chemistry
data
remain
outstanding
for
the
Inquinosa
99.5%
T/
TGAI
concerning
product
identity,
starting
materials
and
production
process,
preliminary
analysis,
certified
limits,
oxidation/
reduction,
explodability,
storage
stability,
corrosion
characteristics,
and
UV/
visible
absorption
(OPPTS
830.1550,
1600,
1620,
1700,
1750,
6314,
6316,
6317,
6320,
and
7050).
These
data
have
been
submitted
and
are
currently
under
review
by
HED
(T.
Morton,
D276302).
Technical
products
registered
to
Kanoria
Chemicals
&
Industries
were
suspended
effective
12/
5/
00
for
failure
to
comply
with
a
cost
sharing
agreement
with
Inquinosa.
Therefore,
all
technicals
registered
which
are
repackages
of
the
Kanoria
products
would
be
required
to
change
suppliers.
The
Kanoria
products
are
shown
in
data
summary
tables
which
are
attached
to
the
Revised
Residue
Chemistry
Chapter
(T.
Morton,
12/
11/
01,
D279259)
for
informational
purposes
only.
The
Prentiss,
Drexel,
and
Amvac
99.
5%
technicals
are
repackaged
from
EPA­
registered
products,
and
all
data
requirements
will
be
satisfied
by
data
for
the
technical
source
products.
Provided
that
the
registrants
submit
the
data
required
in
the
data
summary
tables
for
the
lindane
T/
TGAIs
in
the
Product
and
Residue
Chemistry
Chapters
(T.
Morton,
279259)
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages,
the
Branch
has
no
objections
to
the
reregistration
of
lindane
with
respect
to
product
chemistry
data
requirements.

Residue
Chemistry
­
The
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30­
day
plantback
interval
for
leafy
vegetables
and
a
12­
month
plantback
interval
for
all
other
unregistered
crops
on
all
of
their
end­
use
product
labels
for
lindane.

­
New
nature
of
the
residue
study
is
required
for
application
of
lindane
as
a
seed
treatment
to
a
cereal
grain.

­
If,
after
submission
of
an
acceptable
cereal
grain
seed
treatment
metabolism
study,
the
HED
Metabolism
Assessment
Review
Committee
determines
the
residues
of
concern
to
include
metabolites
in
addition
to
lindane,
additional
crop
field
trial
data,
magnitude
of
the
residue
in
poultry
and
cattle,
and
processing
studies
will
be
required.
In
addition,
an
adequate
residue
analytical
method
and
storage
stability
data
will
be
required.
48