Pesticides
and
Childhood
Cancer
Shelia
Hoar
Zahm
and
Mary
H.
Ward
Occupational
Epidemiology
Branch,
Division
of
Cancer
Etiology,
National
Cancer
Institute,
Rockville,
Maryland
Children
are
exposed
to
potentially
carcinogenic
pesticides
from
use
in
homes,
schools,
other
buildings,
lawns
and
gardens,
through
food
and
contaminated
drinking
water,
from
agricultural
application
drift,
overspray,
or
off-gassing,
and
from
carry-home
exposures
of
parents
occupationally
exposed
to
pesticides.
Parental
exposure
during
the
child's
gestation
or
even
preconception
may
also
be
important.
Malignancies
linked
to
pesticides
in
case
reports
or
case-control
studies
include
leukemia,
neuroblastoma,
Wilms'
tumor,
soft-tissue
sarcoma,
Ewing's
sarcoma,
non-Hodgkin's
lymphoma,
and
cancers
of
the
brain,
colorectum,
and
testes.
Although
these
studies
have
been
limited
by
nonspecific
pesticide
exposure
information,
small
numbers
of
exposed
subjects,
and
the
potential
for
case-response
bias,
it
is
noteworthy
that
many
of
the
reported
increased
risks
are
of
greater
magnitude
than
those
observed
in
studies
of
pesticide-exposed
adults,
suggesting
that
children
may
be
particularly
sensitive
to
the
carcinogenic
effects
of
pesticides.
Future
research
should
include
improved
exposure
assessment,
evaluation
of
risk
by
age
at
exposure,
and
investigation
of
possible
genetic-environment
interactions.
There
is
potential
to
prevent
at
least
some
childhood
cancer
by
reducing
or
eliminating
pesticide
exposure.
-
Environ
Health
Perspect
106(Suppl
3):893-908
(1998).
http.//ehpnetl.niehs.nih.gov/
docs/1998/Suppl-3/893-908zahm/abstract.html
Key
words:
children,
cancer,
pesticides,
insecticides,
herbicides,
leukemia,
brain
tumors,
neuroblastoma,
Wilms'
tumor
sarcoma,
lymphoma,
colorectum,
testes
Introduction
Pesticides
are
agents
designed
to
kill
insects,
weeds,
fungi,
rodents,
and
other
unwanted
animals
and
plant
life.
Many
are
carcino-
genic
in
animal
bioassays
and
some
are
known
or
suspected
to
be
human
carcino-
gens.
Of
51
pesticides
evaluated
by
the
U.S.
National
Cancer
Institute
and
the
U.S.
National
Toxicology
Program
as
of
1990,
24
demonstrated
carcinogenicity
in
chronic
bioassays
(1).
As
of
1997,
the
International
Agency
for
Research
on
Cancer
had
classi-
fied
26
pesticides
as
having
sufficient
evi-
dence
of
carcinogenicity
in
animals
and
19
as
having
limited
evidence
in
animals
(2,3).
Of
these,
8
and
15
pesticides,
respectively,
This
paper
is
based
on
a
presentation
at
the
U.S.
EPA
Conference
on
Preventable
Causes
of
Cancer
in
Children
held
15-16
September
1997
in
Arlington,
Virginia.
Manuscript
received
at
EHP
4
December
1997;
accepted
19
February
1998.
Address
correspondence
to
Dr.
S.H.
Zahm,
National
Cancer
Institute,
6130
Executive
Boulevard,
Room
418,
Rockville,
MD
20892.
Telephone:
(301)
496-8157.
Fax:
(301)
402-1819.
E-mail:
zahms@
epndce.nci.nih.gov
Abbreviations
used:
ALL,
acute
lymphocytic
leukemia;
AML,
acute
myelogenous
leukemia;
ANLL,
acute
nonlymphocytic
leukemia;
Cl,
confi-
dence
interval;
CML,
chronic
myelogenous
leukemia;
2,4-D,
2,4-dichlorophenoxyacetic
acid;
OR,
odds
ratio;
RR,
rate
ratio;
U.S.
EPA,
U.S.
Environmental
Protection
Agency.
are
still
registered
for
use
in
the
United
States
(4,5)
(Table
1).
Furthermore,
many
compounds
banned
or
severely
restricted
in
the
United
States,
notably
many
organo-
chlorine
insecticides,
are
still
in
use
in
other
countries.
Sources
of
Pesticide
Exposure
The
majority
of
pesticide
use
in
this
country
is
related
to
agriculture.
Children
living
on
or
near
treated
croplands
can
be
exposed
through
agricultural
application
drift,
over-
spray,
or
off-gassing
(6,7).
Pesticide-laden
dust
is
tracked
into
homes
on
shoes
and
on
pets
(7,8)
and
is
a
major
source
of
expo-
sure
within
the
home
(9,10).
Farmers
and
other
occupationally
exposed
parents
may
bring
pesticides
into
the
home
on
their
clothing
and
equipment
(11).
Young
children,
who
are
likely
to
spend
a
large
proportion
of
their
time
on
the
floor
or
ground
and
who
frequently
put
hands
and
objects
in
their
mouths
(10),
may
be
at
particularly
high
risk
of
exposure.
Contamination
of
ground
and
surface
water
from
agricultural
runoff
can
also
result
in
the
exposure
of
children
to
pesti-
cides.
The
U.S.
Department
of
Agriculture
estimates
that
50
million
people
in
the
United
States
obtain
their
drinking
water
from
groundwater
that
is
potentially
contaminated
by
pesticides
and
other
agricultural
chemicals
(12).
The
U.S.
Environmental
Protection
Agency
(U.S.
EPA)
National
Pesticide
Survey
of
drinking
water
wells
found
one
or
more
pesticides
or
pesticide
degradates
in
10.4%
of
commu-
nity
water
systems
and
4.2%
of
rural
domestic
wells (13).
Conventional
drinking
water
treatment
techniques
do
not
remove
the
pesticide
contaminants.
A
1994
study
of
tests
for
five
herbicides
in
20,000
sam-
ples
of
tap
water
and
drinking
water
sources
found
that
14.1
million
people
routinely
drink
water
contaminated
with
atrazine,
cyanazine,
simazine,
alachlor,
and
meto-
lachlor
(14).
Many
samples
contained
two
or
more
herbicides.
In
1995
another
survey
by
the
same
environmental
organization
also
found
widespread
contamination
of
tap
water
by
herbicides,
frequently
at
levels
exceeding
the
U.S.
EPA
lifetime
health
advisory
level
(15).
Again,
multiple
pesti-
cides
were
found
simultaneously
in
approx-
imately
two-thirds
of
the
cities.
Pesticides
can
persist
in
the
groundwater
even
after
use
has
been
curtailed.
For
example,
dibro-
mochloropropane,
a
soil
fumigant
banned
in
California
in
1977,
is
still
found
in
suffi-
cient
concentrations
in
California
ground-
water
(16,17)
to
"pose
a
significant
health
risk
in
agricultural
areas"
(17).
A
recent
report
found
increased
concentrations
of
triazine
and
acetanilide
herbicides
in
rainfall
during
the
late
spring
and
summer
in
the
United
States
(18).
The
highest
concentrations
were
observed
in
Midwest
Corn
Belt
states
following
herbicide
applications
to
cropland.
Food
can
become
contaminated
by
pesticides,
particularly
insecticides,
as
a
result
of
treatments
in
the
field,
during
stor-
age,
or
in
the
home
(7).
Although
diet
does
not
appear
to
be
a
major
route
of
exposure
for
most
pesticides
(19),
concerns
exist
over
the
occasional
single
food
item
that
may
have
extremely
high
residues
(e.g.,
one
potato
had
lethal
levels
of
aldicarb)
(20)
and
the
effects
on
children,
who
typically
eat
more
fruits
per
unit
of
body
weight
than
adults
and
who
may
be
particularly
sensi-
tive
to
toxic
effects
because
of
immature
metabolism
and
other
factors
(21).
One
report
estimated
that
one
out
of
every
four
times
a
child
5
years
of
age
or
under
eats
a
peach,
he
or
she
is
exposed
to
an
unsafe
level
of
organophosphate
insecticides
(22).
A
1995
survey
of
76
jars
of
baby
food
from
grocery
stores
found
16
pesticides
in
eight
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
893
ZAHM
AND
WARD
Table
1.
Pesticides
with
limited
or
sufficient
evidence
of
carcinogenicity
in
animals
[International
Agency
for
Research
on
Cancer
(2)].
Animal
evidence
Currently
registered
Pesticide
of
carcinogenicity
in
the
United
Statesa
Herbicides
Amitrole
Atrazine
Diallate
Monuron
Nitrofen
Picloram
Sulfallate
Trifluralin
Insecticides
Aldrin
Aramite
Arsenic
and
arsenical
compounds
Chlordane/heptachlor
Chlordecone
Chlorobenzilate
DDT
Dichlorvos
Dicofol
Dieldrin
HCH,
ax-HCH
,B-HCH,
y-HCH
(lindane)
Methyl
parathion
Mirex
Tetrachlorvinphos
Toxaphene
Nonarsenical
insecticides
Fungicides
Captafol
Captan
Chlorothalonil
Ethylene
thiourea
Formaldehyde
Hexachlorobenzene
Pentachloronitrobenzene
Pentachlorophenol
ortho-phenyl
phenol
Sodium
ortho-phenyl
phenate
2,4,6-Trichlorophenol
Ziram
Other
Creosote
1
,2-Dibromo-3-chloropropane
1
,3-Dichloropropene
Dimethylcarbamoyl
chloride
1,1-Dimethyl
hydrazine
Ethylene
dibromide
Methyl
bromide
Methylmercury
chloride
Abbreviations:
-,
could
not
be
detei
the
U.S.
EPA
(4,5).
bSeverely
restric
Sufficient
Limited
Limited
Limited
Sufficient
Limited
Sufficient
Limited
Limited
Sufficient
Limited
Sufficient
Sufficient
Limited
Sufficient
Sufficient
Limited
Limited
Sufficient
Limited
Limited
Sufficient
Limited
Sufficient
Limited
y
y
y
y
N
y
N
y
N
N
Nb
N
N
N
N
y
y
N
N
y
y
N
y
N
y
Sufficient
Limited
Limited
Sufficient
Sufficient
Sufficient
Limited
Sufficient
Sufficient
Sufficient
Sufficient
Limited
N
y
y
yc
y
N
y
y
N
N
y
y
Sufficient
Y
Sufficient
N
Sufficient
yb
Sufficient
Sufficient
Sufficient
N
Limited
Y
Sufficient
N
brmined.
HCH,
hexachlorocyclohexane;
N,
no;
Y,
yes.
'Data
from
IARC
(2,3)
and
ted.
cContaminant
or
metabolite
of
a
registered
product.
brand-name
products
(23).
The
pesticides
detected
included
three
probable
human
carcinogens
and
five
possible
human
car-
cinogens,
as
classified
by
the
U.S.
EPA.
Infants
can
also
be
exposed
to
pesticides
and
pesticide
metabolites
in
breast
milk
and
via
placental
transfer
(24,25).
Exposure
may
occur
from
leaks,
spills,
and
accidents
during
the
manufacture,
dis-
tribution,
and
application
of
pesticides
and
from
routine
pollution
from
manufactur-
ing
and
disposal
sites.
For
example,
20%
of
Arkansas
children
who
lived
near
an
herbi-
cide
manufacturing
plant
had
residues
of
2,4-dichlorophenoxyacetic
acid
(2,4-D)
in
their
urine
(26).
The
majority
of
most
children's
exposure
to
pesticides,
however,
is
from
home,
lawn,
and
garden
use
of
pesticides
(27).
The
National
Home
and
Garden
Pesticide
Use
Survey
conducted
by
the
U.S.
EPA
found
that
82%
of
U.S.
households
used
pesti-
cides
with
an
average
of
three
to
four
differ-
ent
pesticide
products
per
home
(28).
Sixty-six
percent
of
households
treated
the
home's
primary
living
areas
one
or
more
times
per
year
(28).
Thirty-seven
percent
of
households
reported
insecticide
treatments
when
there
was
no
major
insect
problem
(28).
These
data
were
consistent
with
the
earlier
National
Household
Pesticide
Usage
Study
(29),
which
reported
that
84%
of
households
used
pesticides
inside
the
home.
In
data
from
a
childhood
cancer
case-con-
trol
study,
Leiss
and
Savitz
(30)
reported
that
26%
of
control
households
had
a
his-
tory
of
home
extermination
and
27%
reported
use
of
pest
strips.
Use
of
termiti-
cides
outside
and
beneath
a
home
can
also
result
in
indoor
pesticide
exposure
(7).
There
are
also
case
reports
of
extreme
pesti-
cide
use,
such
as
the
report
of
a
child
whose
mattress
was
sprayed
two
times
per
week
for
most
of
his
life
with
DDVP-
Baygon
(Bayer,
Leverkusen,
Germany),
a
combination
of
an
organophosphate
and
a
carbamate
insecticide
(31).
Pesticide
use
on
gardens
and
lawns
may
also
result
in
exposure
to
children
either
during
application
or
if
engaging
in
activi-
ties
on
the
lawn
within
one
day
of
applica-
tion
(32,33).
The
National
Home
and
Garden
Pesticide
Survey
(28)
found
that
2%
of
households
used
herbicides
on
the
yard
or
garden
annually.
Similar
frequen-
cies
of
use
ranging
from
21
to
33%
have
been
reported
in
other
surveys
(7,29,34).
The
use
of
lawn
care
pesticides
is
increas-
ing
5
to
8%
annually
(35).
Use
of
lawn
chemicals
at
any
time
(ever)
was
reported
to
be
63%
(30)
and
68%
(36)
in
the
con-
trol
populations
of
two
cancer
case-control
studies.
The
amount
of
pesticides
per
treated
acre
of
household
lands
is
almost
five
times
the
application
rate
for
treated
agricultural
lands
(37).
A
biomonitoring
study
of
dogs
found
that
animals
having
contact
with
lawns
treated
with
2,4-D
had
measurable
levels
in
their
urine
for
several
days
after
application
(38).
Thus,
inciden-
tal
contact
with
lawn
care
pesticides
may
lead
to
exposures.
Public
lands
such
as
school
yards,
parks,
and
golf
courses
are
often
treated
with
pesticides
and
may
result
in
exposure
to
children.
Both
indoor
and
outdoor
pesticide
use
can
result
in
household
contamination,
par-
ticularly
in
carpets
(7,9,39),
that
can
persist
for
years
because
of
the
lack
of
sun,
rain,
and
other
factors
that
speed
pesticide
degra-
dation
outdoors
(40-43).
The
number
and
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
894
PESTICIDES
AND
CHILDHOOD
CANCER
concentration
of
pesticides
found
in
household
dust
are
greater
than
those
found
in
air,
soil,
or
food
(41,43).
These
residues
are
of
great
concern
for
children.
In
one
study
of
a
broadcast
flea
treatment,
the
household
residues
had
a
vertical
(floor
to
ceiling)
concentration
gradient
so
the
resulting
respiratory
dose
estimated
for
a
child
was
4
to
6
times
greater
than
that
for
an
adult;
dermal
dose
estimates
were
30
times
greater
(44).
Children's
toys
can
also
serve
as
a
reservoir
for
pesticides
(45).
The
organophosphate
insecticide
chlorpyrifos
accumulates
on
plastic
and
in
plush
toys
through
a
two-stage
process
whereby
the
pesticide
was
deposited
on
surfaces
during
application,
then
released
as
a
vapor,
rede-
posited,
and
sorbed
by
furniture
and
toys
for
at
least
2
weeks
postapplication
(45).
Children
may
be
exposed
to
pesticides
through
pet
products
and
through
use
of
insecticidal
shampoos
for
lice
infesta-
tions,
sometimes
with
a
large
number
of
applications
per
child.
Epidemiologic
Studies
Study
Designs
The
evidence
that
pesticide
exposure
may
be
associated
with
childhood
cancer
comes
from
case
reports
and
several
types
of
epidemiologic
studies.
Case
reports
are
observations
of
unusual
cancer-exposure
combinations
in
one
or
more
individuals.
Reports
involving
several
cases
are
often
called
clusters.
Case
reports
may
reflect
a
causal
relationship
or
may
be
due
to
chance.
The
specific
pesticide
exposures
are
often
clearly
identified
in
case
reports,
much
more
so
than
in
larger
studies,
and
often
demonstrate
excessive
use
of
pesti-
cides
around
children
[e.g.,
a
child's
mat-
tress
sprayed
with
propoxur
twice
weekly
for
most
of
the
child's
life
(31)].
Case
reports
can
stimulate
further
investigation
using
more
rigorous
research
techniques.
Cross-sectional,
or
ecologic,
studies
evaluate
the
correlation
between
rates
of cancer
and
exposure
based
on
population-level
data
(e.g.,
county
pesticide
use
and
county
cancer
incidence
rates).
Typically,
they
are
not
based
on
data
on
the
individual
level,
have
little
information
on
potential
con-
founders,
do
not
take
disease
latency
into
account,
and
do
not
account
for
migration
into
or
out
of
the
geographic
area
under
investigation.
They
can,
however,
provide
clues
to
cancer
etiology,
usually
at
low
cost.
The
most
rigorous
study
designs
are
the
case-control
and
cohort
approaches.
In
case-control
studies,
past
pesticide
exposures
of
cases
and
controls
are
compared.
Using
the
cohort
approach,
study
groups
are
selected
on
the
basis
of
exposure
status
(e.g.,
pesticide-exposed
group
vs
unexposed
group)
and
disease
rates
in
the
two
groups
are
compared.
The
advan-
tages
and
limitations
of
each
approach
are
described
by
Grufferman
(46).
Most
of
the
data
on
childhood
cancer
and
pesticides
are
from
case-control
studies.
There
have
been few
case
reports
for
most
of
the
childhood
cancers
and
only
one
relevant
cohort
study,
an
investigation
of
cancer
among
children
of
Norwegian
farmers
(47,48).
Most
of
the
research
has
focused
on
leukemia
and
brain
cancer,
with
little
attention
given
to
other
childhood
malignancies.
This
is
probably
a
reflection
of
the
rarity
of
these
other
cancers,
which
makes
them
difficult
to
study.
The
studies
are
reviewed
by
cancer
type,
identifying
the
study
design,
the
number
of
cases,
the
exposure
(e.g.,
occupational
exposure
to
pesticides,
household
use
of
pesticides,
specific
chemicals),
the
person
exposed
(e.g.,
mother,
father,
child),
the
amount,
the
timing
of
exposure
(e.g.,
pre-
conception,
during
pregnancy,
at
birth,
dur-
ing
childhood),
the
number
of
exposed
cases,
risk
estimate,
and
confidence
intervals
(CI),
when
available.
Some
studies
investi-
gated
more
than
one
cancer
type
and
appear
in
multiple
tables
in
this
paper.
Studies
that
presented
data
only
for
all
childhood
cancers
combined
are
not
included.
Leukemia
Beginning
in
the
late
1970s,
there
were
several
case
reports
of
leukemia
among
chil-
dren
exposed
to
pesticides
(Table
2).
The
termiticide
chlordane,
the
organophosphate
insecticide
dichlorvos,
and
the
carbamate
propoxur
were
linked
to
leukemia
among
children
(31,49,50).
A
cluster
of
cancers
including
leukemia
was
noted
among
children
in
the
farm
community
of
McFarland,
California
(51).
These
excess
cancer
rates
remain
controversial
and
under
investigation
almost
10
years
after
the
initial
report.
This
review
of
17
case-control
studies
and
one
cohort
study
supports
a
possible
role
for
pesticides
in
childhood
leukemia
(30,48,52-67).
Most,
but
not
all,
of
the
studies
report
elevated
risks
among
children
whose
parents
were
occupationally
exposed
to
pesticides
or
who
used
pesticides
in
the
home
or
garden.
Parental
use
of
pesticides
in
the
home
or
garden
during
pregnancy
(father
or
mother)
or
nursing
(mother
only)
was
associated
with
3-
to
9-fold
increases
in
childhood
leukemia
in
a
case-control
study
in
Los
Angeles
County,
California
(55).
Maternal
employment
in
agricultural
occu-
pations
(odds
ratio
[OR]
1.8)
or
reported
exposure
to
pesticides
during
pregnancy
(OR
3.5)
was
associated
with
acute
lymphocytic
leukemia
(ALL)
in
a
case-control
study
in
China
(57).
Occupational
exposure
to
pesti-
cides
by
either
parent
and
use
of
pesticides
in
the
home
or
garden
during
childhood
was
linked
to
acute
myeloid
leukemia
(AML)
in
U.S.
children
(58).
Some
of
the
studies
report
excesses
that
are
not
statistically
signif-
icant,
possibly
because
of
the
extremely
small
numbers
of
exposed
subjects.
Many
of
the
studies
evaluated
parental
occupations
obtained
from
birth
certificates
or
other
records,
assuming
that
employment
as
a
farmer
or
in
other
agricultural
occu-
pations
implied
pesticide
exposures.
Buckley
et
al.
(58)
obtained
lifetime
occupational
histories
and
calculated
the
number
of
days
of
pesticide
exposure.
The
ORs
increased
to
2.7
among
children
whose
fathers
were
exposed
for
more
than
1000
days.
Seven
cases
and
no
controls
had
mothers
with
more
than
1000
days
of
pesticide
exposure.
Some
studies
evaluated
risk
of
leukemia
according
to
reports
of
pesticide
use
in
the
home
or
garden
and,
in
some,
analyzed
sep-
arately
for
parental
exposure
and
for
the
child's
exposure.
Household
pesticide
use
might
be
assumed
to
be
insecticides
only,
whereas
garden
and
lawn
pesticides
include
both
insecticides
and
herbicides.
Leiss
and
Savitz
(30)
evaluated
pesticide
products
and
found
significant
excesses
of
leukemia
asso-
ciated
with
use
of
pest
strips,
but
not
for
household
extermination
or
yard
pesticide
treatments.
Only
one
study
analyzed
levels
of
pesticides
or
their
metabolites
in
biologic
specimens.
Scheele
et
al.
(63)
found
no
sig-
nificant
differences
in
levels
of
DDT,
1,1,1
-
trichloro-2,2-bis(p-chlorophenyl)ethylene,
hexachorobenzene,
hexachlorocyclohexane,
or
dieldrin
in
the
bone
marrow
of
child-
hood
leukemia
cases
at
diagnosis
when
compared
to
controls.
When
all
studies
were
reviewed,
no
clear
patterns
of
risk
by
which
parent
was
exposed,
by
timing
of
exposure,
or
by
histologic
type
of
leukemia
were
apparent.
Exposure-response
gradients
were
seen
in
the
two
studies
that
assessed
levels
of
the
child's
direct
exposure
to
pesticides.
Children
who
were
exposed
to
pesticides
less
than
once
per
week,
one
to
two
times
per
week,
or
most
days
of
their
lives
had
ORs
of
1.8,
2.0,
and
3.5,
respectively,
in
a
study
of
acute
nonlymphocytic
leukemia
by
Buckley
et
al.
(58).
Mulder
et
al.
(66)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
895
ZAHM
AND
WARD
Table
2.
Summary
of
studies
on
pesticides
and
childhood
leukemia.
Total
Study
design
Reference
Cancer
cases,
no.
Exposure
Case
report
Infante
et
al.,
Acute
stem
1
Chlordane
1978
(49)
cell
Case
report
Reeves
et
al.,
1981
(50)
Case
report
Reeves,
1982
(31)
ALL
CML,
AlL
Case
report
Moses,
Leukemia
1989
(51)
Case-control
Hemminki
et
al.,
Leukemia
1981
(52)
Case-control
Gold
et
al.,
Leukemia
1982
(53)
Case-control
VanSteensel-Moll
Leukemia
etal.,
1985
(54)
Case-control
Lowengart
et
al.,
Leukemia
1987
(55)
1
Dichlorvos
Propoxur
13
Propoxur
Dichlorvos,
propoxur
Exposed
Timing
of
exposure
cases,
no.
Annual
house
treatment
1
Used
in
home
30
times
1
Mattress
sprayed
2
times/
13
week
for
most
of
life.
One
case:
seven
cans
sprayed
in
house
2
weeks
prior
to
diagnosis
NA
Residence
in
McFarland,
CA,
Prenatal
and
childhood
NA
farm
town
319
Paternal
occupation
as
farmer
Pregnancy
1
56a
43
Paternal
occupation
Before
birth
as
farmer
Childhood
519
Maternal
occupation
Pregnancy
in
agriculture
1
year<diagnosis
Maternal
pesticide
Pregnancy
exposure
Paternal
occupation
Pregnancy
in
agriculture
1
year<diagnosis
Paternal
pesticide
exposure
Pregnancy
123
Parental
pesticide
use
Pregnancy
and
(mother
in
home:
either
only)
nursing
Maternal
Paternal
Parental
pesticide
use
in
garden:
either
Maternal
Paternal
Case-control
Laval
and
Tuyns,
Leukemia
201
Parental
occupational
1988
(56)
exposure
to
pesticides
Case-control
Shu
et
al.,
Leukemia
309
Occupation
in
agriculture
1988
(57)
ALL
Maternal
ALL
ANLL
Case-control
Buckley
et
al.,
ANLL
1989
(58)
ANLL
Leukemia
Paternal
Pesticide
exposure:
Maternal
204
Occupational
pesticide
exposure:
Paternal
Maternal
If
diagnosed
under
age
6
If
myelo-/monocytic
Household
pesticide
exposure:
Maternal
Child
Case-control
Gardner
et
al.,
Leukemia
1990
(59)
52
Paternal
occupation
as
farmer
Ever
e:
Pregnancy
Ever
(1000+
days)
Before
pregnancy
During
pregnancy
After
pregnancy
Ever
(1000+
days)
Before
pregnancy
During
pregnancy
After
pregnancy
<
1/week
1-2/week
Most
days
<
1/week
1-2/week
Most
days
Birth
2a
2a
3
3
4
35
32
36
lga
13a
12a
13a
ga
5a
12
12
6
4
2
12
7
3
17
NA
NA
NA
7
NA
NA
NA
NA
NA
50
12
8
46
13
8
Risk
estimate/
comment
Age
9,
included
1
year
removal
of
floor
boards
with
heavy
treatment
Age
11,
diagnosed
16
weeks
after
last
use
a
1.3
(not
significant)
vs
0
controls
vs
0
controls
0.4
(0.1,
1.7)
0.4
(0.1,
1.3)
0.7
(0.2,
2.5)
0.9
(0.5,
1.5)
0.9
(0.5,
1.5)
1.0
(0.6,
1.7)
3.8
(significant)
3.2
(significant)
4.0
(significant)
6.5
(significant)
9.0
(significant)
5.0
(significant)
vs
3
controls
2.3
(0.9,
6.3)
1.8
(0.6,
5.4)
1.6
(0.4,
6.3)
0.3
(0.1,
1.6)
2.6
(0.8,
9.1)
3.5
(1.1,
1
1.2)
2.4
(0.5,
11.0)
2.7
(1.0,
7.0)
1.7
(not
significant)
1.9
(not
significant)
1.8
(not
significant)
vs
0
controls
3.0
(significant)
6.0
(significant)
7.0
(significant)
11.4
(significant)
13.6
(significant)
1.4
(0.8,
2.2)
0.9
(0.4,
2.1)
vs
0
controls
1.8
(1.0,
3.0)
2.0
(0.8,
5.0)
3.5
(0.9,
13.8)
5
12.6(0.8,
9.0)
(Continued)
Environmental
Health
Perspectives
-
Vol
106,
Supplement
3
*
June
1998
896
PESTICIDES
AND
CHILDHOOD
CANCER
Table
2.
Continued.
Total
Exposed
Risk
estimate/
Study
design
Reference
Cancera
cases,
no.
Exposure
Timing
of
exposure
cases,
no.
comment
Case-control
Magnani
et
al.,
1990
(60)
Case-control
Infante-Rivard
et
al.,
1991
(61)
Case-control
Schwartzbaum
et
al.,
1991
(62)
Case-control
Scheele
et
al.,
1992
(63)
Case-control
Deschamps
and
Band,
1993
(64)
Case-control
Roman
et
al.,
1993
(65)
Case-control
Mulder
et
al.,
1994
(66)
Case-control
Leiss
and
Savitz,
1995
(30)
Case-control
Meinert
et
al.,
1996
(67)
Cohort
Kristensen
et
al.,
1996
(48)
ALL
ANLL
ALL
ALL
ANLL
ALL
AML
Leukemia
ALL
Other
leukemia
Non-Hodgkin's
lymphoma
Leukemia,
lymphoma
Combined
Leukemia
Leukemia
Leukemia,
Acute
ALL
AML
Other
142
Paternal
occupation
Before
birth
4
1.8
(0.5,
6.5)
22
128
522
107
35
3
as
farmer
Maternal
occupation
in
agriculture
Maternal
insecticide
exposure
Parental
gardening
with
pesticides
Bone
marrow
levels
of
DDT/DDE,
HCB,
HCH,
dieldrin
15
Pesticides
sprayed
in
nearby
parks,
mosquito
control,
census
data
39
Paternal
occupation
11
in
agriculture
6
7
Pesticide
exposure:
7
Child
Paternal
Summary
pesticide
indicator
NA
Pest
strips
House
extermination
Yard
pesticide
treatment
173
Farmer:
paternal
Maternal
Occupational
exposure
to
pesticides:
Patemal
Maternal
Either
parent
Pesticide
use:
any
Garden
Farm
House
extermination:
any
By
pest
controller
323,
292
Parental
agricultural
work,
cohort
Census
pesticide
expenditures
Birth
to
diagnosis
Pregnancy
Birth
to
diagnosis
At
diagnosis
Childhood
Birth
At
interview
Ever
3
hr/week
Ever
3
hr/week
>
2
indicators
>
3
indicators
>
4
indicators
Last
3
months
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
Last
3
months
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
Last
3
months
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
2
years
<
birth
to
diagnosis
Ever
Year
<
pregnancy
Pregnancy
Childhood
Ever
Year
<
pregnancy
Pregnancy
Childhood
Ever
Year
<
pregnancy
Pregnancy
Childhood
Ever
2
years
<birth
to
diagnosis
Before
birth
5
NA
ga
7a
NA
NA
38
5.6
(1.3,
24.3)
No
association
1.8
(0.6,
6.4)
1.4
(0.4,
4.1)
1.3
(not
significant)
0.9
(not
significant)
No
significant
differences
15
No
difference
11
1.1
(0.1,5.9)
15
0.8
(0.1,
3.3)
Results
for
leukemia
and
non-Hodgkin's
lymphoma
combined
2
2
6
5
5
4
3
21
21
18
4
6
7
27
36
33
6
4
9
9
5
9
4
2
2
4
12
11
7
12
27
20
7
37
3
113
52
29
12
11
1.3
(0.1,
11.4)
6.0
(0.3,
368.3)
1.0
(0.2,
6.1)
2.1
(0.4,
12.5)
0.8
(0.1,
4.4)
1.7
(0.3,
10.5)
3.1
(0.3,
28.3)
3.0
(1.6,
5.7)
1.7
(1.2,
2.4)
2.6
(1.7,
3.9)
0.4
(0.1,
1.2)
0.3
(0.1,
0.8)
0.9
(0.5,
1.4)
1.1
(0.6,1.9)
0.9
(0.5,
1.8)
1.1
(0.8,
1.5)
1.6
(not
significant)
3.2
(not
significant)
1.2
1.8
1.3
1.2
1.6
1.6
1.5
2.2
2.0
1.5
2.5
(1.1,
5.4)
2.5
(1.0,
6.1)
1.6
0.8
1.0
1.0
(0.8,
1.2)
1.1
(0.8,
1.5)
1.2
(0.9,1.7)
1.4
(0.6,
2.9)
0.9
(0.4,
1.9)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
Abbreviations:
ALL,
acute
lymphocytic
leukemia;
AML,
acute
myelogenous
leukemia;
ANLL,
acute
nonlymphocytic
leukemia;
CML,
chronic
myelogenous
leukemia;
dx,
diagnosis;
NA,
not
available
in
published
report.
&Number
of
discordant
pairs
with
exposed
cases.
897
ZAHM
AND
WARD
reported
that
children
with
greater
than
two,
greater
than
three,
or
greater
than
four
indicators
of
pesticide
exposure
had
ORs
of
0.8,
1.7,
and
3.1,
respectively,
in
a
study
of
leukemia
and
lymphoma
combined.
Brain
Cancer
The
role
of
pesticides
in
the
development
of
childhood
brain
cancer
was
evaluated
in
one
case
report,
16
case-control
studies,
and
one
cohort
study
(30,47,48,52,53,68-81)
(Table
3).
Significant
elevations
in
brain
cancer
risk
related
to
at
least
one
measure
of
pesticide
exposure
were
observed
in
nine
studies
(30,47,48,71,72,76-79,81).
Nonsignificant
elevations
were
observed
in
an
additional
five
studies
(52,53,70,74,75),
with
deficits
or
no
association
reported
in
three
studies
(69,73,80).
The
largest
risk
estimates,
reported
by
Davis
et
al.
(76),
Cordier
et
al.
(77),
and
Pagoda
and
Preston-Martin
(81),
were
based
on
parent-reported
use
of
pesti-
cides
in
the
home
or
garden
or
on
pets,
in
contrast
to
the
lower
risks
associated
with
parental
employment
in
occupations
or
industries
thought
to
involve
pesticide
expo-
sure.
Most
(30,71,74-76,81),
but
not
all
(30,77,79),
of
the
studies
that
evaluated
timing
of
exposure
found
greater
risks
asso-
ciated
with
prenatal
exposure
than
for
expo-
sures
sustained
during
childhood.
Three
studies
(53,70,76)
had
both
cancer
and
noncancer
control
series.
In
general,
the
ORs
based
on
noncancer
controls
were
higher
than
those
based
on
cancer
controls.
Exposure-response
gradients,
although
based
on
crude
measures
of
exposure,
were
evaluated
in
the
studies
of
Bunin
et
al.
(78),
Kristensen
et
al.
(48),
and
Pagoda
and
Preston-Martin
(81).
Maternal
use
of
household
insecticide
sprays
or
other
pesti-
cides
ever
and
on
at
least
a
weekly
basis
was
associated
with
ORs
of
1.5
and
2.2,
respec-
tively
(78).
Children
of
fathers
engaged
in
agricultural
work
had
rate
ratios
(RRs)
of
2.0,
2.9,
and
3.3
for
nonastrocytic
neuroep-
ithelial
tumors
for
levels
1,
2,
and
3
of
pes-
ticide
expenditures,
respectively
(48).
Pagoda
and
Preston-Martin
(81)
reported
increasing
risk
of
childhood
brain
cancer
with
the
number
of
pets
and
the
number
of
hours
per
day
children
spent
with
their
pets,
presumably
a
surrogate
for
increasing
exposure
to
pesticides
used
on
pets.
Neuroblastoma
Table
4
presents
three
case
reports,
four
case-control
studies,
and
one
cohort
study
with
information
on
pesticides
and
neuroblastoma
(47,49,51,62,82-85).
There
is
little
evidence
for
a
role
of
pesticides
in
the
etiology
of
this
tumor,
with
four
comparisons
showing
decreased
risks
(83-85),
two
showing
nonsignificant
excesses
of
1.1
and
3.5
(62,85),
and
only
one
study
with
a
significant
excess
(47).
Kristensen
et
al.
(47)
reported
a
RR
of
2.5
(95%
CI
1.0,
6.1),
based
on
seven
cases
of
neuroblastoma,
among
a
cohort
of
children
of
Norwegian
farmers
who
grew
field
vegetables.
Four
of
the
five
analytical
studies,
however,
were
based
solely
on
potential
pesticide
exposure
imputed
from
parental
employment
in
agricultural
occupations
(47,83-85).
One
study
assessed
risk
associ-
ated
with
parental
gardening
with
pesti-
cides
(62).
No
studies
evaluated
detailed
information
on
pesticides
used
in
the
home
prenatally
or
during
childhood.
Non-Hodgns
Lymphoma
The
relationship
between
pesticides
and
childhood
non-Hodgkin's
lymphoma
was
investigated
in
one
case
report,
six
case-
control
studies,
and
one
cohort
study
[(30,48,51,60,62,65,66,86);
(Table
5)].
Two
case-control
studies,
however,
were
based
on
leukemia
and
lymphoma
cases
combined
with
no
data
presented
sepa-
rately
for
each
histologic
type
(65,66).
Another
case-control
study
was
presented
at
a
U.S.
National
Cancer
Institute
work-
shop
but
has
not
yet
been
published
(86).
Several
of
the
reports
did
not
include
the
number
of
total
cases
or
the
number
of
exposed
cases
(30,51,60,62,86).
All
appear
to
have
very
few
exposed
cases.
Despite
these
limited
data,
there
are
some
notable
findings
concerning
child-
hood
non-Hodgkin's
lymphoma
and
pesti-
cides.
Risk
increased
with
level
of
pesticide
expenditures
(level
1:
RR=
1.3;
level
2:
RR
=
1.6;
level
3:
RR
=
2.5)
among
a
cohort
of
children
of
Norwegian
farmers
(48).
Excess
non-Hodgkin's
lymphoma
was
observed
among
children
whose
homes
had
been
exterminated
or
had
pest
strips,
although
the
excesses
were
not
statistically
significant
except
for
home
extermination
during
the
time
period
from
birth
to
2
years
prior
to
diagnosis
(30).
Buckley
(86)
reported
ORs
of
1.0,
2.2,
and
5.2
for
child-
hood
non-Hodgkin's
lymphoma
associated
with
maternal
household
insecticide
use
less
than
once
per
week,
one
to
two
times
per
week,
and
daily,
respectively.
Garden
insecticide
sprays
and
home
extermination
were
also
associated
with
excess
childhood
non-Hodgkin's
lymphoma
in
the
same
study
(86).
The
study
by
Mulder
et
al.
(66),
based
on
seven
leukemia
and
seven
non-Hodgkin's
lymphoma
cases
combined,
reported
increased
risk
with
increasing
pesticide
exposure
of
the
child
or
father;
however,
results
for
non-Hodgkin's
lym-
phoma
alone
were
not
presented.
Wilms'
Tumor
The
early
case-control
studies
on
Wilms'
tumor
did
not
report
elevated
risks
associ-
ated
with
possible
pesticide
exposure,
as
determined
by
parental
occupational
titles
only
or
imputed
from
occupational
titles
using
job-exposure
matrices
[(62,87,88);
(Table
6)].
The
later
studies
(89,90),
which
were
based
on
subjects'
reports
of
house-
hold
or
occupational
use
of
pesticides,
reported
elevated
risks.
Olshan
et
al.
(89)
found
that
children
whose
homes
had
been
exterminated
had
2.2
times
the
risk
of
Wilms'
tumor
than
children
in
untreated
homes.
The
risk
did
not
increase
with
the
frequency
of
extermination,
however.
In
a
study
of
Wilms'
tumor
in
Brazil
(90),
risk
increased
with
frequency
of
parental
agri-
cultural
use
of
pesticides.
Children
whose
fathers
or
mothers
used
agricultural
pesti-
cides
10
times
or
more
had
ORs
for
Wilms'
tumor
of
3.2
(95%
CI
1.2,
9.0)
and
128.6
(95%
CI
6.4,
2569),
respec-
tively.
The
risk
associated
with
pesticide
use
particularly
increased
among
children
of
parents
with
longer
farming
duration.
Ewing's
Saroma
Reports
related
to
pesticides
and
Ewing's
sarcoma
are
presented
in
Table
7
(91-95).
Paternal
employment
as
a
farmer
or
in
other
agricultural
occupations
was
associ-
ated
with
an
approximately
9-fold
signifi-
cantly
increased
risk
of
Ewing's
sarcoma
in
two
studies
(93,94)
and
a
nonsignificant
3-
fold
excess
in
a
third
study
(95).
Parental
exposure
to
pesticides
in
any
occupation
was
associated
with
a
6-fold
increase
of
Ewing's
sarcoma
in
children
(94).
More
direct
exposure
of
children
to
pesticides,
either
through
household
extermination,
liv-
ing
on
a
farm
or
ranch,
or
through
house-
hold
pets,
was
associat&d
with
modest
nonsignificantly
elevated
ORs
less
than
1.5
(95)
or
deficits
(94).
Other
Maligances
Table
8
presents
data
on
studies
of
childhood
osteosarcoma
(62),
soft-tissue
sarcoma
(30,48,96),
colorectal
cancer
(97-99),
testicular
cancer
(48,100),
other
germ
cell
malignancies
(101),
Hodgkin's
disease
(48,62),
and
retinoblastoma
(48,102).
With
three
or
fewer
reports
per
cancer,
little
can
be
definitively
conduded
about
the
possible
role
of
pesticides.
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
a
June
1998
898
PESTICIDES
AND
CHILDHOOD
CANCER
Table
3.
Summary
of
studies
on
pesticides
and
childhood
brain
cancer.
Total
Exposed
.
Risk
estimate/
Study
design
Reference
cases,
no.
Exposure
Timing
of
exposure
cases,
no.
comment
Case
report
Chadduck
et
al.,
1
Heptachlor
Pregnancy
and
nursing
1
Gliosarcoma
diagnosed
in
an
1987
(68)
Case-control
Fabia
and
Thuy,
1974
(69)
Case-control
Gold
et
al.,
1979
(70)
Case-control
Hemminki
et
al.,
1981
(52)
Case-control
Gold
et
al.,
1982
(53)
Case-control
Sinks,
1985
(71)
101
Paternal
occupation
as
farmer
Birth
84
Household
extermination
Before
diagnosis
Farm
residence
282
Paternal
occupation
as
farmer
Pregnancy
70
Paternal
occupation
as
farmer
Before
birth
Childhood
NA
Maternal
aerosol
pesticide
use
Pregnancy
Childhood
Case-control
Wilkins
and
Koutras,
110
Paternal
occupation
1988
(72)
in
agriculture
Agriculture
industry
Case-control
Howe
et
al.,
1989
(73)
Case-control
Wilkins
and
Sinks,
1990
(74)
Case-control
Kuijten
et
al.,
1992
(75)
Case-control
Davis
et
al.,
1993
(76)
74
Child
exposed
to
herbicides
or
insecticides
110
Paternal
occupation
in
agriculture
Paternal
industry
in
agriculture,
forestry,
or
fishing
163
Paternal
agricultural
industry
45
Pesticides
at
home
Pest
strips
Termiticides
Kwell
Flea
collar
Garden
insecticides
Flea
bombs
Carbaryl
Diazinon
Herbicide
Case-control
Cordier
et
al.,
1994
(77)
75
Farm
residence
Home
treatment
with
pesticides
Birth
Childhood
Preconception
Pregnancy
Childhood
Preconception
Pregnancy
Childhood
Preconception
Pregnancy
Childhood
7
months
to
diagnosis
Pregnancy
Birth-6
months
7
months
to
diagnosis
Ever
7
months
to
diagnosis
Birth-6
months
7
months
to
diagnosis
7
months
to
diagnosis
Pregnancy
7
months
to
diagnosis
Ever
Ever
Birth-6
months
7
months
to
diagnosis
Pregnancy
Childhood
Pregnancy
Childhood
infant
7
weeks
of
age
6
0.6
(calculated)
16a
2.3
(p=
0.10),
noncancer
controls
14a
1.2
(p=
0.84),
cancer
controls
12a
4.0
(not
significant),
noncancer
controls
ga
1.0
(not
significant),
cancer
controls
107a
1.2
(not
significant)
1
vs
0
noncancer
controls
vs
2
cancer
controls
1
vs
0
noncancer
controls
vs
2
cancer
controls
NA
1.7
(significant)
1.6
(significant)
30
1.8
(0.9,
3.5)
32
2.4
(1.2,
4.9)
19
0.9(0.5,
1.9)
6
2.7
(0.8,
9.1)
4
1.6
(0.4,
6.1)
4
0.9
(0.3,
2.9)
8
2.8
(0.9,
8.4)
6
2.0
(0.6,
6.6)
6
1.0
(0.3,
2.8)
11a
1.8
(0.6,
6.0)
5a
1.0
(0.2,
4.3)
5a
1.3
(0.7,
6.3)
38
3.4
(1.1,
10.6),
friend
controls
8
5.2
(1.2,
22.2),
friend
controls
6
3.7
(0.9,
15.2),
friend
controls
8
3.7
(1.0,
13.7),
friend
controls
21
2.9
(1.3, 7.1),
friend
controls
3.0
(1.3,
7.4),
cancer
controls
7
4.6
(1.0,
21.3),
friend
controls
1.9
(0.6,
6.9),
cancer
controls
9
5.5
(1.5,
20.0),
friend
controls
4.4
(1.4,
14.3),
cancer
controls
25
2.4
(1.1,
5.6),
friend
controls
1.3
(0.6, 2.9),
cancer
controls
22
1.6
(0.7,
3.6),
friend
controls
2.6
(1.1,
5.9),
cancer
controls
5
2.1
(0.5,
8.3),
friend
controls
6.2
(1.4,
28.4),
cancer
controls
6
1.1
(0.3,
3.1),
friend
controls
0.6
(0.2,
2.0),
cancer
controls
19
1.5
(0.7,
3.3),
friend
controls
2.4
(1.1,
5.6),
cancer
controls
7
4.6
(1.2,
17.9),
friend
controls
1.4
(0.4,
4.7),
cancer
controls
15
1.7
(0.7,
3.9),
friend
controls
3.4
(1.2,
9.3),
cancer
controls
30
2.4
(1.0,
5.7),
friend
controls
1.7
(0.7,
3.9),
cancer
controls
4
2.5(0.4,
16.1)
8
6.7
(1.2,
38)
18
1.8(0.8,4.1)
31
2.0
(1.0,
4.1)
(Continued
on
next
page)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
899
ZAHM
AND
WARD
Table
3.
Continued.
Total
Exposed
Risk
estimate/
Study
design
Reference
cases,
no.
Exposure
Timing
of
exposure
cases,
no.
comment
Case-control
Bunin
et
al.,
1994
(78)
Case-control
McCredie
et
al.,
1994
(79)
Case-control
McCredie
et
al.,
1994
(80)
Case-control
Leiss
and
Savitz,
1995
(30)
Case-control
Pagoda
and
Preston-
Martin,
1997
(81)
Cohort
Kristensen
et
al.,
1995,
1996
(47,48)
1
55b
Maternal
household
insecticide
sprays
or
pesticides:
ever
At
least
weekly
Maternal
household
extermination
Farm
residence:
maternal
Child
166c
Maternal
household
insecticide
sprays
or
pesticides:
ever
At
least
weekly
Maternal
household
extermination
Farm
residence:
maternal
Child
82
Maternal
live
or
work
on
farm
House
treatment
with
pesticides
82
Live
or
work
on
farm
Regular
contact
with
horses
House
pesticide
treatment
NA
Home
extermination
Yard
pesticide
treatment
Pest
strips
224
Flea
and
tick
treatment
Spray
and
foggers
Termiticides
Nuisance
pest
pesticides,
not
otherwise
specified
Lice
treatments
Insecticides
Herbicides
Fungicides
Snail
killer
Number
of
pets:
1
>1
Number
of
pets:
1
>1
Hr/day
with
pet:
<
3
>3
Hr/day
with
pet:
<3
>3
No
evacuation
after
spray
No
delay
in
harvesting
food
after
treatment
Labels
not
followed
323,
292
Paternal
agricultural
work:
cohort
pesticide
expendituresd
Ever
Ever
Level
1d
Level
2d
Level
3d
Pregnancy
Pregnancy
.1
year
childhood
Pregnancy
Pregnancy
>
1
year
childhood
Pregnancy
Childhood
Last
3
months
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
Last
3
months
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
Last
3
months
pregnancy
Birth-2
years
<dx
2
years
<
dx
to
dx
Pregnancy
Diagnosed
<
5
years
Pregnancy
Pregnancy
Childhood
Pregnancy
Childhood
Pregnancy
Childhood
Pregnancy
Childhood
Pregnancy
Childhood
Pregnancy
Childhood
Pregnancy
Childhood
Childhood
Diagnosed
<
5
years
Childhood
Diagnosed
<
5
years
Childhood
Before
birth
34
8
24
5
6
31
5
34
14
14
5
20
1.5
(0.8,
2.7)
2.2
(0.6,
7.4)
0.7
(0.4,
1.4)
0.5
(0.1,
1.8)
0.4
(0.1,
1.6)
0.7
(0.4,1.4)
1.0
(0.2,
4.9)
1.0
(0.6,1.9)
3.7
(0.8,
23.9)
5.0
(1.1,
46.8)
0.9
(0.3,
2.6)
2.0
(1.0,
3.9)
4
0.6
(0.2,
1.9)
6
0.7
(0.3,
1.8)
NA
No
association
8
1.3
(0.7,
2.1)
1
2
1.4
(0.6,
2.7)
5
1.1
(0.4,
3.0)
12
0.6
(0.3,
1.1)
17
0.5(0.2,
0.9)
16
0.5(0.4,
0.8)
10
1.5
(0.9,
2.4)
13
1.4(0.7,2.9)
9
1.8
(1.2,
2.9)
76
1.7
(1.1,
2.6)
29
2.5
(1.2,
5.5)
17
10.8(1.3,89.1)
5
2.7
(0.5,
14.2)
23
0.7
(0.4,
1.3)
106
1.1
(0.8,
1.7)
150
1.0
(0.6,
1.5)
2
38
0.6
(0.4,
1.0)
26
1.3
(0.7,
2.4)
57
1.2
(0.8,
2.0)
2
0.9
(0.1,
6.1
4
1.2
(0.3,
4.9)
0
1
0.1
(0.0,
1.0)
21
1.1
(0.6,
2.1)
41
1.0
(0.6,
1.8)
43
1.4
(0.9,
2.4)
30
2.0
(1.0,
4.0)
16
2.0
(0.8,
4.8)
11
3.5(1.1,
11.4)
33
1.1
(0.6,1.8)
21
1.9
(0.9,
4.2)
10
1.3
(0.5,
3.6)
8
3.2
(0.8,
12.2)
NA
1.6(1.0,2.1)
NA
3.6(1.0,
13.7)
NA
3.7
(1.5,
9.6)
31
60
7
17
7
2.7
(1.6,
4.8)e
1.4
(1.0,
1.9)f
2.0
(0.9,
4.7)
2.9
(1.5,
5.6)
3.3
(1.4,
7.8)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
&Number
of
discordant
pairs
with
exposed
cases.
bAstrocytoma.
cPrimitive
neuroectodermal
tumor.
dExpenditures-levels
are
levels
of
money
spent.
eNonastrocytic
gliomas.
fNonastrocytic
neuroepithelioma
tumor.
900
PESTICIDES
AND
CHILDHOOD
CANCER
Table
4.
Summary
of
studies
on
pesticides
and
neuroblastoma.
Total
Reference
cases,
no.
Exposure
Infante
and
Newton,
1
Maternal
exposure
to
chlordane,
1975
(82)
spent
25-30
hr/week
in
basement
with
strong
odor
from
household
treatment
Infante
et
al.,
1978
(49)
14
Chlordane
Moses,
1989
(51)
NA
Residence
in
McFarland,
CA,
farm
town
Case-control
Spitz
and
Johnson,
1985
(83)
Case-control
Wilkins
and
Hundley,
1990
(84)
157
Paternal
occupation
in
agriculture
101
Paternal
occupation
in
agriculture,
forestry,
or
fishing
Paternal
industry
in
agriculture,
forestry,
or
fishing
Case-control
Bunin
et
al.,
1990
(85)
104
Paternal
occupation
as
farmer
Case-control
Schwartzbaum
et
al.,
1991
(62)
Kristensen
et
al.,
1995
(47)
104
Parental
gardening
with
pesticides
323,
292
Parental
agricultural
work
cohort
Exposed
Risk
estimate/
Timing
of
exposure
cases,
no.
comment
First
trimester
of
pregnancy
1
Case
diagnosed
at
2
years,
8
months
of
age
Pregnancy
and
childhood
5
Pregnancy
and
childhood
NA
Birth
6
0.6
(0.2,
1.4)
At
birth
Preconception
Pregnancy
Childhood
Before
birth
7
0.9
(0.4,
2.2)
9
0.8
(0.4,
2.0)
7a
3.5
(0.7,
34.5)
2a
0.7
(0.1,
5.8)
NA
1.1
(not
significant)
7
2.5
(1.0,
6.1)
'Number
of
discordant
pairs
with
exposed
cases.
Table
5.
Summary
of
studies
on
pesticides
and
childhood
non-Hodgkin's
lymphoma.
Study
design
Case
report
Case-control
Reference
Moses,
1989
(51)
Magnani
et
al.,
1990
(60)
Total
cases,
no.
NA
19
Case-control
Schwartzbaum
et
al.,
104
1991
(62)
Case-control
Buckley,
1991
(86)
Case-control
Roman
et
al.,
1993
(65)
Case-control
Mulder
et
al.,
1994
(66)
Case-control
Leiss
and
Savitz,
1995
(30)
Cohort
Kristensen
et
al.,
1996
(48)
Exposed
Risk
estimate/
Exposure
Timing
of
exposure
cases,
no.
comment
Residence
in
McFarland,
CA,
farm
town
Pregnancy
and
childhood
NA
Parental
occupation
as
farmer
Pregnancy
and
childhood
NA
No
association
Parental
gardening
with
pesticides
NA
Maternal
household
insecticide
use:
<
1/week
1-2/week
Daily
Garden
insecticide
spraying:
<
1
/month
1
/month
Home
extermination
39a
Paternal
occupation
in
agriculture
11b
6C
7,
7d
Pesticide
exposure:
child
Paternal
Summary
pesticide
indicator
NA
Home
extermination
Yard
treatment
Pest
strips
323,
292
Parental
agricultural
work,
census
cohort
pesticide
expenditures
Level
1e
Level
2e
level
3e
Horticultural/pesticide
products
Birth
to
diagnosis
Pregnancy
NA
1.3
(not
significant)
NA
1.0
2.2
5.2
4.2
2.1
2.8
Birth
11
d
Results
are
for
At
interview
1
5d
leukemia
and
lymphoma
combined
Ever
2
1.3
(0.1,
11.4)
>
3
hr/week
2
6.0
(0.3,
368.3)
Ever
6
1.0
(0.2,
6.1)
>3
hr/week
5
2.1
(0.4,12.5)
>
2
indicators
5
0.8
(0.1,
4.4)
>
3
indicators
4
1.7
(0.3,
10.5)
>
4
indicators
3
3.1
(0.3,
28.3)
Last
3
months
of
pregnancy
4
1.2
(0.4,
3.9)
Pregnancy-2
years
<
dx
9
1.8
(1.1,
2.9)
2
years
<
dx
6
1.6
(0.9,
2.9)
last
3
months
of
pregnancy
6
0.5
(0.2,
1.2)
Pregnancy-2
years
<
dx
15
0.8
(0.3,
1.8)
2
years
<
dx
10
0.6
(0.4,
1.0)
Last
3
months
of
pregnancy
5
1.4
(0.7,
2.5)
Pregnancy-2
years
<
dx
7
1.3
(0.4,
2.7)
2
years
<
dx
4
1.1
(0.6,
1.9)
Before
birth
5
1.3
(0.5,
3.4)
10
1.6(0.8,
3.3)
6
2.5
(1.0,
6.2)
11
2.1
(1.0,4.3)
'ALL.
bOther
leukemia.
CNon-Hodgkin's
lymphoma.
dLeukemia
and
lymphoma
combined.
'Levels
of
money
spent.
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
Study
design
Case
report
Case
report
Case
report
Cohort
901
ZAHM
AND
WARD
Table
6.
Summary
of
studies
on
pesticides
and
Wilms'
tumor.
Total
Study
design
Reference
cases,
no.
Case
report
Moses,
1989(51)
NA
Case-control
Kantor
et
al.,
1979
(87)
149
Case-control
Wilkins
and
Sinks,
62
1984
(88)
Case-control
Schwartzbaum
et
al.,
1991
(62)
Case-control
Olshan
et
al.,
1993
(89)
Case-control
Sharpe
et
al.,
1995
(90)
Cohort
Kristensen
et
al.,
1995,
1996
(47,48)
101
200
109
323,
292
cohort
Exposed
Risk
estimate/
Exposure
Timing
of
exposure
cases,
no.
comment
Residence
in
McFarland,
CA,
farm
town
Pregnancy
and
childhood
NA
Paternal
occupation
as
farmer
Birth
1
vs
8/145
controls
Paternal
occupational
exposure:
At
birth
DDT
3
0.4
(not
significant)
Ethylene
dibromide
3
1.0
(not
significant)
Endrin
3
0.4
(not
significant)
Insecticides,
not
otherwise
specified
1
0.3
(not
significant)
Parental
gardening
with
pesticides
Birth
to
diagnosis
NA
0.7
(not
significant)
Household
insecticide
extermination
Childhood:
ever
78
2.2
(1.2,
3.8)
Once/year
33
2.4
(1.1,
5.1)
Twice
or
more/year
31
2.2
(0.9,
5.1)
Agricultural
use
of
pesticides:
Before
birth
Gender
differencea
Maternal:
<lOtimes
2
0.3(0.1,2.3)
2
10
times
6
128.6(6.4,
2569)
Paternal:
<
10
times
6
2.7
(0.8,
9.8)
.l0times
15
3.2(1.2,9.0)
Paternal
farmwork:
0-24
months:
no
exposure
3
0.6
(0.1,
2.4)
Exposed
5
0.9
(0.2,
4.8)
25-48
months:
no
exposure
16
2.9
(0.9,
9.0)
Exposed
6
4.8
(1.0,
22.4)
49-108
months:
no
exposure
4
1.0
(0.2,
4.3)
Exposed
10
4.1
(1.0,
17.5)
Maternal
farmwork:
0-24
months:
no
exposure
7
1.3
(0.4,
4.4)
Exposed
2
0.5
(0.0,
4.6)
25-48
months:
no
exposure
15
2.3
(0.9,
5.9)
Exposed
1
2.2
(0.1,
38.3)
49-108
months:
no
exposure
5
0.3
(0.1,
1.2)
Exposed
5
14.8
(2.2,
98.8)
Parental
agricultural
work,
Before
birth
4
8.9
(2.7,
29.5)
census
pesticide
expenditures
Orchards
or
greenhouse
4
4.8(1.6,
14.7)
Pesticide
spraying
9
2.5
(1.0,
6.6)
Orchards
or
greenhouse
and
4
8.9
(2.7,
29.5)
pesticide
spraying
fin
general,
risks
were
higher
for
boys
than
for
girls.
Table
7.
Summary
of
studies
on
pesticides
and
Ewing's
sarcoma.
Total
Study
design
Reference
cases,
no.
Case
report
Holman
et
al.,
1983
(91)
6
Case
report
Zamora
et
al.,
1986
(92)
2
Case-control
Daigle,
1987
(93)
98
Case-control
Schwartzbaum
et
al.,
49
1991
(62)
Case-control
Holly
et
al.,
1992(94)
43
Case-control
Winnetal.1992(95)
208
Exposure
Rural
residents,
exposure
to
farm
animals
and
agricultural
exposures
Paternal
occupation
in
agriculture,
contact
with
farm
animals
Paternal
occupation
in
agriculture
Parental
gardening
with
pesticides
Paternal
occupation
in
agriculture
Paternal
exposure
to
herbicides,
pesticides,
fertilizers
Household
extermination
Paternal
occupation
as
farmer
Lived
on
farm
or
ranch
Pets
Household
extermination
Timing
of
exposure
Childhood
Childhood
At
conception
Childhood
Childhood
6
months
<
conception
to
dx
Pregnancy
Childhood
Pregnancy
Usual
occupation
Childhood
Childhood
Pregnancy
Exposed
Risk
estimate/
cases,
no.
comment
6
Ages
12-34
2
Two
brothers
diagnosed
at
8
and
15
years
of
age
NA
9.0
(significant)
NA
9.0
(significant)
NA
1.1
(not
significant)
7
8.8
(1.8,
42.7)
7
6.1
(1.7,
21.9)
1
0.3
(0.02,
2.1)
15
0.6
(0.3,
1.2)
13
2.2
(0.7,
6.5)
14
3.1
(0.9,
9.5)
43
1.4
(0.8,
2.4)
160
1.5(0.9,
2.4)
60
1.3
(0.8,
2.1)
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
902
PESTICIDES
AND
CHILDHOOD
CANCER
Table
8.
Summary
of
studies
on
pesticides
and
childhood
osteosarcoma,
soft-tissue
sarcoma,
colorectal
cancer,
germ
cell
cancer,
Hodgkin's
disease,
and
retinoblastoma.
Study
design
Reference
Case-control
Schwartzbaum
et
al.,
1991
(62)
Case-control
Magnani
et
al.,
1989
(96)
Case-control
Leiss
and
Savitz,
1995
(30)
Cancer
Osteosarcoma
Soft-tissue
sarcoma
Soft-tissue
sarcoma
Total
cases,
no.
78
52
Exposure
Parental
gardening
with
pesticides
Maternal
farming
occupation
NA
Yard
pesticide
treatment
Home
extermination
Pest
strips
Cohort
Kristensen
et
al.,
1996
(48)
Case
report
Pratt
et
al.,
1977
(97)
Case
report
Pratt
et
al.,
1987
(98)
Case-control
Caldwell
et
al.,
1981
(99)
Case-control
Mills
et
al.,
1984(100)
Case-control
Shu
et
al.,
1995(101)
Cohort
Kristensen
et
al.,
1996
(48)
Case-control
Schwartzbaum
et
al.
1991
(62)
Cohort
Kristensen
et
al.,
1990
(48)
Case-control
Bunin
et
al.,
1990
(102)
Soft-tissue
sarcoma
Colorectal
Colorectal
Colorectal
Germ
cell
(testes)
Germ
cell
Germ
cell
(testes)
Hodgkin's
disease
Hodgkin's
disease
Retino-
blastoma
323,
292
cohort
13
1
Parental
agricultural
work
Pesticide
spraying
equipment
Chemicals
used
in
production
of
cotton
and
soybeans
Environmental
dioxin
in
Missouri
10
Serum
levels
of
DDT,
dieldrin,
chlordane,
heptachlor
347
Farming
occupation
105
Insecticides
or
herbicides:
Maternal
Paternal
323,
292
Parental
agricultural
work:
cohort
pesticides
133
Parental
gardening
with
pesticides
323,
292
Parental
agricultural
work:
cohort
Pesticide
use
Pesticide
spraying
equipment
182
Maternal
grandfather
occupation:
Farmer
or
farm
worker
Timing
of
exposure
Birth
to
diagnosis
Ever
before
birth
Birth
to
diagnosis
Last
3
months
of
pregnancy
Birth-2
years
<
dx
2
years
<
dx
to
dx
Last
3
months
of
pregnancy
Birth-2
years
<dx
2
years
<
dx
to
dx
Last
3
months
of
pregnancy
Birth-2
years
<dx
2
years
<
dx
to
dx
Before
birth
Childhood
Childhood
Diagnosis
Ever
Ever
Ever
Before
birth
Childhood
Before
birth
At
mother's
birth
Farm
worker
Cohort
Kristensen
et
al.,
1996
(48)
Eye
323,
292
Parental
agricultural
work:
cohort
Ever
Field
work
and
pesticide
purchases
Before
birth
Exposed
cases,
no.
NA
2
2
10
14
10
1
2
1
2
2
0
16
8
9
Risk
estimate/
comment
2.6
(p=
0.01)
7.0
(1.5,
33.2)
17.2
(3.3,
88.9)
0.8
(0.5,
1.3)
4.1
(1.0,
16.0)
3.9
(1.7,
9.2)
0.3
(0.0,
18)
0.5
(0.1,
24)
0.7
(0.1,
5.3)
0.6
(0.1,
2.6)
0.5
(0.1,
2.3)
0.9
(0.5,
1.5)
1.3
(0.5,
2.9)
10
Generally,
cases
had
higher
levels
than
controls;
cases
were
from
rural
area
18
6.3
(1.8,
21.5)
6
6
97
10
NA
2.4
(0.9,
6.9)
1.8
(0.7,
5.0)
1.2
(1.0,
1.5)
0.8
(0.4,
1.5)
1.4
(not
significant)
46
1.2
(0.8,
1.6)
22
1.3
(0.8,
2.1)
3a
1.0
(0.1,
7.5),
sporadic
heritable
loa
10.0
(1.4,
433),
nonheritable
9
0.8
(0.4,
1.6)
4
3.2
(0.9,
10.9)
aNumber
of
discordant
pairs
with
exposed
cases.
Leiss
et
al.
(30)
found
a
4-fold
increased
risk
of
soft-tissue
sarcoma
among
children
whose
yards
had
been
treated
with
pesticides
during
their
childhood,
but
not
if
the
treat-
ment
occurred
prenatally.
Kristensen
et
al.
(48)
found
little
evidence
for
an
increased
risk
of
soft-tissue
sarcoma
in
children
of
Norwegian
farmers.
The
farming
status
was
ascertained
before
the
children's
births,
not
at
birth
or
during
childhood,
but
little
change
probably
occurred.
Magnani
et
al.
(96)
found
elevated
risks
of
soft-tissue
sarcoma
among
children
whose
mothers
were
farmers
either
before
birth
or
between
birth
and
diagnosis,
but
the
numbers
of
exposed
cases
were
extremely
small.
Nine
of
13
extremely
rare
cases
of
colorectal
cancer
among
children
had
expo-
sure
to
insecticides
used
in
the
production
of
cotton
and
soybeans
(97).
A
case-control
study
of
rural
children
with
colorectal
cancer
found
that
cases
had
higher
serum
levels
of
DDT,
dieldrin,
chlordane,
and
heptachlor
than
controls
(99).
Testicular
cancer,
with
peak
incidence
at
20
to
39
years
of
age,
is
not
typically
considered
a
childhood
cancer.
The
tumor,
however,
is
likely
to
have
been
initiated
during
the
prenatal
or
childhood
period.
Mills
et
al.
(100)
found
a
6-fold
excess
of
testicular
cancer
among
men
employed
as
farmers
or
farmworkers.
Kristensen
et
al.
(48),
however,
found
no
excess
of
testicu-
lar
cancer
among
children
whose
parents
were
farmers.
Parental
exposures
to
pesti-
cides
were
associated
with
nonsignificant
Environmental
Health
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*
Vol
106,
Supplement
3
*
June
1998
903
ZAHM
AND
WARD
excesses
of
other
germ
cell
malignancies
in
a
study
by
Shu
et
al.
(101).
Two
studies
of
Hodgkin's
disease
reported
small
nonsignificant
excesses
among
children
whose
parents
used
pesti-
cides
occupationally
or
in
the
garden
(48,62).
A
10-fold
risk
of
nonheritable
retinoblastoma
was
observed
among
children
whose
maternal
grandfather
was
a
farmer
or
farmworker
at
the
time
of
the
mother's
birth
(102).
There
was
no
excess
risk
observed
for
sporadic
heritable
retinoblastoma.
Methodologic
Issues
Based
on
the
research
to
date
on
the
role
of
pesticides
in
the
etiology
of
childhood
can-
cers,
little
can
be
definitively
concluded,
particularly
for
specific
pesticides.
There
are
methodologic
issues
that
limit
the
informativeness
or
affect
the
interpretation
of
most
of
the
studies
in
this
review.
Case
Definition
Many
types
of
childhood
cancer
are
comprised
of
heterogeneous
histologic
sub-
types.
For
example,
childhood
leukemia
consists
of
ALL,
AML,
chronic
lymphocytic
leukemia,
and
other
forms.
Soft-tissue
sar-
coma
includes
rhabdomyosarcoma,
fibrosar-
coma,
and
other
types.
If
these
subtypes
have
different
etiologies,
grouping
them
may
mask
associations.
If
chronic
lympho-
cytic
leukemia
is
associated
with
pesticide
use
but
ALL,
which
is
far
more
common,
is
not,
then
studies
of
all
childhood
leukemia
combined
may
not
show
any
excess
risk.
Similarly,
there
may
be
different
expo-
sures
or
different
impact
from
the
same
exposure
by
age
at
diagnosis.
Leukemia
among
infants
under
1
year
of
age
may
be
a
different
disease
with
different
etiology
than
leukemia
diagnosed
at
older
ages.
Buckley
et
al.
(58)
reported
ORs
of
1.7
to
7.0
for
acute
nonlymphocytic
leukemia
associated
with
parental
pesticide
use
for
all
ages
combined,
but
an
OR
of
11.4
for
cases
diagnosed
under
6
years
of
age.
The
pesticide
associa-
tion
was
also
stronger
among
brain
cancer
cases
diagnosed
under
5
years
of
age
in
the
study
by
Pagoda
and
Preston-Martin
(81).
Larger
studies
with
the
ability
to
evaluate
exposures
by
histology
and
other
case
char-
acteristics
may
result
in
increased
sensitivity
and
more
informative
studies.
Choice
of
Controls
The
case-control
studies
of
pesticides
and
childhood
cancer
have
generally
used
one
or
more
of
four
types
of
controls:
general
pop-
ulation
controls,
friends,
siblings,
or
other
cancer
cases.
General
population
controls
have
been
criticized
for
introducing
possible
recall,
or
case-response,
bias.
Childhood
cancer-case
parents,
who
have
probably
anxiously
pondered
possible
rea-
sons
for
their
child's
disease,
may
report
exposures
that
parents
of
healthy
children,
who
have
not
been
vigorously
examining
their
past
exposures,
may
fail
to
remember
and
report.
False
positive
associations
may
be
observed.
Using
friends
of
the
cases
as
controls
may
result
in
overmatching
on
exposure
status.
Friends
may
have
parents
in
similar
occupations,
may
live
in
the
same
neighborhoods,
attend
the
same
school,
and
may
play
on
the
same
pesti-
cide-treated
soccer
fields.
False
negative
results
may
be
observed.
Sibling
controls
would
suffer
even
more
from
overmatch-
ing.
Using
other
cancer
cases
as
controls
should
minimize
recall
bias
because
the
parents
of
both
the
case
and
the
control
children
are
equally
motivated
to
recall
and
report
their
children's
exposures.
If
pesti-
cides
are
also
associated
with
the
other
cancer
with
which
the
controls
are
diag-
nosed,
however,
false
negative
results
may
occur.
For
example,
some
childhood
brain
cancer
studies
had
other
childhood
cancer
cases
for
controls,
which,
given
childhood
cancer
patterns,
must
have
been
almost
entirely
leukemia
cases.
If
leukemia
is
associ-
ated
with
pesticide
exposure,
little
elevation
in
risk
would
have
been
apparent
among
the
brain
cancer
cases
even
if
pesticides
truly
played
a
role.
More
information
on
the
extent
of
recall
bias,
if
any,
is
needed
and
more
objective
methods
of
obtaining
exposure
information
must
be
developed
so
we
can
use
general
population
controls,
which
appear
to
maximize
the
sensitivity
of
childhood
cancer
studies.
Exposure
Assessment
Most
of
the
studies
on
childhood
cancer
and
pesticides
were
based
on
crude
exposure
information
with
little
specificity
in
pesti-
cide
type
or
amount.
The
most
specific
data
were
presented
in
case
reports.
The
analyti-
cal
epidemiologic
studies
were
generally
based
on
measures
such
as
parental
occupa-
tion,
self-reported
or
imputed
parental
occupational
exposure
to
pesticides
(not
otherwise
specified),
farm
crop,
type
of
live-
stock,
broad
pesticide
class
(e.g.,
insecti-
cide),
or
pesticide
product
type
(e.g.,
flea
powder).
The
more
crude
and
encompass-
ing
the
exposure
classifications
are,
the
greater
possibility
that
the
increased
risks
from
individual
pesticides
or
chemical
classes
of
pesticides
will
be
diluted
and
go
undetected.
In
addition,
crude
exposure
measures
may
reflect
a
nonpesticide
risk
factor.
Examination
of
dose-
or
exposure-
response
relationships
can
aid
interpretation
of
causality.
Evidence
of
an
exposure-
response
gradient
decreases
the
likelihood
that
an
association
is
due
to
chance.
Some
childhood
cancer
studies
of
pesticides
have
used
these
surrogate
measures
for
dose:
duration
in
occupation
with
pesticide
exposure,
total
number
of
average
fre-
quency
of
pesticide
applications,
number
of
pets,
number
of
hours
with
pets,
num-
ber
of
hours
in
treated
homes,
farming
census
data
on
pesticide
expenditures,
and
biologic
measures.
Modifications
of
risk
by
protective
practices,
such
as
staying
in
the
home
after
pesticide
treatment,
lack
of
delay
in
harvesting
food
after
treatment,
and
failing
to
follow
pesticide
label
applica-
tion
instructions
were
also
used
as
crude
indicators
of
exposure
amount
(81).
The
studies
by
Scheele
et
al.
(63)
and
Caldwell
et
al.
(99)
were
based
on
measures
of
pesticides
and
their
metabolites
in
bio-
logic
specimens.
Biologic
measures
avoid
the
problems
of
recall
bias
and
lack
of
speci-
ficity
of
pesticide
type,
but
may
be
affected
by
disease
or
treatment
and
generally
reflect
only
very
recent
exposures.
Compounds
for
which
biologic
measures
reflect
lifetime
exposures
are
limited
generally
to
the
per-
sistent
organochlorines.
Biologic
measures
for
lifetime
exposure
to
pesticides
that
are
more
quickly
metabolized
and
excreted
are
not
available.
One
ongoing
study
of
childhood
cancer
is
measuring
potential
household
pesticide
exposure
by
analyzing
pesticide
residues
in
carpet
dust
collected
by
high-volume
surface
sampler
vacuums
(103).
Pesticide
residues
indoors
are
protected
from
degradation
by
the
sun
and
microbial
activity
and
therefore
are
more
persistent
than
pesticide
residues
outdoors.
This
approach
can
give
a
picture
of
cumulative
exposure
to
some
of
the
more
persistent
pesticides
such
as
organochlorine
insecticides,
but
does
not
assess
exposure
to
short-lived
volatile
chemicals.
Children
living
near
agricultural
lands
treated
with
pesticides
have
higher
levels
of
pesticides
in
their
homes
than
children
of
nonfarm
families
living
away
from
agri-
cultural
land
(10).
Pesticide
levels
in
house
dust
were
inversely
correlated
with
the
distance
of
the
home
from
sprayed
orchards.
Pesticide
detections
in
ground-
water
also
have
been
associated
with
the
proximity
to
sprayed
crops
(104).
Methods
have
been
developed
to
use
remote
sensing
Environmental
Health
Perspectives
a
Vol
106,
Supplement
3
*
June
1998
904
PESTICIDES
AND
CHILDHOOD
CANCER
(i.e.,
satellite
images)
and
geographic
infor-
mation
systems
to
characterize
the
types
of
crops
near
the
subjects'
residences
(105,106).
By
combining
the
crop
pattern
data
and
crop-specific
pesticide
use
infor-
mation
with
the
proximity
of
residence
to
cropland,
the
probability
of
exposure
to
individual
pesticides
can
be
estimated
(107).
This
technique
was
used
to
recon-
struct
exposure
for
a
short
and
recent
time
frame
in
a
study
of
pesticide
exposure
and
low
birth
rate
in
Colorado
(106)
and
for
historical
exposures
from
the
1980s
using
satellite
imagery
and
historical
U.S.
Farm
Service
Administration
records
in
a
pilot
study
in
Nebraska
(107).
These
techniques
have
not
yet
been
used
in
childhood
cancer
research,
but
may
enhance
future
efforts.
Indirect
measures
of
potential
exposure
may
be
less
preferable
than
direct
home
or
biologic
measurements.
Direct
measures,
however,
are
usually
expensive
and
often
difficult
to
obtain
in
large
studies
with
hun-
dreds
or
thousands
of
subjects.
In
addition,
direct
measures
usually
reflect
recent
expo-
sures,
whereas
historical
data,
even
if
indi-
rect,
may
be
more
important
for
diseases
of
long
latency.
More
studies
with
crude
exposure
assess-
ments
(e.g.,
pesticides,
not
otherwise
speci-
fied)
will
not
make
major
contributions
to
our
understanding
or
to
prevention
strate-
gies.
To
facilitate
epidemiologic
research
on
specific
pesticides,
improvements
are
needed
to
identify
the
type
and
amount
of
pesticide
exposure,
including
validity
and
reliability
studies.
In
addition,
continued
efforts
should
be
made
to
make
information
avail-
able
on
the
identity
of
the
so-called
inert
ingredients
in
pesticide
formulations.
These
ingredients,
although
not
responsible
for
the
pesticidal
action
of
the
formulations,
are
not
biologically
inert
and
can
be
extremely
important
when
trying
to
correctly
assess
the
carcinogenic
potential
of
a
pesticide.
Timing
of
Exposur
Some
childhood
cancer
studies
have
evaluated
pesticide
exposure
during
critical
time
periods
such
as
preconception
(e.g.,
ever,
3
months
prior
to
conception,
and
6
months
prior
to
conception),
during
preg-
nancy
(e.g.,
ever,
the
first
trimester,
and
the
last
trimester),
and
postnatally,
including
while
nursing,
during
infancy,
and
at
speci-
fied
numbers
of
years
prior
to
diagnosis.
Information
on
time
periods
of
higher
risk
might
provide
insight
into
mechanism,
such
as
whether
there
had
been
a
germ
line
versus
somatic
mutation,
or
whether
risks
were
related
to
age-dependent
metabolic
capabilities.
Such
information
might
also
influence
judgments
concerning
causality.
Large
numbers
of
subjects
are
needed,
with
variation
in
timing,
to
evaluate
whether
risks
differ
by
time
period.
Most
studies
conducted
to
date,
however,
have
a
small
number
of
subjects,
with
most
subjects
exposed
preconception
through
diagnosis,
offering
little
chance
of
identifying
when
pesticides
might
act
to
initiate
the
cancer
under
investigation.
Genetic-Environmental
Interactions
Within
the
population
there
are
subgroups
of
children
who
may
differ
in
their
suscepti-
bility
to
cancer
because
of
genetically
deter-
mined
metabolic
polymorphisms
or
by
mutations
in
major
cancer
genes.
Among
adults,
genetics
play
a
role
in
the
ability
to
metabolize
pesticides.
At
least
a
15-fold
dif-
ference
in
the
ability
to
detoxify
organophos-
phate
insecticides
has
been
observed
(27).
Metabolic
polymorphisms
important
to pes-
ticide
carcinogenicity
may
also
exist
and
should
be
investigated.
A
family
history
of
cancer,
a
crude
measure
of
genetic
suscepti-
bility,
appeared
to
enhance
the
carcinogenic
effects
of
pesticides
in
case-control
studies
of
adults
(108,109).
Similar
research
among
children
should
be
conducted.
Statstical
Power
The
statistical
power
of
existing
studies
on
childhood
cancer
and
pesticides
is
limited.
Most
studies
had
small
numbers
of
cases,
typically
in
the
range
of
50
to
200
subjects,
with
most
comparisons
based
on
less
than
20,
and
usually
less
than
10,
exposed
cases.
These
numbers
are
insufficient
to
evaluate
dose
response,
timing
of
exposure,
multiple
pesticide
exposures,
or
genetic-environment
interactions.
Large
national
or
international
efforts
will
be
needed
to
provide
enough
exposed
cases
to
adequately
address
these
issues.
Studies
of
intermediate
effects
such
as
chromosomal
aberrations
and
DNA
adducts,
which
may
be
more
prevalent
than
cancer,
may
be
informative
and
should
be
considered.
Strength
of
Association
Most
of
the
methodologic
limitations
noted
for
existing
studies
on
childhood
cancer
and
pesticides
would
cause
studies
to
underesti-
mate
risk.
For
example,
heterogeneity
of
dis-
ease,
poor
exposure
assessment,
and
use
of
cancer
controls
would
bias
true
positive
associations
toward
the
null.
Despite
these
limitations
and
the
almost
certain
underesti-
mation
of
risks
that
is
occurrin
i
i
rik-
iung
tht
manysof
thea
repocurtedg,
it
as
stks
ing
that
many
of
the
reported
increased
risks
are
of
greater
magnitude
than
those
observed
in
studies
of
pesticide-exposed
adults
(110).
For
example,
childhood
studies
have
reported
increases
in
risk
as
large
as
4-
to
9-fold
for
leukemia
(55,58)
and
6-
to
7-fold
for
brain
cancer
(76,77),
whereas
studies
of
farmers
and
other
exposed
adults
have
rarely
reported
relative
risks
greater
than
2
(110).
Children
may
be
particularly
sensitive
to
possible
carcino-
genic
effects
of
pesticides.
This
is
of
con-
cern,
given
the
children
working
on
farms
and
the
high
prevalence
of
use
of
pesticides
in
the
home
in
the
general
population.
Conclusions
Many
of
the
cancers
associated
with
pesti-
cides
among
children,
such
as
leukemia,
brain
cancer,
non-Hodgkin's
lymphoma,
soft-tissue
sarcoma,
and
Hodgkin's
disease,
are
the
same
cancers
that
are
repeatedly
associated
with
pesticide
exposure
among
adults
(110),
suggesting
that
a
role
among
children
is
highly
plausible.
Furthermore,
although
the
research
has
been
limited
by
nonspecific
pesticide
exposure
informa-
tion,
small
numbers
of
exposed
subjects,
potential
for
recall
bias,
and
a
small
number
of
studies
for
most
cancers,
the
magnitude
of
the
risks
is
often
greater
than
among
adults,
indicating
greater
susceptibility.
There
is
a
need
to
study
and
better
quantify
these
exposures.
Studies
must
entail
sophisticated
exposure
assessment,
such
as
that
used
in
epidemiologic
studies
of
occupational
exposures
and
adult
can-
cers,
and
consideration
of
possible
genetic
and
environmental
interactions.
Future
research
should
incorporate,
where
appropriate,
techniques
such
as
prospectively
collected
parental
use
of
pesticides
in
agriculture,
more
detailed
occupational
histories,
environmental
measures
for
pesticide
residues,
geographic
information
systems,
and
biologic
mea-
sures
of
pesticides
and
their
metabolites.
Special
heavily
exposed
populations
such
as
children
of
migrant
farmworkers
should
be
studied
(111,112).
Although
research
is
underway
to
characterize
the
risks
of
childhood
cancer
associated
with
pesticides
and
identify
the
specific
pesticides
responsible,
it
is
prudent
to
reduce
or,
where
possible,
eliminate
pesti-
cide
exposure
to
children,
given
their
increased
vulnerability
and
susceptibility.
In
particular,
efforts
should
be
focused
to
reduce
exposure
to
pesticides
used
in
homes
and
gardens
and
on
lawns
and
public
lands,
which
are
the
major
sources
of
pesticide
exposure
for
most
children.
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
905
ZAHM
AND
WARD
REFERENCES
AND
NOTES
1.
Blair
A,
Axelson
0,
Franklin
C,
Paynter
OE,
Pearce
N,
Stevenson
D,
Trosko
JE,
Vainio
H,
Williams
G,
Woods
J,
et
al.
Carcinogenic
effects
of
pesticides.
In:
Advances
in
Modern
Environmental
Toxicology
(Mehlman
MA,
ed).
Vol
XVIII:
The
Effects
of
Pesticides
on
Human
Health
(Baker
SR,
Wilkinson
CF,
eds).
Princeton,
NJ:Princeton
Scientific,
1990;201-260.
2.
IARC.
IARC
Monographs
on
the
Evaluation
of
Carcinogenic
Risks
to
Humans.
Vol
1-69.
Lyon:International
Agency
for
Research
on
Cancer,
1972-1997.
3.
IARC.
IARC
Monographs
on
the
Evaluation
of
Carcinogenic
Risks
to
Humans.
Vol
53:
Occupational
Exposures
in
Insecticide
Application,
and
Some
Pesticides.
Lyon:International
Agency
for
Research
on
Cancer,
1991.
4.
U.S.
EPA
Office
of
Pesticides
and
Toxic
Substances.
Suspended,
Canceled,
and
Restricted
Pesticides.
Rpt
no
1990-
259-158.
Washington:U.S.
Government
Printing
Office,
1990.
5.
U.S.
EPA
Office
of
Pesticide
Programs
(updated
1
August
1997).
List
of
Pesticides
Banned
and
Severely
Restricted
in
the
US
[Online].
http://www.epagov/oppfeadl/international/piclist.htm
6.
Moses
M,
Johnson
ES,
Anger
WK,
Burse
VW,
Horstman
SW,
Jackson
RJ,
Lewis
RG,
Maddy
KT,
McConnell
R,
Meggs
WJ,
et
al.
Environmental
equity
and
pesticide
exposure.
Toxicol
Ind
Health
9:913-959
(1993).
7.
Nigg
HN,
Beier
RC,
Carter
0,
Chaisson
C,
Franklin
C,
Lavy
T,
Lewis
RG,
Lombardo
P,
McCarthy
JF,
Maddy
KT.
Exposure
to
pesticides.
In:
Advances
in
Modern
Environmental
Toxicology
(Mehlman
MA,
ed).
Vol
XVIII:
The
Effects
of
Pesticides
on
Human
Health
(Baker
SR,
Wilkinson
CF,
eds).
Princeton,
NJ:Princeton
Scientific,
1990;35-130.
8.
Murphy
RS,
Kutz
FW,
Strassman
SC.
Selected
pesticide
residues
or
metabolites
in
blood
and
urine
specimens
from
a
general
pop-
ulation
survey.
Environ
Health
Perspect
48:81-86
(1983).
9.
Camann
DE.
Carpet
dust:
an
indicator
of
exposure
at
home
to
pesticides,
PAHs,
and
tobacco
smoke
[Abstract].
Presented
at
the
International
Society
of
Environmental
Engineering/
International
Society
of
Exposure
Assessment
Joint
Conference,
18-21
September
1994,
Research
Triangle
Park,
NC,
1994;
141.
10.
Simcox
NJ,
Fenske
RA,
Wolz
SA,
Lee
IC,
Kalman
DA.
Pesticides
in
household
dust
and
soil:
exposure
pathways
for
children
of
agricultural
families.
Environ
Health
Perspect
103:1126-1134
(1995).
11.
Camann
DE,
Geno
PW,
Harding
HJ,
Giardino
NJ,
Bond
AE,
Lewis
RG,
Akland
GG.
A
pilot
study
of
pesticides
in
indoor
air
in
relation
to
agricultural
applications.
In:
Indoor
Air
'93,
Proceedings
of
the
Sixth
International
Conference,
Helsinki,
Finland.
Vol
2.
Solna,
Sweden:National
Library
for
Working
Life,
1993;207-212.
12.
Nielsen
EG,
Lee
LK.
The
Magnitude
and
Costs
of
Groundwater
Contamination
from
Agricultural
Chemicals:
A
National
Perspective.
Agricultural
Economic
Rpt
no
576.
Washington:U.S.
Department
of
Agriculture,
1987.
13.
U.S.
EPA
Office
of
Water,
Office
of
Pesticides
and
Toxic
Substances.
Summary
results
of
EPA's
national
survey
of
pesticides
in
drinking
water
wells.
In:
National
Pesticide
Survey.
Washington:U.S.
Government
Printing
Offfice,
1990;1-16.
14.
Wiles
R,
Cohen
B,
Campbell
C,
Elderkin
S.
Tap
Water
Blues:
Herbicides
in
Drinking
Water.
Washington:Environmental
Working
Group,
1994.
15.
Cohen
B,
Wiles
R,
Condon
E.
Executive
summary.
In:
Weed
Killers
by
the
Glass:
A
Citizens'
Tap
Water
Monitoring
Project
in
29
Cities.
Washington:Environmental
Working
Group,
1995;1-5.
16.
Kloos
H.
1,2
Dibromo-3-chloropropane
(DBCP)
and
ethyl-
ene
dibromide
(EDB)
in
well
water
in
the
Fresno/Clovis
met-
ropolitan
area,
California.
Arch
Environ
Health
51:291-299
(1996).
17.
University
of
California
Berkeley
School
of
Public
Health.
Pesticide
Contamination
of
Groundwater
in
California.
Berkeley,
CA:University
of
California,
1995.
18.
Goolsby
DA,
Thurman
EM,
Pomes
ML,
Meyers
MT,
Battaglin
WA.
Herbicides
and
their
metabolites
in
rainfall:
ori-
gin,
transport
and
deposition
patterns
across
the
midwestern
and
northeastern
United
States,
1990-1991.
Environ
Sci
Technol
31:1325-1333
(1997).
19.
Immerman
FW,
Firestone
MP.
Non-Occupational
Pesticides
Exposure
Study
(NOPES).
Summary
Report.
Rpt
no
RTI/
136/01
-03D.
Research
Triangle
Park,
NC:Research
Triangle
Institute,
1989.
20.
Physicians
for
Social
Responsibility.
Pesticides
and
Children:
What
the
Pediatric
Practitioner
Should
Know.
Washington:
Physicians
for
Social
Responsibility,
1995;
1-8.
21.
National
Research
Council.
Pesticides
in
the
Diet
of
Infants
and
Children.
Washington:National
Academy
Press,
1993.
22.
Wiles
R,
Davies
K,
Campbell
C.
Overexposed:
Organophosphate
Insecticides
in
Children's
Food.
Washington:Environmental
Working
Group/The
Tides
Center,
1998.
23.
Wiles
R,
Davies
K.
Pesticides
in
Baby
Food.
Washington:
Environmental
Working
Group,
1995.
24.
Gladen
BC,
Rogan
WC.
DDE
and
shortened
duration
of
lactation
in
a
northern
Mexican
town.
Am
J
Public
Health
85:504-508
(1995).
25.
Rogan
WJ,
Gladen
BC.
Study
of
human
lactation
for
effects
of
environmental
contaminants:
the
North
Carolina
Breast
Milk
and
Formula
Project
and
some
other
ideas.
Environ
Health
Perspect
60:215-221
(1985).
26.
Hill
RH
Jr,
To
T,
Holler
JS,
Fast
DM,
Smith
SJ,
Needham
LL,
Binder
S.
Residues
of
chlorinated
phenols
and
phenoxy
acid
herbicides
in
the
urine
of
Arkansas
children.
Arch
Environ
Contam
Toxicol
18:469-474
(1989).
27.
Grossman
J.
What's
hiding
under
the
sink:
dangers
of
house-
hold
pesticides.
Environ
Health
Perspect
103:550-554
(1995).
28.
Whitmore
RW,
Kelly
JE,
Reading
PL.
The
National
Home
and
Garden
Pesticide
Survey.
Vol
1.
Executive
summary,
results,
and
recommendations.
Prepared
by
Research
Triangle
Institute.
Rpt
no
RTI/5100/17-01
F.
Washington:U.S.
Environmental
Protection
Agency,
1992.
29.
Savage
EP,
Keefe
TJ,
Wheeler
HW,
Mounce
LM,
Helwic
L,
Applehaus
F,
Goes
E,
Goes
T,
Mihlam
G,
Rouch
J.
Household
pesticide
usage
in
the
United
States.
Arch
Environ
Health
36:304-309
(1981).
30.
Leiss
JK,
Savitz
DA.
Home
pesticide
use
and
childhood
cancer:
a
case-control
study.
Am
J
Public
Health
85:249-252
(1995).
31.
Reeves
JD.
Household
insecticide-associated
blood
dyscrasias
in
children.
Am
J
Hematol
Oncol
4:438-439
(1982).
32.
Harris
SA,
Solomon
KR.
Human
exposure
to
2,4-D
following
controlled
activities
on
recently
sprayed
turf.
J
Environ
Sci
Health
B27:9-22
(1992).
33.
Harris
SA,
Solomon
KR,
Stephenson
GR.
Exposure
of
home-
owners
and
bystanders
to
2,4-dichlorophenoxyacetic
acid
(2,4-
D).
J
Environ
Sci
Health
B27:23-38
(1992).
34.
General
Accounting
Office.
Lawn
Care
Pesticides:
Risks
Remain
Uncertain
While
Prohibited
Safety
Claims
Continue.
U.S.
GAO/RCED-90-
134.
Washington:U.S.
Government
Printing
Office,
1990.
35.
Stevens
WK.
Public
said
to
disregard
dangers
of
manicuring
the
greensward.
The
New
York
Times,
17
April
1990.
36.
Hayes
HM,
Tarone
RE,
Cantor
KP,
Jessen
CR,
McCurnin
DM,
Richardson
RC.
Case-control
study
of
canine
malignant
lymphoma:
positive
association
with
dog
owner's
use
of
2,4-
dichlorophenoxyacetic
acid
herbicides.
J
Natl
Cancer
Inst
83:1226-1231
(1991).
37.
Pimental
D,
McLaughlin
L,
Zepp
A,
Lakitan
B,
Kraus
T,
Kleinman
P,
Vancini
F,
Roach
WJ,
Graap
E,
Keeton
WS,
et
al.
Environmental
and
economic
impacts
of
reducing
U.S.
906
Environmental
Health
Perspectives
a
Vol
106,
Supplement
3
*
June
1998
PESTICIDES
AND
CHILDHOOD
CANCER
agricultural
pesticide
use.
In:
Handbook
of
Pest
Management
in
Agriculture.
2nd
ed.
Vol
1
(Pimentel
D,
ed).
Boca
Raton,
FL:CRC
Press,
1991;679-680.
38.
Reynolds
PM,
ReifJS,
Ramsdell
HS,
Tessari
JD.
Canine
expo-
sure
to
herbicide-treated
lawns
and
urinary
excretion
of
2,4-
dichlorophenoxyacetic
acid.
Cancer
Epidemiol
Biomarkers
Prev
3:233-237
(1994).
39.
Nishioka
M,
Burkholder
HM,
Brinkham
MC,
Gordon
SM,
Lewis
RG.
Measuring
transport
of
lawn-applied
herbicide
acids
from
turf
to
home:
correlation
of
dislodgeable
2,4-D
turf
residues
with
carpet
dust
and
carpet
surface
residues.
Environ
Sci
Technology
30:3313-3320
(1996).
40.
Davies
JE,
Edmundson
WF,
Raffonelli
A.
Role
of
household
dust
in
human
DDT
pollution.
Am
J
Public
Health
65:53-57
(1975).
41.
Lewis
RG,
Fortmann
RC,
Camann
DE.
Evaluation
of
methods
for
monitoring
the
potential
exposure
of
small
children
to
pesti-
cides
in
the
residential
environment.
Arch
Environ
Cont
Toxicol
26:1-10
(1994).
42.
Starr
HG,
Aldrich
FD,
McDougall
WD
III,
Mounce
LM.
Contribution
of
household
dust
to
the
human
exposure
to
pes-
ticides.
Pestic
Monit
J
8:209-211
(1974).
43.
Whitmore
RW,
Immerman
FW,
Camann
DE,
Bond
AE,
Lewis
RG,
Schaum
JL.
Non-occupational
exposures
to
pesti-
cides
for
residents
of
two
U.S.
cities.
Arch
Environ
Contam
Toxicol
26:47-59
(1994).
44.
Fenske
RA.
Differences
in
exposure
potential
for
adults
and
children
following
residential
insecticide
applications.
In:
Similarities
and
Differences
between
Children
and
Adults:
Implications
for
Risk
Assessment
(Guzelian
PS,
Henry
CJ,
Olin
SS,
eds).
Washington:ILSI
Press,
1992;214-225.
45.
Gurunathan
S,
Robson
M,
Freeman
N,
Buckley
B,
Roy
A,
Meyer
R,
Bukowski
J,
Lioy
P.
Accumulation
of
chlorpyrifos
in
residential
surfaces
and
toys
accessible
to
children.
Environ
Health
Perspect
106:9-16
(1998).
46.
Grufferman
S.
Commentary:
Methodologic
approaches
to
studying
environmental
factors
in
childhood
cancer.
Environ
Health
Perspect
106(Suppl
3):881-886
(1998).
47.
Kristensen
P,
Andersen
A,
Irgens
LM.
Childhood
cancer
at
young
age
and
pesticide
use
on
the
parents'
farm:
a
register
link-
age
study
in
Norway
[Abstract].
Epidemiology
6:S125
(1995).
48.
Kristensen
P,
Andersen
A,
Irgens
LM,
Bye
AS,
Sundheim
L.
Cancer
in
offspring
of
parents
engaged
in
agricultural
activities
in
Norway:
incidence
and
risk
factors
in
the
farm
environment.
Int
J
Cancer
65:39-50
(1996).
49.
Infante
P,
Epstein
SS,
Newton
WA
Jr.
Blood
dyscrasias
and
childhood
tumors
and
exposure
to
chlordane
and
heptachlor.
Scand
J
Work
Environ
Health
4:137-150
(1978).
50.
Reeves
JD,
Driggers
DA,
Kiley
VA.
Household
insecticide
asso-
ciated
aplastic
anaemia
and
acute
leukaemia
in
children
[Letter].
Lancet
8241:300
(1981).
51.
Moses
M.
Pesticide-related
health
problems
and
farmworkers.
Am
Assoc
Occup
Health
Nurses
J
37:115-130
(1989).
52.
Hemminki
K,
Saloniemi
I,
Salonen
T,
Partanen
T,
Vainio
H.
Childhood
cancer
and
parental
occupation
in
Finland.
J
Epidemiol
Community
Health
35:11-15
(1981).
53.
Gold
EB,
Diener
MD,
Szklo
M.
Parental
occupations
and
cancer
in
children:
a
case-control
study
and
review
of
the
methodologic
issues.
J
Occup
Med
24:578-584
(1982).
54.
VanSteensel-Moll
HA,
Valkenburg
HA,
Van
Zanen
GE.
Childhood
leukemia
and
parental
occupation:
a
register-based
case-control
study.
Am
J
Epidemiol
121:216-224
(1985).
55.
Lowengart
RA,
Peters
JM,
Cicioni
C,
Buckley
J,
Bernstein
L,
Preston-Martin
S,
Rappaport
E.
Childhood
leukemia
and
par-
ents'
occupation
and
home
exposures.
J
Natl
Cancer
Inst
79:39-46
(1987).
56.
Laval
G,
Tuyns
AJ.
Environmental
factors
in
childhood
leukaemia.
Br
J
Ind
Med
45:843-844
(1988).
57.
Shu
XO,
Gao
YT,
Brinton
LA,
Linet
MS,
Tu
JT,
Zheng
W,
Fraumeni
JF
Jr.
A
population-based
case-control
study
of
child-
hood
leukemia
in
Shanghai.
Cancer
62:635-644
(1988).
58.
Buckley
JD,
Robison
LL,
Swotinsky
R,
Garabrant
DH,
LeBeau
M,
Manchester
P,
Nesbit
ME,
Odom
L,
Peters
JM,
Woods
WG,
et
al.
Occupational
exposures
of
parents
of
children
with
acute
nonlymphocytic
leukemia:
a
report
from
the
Children's
Cancer
Study
Group.
Cancer
Res
49:4030-4037
(1989).
59.
Gardner
MJ,
Snee
MP,
Hall
AJ,
Powell
CA,
Downes
S,
Terrell
JD.
Results
of
case-control
study
of
leukaemia
and
lymphoma
among
young
people
near
Sellafield
nuclear
plant
in
West
Cumbria.
Br
Med
J
300:423-439
(1990).
60.
Magnani
C,
Pastore
G,
Luzatto
L,
Terracini
B.
Parental
occu-
pational
and
other
environmental
factors
in
the
etiology
of
leukemias
and
non-Hodgkin's
lymphomas
in
childhood:
a
case-
control
study.
Tumori
76:413-419
(1990).
61.
Infante-Rivard
C,
Mur
P,
Armstrong
B,
Alvarez-Dardet
C,
Bolumar
F.
Acute
lymphoblastic
leukaemia
among
Spanish
children
and
mothers'
occupation:
a
case-control
study.
J
Epidemiol
Community
Health
45:11-15
(1991).
62.
Schwartzbaum
JA,
George
SL,
Pratt
CB,
Davis
B.
An
exploratory
study
of
environmental
and
medical
factors
poten-
tially
related
to
childhood
cancer.
Med
Pediatric
Oncology
19:115-121
(1991).
63.
Scheele
J,
Teufel
M,
Niessen
KH.
Chlorinated
hydrocarbons
in
the
bone
marrow
of
children:
studies
on
their
association
with
leukaemia.
Eur
J
Pediatr
151:802-805
(1992).
64.
Deschamps
M,
Band
P.
Study
of
a
cluster
of
childhood
leukemia.
Stat
Canada
Health
Rep
5:81-85
(1993).
65.
Roman
E,
Watson
A,
Beral
V,
Buckle
S,
Bull
D,
Baker
K,
Ryder
H,
Barton
C.
Case-control
study
of
leukaemia
and
non-
Hodgkin's
lymphoma
among
children
aged
0-4
living
in
West
Berkshire
and
North
Hampshire
health
districts.
Br
Med
J
306:615-621
(1993).
66.
Mulder
YM,
Drijver
M,
Kreis
IA.
Case-control
study
on
the
association
between
a
cluster
of
childhood
haematopoietic
malignancies
and
local
environmental
factors
in
Aalsmeer,
The
Netherlands.
J
Epidemiol
Community
Health
48:161-165
(1994).
67.
Meinert
R,
Kaatsch
P,
Kaletsch
U,
Krummenauer
F,
Miesner
A,
Michaelis
J.
Childhood
leukaemia
and
exposure
to
pesti-
cides:
results
of
a
case-control
study
in
Northern
Germany.
Eur
J
Cancer
32A:1943-1948
(1996).
68.
Chadduck
WM,
Gollin
SM,
Gray
BA,
Norris
JS,
Araoz
CA,
Tryka
AF.
Gliosarcoma
with
chromosome
abnormalities
in
a
neonate
exposed
to
heptachlor.
Neurosurgery
21:557-559
(1987).
69.
Fabia
J,
Thuy
TD.
Occupation
of
father
at
time
of
birth
of
children
dying
of
malignant
diseases.
Br
J
Prev
Soc
Med
28:98-100
(1974).
70.
Gold
E,
Gordis
L,
Tonascia
J,
Szklo
M.
Risk
factors
for
brain
tumors
in
children.
Am
J
Epidemiol
109:309-319
(1979).
71.
Sinks
TH
Jr.
N-Nitroso
compounds,
pesticides,
and
parental
exposures
in
the
workplace
as
risk
factors
for
childhood
brain
cancer:
a
case-control
study.
Ph.D.
dissertation.
Ohio
State
University,
Columbus,
OH,
1985.
72.
Wilkins
JR,
Koutras
RA.
Paternal
occupation
and
brain
cancer
in
offspring:
a
mortality-based
case-control
study.
Am
J
Ind
Med
14:299-318
(1988).
73.
Howe
GR,
Burch
JD,
Chiarelli
AM,
Risch
HA,
Choi
BCK.
An
exploratory
case-control
study
of
brain
tumors
in
children.
Cancer
Res
49:4349-4352
(1989).
74.
Wilkins
JR,
Sinks
TH.
Parental
occupation
and
intracranial
neoplasms
of
childhood:
results
of
a
case-control
interview
study.
Am
J
Epidemiol
132:275-292
(1990).
75.
Kuijten
RR,
Bunin
GR,
Nass
CC,
Meadows
AT.
Parental
occupational
and
childhood
astrocytoma:
results
of
a
case-con-
trol
study.
Cancer
Res
52:782-786
(1992).
76.
Davis
JR,
Brownson
RC,
Garcia
R,
Bentz
BJ,
Turner
A.
Family
pesticide
use
and
childhood
brain
cancer.
Arch
Environ
Contam
Toxicol
24:87-92
(1993).
77.
Cordier
S,
Iglesias
M-J,
LeGoaster
C,
Guyot
M-M,
Mandereau
L,
Hemon
D.
Incidence
and
risk
factors
for
childhood
brain
tumors
in
the
Ile
de
France.
Int
J
Cancer
59:776-782
(1994).
78.
Bunin
GR,
Buckley
JD,
Boesel
CP,
Rorke
LB,
Meadows
AT.
Risk
factors
for
astrocytic
glioma
and
primitive
neuroectoder-
mal
tumor
of
the
brain
in
young
children:
a
report
from
the
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
907
ZAHM
AND
WARD
Children's
Cancer
Group.
Cancer
Epidemiol
Biomarkers
Prev
3:197-204
(1994).
79.
McCredie
M,
Maisonneuve
P,
Boyle
P.
Antenatal
risk
factors
for
malignant
brain
tumours
in
New
South
Wales
children.
Int
J
Cancer
56:6-10
(1994).
80.
McCredie
M,
Maisonneuve
P,
Boyle
P.
Perinatal
and
early
postnatal
risk
factors
for
malignant
brain
tumours
in
New
South
Wales
children.
Int
J
Cancer
56:11-15
(1994).
81.
Pagoda
JM,
Preston-Martin
S.
Household
pesticides
and
risk
of
pediatric
brain
tumors.
Environ
Health
Perspect
105(11):1214-1220
(1997).
82.
Infante
PF,
Newton
WA.
Prenatal
chlordane
exposure
and
neuroblastoma.
N
Engl
J
Med
293:308
(1975).
83.
Spitz
MR,
Johnson
CC.
Neuroblastoma
and
paternal
occupa-
tion:
a
case-control
analysis.
Am
J
Epidemiol
121:924-929
(1985).
84.
Wilkins
JR
III,
Hundley
VD.
Paternal
occupational
exposure
to
electromagnetic
fields
and
neuroblastoma
in
offspring.
Am
J
Epidemiol
113:995-1008
(1990).
85.
Bunin
GR,
Ward
E,
Kramer
S,
Rhee
CA,
Meadows
AT.
Neuroblastoma
and
parental
occupation.
Am
J
Epidemiol
131:776-780
(1990).
86.
Buckley
JD.
Childhood
non-Hodgkin's
lymphoma.
Presented
at
the
National
Cancer
Institute
Workshop
on
the
Time
Trends
in
Non-Hodgkin's
Lymphoma:
Current
Knowledge
and
Recommendations
for
Research,
22-23
October
1991,
Bethesda,
MD.
87.
Kantor
AF,
McCrea
Curnen
MG,
Meigs
JW,
Flannery
JT.
Occupations
of
fathers
of
patients
with
Wilms's
tumour.
J
Epidemiol
Community
Health
33:253-256
(1979).
88.
Wilkins
JR
III,
Sinks
TH
Jr.
Occupational
exposures
among
fathers
of
children
with
Wilms'
tumor.
J
Occup
Med
26:427-435
(1984).
89.
Olshan
A,
Breslow
NE,
Falletta
JM,
Grufferman
S,
Pendergrass
T,
Robison
LL,
Waskerwitz
M,
Woods
WG,
Vietti
TJ,
Hammond
GD.
Risk
factors
for
Wilms'
tumor:
report
from
the
National
Wilms'
Tumor
Study.
Cancer
72:938-944
(1993).
90.
Sharpe
CR,
Franco
EL,
de
Camargo
B,
Lopes
LR,
Barreto
JH,
Johnsson
RR,
Mauad
MA.
Parental
exposures
to
pesticides
and
risk
of
Wilms'
tumor
in
Brazil.
Am
J
Epidemiol
141:210-217
(1995).
91.
Holman
CDJ,
Reynolds
PM,
Byrne
MJJ,
Trotter
JM,
Armstrong
BK.
Possible
infectious
etiology
of
six
cases
of
Ewing's
sarcoma
in
Western
Australia.
Cancer
52:1974-1976
(1983).
92.
Zamora
P,
de
Paredes
G,
Gonzalez
Baron
M,
Diaz
MA,
Escobar
Y,
Ordonez
A,
Lopez
Barea
F,
Gonzalez
JM.
Ewing's
tumor
in
brothers:
an
unusual
observation.
Am
J
Clin
Oncol
(CCT)
9:358-360
(1986).
93.
Daigle
AE.
Epidemiologic
study
of
etiologic
factors
in
Ewing's
sarcoma.
University
of
Minnesota.
Diss
Abstr
Int
B
Sci
Eng
47:2861
(1987).
94.
Holly
EA,
Aston
DP,
Ahn
PKA,
Kristiansen
JJ.
Ewing's
bone
sarcoma,
parental
occupational
exposure,
and
other
factors.
Am
J
Epidemiol
135:122-129
(1992).
95.
Winn
DM,
Li
FP,
Robison
LL,
Mulvihill
JJ,
Daigle
AE,
Fraumeni
JF
Jr.
A
case-control
study
of
the
etiology
of
Ewing's
sarcoma.
Cancer
Epidemiol
Biomarkers
Prev
1:525-532
(1992).
96.
Magnani
C,
Pastore
P,
Luzzatto
L,
Carli
M,
Lubrano
P,
Terracini
B.
Risk
factors
for
soft
tissue
sarcomas
in
childhood:
a
case-control
study.
Tumori
75:396-400
(1989).
97.
Pratt
CB,
Rivera
G,
Shanks
E,
Johnson
WW,
Howarth
C,
Terrell
W,
Kumar
APM.
Colorectal
carcinoma
in
adolescents:
implications
regarding
etiology.
Cancer
40:2464-2472
(1977).
98.
Pratt
CB,
George
SL,
O'Connor
D,
Hoffman
RE.
Adolescent
colorectal
cancer
and
dioxin
exposure
[Letter].
Lancet
ii(8562):803
(1987).
'-
99.
Caldwell
GG,
Cannon
SB,
Pratt
CB,
Arthur
RD.
Serum
pesti-
cide
levels
in
patients
with
childhood
colorectal
carcinoma.
Cancer
48:774-778
(1981).
100.
Mills
P,
Newell
GR,
Johnson
DE.
Testicular
cancer
associated
with
employment
in
agriculture
and
oil
and
natural
gas
extrac-
tion.
Lancet
i(8370):207-210
(1984).
101.
Shu
XO,
Nesbit
ME,
Buckley
JD,
Krailo
MD,
Robison
LL.
An
exploratory
analysis
of
risk
factors
for
childhood
malignant
germ-
cel
tumors:
report
from
the
Childrens
Cancer
Group
(Canada,
United
States).
Cancer
Causes
Control
6:187-198
(1995).
102.
Bunin
GR,
Petrakova
A,
McAdams
AT,
Emanuel
BS,
Buckley
JD,
Woods
WG,
Hammond
GD.
Occupations
of
parents
of
children
with
retinoblastoma:
a
report
from
the
Children's
Cancer
Study
Group.
Cancer
Res
50:7129-7133
(1990).
103.
Camann
DE.
Investigating
the
effects
of
pesticide
exposure
in
the
home.
Technol
Today
June:2-7
(1994).
104.
Maas
RP,
Kucken
DJ,
Patch
SC,
Peek
BT,
van
Engelen
DL.
Pesticides
in
eastern
North
Carolina
rural
supply
wells:
land
use
factors
and
persistence.
J
Environ
Qual
24:426-431
(1995).
105.
Nuckols
JR,
Faidi
H,
Xiang
H,
Stallones
L.
Application
of
GIS/RS
Technology
in
a
Rural
Environmental
Health
Study.
Paper
No
96-TI
1.
Columbia,
MO:National
Institute
for
Farm
Safety,
1996.
106.
Nuckols
JR,
Stallones
L,
Xiang
H,
Faidi
H.
Spatial
information
technology
and
analysis
in
health
assessment
of
rural
communi-
ties
[Abstract].
Epidemiology
7:S73
(1996).
107.
Ward
MH,
Nuckols
JR,
Weigel
S,
Maxwell
S,
Cantor
KP.
Unpublished
data.
108.
Zahm
SH,
Weisenburger
DD,
Saal
RC,
Vaught
JB,
Babbitt
PA,
Blair
A.
The
role
of
agricultural
pesticide
use
in
the
devel-
opment
of
non-Hodgkin's
lymphoma
in
women.
Arch
Environ
Health
48:353-358
(1993).
109.
Pottern
LM,
Brown
LM,
Linet
MS,
Blair
A.
Genetic
suscepti-
bility
and
occupational
exposure
in
the
etiology
of
leukemia
and
non-Hodgkin's
lymphoma.
Presented
at
the
Ninth
International
Symposium
on
Epidemiology
in
Occupational
Health,
21-25
September
1992,
Cincinnati,
OH,
1992.
110.
Zahm
SH,
Ward
MH,
Blair
A.
Pesticides
and
cancer.
In:
Occupational
Medicine:
State
of
the
Art
Reviews.
Vol
12:Pesticides
(Keifer
M,
ed).
Philadelphia:Hanley
and
Belfus,
Inc.,
1997;269-289.
111.
Zahm
SH,
Blair
A.
Cancer
among
migrant
and
seasonal
farm-
workers:
an
epidemiologic
review
and
research
agenda.
Am
J
Ind
Med
24:753-766
(1993).
112.
Zahm
SH,
Blair
A,
and
the
Farmworker
Epidemiology
Research
Group.
Cancer
feasibility
studies
among
migrant
farmworkers.
Am
J
Ind
Med
32:301-302
(1997).
908
Environmental
Health
Perspectives
*
Vol
106,
Supplement
3
*
June
1998
