Characterization
of
Epidemiology
Data
Relating
to
Prostate
Cancer
and
Exposure
to
Atrazine
July
17,
2003
Scientific
Advisory
Panel
2
Introduction
The
FIFRA
Scientific
Advisory
Panel
is
being
asked
to
review
and
consider
the
Agency's
analysis
of
evidence
that
exposure
to
atrazine
may
be
associated
with
an
increased
incidence
of
prostate
cancer
in
humans.
The
Agency's
analysis
considers
the
currently
available
epidemiology
data
and
largely
focuses
on
a
study
at
a
manufacturing
plant
in
Louisiana.
This
study,
initially
funded
by
Ciba­
Geigy,
later
by
Novartis,
and
now
by
Syngenta,
has
been
updated
a
number
of
times
over
the
years
as
more
data
on
the
mortality
and
incidence
of
disease
have
become
available.
The
study
was
conducted
by
Dr.
Elizabeth
Delzell
and
her
colleagues
at
the
University
of
Alabama.
In
addition,
the
Agency's
analysis
considers
a
recently
published
study
on
prostate
cancer
results
from
the
Agricultural
Health
Study
(
Alavanja
et
al.
2003)
and
a
correlation
analysis
of
pesticide
use
and
cancer
incidence
in
California
counties
(
Mills
1998).

The
National
Cancer
Institute
has
a
number
of
other
analyses
in
press
or
planned
which
are
relevant
to
atrazine.
Among
these
is
a
re­
analysis
of
earlier
studies
involving
pesticides
and
non­
Hodgkin's
lymphoma
using
hierarchical
techniques
to
adjust
for
the
effects
of
multiple
exposures.
This
report
is
expected
to
be
published
online
in
the
next
2­
3
months.
Further,
enough
additional
prostate
cancer
cases
have
been
added
in
the
Agricultural
Health
Study
since
the
recent
publication
that
the
analysis
can
be
redone
with
approximately
double
the
number
of
cases.
Re­
analysis
is
planned
later
this
year
and
may
be
ready
for
publication
by
next
year.
An
analysis
of
all
the
non­
Hodgkin's
lymphoma
cases
reported
in
the
Agricultural
Health
Study
is
planned
to
start
next
year.
And
a
special
analysis
of
all
cancers
related
to
atrazine
exposure
in
the
same
Agricultural
Health
Study
cohort
is
also
planned
for
this
year
with
publication
expected
next
year.
In
addition,
Syngenta
is
conducting
a
nested
case­
control
study
of
workers
at
the
St.
Gabriel
plant
using
more
detailed
job
histories
to
evaluate
exposure
indices.
This
study
should
be
available
later
this
year.
Given
the
importance
of
incorporating
these
results
into
an
evaluation
of
atrazine
for
prostate
cancer
and
other
cancer
outcomes,
the
Agency
plans
future
analyses
and
absent
compelling
information
in
the
interim,
will
wait
until
all
of
these
analyses
are
in
before
addressing
the
broader
question
of
atrazine
exposure
and
cancer.
This
paper
only
addresses
currently
available
information
on
atrazine
and
prostate
cancer.

Background
Earlier
reviews
of
atrazine
manufacturing
plant
workers
were
performed
by
EPA
in
1990,
1994,
and
1996.
The
latest
submission
by
Syngenta,
completed
October
12,
2001,
underwent
three
reviews
at
EPA
(
12/
13/
01,
3/
25/
02,
and
01/
15/
03).
The
first
review
concluded
that
it
would
be
appropriate
to
obtain
external
peer
review
comments.
Comments
were
obtained
from
epidemiologists
at
the
National
Cancer
Institute
(
NCI)
and
Harvard,
Dr.
Aaron
Blair
and
Dr.
Edward
Giovannucci,
and
incorporated
into
the
revised
review
dated
3/
25/
02.
This
review
led
to
a
request
to
Syngenta
for
additional
information
concerning
the
exposure
status
of
the
workers
at
the
manufacturing
plant.
In
addition,
public
comment
was
received
from
an
expert
peer
review
panel
hired
by
Syngenta
and
the
Natural
Resources
Defense
Council
with
divergent
3
interpretations
of
the
study
results.
A
third
round
of
external
peer
review
was
conducted
including
the
two
original
peer
reviewers
(
Drs.
Blair
and
Giovannucci)
and
two
additional
reviewers:
one
from
Health
and
Welfare
Canada
(
Dr.
Howard
Morrison)
and
one
from
the
National
Cancer
Institute
(
Dr.
Richard
Hayes).
Once
the
exposure
data
and
the
four
review
comments
were
received,
they
were
incorporated
into
the
EPA
review
dated
January
15,
2003.

The
overall
conclusion
of
the
most
recent
EPA
review
was
that
"
It
appears
that
most
of
the
increase
in
prostate
cancer
incidence
at
the
St.
Gabriel
plant
in
Louisiana
is
likely
due
to
intensive
PSA
screening.
The
study
was
insufficiently
large
and
suffered
from
other
limitations
that
prevent
ruling
out
atrazine
as
a
potential
contributor
to
the
increase
observed.
On
balance,
however,
a
role
for
atrazine
seems
unlikely
because
prostate
cancer
was
found
primarily
in
active
employees
who
received
intensive
PSA
screening,
there
was
no
increase
in
advanced
tumors
or
mortality,
and
proximity
to
atrazine
manufacturing
did
not
appear
to
be
correlated
with
risk."

The
key
data
to
be
addressed
by
the
Scientific
Advisory
Panel
primarily
involve
the
most
recent
analysis
of
incidence
at
the
St.
Gabriel
manufacturing
plant
in
Louisiana.
Workers
at
the
plant
received
intensive
screening
for
prostate
cancer
using
the
Prostate
Specific
Antigen
(
PSA)
test
which
increases
the
ability
to
detect
disease
that
would
not
otherwise
be
identified.
Additional
data
was
requested
and
received
concerning
the
relative
exposure
status
of
workers
who
were
diagnosed
with
prostate
cancer.
Further,
a
new
Agricultural
Health
Study
has
published
results
germaine
to
determining
the
risk
of
prostate
cancer
among
farmers
and
other
applicators
who
use
this
herbicide.
Each
of
these
studies
is
addressed
in
turn
below.

PSA
Screening
and
its
Effect
on
Prostate
Cancer
Incidence
An
epidemiology
study
was
conducted
of
workers
at
the
Syngenta
St.
Gabriel
plant
where
atrazine
is
manufactured
(
Delzell
et
al.
2001).
That
study
reported
a
statistically
significant
increase
in
the
incidence
of
prostate
cancer
among
plant
workers.
The
Standardized
Incidence
Ratio
(
SIR)
ranged
from
178
to
255
depending
on
the
comparison
population.
Workers
at
the
plant
received
an
extraordinarily
high
rate
of
PSA
screening
and
reports
in
the
literature
suggest
that
such
screening
could
easily
double
the
detection
of
prostate
cancer
(
see
citations
in
Adami
et
al.
2002
and
Blondell
2003
including
peer
review
by
Dr.
Giovannucci).
What
is
not
known
is
whether
the
PSA
screening
could
explain
the
entire
increase
observed
in
the
plant
workers,
especially
those
less
than
50
years
of
age.
Based
on
five
observed
cases,
workers
in
this
age
group
had
a
prostate
cancer
incidence
that
was
6.7
times
higher
than
the
Louisiana
State
population
(
95%
confidence
interval
was
2.2
to
15.7
times
higher)
and
4.0
times
higher
than
the
nearby
industrial
corridor
(
95%
confidence
interval
was
1.3
to
9.3
times
higher).

The
report
from
a
group
of
expert
scientists
(
Adami
et
al.
2002)
hired
by
Syngenta
concluded
that
an
apparent
5­
fold
increase
is
plausible
following
systematic
widespread
screening.
The
panel
pointed
out
the
observed
increase
is
fully
compatible
with
the
empirical
evidence
from
outside
sources.
With
respect
to
the
workers
in
the
Syngenta
St.
Gabriel
Plant,
the
expected
4
increase
among
those
screened
for
PSA,
many
of
whom
were
young
and
screened
repeatedly,
would
be
at
least
3
and
probably
around
3.5
given
the
young
age
of
those
screened
and
the
occurrence
of
repeated
screening
on
the
same
individual.
Since
92%
of
the
workers
had
been
screened
at
least
once
with
PSA,
the
expected
incidence
of
prostate
cancer
in
comparison
to
the
pre­
screen
incidence
would
be
3.3
times
higher
(
if
A=
prostate
cancer
incidence
identified
without
PSA
screening
and
92%
of
the
workers
have
been
screened,
then
prostate
cancer
detected
with
screening
is
0.08
x
A
+
0.92
x
3.5
x
A
=
3.3
x
A).
The
ratio
of
3.3/
1.48
[
1.48
is
the
expected
incidence
increase
in
Louisiana
due
to
PSA
screening
in
the
general
population]
equals
2.23,
which
multiplied
by
100
is
essentially
identical
to
the
SIR
estimates
for
prostate
cancer
among
the
workers
in
the
Novartis
St.
Gabriel
Plant
(
255
with
LA
state
comparison
and
178
with
industrial
corridor
comparison).
Later,
the
panel
supports
the
plausibility
of
a
5­
fold
increase
by
citing
the
Olmstead
County,
Minnesota
study
(
Roberts
et
al.
1999)
which
found
a
3.5­
fold
increase.
The
panel
of
expert
scientists
hired
by
Syngenta
concluded
that
the
"
prostate
cancer
incidence
has
increased
as
much
as,
but
no
more
than,
would
have
been
expected
.
.
.
There
is
neither
a
need
to
invoke,
nor
evidence
to
support,
the
contribution
of
environmental
factors
in
the
particular
occupational
setting
on
prostate
carcinogenesis."

EPA
asked
four
external
peer
reviewers
to
comment
on
the
comments
and
analysis
by
Adami
et
al.
(
2002).
One
of
the
external
reviewers,
Dr.
Giovannucci,
cited
other
studies
where,
in
his
opinion,
PSA
screening
was
responsible
for
sharp
increases
in
the
reported
incidence
of
prostate
cancer:
For
example,
in
one
study,
the
ratio
of
prostate
cancer
incidence
in
men
who
were
screened
with
PSA
was
6.5
times
higher
than
the
control
group.
In
essence,
there
were
6.5
times
more
prostate
cancers
diagnosed
due
solely
to
PSA
screening
(
BJU
International
2001;
88:
811­
17).
In
a
screening
trial
in
a
Finnish
population,
the
ratio
of
the
number
of
cases
detected
through
PSA
screening
in
the
first
year
relative
to
the
number
expected
based
on
age­
specific
incidence
rate
in
Finland
was
14.4
for
men
aged
55
years
(
Cancer
Causes
and
Control
2002;
13:
279­
285).
This
ratio
of
screened
detected
cases
to
unscreened
population
incidence
increased
with
age
so
the
potential
bias
in
men
aged
younger
than
55
years
would
be
even
greater
based
on
these
data.
Thus,
the
increased
excess
of
prostate
cancer
observed
in
the
Novartis
study
is
compatible
with
increases
expected
in
a
population
that
is
receiving
intensive
PSA
screening.

Note
that
Dr.
Giovannucci
finds
a
greater
effect
on
younger
ages
because
PSA
screening
detects
cases
years
before
the
other
evidence
would
make
a
prostate
cancer
case
evident.
Another
external
peer
reviewer,
Dr.
Blair,
agreed
that
the
report
by
Adami
et
al.
(
2002)
"
suggest[
s]
that
PSA
screening
may
well
explain
the
excess
incidence
of
prostate
cancer
in
this
cohort.
It
would
be
helpful,
however,
to
have
more
information
supporting
the
selection
of
[
the]
multiplication
factor
regarding
the
impact
of
age
and
other
factors
that
might
differ
between
a
cohort
of
working
individuals
and
the
general
population."
The
peer
reviewers
supported
the
idea
that
PSA
screening
was
responsible
for
ascertainment
bias
resulting
in
differential
detection
of
prostate
cancer
in
the
study
and
comparison
populations.
However,
they
did
not
all
agree
that
this
bias
ruled
out
atrazine
as
a
possible
contributor
to
the
excess
prostate
cancer
incidence
observed.
5
Additional
Exposure
Analysis
of
Manufacturing
Plant
Workers
At
EPA's
request,
Syngenta
prepared
an
atrazine
exposure
profile
of
employees
diagnosed
with
prostate
cancer.
There
were
17
cases,
including
14
Syngenta
cases
and
3
contract
employees.
Exposure
information
was
obtained
for
12
of
the
14
Syngenta
employees.
Two
of
the
14
Syngenta
cases
did
not
have
the
necessary
information
to
classify
by
exposure
but
were
concluded
to
have
low
exposure
based
upon
their
job
titles.
There
was
no
exposure
information
available
for
the
three
prostate
cancer
cases
among
contract
workers.
However,
contract
workers
accounted
for
62%
of
the
person
years
examined
and
their
period
of
exposure
was
a
median
of
2.6
years
compared
to
20
years
for
Syngenta
employees.
These
contract
employees
did
not
generally
receive
PSA
screening
and
the
incidence
of
prostate
cancer
in
the
contract
workers
was
not
significantly
higher
than
the
1.8
cases
expected,
based
on
using
Louisiana
as
the
comparison
population.
Using
the
local
industrial
corridor
as
a
comparison
population,
the
comparison
would
be
3
observed
prostate
cancer
cases
and
2.7
expected.
Therefore,
the
Agency
concludes
that
the
absence
of
exposure
information
for
contract
employees
is
not
of
particular
concern
because
the
observed
number
of
cases
is
close
to
expectation
and
the
duration
of
exposure
to
atrazine
is
relatively
low.

Analysis
was
performed
on
the
12
of
14
Syngenta
cases
for
which
exposure
information
was
available
using
two
methods.
First,
job
titles
were
obtained
from
commencement
of
employment
until
September
2002
or
when
employment
ended.
Jobs
were
then
classified
by
their
"
proximity
to
locations
in
the
plant
where
atrazine
is
manufactured,
handled,
or
packaged."
Of
the
30
different
jobs,
5
were
classified
as
remote,
17
were
classified
as
low,
4
were
classified
as
mid,
and
4
were
classified
as
high
physical
proximity
to
atrazine
production.
For
each
case,
the
proportion
of
time
in
each
category
of
exposure
was
assessed
and
then
cumulated
up
until
the
time
of
prostate
cancer
diagnosis.
For
the
second
method,
a
relative
atrazine
proximity
scale
was
developed.
Based
on
atrazine
airborne
dust
monitoring
data,
remote,
low,
mid
and
high
proximity
areas
were
found
to
differ
by
an
order
of
magnitude.
Thus,
each
category
could
be
assigned
a
relative
exposure
factor
of
0.1,
1,
10,
and
100.
This
value
was
multiplied
by
the
duration
at
each
type
of
location
and
cumulated
to
create
an
index
of
exposure.
This
index
of
exposure
was
adjusted
for
reductions
in
exposure
due
to
changes
at
the
plant
in
1984­
85.

Results
from
the
method
of
classifying
jobs
by
proximity
found
that
the
12
cancer
cases
spent
46%
of
their
plant
time
in
low
proximity
positions,
26%
in
medium
proximity,
and
28%
in
high
proximity
to
atrazine
production.
The
majority
of
the
high
proximity
time
was
due
to
three
of
the
cancer
cases
spending
the
majority
of
their
working
time
in
these
positions.

This
analysis
was
supported
by
the
cumulative
index
of
exposure
method.
Three
cases
had
high
proximity
to
atrazine
production
throughout
their
working
career
at
the
plant
with
a
cumulative
index
greater
than
10,000.
Four
cases
had
a
medium
exposure
with
a
cumulative
index
greater
than
1,000
and
less
than
10,000.
The
remaining
five
cases
had
a
low
exposure
index
(
less
than
1,000).
As
noted
above,
the
two
unassessed
cases
were
likely
to
be
low
proximity
based
on
their
job
titles.
6
Further
analysis
did
not
find
any
relationship
between
age
at
diagnosis
and
proximity
to
atrazine.
Had
their
been
such
a
relationship,
it
would
have
supported
the
possibility
that
atrazine
was
a
causative
factor
in
the
subsequent
diagnosis.
At
least
12
of
the
employees
with
prostate
cancer
participated
in
the
screening
program
and
10
of
them
were
initially
detected
due
to
the
PSA
screening.
Of
the
total
14
Syngenta
cases,
12
had
early
stage
localized
prostate
cancer
and
2
had
regional
cancer
within
the
prostate.
"
No
distant,
advanced
stage,
metastasized
cancer
was
detected
in
Syngenta
employees."
Together
these
results
are
consistent
with
the
conclusion
that
the
observed
significant
excess
in
prostate
cancer
at
the
Syngenta
plant
in
Louisiana
was
more
likely
an
artifact
of
the
extensive
PSA
screening
program
than
a
result
of
exposure
to
atrazine.

A
major
difficulty
with
the
above
information
was
the
lack
of
comparable
information
for
the
workers
without
prostate
cancer.
This
additional
information
was
requested
and
provided
in
tabular
form,
although
it
was
not
available
to
peer
reviewers.
A
copy
is
provided
below:

Table
1.
Estimated
Number
(%)
of
Male
Employees
at
St.
Gabriel
at
the
End
of
Each
Year
(
Syngenta
Male
Employees
Only)

Proximity
to
Atrazine
Manufacturing
Year
1977
1986
1996
2002
Low
205
(
72%)
275
(
77%)
306
(
79%)
291
(
80%)

Moderate
20
(
7%)
20
(
6%)
20
(
5%)
19
(
5%)

High
60
(
21%)
60
(
17%)
63
(
16%)
55
(
15%)

Total
Number
285
355
389
365
Based
on
this
Table,
an
average
of
77%
of
Syngenta
employees
had
low
proximity
to
atrazine
manufacturing;
an
average
of
6%
had
moderate
proximity;
and
17%
had
high
proximity
to
atrazine
manufacturing.
Of
the
14
prostate
cancer
cases,
50%
were
classified
as
low
proximity
to
atrazine
manufacturing,
28%
were
classified
as
moderate
proximity,
and
21%
were
classified
as
high
proximity.
It
appears
that
there
would
be
no
strong
evidence
of
dose­
response,
although
a
higher
proportion
of
diagnosed
workers
(
50%
versus
23%)
were
involved
in
jobs
with
moderate
or
high
proximity
to
atrazine
manufacturing.
Chi­
square
tests
performed
by
Breckenridge
(
2003)
found
a
higher
than
expected
incidence
of
prostate
cancer
cases
was
distributed
to
the
moderate
proximity
subgroup.
EPA
determined
that
no
strong
conclusions
should
be
drawn
from
this
crude
comparison.
A
proper
comparison
would
require
measuring
the
exposure
of
cases
and
non­
cases
in
the
same
manner
and
taking
into
account
confounders
such
as
age
and
person­
years
of
exposure.
Syngenta
acknowledges
this
shortcoming
and
is
planning
a
case­
control
study
within
the
cohort
to
address
this
issue.
External
peer
reviewers
only
had
access
to
the
exposure
catagorization
of
the
prostate
cancer
cases,
not
the
other
plant
workers.
So
their
conclusions
were
limited
because
they
could
not
examine
the
data
presented
above.
7
New
Results
from
Agricultural
Health
Study
in
Iowa
and
North
Carolina
Tied
into
the
assessment
of
atrazine
and
prostate
cancer
is
the
recently
published
study
Alavanja
et
al.
(
2003).
This
large
prospective
cohort
study
of
55,332
male
pesticide
applicators,
known
as
the
Agricultural
Health
Study,
reported
on
the
risk
of
prostate
cancer
and
computed
odds
ratios
for
individual
pesticides
within
the
cohort.
Results
for
atrazine,
presented
in
Table
5,
reported
an
odds
ratio
of
0.94
for
ever/
never
use
reported
by
questionnaire
with
a
95%
confidence
interval
of
0.78
to
1.14.
The
Agricultural
Health
Study
has
a
number
of
advantages
over
other
epidemiologic
studies
of
pesticides.
It
is
the
largest
study
of
its
kind,
determines
exposure
prior
to
disease
(
thus,
eliminating
recall
bias),
analyzes
a
wide
variety
of
potential
and
known
confounders
including
other
pesticide
exposures,
and
has
greater
statistical
power
to
detect
small
effects.
Given
the
relatively
tight
confidence
interval
and
based
on
this
study
alone,
the
Agency
concludes
that
atrazine
is
an
unlikely
cause
of
prostate
cancer
among
farmers.
Seasonal
exposure
among
commercial
and
private
applicators
in
the
Agricultural
Health
Study
is
very
different
from
the
year
round
exposure
in
the
Delzell
et
al.
study
described
above.
On
the
one
hand
intensity
of
exposure
in
an
uncontrolled
agricultural
environment
may
be
greater
for
certain
individuals
(
e.
g.,
exposed
to
spill
or
hose
break
without
personal
protective
equipment),
but
the
duration
of
exposure
(
days
per
year)
is
considerably
less.
This
raises
the
question
about
the
ability
to
compare
workers
in
the
field
versus
workers
in
a
manufacturing
plant
which
the
Agency
is
asking
the
Scientific
Advisory
Panel
to
address.

Correlational
analysis
of
pesticide
use
data
and
cancer
incidence
in
California
counties
California
has
maintained
a
population­
based
cancer
registry
since
1988
and
a
state­
wide
pesticide
use
reporting
system.
Mills
(
1998)
obtained
1993
pesticide
usage
data
for
six
pesticides
with
a
suspicion
of
carcinogenicity
based
on
other
toxicologic
and
epidemiologic
studies.
These
data
were
compared
using
regression
analysis
with
county
age­
and
race­
adjusted
cancer
incidence
rates
(
1988­
92).
A
borderline
statistically
significant
correlation
was
found
between
atrazine
usage
and
prostate
cancer
in
black
males.
This
study
is
subject
to
aggregation
bias
because
exposure
of
individuals
in
the
county
were
not
measured.
EPA
considers
such
studies
useful
for
guiding
future
studies,
but
not
for
reaching
conclusions
about
causation.

Table
2
below
summarizes
the
pertinent
epidemiologic
studies
relating
prostate
cancer
and
atrazine
exposure.
The
table
includes
a
new
study
by
Mills
and
Yang
(
2003)
which
was
not
considered
in
this
background
paper
because
it
did
not
consider
exposure
to
atrazine.
However,
it
is
included
in
the
table
because
its
result
may
affect
the
Scientific
Advisory
Panel's
interpretation
of
the
Mills
(
1998)
study.
The
later
study
by
Mills
and
Yang
(
2003)
did
not
include
atrazine
as
one
of
the
chemicals
for
analysis.
This
suggests
that
the
authors
did
not
consider
the
earlier
finding
strong
enough
to
warrant
follow­
up
or,
perhaps,
the
relatively
low
usage
of
atrazine
in
California
was
insufficient
for
the
more
detailed
analysis
employed
in
their
later
study.
8
Table
2.
Summary
of
epidemiologic
studies
related
to
atrazine
and
prostate
cancer
Reference,
location
Subjects
Exposure
contrast
SIR*
or
OR*
(
95%
CI)

Alavanja
et
al.
2003,
Iowa,
North
Carolina
364
cases
with
use
202
never
used
ever
exposed
to
atrazine
versus
never
exposed
(
cohort
55,332)
OR
=
0.9
(
0.8­
1.1)

Delzell
et
al.
2001,
LA
manuf.
plant
757
plant
workers
screened
for
PSA
plant
worker
incidence
compared
to
Louisiana
State
SIR
=
255**
(
148­
408)

same
as
above
same
as
above
plant
worker
incidence
compared
to
industrial
corridor
SIR
=
178
(
104­
285)

Mills
and
Yang
2003,
California***
222
cases
1110
controls
high
area
use
of
simazine
versus
low
use
(
atrazine
not
measured)
OR
=
1.5
(
1.02­
2.3)

Mills
1998,
California
geographic
analysis
by
county
significant
correlation
between
prostate
cancer
in
Black
males
and
atrazine
use
by
county
r
=
0.67
(
CI
=
.01­.
97)

*
SIR
=
Standardized
Incidence
Ratio,
OR
=
Odds
Ratio.
**
Statistically
significant
findings
in
bold
type.
***
This
study
is
provided
because
it
is
a
follow­
up
to
the
earlier
Mills
1998
study.

Conclusion
EPA
concludes
that
the
available
data
do
not
support
a
likely
relationship
between
atrazine
exposure
and
prostate
cancer.
It
appears
that
most
of
the
apparent
increase
in
prostate
cancer
incidence
at
the
St.
Gabriel
plant
in
Louisiana
is
likely
due
to
more
complete
detection
through
intensive
PSA
screening.
The
study
was
insufficiently
large,
which
prevented
more
detailed
analyses
that
could
have
better
defined
the
relationships
between
exposure
and
disease.
The
study
suffered
from
lack
of
careful
assessment
of
exposure
in
cases
and
comparison
populations.
These
limitations
prevent
ruling
out
atrazine
as
a
potential
contributor
to
the
increase
observed.
On
balance,
however,
a
role
for
atrazine
seems
unlikely
because
prostate
cancer
was
found
primarily
in
active
employees
who
received
intensive
PSA
screening,
there
was
no
increase
in
advanced
tumors
or
mortality,
and
proximity
to
atrazine
manufacturing
did
not
appear
to
be
correlated
with
risk.
The
Agricultural
Health
Study
did
have
sufficient
power
but
did
not
find
an
association
between
atrazine
use
among
agricultural
applicators
in
Iowa
and
North
Carolina
and
incidence
of
prostate
cancer.

This
background
paper
is
based
primarily
on
EPA's
"
Review
of
Additional
Data
on
Potential
Atrazine
Exposure
and
Review
Comments
Submitted
by
Syngenta
and
NRDC
on
the
Atrazine
Cancer
Epidemiology
Study"
(
Blondell
2003).
This
complete
16
page
review
should
be
used
by
the
Scientific
Advisory
Panel
as
a
primary
document
stating
the
Agency's
position.
Attached
to
the
16
page
review
are
copies
of
all
four
external
peer
reviews.
9
Epidemiologic
studies
and
reviews
relevant
to
prostate
cancer
and
atrazine
Alavanja
MCR,
Samanic
C,
Dosemeci
M,
et
al.
2003.
Use
of
agricultural
pesticides
and
prostate
cancer
risk
in
the
Agricultural
Health
Study
cohort.
Am
J
Epidemiol
157:
800­
814.

Breckenridge
CB.
2002.
Summary
of
information
on
potential
atrazine
exposure
for
12
out
of
17
prostate
cancer
cases
reported
by
Delzell
et
al.
2001.
Nov.
1,
2002.
[??
resolve
confidentiality]

Breckenridge
C.
Jan.
16th
and
17th,
2003.
St.
Gabriel
Workforce:
male
Syngenta
Employees
excluding
contract
manufacturers.
Two
Emails
to
Jerry
Blondell
with
Attached
Table.

Delzell
E,
et
al.
2001.
Cancer
Incidence
Among
Workers
in
Triazine­
related
Operations
at
the
Novartis
St.
Gabriel
Plant"
Oct.
12,
2001.
MRID#
451521­
01
and
455184­
01,
Chemical
#
080803.
[
Technical
Report
170
pp.]

MacLennan
PA,
Delzell
E,
Sathiakumar
N,
et
al.
2002.
Cancer
incidence
among
triazine
herbicide
manufacturing
workers.
J
Occup
Environ
Med.
44:
1048­
1058.

MacLennan
PA,
Delzell
E,
Sathiakumar
N,
et
al.
2003.
Mortality
among
triazine
herbicide
manufacturing
workers.
J
Toxicol
Environ
Health
A
66(
6):
501­
517.

Mills
PK,
Yang
R.
Prostate
cancer
risk
in
California
farm
workers.
2003.
J
Occup
Environ
Med.
45:
249­
258.

Mills
PK.
1998.
Correlation
analysis
of
pesticide
use
data
and
cancer
incidence
rates
in
California
counties.
Arch
Environ
Health.
53:
410­
3.
[
also
relevant
to
other
cancers]

Review
comments
on
the
above
studies
Adami
H,
Colditz
G,
Mandel
J,
Trichopoulos
D.
2002.
An
evaluation
of
the
report
by
Dr.
Delzell
et
al.,
2001
on
"
A
follow­
up
study
of
cancer
incidence
among
workers
in
triazine
operations
at
the
Novartis
St.
Gabriel
plant".
July
2002.

Blondell
J.
Jan.
15,
2003.
Review
of
Additional
Data
on
Potential
Atrazine
Exposure
and
Review
Comments
Submitted
by
Syngenta
and
NRDC
on
Atrazine
Cancer
Epidemiology
Study:
"
Followup
Study
of
Cancer
Incidence
Among
Workers
in
Triazine­
related
Operations
at
the
Novartis
St.
Gabriel
Plant"
by
Elizabeth
Delzell
et
al.
DP
Barcode
D287278,
MRID#
455184­
01,
Chemical
#
080803.
Includes
attached
are
external
peer
review
comments
by
Dr.
Howard
Morrison,
Health
and
Welfare
Canada
(
12/
23/
02),
Dr.
Edward
Giovannucci,
Harvard
School
of
Public
Health
(
12/
31/
02),
Dr.
Richard
Hayes,
National
Cancer
Institute
(
1/
8/
03),
and
Dr.
Aaron
Blair,
National
Cancer
Institute
(
12/
23/
03).

Natural
Resources
Defense
Council.
2003.
Comments
on
the
Atrazine
IRED.
May
5,
2003.
10
Questions
for
the
Science
Advisory
Panel
1.
After
reviewing
the
study
of
manufacturing
workers
at
the
Syngenta
St.
Gabriel
plant;
the
comments
of
EPA
external
peer
reviewers;
and
public
comments
from
the
Syngenta
sponsored
peer
review
and
the
Natural
Resources
Defense
Council,
and
the
supplemental
exposure
analysis
conducted
for
the
St.
Gabriel
plant
workers,
EPA
has
concluded
that
the
increase
in
prostate
cancer
observed
in
the
St.
Gabriel
manufacturing
plant
workers
could
be
explained
by
the
increase
in
PSA
screening
for
these
workers.
Due
to
lack
of
detailed
exposure
analysis
based
on
job
history
and
the
limited
statistical
power
due
to
small
sample
size,
atrazine
could
not
be
ruled
out
as
a
potential
cause
but
a
role
for
atrazine
seems
unlikely.
Please
comment
on
EPA's
conclusion.
Please
identify
any
additional
data
or
analyses
of
the
St.
Gabriel
cohort
that
the
Agency
should
consider
before
reaching
a
final
conclusion.

2.
Other
available
studies
may
assist
the
assessment
of
the
potential
for
association
between
atrazine
exposure
and
prostate
cancer.
Agricultural
workers
generally
have
much
shorter
duration
of
exposure
compared
to
workers
at
a
manufacturing
plant.
In
addition,
agricultural
workers
are
expected
to
have
a
different
pattern
of
exposure
compared
to
manufacturing
workers
(
e.
g.,
intensity,
seasonality,
routes
of
exposure).
Please
comment
on
comparing
the
results
of
the
epidemiology
study
of
prostate
cancer
conducted
in
the
St.
Gabriel
plant
to
the
results
of
the
Agricultural
Health
Study,
considering
that
the
participants
in
these
two
studies
were
likely
to
have
experienced
different
exposures.
Discuss
what
such
a
comparison
indicates
about
a
relationship
between
exposure
to
atrazine
and
prostate
cancer.
