UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
January
14,
2004
MEMORANDUM
SUBJECT:
Review
of
2,4­
D
Incident
Reports
DP
Barcode
D297233,
Chemical#
030001­
81
(
includes
all
salts,
esters)

FROM:
Jerome
Blondell,
Ph.
D.,
Health
Statistician
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)

Monica
S.
Hawkins,
M.
P.
H.,
Environmental
Health
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)

THRU:
Francis
B.
Suhre,
Chief
Chemistry
and
Exposure
Branch
Health
Effects
Division
(
7509C)

TO:
Timothy
Dole,
Industrial
Hygienist
Reregistration
Branch
1
Health
Effects
Division
(
7509C)

BACKGROUND
The
following
data
bases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
2,4­
D
(
PC
Code:
030001):

1)
OPP
Incident
Data
System
(
IDS)
­
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
2)
Poison
Control
Centers
­
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
2
Poison
Control
Centers
(
PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65­
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.

3)
California
Department
of
Pesticide
Regulation
­
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(
worker
activity),
type
of
illness
(
systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.

4)
National
Pesticide
Telecommunications
Network
(
NPTN)
­
NPTN
is
a
toll­
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984­
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.

2,4­
D
REVIEW
I.
Incident
Data
System
Incident#
1317­
1
A
pesticide
incident
occurred
in
1994,
when
a
male
pesticide
applicator
applied
herbicides
that
contained
the
product
for
nine
years.
The
man
reported
sinus
problems
and
a
pre­
existing
tremor
condition
that
worsened
after
eight
years.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
1332­
1
A
pesticide
incident
occurred
in
1973,
after
a
man
applied
herbicides
containing
the
product
for
about
15
years.
After
13
years,
he
reported
psoriasis
and
dermatitis.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
1534­
1
A
pesticide
incident
occurred
in
1994,
when
a
seaman
used
herbicides
that
contained
the
product.
Fifteen
years
later,
he
reported
damage
to
end
organs
and
respiratory
system,
nervous
system
disorders,
neurological
damage,
the
inability
to
heal
properly,
skin
problems,
skin
rash,
and
chloracne.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
2796­
67
A
pesticide
incident
occurred
in
1994,
when
an
organic
grower's
neighbor
applied
the
3
product
that
drifted
toward
his
nursery.
The
man
reported
a
sore
throat.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
2796­
99
A
pesticide
incident
occurred
in
1994,
when
an
individual
reported
watery
eyes,
nausea,
vomiting,
grogginess,
and
a
headache
that
lasted
for
two
days
after
the
product
was
applied
to
crops.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
3258­
1
A
pesticide
incident
occurred
in
1996,
when
an
aerial
applicator
treated
a
large
field
with
the
product.
The
applicator
passed
over
a
house
that
was
adjacent
to
the
field
and
apparently
did
not
shut
off
the
spray.
Two
men
were
standing
in
the
yard
at
the
same
time.
One
of
the
men
returned
home
and
immediately
showered.
The
second
man
reported
skin
irritation
and
a
burning
sensation
on
his
face,
neck,
head,
and
chest,
and
a
sore
throat.
He
was
treated
by
a
physician
and
released
from
the
hospital
and
referred
to
a
dermatologist.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
3965­
16
A
pesticide
incident
occurred
in
1994,
when
the
product
was
applied
in
the
right­
of­
way.
Specific
symptoms
were
not
mentioned.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
3965­
34
A
pesticide
incident
occurred
in
1996,
when
the
product
was
applied
to
the
lawn.
An
individual,
who
has
severe
asthma,
was
exposed
to
the
product.
Specific
symptoms
were
not
mentioned.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
4426­
1
A
pesticide
incident
occurred
in
1996,
when
a
woman
applied
the
product
that
spilled
on
her
legs
and
feet.
She
reported
thrombocytopenia.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
6167­
1
A
pesticide
incident
occurred
in
1997,
when
an
individual,
who
did
not
wear
personal
protective
equipment,
applied
the
product
regularly.
The
individual's
face,
legs,
and
arms
are
usually
soaked
with
the
product.
The
individual
reported
tremors
and
facial
fasciculation
for
eight
months
and
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
7096­
1
A
pesticide
incident
occurred
in
1998,
when
an
individual
reported
nausea,
vomiting,
respiratory
problems,
coughing,
and
a
fever
of
102
degrees.
After
reviewing
the
label
and
the
4
MSDS,
a
physician,
who
treated
the
individual,
stated
that
the
symptoms
may
have
been
caused
by
something
other
than
exposure
to
the
product.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
7587­
72
A
pesticide
incident
occurred
in
1996,
when
a
fifty­
seven
year
old
woman
applied
the
product
to
control
blackberries
on
her
property.
She
accidentally
wiped
her
eyes
with
her
hands
and
reported
eye
irritation.
The
woman
was
treated
in
the
emergency
room.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
7587­
98
A
pesticide
incident
occurred
in
1996,
when
a
forty­
three
year
old
man,
who
is
a
nursery
employee,
reported
dizziness
after
mowing
the
grass
in
an
area
that
was
sprayed
with
the
product.
The
product
was
applied
the
previous
day.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
7587­
131
A
pesticide
incident
occurred
in
1996,
when
a
fifty­
three
and
forty­
seven
year
old
woman
reported
malaise.
The
two
women
noticed
an
odor
after
the
product
was
applied
near
their
home.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
8376­
1
A
pesticide
incident
occurred
in
1998,
when
a
man
reported
burning
and
red
skin
after
the
product
soaked
through
his
clothes
to
his
skin.
The
man
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
8766­
1
A
pesticide
incident
occurred
in
1999,
when
a
17
year
old
female
reported
hives
on
her
neck.
Five
days
earlier,
the
lawn
at
her
school
was
treated
with
the
product.
The
female
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
8766­
2
A
pesticide
incident
occurred
in
1999,
when
an
adult
developed
a
rash
4­
5
days
after
application.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
9057­
1
A
pesticide
incident
occurred
in
1999,
when
a
seventy­
two
year
old
woman
hoed
an
area
in
her
yard
after
her
grandson
sprayed
thistles
in
the
yard.
She
reported
leg
and
stomach
pain
three
weeks
later
and
was
later
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
9694­
1
A
pesticide
incident
occurred
in
1999,
when
a
thirty­
six
year
old
man
reported
second
and
third
degree
burns,
edema,
erythema,
and
respiratory
irritation.
The
product
was
applied
to
an
5
area
adjacent
to
the
man
who
was
exposed
to
the
drift.
He
was
admitted
to
the
hospital
for
six
days.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
10075­
2
A
pesticide
incident
occurred
in
2000,
when
a
sixty­
three
year
old
man
reported
ocular
irritation
and
pain
while
mixing
and
loading
the
product.
He
was
treated
in
an
emergency
room
and
diagnosed
with
corneal
abrasion.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
10112­
1
A
pesticide
incident
occurred
in
2000,
when
a
sixty­
nine
year
old
man
reported
dizziness.
He
was
mixing
and
loading
the
product
that
splashed
in
his
face.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
10621­
1
A
pesticide
incident
occurred
in
1999,
when
a
sixty­
nine
year
old
man,
who
did
not
wear
personal
protective
equipment,
reported
coughing
up
blood
and
choking
four
days
after
after
he
applied
the
product.
He
was
treated
by
a
physician
and
was
diagnosed
with
pneumonia.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
10629­
1
A
pesticide
incident
occurred
in
2000,
when
a
man
sprayed
his
lawn
and
became
dizzy
the
following
day
and
again
four
days
later.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
10831­
17
A
pesticide
incident
occurred
in
2000,
when
a
man,
who
was
doing
a
line
opening
procedure,
reported
skin
irritation
on
his
neck.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
11251­
7
A
pesticide
incident
occurred
in
2001,
when
a
woman
was
working
in
a
building
packaging
the
herbicide
and
reported
coughing,
lightheadedness,
dry
heaves,
vomiting,
headache,
and
a
burning
sensation
on
her
left
lateral
thigh.
She
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
11251­
8
In
2000,
a
news
article
reported
a
suspicious
case
in
New
Zealand
where
a
man
was
exposed
to
2,4­
D
drift
and
later
developed
Parkinsonism.
Details
of
the
exposure
and
documentation
are
not
provided
in
this
new
article.

Incident#
11633­
2
A
pesticide
incident
occurred
in
2001,
when
a
sprayer
was
exposed
after
their
back
pack
leaked
the
product.
The
sprayer
reported
skin
irritation.
No
further
information
on
the
6
disposition
of
the
case
was
reported.

Incident#
11639­
1
A
pesticide
incident
occurred
in
2001,
when
a
forty­
three
year
old
man
reported
nausea,
myalgia,
and
a
fever
after
the
hose
unhooked
and
the
product
got
on
his
clothes.
An
hour
later,
he
removed
his
clothes
and
then
showered.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
11639­
2
A
pesticide
incident
occurred
in
2001,
when
a
sixty­
seven
year
old
man
reported
malaise,
anorexia,
and
weight
loss.
The
man
used
the
product
the
previous
week.
He
also
had
major
surgery
about
the
same
time.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
11987­
1
A
pesticide
incident
occurred
in
2001,
when
a
thirty­
nine
year
old
man
reported
nausea,
abdominal
pain,
and
weight
loss
after
he
applied
the
product
to
his
lawn.
He
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12120­
1
A
pesticide
incident
occurred
in
2001,
when
a
man
reported
anorexia,
nausea,
muscle
weakness,
chills,
and
sweating
after
he
applied
the
product
while
working
for
three
consecutive
days.
He
was
treated
by
his
physician
who
reportedly
diagnosed
an
infection.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12399­
1
A
pesticide
incident
occurred
in
2000,
when
a
forty­
four
year
old
woman
reported
a
miscarriage,
chest
tightness
and
pain,
headache,
and
prolonged
bleeding.
The
product
was
applied
to
a
pasture.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12771­
4
A
pesticide
incident
occurred
in
2002,
when
a
man
got
some
of
the
product
on
his
foot
and
reported
skin
irritation.
He
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12887­
1
A
pesticide
incident
occurred
in
2002,
when
a
eight
year
old
boy
reported
vomiting
and
strep
throat.
The
boy
drove
his
off­
road
wheeler
in
a
pasture
that
was
treated
with
the
product.
Significant
exposure
from
the
pasture
is
very
unlikely
and
symptoms
are
not
consistent
with
exposure.
He
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12936­
1
A
pesticide
incident
occurred
in
2002,
when
a
fifty­
nine
year
old
man
reported
lightheadedness,
chest
pain,
hypertension,
dizziness,
hypertension,
and
other
cardiovascular
7
symptoms
similar
to
a
heart
attack.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
12991­
1
A
pesticide
incident
occurred
in
2002,
when
a
man
reported
nausea
and
diarrhea
after
spraying
the
diluted
product
two
days
earlier.
The
product
accidentally
got
on
his
skin.
Symptoms
are
considered
inconsistent
with
short­
term
skin
contact.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
13109­
1
A
pesticide
incident
occurred
in
2002,
when
a
neighbor
was
accused
of
maliciously
using
the
product
to
poison
the
water
supply
of
another
neighbor.
The
individual
drank
contaminated
water
for
about
a
week
and
reported
abdominal
and
kidney
pain.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
13251­
1
A
pesticide
incident
occurred
in
2002,
when
a
woman,
who
did
not
wear
personal
protective
equipment,
reported
skin
irritation,
pain,
and
a
rash
after
the
diluted
product
spilled
on
her
hands.
She
did
not
wash
her
hands
for
three
hours
after
the
exposure.
The
woman
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
13281­
14
A
pesticide
incident
occurred
in
2002,
when
a
fifty­
one
year
old
man,
who
is
a
truck
driver,
reported
difficulty
breathing,
vomiting,
nausea,
and
a
headache.
The
product
was
on
the
inside
of
his
truck
and
a
strong
odor
was
present.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
13578­
1
A
pesticide
incident
occurred
in
2002,
when
an
individual
ingested
approximately
150
ml
of
a
640
g/
l
solution
(
96
grams
swallowed)
of
the
product
in
a
suicide
attempt.
The
individual
was
transported
to
the
hospital
and
later
died
of
multiple
organ
failure.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
13883­
14
A
pesticide
incident
occurred
in
1997,
when
the
product
was
applied
and
drifted
onto
a
person,
car,
and
a
garden.
Specific
symptoms
were
not
mentioned.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
14150­
1
A
pesticide
incident
occurred
in
2002,
when
a
seventy­
eight
year
old
woman
reported
nausea,
dizziness,
fatigue,
and
difficulty
sleeping.
She
sprayed
crops
with
a
backpack
sprayer
and
did
not
wear
personal
protective
equipment.
The
woman
was
treated
by
a
physician.
No
further
8
information
on
the
disposition
of
the
case
was
reported.

Incident#
14167­
1
A
pesticide
incident
occurred
in
2003,
when
a
thirty­
two
year
old
man
reported
melena,
weight
loss,
and
bleeding
ulcers.
He
used
the
product
at
work
at
unknown
concentrations
for
several
hours
at
a
time.
He
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
14318­
5
A
pesticide
incident
occurred
in
2002,
when
the
product
was
applied
to
the
lawn
by
an
individual's
neighbor.
The
individual
reported
coughing,
a
sore
and
swollen
throat,
and
chest
pain.
The
individual
was
treated
by
a
physician
and
diagnosed
with
severe
respiratory
distress
and
chemical
inhalation
injury.
A
few
days
later,
the
individual
was
admitted
to
the
hospital
overnight
with
dehydration,
nausea,
and
muscle
cramps.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
14457­
2
A
pesticide
incident
occurred
in
2003,
when
a
seventy­
three
year
old
man
reported
pruritis
on
his
hands,
feet,
legs,
and
arms
which
persisted
for
3
weeks.
The
man
was
treated
by
a
physician.
No
further
information
on
the
disposition
of
the
case
was
reported.

II.
Poison
Control
Center
Data
­
1993
through
1998
Results
for
the
years
1993
through
1998
are
presented
below
for
occupational
cases,
nonoccupational
involving
adults
and
older
children,
and
for
children
under
age
six.
Cases
involving
exposures
to
multiple
products
and
cases
with
unrelated
medical
outcome
are
excluded.
Tables
1­
4
present
the
hazard
information
for
2,4­
D
compared
with
all
other
pesticides
on
six
measures:
percent
with
symptoms,
percent
with
moderate,
major,
or
fatal
outcome,
percent
with
major
or
fatal
outcome,
percent
of
exposed
cases
seen
in
a
health
care
facility,
and
percent
hospitalized
and
percent
seen
in
a
critical
care
facility.
Table
1
reports
the
number
of
cases
on
which
the
data
derived
in
Tables
2­
4
are
based.
Table
2
presents
this
information
for
occupational
cases,
Table
3
for
non­
occupational
cases
involving
adults
and
older
children
(
six
years
or
older),
and
Table
4
for
children
under
age
six.

Table
1.
Number
of
2,4­
D
exposures
reported
to
the
Toxic
Exposure
Surveillance
System
(
AAPCC),
number
with
determined
outcome,
number
seen
in
a
health
care
facility
for
occupational
and
non­
occupational
cases
(
adults
and
children
six
years
and
older)
and
for
children
under
six
years
of
age
only,
1993­
1998
.
9
Subgroup
Exposures
Outcome
determined
Seen
in
Health
Care
Facility
Occupational:
adults
and
older
children
273
171
102
Non­
occupational:
adults
and
older
children
3150
1561
355
Children
under
age
six
1341
602
63
Table
2.
Comparison
between
2,4­
D
and
all
pesticides
for
percent
cases
with
symptomatic
outcome
(
SYM),
moderate
or
more
severe
outcome
(
MOD),
life­
threatening
or
fatal
outcome
(
LIFE­
TH),
seen
in
a
health
care
facility
(
HCF),
hospitalized
(
HOSP),
or
seen
in
an
intensive
care
unit
(
ICU)
reported
to
Poison
Control
Centers,
1993­
1998
for
occupational
cases
only.

Pesticide
SYM*
MOD*
LIFE­
TH*
HCF*
HOSP*
ICU*

2,4­
D
81.9%
14.6%
0.585%
37.4%
7.84%
2.94%

All
Pesticides
86.0%
18.8%
0.621%
47.0%
6.08%
2.36%

Ratio
0.95
0.78
0.94
0.80
1.29
1.24
*
Symptomatic
cases
based
on
those
cases
with
a
minor,
moderate,
major,
or
fatal
medical
outcome.
Denominator
for
SYM,
MOD,
and
LIFE­
TH
is
the
total
cases
where
medical
outcome
was
determined.
Denominator
for
HCF
is
all
exposures.
Denominator
for
HOSP
and
ICU
is
all
cases
seen
in
a
health
care
facility.

Table
3.
Comparison
between
2,4­
D
and
all
pesticides
for
percent
cases
with
symptomatic
outcome
(
SYM),
moderate
or
more
severe
outcome
(
MOD),
life­
threatening
or
fatal
outcome
(
LIFE­
TH),
seen
in
a
health
care
facility
(
HCF),
hospitalized
(
HOSP),
or
seen
in
an
intensive
care
unit
(
ICU)
reported
to
Poison
Control
Centers,
1993­
1998
for
non­
occupational
cases
involving
adults
and
older
children.

Pesticide
SYM*
MOD*
LIFE­
TH*
HCF*
HOSP*
ICU*

2,4­
D
65.8%
9.67%
0.128%
11.3%
5.35%
1.69%

All
Pesticides
68.5%
10.5%
0.359%
16.5%
6.24%
2.67%

Ratio
0.96
0.92
0.36
0.68
0.86
0.63
*
Symptomatic
cases
based
on
those
cases
with
a
minor,
moderate,
major,
or
fatal
medical
outcome.
Denominator
for
SYM,
MOD,
and
LIFE­
TH
is
the
total
cases
where
medical
outcome
was
determined.
Denominator
for
HCF
is
all
exposures.
Denominator
for
HOSP
and
ICU
is
all
cases
seen
in
a
health
care
facility.
10
Table
4.
Comparison
between
2,4­
D
and
all
pesticides
for
percent
cases
with
symptomatic
outcome
(
SYM),
moderate
or
more
severe
outcome
(
MOD),
life­
threatening
or
fatal
outcome
(
LIFE­
TH),
seen
in
a
health
care
facility
(
HCF),
hospitalized
(
HOSP),
or
seen
in
an
intensive
care
unit
(
ICU)
for
adults
and
children
six
years
and
older
reported
to
Poison
Control
Centers,
1993­
1998
for
children
under
six
years
old..

Pesticide
SYM*
MOD*
LIFE­
TH*
HCF*
HOSP*
ICU*

2,4­
D
23.1%
1.33%
0.166%
4.70%
3.17%
1.59%

All
Pesticides
21.8%
1.40%
0.120%
16.4%
4.78%
1.36%

Ratio
1.06
0.95
1.38
0.29
0.66
1.17
*
Symptomatic
cases
based
on
those
cases
with
a
minor,
moderate,
major,
or
fatal
medical
outcome.
Denominator
for
SYM,
MOD,
and
LIFE­
TH
is
the
total
cases
where
medical
outcome
was
determined.
Denominator
for
HCF
is
all
exposures.
Denominator
for
HOSP
and
ICU
is
all
cases
seen
in
a
health
care
facility.

In
general,
2,4­
D
is
less
likely
to
cause
minor,
moderate,
or
life­
threatening
symptoms
than
other
pesticides
and
less
likely
to
cause
effects
which
would
require
medical
treatment,
hospitalization,
or
critical
care.
There
was
a
slightly
elevated
requirement
for
hospitalization
or
critical
care
among
occupational
cases
seen
in
a
health
care
facility,
but
this
was
based
on
eight
cases
(
3
of
the
8
were
seen
in
an
ICU).
Among
children
less
than
six
years
old,
the
percentage
with
life­
threatening
symptoms
and
attention
in
a
critical
care
unit
was
higher,
but
this
was
based
on
a
single
case.
Therefore,
one
should
be
cautious
about
over­
interpreting
the
results
for
children
on
these
two
measures.
In
all
three
groups,
the
most
common
symptoms
were
ocular
and
dermal,
accounting
for
over
400
symptomatic
(
minor,
moderate,
or
major
medical
outcome)
each.
Primary
symptoms
included
irritation,
rash,
erythema,
and
itching.
There
were
more
complaints
of
eye
problems
than
dermal
problems
suggesting
that
getting
sprayed
in
the
eye
was
a
leading
cause
of
symptomatic
illness.
A
total
of
53
cases
reported
edema
or
hives,
suggesting
an
allergic­
type
reaction.
Gastrointestinal,
neurological,
and
respiratory
effects
were
also
reported,
primarily
nausea,
vomiting,
throat
irritation,
headache,
dizziness,
coughing,
and
difficulty
breathing.

III.
California
Data
­
1982
through
2001
Detailed
descriptions
of
127
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(
1982­
2001)
were
reviewed.
In
33
of
these
cases,
2,4­
D
was
used
alone
or
was
judged
to
be
responsible
for
the
health
effects.
Only
cases
with
a
definite,
probable
or
possible
11
relationship
were
reviewed.
2,4­
D
ranked
74th
as
a
cause
of
systemic
poisoning
in
California
based
on
data
for
1982
through
2001.
Table
1
presents
the
types
of
illnesses
reported
by
year.
Table
2
gives
the
total
number
of
workers
that
took
time
off
work
as
a
result
of
their
illness
and
how
many
were
hospitalized
and
for
how
long.

Table
1.
Cases
Due
to
2,4­
D
in
California
Reported
by
Type
of
Illness
and
Year,
1982­
2001.

Year
Illness
Type
Systemica
Eye
Skin
Respiratoryb
Combinationc
Total
1982
1
­
1
­
­
2
1983
­
­
3
­
­
3
1984
­
2
1
­
­
3
1985
­
2
­
­
­
2
1986
­
1
1
­
­
1
1987
1
­
­
­
­
1
1988
­
­
1
­
­
1
1989
7
­
­
­
­
7
1990
­
2
­
­
­
2
1991
­
­
1
­
­
1
1992
1
1
­
­
­
2
1993
­
­
1
­
­
1
1994
­
1
­
­
­
1
1995
­
­
­
­
­
­

1996
1
­
­
­
­
1
1997
­
­
­
­
­
­

1998
1
­
­
1
­
2
1999
1
­
­
­
1
2
2000
­
­
­
­
­
­
12
Year
Illness
Type
Systemica
Eye
Skin
Respiratoryb
Combinationc
Total
2001
­
­
­
­
­
­

Total
13
9
9
1
1
33
a
Category
includes
cases
where
skin,
eye,
or
respiratory
effects
were
also
reported.
b
Category
not
used
until
1990.
Prior
respiratory
cases
classified
as
systemic.
c
Category
includes
combined
irritative
effects
to
eye,
skin,
and
respiratory
system.

Table
2.
Number
of
Persons
Disabled
(
taking
time
off
work)
or
Hospitalized
for
Indicated
Number
of
Days
After
2,4­
D
Exposure
in
California,
1982­
2001.

Time
period
Number
of
Persons
Disabled
Number
of
Persons
Hospitalized
One
day
4
­

Two
days
1
­

3­
5
days
3
­

6­
10
days
­
­

more
than
10
days
­
­

Unknown
3
­

Indefinite
­
­

Note
that
no
cases
were
hospitalized
and
only
a
few
workers
took
time
off
work
for
a
relatively
short
period
of
time.
A
variety
of
worker
activities
were
associated
with
exposure
to
2,4­
D
as
illustrated
in
Table
3
below.

Table
3.
Illnesses
by
Activity
Categories
for
2,4­
D
Exposure
in
California,
1982­
2001
13
Activity
Category
Illness
Category
Systemica
Eye
Skin
Respiratoryb
Combinationc
Total
Applicator
3
5
7
15
Mixer/
loader
1
4
5
Storage/
disposal
1
1
2
Drift
7
7
Field
worker
1
1
Other
1
1
1
3
Total
13
9
9
1
1
33
a
Category
includes
cases
where
skin,
eye,
or
respiratory
effects
were
also
reported.
b
Category
not
used
until
1990.
Prior
respiratory
cases
classified
as
systemic.
c
Category
includes
combined
irritative
effects
to
eye,
skin,
and
respiratory
system.

According
to
the
above
activity
categories,
handlers
(
applicators
and
mixer/
loaders)
were
associated
with
the
majority
(
61%)
of
illnesses.
Nearly
half
of
these
cases
occurred
during
cleaning
or
repair
operations
or
when
a
hose
broke.
One
of
the
drift
incidents
involved
six
workers
who
experienced
drift
from
a
helicopter
application.
These
illnesses
included
symptoms
of
rash,
eye
irritation
and
pain,
headache,
muscle
twitching,
numbness,
corneal
abrasion,
eye
irritation,
nausea,
weakness,
and
vomiting.
Two
cases,
classified
as
possibly
related
to
2,4­
D
mentioned
extreme
sensitivity
to
a
nearby
application.
A
third
case
mentioned
allergic
reaction
in
an
applicator
on
the
upper
extremities.

IV.
National
Pesticide
Information
Center
On
the
list
of
the
top
200
chemicals
for
which
NPIC
received
calls
from
1984­
1991
inclusively,
2,4­
D
was
ranked
8th
with
429
incidents
in
humans
reported
and
108
in
animals
(
mostly
pets).

V.
Scientific
Literature
14
The
World
Health
Organization
(
WHO)
sponsored
a
review
of
2,4­
D
by
the
International
Programme
on
Chemical
Safety
that
was
published
in
Environmental
Health
Criteria
in
1984.
This
comprehensive
review
includes
a
chapter
on
the
"
effect
on
man,
clinical
and
epidemiological
studies".
Pertinent
sections
of
this
review
are
quoted
below:

Signs
and
symptoms
of
acute
over­
exposure
to
2,4­
D
or
its
derivatives
occurred
after
ingestion
or
absorption
of
large
amounts,
or
where
poor
occupational
hygiene
was
practiced
leading
to
pronounced
dermal
absorption
of
the
material.
It
is
unlikely
that,
with
good
agricultural
practice,
good
personal
protection,
and
occupational
hygiene,
resulting
in
exposures
to
low
concentrations
of
2,4­
D,
any
of
the
acute
symptoms
and
signs
reported
below
would
be
expected
to
occur.

From
the
point
of
view
of
occupational
and
bystander
safety,
it
is
reassuring
that
no
reports
were
found
of
fatal
poisonings
following
dermal
exposure
or
inhalation,
though
temporary
unconsciousness
and
other
severe
acute
effects
have
been
attributed
to
massive
combined
dermal
and
inhalation
exposures
to
2,4­
D
herbicides.

In
addition
to
subjective
symptoms
of
the
central
nervous
system,
impaired
coordination,
impaired
responses
to
external
stimuli,
unconsciousness,
coma,
and
death
have
been
observed
in
human
beings
mainly
after
absorption
of
lethal
or
nearly
lethal
doses
of
2,4­
D.

Long­
lasting
flaccid
paraparesis
or
quadriparesis
following
skin
contact
with
2,4­
D
herbicides
was
reported
.
.
.
Cases
of
sensory
neuropathy
attributed
to
the
ingestion
of,
or
dermal
exposure
to,
2,4­
D
herbicides
have
also
been
reported.

Herbicide
ingredients
other
than
2,4­
D
and
related
compounds
might
be
at
least
partly
responsible
for
the
observed
neurotoxic
effects.
In
particular,
organic
solvents,
emulsifiers,
and
ethylene
glycol
present
in
herbicide
formulations
have
been
mentioned
in
this
connection.

Muscle
fibrillations,
myotonia,
myoglobinuria,
muscular
weakness
and
other
indications
of
a
myotoxic
effect
of
2,4­
D
have
been
reported
in
patients
treated
with
large
doses
of
purified
2,4­
D
products
.
.
.
as
well
as
in
cases
of
suicidal
or
accidental
ingestion
of
2,4­
D
herbicides
or
following
occupational
over­
exposure
.
.
.
In
human
beings,
the
threshold
dose
for
gross
myotoxic
effects
certainly
exceeds
5
mg/
kg
body
weight
per
day,
and
may
be
above
36
mg/
kg
body
weight
per
day.

Dyspnea
or
respiratory
tract
irritation
were
occasionally
reported
following
occupational
over­
exposure
of
2,4­
D
production
workers
or
herbicide
sprayers.

Degeneration
of,
or
fatty
changes
in
kidney
tubules,
or
proteinuria,
increased
blood
urea
levels,
and
other
indications
of
a
nephrotoxic
effects
were
observed
in
cases
of
fatal
or
nearly
fatal
herbicide
ingestion.
15
Vomiting,
diarrhea,
nausea,
and
other
indications
of
toxic
effects
on
the
digestive
tract
were
observed
.
.
.
after
ingestion
of
large
doses
of
2,4­
D
herbicides,
or
combined
inhalation
and
dermal
over­
exposure.
.
.
However,
no
gastrointestinal
symptoms
were
reported
by
volunteers
who
ingested
a
single
dose
of
5
mg
pure
2,4­
D/
kg
body
weight.
.
.
Thus,
an
intake
of
more
than
300
mg
2,4­
D
per
adult
appears
to
be
required
to
induce
acute
toxic
effects
on
the
gastrointestinal
tract.

Chronic
tonsillitis
and
paranasal
sinusitis
were
reported
in
workers
packaging
2,4­
D
sodium
salt.

Based
on
clinical
studies
in
which
2,4­
D
was
injected
into
patients
as
a
drug,
the
noobserved
adverse­
effect
level
for
signs
and
symptoms
of
acute
2,4­
D
poisoning
in
children
and
adults
appears
to
be
at
or
near
36
mg/
kg
body
weight.

A
more
recent
review
of
the
potential
for
chlorophenoxy
herbicides
to
cause
poisoning
was
completed
by
Reigart
and
Roberts
in
1999
(
Recognition
and
Management
of
Pesticide
Poisonings,
Fifth
Edition,
EPA
publication
735­
R­
98­
003).
Key
passages
related
to
symptoms
and
dose
are
quoted
below:

Some
of
the
chlorophenoxy
acids,
salts,
and
esters
are
moderately
irritating
to
skin,
eyes,
and
respiratory
and
gastrointestinal
linings.
In
a
few
individuals,
local
depigmentation
has
apparently
resulted
from
protracted
dermal
contact
with
chlorophenoxy
compounds.

Ingestion
of
large
amounts
of
chlorophenoxy
acids
has
resulted
in
severe
metabolic
acidosis
in
humans.
Such
cases
have
been
associated
with
electrocardiographic
changes,
myotonia,
muscle
weakness,
myoglobinuria,
and
elevated
serum
creatine
phophokinase,
all
reflecting
injury
to
striated
muscle.

The
medical
literature
contains
reports
of
peripheral
neuropathy
following
what
seemed
to
be
minor
dermal
exposures
to
2,4­
D.
It
is
not
certain
that
exposures
to
other
neurotoxicants
were
entirely
excluded
in
these
cases.
Single
doses
of
5
mg/
kg
body
weight
of
2,4­
D
and
2,4,5­
T
have
been
administered
to
human
subjects
without
any
adverse
effects.
One
subject
consumed
500
mg
of
2,4­
D
per
day
for
3
weeks
without
experiencing
symptoms
or
signs
of
illness.

Chlorophenoxy
compounds
are
moderately
irritating
to
skin
and
mucous
membranes.
Inhalation
of
sprays
may
cause
burning
sensations
in
the
nasopharynx
and
chest,
and
coughing
may
result.
Prolonged
inhalation
sometimes
causes
dizziness.
Adjuvant
chemicals
added
to
enhance
foliage
penetration
might
account
for
the
irritant
effects
of
some
formulations.

Manifestations
of
systemic
toxicity
of
chlorophenoxy
compounds
are
known
mainly
from
clinical
experience
with
cases
of
deliberate
suicidal
ingestion
of
large
quantities.
Most
reports
of
fatal
outcomes
involves
renal
failure,
acidosis,
electrolyte
imbalance,
and
a
16
resultant
multiple
organ
failure.

Patients
will
present
within
a
few
hours
of
ingestion
with
vomiting,
diarrhea,
headache,
confusion,
and
bizarre
or
aggressive
behavior.
Mental
status
changes
occur
with
progression
to
coma
in
severe
cases.
.
.
Muscle
weakness
and
peripheral
neuropathy
have
been
reported
after
occupational
exposure.

Myotonia
and
muscle
weakness
may
persist
for
months
after
acute
poisoning.
Electromyographic
and
nerve
conduction
studies
in
some
recovering
patients
have
demonstrated
a
mild
proximal
neuropathy
and
myopathy.

In
a
study
of
asymptomatic
herbicide
applicators,
their
urinary
excretion
of
chlorophenoxy
compounds
rarely
exceeded
1­
2
mg/
L.

The
following
studies
provide
additional
insight
into
the
relationship
between
poisoning
and
route
of
exposure
and
the
dose
that
can
be
fatal
in
the
case
of
ingestions.
Friesen
et
al.
(
1990)
reported
on
a
61
year­
old
woman
who
ingested
2,4­
D
and
was
treated
successfully
with
alkaline
diuresis.
Their
review
of
earlier
cases
noted
fatalities
had
been
reported
following
ingestions
of
amounts
ranging
from
250
mg/
kg
to
1,200
mg/
kg
body
weight.

Flanagan
et
al.
(
1990)
reported
prospectively
on
41
patients
acutely
poisoned
by
chlorophenoxy
herbicides
and
ioxynil
during
1984­
87.
Of
these
41
patients,
30
were
reported
to
have
ingested
chlorophenoxy
compounds
alone,
of
whom
six
died.
How
many
of
the
30
patients
ingested
2,4­
D
alone
was
not
reported.
Lack
of
information
about
the
patients
who
were
exposed
only
to
2,4­
D
make
this
report
of
limited
value
for
the
purposes
of
this
review.

Durakovic
et
al.
(
1992)
reported
on
four
suicides,
each
involving
ingestion
of
a
40%
solution
of
2,4­
D
alone
as
the
active
ingredient.
The
quantity
of
2,4­
D
ranged
from
250
to
2,000
mg/
kg
body
weight.
Signs
of
poisoning
with
2,4­
D
were
listed
as
pain
in
the
tongue
and
pharnyx,
erythema,
vomiting,
pain
and
weakness
in
muscles,
lethargy,
stupor,
increased
or
lowered
body
temperature,
weakness
or
respiratory
muscle
paralysis,
coma,
convulsions,
and
cardiac
arrhythmias.
The
lowest
dose
reported
to
cause
death,
40
grams
occurred
in
an
agricultural
worker
aged
80
years.
A
second
case,
involving
an
accidental
ingestion
of
40­
80
grams
of
2,4­
D
in
a
50
year
old
miner
who
mistook
the
product
for
an
alcoholic
drink.

Keller
et
al.
(
1994)
reported
on
an
ingestion
of
an
unknown
quantity
of
relatively
pure
2,4­
D
by
a
49
year
old
man
in
a
suicide
attempt.
His
symptoms
included
vomiting,
blood
in
diarrhea,
disorientation,
rapid
pulse,
pain
in
abdomen,
deterioration
of
respiration,
and
massive
hemorrhage
of
stomach
mucosa.
Based
on
serum
concentrations
in
various
tissues,
the
authors
concluded
that
at
least
25­
35
grams
of
2,4­
D
were
ingested.

Jorens
et
al.
(
1995)
also
reported
on
the
fatal
case
of
a
60
year
old
farmer
who
ingested
only
2,4­
D
at
an
estimated
dose
of
3,000
mg/
kg
and
in
addition
to
the
other
symptoms
had
profuse
gastrointestinal
bleeding
and
metabolic
acidosis
due
to
the
caustic
effects
of
the
acid.
17
Leonard
et
al.
(
1997)
reported
on
an
unusual
case
of
a
65
year
old
man
who
developed
lethargy
over
a
period
of
two
months,
and
then
dark
urine
and
upper
abdominal
discomfort.
He
was
diagnosed
with
hepatitis
and
it
was
considered
due
to
his
habit
of
licking
his
golf
ball
to
clean
it,
particularly
on
the
greens
where
the
herbicide
was
applied.
The
patient
was
skeptical
of
the
diagnosis
and
it's
relationship
to
licking
his
golf
ball
and
later
resumed
the
practice.
He
then
requested
repeat
testing
a
month
afterwards,
which
confirmed
renewed
altered
liver
function
and
convinced
the
patient
that
his
exposure
was
affecting
his
liver.
In
a
letter
to
the
editor,
Leonard
et
al.
(
1998)
reported
a
similar
case
in
a
23
year
old
man
who
had
hepatitis
and
evidence
of
cirrhosis
despite
only
moderate
alcohol
consumption.

Bradberry
et
al.
(
2000)
reviewed
the
mechanisms
of
poisoning
and
clinical
features
of
chlorophenoxy
poisoning.
Between
1962
and
1999,
66
cases
of
chlorophenoxy
poisoning
following
ingestion
were
identified.
Symptoms
and
signs
of
ingestion
included
vomiting,
gastrointestinal
pain,
diarrhea,
coma,
hypertonia,
ataxia,
miosis,
convulsions,
fasciculation,
and
paralysis.
Myopathic
symptoms
included
limb
muscle
weakness,
loss
of
tendon
reflexes,
and
myotonia.
Other
symptoms
included
metabolic
acidosis,
rhabdomyolysis,
and
renal
failure.
Twenty­
two
of
the
66
patients
died.
The
authors
noted
that
it
was
not
possible
to
determine
a
dose/
response
relationship
among
these
cases
because
the
dose
was
rarely
known
with
accuracy.
Dermal
and
inhalation
exposure,
on
the
other
hand,
only
occasionally
led
to
systemic
poisoning.
The
authors
noted
five
cases
of
systemic
toxicity
reported
between
1959
and
1963
which
involved
inadvertent
spillage
of
2,4­
D
on
the
limbs
with
little
or
no
protective
clothing.
One
such
case
was
a
39
year
old
farmer
who
complained
of
paresthesia
in
the
fingers
and
toes
and
myalgia.
Over
the
next
two
weeks,
he
developed
weakness
and
incoordination
of
the
hands
with
reduced
reflexes.
Symptoms
resolved
almost
completely
over
the
next
9
months.
In
each
of
the
other
four
cases
of
peripheral
neuropathy
after
dermal
exposure,
there
was
typically
a
latent
period
of
several
days
before
the
onset
of
nausea
and
vomiting,
sometimes
with
anorexia
or
diarrhea.
"
Pain,
paresthesiae,
and
weakness
affecting
mainly
the
lower
limbs
followed.
Clinical
findings
were
of
a
flaccid
paralysis
(
in
2
cases
so
severe
that
the
patients
could
not
walk)
with
impaired
light
touch,
pain
and
temperature
sensation,
and
reduced
or
absent
reflexes.
There
was
EMG
evidence
of
denervation
in
2
cases,
described
as
`
minimal'
in
one
of
these."
These
other
four
cases
all
eventually
recovered
though
mild
weakness
was
present
at
the
2­
3
year
follow­
up
examination
in
3
of
the
cases.
Inhalation
exposure
has
been
reported
to
lead
to
gastrointestinal
and
peripheral
neuromuscular
symptoms
including
nausea,
vomiting,
constipation,
abdominal
pain,
limb
paresthesia
and
pain,
myalgia,
weakness,
and
hypertonia.
In
some
cases
these
symptoms
persisted
several
weeks
after
a
single
exposure.

Reproductive
effects
Schreinemachers
(
2003)
compared
43,500
birth
outcomes
compiled
by
the
National
Center
for
Health
Statistics
in
selected
counties
of
Minnesota,
North
Dakota,
South
Dakota
and
Montana
with
high­
wheat
and
low­
wheat
acreage
in
those
states.
She
found
that
in
high­
wheat
counties,
combined
circulatory
and
respiratory
malformations
increased
by
more
than
two­
fold,
and
musculoskeletal
malformations
increased
by
50%
relative
to
low­
wheat
counties.
Death
rates
18
from
birth
malformations
among
male
infants
in
high­
wheat
counties
were
more
than
twice
the
rates
in
low­
wheat
counties.
This
study
suggests
a
possible
association
between
rates
of
birth
malformations
and
indirect
measures
of
human
exposure
to
chlorophenoxy
herbicides,
a
common
weed
killer
sold
commercially
and
used
in
agriculture.

Since
this
study
used
wheat
acreage
rather
than
actual
measurements
of
human
exposure
to
determine
associations
with
birth
malformations,
it
is
not
known
whether
birth
malformations
occurred
among
families
with
actual
exposure
to
the
herbicides
in
question
in
the
selected
counties.
Such
epidemiologic
studies
are
used
to
generate
hypotheses.
Then
they
must
be
followed
up
with
studies
that
measure
exposure
in
individuals
rather
than
just
on
a
county
basis
to
determine
whether
the
suggested
relationship
still
holds.
Although
individual
exposures
cannot
be
determined
from
this
research,
the
results
may
be
indicative
of
potential
hazards
in
connection
with
environmental
exposures
to
chlorophenoxy
herbicides.
The
author
concluded
"
The
purpose
of
this
exploratory
study
is
to
identify
a
potential
regional
hazard.
Results
should
be
viewed
in
this
light".

One
strong
point
for
this
study
was
the
apparent
restriction
to
rural
farm
counties
so
that
factors
affecting
urban
counties
would
not
confound
results.
Information
on
percent
people
living
in
rural­
farm
and
rural­
nonfarm
areas
should
have
been
provided
to
confirm
this
result
rather
than
just
relying
on
50%
of
the
population
being
rural
(
criteria
for
a
counties'
inclusion
in
the
study).

The
weakest
aspect
of
the
study
is
the
grouping
of
counties
into
high
and
low
exposure
based
on
percent
wheat
acreage.
A
large
percent
of
the
population
in
many
of
these
counties
may
not
have
resided
on
a
farm
at
all.
Their
exposure
to
wheat
versus
corn
and
soybeans
meant
that
over
factors
including
exposure
to
fungal,
viral
and
bacterial
flora
was
likely
very
different
and
a
potential
confounder.
Most
importantantly,
you
don't
know
if
the
birth
defects
actually
involve
persons
exposed
to
2,4­
D;
just
that
they
resided
in
counties
where
relatively
larger
amounts
of
2,4­
D
were
likely
to
be
used.
This
is
known
as
aggregation
bias
and
such
studies
are
referred
to
as
having
an
ecologic
design
and
subject
to
the
ecologic
fallacy.

Carcinogenicity
A
Science
Advisory
Board/
Scientific
Advisory
Panel
Special
Joint
Committee
reviewed
available
data
on
2,4­
D
in
1994
and
concluded
that
"
the
data
are
not
sufficient
to
conclude
that
there
is
a
cause
and
effect
relationship
between
exposure
to
2,4­
D
and
non­
Hodgkin's
lymphoma"
and
2,4­
D
has
been
classified
in
Group
D,
not
classifiable
as
to
human
carcinogenicity
(
EPA,
1994).
In
1996,
HED
reviewed
the
following
five
additional
studies:

1.
Waterhouse
D,
Carman
WJ,
Schottenfeld
D,
Gridley
G,
McLean
S.
Cancer
incidence
in
the
rural
community
of
Tecumseh,
Michigan:
A
pattern
of
increased
lymphopoietic
neoplasms.
Cancer
77:
763­
770,
1996.

2.
Zahm
SH,
Babbit
PA,
Weisenburger
DD,
Blair
A,
Saal
RC,
Vaught
JB.
The
role
of
agricultural
pesticide
use
in
the
19
development
of
non­
Hodgkin's
lymphoma
in
women.
Archives
of
Environmental
Health
48:
353­
358,
1993.

3.
Morrison
HI,
Semenciw
RM,
Wilkins
K,
Mao
Y,
Wigle
DT.
Non­
Hodgkin's
lymphoma
and
agricultural
practices
in
the
prairie
provinces
of
Canada.
Scandinavian
Journal
of
Work,
Environment
and
Health
20:
42­
47,
1994.

4.
Persson
B,
Fredriksson
M,
Olsen
K,
Beoryd
B,
Axelson
O.
Some
occupational
exposures
as
risk
factors
for
malignant
lymphomas.
Cancer
72:
1173­
1778,
1993.

5.
Kogevinas
M,
Kauppinen
T,
Winkelmann
R,
et
al.
Soft
tissue
sarcoma
and
non­
Hodgkin's
lymphoma
in
workers
exposed
to
phenoxy
herbicides,
chlorophenols,
and
dioxins:
two
nested
case­
control
studies.
Epidemiology
6:
396­
402,
1995.

HED
concluded
after
reviewing
these
five
studies
that:
These
studies
are
not
sufficient
to
change
the
conclusions
drawn
by
the
Science
Advisory
Panel/
Scientific
Advisory
Board.
Only
two
studies,
Zahm
et
al.
1993
and
Kogevinas
et
al.
1995
looked
specifically
at
exposure
to
2,4­
D
and
even
in
these
studies,
there
were
problems
with
correlation
with
exposure
to
other
pesticides.
Statistical
significance
was
achieved
for
two
types
of
cancer
(
Hodgkin's
disease
and
soft
tissue
sarcoma).
However,
the
earlier
evidence
for
these
two
sites
was
generally
much
less
supportive
than
it
was
for
non­
Hodgkin's
lymphoma.

Since
the
1996
review,
very
few
new
studies
have
examined
the
relationship
between
exposure
to
2,4­
D
and
cancer.
The
most
recent
review
was
in
Critical
Reviews
in
Toxicology
by
Garabrant
and
Philbert
at
the
University
of
Michigan
School
of
Public
Health
(
2002).
Their
conclusion
was
"
Overall,
the
available
evidence
from
epidemiologic
studies
is
not
adequate
to
conclude
that
any
form
of
cancer
is
causally
associated
with
2,4­
D
exposure."
This
review
was
conducted
at
the
request
of
the
Industry
Task
Force
II
on
2,4­
D
Research.
Many
of
the
studies
reviewed
by
Garabrant
and
Philbert
measured
cancer
risk
among
workers
exposed
to
a
variety
of
herbicides.
For
example,
studies
of
licensed
pesticide
applicators
included
a
number
of
exposures
in
addition
to
2,4­
D,
in
such
a
manner,
that
2,4­
D
relative
contribution
to
risk
could
not
be
determined.
These
studies
are
excluded
from
this
review
unless
there
was
information
on
risks
specific
to
2,4­
D
or
just
2,4­
D
and
2,4,5­
T.
Only
five
studies,
four
cohort
and
one
case­
control
study,
were
identified
that
specifically
assess
the
carcinogenicity
of
2,4­
D
(
Kogevinas
et
al.
1997,
Zahm
1997,
Lynge
1998,
Burns
et
al.
2001,
and
Hardell
et
al.
1999).

Investigators
at
IARC
updated
an
earlier
study
(
Kogevinas
et
al.
1995)
of
a
multinational
cohort
of
primarily
manufacturing
workers
exposed
to
chlorophenoxy
herbicides
(
Kogevinas
et
al.
1997).
There
was
no
significant
associations
between
2,4­
D
exposure
and
soft­
tissue
sarcoma
(
STS),
NHL,
and
Hodgkin's
disease
among
those
not
exposed
to
TCDD
dioxin
contaminants.
The
Odds
ratio
for
STS
was
1.35
(
95%
CI
0.16
­
4.88)
based
on
two
observed
cases.
The
Odds
20
ratio
for
NHL
was
1.00
(
95%
CI
0.46
to
1.90)
based
on
nine
observed
cases.
The
Odds
ratio
for
Hodgkin's
disease
was
0.27
(
95%
CI
0.01
to
1.51)
based
on
one
observed
case.

Zahm
(
1997)
reported
on
a
cohort
of
pesticide
applicators
potentially
exposed
to
2,4­
D
up
to
90­
120
days
per
year.
There
were
no
cases
of
STS
or
Hodgkin's
disease.
The
estimated
odds
ratio
for
NHL
was
1.63
(
95%
CI
0.33
to
4.77)
based
on
three
cases.
However,
all
three
cases
had
potential
exposure
to
DCPA,
MCPP,
dicamba,
and
organophosphate
insecticides
as
well
as
2,4­
D.
Therefore,
the
risk
from
exposure
to
2,4­
D
alone
cannot
be
specified.

Lynge
(
1998)
examined
cancer
incidence
in
a
cohort
of
2,119
Danish
phenoxy
herbicide
workers
exposed
between
1947
and
1993.
However,
most
of
these
workers
were
exposed
to
MCPA
rather
than
2,4­
D.
No
odds
ratios
were
calculated
for
those
workers
primarily
exposed
to
2,4­
D.

Burns
et
al.
(
2001)
updated
earlier
studies
of
a
cohort
of
1,517
chemical
workers
who
manufactured
or
formulated
2,4­
D
between
1945
and
1994.
The
odds
ratio
for
NHL
was
1.00
(
95%
CI
0.21
to
2.92)
based
on
three
cases.
These
three
cases
had
relatively
low
exposures
based
on
cumulative
dose
estimates
compared
to
other
workers
in
the
cohort.
There
was
one
case
of
Hodgkin's
disease
compared
to
0.6
expected
which
was
not
significant.
Soft
tissue
sarcomas
were
not
measured
in
this
study.
Burns
et
al.
concluded
there
was
"
no
evidence
of
an
increased
risk
of
death
due
to
all
causes
or
total
malignant
neoplasms.
No
significant
risk
of
NHL
was
found".

The
case­
control
study
by
Hardell
et
al.
(
1999)
examined
404
cases
of
non­
Hodgkin's
lymphoma
and
741
controls.
None
of
the
subjects
had
exposure
to
2,4­
D
alone
and
exposure
to
2,4­
D
and
2,4,5­
T
were
not
significantly
associated
with
NHL
(
Odds
Ratio
=
1.3,
95%
CI
0.7
to
2.3).
A
higher
estimated
odds
ratio
was
found
for
those
with
less
than
30
days
exposure
than
for
those
with
more
than
30
days
exposure,
a
finding
that
does
not
support
dose­
response.

Two
additional
studies
that
should
be
mentioned
used
an
ecologic
study
design
to
determine
whether
chlorophenoxy
herbicides
were
associated
with
cancer.
One
study
examined
cancer
rates
in
four
northern
wheat
producing
states
in
the
U.
S.
(
Schreinemachers
2000).
This
study
used
wheat
acreage
as
a
surrogate
for
exposure
to
chlorophenoxy
herbicides
and
determined
cancer
rates
for
grouped
counties
or
individual
counties
based
on
tertiles
of
wheat
acreage.
As
the
author
points
out,
this
study
"
will
generate
hypotheses
for
more
resourceintensive
and
definitive
cohort
and
case­
control
studies
where
exposure
information
can
be
determined
for
individual
subjects,
thereby
avoiding
ecologic
fallacies."
Although
a
number
of
possible
associations
between
high
wheat
acreage
and
cancer
were
identified,
it
is
not
possible
to
determine
which
cancer
sites
were
due
to
chance,
confounding,
and
other
factors
without
further
studies.

A
second
study
in
northern
Italy
examined
incidence
rates
of
lymphomas
in
rice­
growing
areas
where
chlorophenoxy
herbicides
were
used
(
Fontana
et
al.
1998).
This
study
identified
cases
of
Hodgkin's
disease
and
non­
Hodgkin's
lymphoma
in
two
provinces
in
both
men
and
21
women
for
the
time
periods
1985­
88
and
1991­
93.
Results
of
soil
and
water
analyses
performed
in
1974­
75
were
used
to
classify
13
municipalities
as
having
high
exposure
to
2,4­
D
and
2,4,5­
TP.
Levels
of
water
contamination
were
similar
for
2,4­
D
and
2,4,5­
TP
and
there
were
no
measurements
of
tetrachlorodibenzodioxin
(
TCDD).
Although
there
was
a
significant
association
between
non­
Hodgkin's
lymphoma
in
men
and
the
high
exposure
area,
it
was
not
possible
to
say
whether
2,4­
D,
2,4,5­
TP
or
TCDD
was
responsible
for
the
association.
Other
confounding
factors
might
also
account
for
the
observed
association.
A
supplemental
case­
control
study
examined
hematolymphopoietic
cancers
(
NHL,
Hodgkin's
disease,
and
leukemias)
and
found
some
evidence
for
elevated
risk
among
those
with
occupations
in
rice
fields,
but
the
odds
ratios
were
not
statistically
significant
and,
as
before,
the
association
could
not
be
tied,
specifically
to
2,4­
D.

Based
on
the
above
reviews
of
the
above
studies,
HED
concludes
there
is
no
additional
evidence
that
would
implicate
2,4­
D
as
a
cause
of
cancer.

VI.
Conclusion
A
number
of
effects
reported
in
humans
were
associated
with
a
specific
dose.
These
reports
are
summarized
below:

In
human
beings,
the
threshold
dose
for
gross
myotoxic
effects
certainly
exceeds
5
mg/
kg
body
weight
per
day,
and
may
be
above
36
mg/
kg
body
weight
per
day
(
WHO
1984).

no
gastrointestinal
symptoms
were
reported
by
volunteers
who
ingested
a
single
dose
of
5
mg
pure
2,4­
D/
kg
body
weight.
.
.
Thus,
an
intake
of
more
than
300
mg
2,4­
D
per
adult
appears
to
be
required
to
induce
acute
toxic
effects
on
the
gastrointestinal
tract
(
WHO
1984).

Based
on
clinical
studies
in
which
2,4­
D
was
injected
into
patients
as
a
drug,
the
noobserved
adverse­
effect
level
for
signs
and
symptoms
of
acute
2,4­
D
poisoning
in
children
and
adults
appears
to
be
at
or
near
36
mg/
kg
body
weight
(
WHO
1984).

Single
doses
of
5
mg/
kg
body
weight
of
2,4­
D
and
2,4,5­
T
have
been
administered
to
human
subjects
without
any
adverse
effects.
One
subject
consumed
500
mg
of
2,4­
D
per
day
for
3
weeks
without
experiencing
symptoms
or
signs
of
illness
(
Reigart
and
Roberts
1999).

In
a
study
of
asymptomatic
herbicide
applicators,
their
urinary
excretion
of
chlorophenoxy
compounds
rarely
exceeded
1­
2
mg/
L
(
Reigart
and
Roberts
1999).

fatalities
had
been
reported
following
ingestions
of
amounts
ranging
from
250
mg/
kg
to
1,200
mg/
kg
body
weight
(
Friesen
et
al.
1990
).

Durakovic
et
al.
(
1992)
reported
on
four
suicides,
each
involving
ingestion
of
a
40%
22
solution
of
2,4­
D
alone
as
the
active
ingredient.
The
quantity
of
2,4­
D
ranged
from
250
to
2,000
mg/
kg
body
weight.
.
.
The
lowest
dose
reported
to
cause
death,
40
grams
occurred
in
an
agricultural
worker
aged
80
years.
A
second
case,
involving
an
accidental
ingestion
of
40­
80
grams
of
2,4­
D
in
a
50
year
old
miner
who
mistook
the
product
for
an
alcoholic
drink
(
Durakovic
et
al.
1992).

The
information
above
suggests
a
no
observed
effect
level
in
humans
of
around
5­
10
mg/
kg
body
weight.
Low
observed
lethal
dose
by
ingestion
appears
to
be
around
250­
500
mg/
kg
body
weight.

Based
on
California
data,
the
majority
of
illnesses
and
injury
due
to
2,4­
D
occur
among
handlers
and
not
among
bystanders
exposed
to
drift
or
residue.
One
drift
case
did
occur
when
six
person
exposed
to
drift
from
a
helicopter
application
experienced
nausea,
headache,
throat
and
eye
irritation.
This
particular
application
violated
label
directions.
Handler
associated
cases
often
occur
due
to
equipment
failure
or
during
repair
and
maintenance
of
application
equipment.

Of
particular
concern
are
the
observations
by
Bradberry
et
al.
(
2000)
that
found
five
cases
of
systemic
toxicity
reported
between
1959
and
1963
which
involved
inadvertent
spillage
of
2,4­
D
on
the
limbs
with
little
or
no
protective
clothing.
One
such
case
was
a
39
year
old
farmer
who
complained
of
paresthesia
in
the
fingers
and
toes
and
myalgia.
Over
the
next
two
weeks,
he
developed
weakness
and
incoordination
of
the
hands
with
reduced
reflexes.
Symptoms
resolved
almost
completely
over
the
next
9
months.
In
each
of
the
other
four
cases
of
peripheral
neuropathy
after
dermal
exposure,
there
was
typically
a
latent
period
of
several
days
before
the
onset
of
nausea
and
vomiting,
sometimes
with
anorexia
or
diarrhea.
"
Pain,
paresthesiae,
and
weakness
affecting
mainly
the
lower
limbs
followed.
Clinical
findings
were
of
a
flaccid
paralysis
(
in
2
cases
so
severe
that
the
patients
could
not
walk)
with
impaired
light
touch,
pain
and
temperature
sensation,
and
reduced
or
absent
reflexes.
There
was
EMG
evidence
of
denervation
in
2
cases,
described
as
`
minimal'
in
one
of
these."
These
other
four
cases
all
eventually
recovered
though
mild
weakness
was
present
at
the
2­
3
year
follow­
up
examination
in
3
of
the
cases.
Inhalation
exposure
has
been
reported
to
lead
to
gastrointestinal
and
peripheral
neuromuscular
symptoms
including
nausea,
vomiting,
constipation,
abdominal
pain,
limb
paresthesia
and
pain,
myalgia,
weakness,
and
hypertonia.
In
some
cases
these
symptoms
persisted
several
weeks
after
a
single
exposure.
Bradberry
et
al.
(
2000)
noted
that
no
such
cases
have
been
reported
in
the
past
20
years
which
may
suggest
that
impurities
or
differences
in
formulation
may
be
responsible
for
the
earlier
reported
cases.
Nevertheless,
the
potential
for
2,4­
D
to
cause
relatively
long­
term
(
9
months
in
one
case)
serious
effects
(
two
cases
unable
to
walk)
from
just
dermal
or
inhalation
exposure,
though
rare,
suggests
a
very
serious
hazard.

VII.
Recommendations
Personal
protective
equipment
to
prevent
excessive
dermal
exposure
may
be
important
not
only
to
prevent
minor
irritant
effects,
but
also
long­
term
effects
to
the
muscles.
Labels
should
clearly
warn
that
significant
amounts
of
2,4­
D
spilled
on
the
skin
should
be
rinsed
off
with
copious
amounts
of
soap
and
water
immediately
after
exposure.
23
A
large
number
of
problems
have
occurred
among
workers
and
residential
users
who
got
2,4­
D
in
their
eyes.
Thus,
eye
protection
for
both
occupational
and
residential
users
is
warranted.

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cc:
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D
file
(
030001)
William
Hazel,
HED
(
7509C)
Mark
Seaton,
SRRD
(
7508C)
25
