1
Methyl
Isothiocyanate
(
MITC):

Weight
of
the
Evidence
for
Use
of
Human
Eye
Irritation
Study
Anna
Lowit,
Ph.
D.

Anna
Lowit,
Ph.
D.

U.
S.
EPA
U.
S.
EPA
Office
of
Pesticide
Programs
Office
of
Pesticide
Programs
May
3,
2006
May
3,
2006
2
Overview
Overview

Key
exposure
pathways
for
soil
fumigants

MITC
toxicology
database

Design
and
results
of
the
MITC
human
eye
irritation
study

Incorporation
of
MITC
human
eye
irritation
in
risk
assessment
3
Overview:
Soil
Fumigants
Overview:
Soil
Fumigants

OPP
is
evaluating
the
risk
from
the
soil
fumigants:


Methyl
bromide

Methyl
iodide

Chloropicrin

Metam
sodium
&
Metam
potassium
(
degrade
to
MITC)


Dazomet
(
degrades
to
MITC)


Public
Technical
briefing
for
Soil
Fumigants
in
July,
2005
4
Overview:
MITC
Overview:
MITC

Exposure
pathways

Can
be
used
directly
to
treat
wood
poles

Key
degradate
of
metam
sodium,
metam
potassium
and
dazomet
 
It
is
believed
that
MITC
that
provides
the
fumigating
properties
 
Metam
sodium
and
metam
potassium
are
used
to
treat
sewage
systems
 
Major
pathway:
Metam
sodium,
metam
potassium,
and
dazomet
are
used
as
a
soil
fumigants
5
Human
Health
Assessment:

Residential
Bystander
Exposure
Wind
blows
Wind
blows
emissions
from
emissions
from
a
treated
field
to
a
a
treated
field
to
a
receptor
of
concern
receptor
of
concern
(
e.
g.,
house
or
school)

(
e.
g.,
house
or
school)

Wind
direction
Wind
direction
Occurs
from
known
sources,
single
Occurs
from
known
sources,
single
applications
used
in
assessment
applications
used
in
assessment
6
MITC:
Toxicity
Profile
MITC:
Toxicity
Profile 
Animal
Animal

Majority
of
studies
via
oral
route

Limited
animal
database
via
the
inhalation
route

28­
day
rat
inhalation
study
 
6.8
ppm:
clinical
signs
(
eyelid
closure,
somnolence,
and
ruffled
fur
from
the
3
rd
day
of
exposure
onwards)

 
34
ppm:
nasal
pathology
(
metaplasia
of
respiratory
epithelium
and
atrophy
of
the
olfactory
epithelium).


Acute
lethality
study
in
rats
 
Approx.
80
ppm:
clinical
signs
(
rales)
and
increased
lung
weights
Animal
database
does
not
provide
characterization
for
the
progression
of
possible
toxic
effects
from
acute
inhalation
exposure
7
MITC:
Toxicity
Profile
MITC:
Toxicity
Profile 
Human
Human

Incident
Data

Provide
support
for
irritating
properties
of
MITC
 
Headache,
eye,
skin,
nose,
and
throat
irritation,
nausea,
dizziness,

coughing,
shortness
of
breath,
diarrhea,
and
chest
tightness.


Insufficient
exposure
data
prevents
use
of
incident
data
in
quantitative
risk
assessment

Human
Odor
Threshold
Study

Geometric
mean
of
1.7
ppm
(
ranged
from
0.2
to
8
ppm)


Odor
threshold
less
sensitive
than
results
of
eye
irritation
study
 
Thus,
less
useful
in
risk
assessment

Human
Eye
Irritation
Study

Used
in
EPA s
risk
assessments
in
2004
&
2005
for
estimation
of
acute
(
1­
day)
bystander
and
worker
risk
8
Study
Design:
Human
Eye
Irritation
Study
Design:
Human
Eye
Irritation

70
individuals
(
38
males,
32
females)


Mean
age
of
32
years
(
range,
18­
67
years;
median
age,
28
years)


Information
about
individual
subjects:


Some
individuals
were
tested
for
more
than
one
exposure
duration.


The
subject
identification
numbers
were
changed
with
each
session

Can
not
determine
which
subjects
were
included
repeatedly

Sex
and
age
unknown
9
Study
Design:
Parameters
Measured
Study
Design:
Parameters
Measured

Eyes
only 
specialized
goggle
system

Subjective
estimation
of
irritation
using
the
"
Likert"

scale

 
No
irritation 
to
 
so
much
that
you
feel
you
should
end
the
exposure 


Mid­
level
similar
to
that
for
cutting
up
an
onion;


Blink
rate
as
measured
by
electromyography

Photographs
of
the
subjects'
eyes
prior
to
and
after
exposure
to
evaluate
degree
of
redness
and
swelling

Effect
upon
visual
acuity
using
a
standard
eye
chart

Tear
production
9
3.3
ppm
9
1.9
ppm
9
0.6
ppm
0
Acetic
acid
control
10
Air
only
control
4/
18/
95
 
4/
26/
95
14
minute
9
0.8
ppm
12
0.23
ppm
14
Acetic
acid
control
12
Air
only
control
3/
13/
95
 
3/
31/
95
4
hour
trial
16
0.22
ppm
7
Acetic
acid
control
12
Air
only
control
12/
8/
94
 
1/
9/
95
8
hour
trial
Number
of
subjects
Concentration(
s)

Tested
Dates
Duration
Study
Design:
Treatment
Groups
Study
Design:
Treatment
Groups
11
Results:
Human
Eye
Irritation
Results:
Human
Eye
Irritation

Tearing

No
statistically
positive
tearing
responses
were
observed
at
any
concentration
or
duration

Visual
acuity
and
photographs

Data
not
provided
in
report

Director
concludes
these
did
not
provide
"
any
meaningful
information
on
chemical
exposure"
12
Results:
Subjective
Scoring
Results:
Subjective
Scoring
N/
A
0.22
ppm
8
hour
0.8
ppm
0.22
ppm
1­
4
hour
1.9
ppm
0.6
ppm
4­
14
min
N/
A
3.3
ppm
1
min
LOAEL
NOAEL
Duration
Most
subjects
scored
<
50%
at
most
time
points.

Some
reached
scores
>
75%
13
Results:
Blinking
Rate
Results:
Blinking
Rate
N/
A
0.22
ppm
8
hour
0.8
ppm
0.22
ppm
1­
4
hour
3.3
ppm
1.9
ppm
4­
14
min
N/
A
3.3
ppm
1
min
LOAEL
NOAEL
Duration
14
Overall:
Human
Eye
Irritation
Overall:
Human
Eye
Irritation

Weaknesses:


Information
about
subjects
limits
ability
to:

°
consider
age
or
gender
sensitivity
°
within
subject
variation

Eye
photographs
and
visual
acuity
not
provided

Positive
control
data
not
included
in
study

Goggle
study
only
15

Strengths:


Multiple
exposure
concentrations

Durations
ranging
from
1
min
to
8
hours

Subject
number

Both
sexes
included

Objective
and
subjective
measurements
Overall:
Human
Eye
Irritation
Overall:
Human
Eye
Irritation
16

1
minute:
NOAEL
is
3.3
ppm

Lack
of
response
in
any
parameter
tested.


4­
14
minutes:
NOAEL
is
0.6
ppm

Responses
on
the
Likert
subjective
scale
at
1.9
ppm.


1­
8
hours:
NOAEL
is
0.22
ppm

Responses
on
the
Likert
subjective
scale
at
0.8
ppm
at
1­
4
hours

Eyeblink
responses
at
2
and
3
hours
Overall:
Human
Eye
Irritation
Overall:
Human
Eye
Irritation
