Appendix
A:
Toxicity
Profile
Acute
Neurotoxicity
Study
Executive
Summary
for
Acute
Reference
Dose
in
the
General
Population
In
an
acute
neurotoxicity
study
(
MRID
No.
42793601),
CD
rats
(
15
rats/
sex/
dose)
were
exposed
by
whole
body
inhalation
to
0,
30,
100
or
350
ppm
MeBr
vapor
for
6
hours
(
equivalent
to
males:
0,
27,
90
or
314
mg/
kg/
day
and
females:
0,
30,
101,
or
354
mg/
kg/
day).
Test
animals
were
observed
for
16
days.
Functional
observation
battery
(
FOB)
was
conducted
at
pre­
test
and
days
1,
2,
8
and
15
post­
treatment.
Motor
activity
measurements
was
conducted
at
pre­
test
and
days
1,
8
and
15
post­
treatment.

Under
the
conditions
of
this
study,
MeBr
did
not
produce
any
mortality,
body
weight
loss,
gross
or
microscopic
changes
at
all
dose
levels.
However,
at
350
ppm,
decreased
activity,
increase
in
number
of
animals
with
drooping/
half­
closed
eyelids
and
alertness
as
measured
in
a
FOB
examination,
decreased
rears,
decreased
motor
activity,
increased
piloerection
and
decreased
body
temperature
in
males
and
females
were
observed.
A
slight
decrease
in
hind­
limb
grip
strength
in
males
may
have
been
treatment­
related.
Effects
were
transient
and
all
animals
were
assessed
to
be
normal
by
1
week
post­
exposure.
At
30
or
100
ppm,
no
treatment­
related
effects
on
FOB
or
motor
activity
were
observed.

This
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirement
(
§
81­
81­
8)
for
an
acute
neurotoxicity
study
in
rats.

Developmental
Toxicity
Study
Executive
Summaries
for
Selection
of
Acute
Reference
Dose
in
Females
13­
49
Years
of
Age
In
a
developmental
toxicity
study
(
MRID
No.
41580401),
pregnant
New
Zealand
White
rabbits
(
26
animals/
dose)
were
exposed
by
whole
body
inhalation
to
0,
20,
40
or
80
ppm
MeBr
vapor
for
6
hr/
day
on
Days
6­
16
of
gestation.
Mating
was
conducted
using
artificial
insemination.
Based
on
the
insemination
record
the
females
were
inseminated
with
sperm
pooled
from
several
bucks.

Maternal
Toxicity
At
80
ppm,
clinical
signs
of
maternal
toxicity
including
decreased
appetite,
lethargy,
right
side
head
tilt,
slight
ataxia
and
slight
lateral
recumbency
were
observed.
These
signs
were
mostly
observed
in
three
rabbits:
#
5427,
#
5428
and
#
5431.
One
doe
(#
5428)
in
this
treatment
group
delivered
on
gestation
day
27
and
it
was
determined
that
this
early
delivery
may
have
been
related
to
the
toxicity
that
this
animal
was
experiencing.
In
addition,
a
treatment­
related,
but
not
doserelated
decrease
in
body
weight
was
observed
in
the
maternal
animals
in
the
high
dose
group.
Three
animals
(#
5427,
5428,
and
5431)
caused
decrease
in
the
mean
body
weights
of
the
high
dose
group.
The
body
weight
loss
of
these
animals
prior
to
delivering
their
litters
were
604,
464,
and
136
g,
respectively.
No
clinical
signs
of
toxicity
were
present
in
the
lower
treatment
groups.
Developmental
Toxicity
The
fetal
data
indicate
an
increase
in
the
incidence
of
agenesis
(
absence)
of
the
gall
bladder
in
the
fetuses
of
the
high
dose
group
(
13/
159)
(
8.2%)
relative
to
the
control
group
(
2/
190)
(
1.1%).
The
litter
incidences
of
agenesis
of
the
gall
bladder
were
5/
19
(
26.3%)
in
the
high
dose
group
and
1/
21
(
4.8%)
in
the
control
group.
The
litter
incidences
of
agenesis
of
the
gall
bladder
in
the
low­
and
mid­
dose
groups
were
1/
15
(
6.7%)
and
1/
19
(
5.3%),
respectively.
The
individual
animal
data
indicate
9
fetuses
with
missing
gall
bladder
were
from
4
does
with
maternal
toxicity
in
the
high
dose
group.
The
litter
incidences
of
agenesis
was
seen
in
6
fetuses
from
one
litter
(
animal
#
5427)
and
1
fetus
each
from
3
litters
[
animal
#
5428,
5431
and
5430].
One
doe
(
animal
#
5432)
with
no
maternal
toxicity
had
4
fetuses
with
missing
gall
bladder.
Two
does
(
animal
#
5426
and
5433)
with
maternal
toxicity
(
lethargy
only)
had
normal
fetuses.

In
a
repeated
study,
it
was
confirmed
that
the
observed
finding
of
agenesis
of
the
gall
bladder
was
related
to
treatment
and
was
not
attributed
to
a
particular
male
used
for
artificial
insemination.
The
incidence
of
agenesis
of
the
gall
bladder
found
in
this
repeat
study
is
similar
to
the
incidence
in
the
main
study.
The
incidence
of
agenesis
of
the
gall
bladder
in
the
fetuses
were
4/
92
(
4.3%)
in
the
high
dose
group
and
1/
114
(
0.9%)
in
the
control
group.
The
incidence
of
agenesis
of
the
gall
bladder
in
the
litters
were
4/
14
(
28.6%)
in
the
high
dose
group
and
1/
16
(
6.3%)
in
the
control
group.
At
80
ppm,
the
signs
of
severe
maternal
toxicity
(
lethargy,
right
side
head
tilt,
slight
ataxia
and
slight
lateral
recumbency)
were
not
observed
in
this
repeat
study.

At
80
ppm,
the
number
of
fused
sternebrae
were
increased
in
the
high
dose
group
(
12.6%)
when
compared
to
the
control
group
(
0%).
In
addition,
mean
fetal
body
weight
was
slightly
lower
(
4.4%;
non­
statistically
significant)
compared
to
the
control
group.
Although
the
nominal
fetal
weight
decrement
was
not
statistically
significant,
the
decrease
is
consistent
with
other
effects
occurring
at
the
high
dose.

The
data
seemed
to
indicate
that
the
failure
of
gall
bladder
development
was
due
to
the
direct
effects
of
MeBr
and
it
might
not
be
caused
by
the
parental
influence.

This
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirement
(
§
83­
3)
for
a
developmental
toxicity
study
in
rabbits.

Chronic/
Carcinogenicity
Study
Executive
Summaries
for
Selection
of
Chronic
Reference
Dose
in
All
Populations
In
a
combined
chronic
toxicity/
carcinogenicity
study
(
MRID
44462501),
micro
encapsulated
MeBr
was
administered
to
4
groups
of
male
and
female
Crl:
CD
®
(
SD)
BR
rats
for
a
period
of
12
or
24
months
(
interim
and
main
study,
respectively)
in
the
diet
at
concentrations
of
0
(
diet
control),
0
(
placebo
control),
0.5,
2.5,
50,
or
250
ppm.
These
concentrations
were
equivalent
to
0,
0.02,
0.11,
2.20
and
11.10
mg/
kg/
day
in
males
and
0,
0.03,
0.15,
2.92
and
15.12
mg/
kg/
day
in
females.
Groups
of
50
males
and
50
females
were
designated
for
the
main
study
and
were
maintained
on
the
treated
food
for
up
to
104
weeks.
Groups
of
20
males
and
20
females
were
sacrificed
at
52
weeks
in
the
diet
control,
placebo
control,
50
ppm
group
and
the
250
ppm
group.
Survival
was
not
affected
by
the
test
substance
in
any
of
the
treated
groups
compared
to
either
of
the
control
groups.
No
treatment­
related
clinical
signs
or
effects
on
hematology,
serum
chemistry,
urinalysis,
or
organ
weight
data
were
observed.
The
test
article
did
not
produce
changes
in
ophthalmoscopic
examinations
for
the
treated
groups
compared
to
the
controls.
Macroscopic
and
microscopic
evaluations
of
organs
and
tissues
at
the
interim
and
final
sacrifices
revealed
only
normal
age­
related
changes,
changes
that
were
observed
with
equal
frequency
in
the
controls.
No
treatment­
related
increase
in
tumor
incidence
was
found
in
this
carcinogenicity
study.

Statistically
significant
treatment­
related
effects
were
observed
on
body
weights,
body
weight
gains
and
food
consumption
in
males
and
females
treated
with
250
ppm
of
the
test
substance
during
the
first
12
to
18
months
of
the
study.
Males
in
the
250
ppm
group
had
decreases
of
5.5%
in
mean
body
weight
compared
to
the
diet
control
at
week
2,
by
week
14
this
decrease
was
10%
and
remained
consistently
lower
through
week
70.
During
the
second
year
of
the
study
these
animals
gradually
regained
the
weight
and
were
comparable
to
controls
at
the
end
of
the
study.
Females
in
the
250
ppm
group
had
a
decrease
of
3.7%
in
mean
body
weight
compared
to
the
diet
control
at
week
2,
by
week
14
this
decrease
was
8.3%
and
also
remained
consistently
lower
through
week
57.
After
week
57
females
in
the
250
ppm
group
gained
weight
gradually
and
the
decreases
disappeared
by
the
end
of
the
study
(
week
104)
at
which
time
this
group
had
mean
body
weight
values
that
were
similar
to
controls.
Mean
body
weight
gain
was
markedly
decreased
during
the
first
18­
months
of
the
study
for
animals
treated
with
250
ppm
MeBr;
decreases
of
9­
18%
and
12­
21%
were
observed
for
males,
and
7­
22%
and
11­
19%
were
observed
for
females
when
compared
to
the
basal
diet
and
placebo
control
groups,
respectively.
Males
receiving
250
ppm
had
decreased
food
consumption
that
ranged
from
3.7
­
11.5
%
for
week
71­
72,
and
females
at
this
concentration
had
decreases
of
4.8
­
10.5%
for
week
54­
55
compared
to
their
respective
control
groups.

This
chronic
toxicity/
carcinogenicity
study
in
the
rat
is
Acceptable/
guideline
and
satisfies
the
guideline
requirements
for
a
combined
chronic
toxicity/
carcinogenicity
oral
study
(
§
83­
5)
in
rats.

Subchronic
Inhalation
Study
Executive
Summaries
for
Short­
and
Intermediate
Term
Inhalation
Risk
Executive
Summary
(
5­
7
week):

In
a
subchronic
(
5­
to
7­
week)
inhalation
toxicity
study
(
MRID
43386802),
MeBr
(
tech.,
100%
a.
i.)
was
administered
7
hours/
day,
5
days/
week
to
4
beagle
dogs/
sex/
dose
by
whole
body
exposure
at
target
concentrations
of
0,
5,
10/
150,
25,
50
or
100
ppm
(
actual
mean
concentrations
0,
5.3,
11.0/
158.0,
26.0,
53.1
or
102.7
ppm;
equivalent
to
0,
0.021,
0.043/
0.614,
0.101,
0.206
or
0.399
mg/
L),
as
follows:

5
Week
sacrifice
­
2
dogs/
sex,
0
ppm
group
and
all
dogs,
25,
50
and
100
ppm
groups,
for
5
weeks
(
total
24
exposures);
7
Week
sacrifice
­
2
dogs/
sex,
0
ppm
group
and
all
dogs,
5
ppm
group
for
7
weeks
(
total
34
exposures);
and
all
dogs,
10/
150
ppm
group
for
5
weeks
at
10
ppm
(
24
exposures),
then
at
150
ppm
for
6
additional
exposures
and
terminated.
In
addition
to
standard
evaluations
performed
in
a
guideline
subchronic
study,
a
neurological
examination
was
performed
by
a
veterinarian
after
termination
of
exposures
and
serum
bromide
levels
were
measured
weekly.

5
Week
sacrifice:

At
5.3,
11,
or
26
ppm,
there
were
no
treatment­
related
effects
on
food
consumption,
ophthalmological
findings,
hematology
parameters,
organ
weights
or
gross
findings
(
Table
2).
However,
at
53.1
ppm,
2/
8
dogs
showed
decreased
activity
during
exposure
beginning
day
14.
And,
at
102.7
ppm,
3/
8
dogs
showed
decreased
activity
beginning
exposure
day
9,
and
by
exposure
day
12
and
continued
until
sacrifice
all
dogs
showed
decreased
activity.
One
male
developed
tremors
on
day
10.
In
addition,
these
dogs
at
102.7
ppm
lost
body
weight
(
9%
less
than
controls).
Cumulative
weight
loss
of
males
and
females
were
0.6
kg
and
1.0
kg,
respectively.
The
systemic
toxicity
NOAEL
for
5
weeks
(
24
exposures)
is
26
ppm.
The
LOAEL
is
53.1
ppm
based
on
decreased
activity.

7
Week
sacrifice:

In
this
study,
MeBr
at
5
ppm
dose
demonstrated
an
unresponsiveness
in
1
female
dog
and
unresponsiveness
and
depressed
appearance
in
another
female
at
the
end
of
34
exposures.
However,
these
effects
are
not
considered
as
treatment­
related
because
these
effects
did
not
show
clear
dose­
response
relationship
(
similar
effects
of
unresponsiveness
and
depressed
appearance
were
not
observed
at
higher
exposure
levels
of
shorter
duration)
and
were
not
corroborated
with
other
findings.

No
clinical
signs
of
toxicity
were
observed
at
#
26
ppm.
At
53
ppm,
decreased
activity
(
lack
of
interest
when
approached)
was
first
observed
in
2
dogs
on
day
14.
Thereafter,
1
to
4
of
the
dogs
in
that
group
showed
decreased
activity
on
most
exposure
days.
At
103
ppm,
3
dogs
showed
decreased
activity
on
day
9;
by
day
12,
all
animals
had
decreased
activity
during
most
of
the
remainder
of
the
exposure
period.
One
animal
(
sex
not
indicated)
had
tremors
on
day
10.
When
exposure
of
Group
III
animals
(
11
ppm)
was
increased
to
158
ppm
on
exposure
day
25,
decreased
activity
was
observed
in
all
animals
beginning
on
day
27.
All
dogs
were
in
poor
condition
by
day
30,
including
one
male
that
was
prostrate
and
had
tremors.

This
subchronic
toxicity
study
is
classified
Acceptable/
Non­
Guideline
(
§
82­
4)
and
fulfills
the
intent
of
the
study.
A
subchronic
inhalation
study
in
the
dog
was
not
required
by
the
US
EPA
for
reregistration
of
MeBr;
this
study
was
conducted
as
a
range­
finding
study
for
a
chronic
inhalation
study
in
dogs
to
satisfy
CDPR's
data
requirements.

Executive
Summary
(
6
week):

In
a
six­
week
nonguideline
inhalation
toxicity
study
(
MRID
45722801),
four
groups
of
beagle
dogs
consisting
of
4
males
and
4
females/
group
were
administered
MeBr
(
Lot
No:
1010PK15A;
purity:
100%
a.
i.)
by
whole
body
exposure
at
concentrations
of
0,
5.3,
10,
and
20
ppm
(
equivalent
to
0,
1.8,
3.4
and
6.9
mg/
kg/
day).
The
exposures
were
for
seven
hours/
day,
five
days/
week
for
six
weeks
(
total
of
30
exposures).
There
were
no
compound
related
effects
on
mortality,
clinical
signs,
body
weight,
food
consumption,
spleen
weights,
or
gross
or
histological
pathology.
Functional
observational
battery
and
locomotor
activity
tests
showed
no
abnormalities
relative
to
controls
with
one
exception.
In
this
study,
one
male
at
10
ppm
dose
demonstrated
an
absence
of
proprioceptive
placing
response,
although
no
evidence
of
weakness
in
motor
strength
or
other
signs
of
neurotoxicity
was
found.
These
effects
are
considered
treatment­
related
because,
all
dogs
also
had
the
increased
incidence
(
not
supported
by
statistics)
of
feces­
findings
(
soft,
mucoid
feces,
and/
or
diarrhea)
mostly
later
in
the
study.
At
the
20
ppm
dose,
one
male
and
one
female
demonstrated
an
absence
of
proprioceptive
placing
response
due
to
treatment.
In
addition,
all
dogs
had
the
increased
incidence
of
feces­
findings
(
soft,
mucoid
feces,
and/
or
diarrhea)
and
2
dogs
at
this
dose
showed
higher
incidence
of
discharge
around
the
eyes
compared
to
the
controls.

The
LOAEL
for
MeBr
was
10
ppm
for
male
dogs
and
20
ppm
for
female
dogs
based
on
the
absence
of
proprioceptive
placing
and
the
increased
incidence
(
not
supported
by
statistics)
of
feces­
findings
(
soft,
mucoid
feces,
and/
or
diarrhea).
The
NOAELs
was
5.3
ppm
for
male
dogs
and
10.0
ppm
for
female
dogs.
This
six­
week
inhalation
toxicity
study
in
beagle
dogs
is
Acceptable/
Nonguideline
and
fulfills
the
intent
of
the
study.

Use
of
the
endpoint
from
the
subchronic
inhalation
studies
conducted
in
dogs
is
appropriate
for
the
exposure
time
period
of
1day
to
6
months.

Chronic/
Carcinogenicity
Inhalation
Study
Executive
Summaries
for
Long
Term
Inhalation
Risk
In
a
chronic
toxicity/
carcinogenicity
study
(
MRIDs
41213301,
42418301,
44359101),
50
Wistar
(
Cpb:
Wu)
rats/
sex/
dose
were
exposed
to
MeBr
(>
98.8%
a.
i.)
by
whole
body
exposure
at
concentrations
of
0,
3,
30
or
90
ppm
(
0,
0.0117,
0.117
or
0.335
mg/
L)
for
127
weeks
(
males)
or
129
weeks
(
females).
Four
additional
groups
of
10
animals/
sex/
dose
were
also
included
for
sacrifice
as
follows:
(
a)
week
13,
clinical
chemistry/
hematology
evaluations;
(
b)
week
53,
clinical
chemistry/
hematology
evaluations
and
gross/
microscopic
pathology;
(
c)
week
105,
gross/
microscopic
pathology
and
(
d)
week
41,
behavioral
evaluations
(
males
only).
A
reexamination
of
nasal
cavity
microscopic
lesions
was
later
conducted
by
an
independent
reviewing
pathologist
and
the
final
diagnosis
reached
after
discussion
with
the
study
pathologist
(
MRID
44359101).
(
The
reexamination
was
not
performed
according
to
recommended
protocol
for
peer
review
and
therefore
the
conclusions
of
this
review
are
based
on
the
results
from
the
original
report).

At
3
ppm,
statistically
significant
increases
in
incidence
(
but
not
severity)
of
basal
cell
hyperplasia
of
the
nasal
cavity
were
observed
at
termination
(
27.0%,
males
and
31.7%,
females,
vs.
8.7%
and
11.9%,
controls,
respectively.
The
severity
of
most
lesions
was
very
slight.
At
30
ppm,
severity
as
well
as
incidence
of
basal
cell
hyperplasia
of
the
nasal
cavity
was
increased
at
termination
(
46.9%,
males
and
40.8%,
females).
The
severity
of
lesions
was
slight
or
moderate.

At
90
ppm,
decreased
survival
(
at
termination,
males
30%
vs.
16%,
controls
and
females
14%
vs.
30%,
controls;
statistically
significant
only
on
a
few
occasions
in
each
sex),
decreased
mean
body
weight
(
at
termination
5%,
males;
significant
frequently
during
study
and
12%,
females;
significant
throughout
most
of
study
after
Week
4).
There
were
also
increased
incidence
of
grossly
visible
hemothorax
in
animals
found
dead
or
sacrificed
in
extremis,
significantly
increased
incidence
of
thrombus
(
43%
vs.
10%,
controls,
males
and
33%
vs.
8%,
females),
cartilaginous
metaplasia
(
24%
vs.
4%,
controls,
males)
and
moderate
to
severe
myocardial
degeneration
(
73%
vs.
41%,
controls,
females;
not
significant
in
males
­
84%
vs.
65%).
Irritation
of
the
esophagus
and
forestomach
may
have
been
related
to
inadvertent
ingestion
of
test
material
(
e.
g.,
during
grooming).
In
males,
increases
in
hyperkeratosis
of
the
esophagus
(
67%
vs.
39%,
controls;
statistically
significant)
and
stomach
(
52%
vs.
30%,
controls;
not
significant)
were
observed.
However,
in
these
males
at
90
ppm,
MeBr
did
not
produce
treatment­
related
effects
on
clinical
signs,
hematology,
clinical
chemistries,
urinalysis
parameters
or
behavioral
parameters.

There
were
no
increases
in
the
incidence
of
neoplastic
lesions
attributed
to
exposure
to
MeBr
in
males
or
females.

This
chronic
toxicity/
carcinogenicity
study
is
classified
Acceptable/
Guideline
for
83­
2(
a)
carcinogenicity
study
and
satisfies
the
guideline
requirements
for
an
inhalation
carcinogenicity
study
in
the
rodent.

Acute
Toxicity
Data
on
MeBr
Technical
Guideline
No.
Study
Type
MRID
#
(
s)
Results
Toxicity
Category
870.1100
Acute
oral
(
MeBr
in
vegetable
oil)
43510301
LD50
=
120­
160
mg/
kg
(
males)
LD50
=
86
mg/
kg
(
females)
II
870.1200
Acute
dermal
N/
Ad
N/
Ad
N/
A
870.1300
Acute
inhalation
Kato
et
al
(
1986)
a
LC50
=
3.03
mg/
L,
4
hr
exposure
IV
870.2400
Primary
eye
irritation
Alexeef,
G.;
Kilgore,
W.
(
1983)
b
and
Hezemans­
Boer
et
al
(
1988)
c
Severe
irritation
following
accidental
exposure
to
humans
I
870.2500
Primary
skin
irritation
Alexeef,
G.;
Kilgore,
W.
(
1983)
and
Hezemans­
Boer
et
al
(
1988)
Severe
irritation
following
accidental
exposure
to
humans
I
870.2600
Skin
sensitization
N/
Ad
N/
Ad
N/
A
Acute
Toxicity
Data
on
MeBr
Technical
Guideline
No.
Study
Type
MRID
#
(
s)
Results
Toxicity
Category
a:
Kato,
N.;
Morinobu,
S.;
Ishizu,
S.
(
1986)
Subacute
inhalation
Experiment
for
MeBr
in
Rats.
Industr.
Health.
24:
87­
103.

b:
Alexeef,
G.;
Kilgore,
W.
(
1983)
MeBr.
In:
Gunther,
F.;
Gunther,
J.,
ed.
Residue
Reviews.
Residues
of
Pesticides
and
Other
Contaminants
in
the
Total
Environment,
Vol.
88,
p.
102­
153.
New
York,
Springer
Verlag.

c:
Hezemans­
Boer,
M;
Toonstra,
J.;
Meulenbelt,
J.;
et
al.
(
1988)
Skin
Lesions
Due
to
Exposure
to
MeBr.
Arch.
Derm.
124:
917­
921.

d:
N/
A
(
Not
Available):
Acute
dermal
toxicity
and
dermal
sensitization
potential
studies
were
not
required
because
there
is
already
a
clear
evidence
that
severe
irritation
to
skin
occurs
after
acute
dermal
exposure
to
MeBr.
Subchronic,
Chronic
and
Other
Toxicity
Table
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
in
rats
(
peanut
oil)
00154564
(
1984)
classification:
no
DER
available.
NOAEL
=
2
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
slight
hyperplasia
of
the
stratified
squamous
epithelium
of
the
forestomach.
HDT
was
50
mg/
kg/
day.

870.3150
4­
week
oral
toxicity
in
rats
(
capsule)
43776401
(
1995)
acceptable/
nonguideline
NOAEL
=
0.835
mg/
kg/
day.
LOAEL
=
7.99
mg/
kg/
day
(
HDT),
based
on
slightly
decreased
body
weight
gain
and
food
consumption.

870.4300
Chronic
toxicity
and
carcinogenicity
in
rats
(
micro
capsulated)
44462501
(
1997)
acceptable/
guideline
0,
0.5,
2.5,
50,
or
250
ppm
(
M:
0,
0.02,
0.11,
2.2,
or
11.1;
F:
0,
0.03,
0.15,
2.92,
and
15.12
mg/
kg/
day
for
24
months.
NOAEL
=
50
ppm
(
2.2
mg/
kg/
day
for
males
and
2.92
mg/
kg/
day
for
females).
LOAEL
=
250
ppm
(
11.1
mg/
kg/
day
for
males
and
15.12mg/
kg/
day
for
females),
based
on
decreased
body
weight,
body
weight
gain,
and
food
consumption
in
males
and
females
during
the
first
18
months
of
the
study.
No
evidence
of
carcinogenicity
870.4100b
Chronic
toxicity
dogs
(
fumigated
feed)
43885201
(
1996)
acceptable/
guideline
0,
0.5,
1.5
or
5
ppm
(
M:
0,
0.06,
0.13
or
0.27;
F:
0,
0.07,
0.12
or
0.27
mg/
kg/
day
for
12
months.
NOAEL/
LOAEL
>
5
ppm
(
HDT)
(
equivalent
to
0.27
mg/
kg/
day)
It
is
noted
that
this
study
was
conducted
to
establish
a
margin
of
safety
for
human
dietary
exposure
rather
than
to
determine
a
LOAEL.

870.6200a
Acute
neurotoxicity
screening
battery
in
CD
rats
(
Via
inhalation)
42793601
(
1993)
acceptable/
guideline
0,
30,
100
or
350
ppm,
for
6
hrs
(
M:
27,
90
or
314;
F:
30,
101,
or
354
mg/
kg/
day).
NOAEL
=
100
ppm
LOAEL
=
350
ppm
based
on
decreased
activity
and
alertness
as
measured
in
a
functional
observation
battery
examination,
decreased
motor
activity
and
decreased
body
temperature
in
males
and
females
were
observed.
A
slight
decrease
in
hind­
limb
grip
strength
in
males
may
have
been
treatment­
related.
Effects
were
transient
and
all
animals
were
assessed
to
be
normal
by
1
week
post­
exposure.

870.3700a
Prenatal
developmental
in
Wistar
rats
(
via
inhalation)
00102990
(
1981)
acceptable/
guideline
0,
20
or
70
ppm
(
equivalent
to
0,
20,
or
71
mg/
kg/
day) 
7
hrs/
day;
5
days/
wk
Maternal
NOAEL/
LOAEL
>
70
ppm
(
HDT).
Slightly
increased
incidence/
severity
of
interstitial
nephritis
at
70
ppm
may
represent
threshold
effect.

Developmental
NOAEL
/
LOAEL
>
70
ppm
(
HDT)

870.3700b
Prenatal
developmental
in
rabbits
(
via
inhalation)
41580401
(
1990)
acceptable/
guideline
0,
20,
40,
or
80
ppm
(
equivalent
to
0,
7.1,
14
or
28
mg/
kg/
day)
­
6
hrs/
day
for
17
days
Maternal
NOAEL
=
40
ppm;
LOAEL
=
80
ppm
based
on
decreased
appetite,
lethargy,
right
side
head
tilt,
ataxia
and
lateral
recumbency.

Developmental
NOAEL
=
40
ppm;
LOAEL
=
80
ppm
based
on
agenesis
of
the
gall
bladder,
increased
incidence
of
fused
sternebrae
and
decreased
fetal
body
weight
Subchronic,
Chronic
and
Other
Toxicity
Table
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.6200b
Subchronic
neurotoxicity
screening
battery
(
via
inhalation)
in
rats
42964301;
43077401
(
1993)
acceptable/
guideline
0,
30,
70
or
140
ppm
6
hr/
day,
5
days/
week
 
13
weeks
(
equivalent
to
males:
0,
19,
45,
or
90
mg/
kg/
day;
females:
0,
22,
51,
101
mg/
kg/
day)
NOAEL
=
30
ppm
(
F)
LOAEL
=
70
ppm
(
F)
based
on
decreased
body
weight
and
motor
activity.
NOAEL
=
70
ppm
(
M)
LOAEL
=
140
ppm
(
M)
based
on
decreased
body
weight,
increased
mortality
(
2
animals),
convulsions
(
2
animals
affected),
effects
on
several
FOB
parameters
and
brain
histopathology
in
males.

870.3465
Subchronic
Inhalation
Toxicity
in
dogs
43386802
(
1994)
acceptable/
guideline
0,
5,
10/
150,
25,
50
or
100
ppm
(
actual
mean
concentrations
0,
5.3,
11.0/
158.0,
26.0,
53.1
or
102.7
ppm;
equivalent
to
1.43,
2.97/
42.7,
7.02,
14.3,
27.7
mg/
kg/
day).
7
hours/
day
Systemic
toxicity
for
a
7
weeks
(
34
exposures)
NOAEL
(
threshold)
=
<
5
ppm.
LOAEL
(
threshold)=
5
ppm
(
0.021
mg/
L),
based
on
decreased
responsiveness
in
females.

870.3800
Reproduction
and
fertility
effects
in
CD
rats
(
via
inhalation)
00160477
(
1986)
acceptable/
guideline
0,
3,
30,
or
90
ppm
for
6
hours/
day
(
equivalent
to
males:
0,
2.4,
24
or
73
mg/
kg/
day;
females:
0,
2.8,
28
or
85
mg/
kg/
day)
Parental/
Systemic
NOAEL
=
30
ppm
Parental/
Systemic
LOAEL
=
90
ppm
based
on
reduced
body
weight
Reproductive
NOAEL
=
3
ppm
Reproductive
LOAEL
=
30
ppm
based
on
reduced
pregnancy
rates
(
23%,
F2b)
Offspring
NOAEL
=
3
ppm
Offspring
LOAEL
=
30
ppm
based
on
reduced
pup
weight
on
post­
natal
day
21
(
F1a,
F2a,
F2b
generations)
ranging
from
10­
20%.

870.4300
Chronic
toxicity
and
carcinogenicity
(
29­
month)
in
rats
(
via
inhalation) 
Wis
tar
rats
41213301
(
1987);
42418301;
44359101
acceptable/
guideline
0,
3,
30
or
90
ppm
(
0,
0.0117,
0.117
or
0.335
mg/
L)
(
equivalent
to
males:
0,
1.9,
19
or
58
mg/
kg/
day;
females:
0,
2.2,
22
or
65
mg/
kg/
day)
Local
irritation
NOAEL
<
3
ppm
(
0.0117
mg/
L);
LOAEL
=
3
ppm
(
0.0117
mg/
L),
based
on
increased
incidence
of
basal
cell
hyperplasia
of
the
nasal
cavity
in
both
sexes.
Systemic
toxicity
NOAEL
=
30
ppm
(
0.117
mg/
L);
LOAEL
=
90
ppm
(
0.335
mg/
L),
based
on
increased
mortality,
decreased
body
weight
and
relative
brain
weight,
hemothorax,
increased
incidence
of
thrombus,
cartilaginous
metaplasia,
myocardial
degeneration
and
irritation
of
the
esophagus
and
forestomach.
No
evidence
of
carcinogenicity
870.4300
Chronic
toxicity
and
carcinogenicity
in
mice
 
B6C3F1
(
via
inhalation) 
2
years
National
Toxicology
Program
Study
TR
385
42504101
(
1992)

acceptable/
guideline
for
carcinogenicity
study.
0,
10,
33
or
100
ppm 
6
hrs/
day;
5
days/
week
(
0,
11.8,
38.9
or
118
mg/
kg/
day)
Local
irritation
NOAEL/
LOAEL
=
not
reported
Systemic
toxicity
NOAEL
=
33
ppm
(
0.1279
mg/
l);
LOAEL
=
100
ppm
(
0.3876
mg/
l),
based
on
mortality
(
males),
neurological
signs
(
abnormal
posture,
tremors,
ataxia,
limb
paralysis
and
emaciation)
decreased
body
weight/
weight
gain
and
microscopic
lesions
in
the
brain,
heart,
sternum
and
olfactory
epithelium.
No
evidence
of
carcinogenicity
[
No
data
on
clinical
chemistry,
urinalysis,
and
gross
findings]
Subchronic,
Chronic
and
Other
Toxicity
Table
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Cytogenetic
870.5395
Study
type:
Micro
nucleus
assay
in
mice
and
rats
43786501
(
1986?)
Acceptable/
guideline
Dose
range:
0,
154,
200,
260,
338
or
440
ppm
(
equivalent
to
0,
0.597,
0.776,
1.008,
1.311
or
1.706
mg/
L)
for
6
hrs/
day,
5
days/
week
for
14
days,
or
10
exposures.
The
test
was
positive.

Micro
nucleus
(
MN)
induction
was
evaluated
in
bone
marrow
of
rats
and
mice
and
in
peripheral
blood
of
mice.

Other
Genotoxicity
study
870.
Study
Type:
Rat
testicular
DNA
alkaline
elution
assay
43180201
(
1994)
Acceptable/
nonguideline
Dose
range:
0,
75,
150
or
250
ppm
(
0,
291,
581
or
969
mg/
m3)
for
6
hr/
day
over
5
consecutive
days
The
test
was
positive.

870.7485
Metabolism
and
pharmacokinetic
s
International
Agency
for
Research
on
Cancer
(
IARC)
Monographs
Vol
41,
p198
Rats
received
a
single
gavage
dose
(
preparation
of
test
solution
was
unspecified)
of
24
mg/
kg/
b.
w.
14C­
MeBr.
Over
a
3­
day
period,
the
radioactivity
recovered
were
as
follows:
carcass
(
14­
17%),
expired
carbon
dioxide
(
32%),
urine
(
43%),
and
feces
(
less
than
3%).

During
a
6­
hour
exposure
of
rats
to
4.75­
9874
mg/
cu.
m
14C­
MeBr
vapor,
approximately
27­
50%
of
the
compound
inhaled
was
absorbed.

870.6300
Developmental
Neurotoxicity
Study
46665001
(
2004)
Acceptable/
nonguideline
Dose
Range:
0,
5,
25,
or
50
ppm
Maternal
NOAEL
=
50
ppm;
LOAEL
=
not
identified
Developmental
NOAEL
=
5
ppm;
LOAEL
=
25
ppm
based
on
decreased
motor
activity
on
PND21
(*)
A
new
90­
day
inhalation
study
in
rodents
is
not
required
for
reregistration
of
MeBr.
Acceptable
rat
chronic
inhalation
toxicity
(
MRIDs
41213301,
42418301;
reviewed
in
HED
doc.
nos.
007017,
007845,
009843
and
14130)
and
rat
90­
day
inhalation
neurotoxicity
(
MRIDs
42933901
and
43077401;
reviewed
in
HED
doc.
no.
010820)
studies
have
been
received.
These
studies
provide
adequate
descriptions
of
systemic
toxicity
to
rodents
from
inhalation
exposures
of
intermediate
duration.
Appendix
B
Methodologies
for
Inhalation
Risk
Calculations
and
Human
Equivalent
Concentration
Arrays
METHODOLOGIES
FOR
INHALATION
RISK
CALCULATIONS
In
evaluating
the
risks
that
a
compound
may
pose
to
human
health
after
exposure
via
the
inhalation
route,
different
methodologies
have
been
historically
used
by
the
USEPA
and
CDPR.

The
Agency's
approach
to
calculating
risks
due
to
inhalation
exposure
is
based
on
the
guidance
methodology
developed
by
the
Office
of
Research
and
Development
(
ORD)
for
the
derivation
of
inhalation
reference
concentrations
(
RfCs)
and
human
equivalent
concentrations
(
HECs)
for
use
in
margin
of
exposure
(
MOE)
calculations
(
RfC
methodology).
An
example
of
CDPR's
methodology,
and
the
species­
specific
parameters
used
in
this
approach
can
be
found
in
the
CDPR
methyl
bromide
risk
assessment,
Appendix
G
(
www.
cdpr.
ca.
gov/
docs/
dprdocs/
methbrom/
append_
g.
pdf).
As
OPP
understands
the
importance
to
harmonize,
to
the
extent
possible,
with
other
regulatory
agencies,
this
risk
assessment
will
present
HECs
derived
using
both
methodologies.

The
RfC
methodology
applies
a
dosimetric
adjustment
that
takes
into
consideration
not
only
the
differences
in
ventilation
rate
(
MV)
but
also
the
physicochemical
properties
of
the
inhaled
compound,
the
type
of
toxicity
observed
(
e.
g.
systemic
vs.
port
of
entry)
and
the
pharmacokinetic
(
PK)
but
not
pharmacodynamic
(
PD)
differences
between
animals
and
humans.
Based
on
the
RfC
guidance
(
1994),
the
methodology
for
RfCs
derivation
is
an
estimate
of
the
quantitative
dose­
response
assessment
of
chronic
non­
cancer
toxicity
for
individual
inhaled
chemicals
and
includes
dosimetric
adjustment
to
account
for
the
species­
specific
relationships
of
exposure
concentration
to
deposited/
delivered
dose.
This
adjustment
is
influenced
by
the
physicochemical
properties
of
the
inhaled
compound
as
well
as
the
type
of
toxicity
observed
(
e.
g.
systemic
vs.
port
of
entry),
and
takes
into
consideration
the
PK
differences
between
animals
and
humans.
Though
the
RfC
methodology
was
developed
to
estimate
toxicity
of
inhaled
chemicals
over
a
lifetime,
it
can
be
used
for
other
inhalation
exposures
(
e.
g.
acute
and
short­
term
exposures)
since
the
dosimetric
adjustment
incorporates
mechanistic
determinants
of
disposition
that
can
be
applied
to
shorter
duration
of
exposures
provided
the
assumptions
underlying
the
methodology
are
still
valid.
These
assumptions,
in
turn,
vary
depending
on
the
type
of
toxicity
observed
and
will
be
discussed
later
on
in
this
document.
Thus
the
derivation
of
a
HEC
for
inhaled
gases
is
described
by
the
following
equation:
HEC
=
POD
*
D
D
*
W
W
*
RGDR
study
animal
exposure
(
hrs
/
day)

human
exposure
(
hrs
/
day)
animal
exposure
(
days
/
wk)

human
exposure
(
days
/
wk)

Where:

POD
study
:
Point
of
departure
identified
in
the
critical
toxicology
study
D
animal
exposure
:
Duration
of
animal
exposure
(
hrs/
day;
days/
wk)
D
anticipated
exposure
:
Anticipated
human
duration
of
exposure
(
hrs/
day;
days/
wk)
RGDR:
Regional
Gas
Dose
Ratio
For
gases
eliciting
both
port
of
entry
and
systemic
effects,
calculations
to
estimate
the
inhalation
risk
to
humans
are
dependent
on
the
regional
gas
dose
ratio
(
RGDR).
In
the
case
of
systemic
effects,
the
RGDR
is
defined
as
the
ratio
of
the
blood:
gas
partition
coefficient
of
the
chemical
for
the
test
species
to
humans
(
H
b/
g
animal
/
H
b/
g
human
).
When
this
ratio
is
unknown
or
when
the
H
b/
g
animal
>
H
b/
g
human
a
default
value
of
1.0
is
used
as
the
RGDR.
This
default
is
based
on
the
observation
that
for
chemicals
where
partition
coefficient
data
are
available
in
both
rats
and
humans
the
RGDR
value
has
usually
been
comparable
or
slightly
higher
than
1.
Thus,
the
use
of
an
RGDR
of
1
results
in
a
protective
calculation
of
the
inhalation
risk.
Some
of
the
key
assumptions
fundamental
to
the
use
of
the
RfC
methodology
to
derive
a
HEC
based
on
systemic
effects
include:

1)
all
the
concentrations
of
inhaled
gas
within
the
animal's
body
are
periodic
with
respect
to
time
(
i.
e.
periodic
steady
state
­
the
concentration
vs
time
profile
is
the
same
for
every
week).
Periodicity
must
be
attained
for
at
least
90%
of
the
exposure.
2)
in
the
respiratory
tract,
the
air,
tissue,
capillary
blood
concentration
are
in
equilibrium
with
respect
to
each
other.
3)
systemically,
the
blood
and
tissue
concentrations
are
in
equilibrium
with
respect
to
each
other.

In
the
case
of
MeBr,
the
physicochemical
properties
and
metabolism
data
for
the
compound
indicate
that
these
conditions
(
i.
e.
periodicity
and
equilibrium
between
different
compartments)
will
be
achieved
in
a
very
short
period
of
time.
Under
these
conditions,
therefore,
the
use
of
the
RfC
methodology
to
estimate
acute
inhalation
risk
is
appropriate.

When
the
critical
toxic
effect
in
a
study
occurs
in
the
respiratory
tract
(
i.
e
port
of
entry
effects),
the
RGDR
is
not
related
to
the
blood:
gas
partition
coefficient
of
the
compound
but
rather
the
ratio
of
the
minute
volume
(
MV)
to
the
surface
area
(
SA)
of
the
affected
region.
In
these
instances,
attaining
periodicity
or
equilibrium
between
the
compartments
is
not
critical
(
since
the
effect
is
a
function
of
the
direct
interaction
between
the
inhaled
compound
and
the
affected
region
in
the
respiratory
tract)
and
the
RGDR
may
be
calculated
using
the
following
equation:

RGDR
=
MV
SA
MV
SA
animal
animal
human
human
Where:
MV
animal
:
Minute
volume
for
the
test
species
(
varies
depending
on
body
weight)
SA
animal
:
Surface
area
of
the
affected
region
in
animals
MV
human
:
Minute
volume
for
humans
(
default
value
is
13.8
l/
min)
SA
human
:
Surface
area
of
the
affected
region
in
humans
The
MV
animal
is
calculated
using
the
allometric
scaling
provided
in
USEPA
(
1988a).
The
equation
for
calculation
of
the
MV
animal
is:

lnMV
animal
=
b
0
+
b
1
ln(
BW)

Where:
ln
MV
animal
:
natural
logarithm
of
the
minute
volume
b
0
:
species
specific
intercept
used
in
the
algorithm
to
calculate
minute
volumes
based
on
body
weight
b
1
:
species
specific
coefficient
used
in
the
algorithm
to
calculate
minute
volumes
based
on
body
weight
ln
BW:
natural
logarithm
of
the
body
weight
(
expressed
in
kg)

The
values
for
the
species­
specific
parameters
used
to
calculate
the
MV
animal
based
on
body
weight
and
the
values
for
the
surface
areas
of
various
regions
of
the
respiratory
tract
(
extrathoracic,
thoracic,
and
pulmonary)
are
provided
in
the
EPA
document
"
Methods
for
Derivation
of
Inhalation
Reference
Concentrations
and
Application
of
Inhalation
Dosimetry"
(
1994).

The
magnitude
of
the
UFs
applied
is
dependent
on
the
methodology
used
to
calculate
risk.
When
using
the
methodology
developed
by
CDPR,
a
100X
UF
is
applied
(
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variation).
In
contrast,
the
RfC
methodology
takes
into
consideration
the
PK
differences
but
not
the
PD
differences.
Consequently,
the
UF
for
interspecies
extrapolation
may
be
reduced
to
3X
(
to
account
for
the
PD
differences)
while
the
UF
for
intraspecies
variation
is
retained
at
10X.
Thus,
the
UF
when
using
the
RfC
methodology
is
customarily
30X..
Hazard
Assessment
Array
HEC
Array
for
Non­
Occupational
Risk
Assessment
§

Relevant
Study
LOAEL
(
ppm)
NOAEL
(
ppm)
Da
Dh
Wa
Wh
RGDR
HEC
(
ppm)
Inter
Intra
UF
Acute
Exposure
ACN­
Rat
Systemic
350
100
6
24
1
1
1
25
10
3
1
Dev
Rat
Systemic
NA
NA
6
24
1
1
NA
NA
NA
NA
1
Dev
Rabbit
Systemic
80
40
6
24
1
1
1
10
10
3
1
Short
Term
Exposure
ACN­
Rat
Adult
350
100
6
24
1
1
1
25
10
3
1
Dev
Rat
Maternal
Systemic
70
20
6
24
5
7
1
3.6
10
3
1
Developmental
NA
70
6
24
5
7
1
13
10
3
1
Dev
Rabbit
Maternal
Systemic
80
40
6
24
5
7
1
7.1
10
3
1
Developmental
80
40
6
24
5
7
1
7.1
10
3
1
SCN­
Rat
Systemic
140
70
6
24
5
7
1
13
10
3
1
90D
Dog
Systemic
10
5
7
24
5
7
1
1.0
10
3
1
MultiGen
Repro:
Rat
Maternal
Systemic
90
30
6
24
5
7
1
5.4
10
3
1
Offspring
Systemic
30
3
6
24
5
7
1
0.54
10
3
1
DNT
Maternal
Systemic
NA
50
6
24
7
7
1
12.50
10
3
1
Offspring
Systemic
25
5
6
24
7
7
1
1.25
10
3
1
Intermediate
Term
Exposure
SCN­
Rat
Systemic
70
30
6
24
5
7
1
5.4
10
3
1
90D
Dog
Systemic
10
5
7
24
5
7
1
1.0
10
3
1
MultiGen
Repro:
Rat
Maternal
Systemic
90
30
6
24
5
7
1
5.4
10
3
1
Offspring
Systemic
30
3
6
24
5
7
1
0.54
10
3
1
DNT
Maternal
Systemic
NA
50
6
24
7
7
1
12.50
10
3
1
Offspring
Systemic
25
5
6
24
7
7
1
1.25
10
3
1
Long
Term
Exposure
SCN­
Rat
Systemic
70
30
6
24
5
7
1
5.4
10
3
1
90D
Dog
Systemic
10
5
7
24
5
7
1
1.0
10
3
1
MultiGen
Repro:
Rat
Maternal
Systemic
90
30
6
24
5
7
1
5.4
10
3
1
HEC
Array
for
Non­
Occupational
Risk
Assessment
§

Relevant
Study
LOAEL
(
ppm)
NOAEL
(
ppm)
Da
Dh
Wa
Wh
RGDR
HEC
(
ppm)
Inter
Intra
UF
Offspring
Systemic
30
3
6
24
5
7
1
0.54
10
3
1
Chronic
Rat
Local
3
NA
6
24
5
7
0.244
0.13
10
3
3
¶

Systemic
90
30
6
24
5
7
1
5.36
10
10
1
Chronic
Mouse
Systemic
100
33
6
24
5
7
1
5.9
10
3
1
§
Bolded
studies
used
for
endpoint
selection.
¶
A
3X
UF
for
LOAEL
to
NOAEL
extrapolation
is
recommended
due
to
the
minimal
severity
of
the
portal
of
entry
effects
noted
at
the
lowest
dose
tested.
HEC
Array
for
Occupational
Risk
Assessment
§

Relevant
Study
LOAEL
(
ppm)
NOAEL
(
ppm)
Da
Dh
Wa
Wh
RGDR
HEC
(
ppm)
Inter
Intra
UF
Acute
Exposure
ACN­
Rat
Systemic
350
100
6
8
1
1
1
75
3
10
1
Dev
Rat
Systemic
NA
NA
6
8
1
1
NA
NA
NA
NA
NA
Dev
Rabbit
Systemic
80
40
6
8
1
1
1
30
3
10
1
Short
Term
Exposure
ACN­
Rat
Systemic
350
100
6
8
1
1
1
75
3
10
1
Devel
Rat
Maternal
Systemic
70
20
6
8
5
5
1
15
3
10
1
Developmenta
l
NA
70
6
8
5
5
1
53
3
10
1
Dev
Rabbit
Maternal
Systemic
80
40
6
8
5
5
1
30
3
10
1
Developmenta
l
80
40
6
8
5
5
1
30
3
10
1
SCN­
Rat
Systemic
140
70
6
8
5
5
1
53
3
10
1
90D
Dog
Systemic
10
5
7
8
5
5
1
4.4
3
10
1
DNT
Maternal
Systemic
NA
50
6
8
7
7
1
37.50
10
3
1
Offspring
Systemic
25
5
6
8
7
7
1
3.75
10
3
1
Offspring
Systemic
30
3
6
8
5
5
1
2.3
3
10
1
Intermediate
Term
Exposure
SCN­
Rat
Systemic
70
30
6
8
5
5
1
23
3
10
1
90D
Dog
Systemic
10
5
7
8
5
5
1
4.4
3
10
1
MultiGen
Repro:
Rat
Maternal
Systemic
90
30
6
8
5
5
1
23
3
10
1
Offspring
Systemic
30
3
6
8
5
5
1
2.3
3
10
1
Chronic
Mouse
Systemic
100
33
6
8
5
5
1
25
3
10
1
DNT
Maternal
Systemic
NA
50
6
8
7
7
1
37.50
10
3
1
Offspring
Systemic
25
5
6
8
7
7
1
3.75
10
3
1
Long
Term
Exposure
HEC
Array
for
Occupational
Risk
Assessment
§

Relevant
Study
LOAEL
(
ppm)
NOAEL
(
ppm)
Da
Dh
Wa
Wh
RGDR
HEC
(
ppm)
Inter
Intra
UF
SCN­
Rat
70
30
6
8
5
5
1
23
3
10
1
90D
Dog
10
5
7
8
5
5
1
4.4
3
10
1
MultiGen
Repro:
Rat
Maternal
90
30
6
8
5
5
1
23
3
10
1
Offspring
Systemic
30
3
6
8
5
5
1
2.3
3
10
1
Chronic
Rat
Local
3
NA
6
8
5
5
0.244
0.55
3
10
3
¶

Systemic
90
30.0
6
8
5
5
1
22.50
3
10
1
Chronic
Mouse
100
33
6
8
5
5
1
25
3
10
1
§
Bolded
studies
used
for
endpoint
selection.
¶
A
3X
UF
for
LOAEL
to
NOAEL
extrapolation
is
recommended
due
to
the
minimal
severity
of
the
portal
of
entry
effects
noted
at
the
lowest
dose
tested.
Key
for
Array
Table
LOAEL:
Lowest
observed
adverse
effect
level
NOAEL:
No
observed
adverse
effect
level
Da:
Daily
animal
exposure
(
hrs/
day)
Dh:
Anticipated
daily
human
exposure
(
hrs/
day)
Wa:
Weekly
animal
exposure
(
days/
week)
Wh:
Anticipated
weekly
human
exposure
(
days/
week)
RGDR:
Regional
Gas
Dose
Ratio
HEC:
Human
Equivalent
Concentration
inter:
interspecies
extrapolation
uncertainty
factor
intra:
intraspecies
variation
uncertainty
factor
UF:
Other
uncertainty
factor(
s)
Appendix
C:
Bibliography
Of
MeBr
Exposure
Data
Appendix
D:
Summary
Datasheets
For
Commodity
&
Industrial
Facility
Fumigation
Events
Appendix
E:
Analysis
Of
Monitoring
Data
For
Commodity
&
Industrial
Facility
Fumigations
Appendix
F:
Downwind
MeBr
Risk
Estimates
Calculated
With
PERFUM
For
Commodity
Uses
Appendix
G:
Summary
Datasheets
For
Ambient
Monitoring
Data
