SUBACUTE
INHALATION
TOXICITY
STUDY
IN
RATS
PHOSPHOROUS
TRICHLORIDE
FINAL
REPORT
&­
72­

November
2
9
,
1983
Sabmiifed
to
Monsanfo
Company
Sf.
Louis.
Missouri
CONTP(!
N
NO
CF
OFFICE
OF
QUALITY
ASSURANCE
Project
Title:

Project
No.
:
Subacute
Inhalation
Toxicity
Study
of
PC13
i
n
Rats
Quality
Assurance
inspections
of
t
h
e
study
and
review
of
the
final
report
of
the
above
referenced
project
were
conducted
according
t
o
the
standard
operating
procedures
of
the
Office
of
Quality
Assurance
and
according
t
o
the
general
requirements
o
f
the
Good
Laboratory
Practice
regulations
that
were
issued
on
December
22,
1978,
by
the
Food
and
Drug
Administration
for
compliance
on
and
after
June
20,
1979.
Findings
from
the
inspections
and
final
report
review
were
reported
t
o
management
and
t
o
the
study
director
on
the
following
dates:

I
n
s
pecti
ons/
Rev.
f
ew
Findings
Reported
Inspector/
Revi
ewer
Protocol
1/
6/
83
1/
7/
83
E.
B.
P
r
i
n
s
Inspection
No.
1
2/
8,9/
83
2/
16/
83
M.
Woodmansee
Final
Report
8/
30,31;
9/
1,5/
83
9/
14/
83
P.
Miller
Addendum
10/
11/
84
10/
12/
84
E.
Burroughs
I
241­
141
Office
o
f
Quality
Assurance
000002
HmmoN
UBORATORIES
AMERICA,
INC.

SZOO
LEEQ8USG
TUPNPlUe.
VIENNA..
VtDOlNlA
lillS0.
USA.

SUBJECT:
Subacute
Inhal
a
t
i
on
Toxi
c
i
t
y
Study
i
n
Rats
Project
No.
241­
141
We,
t
h
e
undersigned,
hereby
declare
t
h
a
t
the
work
was
performed
under
our
supervision,
according
t
o
the
procedures
herein
descri.
bed.

Study
Director:

A/*&­
WILLIAM
5.
COATE.
Ph.
D.
Director
I
ha1
a
t
i
on
Toxi
col
ogy
Department
Health
Status
and
Ophthalmology:

Staff
Scientist
Department
of
Vet
eri
n
ar
y
Medi
ci
ne
'
Histopathology:
Lab
Supervi
si
on:

ROBERT
J.
H#
R
DY
A
Secti
on
Supervisor
i/

Inhal
a
t
i
on
Toxi
col
ogy
Department
Diplomate,
American
College
o
f
Patholo&
Department
Veterinary
Pathologists
Report
Preparation:

.A.
Dip1
mate.
Ameri
can
Coll
eue
of
Vet
eri
n
&y
Pat
ho
1
o
g
i
s
t
s
­
Pathology
Department
mss
Research
Assist&
S
c
i
e
n
t
i
f
i
c
Resources
Department
HMmBN
LABORATORIES
AMERICA.
INC.

9poO
LEESBURG
TUC1NPIXE.
VIENNA.
VlRGlNIA
D
I
l
B
O
.U
s
.

TABLE
OF
CONTENTS
SUMMARY
INTRODUCTION
TEST
MATERIAL
TEST
ANIMALS
ENVIRONMENTAL
AND
EXPOSURE
CONDITIONS
.

METHODS
Groups
and
Exposure
Levels
Generation
of
Test
Yateri
a7
Chamber
Concentration
Monitoring
Part
i
cl
e
S
i
t
e
Determi
nat
i
OTIS
ODhthalmoscopi
c
Examinations
Observations
and
Records
C
1
i
n
i
ca
1
Pat
ho1og.
y
Organ
Weights
H
i
stopathol
ogy
S
t
a
t
i
s
t
i
c
a
l
Analyses
Specimen,
Raw
Da%
a,
and
Final
Report
Storage
Nominal
Concentration
Anal
.yti
c
a
l
Concentration
j
P
a
r
t
i
c
l
e
Size
Determinations
ODhthalmoscopi
c
Examinations
Mortality
and
Clinical
Observations
Body
Weights
C1
i
n
i
cal
Pat
ho
I
ogy
Gross
Pathology
Organ
Weiqhts
Histopathology
.
Terminal
Sacrifice,
Necropsy
and
Tissue
Preservation
RESULTS
TABLES
Table
1
­
Mean
Nominal
and
Analytical
Concentrations
Table
2
­
Weekly
and
Mean
P
a
r
t
i
c
l
e
Size
Results
241­
141
Paoe
1
­

3
3
3
4
5
5
6
6
7
7
8
8
9
9
10
l
o
11
12
12
12
12
13
13
13
18
18
19
19
21
22
000004
HAZL­
crrON
LABORATORIES
AMERICA.
NC.
241
­141
9300
LEESBURG
TURNPIUE
VIENNA,
VIRGINIA
22
180
U
S
A
TABLE
OF
CONTENTS
­
CONTINUED
TABLES
­
CONTINUED
Table
3
­
Ophthalmoscopic
Findings
Prior
to
Terminal
Sacrifice
Table
4A
­
Hean
Body
Weights
and
Standard
Deviations
Table
46
­
Mean
Body
Weight
Gains
and
Standard
Deviations
Table
5
­
Mean
Clinical
Hematology
Values
Table
6
­
Mean
Clinical
Chemistry
Values
Table
7
­
Clinical
Pathology
Reference
Ranges
Table
8
­
Gross
Pathology
Incidence
Sumnary
Table
9A
­
Absolute
Organ
Weight
Means
Table
98
­
Organ­
to­
Terminal
Body
Weight
Ratio
Means
Table
9C
­
Organ­
to­
Brain
Weight
Ratio
Means
Table
10
­
Histopathology
Incidence
Sumnary
APPENDICES
Appendix
1
­
Daily
and
Mean
Weekly
Nominal
Concentrations
Appendix
2
­
Individual
and
Hean
Weekly
Total
Chloride
Results
Animal
Number
Correlation
Table
for
Appendix
3A
Appendix
3A
­
Individual
Body
Weights
Appendix
38
­
Individual
Body
Weight
Gains
Standard
Key
to
Hematology
Appendix
4
­
Individual
and
Hean
Clinical
Hematology
Values
Standard
Key
to
Serum
Hemolysis
Appendix
5
­
Individual
and
Mean
Clinical
Chemistry
Values
Standard
Key
to
Urinalysis
Appendix
6
Animal
Number
Correlation
Table
for
Appendix
7
Standard
Key
to
Gross
Pathology
Appendix
7
­
Individual
Gross
Pathology
Animal
Number
Correlation
Table
for
Appendix
8A
Appendix
8A
­
Absolute
Organ
Weights
Appendix
86
­
Organ­
to­
Terminal
Body
Weight
Ratios
Appendix
8C
­
Organ­
to­
Brain
Weight
Ratios
Animal
Number
Correlation
Table
f
o
r
Appendix
9
Standard
Key
to
Histopathology
Findings
Appendix
9
­
Individual
Histopathology
Findings
Appendix
10
­
References
Appendix
11
­
Pathology
Addendum
>
­
Individual
and
Mean
Clinical
Urinalysis
Values
23
24
26
28
29
31
32
36
39
42
45
50
51
53
54
67
84
85
102
103
112
113
122
7
23
124
165
166
7
73
180
187
188
2
09
21
7
I
a9
!
..

9200
LEES8URG
TURNPIKE.
VIENNA.
VIRGINIA
22180.
U
S
A
.

SPONSOR:
Monsanto
Company
DATE:
November
29,
1983
MATER
J
A
L:
PhosDhorous
T
r
i
ch
1
o
r
i
de
SUBJECT:
FINAL
REPORT
Subacute
Inhalation
Study
i
n
Rats
Project
No.
241­
141
SUMMARY
T
h
i
s
study
was
designed
t
o
evaluate
the
potential
subacute
t
o
x
i
c
i
t
y
of
phosphorous
t
r
i
c
h
l
o
r
i
d
e
(PC13)
vapor/
aerosol
following
repeated
exposures
via
inhalation
f
o
r
one
month
(20
exposures).
The
study
was
initiated
on
January
26,
1983,
and
was
terminated
on
February
24,
1983,

Three
groups
o
f
15
Sprague­
Dawley
rats/
sex
were
exposed
t
o
t
a
r
g
e
t
concentrations
o
f
0.5,
3.0,
and
10.0
ppm
of
PCI3
vapor/
aerosol
f
o
r
six
hours/
day,
five
days/
week
f
o
r
four
weeks.
A
fourth
group
of
15
rats/
sex
was
exposed
t
o
filtered
a
i
r
only
under
the
same
conditions
and
served
as
the
control
group.
Food
and
water
were
available
libitum
between
exposure
periods
only,
A
l
l
r
a
t
s
were
sacrificed
and
necropsied
following
20
days
of
exposure
(on
Day
29
of
the
study).

C
r
i
t
e
r
i
a
used
t
o
evaluate
exposure­
related
e
f
f
e
c
t
s
included:

results
of
ophthalmoscopic
examinations,
mortality,
moribundity,
c
l
i
n
i
c
a
l
observations,
body
weights
and
weight
gains,
c
l
i
n
i
c
a
l
pathology
results,

absolute
and
r
e
l
a
t
i
v
e
organ
weights,
gross
pathology,
and
histopathology.
6%
f
l
E
m
O
N
LABORATORfES
AMERICA
INC.
­
­­
­
­­
'I
9000
LEESOURG
IURNPIKE.
W
I
E
N
N
P
.
VIRGlNIP2PIBO.
USA.
241­
141
­2
­

No
mortality
occurred
during
the
'study
and
no
consistent
exposure­
related
effects
were
apparent
i
n
t
h
e
data
used
as
criteria
o
f
Pel3
subacute
t
o
x
i
c
i
t
y
with
the
following
exception:
exposure
o
f
t
h
e
Group
4
r
a
t
s
t
o
PC13
a
t
a
concentration
of
10
ppm
i
n
a
i
r
resulted
in
compound­
related
histopathology
findings
i
n
sections
of
nasal
c
a
v
i
t
y
and
nasal
turbinates
from
7
of
10
male
and
4
of
10
female
rats.

Compound­
related
findings
were
not
present
i
n
other
tissues
examined
and
the
incidence/
severity
o
f
spontaneous
disease
lesions
was
not
increased
by
treatment.
@)
HEmoN
LABORATORIES
AMERICA,
INC.
{:
241­
141
~
9200
LEESBURG
TURNPIKE.
VIENNA.
VIRGlNIA22180.
USA.

­3
­

INTRODUCTION
The
ob.
iective
of
t
h
i
s
study
was
t
o
evaluate
the
subacute
t
o
x
i
c
i
t
y
of
phosphorous
t
r
i
c
h
l
o
r
i
d
e
(PCI
3)
vapor/
aerosol
following
repeated
exposures
via
inhalation.
The
study
was
i
n
i
t
i
a
t
e
d
on
January
26,
1983,
and
was
terminated
on
February
25,
1983.

TEST
MATERIAL
The
test
material
,
phosphorous
t
r
i
c
h
l
o
r
i
d
e
,
a
clear
l
i
q
u
i
d
,
was
received
from
t
h
e
Monsanto
Company,
St.
Louis,
Missouri,
as
follows:

Lot
Number
KB­
11­
1279
KB­
11­
1279
KC02­
1037
KCOI­
1001
Amount
Recieved
4
p
i
n
t
s
3
p
i
n
t
s
4
b
o
t
t
l
e
s
4
p
i
n
t
s
Date
Received
The
test
material
was
stored
i
n
a
walk­
in
r
e
f
r
i
g
e
r
a
t
o
r
when
not
i
n
use.
Purity
o
f
the
test
material
was
given
as
99.9%.
Information
on
t
h
e
methods
o
f
synthesis,
s
t
a
b
i
l
i
t
y
,
as
well
as
data
on
composition
or
other
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
which
define
the
test
material
are
on
f
i
l
e
w
i
t
h
the
sponsor.

TEST
ANIMALS
One­
hundred
f
orty­
four
(
72/
sex)
Sprague­
Dawley
descended
(COBS)

r
a
t
s
were
obtained
from
Charles
River
Breeding
Laboratories,
Kingston,

(­!
c?
0
808
HM'aN
LABORATORIES
AMERICA.
INC.
241­
141
Sa00
LEeS8UPG
TUONPtlLE.
VIENNA.
VIRGINIA
S33SQ.
U.
SA.

­4
­

New
York,
on
January
12,
1983,
A
l
l
rats
were
housed
under
quarantine
conditions
f
o
r
14
days
p
r
i
o
r
t
o
i
n
i
t
i
a
t
i
o
n
of
the
study.
During
t
h
i
s
time
a
l
l
animals
were
examined
f
o
r
health­
status
by
a
s
t
a
f
f
veterinarian,

This
species
was
chosen
because
rats
have
h
i
s
t
o
r
i
c
a
l
l
y
been
used
i
n
safety
evaluation
studies
designed
t
o
evaluate
inhalation
effects.

ENVIRONMENTAL
AND
EXPOSURE
CONDITIONS
During
quarantine
and
throughout
t
h
e
study
a
l
l
animals
were
housed
individuatly
i
n
stainless­
steel
wire­
mesh
cages.
During
.the
study
a17
animals
were
housed
i
n
the
same
chambers
where
their
respective
exposures
occurred.
Food
(Purin#
Certified
Rodent
Chow
4t5002)
and
tap
water
(v
i
a
automated
watering
system)
were
available
ad
l
i
b
i
t
u
m
except
during
exposures.

Exposures
were
conducted
i
n
f
o
u
r
6000­
1
glass
and
stainless­

.
steel
inhalation
chambers
(one
per
group)
located
i
n
one
room
and
ventilated
w
i
t
h
HEPA­
fil
tered
room
a
i
r
a
t
1500
L
h
i
n
u
t
e
under
negative
pressure.
A
i
r
flows
were
monitored
with
c
a
l
i
b
r
a
t
e
d
Magnehelic
gauges
on
the
a
i
r
input
ducts.
Exposures
were
conducted
f
o
r
six
hours/
day,
f
i
v
e
days/
week,
f
o
r
four
weeks
(20
exposures)
a.
Temperature
and
r
e
l
a
t
i
v
e
humidity,
monitored
i
n
the
control
exposure
chamber,
ranged
from
a
Due
t
o
inclement
weather
(blizzard
on
2/
11/
83),
t
h
e
Day
16
exposure
was
r
u
n
f
o
r
only
four
hours.
@
H
E
m
O
N
LABORATOR~
ES
AMERICA.
INC.

SZ!
OO
LEES8UlG
TURNPIKE.
VIENNA.
VlPGlNlP
nl80.
USA
­5
­
241­
141
71­
79OF
and
26­
50%,
respectively
during
non­
exposure
periods,
and
from
71­
79OF
and
26­
45%,
respectively
during
exposures.
The
positions
of
the
animal
cages
within
each
exposure
chamber
were
systematically
rotated
after
every
exposure
day
to
compensate
for
any
heterogeneity
of
PC13
concentrations
within
the
chambers.
The
control
group
was
exposed
to
HEPA­
filtered
air
only,
under
identical
conditions
to
the
treated
groups.

METHODS
Groups
and
Exposure
Levels
Prior
to
initiation
of
exposures,
120
rats
(60/
sex)
out
o
f
144
(72/
sex)
were
randomly
assigned
to
the
following
groups
using
a
computer­

ized
randomization
process
which
eliminated
weight
outliers,

Group
1
2
3
4
No.
of
Animals
Males
Females
15
15
15
15
15
15
15
15
PCl3
Exposure
Level
(pgm)

0
(Air
Control)
0.5
3.0
10.0
The
animals
were
individually
identified
by
eartags.
Each
group
of
animals
was
subdivided
into
three
squads
'of
five
animals/
sex
each.

Exposures
were
initiated
and
clinical
observations,
body
weights,

sacrifices,
and
necropsies
were
performed
on
three
consecutive
days
by
squads.
Blood
s
m
l
i
n
g
from
predesignated
squads
1
and
2
animals
was
conducted
on
two
consecutive
days
(by
squads).
The
animals
placed
on
study
were
approximately
six
weeks
of
age
at
initiation
of
exposures.
COO010
241­
141
­6
­

Generation
o
f
Test
Material
Phosphorous
trichloride
was
generated
into
each
test
chamber
as
a
vapor/
aerosol
by
sweeping
the
headspwe
above
a
volume
of
test
material
in
a
glass
flask
with
air.
The
generation
flasks
were
placed
in
ice
baths
and
each
generation
system
was
enclosed
in
a
plastic
box
maintained
under
negative
air
pressure.
Generation
system
airflows
were
monitored
and
maintained
at
200­
220,
625­
770,
and
928­
990
cc/
minute
for
Groups
2,

3,
and
4,
respectively.
Vapor
laden
air
was
carried
from
the
generation
systems
into
the
makeup
air­
input
ducts
of
the
chambers
via
Teflofl
tubing.

Chamber
Concentration
Monitorinq
The
nominal
concentration
of
PC13
in
each
charrber
was
calculated
daily
for
each
exposure
level
by
preweighing
and
postweighing
the
generation
flask
and
dividing
the
weight
difference
by
the
total
volume
of
air
passed
through
the
chamber
during
generation.

Samples
for
analytical
concentration
determinations
were
obtained
by
pulling
air
volumes
through
impingers
containing
20
mls
of
0.0078M
NaOH.
The
sampling
rate
for
all
chambers
was
10
L/
minute
for
the
following
durations
and
frequencies:

Sampling
Group
Durations
Number
of
Daily
Samples
Obtained
2
3
4
120
minutes
60
minutes
30
minutes
@
Hm'._
F7ZON
LABORATORIES
AMERICA,
INC.

SZOO
LEESaURG
TUF1NPIKE.
VIENNA.
VlPGINlA
OZnaO.
UZP.
241
­
141
­7
­

These
samples
were
analyzed
f
o
r
t
o
t
a
l
chloride
concentration
using
a
Corning
Model
92OM
Chloride
Meter
and
expressed
as
ppm
PC13
using
t
h
e
f
077
owing
formula.

meq
C1
x
t
o
t
a
l
f
i
n
a
l
Sample
Volume
(amount
l
e
f
t
i
n
bubbler)
x
25
(~l
/m
n
o
l
)

3(
C1/
PC'13)
x
Sampled
v
o
l
m
(time
sampled
x
sampling
flawrate)

P
a
r
t
i
c
l
e
Size
Determinations
.One
sample
was
obtained
weekly
from
each
exposure
level
using
an
Andersen
Mini
­Sampl
e@
cascade
impactor
which
s
amp1
ed
the
chamber
atmosphere
a
t
a
rate
of
1.4
t/
minute
f
o
r
600
minutes
(Group
Z
),
300
minutes
(Group
3),
o
r
180
minutes
(Group
4).
Percentages
of
t
o
t
a
l
weight
,

gain
on
t
h
e
collection
plates
and
backup
f
i
l
t
e
r
were
cumulatively
platted
against
size
c
u
t
o
f
f
s
on
log­
normal
paper
from
which
t
h
e
mass
median
aerodynamic
diameter
(MMAD)
and
geometric
standard
deviation
were
extrapol
ated
.

Ophthalmoscopic
Examinations
Ophthalmoscopic
examinations
were
conducted
on
a
l
l
animals
p
r
i
o
r
t
o
i
n
i
t
i
a
t
i
o
n
of
the
study
and
,just
p
r
i
o
r
t
o
terminal
sacrifices.
These
examinations
included
gross
examination
o
f
t
h
e
l
i
d
s
,
lacrimal
apparatus,

and
conjunctiva;
w
h
i
l
e
the
cornea,
anterior
chamber,
l
e
n
s
,
vitreous
humor,
r
e
t
i
n
a
,
and
o
p
t
i
c
d
i
s
k
were
examined
by
indirect
ophthalmoscope
using~
Mydri
acyl@
as
the
mydriatic
agent.

3
@
HAZUZTON
LABORATORIES
AMERICA
INC.
241­
141
­8
­

Observations
and
Records
Each
animal
was
observed
twice
daily
(pre­
and
postexposure
during
the
week
and
A.
M.
and
P.
M.
on
the
weekends)
for
moribundity
and
mortal
i
ty.

Individual
body
weights
were
recorded
for
each
animal
prior
to
initiation
o
f
exposures
and
weekly
throughout
the
study
at
which
time
the
results
of
detailed
examinations
for
signs
o
f
interexposure
toxicity
were
a1
so
recorded.

Cl
i
n
i
cal
Pat
ho
1
oqy
A
t
termination
of
the
study
(Day
29
o
f
study),
blood
was
collected
from
10
anesthetized
animals/
sex/
group
just
prior
to
exsanguination
via
the
abdominal
aorta,
and
the
following
clinical
pathology
studies
were
performed:

Hematology:
total
leukocyte
count
(me),
differenti
a1
leukocyte
count,

erythrocyte
count
(RBC)
,
leukocyte
and
er­
ythrocyte
morphology,

hemoglobin
concentration
(HGB)
,
and
hematocrit
(HCT).

Serum
Chemistry:
sodium
(SODIUM)
,
potassium
(POTAS)
,
chlorid;

(CHLORIDE)
,
total
protein
(T
PROT)
,
albumin
(ALBUMIN)
,

aJbumin/
globulin
ratio
(ALWGLOB
RATIO),
calcium
(CALCIUM),

alkaline
phosphatase
(ALK
PHOS),
total
'bilirubin
(T
BLLI),
blood
urea
nitrogen
(BUN)
,
aspartate
aminotransferase
(AST)~,

a?
anine
aminotransferase
(ALT)
b,
inorganic
phosphorus
(
IN
PHOS)
,
and
7
actate
dehydrogenase
(LDH)
.

a
Also
called
SGOT.
Also
called
SGPT.
241­
141
­9
­

Prior
to
the
day
of
terminal
sacrifice
each
animal
scheduled
for
blood
sampling
was
placed
overnight
in
a
metabolism
cage
without
food,

its
urine
collected,
and
the
followinq
urinalysis
tests
perfonned:

Urinalysis:
appearance
(APPEAR),
PH,
specifi.
c'
gravity
(SPGR),

,glucose,
ketones,
protein,
occutt
blood
(OC
BLD­
U)
,
volume
(U­
VOL)
a,
and
microscopic
examination
o
f
sediment.

All
urine
samples
were
frozen
for
shipment
to
the
sponsor
following
urinalysis.

Terminal
Sacrifice,
Necrowy,
and
Tissue
Preservation
Following
the
20th
exposure
[Day
29
of
the
study),
all
animals
were
fasted
overnight
then
weighed
and
sacrificed
by
exsanguination
under
sodium
pentobarbital
anesthesia.
Necropsies
were
performed
(on
a1
1
animals),
which
included
examination
of
external
surfaces;
all
orifices;

cranial
cavity;
carcass;
external
and
cut
surfaces
of
the
brain
and
spinal
*
cord;
thoracic,
abdominal,
and
pelvic
cavities
and
their
viscera;
and
the
cervical
tissues
and
organs.
All
organs
from
each
animal
listed
under
the
section
entitled
histopathology,
except
for
the
e.
yes
and
testes
(with
epididymides)
which
were
fixed
in
Bouin's
solution
and
preserved
in
70%

alcohol,
were
preserved
whole
in
10%
neutral
buffered
formalin.

Orqan
We
i
qh
ts
Prior
to
fixation,
weights
of
the
following
organs
from
each
animals
were
recorded
and
organ/
terminal
body
weight
and
organ/
brain
a
Urine
volume
was
entered
and
is
presented
with
serum
chemistry
values
to
facilitate
computer
analysis.

000014
LABORATORIES
AMERICA,
INC.
CORRECTION
?AGE
241
­1
41
9200
LEESBURF
TUE(
NPI<
E.
VIENNA.
VIRGINIA
22
7
80.
U
S
A
­
10
­

weight
ratios
calculated:
lungs,
liver,
kidneys,
brain,
heart
(without
major
vessels),
adrenals,
spleen,
and
testes
(with
epididymides).

Hi
stoDathology
The
following
tissues
from
10
males
and
10
females
(Squads
1
and
2)
from
Groups
1
and
4
were
dehydrated
in
graded
alcohol,
infiltrated
and
embedded
in
Paraplast*,
sectioned
at
approximately
Sp,
mounted
on
glass
slides,
stained
with
hematoxylin
and
eosin,
and
examined
microscopically
by
a
veterinary
pathologist.

eyes
duodenum,
jejunum,
ileum
colon,
cecum
mesenteric
lymph
node
urinary
bladder
prostate
ovaries
uterus
femur
bone
marrow
(sternum)
lungs
(two
sections,
all
lobes)
nasal
turbinates
(three
sections)
liver
(two
lobes)
ki
dneys
thyroid
(with
parathyroid)
seminal
vesicles
peri
phera
1
nerve
brain
(fore­,
mid­,
hind­)
pituitary
thoracic
spinal
cord
skin
salivary
glands
(mandibular)
stomach
trachea
thymus
esophagus
heart
spleen
adrena
1
s
pancreas
unusual
lesions
aorta
testes/
epididymides
skeletal
muscle
mamnary
gland
Microscopic
evaluation
was
also
conducted
on
hematoxylin
and
eosin
stained
sections
o
f
nasal
turbinates
from
70
male
and
10
female
rats
in
Groups
2
and
3.
HAZLETON
LA8ORATORlES
AMERICA.
1NC.
CORRECTION
PAGE
241
­1
41
9200
LEESBURG
TURNPIkCE.
VIENNA.
VIRGINIA
at180
U
S
A
­
71
­

Statistical
Analyses
Clinical
pathology,
body
weights
and
body
weight
gains,
and
organ
weight
and
ratio
data
of
the
control
groups
were
compared
statisti­

cally
to
those
of
the
treated
groups
o
f
the
same
s
e
x
.

Analyses
of
the
above
data
were
performed
in
the
following
order.
Each
analysis
began
with
BOX'S
test
for
homogeneity
of
variances
(Box,
1949).
This
test
was
followed
by
one­
way
classification
analysis
of
variance
(ANOVA)
(Miner,
1971)
if
the
variances
proved
to
be
homo­

geneous.
If
the
variances
proved
to
be
heterogeneous,
a
rank
transforma­

tion
of
data
was
performed,
which
was
followed
by
BOX'S
test
and
ANOVA.

If
ANOVA
of
nontransformed
o
r
transformed
data
was
significant,
Dunnett's
­
t­
test
(Dunnett,
1955
and
1964)
was
used
for
control
vs.
treatment
group
mean
comparisons
A1
1
control
vs.
treatment
group
comparisons
were
evaluated
at
the
5.0%
probability
level
(two­
tailed).

Statistical
references
are
appended
to
this
report,
and
statisti­

cally
significant
differences,
as
indicated
by
the
aforementioned
tests,

are
designated
throughout
this
report
by
the
term
"significant"
and/
or
as
f
01
lows
:

S+
=
Significantly
higher
than
the
control
value.

S­
=
Significantly
lower
than
the
control
value.

Specimen,
Raw
Data.
and
Final
Report
Storaqe
All
specimens,
raw
data,
and
the
final
report
are
stored
in
the
archives
of
Hazleton
Laboratories
America,
Inc.
@
HF\
Z­
ON
LABORATORIES
AMERICA,
INC.

SPOO
LEESBUmC
TURNDIKE.
VIENNA.
VI~
GlNlP
207BO.
Y
.u
241­
141
.
­1
2
­

RESULTS
Nominal
Concentration
Daily
nominal
concentrations
are
presented
i
n
Appendix
1
and
sumnarited
i
n
Table
1.

Analytical
Concentration
Daily
analytical
concentration
results
are
presented
i
n
Appendix
2
and
s
m
a
r
i
z
e
d
i
n
Table
1.

Overall
mean
PC13
concentrations
(derived
from
total
chloride
measurements)
(Weeks
1­
4),
deviated
from
target
l
e
v
e
l
s
by
­2.0,
+12.3,

and
+9.6%
f
o
r
t
h
e
Groups
2,
3,
and
4
exposures,
respectively.

P
a
r
t
i
c
l
e
Sire
Determinations
Weekly
p
a
r
t
i
c
l
e
s
i
z
e
data
are
presented
i
n
Table
2.

I
n
a
l
l
samples,
p
a
r
t
i
c
u
l
a
t
e
s
i
z
e
was
obtained
as
inferred
from
weight
gains
on
stages
and
backup
filter,
Mass
median
aerodynamic
diameters
apparently
ranged
from
<0­
65
t
o
1.381.1
f
o
r
t
h
e
Group
2
exposures,
(0.65
t
o
1.2%
f
o
r
the
Group
3
exposures,
and
were
a
l
l
less
t
h
a
n
0.651~
for
t
h
e
Group
4
exposures­
Geometric
standard
deviations
ranged
from
3.07
­
9.15
f
o
r
t
h
e
Group
2
exposures,
and
the
only
value
t
h
a
t
could
be
calculated
f
o
r
the
Group
3
exposures
was
4­
17,
There
were
no
geometric
standard
deviations
f
o
r
the
Sroup
4
exposures.
The
gravimetric
data
on
which
tbese
results
are
based
indicate
t
h
a
t
generally
any
aerosol
i
n
the
chambers
was
of
respirable
s
i
z
e
.
These
results,
!

@)
HAZLET­­
cTON
LABORATORIES
AMERICA,
INC.

9200
LEeSaURG
TURNUCIKE.
VIENNA.
VWGINIA
2
2
7
8
0
.
USA.
J
I
\%

241­
141
­
13
­

if
taken
a
t
face
value,
i
n
d
i
c
a
t
e
that
approximately
2025%
o
f
the
t
o
t
a
l
mass
of
PC13
i
n
the
chamber
atmospheres
may
have
been
i
n
the
form
o
f
a
particulate.

Ophthalmoscopic
Examinations
No
s
i
g
n
i
f
i
c
a
n
t
ophthalmoscopic
abnormalities
were
observed
i
n
the
t
e
s
t
animals
placed
on
study.

Individual
ophthalmoscopic
findings
p
r
i
o
r
t
o
the
terminal
sacrifice
are
presented
i
n
Table
3.
No
exposure­
related
trends
are
apparent
i
n
these
data.

Mortality
and
Clinical
Observations
No
animals
died
during
the
study.

A
l
l
animals
appeared
noma1
throughout
the
study
w
i
t
h
the
exception
of
Group
4
male
No.
46111
observed
w
i
t
h
­
a
bloody
crust
on
t
h
e
penis
a
t
Week
4.

Body
Wei
qhts
Individual
body
weights
and
body
weight
gains
are
presented
i
n
Appendices
3A
and
3B,
respectively,
and
summarized
i
n
Tables
4A
and
43,

respectively.
These
data
are
represented
graphically
i
n
Figures
1A
and
lB,
respectively.

The
mean
Group
3
female
body
weight
and
mean
Group
4
female
weight
gain
were
significantly
decreased
compared
t
o
the
control
group
a
t
Week
1.
However
,
no
concentration­
response
trends
a
r
e
apparent
i
n
either
t
h
e
body
weight
o
r
weight
gain
data.
(?
cmdEP3
­
14
­

M
LL
&
0
m
n
:
=:
8
:
a
:

1
n
t
P,
3
e
E
cy
9
I2
Q
1
­
15
­

*:
n
:
=:

Q
:
3
:

I
I
I
I
I
1
I
I
I
1
I
­
16
­

P
a
3
8
­
17
­

I
I
1
I
1
I
1
I
I
I
I
@
HAZ'­
CTON
LABORATORIES
AMERICA.
INC.

SPOO
LEESSURS
TURNPIKE
VIENNA.
VlRGlUiA
IS?
lSO.
USA.
241­
141
­
18
­

Clinical
Patholoqy
Individual
and
mean
clinical
pathology
data
are
presented
as
f
0
1
1
ows
:

Data
Appendix
No.
Table
No.
(Individual)
(Group
Means
1
Clinical
Hematology
4
Clinical
Chemistry
5
Clinical
Urinalysis
6
Clinical
Pathology
References
Ranges
5
6
7
Hematology
and
urinalysis
data
(by
sex)
of
all
treated
groups
were
comparable
to
those
of
the
control
group.

The
following
mean
clinical
chemistry
values
were
significantly
lower
then
those
of
respective
control
groups.

Group
(s
)
Sex
Parameter
3
and
4
3
and
4
3
and
4
3
and
4
4
Mal
e
Albumin.
Mal
e
Mal
e
Blood
Urea
Nitrogen
Mal
e
Alanine
Aminotransferase
Female
Alanine
Aminotransferase
Al
bumi
n/
G1
obu
1
i
n
Ratio
However,
all
o
f
these
mean
values
are
within
or
slightly
above
the
normal
(H
U
control)
ranges
f
o
r
this
species
and
strain.
The
remaining
clinical
chemistry
data
of
the
treated
groups
were
comparable
to
the
controls.

Gross
Pathology
Individual
gross
pathology
is
presented
in
Appendix
7
and
is
sumnarized
in
Table
8.

:.
(J(­
69023
HAZETON
LA6ORATORlES
AMERICA.
INC.
comEcnm
PAGE
241
­1
41
t*

9200
LEESBURG
TURNPIKE.
VIENNA,
VlUGINlA
22
1
BO.
U
S
A
­
19
­

No
consistent
exposure­
related
trends
were
apparent
in
the
gross
*

pathology
data.

Organ
Weights
Organ
weight
data
are
presented
as
follows:
.

Oata
­
Appendix
No.
Individual
Table
No.
Group
Means
L
Absolute
organ
weights
0
A
9A
Organ/
teminal
body
weight
ratio
86
.
9B
Organ/
brai
n
weight
ratio
8
C
9c
All
organ
weight
and
ratio
data
of
the
treated
groups
were
comparable
to
those
of
the
controls.

i
HistoDathology
Individual
histopathology
findings
are
presented
in
Appendix
9
and
summarized
in
Table
10.
Pathology
addendum
(nasal
turbinates
from
Groups
2
and
3)
is
presented
as
Appendix
11.
­

Compound­
related
histomorphologic
alterations
were
present
in
the
nasal
cavities
of
(iroup
4
animals
which
involved
the
maxillo­
and
nasoturbinates
and
the
lateral
wall
of
the
nasal
cavity
i
n
the
region
of
the
middle
meatus
just
posterior
to
the
upper
incisor
teeth.
The
compound
effects
consisted
of
the
presence
o
f
proteinaceous
fluid
in
the
ethmoid
region
which
was
invariably
associated
with
focal
suppurative
inflammation
in
the
anterior
nasal
region
at
a
level
just
posterior
to
the
upper
incisor
tooth.
The
nasoturbinate,
maxilloturbinate,
and
wall
of
the
nasal
cavity
in
the
region
of
the
middle
meatus
were
affected
by
CORRECTION
PAGE
HAZETON
LAEOR4TORIES
AMERICA,
INC.
241
­1
41
9200
LEESBURG
TURNPtKE.
VIENNA.
VIRGINIA
22
180
U
S
A
­
20
­

the
inf
lamnatory
process;
and
squamous
metaplasia
of
the
respiratory
epithelium
was
present
in
six
male
and
four
female
rats.
Sections
o
f
nasal
cavity
and
turbinates
from
three
high­
level
males
and
si.
x
high­
level
females
were
within
normal
histologic
limits.
In
one
control
male
rat
(animal
#43788)
focal
suppurative
inflamnation
was
present
in
the
nasal
cavity
in
the
region
of
the
maxillary
and
nasoturbinates
as
a
spontaneous
disease
lesion.

Spontaneous
disease
lesions
and
.incidental
findings
occurred
as
follows:
Lung
sections
revealed
early
lesions
o
f
chronic
murine
pneumonia
character3
zed
by
peri
vascular/
peribronchia
1
lymphoid
hyperplasia,
alveolar
macrophages,
and
focal
pneumonitis.
Heart
sections
revealed
minimal
focal
non­
suppurative
myocarditis
in
occasional
animals.

Slight
or
moderate
focal
mononuclear
inflamnatory
infiltrate
was
noted
in
liver
sections
from
nearly
all
animals.

In
the
ki%
dneys,
minimal
or
slight
focal
nephropathy
occurred
in
control
and
treated
rats
and
was
observed
with
greatest
frequency
in
the
male
rats.
In
control
female
#43797,
a
renal
calculus
was
present
in
the
pelvis
o
f
the
kidney
with
an
associated
non­
suppurative
pyelitis.

Sections
of
gonads
revealed
normal
appearance
with
no
evidence
o
f
compound
effect
in
male
or
female
rats.
A
focal
mononuclear
infiltrate
was
present
in
the
prostate
o
f
occasional
animals.
A
variety
of
other
incidental
findings
occurred
infrequently
and
without
relationship
to
treatment.
­
21
­

...
.
;
,
j,

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.
.;
.
...

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c.
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o
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w
0)
YYY­
Y
l
n
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n
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pnpon
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&k
W
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z
c
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4
­
N
­
24
­

TABLE
4A
C
5241141
7/
19/
63
MALES
1
STUDY
T
I
T
L
E
SUBACUTE
PHJS­
TRICHLORIDE
STUDY
I
N
RATS
COMPOUNO
T
I
T
L
E
PHOSPHORUS
TRICHLORIDE
MEAN
BODY
YEXGHTS
AX0
STAN9ARD.
DEVIATIONS
SROUP
LtTVEt
MEAN
(GRAUSI
182.2
180­
5
183.7
179­
8
START
STDIDEVI
i3.
za
13­
21
7­
63
14.12
l
a
2
3
0
AOJUSTED
SURVIVAL
151
15
1%
15
2%
1
5
1
5
f
15
UEAN
(GRAUSI
232­
1
2361
0
237­
9
229­
5
STD­
OEV­
.
24­
91
16­
59
11­
70
14­
16
ADJUSTED
SURVIVAL
1S/
15
15/
15
15/
15
131
15
MEAN
(GRAMS1
274.7
279­
4
282.4
271­
5
STO­
DEV
­
24
75
22­
51
25­
32
15­
74
ADJUSTED
SURVIVAL
15f
1
5
f5f
15
15f
15
1%
15
MEAN
(GRAHS)
307­
7
313.0
317­
7
30505
STO
.3EV
30.94
'
26.94
17.95
la045
ADJUSTED
SURVIVAL
151
1
5
1
5
f
1
5
1
5
/
15
i5/
15
nEAN
(GRAHS)
334­
8
3
4
0
­4
345
3
331­
2
ST3+
DEY­
32­
65
31.55
21.50
23­
41
ADJUSTED
SURVIVAL
151
15
15f
15
151
15
15/
15
a
Rank­
transformed
data
analyzed.
­
25
­

CORRECTION
PAGE
C
S241141
7/
19/
83
FEUALES
a
coflrHuED
1
STUDY
T
I
T
L
E
SUBACUTE
PHOS­
TRICHLORIDE
STUDY
IN
RATS
COMPOUND
T
I
T
L
E
PHOSPHORUS
TRICHLORIDE
MEAN
BODY
YEIGHTS
AN0
STANDARD
OEVIATIONS
*.)**
e
FEMALES
****
e
........................................

6ROUP
1
2
3
4
LEVEL
­00
50
3.00
1
0
­0
0
­­­­
­­­­­­
­­­­­
­­­­­­

UEEKS
ON
STUDY
­
­­
­­­­­­­­­­­

MEAN
(GRAHS)
1540s
155­
7
145­
7
151.1
START
STD­
DEV­
'
11­
28
9­
34
12­
16
8­
18
ADJUSTED
SURVIVAL
MEAN
(GRAUS)

ADJUSTED
SURVIVAL
MEAN
(6RAUS)

ADJUSTED
SURVIVAL
YEAN
(GRAUS)
STDeOEVt
AbJUSTED
SURVIVAL
MEAN
(GRAMS)

ADJUSTED
SURVIVAL
STD­
OEV­

STD
­DEV
STD­
DEV­
151
1s
185.1
11­
81
151
15
2
0
0
­8
13­
94
151
1s
215.7
16­
85
151
1s
226­
6
17­
93
151
IS
151
15
183­
2
9­
40
151
15
202.2
151
15
215­
1
12.51
I
S
/
15
223­
1
10.36
151
15
io­
53
151
15
174­
9s'
13­
87
151
1s
193­
3
16­
70
15/
15
205­
7
18­
77
151
15
216­
2
21­
03
151
15
15/
15
177.1
9­
21
lS/
15
194.4
11­
81
151
15
20909
15­
09
151
15
21704
14­
50
151
1s
­
26
­

TABLE
48
C
5291141
7/
19/
83
HALES
1
STUDY
T
I
T
L
E
SUBACUTE
PHOS.
TRICHLORIOf
STUDY
I
N
RATS
COMPOUNO
T
I
T
L
E
PflOSPHORUS
TRICHL3RI3E
MEAN
BODY
UEIGHT
6AINS
AND
STANDARD
DEVIATIONS
.
GROUP
LEVEL
MEAS
(GRhMSl
.O
00
.O
­a
ADJUSTE3
SURVIVAL
IS/
15
15/
15
151
15
15/
15
REAN
(6RAHSI
49.9
55.5
54.2
49.7
1"
STO.
DEU.
15­
52
9.54
5­
11
7.
09
ADJUSTED
SURVIVAL
:S/
1
5
154
15
151
15
151
15
START
S'TJ­
DEVo
.Off
000
000
.oa
HEIN
<GRAMS)
42.6
43.4
44­
5
42.0
2
STDIOEU.
7
­0
6
8.79
5.96
6­
35
AOJUSTED
SURVIVAL
151
13
151
15
151
15
15/
15
#CAN
(SRAMS).
33.1
33.6
35.3
33r3
3"
S
T
O
I
O
E
V
I
8­
95
8.50
3.75
6­
61
ADJUSTER
SURVIVAL
351
15
1%
15
151
15
151
15
MEAN
(GRAMS1
27.1
27.4
27.6
'25­
7
4
SfJrDEV.
7.05
8.30
5­
69
7­
16
ACIJUSTED
SURUIVAL
lf/
15
151
If
151
15
15/
15
0­
4
Muus(
GWls1
152.6
159.9
161.6
151.4
m.
DEV.
26.64
28.44
17.53
19.45
mum0
SURYIYAL
15/
15
15/
15
E/
15
151
15
"
Rank­
transformed
data
analyzed.
.
..
­
27
­

i
CURRECTlON
PAGE
C
S241141
7
/1
9
/8
3
FEYALES
TABLE
48
­
CONTINUED
1
STUDY
T
I
T
L
E
SUBACUTE
PHOS.
TRICWLORIDC
STUDY
I
N
RATS
COMPOUNO
T
I
T
L
E
.
PHOSPHORUS
TRICHLORIX
flEAN
BODY
UEISHT
GAINS
CNO
STANDARD
OEVIATIONS
.............................................
ttttt
FEMALES
t
*T
+t
GROUP
LEVEL
WEEKS
OM
STUDY
­­­­­­­­­­­­­­

START
1
sa
3
4
0­
4a
MEAN
(9RAflSI
ADJUSTED
SURVIVAL
MEAN
(GRAMS)

ADJUSTED
SURVIVAL
UEAN
(6RAMS)

ADJUSTED
SURVIVAL
MEAN
<GRAMS1
ADJ'JSTED
SURVIVAL
ME&
N
(BRAXSI
ADJUSTED
SURVIVAL
STD­
DEV­

STD­
PEV.

STD­
OEY
STrJ.
DEV
ST9oDEV.

MEAN
(­
1
s17).
DN.
ADJUSTED
SURVIVAL
­0
000
151
15
30.6
4.98
15/
15
15.7
8.36
IS/
15
14.9
6­
72
15/
15
10.3
5.31
15/
15
72.1
14.43
15/
15
­0
­0
0
1%
15
27.5
4.68
1S/
15
19.0
15/
15
12­
9
4.96
15/
15
8.
C
4
­5
8
1
5
f
15
67.4
8.06
15/
15
3­
51
0
0
.oo
151
15
29­
2
4.73
15/
15
18­
5
5.73
1S/
15
12.3
15/
15
7.
a9
10.5
5.11
15f
15
70.5
15.42
15/
15
.o
­00
1s/
15
25.9''
3
.a9
15/
19
17.3
4.63
151
15
15.5
15/
15
7.5
2­
61
15/
15
66.3
8.69
15/
15
6­
25
Rank­
transformed
data
analyzed.
­
28
­
­
29
­

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IrJ
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h
91
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g
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31
­

241­
141
i
.
Table
7
C
l
i
n
i
c
a
l
Pathology
Reference
Rangesa
Subacute
Inhalation
Study
of
P
C
l
3
i
n
Rats
These
reference
ranges
were
developed
from
control
animal
data
t
h
a
t
a
r
e
retained
by
Hazleton's
c
l
i
n
i
c
a
l
­
pathology
computer
system.
For
each
range,
the
data
were
ranked,
and
2.5%
of
t
h
e
uDper
and
lower
values
were
deleted.
The
resulting
values
represent
a
nonparametrically
derived
range
t
h
a
t
aoproximated
t
h
e
i
n
t
e
r
v
a
l
i
n
t
o
each
95%
of
the
tabulated
values
f
e
l
l
.
Data
from
which
t
h
i
s
t
a
b
l
e
was
generated
a
r
e
on
f
i
l
e
i
n
the
o
f
f
i
c
e
of
the
Section
Supervisor
of
the
C
l
i
n
i
c
a
l
Pathology
Laboratory.

SP
RAGUE
­DAWLE
Y
RATS
TEST
NAME
T
Prot
A1
bumi
n
Globulin
A/
G
Ratio
A
l
k
Phos
T
B
i
f
i
B
UN
AST
(
SGOT)
ALT
(SGPT
L
DH
Gal
ci
um
I
n
Phos
Sodium
Potas
.

Ch7
o
r
i
de
HCT
HGB
RBC
WBC
N
RANGE
56
5.9­
8.0
56
3.1­
4.5
46
106
56
106
96
106
36
36
0.94­
1.45
18­
127
0.19­
0.71
11.0­
22.7
46­
118
10­
35
121­
930
9.3­
12.9
46
I42
­
147
46
4.7
­6.8
46
97
­106
559(
534)..
32.3­
50.1(
34.7­
48.6)
549(
524)
11.7­
18.3(
12.
l­
17.9)
549(
524)
5.49­
9.36(
5.44­
8.60)
559(
534)
5.6­
17.8(
3.2­
l3.2)
UNITS
­
gm/
dl
gm/
dl
gm/
dl
Ratio
ru/
L
mg/
dl
mg/
dl
I
U/
L
IU/
L
I
U/
L
mg/
dl
mg/
dl
m
o
l
/
1
mnol/
l
mEq/
L
%
gm/
dl
m
i
/u
l
t
h
/u
l
a
Blanks
s
i
g
n
i
f
y
tests
f
o
r
which
no
normal
range
data
was
a
v
a
i
l
a
b
l
e
f
o
r
t
h
i
s
NOTE:
Chemistry
from
aorta
and
o
r
b
i
t
a
l
bleedinq;
hernato1og.
y
from
o
r
b
i
t
a
l
bleeding
only.
Hemato1og.
v
ranges
are
presented
by
sex
(females
values
i
n
parentheses).
species
and
s
t
r
a
i
n
.
­
32
­

Table
a
Gross
Pathology
Incidence
S
m
a
r
y
Subacute
Inhalation
Study
o
f
PCl3
in
Rats
241­
141
­
33
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o
f
PCl3
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141
Table
9C
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241
­141
`I
ANIMAL
NUMBER
CORRELATION
TABLE
Animal
Computer
Animal
Conputer
Animal
Computer
Animal
Computer
Number
Nuber
Number
Number
Number
Number
Number
Number
Males
46001
46002
46003
46004
46005
46011
46012
46013
46014
46015
46021
46022
46023
46024
46025
46006
46007
46008
46009
46010
,46016
46017
46018
46019
46020
46026
46027
46028
46029
46030
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
46031
46032
46033
46034
46035
46041
46042
46043
46044
46045
46051
46052
46053
46054
46055
46036
46037
46038
46039
46040
46046
46047
46048
46049
46050
46056
46057
46058
46059
46060
31
46061
32
46062
33
46063
34
46064
35
46065
36
46071
37
46072
38
46073
39
46074
40
46075
41
46081
42
46082
43.
46083
44
46084
45
46085
Females
46
46066
47
46067
48
46068
49
46069
50
46070
51
46076
52
46077
53
46078
54
46079
55
46080
56
46086
57
46087
58
46088
59
46089
60
46090
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
a
i
a5
82
83
84
86
87
88
89
90
46091
46092
46093
46094
46095
46101
46102
46103
46104
46105
46111
46112
46113
46114
46115
46096
46097
46098
46099
46100
46106
46107
46108
46109
46110
46116
46117
46118
46119
46120
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
11
1
112
11
3
114
11
5
116
11
7
118
119
120
­
54
­

241­
141
Appendix
3A
Individual
Body
Weights
Subacute
Inhalation
Study
o
f
PCl3
in
Rats
i
,.
­
55
­

APPENDIX
­
3A
INDIVIDUAL
aouY
UEIGHTS
(GRAMS)
PAGE
1
S241141
KEY
TC
SYMBOLS:
*
OEAD
ANIMAL
GROUP
1
­
CONTROL
MALES
INTERVALS
ANINAL
NUMBER
5
3
236.0
3
285.0
3
275.0
3
330.13
3
323.0
3
312­
0
­
2
282.0
3
33.500
3
330
0
3
303.0
4
266­
0
1
2
154.0
209­
0
0
155.0
0
177.0
D
IS7eO
0
187.0
0
135.0
0
185.0
0
180.0
0
175.0
0
193.0
1
INTERVALS
ANIMAL
NUMBER
5
4
312.0
1
2
225.0
259.0
2
INTERVALS
4NIMAL
NUMSER
5
4
312.0
1
2
207.0
245.0
3
INTERVALS
ANIMAL
NUMBER
5
4
355.0
1
2
244.0
293.0
4
INTERVALS
ANIMAL
NUMBER
4
355.
0
1
2
235­
0
285.0
5
INTERVALS
ANIMAL
NUMaER
4
331.0
6
INTERVALS
ANIMAL
NUMBER
4
310.0
1
2
228­
0
260­
0
7
INTERVALS
1
2
235­
0
279.0
ANIMAL
NUMBER
4
334.0
5
a
I
NTE
R
V
AL
S'
ANIYAL
NUMBER
5
4
3520.0
1
2
250
C
295.0
9
ANIMAL
NUMBER
INTERVALS
0
1
179.0
233.0
4
5
323.0
2
275.0
1
C
­
56
­

APPENDIX
­
3A
CONTINUED
8241141
INDIVIDUAL
BCDY
WEIGHTS
(GRAMS)
PAGE
2
ANIHAL
NUYBER
INTERVALS
3
4
335.
0
361.0
3
0
1
2
181.0
245.0
293.0
11
ANIPIAL
NUMBER
INTERVALS
0
1
2
183.0
246.0
288.0
3
4
335­
0
3640
0
12
ANIMAL
NUMBER
INTERVALS
0
1
2
197.0
254.
0
297.0
3
4
345.0
3840
0
13
ANIMAL
NUMBER
INTERVALS
0
1
2
196.0
232.0
260.0
3
4
275­
0
290.0
14
ANIMAL
NUMBER
I
TJ
TE
R
V
AL
S
0
1
2
203.0
254.0
303.0
3
4
335.0
363.0
5
15
GROUP
1
­
CONTROL
FEMALES
INTERVALS
0
1
2
140.0
1680'2
182­
0
AIYIHAL
NUMB€
R
3
195.0
4
204.0
16
ANIMAL
NUMBE2
INTERVALS
0
1
2
168.0
194.0
208.0
3
209.0
4
232.
C
17
ANIMAL
NUMBER
INTERVALS
0
1
2
154­
0
177.0
182.0
3
205.0
4
220.0
5
ANIMAL
NUMBER
INTERVALS
5
0
1
2
208.0
158.0
191.0
3
225.0
4
226­
0
19
ANIMAL
NUMSE
R
­1
N
TE
R
V
A
L
S
0
1
2
164­
0
196­
0
­
222.0
3
233­
0
4
246­
0
5
­
57
­

APPENDIX
­
3A
CONTINUED
S241141
INDIVIDUAL
BOOY
kEIGHTS
(GRAMS)
PAGE
3
I
N
T
E
R
V
AL
S
ANIYAL
NUMBER
0
1
2
3
14500
175.0
187.0
20100
4
2
0
7
0
0
5
21
ANIMAL
NUMBER
­1NTEiiVALS
5
4
228.0
0
157.0
1
2
18400
19800
3
21000
22
INTERVALS
ANIMAL
NilMBER
5
1
2
162.0
18200
3
15100
4
202.0
0
12600
23
INTE3VALS
ANIMAL
NUMSER
3
239­
0
4
253.0
5
0
15500
1
2
19300
217.0
24
INTERVALS
ANIMAL
NUMBER
3
199
0
4
208­
0
5
I
2
17500
19300
0
15100
25
INTERVALS
1
2
20000
208.0
ANIMAL
NUMBER
3
226­
0
4
235.0
5
0
163.0
26
INTERVALS
4NIMAL
NUMBER
3
230.0
4
23900
0
162.0
1
2
197.0
20800
27
INTERVALS
ANIMAL
NUMBER
5
1
2
18700
22200
3
246­
0
4
258.0
0
15100
28
INTERVALS
ANIVAL
NUMBER
5
1
2
19800
200.0
3
220.0
4
231.0
0
170.0
29
INTERVALS
ANIMAL
NUMBER
5
0
1
2
3
­153.0
180.0
195.0
207.0
4
210.0
3
0
­
58
­

APPENDIX
­
3A
CONTINUED
S241141
INDIVIDUAL
BODY
%EIGHTS
(GRAMS)
PAGE
4
CROUP
2
­
.so00
CPPH
HALES
ANIMAL
NUMBER
INTERVALS
0
174.0
1
2
237.
0
2
8
~0
3
323.0
4
252.0
5
31
ANIMAL
NUMSER
INTERVALS
0
130.0
1
2
240.0
293.3
3
345.0
4
383­
0
5
32
ANIMAL
NU
H
S
E
R
INTERVALS
0
169.0
1
2
218.0
255.0
3
287.0
5
4
309­
0
33
ANIMAL
NUMBER
INTERVALS
5
0
16810
1
2
214e.
C
246.
0
3
278
0
4
308.
o
34
ANIMAL
NUMBER
INTERVALS
0
155.0
1
2
217.0
259.0
INTERVALS
1
2
237.0
283.
o
INTERVALS
1
2
212.0
243.0
INTERVALS
1
2
222.0
276.0
INTERVALS.

1
2
237.0
284.0
INTERVALS
1
2
235.0
267.0
3
2970
C
4
334.0
35
ANfNAL
NUMBER
0
180.0
3
4
325.
0
368.0
5
36
.
ANIMAL
NUMBER
0
171.0
3
2157.0
4
281.0
5
27
ANIYAL
N
U
M
B
E
R
0
178.0
3
300.0
4
332.0
5
'3
8
ANIMAL
NUMBER
0
178.0
3
323
0
4
348­
0
5
39
0
182.0
3
289
0
4
314.0
5
40
­
59
­

A
P
P
E
N
O
I
X
­3A
C
O
N
T
I
N
U
E
D
'

S241141
I
N
D
I
V
I
D
U
A
L
B
O
D
Y
U
E
I
G
H
T
S
(G
R
A
M
S
)
P
A
G
E
AN
I
MAL
N
U
H
e
E
R
I
N
T
E
R
V
A
L
S
0
1
2
179.0
259.0
314.0
3
347­
0
4
376.0
'
5
41
ANIMAL
NUMBER
I
N
T
E
R
V
A
L
S
0
1
2
193­
0
243.0
280.0
5
3
310­
0
4
335.0
42
ANIMAL
NUMBER
I
N
T
E
R
V
A
L
S
0
I
2
134­
0
250­
0
28500
3
311.0
4
5
32300
43
ANIMAL
NUMl3ER
I
N
T
E
R
V
A
L
S
0
1
2
204.0
257­
0
305­
0
3
33300
4
5
352­
0
44
A
N
I
M
A
L
NUMBER
I
N
T
E
R
V
A
L
S
@
1
2
20200
262­
0
316­
0
3
36000
4
5
;
395­
0
45
GROUP
2
­
0
5
0
0
0
(PPM
FEMALES
A
N
I
M
A
L
.NUMSER
I
N
T
E
R
V
A
L
S
0
1
2
170.0
187.0
135­
0
3
205.0
4
217.
G
46
ANIMAL
NUMBER
I
N
T
E
R
V
A
L
S
0
1
2
154­
0
176­
0
197­
0
3
200*
0
4
218.
t
47
ANIMAL
NUMBER
I
N
T
E
R
\I
ALS
0
1
2
147.0
173.0
196.0
3
214.0
4
221­
C
48
ANIMAL
NUMBER
I
N
T
E
R
V
A
L
S
'

0
1
2
157­
0
187.0
204.0
3
214­
0
4
220­
0
5
49
A
N
I
N
A
L
NUMBER
I
N
T
E
R
V
A
L
S
0
1
2
190­
0
20500
164­
0
5
3
216.0
4
224.0
50
­
60
­

APPENDIX
­
3A
CONTINUED
INDIVIDUAL
EODY
UEIGHTS
(GRAYS)
PAGE
E:

S241141
INTERVALS
ANIMAL
NUNBER
0
1
16600
185.0
2
205.0
I
N
f
ERV
AL
S
1
2
172.
0
18800
INTERVALS
1
2
183.0
20000
INTERVALS
1
2
193.0
208.0
INTERVALS
1
2
18700
208.0
INTERVALS
1
2
205.0
232.0
INTERVALS
1
2
183.0
202.0
I
NT
E
RY
ALS
1
2
175­
0
194.0
INTERVALS
1
2
190.0
205.0
INTERVALS
1
`2
179.0
202.0
3
210.0
3
200.0
3
212.0
3
.
22600
3
226.
0
3
250.0
3
210.0
3
207.0
3
222.0
.

3
215.
c
4
22100
5
51
ANIMAL
NUMBER
0
143.0
5
4
211.0
52
ANIHAL
NUMSER
0
150.0
4
215.0
5
5
5
53
ANIMAL
NUMBER
0
161.0
4
224.0
5
4
ANIMAL
NUMBER
0
159.0
4
23,100
5
5
ANIMAL
NUMBER
I!
173.0
4
254.0
5
56
ANIHAL
NUMBER
0
157.0
4
21700
3
57
ANIMAL
NUMBER
0
15300
4
5
217.0
ANIMAL
NUMBER
0
153.0
4
5
232.0
59
ANIMAL
NUMBER
0
148­
0
4
3
22100
60
­
61
­

APPENDIX
­
3A
CGNTINUED
S
a
4
1
1
4
1
I
N
D
I
V
I
O
U
A
L
BODY
UEISHTS
(SRAHS)
.,
PAGE
GROUP
3
­
3.0000
(PPM
MALES
I
ANIMAL
INTERVALS
NUMBER
.O
1
2
3
4
61
187.0
247.0
302.0
340
0
369.0
5
ANIMAL
NUMBER
INTERVALS
0
174.0
1
2
224.0
26500
3
247.0
4
21e.
o
5
62
ANIHAL
NUMBER
INTERVALS
0
172.0
1
2
225.0
270.0
3
303.0
4
335.0
5
63
ANIHAL
NUMBER
INTERVALS
5
C
180­
0
1
2
230.0
273.0
3
3
0
7
­0
4
336.0
64
ANIHAL
NUMBER
INTERVALS
1
2
253.0
302­
0
0
189­
0
3
344.0
4
372­
0
5
5
ANIMAL
NUMBER
INTERVALS
0
196,
0
1.
2
262.0
308.0
3
347­
0
4
384­
0
66
ANIMAL
NUMBER
INTERVALS
3
320­
0
0
190.0
1
2
237.@
282.0
4
346.0
67
ANIMAL
NUMBER
INTERVALS
0
174­
0
3
zoo.
0
4
327­
0
5
6
8
ANIMAL
NUMBER
INTERVALS'

5
0
185­
0
1
2
245.0
3
0
0
e
O
3
341­
0
4
380.0
6
3
ANIMAL
NUMBER
INTERVALS
0
193.0
1
2.
240.0
274.0
3
30400
5
4
331.0
70
..

­
62
­

A?
DENDIX
­3A
CONTINUED
S241141
INOIVIDUhL
BODY
WEIGYTS
(GFlAMS)
PAGE
8
ANIPIAL
NUMSER
INTERVALS
0
1
181.0
232,
0
4
345­
c
5
5
5
5
5
2
3
278.0
313.
a
71
ANIMAL
NUMeER
INTERVALS
0
1
2
3
185.0
238.0
277.0
310.0
4
33300
72
ANIMAL
NUMaER
INTERVALS
0
1
2
3
185.0
241mO
23000
320­
0
4
342­
0
73
AN
I
t4
A
L
NUMBER
INTERVALS
0
1
2
3
113.0
220.0
250.0
295.0
4
316.0
74
ANIMAL
NUMBER
INTERVALS
0
1
2
3
189­
0
247.0
2
9
0
0
0
325­
0
4
345.0
75
GROUP
3
­
300000
(PPH
FEMALES
ANIMAL
N
U
M
BE
R
INTERVALS
0
1
2
154.0
188
0
203.
c
3
224mO
4
235
0
76
ANIMAL
NUMBER
INTERVALS
r!
1
2
128.0
152m
0
17200
3
190.0
4
1960
0
77
ANIMAL
NUMBER
INTERVALS
0
1
2
146.0
17800
200.0
3
2160
0
3
4
238.0
78
ANIMAL
NUMBER
INTERVALS
5
0
1
2
156.0
187­
0
2G8.
0
3
230.0
4
234­
0
7
9
ANIMAL
NUMBER
INTERVALS
0
1
2
155.0
185.0
205.0
3
4
21500
225­
0
5
80
­
63
­

APPENDIX
­3
A
CONTINUED
S241141
INDIVIDUAL
BODY
SEIGHTS
(GRAMS)
PAGE
9
INTERVALS
ANIflAL
NLJMBER
0
1
2
3
1
3
0
.0
158.0
1
7
2
­0
187­
G
5
8
1
INTERVALS
ANIMAL
NUMBER
5
0
1
2
3
1
2
4
­0
1
6
3
­0
i
a
7
.0
2
0
7
­0
4
217­
0
a
2
INTERVALS
ANINAL
NUMBER
0
1
2
3
1
5
5
.0
1ao.
o
1
9
6
­0
205.0
4
209­
0
5
83
INTERVALS
ANIMAL
NUMBER
5
0
1
2
3
135.0
159­
0
1
7
3
­0
1
8
0
­0
4
1
9
1
­0
a
4
INTERVALS
ANIMAL
NUMBER
5
0
1
2
3
1
4
2
.0
iks­
o
183.0
1
9
7
­0
4
20610
85
INTERVALS
ANIMAL
NU
PI
B
E
R
s
0
1
2
3
165.0
1
8
7
­0
1
7
7
­0
1
4
2
­0
4
1
8
8
­
0
8
C
INTE8VALS
ANIMAL
NU
M
8
E
R
a7
5
0
1
2
3
190­
0
2
0
4
­0
2
1
0
.0
1
5
7
.0
4
2
2
4
.0
INTERVALS
ANIPIAL
NUMaER
0
1
2
3
1
7
0
­0
182­
0
1
9
6
.0
145.0
4
202.0
8
8
INTERVALS
ANIMAL
NUMBER
0
1
2
.
3
1
7
9
­0
19410.
206.0
1
4
9
.0
4
215­
0
89
INTERVALS
ANIHAL
NUMBER
0
1
2
3
1
6
6
­
0
200­
0
234.0
245­
0
4
2
5
5
­0
9
0
­
64
­

ANIMAL
NUMBER
31
ANIMAL
NUMBER
92
ANIMAL
NUMBER
93
ANIMAL
NUMBER
94
ANIMAL
NUMBER
95
ANIMAL
NUMBER
96
ANIMAL
NUHBER
97
ANIMAL
NUMaER
90
ANIMAL
NUMBER
45
ANIMAL
NUMBER
,
100
APPENDIX
­3A
CONTINUED
INDIVIDUAL
BODY
WEIGifTS
(GRAMS)

GROUP
0
175.0
0
175.0
0
187.0
0
183.0
0
168.0
0
18900
0
162.0
0
184.0
0
135.0
S241141
INTERVALS
1
2
225.0
274­
0
INTERVALS
1
2
222.0
264­
0
INTERVALS
INTERVALS
1
2
241.0
290.0
INTERVALS
1
2
216.0
258
0
I
N
T
ER
V
ALS
1
2
240.0
285.0
INTERVALS
INTERVALS
1
2
234.0
280.0
INTERVALS
1
2
243.
0
277.0
INTERVALS
1
2
216.0
285.0
1
3
310­
0
3
305.0
3
304.
0
3
337.0
3
292.0
3
328
0
3
263.0
3
3i3.
a
3
309.0
3
300.0
4
352.
c
4
335.0
4
32E.
O
4
375.0
4
321.0
4
342.0
4
28o.
a
4
342.0
4
237.0
4
325.0
00
0069
PAGE
10
5
5
5
5
5
5
5
5
5
5
­
65
­
APPENDIX
­
3A
CONTINUED
S241141
INDIVIDUAL
EODY
WEIGHTS
(GRAHS)
<­
PAGE
11
i
:
'.
..

ANIMAL
NUlYBER
INTERVALS
0
155­
0
0
208­
0
0
19700
0
17000
0
178.0
1
2
2
2
4
.0
2720
0
3
310.0
4
3280
0
5
101
ANIMAL
NUMBER
INTERVALS
3
330­
0
4
5
355.0
102
ANIMAL
NUMBER
INTERVALS
3
314.0
4
343.0
103
ANIMAL
NUMBER
INTERVALS
1
2
257­
0
215.0
3
287.0
4
304­
0
104
ANIMAL
NUMB€!?
I
N
T
E
R
V
A
L
S
1
2
223.0
250­
0
3
28U.
O
10s
GROUP
4
I
O
­O
O
O
O
CPPM
­
FEMALES
ANIYAL
N
U
MB
E
R
INTERVALS
1
2
168.0
185.0
3
209.0
4
21700
106
ANIMAL
NUMBER
INTERVALS
0
1
3
1
o
O
1
162.0
1
18200
1
19108
3.
172.0
2
i
f
2
.a
3
184.0
4
1
4
6
~0
107
ANIKAL.
NUMBER
INTERVALS
0
156­
0
2
199.0
3
204.0
4
216­
0
108
ANIMAL
NUMBER
INTERVALS.

0
159.0
2
207­
0
3
233.0
5
4
245.0
103
ANIMAL
NUMBER
INTERVALS
5
,o
14600
2
Y87­
0
3
205­
0
4
214­
0
­
66
­
APPENDIX
­3
A
CONTINUED
5241141
INOIVIDUAL
BODY
WEICi­
1TS
(GRAMS)
PAGE
12
ANIHAL
NUMBER
I
NTEZV
AlS
0
155.0
1
183.0
2
20000
3
213.0
4
21500
5
I
l
l
ANIMAL
NUMBER
INTERVALS
1
2
170.0
185.0
3
195.0
4
204.0
5
112
ANIMAL
NUM3ER
INTERVALS
1
2
172
0.
G
188.0
3
2
0
0
0
0
5
4
207.
C
3
145.0
113
INTERVALS
ANIMAL
NUMBER
0
154.0
3
212.0
4
217.0
5
1
2
177.9
197.0
114
I
N
T
ER
V
A
1
S
ANIMkL
NUMBER
5
3
223.0
0
153.0
1
2
17900
204.0
4
230.0
115
INTERVALS
ANIMAL
NUMBER
0
164.0
3
233.0
4
240.0
5
1
2
193.0
212.0
116
INTERVALS
AN
I
3
A
L
NUMBER
3
21000
5
1
2
177­
0
200.0
4
219.0
117
INTERVALS
ANIMAL
NUMBER
0
147.0
1
16500
2
183.0
3
1
9
5
0
0
4
20000
5
11e
INTERVALS
AN
I
MAL
NUMBER
5
0
148.0
1
2
3
3.7700
185.0
200.0
4
20600
119
INTERVALS
ANIMAL
NUMEIER
5
0
15200
1
2
3
188.0
212.0
229
0
4
23500
120
­
67
­

241­
141
Appendix
38
Individual
Body
Weight
Gains
Subacute
Inhalation
Study
o
f
P
C
l
3
i
n
Rats
­
68
­

241
­141
ANI
MAL
NUMBER
1
ANIMAL
NUMBER
2
ANIMAL
NUMBER
3
ANIMAL
NUMBER
4
ANIMAL
NUMBER
5
ANIMAL
NUMBER
6
ANIMAL
NUMBER
7
APPENDIX
­
3B
INDIVIDUAL
BOOY
WEIGHT
GAINS
(GRAMS)
S241141
KEY
TO
SYMBOLS:
*
DEAD
ANIMAL
GROUP
1
­
CONTROL
MALES
I:
­1.0
1
48
00
1
50
.O
1
57
.O
1
50.0
1
48
.O
1
48
­0
INTERVALS
2
3
54.0
27
.O
INTERVALS
2
34.0
3
26
.O
INTERVALS
2
3
38
.O
30.0
INTERVALS
2
3
49
.O
37
.O
INTERVALS
2
3
50.0
38.0
INTERVALS
2
3
46
.O
33.0
INTERVALS
2
3
32.0
22
"0
4
30.0
4
27
.O
4
5
37.0
4
5
35
­0
4
5
32.0
4
5
19
.o
4
5
28.0
.
..
69
­

r
'
?
F
!

241
­141
APPENDIX
­
3B
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
5241141
ANIMAL
NUMBER
INTERVALS
8
1
60.0
1
57.0
1
54.0
1
64.0
1
63.0
1
57.0
1
36.0
1
56
­0
2
3
44.0
36
­0
4
5
19
­0
ANIMAL
NUMBER
INTERVALS
9
2
3
45
­0
35.0
4
22.0
5
ANIMAL
NUMBER
INTERVALS
10
2
3
42.0
28.0
4
5
20
­0
ANIMAL
NUMBER
INTERVALS
'2
3
48.0
42.0
4
5
26
.O
ANIMAL
'
NUMBER
INTERVALS
12
2
3
42.0
47.0
4
29
.O
5
i
ANIMAL
NUMBER
INTERVALS
13
2
3
43.0
48.0
4
5
39
­0
ANIMAL
NUMBER
INTERVALS
14
2
3
28.0
15.0
4
5
15.0
ANIMAL
NUMBER
IKTERVALS
15
2
3
44.0
32.0
241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
GROUP
1
­
CONTROL
FEMALES
ANIMAL
NUMBER
INTERVALS
16
1
28
.O
2
3
14.0
13.0
4
9
.o
5
I
ANIMAL
NUMBER
.
INTERVALS
1
26
.O
17
2
3
4
14.0
1.0
23.0
INTERVALS
5
ANIMAL
NUMBER
1
23.0
18
2
3
4
5.0
23.0
15
.o
INTERVALS
ANIMAL
NUMBER
19
,
1
33.0
4
1.0
5
2
3
17.0
17
.O
ANIMAL
NUMBER
20
INTERVALS
1
32.0
4
13.0
5
2
3
26
.O
11.0
ANIMAL
NUMBER
.

21
rmvu
1
29.0
2
3
12.0
14
.O
4
6
.O
5
ANIMAL
NUlrlBER
INTERVALS
22
1
27
­0
2
3
14.0
12.0
4
18
.O
5
­
71
­

241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
ANIMAL
NUMBER
INTERVALS
23
1
36
.O
1
38
.O
1
24.0
1
37
.o
1
35.0
1
35.0
2
3
20
.o
9.0
4
5
11.0
ANIMAL
NUMBER
INTERVALS
24
2
3
24.0
22.0
4
5
14.0
ANIMAL
NUMBER
INTERVALS
25
2
3
18
.O
6
.O
INTERVALS
4
9
00
ANIMAL
NUMBER
26
2
3
8
.O
18
.O
4
9
­0
ANIMAL
NUMBER
INTERVALS
27
2
3
11.0
22.0
4
9
.o
5
ANIMAL
NUMBER
INTERVALS
2
35.0
3
24.0
28
4
12.0
5
ANIMAL
NUMBER
INTERVALS
1
28
.O
4
11
.o
5
29
2
3
2.0
20.0
INTERVALS
ANIMAL
NUMBER
30
1
27.0
2
3
15
.O
12
.o
4
5
3.0
­
72
­

ANIMAL
NUMBER
31
ANIMAL
NUMBER
ANIMAL
NUMBER
33
mrw
NUMBER
34
ANIMAL
NUMBER
35
ANIJWL
NUMBER
36
ANIMAL
NUMBER
37
APPENDIX
­
36
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
GROUP
2
­
.50000
(PPM)
MALES
1
63.0
1
60.0
1
49.0
1
46.0
1
62.0
1
57.0
1
41.0
INTERVALS
2
3
48.0
38.0
INTERVALS
2
3
53.0
`
52.0
.
INTERVALS
2
3
37
­0
32.0
INTERVALS
2
3
32.0
32.0
I
r
n
V
A
L
S
2
3
42.0
38.0
INTERVALS
2
3
46
.O
42.0
INTERVALS
.

2
3
31.0
24.0
4
29
­0
4
38.0
4
22
.o
4
30.0
4
37
.O
4
35.0
4
14.0
241
­141
5
5
5
5
5
­
73
­

241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
,

INTERVALS
ANIMAL
NUMBER
1
2
3
4
44.0
54
.o
24.0
32.0
38
INTERVALS
A
N
I
W
NUMBER
1
2
3
4
59
­0
47
­0
39
.O
25
­0
39
INTERVALS
ANIMAL
NUMBER
1
2
3
53
.O
32.0
22.0
4
25.0
5
40
INTERVALS
ANIMAL
NUMBER
1
80
.o
41
2
3
55
.O
33.0
4
29.0
INTERVALS
ANI
MAL
NUMBER
42
..
1
50.0
2
3
37
­0
30.0
4
25
.O
INTERVALS
ANIMAL
NUMBER
1
56
.O
2
3
35
.O
26
.O
4
12.0
43
INTERVALS
ANIMAL
NUMBER
2
3
4
48
.O
28.0
19.0
5
44
1
53.0
ANIMAL
NUM3ER.
1"
ERVALS
2
3
4
5
54.0
44.0
39
.O
45
1
60
.O
­
74
­

241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(G
W
S
)
S241141
GROUP
2
­
.5000
(PPM)
FEMALES
ANIMAL
NUMBER
INTERVALS
1
35.0
4
12.0
5
46
2
3
17.0
18.0
ANIMAL
N
W
E
R
INTERVALS
47
1
22.0
1
26
.O
1
30.0
1
26.0
2
21.0
3
3.0
4
18
­0
5
ANIMAL
NUMBER
INTERVALS
48
2
3
23.0
18.0
4
9.0
5
I
r
n
V
A
l
S
A
N
I
W
NUMBER
2
3
17
­0
10.0
INTERVALS
5
49
*
4
6
.O
ANIMAL
NUFIBER
2
3
15
­0
11
.o
4
8
.O
5
50
ANIMAL
NUMBER
INTERVALS
1
19
.o
2
3
20
.o
5
­0
4
11.0
5
51
ANIMAL
NUMBER
INTERVALS
1
23.0
4
11.0
5
52
2
3
16..
0
12.0
­
75
­

241­
141
ANIMAL
NUMBER
53
ANIMAL
NUMBER
54
ANIMAL
NUMBER
55
ANIMAL
NUMBER
56
ANIMAL
NUMBER
57
ANIMAL
NUMBER
58
ANIMAL
NUMBER
54
ANIMAL
NUMBER
60
1
33.0
1
32.0
1
28.0
1
­32.0
1
26.0
1
22.0
1
27.0
1
31.0
5241141
INTERVALS
2
17.0
3
12
.o
4
3.0
INTERVALS
2
3
4
15
­0
18
­0
­2.0
INTERVALS
2
3
4
21.0
18
.o
7
­0
INTERVALS
5
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRpsrtS)

(?
0
0
8SO
5
5
2
3
4
5
27
.O
18
­0
4.0
INTERVALS
2.
3
4
19
.o
8
­0
7
.O
I
KTERVALS
5
2
19
.o
3
4
13.0
10.0
5
INTERVALS
2
3
4
.5
15.0
17
.O
10
­0
INTERVALS
'

2
3
4
23.0
13
.O
6
­0
5
­
76
­

­
241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
GROUP
3
­
3.0000
(PPM)
MALES
'

ANIMAL
NUMBER
INTERVALS
61
1
60.0
1
50.0
1
53.0
1
50.0
1
64.0
1
66.0
1
47
­0
2
3
55.0
38
.O
4
29
.o
5
ANIMAL
NUMBER
INTERVALS
62
2
3
41
.O
32
.O
4
5
21
.o
ANIMAL
NUMBER
63
INTERVALS
3
33
.O
4
5
32
­0
ANIMAL
NUMBER
64
INTERVALS
4
.5
29
.O
ANIMAL
NUMBER
INTERVALS
65
2
3
49.0
42.0
4
28
.O
5
ANIMAL
NUMBER
INTERVALS
66
'
2
3
46.0
39.0
4
37
.O
5
ANIMAL
NUMBER
INTERVALS
67
2
45.0
3
38.0
4
26
.O
5
­
77
­

,
241­
141
i
ANIMAL
NUMBER
6a
ANIMAL
NUMBER
69
ANIMAL
NUMBER
70
ANIMAL
NUMBER
71
ANIMAL
NUMBER
72
ANIMAL
NUMBER
73
ANIM4L
NUMBER
74
ANIMAL
NUMSER
75
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGKT
GAINS
(GRAMS)
S
2
41
141
1
54.0
1
60.0
1
47
­0
1
51.0
1
.
53.0
I
53.0
1
47
.O
1
58
.o
INTERVALS
2
3
40.0
32.0
INTERVALS
2
3
55.0
41.0
INTERVALS
2
3
34.0
30.0
INTERVALS
2
3
46
.O
35.0
I
NfERVALS
2
3
39
­0
33.0
INTERVALS
2
3
49
.O
30.0
INTERVALS
2
3
40.0
35
­0
INTERVALS
~

2
3
43.0
35.0
4
27
­0
4
39
.o
4
27
.O
4
32.0
4
23
­0
4
23.0
4
21
.o
4
20
.o
5
5
5
5
5
5
5
­
78
­

241­
141
APPENDIX
­
38
­
CONTINUED
.
INDIVIDUAL
BODY
WEIGHT
GAINSGRAMS)
S241141
GROUP
3
­
3.0000
(PPM)
FEMALES
ANIMAL
NUMBER
IJVERVALS
76
1
34.0
1
24.0
1
32.0
2
3
15.0
21
.0
4
11
.o
5
ANIMAL
NUMBER
INTERVALS
77
4
6
.O
5
2
3
20.0
18
.O
ANIMAL
NUMBER
I
NTERVAlS
78
2
22.0
3
16.0
4
22
.o
5
ANIMAL
NUMBER
.
INTERVALS
79
1
31.0
1
30.0
1
28.0
1
39.0
2
3
21.0
22
.o
4
4.0
'
5
ANIMAL
NUMBER
80
INlERVALS
2
20.0
3
10.0
4
5
10.0
ANIMAL
N
W
E
R
INTERVALS
a1
2
3
14.0
15.0
4
5
11.0
ANIMAL
NUMBER
INTERVALS
82
2
3
24.0
20.0
4
10.0
5
­
79
­

241
­
141
APPENDIX
­
3B
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
,

INTERVALS
ANIMAL
NUMBER
83
ANIMAL
NUMBER
84
4
4
­0
5
1
25
­0
1
24.0
1
27
.O
1
23.0
1
33.0
I
24.0
I
30.0
1
34.0
2
3
16.0
9
.o
INTERVALS
2
3
4
14.0
7
.O
11.0
5
ANIMAL
NUMBER
INTERVALS
2
3
4
14.0­
14.0
9
.o
5
85
ANIMAL
NUMBER
INTERVALS
5
86
2
3
4
22.0
­10.0
11.0
INTERVALS
ANIMAL
NUMBER
4
14.0
5
87
2
14.0
3
6.0
,
ANIMAL
NUMBER
INTERVALS
4
6.0
2
3
12.0
14
.O
88
ANIMAL
NUMBER
89
ANIMAL
NUMBER
90
INTERVALS
2
15.0
3
12.0
4
9
­0
INTERVALS'

2
3
34.0
11.0
4
20.0
5
­
80
­

ANIMAL
NUMBER
91
ANIMAL
NUMBER
92
ANIMAL
NUMBER
93
ANIMAL
NUMBER
94
ANIMAL
NUMBER
95
ANIMAL
NUMBER
96
ANIMAL
NUMBER
97
APPENDIX
­
36
­
CONTINUED
INDIVIDUAL
BODY
.WEIGHT
GAINS
(GRAMS)
S241141
GROUP
4
­
10.0000
(PPM)
MALES
1
50.0
1
46
.O
1
57.0
1
58.0
1
43
.O
1
51.0
1
43.0
INTERVALS
2
3
49.0
36.0
INTERVALS
2
3
42.0
41.0
INTERVALS
2
3
31.0
29.0
INTERVALS
2
49.0
3
47.0
INTERVALS
2
3
42.0
34.0
INTERVALS
2
.3
45.0
43.0
INTERVALS
2
3
30.0
28.0
4
42.0
4
30.0
4
22
.o
4
38
.O
4
29
.O
241
­141
4
5
14.0
5
5
4
5
17
.O
­
81
­

APPENDIX
­
3B
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
5241141
241­
141
ANIMAL
NUMBER
INTERVALS
4
5
29
.O
2
3
46.0
33.0
1
50.0
1
48.0
1
46.0
I
69
.O
1
49
.O
1
41.0
1
45
.O
3
98
INTERVALS
ANIMAL
NUMBER
4
5
28
.O
2
3
34.0
32.0
99
INTERVALS
ANIMAL
NUMBER
4
5
25
.O
2
3
49
­0
35.0
100
IKTERVALS
ANIMAL
NUMBER
5
5
5
2
3
48.0
38
­0
4
18
.O
101
INTERVALS
ANIMAL
NUMBER
2
3
42.0
31.0
4
25
­0
102
I
r
n
V
A
L
S
ANIMAL
NUMBER
103
2
3
44.0
32.0
INTERVALS
.
4
29
­0
ANIMAL
NUM8ER
5
2
3
42.0
30.0
INTERVALS
.
4
17
.O
104
ANIMAL
N
U
B
E
R
2
3
`4
5
I
45
.O
37.0
20.0
23.0
105
­
82
­

241­
141
APPENDIX
­
3
B
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(GRAMS)
S241141
6ROUP
4
­
10.0000
(PPM)
FE?
ULES
ANIMAL
NUMBER
I
NTERYALS
106
1
19.0
1
31.0
I
26.0
1
32.0
1
26.0
1
28.0
1
25.0
2
3
17.0
24.0
4
8
.o
5
ANIMAL
NUMBER
INTERVALS
107
5
2
10.0
3
12.0
4
12.0
ANIMAL
N
W
E
R
INTERVALS
108
2
17
.O
3
5.0
4
12.0
5
ANIMAL
NUMBER
INTERVALS
109
2
3
16.0
30.0
4
8.0
5
ANIMAL
NUMBER
INTERVALS
110
2
3
15.0
18
.O
4
9
.o
5
ANIMAL
NUMBER
INTERVALS
111
2
3
17.0
13.0
4
5
2
.o
ANIMAL
NUMBER
INTERVALS
112
2
15.0
3
10.0
4
5
9
­0
­
83
­

241­
141
APPENDIX
­
38
­
CONTINUED
INDIVIDUAL
BODY
WEIGHT
GAINS
(G
W
S
)
S241141
ANIMAL
NUMBER
113
INTERVALS
4
7
.O
5
1
27
­0
1
23.0
1
26
­0
1
29
.o
1
24.0
1
18.0
1
29
.o
1
26
­0
2
3
16.0
12
.o
INTERVALS
ANIMAL
NUMBER
5
3
4
5
.O
2
20.0
15
.O
114
INTERVALS
ANIMAL
N
W
E
R
2
3
4
25
.O
19
.o
7
.O
5
115
INTERVALS
ANIMAL
NUMBER
2
3
4
19
­0
21*
0
7
­0
INTERVALS
116
ANIMAL
NUMBER
2
3
23­
0
10.0
117
4
9
*o
I
KTERVALS
ANIMAL
"
NUMBER
118
5
2
3
,4
18.0
12
.o
5
.O
INTERVALS
ANIMAL
NUMER
5
2
3
4
8.0
15
,O
6
.O
119
ANIMAL
NUMBER
INTERVALS.

5
120
2
3
4
24.0
17
.O
6
.O
­
84
­

241­
141
Standard
Key
t
o
Hematology
Leukocyte
Differentials
BLAST
=
Blast
Cells
LYMPH
=
Lymphocytes
EOSIN
=
Eosinophils.
BAND
=
Band
Neutrophils
MFTA
=
Metamyelocytes
MONO
=
Monocytes
BAS0
=
Basophils
SEG
=
Segmented
Neutrophils
Erythrocyte
and
Leukocyte
Morpholoqy
ANIS0
=
Anisocytes
ECHINO
=
Ech
inocytes
TAR6ET
=
Target
Cells
MICRO
=
Microcytes
POIK
=
Poikilocytes
ACANTH
=
Acanthocytes
POLY
=
Polychromatophilic
Cells
MACRO
=
Macrocytes
BASOSTIP
=
Basophilic
Stippled
Cells
HYPO
=
Hypochromic
Cells
BURR
=
Burr
Cells
CRENATED
=
Crenated
Cells
Presence
of
the
above
cell
types
are
indicated
as:

­
=
No
f
i
n
d
i
n
g
noted
T
=
Trace
numbers
present
1
=
S
l
i
g
h
t
numbers
present
2
=
Moderate
numbers
present
3
=
Marked
numbers
present
4
=
Severe
numbers
present
.

HJBODY
=
Howell­
Jolly
Bodies
.
TOXIC
=
Toxic
Granulation
FILARIA
=
Microfilaria
SMUDGE
=
Smudge
Cells
DOHLE
=
Dohle
Bodies
PLTCLUMP
=
Platelet
Clumps
RECTRBC
=
Rectangular
RBC'
s
Presence
o
f
the
above
cell
types
are
indicated
as:

­
=
No
cells
present
F
=
Few
cells
present
M
=
Many
cells
present
or
­
=
No
cells
present
P
=
Cells
present
(not
quantitated)

NRBC
=
Nucleated
RBC's
IM
LYMPH
=
Imnature
Lymphocytes
o
f
100
white
blood
cells
counted.
REACTLYM
=
Reactive
Lymphocytes
PLASMA
=
Plasma
Cells
Presence
o
f
the
above
cell
types
are
indicated
as
a
percentage
­
85
..

241­
141
Appendix
4
Subacute
Inhalation
Study
o
f
PCl3
in
Rats
Individual
and
Mean
Clinical
Hematology
Values
­
86
­

d
..
w
0
n
m
N
..

>
4
n
v)

w
­J
4
ac
..
x
w
v)

c
U
a
..
v)

w
V
I
2
v)

d
U
rl
d
U
cy
v)

..
I­
o
W
3
0
U
n
I
I
I
+I
V
Y
I
S
I
I
I
I
d
l
m
o
I
(I)\
I
8
I.
I
(I
1
I
I
I
­1
1
u=
J
I
I
X
I
I
I
I
­I
1
v
2
I
=x
I
I
­1
m­.
I
m
­
I
I
I
4
w
I
z!
n
­Is
I
z
>
I
.=
z
I
aa
I
z
n
a
..
c
z
w
u
U
v)
0
Q
I
a
d
0
c
2
0
V
d
LJ
w
2
w
v)
0
0
a
0.

d
0
..
n
3
0
a­
0
d
x
a
Q
..
C
m
z
a
w
?a
­
v)
0
0
Io
0
..
­1
w
>
u
d
w
v)
0
0
cv
0
..
n
a
53
c,

W
I
a
n
..
c
z
3
W
Q
4
v)
0
0
c1
0
.
n
..
2
w
>
w
­I
w
v)
0
n
n
0
P
3
0
c"
..

a
­
87
­

N
..
w
W
U
P
m
.N
..

t
0
a
v)
w
­I
4
E
..
x
W
u)

c
4
E
..
v)
W
u
CI
ii
a
..
us
d
U
H
c(

4
el
v1
..
c
0
W
3
0
a
a
L
u
U
n
I
3
I
a
1
=Io
I
a
\
I
IS
I
W
I
I
I
I
4
1
v
3
I
a\
I
X
I
I
a­
I
r
a.
5
..
C
II
z
3
W
W
a
v)
3
0
0
.
0
d
.I
4
W
>
W
­I
Id
v)
0
0
U
3
..
a
3
0
P
0
­
88
­

PROJECT:
S
2
4
1
1
4
1
SPECIES:
RAT'
SEX:
HALES
ObY
:
29
PAGE
1
APPENOIX
4
IFSOIVIOUAL
LEUKOCYTE
DIFFERENTIALS
SUSAC'JTE
INHALATISti
TOXICITY
STUOY
O
F
PC13
I
N
RATS
WALES
.
DAY
:
29
GROUP:
1
ANIi4AL
NUHBER
­­­­­­

94COCl
846002
346003
34600a
946505
345011
5
4
6
0
1
2
346013
946010
846315
GROLIP:
2
ANIYAL
N
U?
9
E
3
­­­­­­

94i031
846a32
846333
546030
606035
945001
9
46
042
845543
946C44
546045
OOSE
LEVEL:
CONTROL
5E)
SAGE
UNIT:

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
9
12
7
7
13
3
13
19
21
15
as
85
93
92
86
94
93
80
79
a2
2
3
0
1
1
1
2
1
0
1
1
C
0
0
0
2
2
0
0
2
0
0
0
0
0
0
0
0
0
0
3
3
0
0
C
0
0
[I
0
a
0
0
0
0
1
0
0
0
0
0
10
20
9
29
f
C
14
13
2
s
2
7
1
6
89
78
87
7
0
67
83
66
74
69
32
1
0
2
3
1
2
1
1
3
1
0
2
2
I
1
1
P
C'
1
1
0
0
0
0
0
3
0
0
0
0
ba59
X
­­­­

R
0
0
0
0
0
0
0
0
0
­
89
­

PROJEtT:
S241141
SPECIES:
RAT
bPFENCIX
4
­CONTfNUEC
0
J
(1
0
0
0
il
C
3
.0
0
0
0
0
0
0
0
G
.o
a
0
0
1
0
0
0
0
C
C
a
C
0
0
0
c
0
0
0
0
.

a
0
0
n
O
0
0
0
0
I
0
0
0
3
0
C
0
0
0
0
0
12
5
14
21
12
11
12
15
'
6
8
10
2r(
11
16
8
10
11.

18
17
11
Be
93
9s
I?
86
87
86
83
93
51
3
0
1
1
2
0
0
2
1
I
1
1
1
C
1
0
1
0
0
n
e9
e7
16
89
79
31
89
78
33
36
1
0
5
0
0
0
J
0
0
1
3
0
n
"

1
2
i:
0
t
0
c
3
0
0
t
0
a
0
0
3
0
0
0
0
­
90
­

PROJECT:
S241141
SPECIES:
RAT
SEX:
MALES
DAY
:
29
PAGE
1
APPENDIX
4
ERYTHROCYTE
AN0
LEUKOCYTE'MORPHOLOGY
'SUBACUTE
INHALATION
TOXICITY
STUDY
OF
pc13
I
N
RATS
MALES
GROUP:
1
DOSE
LEVEL:
CONTROL
ANIMAL
ANXSO
TARGET
POLY
OOSAGE
UNIT:
PPM
NRBC
846001
846002
846003
846004
846005
846011
846012
846013
846014
a45015
2
3
1
2
1
T
T
T
T
T
2
1
1
1
2
1
T
T
T
T
GROUP:
z
DOSE
LEVEL:
0.5
DOSA6E
UNIT:
PPPl
NRBC
ANIMAL
TARGET
POLY
846031
846032
345033
846034
B46035
846341
846042
946043
846044
846045
2
2
1
2
1
T
­T
T
T
T
1
2
1
1
2
T
T
T
1
1
­
91
­

PROJECT:
$291141
SPECIES:
RAT
SEX:
MALES
DAY
:
29
PAGE
2
~,
ROUP:
3
OOSE
LEVEL:
3.0
ANIMAL'

846061
846062
846063
946064
846065
846071
846072
846074
8
4
~0
7
3
846075
GROL'P:
4
DOSE
LEVEL:
10.0
ANIMAL
ANIS0
TARGET
846091
996052
346093
846094
as6095
046101
896202
546103
846105
a46104
1
3
2
1
1
T
T
T
T
T
APPENDIX
4
­CONTINUED
DOSAGE
UNIT:
PPM
POLY
NRBC
DOSAGE
UNIT:
PPP!

POLY
NRSC
­
92
­

PROJECT:
S241141
SPECIES:
RAT
SEX:
MALES
D
A
Y
:
29
PA65
1
hPPENOIX
4
ERYTHROCYTE
AN0
LEUKOCYTE
YORPHOLOGY
SUBACUTE
INHALATION
TOXICITY
STUDY
OF
PC13
IN
RATS
HALES
DAY
:
29
GROUP:
1
OOSE
LEVEL:
CONTROL
I)
OSAGE
UNIT:
PPM
846001
846002
346003
346004
346005
646011
846012
846013
346014
a46015
3
2
1
1
GROUP:
2
DOSE
LEVEL:
015
DOSIIGE
UNIT:
PPM
ANIMAL
POIK
ECHINO
ACANTH
RE4tTLYR
%46031
846033
946035
0
46041
846043
846044
a46032
e46034
a46042
a45045
2
1
2
3
T
­
1
1
1
­
­
93
­

PROJECT:
S241141
SPECIES:
RAT
SEX:
MALES
OAY
:
29
PAGE
2
APPENDIX
4
­CONTINUED
SROUP:
3
DOSE
LEVEL:
3­
0
ANIHAL
­­­­­­­­

846061
846062
846063
846064
846065
846071
846072
846073
346074
B46U7S
GROUP:
9
e96091
846092
846093
846044
8
46
095
B46101
e46102
~4
c
;i
a
3
946104
POIK
ECHfNO
­
T
1
­
1
­
T
­
1
T
1
"
1
T
1
T
T
­
T
OOSE
LEVEL:
LQIO
POIK
ECWXNO
846105
T
1
DOSAGE
UNIT:
ppn
DOSAGE
UNIT:
ppn
ACANTH
QEACTLYM
­
94
­

.­
l
..
W
U
*a
n
m
cu
..
*
U
0
rA
W
­I
U
S
w
lL
..
x
LJ
v)

c
4
Lc
rn
LL:

U
W
P
rn
..

L
4
U
r(

.d
U
nr
v)

..
C
U
Iz
7
0
`a
c
I
I
I
C
I
o
w
I
S
I
I
I
I
4
8
w
\
I
x
z
i
W
I
1
m
o
I
I
I
2
1
u
3
I
r
l
1
rnx
I
a­:

I
I
­I
1
­3
I
a\
I
3
x
I
4
­1
I
:
I
U
W
I
I
23
1
4
2
1
>a
I
r
m
:
r
a
a
..
c
n
z
3
W
0
4
vl
0
a
­I
0
C
2
0
U
a
..
a
w
>
w
­I
W
v)
0
0
4
0
..
P
3
0
a
­l
m
C
D
m
D
w
a
o
y
)a
N
..........
*n
u
w
Q
)w
u
C
D
*a
u
m
u
e
u
u
u
e
u
u
I
a
a
..
c
z
3
w
0
4.
vl
0
0
I
m
.
D
..
­I
(J
=r
W
d
W
vl
0
0
N
0
..
P
3
0
a
r
a.
a
..
c
z
3
W
W
4
vl
e
­

a
0
n
.
..
­I
W
>
w
­I
w
vl
0
0
n
0
..
P
3
0
p:
W
C
N*)

..
r
n
N
U
e
r
­*

a
.­
l
..

LD
CUN
r)
N
CD
e
.

m
o
a
..
*a
­
95
­

N
..
w
W
4
a
m
Iv
..
*
U
a
v)

w
a
e
E
W
LL
..
x
W
ul
r
P
P
..
c
L1
2
1>

iJ
0
4
v)
0
3
0
0
I
..
­1
w
=.
W
­1
w
m
0
0
e
0
..
c
3
0
c"
a
­
96
­

PROJECT:
S241141
'
SPECIES:
RAT
SEX:
FEMALES
D
A
Y
:
29
PAGE
I
APPENDIX
4
SUBACUTE
INHAiATIGN
TOXICITY
STUDY
OF
Pc13
IN,
RATS
IN3IVIDUAL
LEUKOCYTE
OIFFERENTIALS
346306
846557
B
16
0
0.3
846307
B46G10
946015
346017
846013
846014
a46020
946038
946037
946C33
94E04t
846047
846C48
946003
946050
a46335
a46346
FEHALES
0
0
0
0
0
0
0
3
0
D
0
0
0
0
0
0
'3
0
0
0
C
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
D
0
0
c
c
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
SEG
f
­­­

2
2
11
10
13
15
8
9
7
14
19
SEG
r
­­­

12
19
7
6
17
7
10
21
22
13
C
A
Y
:
29
76
69
89
37
8
2
90
01
0
0
8
3
7s
0
0
1
0
1
0
0
1
3
3
2
0
0
0
2
2
0
2
C
0
85
79
91
33
82
89
90
75
72
86
2
1
0
0
0
2
0
1
2
0
1
1
2
1
1
2
0
3
3
0
ba50
x
­­­­

0
0
0
0
0
0
0
0
0
0
ba50
1
­­­­

0
0
0
0
0
0
0
0
1
1
­
97
­

PROJECT:
Sa41141
SPECIES:
RAT
SEX:
FEnhLES
D
A
Y
:
29
PhGE
2
hPPENQIX
4
­CJNTINUEJ
0
9
0
0
0
0
0
0
0
0
0
0
0
D
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
3
0
c
r?
0
0
0
0
0
0
3
!I
0
!J
0
0
0
0
.
0
0
0
'3
0
0
0
0
0
0
SEG
.I
­­­

18
4
9
11
9
3.1
53
15
4
24
S
E
G
x
­­­

16
17
17
10
14
10
1
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PROJECT:
S241141
SPECIES:
RAT
SEX:
FEMALES
DAY
:
29
PAGE
1
APPENDIX
4
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AND
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3ORPHOLOGY
SUBACUTE
INHALATION
TOXICITY
STUOY
3F
PCl3
IN
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PROJECT:
S241141
SPECIES:
RAT
SEX:
FEMALES
DAY
:
29
PAGE
2
APPENUIX
4
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DSOJECT:
S241141
SPECIES:
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FEHALES
DAY
:
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PAC:
1
APPENOIX
4
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A
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LEUKOCYTE
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PROJECT:
S24114l.
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2
aPPENOIX
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241
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Standard
Key
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Hemolysis
HT
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=
Moderate
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=
Severe
Hemolysis
­
103
­

241­
141
Appendix
5
Individual
and
Mean
C1
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Chemistry
Val
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Subacute
Inhalation
Study
o
f
PC13
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)
­ddcudded.­
ld
0
0
0
0
0
0
0
0
0
0
n
n
n
u
cu
no
R
cu
CJ
..........
­
111
­

tu
m
N
P
rl
E
w
U
..
x
W
v)

c
a
a
..
v)
W
n
V
W
P
UJ
­
v
­.
r(
U
tu
v)

..
c
u
W
3
0
cc
n
I
P
a
..
c
L
z
3
w
i
..
C
E
I
­1
5
Y
n
c
5
5
c
0
L
0,
n
L
0
Y)

n
c
h
m
E
m
V
W
N
c
­

a
n
Transparencv
CL
=
Clear
H
=
Hazy
CY
=
Cloudy
T
=
Turbid
GLUCOSE
:

­
=
Negative
T
=
Trace,
1/
10
g/
dl
1
=
%
g/
dl
2
=
%
g/
dl
3
=
1
g/
dl
4
=
2
o
r
more
g/
dl
OCCULT
BLOOD:

­
=
Negative.

1
=
Small
2
=
Moderate
3
=
Large
NT
=
Nonhemolyzed
trace
H
l
=
Hemol.
yted
trace
'
­
112
­

Standard
Key
t
o
Urinalysis
Color
­
PY
=
Pale
Yellow
Y
=
Yellow
DY
=
Dark
Yellow
B
=
Brawn
CO
=
Colorless
R
=
Red
BL
=
Black
Grading
PROTE
IN
:
BILIRUBIN:

­
=
Negative
­
=
Negative
T
=
Trace
1
=
Small
1
=
30
mg/
dl
2
=
Moderate
2
=
100
rng/
dl
3
=
Large
3
=
300
mg/
dl
4
=
over
1000
mg/
dl
UROBILINOGEN
:
KETONES
:

Values
i
n
­
=
Negative
Ehrlich
Units/
dl
T
=
5
mg/
dl
1
=
15
mg/
dl
2
=
40
mg/
dl
3
=
80
mg/
dl
4
=
160
mg/
dl
SPECIFIC
GRAVITY
+
=
Greater
than
M
i
cros
coDi
c
Fi
ndinqs
RBC/
HPF
=
Red
blood
cells
per
high
power
f
i
e
l
d
WBC/
HPF
=
White
blood
cells
per
high
power
f
i
e
l
d
EPITH/
HPF
=
E
p
i
t
h
e
l
i
a
l
cells
per
high
power
f
i
e
l
d
AMORPHILPF
=
Amorphous
crystals
p
e
r
low
power
f
i
e
l
d
CRYSTAtS/
LPF
=
Crystals
per
low
power
f
i
e
l
d
BACTERIA/
LPF
=
Bacteria
per
low
power
f
i
e
l
d
CASTS/
LPF
=
Casts
per
low
power
f
i
e
l
d
YEAST/
lPF
=
Yeast
per
low
power
f
i
e
l
d
.SPERM/
LPF
=
Sperm
per
low
power
f
i
e
l
d
TNTC
=
Too
numerous
t
o
count
­
113
­

Appendix
6
Individual
and
Mean
Clinical
Urinalysis
Values
Subacute
Inhalation
Study
of
PCl3
i
n
Rats
­
114
..

4
..
w
W
4
a.

c,
01
..

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n
v)
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U
r
..
X
W
Ga
c
4
a
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w
V
I
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N
rn
w
a
w
zc
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V
4
m
3
v)
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D
3
Lc
V
0
z
w
c
0
I
a
n
M
W
z
0
c
W
x
d
v:
0
V
2
3
(1
c
(1
0
v)

r
0
@i
U
W
0
U
n
I
I
I
I
I
1
I
I
8
I
I
I
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I
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1
I
I
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I
I
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I
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t
I
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I
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I
I
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I
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I
I
I
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I
1
I
I
I
1'
r
c
c
..
c
I
2
3
w
W
4
M
0
0
2
0
r
c
z
c
V
..
2
d
=.
LL:
­I
w
v)
0
0
d
0
..
0
3
0
c
5
I
I
I
I
l
l
1
1
1
1
S
n.
n.
..
c
I
z
3
W
W
U
v)

0
0
VI
0
..
­J
w
=.
W
a
W
v)
0
0
01
0
*­
c
3
c
c
W
c
I
I
I
d
I
I
d
M
d
X
1
1
1
1
1
1
1
1
1
1
+
+
+*
o
Q
i~
a
a
u
.no
o
Q
V
J
~~)~J
C
)~~~D
\O
0
0
0
0
0
0
0
0
0
0
..........
d­­
l­
lH­
d­
r(
r(
r:
n
n
..
c
L.

2
3
w
u
4
v)
0
0
c
.
n
..
A
W
>
Li
­I
W
v)
0
a
n
0
..
0
3
0
oz
W
MOOInuIOOOLOOIO
r
­r
­r
D
4
I
a
I
O
­l
­r
D
.n
..........
­
115
­

N
..
LJ
u
U
a
o\
N
..
*
U
0
v)
li
d
t
a
..
X
w
<o
e
4
e
..
cn
W
V
W
;
P
v1
­

r(

U
­
r(

U
N
w
*.
c
V
W
3
0
a
a
2
0
2
(c
V
0
E
W
c
0
e
A
v)
W
2
0
c
w
Y
W
cn
0
u
3
d
(t
a
c
A
v:

S
P
z
4
Li
a
A
4
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
1
I
I
I
I
I
I
I
I
I
I
1
I
I
I
a
I
I
I
1
I
I
I
I
I
I
I
I
1
I
I
I
E
A
c
..
I­

2
3
W
W
4
v)
0
0
I
0
e
0
r(

..
­1
W
=r
w
d
w
vl
0
0
0
..
n
a
3
0
(1
c
c
c
c
.c
c
1
c
c
c
1
1
1
1
1
1
1
1
1
1
**++
**
o
o
o
o
9
*w
o
(v
o
LY
.n
rD
\o
u
In
In
*
u
\c
0
0
0
0
0
0
0
0
0
0
u>
0
0
0
u3
0
0
0
In
In
\C
C
**~*\C
*U
I
.D
..........
­
116
­

SEX:
WALES
J
A
Y
:
2s
PAGE
1
PROJECT:
S241141
SPECIES:
RAT
APPENQIX
6
INQIVIOtlAL
nICROSCOPXC
URINALYSIS
FINDINGS
SUBACUTE
INYALATICN
TOXICITY
STUDY
O
F
Pc13
Ih!
RhTS
YALES
O
A
Y
:
29
846001
846002
9460G3
346004
a46009
846013
246012
546013
846014
345015
H4NI
MANY
MANY
MOO
uoo
%GO
no0
FEU
.MANY
noo
GROUP:
2
DOSE
LEVEL:
0.5
3CSAtE
UNIT:
PPU
SNIRAL
P.
SC
UBC
€PITH
AUORPH
CRYSTALS
BACTERIA
CASTS
YEAST
SPERM
NUHBE2
PERHPF
PERHPF
PERHPF
PERL?
F
PERLPF
PERLPF
PERLPF
PERLPF
PE3L?
F
­­­­­­
­­­­­­
­­­­­­
­­­_­­
­­­­
e­
­­­­­­
­­­­­­
­­­­­..
­­­­­­

E453,
li
346032
346030
346035
846041
646042
846043
846044
846045
946033
FEY
FEU
no
0
FEA
FEU
FEU
FEU
FEU
nao
noo
MOD
.roc
RANI
HANY
MANY
no0
300
WJO
FEU
noo
­
117
­

PROJECT:
S241141
SPECIES:
RAT
SE%:
HALES
DAY
:
29
PAGE
2
APPENDIX
6
­CONTINUED
346051
946052
546063
946054
646065
846071
945372
346073
346074
946075
946091
B46092
946093
845054
e46055
846101
946102
945104
646105
a46103
4
DOSE
LEVEL:
10.0
fl0
D
FEU
MC3
FEY
MOD
FEU
FEY
FEW
FEU
FEY
MANY
FEY
MANY
RO
0
ffcc
W
N
Y
no0
no0
no0
no0
D
O
S
I
G
E
UNIT:
PPFI
MOD
noo
nil3
no0
FEY
300
?I@
0
FEU
MOO
noc
­
FEY
­
­
118
­

i
1.

..
.w
0
4
..

t
4
3
3
C
2
.I
V
0
E
W
I­
3
p:
c
c,
2
W
z
0
c
W
Y
w
c
V
3
­1
a
V
c
lA
TT
c
­
­
a
a
a
W
<
I
I
I
I
I
I
t
I
1
I
I
I
I'
I
I
I
I
I
I
I
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I
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I
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I
I
I
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I
I
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t
1
I
I
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r
a
c
..
c
­
z
3'

Id
'­
9
4
w
3
0
i
G
t
z
c
U
a
..
­1
W
>
w
­1
LJ
m
c
a
4
Q
..
4
d
r
z
(5,
1
1
1
1
l
l
1
1
1
1
1
1
1
1
1
1
1
1
1
1
*'
++
**
0
c
J
0
N
u.
0
5
0
\c
(v
(u
.n
r?
e
3
Q
\(
I
0
0
0
0
0
0
0
0
0
0
..........
a
­a
*a
m
­d
d
­

O
(F
C
S
O
O
E
O
0
O
O
..........
al­
c­**
l­
G­*
I
c
l
l
c
c
c
c
1
I
c
o
o
o
o
o
o
o
o
o
..........
ddddd.
r.­*­
lrn
0
0
0
E
IT,
Y)
0
0
0
0
..........
P
.~w
u
*~Q
=:\D
~
z
a
c
..
c
­
z
3
W
'3
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v)
C
3
0
rr:

..
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iu
>
w
i
W
u)
0
C
n
0
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a
a
5
r
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oouv)
ov)
v)
v)
oo
u)
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(ZL
u)
\i.
a
c
h
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rD
..........
­
119
­

..
W
0
U
P
..
*
U
D
M
W
­I
4
z
w
I&

..
x
I&
M
w
c
G
E
a
VI
W
z
G
c
Lr'
Y
w
VI
,=
u
3
A
0
c:
u
V,
a
X
a
a
a
a
a
4
Y
I
1
I
I
I
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I
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I
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I
.

1
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
I
1
a
I
I
1
I
I
I
I
I
I
I
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I
1
1
I
I
I
I
I
I
I
I
I
a
P
..

c
L
z
3
w
0
4
M
0
a
0
0
.
4
..

A
W
>
w
2
2
v)
0
I
c
0
..
n
a
3
0
'3
*+**
+
++
0
0
0
0
E
0
9
0
Q
=2
.P
u
.G
\)
r
LD
c
­a
\D
G
Q
0
0
0
0
0
0
0
0
e
D
.....
e....
I
­
120
­

PROJECT:
Sa41141
SPECILS:
RAT
SEX:
FEMhLES
DAY
:
29
PAGE
1
APPENDIX
6
1NDIVIi)
UAL
HICROSCOPIC
URINALYSIS
FINDINGS
SUBACUTE
INHALATION
TOXICITY
STUDY
OF
?C13
IN
RATS
FEHALES
3bY
:
29
546006
­
846007
946009
846010
845016
846017
345019
846020
946008
a46018
846036
946037
646038
846040
046046
846047
845049
9
46
OS
0
a
46
1339
e46048
FEL;
FEU
FEil
Moo
FEU
FEU
FEU
FEU
FEU
FEU
MOT)
FEX
no0
RO
0
MO3
NU
0
MOO
MOD
'
ROS
FEU
2
DOSE
LEVEL:
0.5
DOSAGE
UNIT:
PPM
­
no0
FEII
HOD
­
FEU
­
FEU
­
FEU
­
MOD
­
FEU
­
FEU
­
FEU
,
­
noo
NANY
UANY
Moo
no0
FEU
UANY
MOO
%ANY
300
YOD
­
121
­

PROJECT:
S241141
SPECIES:
R
A
T
SEX:
FEMALES
DAY
:
29
PAGE
2
APPENOfX
6
­CONTINUE0
346066
6
46067
346068
e46069
e46070
e46076
946C77
646078
646079
646080
646096
945097
646038
646099
646100
946106
846107
346108
846109
6'46
11
0
3
OOSE
LEVEL:
3­
0
DOSAGE
UNIT:
PPU
RBC
LlBC
EDITH
AUORPH
CRYSTALS
EACTERIA
CASTS
YEAST
SPE33
PERHPF
PERHPF
OESCIPF
PERLPF
PERLPF
PERLPF
PERLPF
PERLPF
PERLPF
­­­­­­
­e­­­­
­­­­­­
­­­­­­
­­­­­­
­­­­­­
­­­­­­
e­­­­­
­­­­­
e
FEW
FEY
no0
no0
FEU
FEU
FEU
FEU
FEU
FEU
FEU
MOD
MANY
MANY
FEU
FEU
no0
MOD
MOO
rimy
FEW
FEY
MOD
FEU
FEY
FEU
FEY
FEY
FEY
FEU
noo
noo
%GO
MOD
HANY
FEU
FEU
UOD
ROO
no0
­
122.­

241­
11..
.

ANIMAL
NUMBER
CORRELATION
TABLE
Animal
Computer
Animal
Computer
Animal
Computer
Animal
Computer
Number
Number
Number
Number
Number
Number
Number
Number
Males
46001
46002
46003
46004
46005
T43781
T43782
T43783
T43784
T43785
46031
46032
46033
46034
4603
5
T43811
T43812
T43813
T43814
T43815
46061
46062
46063
46064
2­
46065
4
60
71
46072
46073
46074
4
60
75
.­
T43841
'T43
842
T43843
T43.844
T43845
46091
46092
46093
46094
46095
T43871
T43872
T43873
T43874
T43875
46011
46012
46013
46014
46015
T43785
T43787
T43788
T43789
T437
90
4
6041
46042
4
6043
46044
46045
T43
81
6.
T43
81
7
T43818
T43
81
9
T43820
T43846
T43847
T43
848
T4384
9
T43850
46101
46102
46103
46104
46105
T43876
T43877
T43
87
8
T43879
T43880
46021
T43791
46051
T43821
46081
T43851
46111
T4
3
881
46022
T43792
46052
T43
822
46082
T43852
46112
T43
882
I
46023
T43793
46053
T43823
46083
T43853
46113
T4
3
883
46024
T437
94
46054
T43
824
460
84
T43854
46114
T43884
'
45025
T43795
46055
T43825
46085
T43855
46115
T43
885
F&
al
es
.
46006
T43796
46036
T43826
46066
T43856
46096
T4
3
886
46007
T437
97
46037
T43827
46067
T43
857
46097
T43887
.
46008
T43798
4603
8
T43828
46068
T43858
46098
T43888
46009
T43799
4
603
9
T43829
46069
T43859
46099
T43889
46010
T43800
46040
T43830
46070
T43860
46100
T43890
46016
4601
7
46018
4601
9
46020
46026
'
46027
4602
8
.
46030
.
46029
T43
801
T43802
T43
803
T43804
T43
805
46046
46047
46048
4604
9
46050
T43
802
T43803
T43804
T43805
T43806
46076
46077
46078
46079
46080
T43
861
T43862
T43863
T43864
T43
865
46106
46107
46108
46109
46110
T43891
14
3
892
T43893
14
3
894
T43
895
T43806
T43
807
T43808
T43m9
T43810
46056
46057
46058
46059
46060
T43807
T43
808
T43809
T43
810
T43811
46086
46087
45088
46089
46090
T43866
T43867
T43868
T43
86
9
T4
3
870
46116
46117
46118
46119
46120
T43896
T43897
T43
898
T43899
T43
900
­
123
­

Standard
Key
t
o
Gross
Pathology
Death
Codes:
"1
n
"1"
"U"
nyn
IIAII
llgn
nDn
"Ma
"P
"R"

:ion
6
Interim
Sacrifices
1
through
6
Terminal
Sacrifice
Post­
Recovery
Sacrifice
81
Post­
Recovery
Sacrifice
82
Accidental
Death/
Sacrif
i
ce
Post­
Acci
dent
found
Dead
S
acr
i
f
i
ced
Mori
bund
Pre­
Experimental
Death
Unscheduled
Recovery
Sacrifice
Other
Type
of
Unscheduled
Death
Symbols
and
Notations:

"GIi
This
Animal
Has
Gross
Observations
Noted
"Un
Organflissue
Not
Macroscopical
7y
Remarkable
II
­
I1
Keyword/
Phrase
Not
Present
or
Observed
npn
.
Indicates
Presence
(Where
Severity
Inappropriate)
"nC"
Free­
Text
Comnent
(
'C"
)
Accompanies
The
Observati
on
Where
n
*
Indicates
Severity
(1­
5)
or
Presence
(P)
"EX"
Indicates
That
Organ
Is
Excluded
From
Calculations
Organ
Weighing
Statuses:

"NOT
TAKEN"
Organ
Weight
Not
Taken,
No
Explanation
Given
"MISSINGR
Organ
Missing
O
r
Lost
"UNSUITABLE"
Organ
Technically
Unsuitable
For
Weighing
"AUTOLYTICu
Organ
Autolytic
And
Could
Not
Be
Weighed
"EXCLUDE"
Weight
Has
Been
Taken,
B
u
t
Will
Be
Excluded
From
A
l
l
Calculations
­
124
­

241
­
141
Appendix
7
Individual
Gross
Pathology
Subacute
Inhalation­
Study
of
PG13
i
n
Rats
125
­

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241­
141
ANIMAL
NUMBER
CORRELATION
TABLE
Animal
Computer
Animal
Computer
Animal
Computer
Animal
Computer
Number
Number
Number
Number
Number
Number
Number
Number
46001
46002
46003
46004
46005
46011
4601
2
46013
46014
46015
46021
46022
46023
46024
46025
46006
46007
46008
46009
46010
46016
4601
7
46018
4601
9
46020
46026
46027
46028
46029
46030
T43781
T43782
143783
T43784
T43785
T43786
T4
3
787
T43788
T43789
T437
90
T43791
T437
92
T43793
T437?
4
T43795
T43796
T437
97
T43798
T437
99
143800
T43
801
T43802
T43803
T43804
T43
805
T43806
T43807
T43808
T43
809
T43810
46031
4
6
032
45033
46034
46035
46041
46042
46043
46044
46045
46051
46052
46053
46054
46055
46036
46037
46038
46039
46040
46046
46047
46048
46049
46050
46056
46057
46058
46059
46060
Males
T43811
46061
T43812
46062
T43813
46063
T43814
46064
T43815
46065
T43816
46071
T43
81
7
46072
T43
81
8
46073
T43819
46074
T43820
46075
T43821
46081
T43
822
46082
T43823
46083
T43824
46084
T43825
46085
Females
T43826
46066
T43827
46067
T4382
8
46068
T43829
46069
T43830
460
70
T43
802
46076
T43803
46077
T43
804
46078
T43805
46079
T43806
46080
T43807
46086
T43808
46087
T43809
46088
T43810
46089
T43811
460
90
T43841
T43
842
T43843
T43
844
T43845
T43
846
T43847
T43
848
T43849
T43850
T43851
T43
852
T43853
T43854
T43855
T43856
T43857
T43858
T43859
T43860
T43861
T43862
T43863
T43864
T43
86
5
T43866
T43
867
T43868
T43869
T43870
46091
46092
46093
46094
46095
461
01
461
02
46103
46104
46105
46111
46112
46113
46114
46115
46096
46097
46098
46099
46100
46106
46107
46108
46109
46110
46116
46117
4611
8
46119
46120
T43871
T43872
T43873
T43
874
T43875
T43876
T43877
T43878
T43879
T43880
T4
3
881
T43882
T4
3
883
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T43885
T4
3
886
T43887
T43888
T43889
T4
3
890
T43891
T4
3
892
T43
893
T43894
T43895
T4
3
896
T43897
T4
3
898
T43899
T43900
­
166
­

241­
141
Appendix
8A
Individual
Absol
ute
Organ
Weight
Subacute
Inhalation
Study
of
P
C
l
3
i
n
Rats
*
167
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241­
141
ANIMAL
NUM5ER
CORRELATION
TABLE
Anima7
Computer
Animal
Computer
Animal
Computer
Animal
Computer
Males
.
Number
Number
Number
Number
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Number
Number
Number
Number
.
46001
46002
46003
46004
46005
T43781
T43782
T43783
1437
84
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46031
46032
45033
46034
46035
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T43815
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46075
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46092
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T43872
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T43875
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46012
46013
4601
4
45015
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T43787
T43788
T43789
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4
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46042
46043
46044
46045
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T43817
T43
81
8
T43819
T43820
T43
846
T43847
T43
848
T43849
T43850
46101
46102
46103
46104
46105
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876
T43877
T43878
T43879
T43880
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46022
46023
46024
46025
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T43793
T43794
T43795
46051
46052
46053
46054
46055
T43821
46081
T43822
46082
T43823
46083
T43824
46084
T43825
46085
T43851
T43852
T43853
T43
854
T43855
46111
46112
46113
46114
46115
T43881
T43882
T43883
T43884
T43885
Females
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46007
46008
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46010
T43796
T43797
T43798
T43799
T43800
46036
46037
46038
46039
46040
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46066
T43827
46067
T43828
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46068
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46069
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460
70
46096
46097
46098
46099
46100
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3
886
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T43
889
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143856
T43857
T43859
T43860
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T43
801
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T43
803
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T43
805
46046
46047
46W8
46049
46050
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802
46076
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46077
T43
804
46078
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805
46079
T43
806
46080
T43
861
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T43
863
T43864
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855
46106
461
07
46108
461
09
46110
T43891
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3
892
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T43894
T43895
45018
4601
9
46020
46026
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46056
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46086
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46116
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3
896
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46027
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46057
T43
808
46087
T43
867
46117
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46028
T43808
46058
T43809
46088
T43868
46118
T43
898
46030
T43810
46060
T43311
46090
T43870
46120
T43
900
46029
T43
809
46059
T43810
46089
T43
86
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46119
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241­
141
Appendix
9
Individual
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Findings
Subacute
Inhalation
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241­
141
'
Appendix
10
References
Subacute
Inhalation
Study
of
PC13
in
Rats
HEMATOLOGY
teukoc,
yte
Differential
and
Erythrocyte
Morpho1oq.
y
Davidsohn,
I.,
and
Henr.
y,
J.,
Todd­
Sanford
Clinical
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,
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150.

Schalm,
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N.
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Schermer,
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Miale,
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Williams,
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Beutler,
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Erslev,
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Wintrobe,
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Patrick,
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Current
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Erythrocyte
Count
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Leukocyte
Count
(WBC),
Hemoqlobin
(HGB),
and
Hematocrit
(HCT).

Coulter
Counter
Model
S­
Plus
Method
­
Coultet
Electronics,
Inc.,
.
590
West
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33010.
­
,711
­

241­
141
Appendix
10
­
Continued
.
References
Subacute
Inhalation
Study
of
PCl3
in
Rats
CLINICAL
CHEMISTRY
.­

Albumin
(ALBUMIN),
Alkaline
Phosphatase
(ALK
PHOS),
Total
Bilirubin
(T
BILI),
Calcium
(CALCIUM),
Lactate
Dehydroqenase'
(LDH),
Phosphorus
(IN
PHOS),
Total
Protein
(T
PROT),
Aspartate
Transaminase
(AST),
Alanine
Transaminase
and
Blood
Urea
Nitroqen
(BUN).

The
Centrifichem
Method
­
Union
Carbide
corporation,
Clinical
Diagnostics,
402
Theodore
Fred
Avenue,
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ye,
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York
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Chl
ori
de
The
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920M
Chloride
Meter,
Corning
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Diagnostics,
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Glass
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Medfield,
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Annino,
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Clinical
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139.

Sodium
and
Potassium
(POTAS)

The
Corning
460
System,
Corning
Medical
Diagnostics,
Corning
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Works,
Medfield,
Mass,

Annino,
J.
and
Giese,
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Clinical
Chemistry,
Little,
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and
Coo,
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1975,
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61,
134.

Total
Globulin
(GLOBULIN)

Total
Protein
­
Albumin
=
GJobulin
(Calculated).

'
Albumin/
Globulin
(ALB/
GLOB
RATIO)

Albumin
t
Globulin
=
Alb/
Glob
Ratio
(Calculated).

000226
I
­
212
­

241­
141
Appendix
10
­
Continued
Refer
en
ces
Subacute
Inhalation
Study
o
f
PCl3
i
n
Rats
URI
NALYS
I
S
Appearance
(APPEAR
1
Benjamin,
Y.,
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f
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t
a
t
e
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Coles,
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Ames
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1982
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.

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n
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Fall
1964,
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Glucose
Ames
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"Factors
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Chemistry
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(chart)
,"
#9854L,
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Ames
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Modern
Urine
Chemistry,
Elkhart,
IN:
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Co.,
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Ames
Co.
Multistix@
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Elkhart,
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h
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s
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1982
.

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Olsen,
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n
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I
l
l
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n
o
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s
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FaJl
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241­
141
Appendix
10
­
Continued
References
Subacute
Inhalation
Study
of
PCl3
i
n
Rats
URI
NAL
YS
IS
Ketones
Ames
Product
Information:
Factors
Affecting
Urine
Chemistry
Tests,
#9854L,
Rev.
726
3OV,
Ames
Co.,
Elkhart,
1973.

Ames
Co.,
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IN:
h
e
s
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1977,
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Free,
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Adams,
E
­:
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Rupe,
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Simplified
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Protein
Ames
Co.
Ames
Product
Information:
Factors
Affecting
Urine
Chemistry
Tests
(chart),
#9854L,
Rev.
726
3oM,
E
l
k
h
a
r
t
,
IN:
Ames
Co.,
1973
Ames
Co.
Modern
Urine
Chemistry.
Elkhart,
IN:
Ames
Co.,
1977;
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30.

Ames
Co.
Multistifl
insert
if2595AD.
E
l
k
h
a
r
t
,
IN:
Ames
Co.,
March,
1982,

Free,
A.;
Adams,
E.;
Smeby,
R.;
Rupe,
C.;
Free,
H.;
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M.
Simp?
i
f
i
e
d
Chemical
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i
n
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E
l
khart,
IN:
Miles­
Ames
Research
Laboratory,
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8.
241­
141
Appendix
10
­
Continued
References
Subacute
Inhalation
Study
of
PC73
i
n
Rats
URI
NALYS
IS
Occult
Blood
(OC
BLD­
U)

Ames
Co.
Ames
Product
Information:
Factors
Affecting
Urine
Chemistry
Tests,
#9854L,
Rev.
726
3OM,
Elkhart,
IN:
Ames
Co.,
1973.

Ames
Co.
Multistixe
insert
#2595AD,
Elkhart,
IN:
Ames
Co.,
March,
1982.

Coles,
E.
Veterinary
Clinical
Pathology,
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Ed.,
W.
B.
Saunders
Co.,
1974,
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Specific
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Co'les,
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Benjamin,
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t
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t
e
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9.

Microscopic
Examinati
on
of
Sediment
Coles,
E.,
Veterinary
Clinical
Pathology,
2nd
Ed,,
GI,
B.
Saunders
Co,,
Philadelphia,
1914
9
PP.
248
­.
254
Benjmin,
M.,
g
u
t
l
i
n
e
of
Veterinary
Clinical
Pathology,
'2nd
Ed.,
Iowa
S
t
a
t
e
University
Press,
Ames,
1961,
pp.
24­
31.

Modern
Urine
Chemistry,
Ames
Co.,
E
l
k
h
a
r
t
,
1977,
pp,
63,
64,
66,
and
0.

Davidsohn,
I.,
and
Hm­
y,
J.,
.Todd­
Sanford
Clinical
Diagnosis
by
Laboratory
Methods,
15th
Ed.,
W
,
B.
Saunders
Cog,
Philadelphia,
19/
4,
P.
23.

Kul
ter,
D.,
van
Oudheusden,
A.,
Helvieis,
A,,
Nechwile,
M.,
van
Bruel
,
T..
and
Killer
­Po.
"The
Usefulness
o
f
a
New
Test­
StriP
f
o
r
t
h
e
Deiection
o
f
Erythrocytes
and
Hemoglobin
in
the
Urine."
'In:
Dtsch.
med.
Wschr.,
1974,
­
215
­

241­
141
Appendix
10
­
Continued
References
Subacute
Inhalation
Study
of
PC13
i
n
Rats
URINALYSIS
Profiles
i
n
Urinalysis,
Ames
Co.,
Elkhart,
1976.

Benbrook,
E.,
and
Sloss,
M.,
Veterinary
Clinical
Parasitoloqy,
3rd
Ed.,
The
Iowa
S
t
a
t
e
University
Press,
Ames,
pp.
80,
103.

Coffin,
D.,
Manual
of
Veterinary
Clinical
Patholoqy,
3rd
Ed.,
Comstock
Publishing
Associates,
Ithaca,
1953,
p.
38.

Kark,
R.,
A
Primer
of
Urinalysis,
2nd
Ed.,
Harper
and
Row,
New
York,
1963,
p.
26.

Frankel,
S.,
Reitman,
S.,
and
Sonnenwirth,
A.,
Gradwohl's
Clinical
Laborat0r.
y
Methods
and
Diaqnosis,
Val.
If,
7th
Ed.,
The
C.
V.
Mosby
Co.,
St.
Louis,
1970,
p.
1900.

Hepler,
O.,
Manual
of
Clinical
Laboratorv
Methods,
4th
Ed.,
1962,
Charles
C.
Thomas,
Springfield,
pp.
19­
23.

F
l
a
t
t
,
R.
and
Carpenter,
A.,
'Identification
of
Crystalline
Material
i
n
Urine
of
Rabbits."
American
Journal
of
veterinary
Research,
32:
655­
658,
April
1971.

Flynn,
Parasites
of
Laboratory
Animals,
The
Iowa
S
t
a
t
e
University
Press,
Ames,
1973,
pp.
256,
262.
­
216
­

241­
141
Appendix
10
­
Continued
*

References
Subacute
Inhalation
Study
of
PCl3
i
n
Rats
STAT
ISTI
CAL
METHODS
/LABORATORY
PROCEDURES
­

BOX,
G.
E.
P.,
"A
General
Distribution
Theory
f
o
r
a
Class
of
Likelihood
C
r
i
t
e
r
i
a
.
5
i
ometri
ka,
36
:
317­
346,
1949.

Dunnett,
C,
W.,
"A
Multiple
Comparison
Procedure
f
o
r
Comparing
Several
Treatments
w
i
t
h
a
Control."
J.
Am.
S
t
a
t
.
Assoc,,
50:
1096­
1121,
1955.

Dunnett,
C.
W.,
"New
Tables
f
o
r
Multiple
Comparisons
with
a
Control."
B
i
ometri
cs
,
20
:482
­491,
1964.

Winer,
5.
J.,
S
t
a
t
i
s
t
i
c
a
l
P
r
i
n
c
i
o
l
e
s
i
n
Exerpimental
Desiqn,
2nd
Ed.,
McGraw­
Hill,
N.
Y.,
Chs.
3­
9,
1971.

0001221
­
217
­

Appendix
71
Pathology
Addendum
Subacute
Inhalation
Study
of
Phosphorous
Trichloride
in
Rats
000222'
LABORATORIES
AMERICA,
INC.

9200
LEESBURG
TURNPIKE.
VIENNA,
VIRGINIA
22
180
U
S
A
247
­147
­
218
­

PATHOLOGY
ADDENDUM
Compound­
related
histomorphologic
alterations
were
not
present
in
the
sections
examined.
Focal
suppurative
inflamnation
as
a
spontaneous
disease
lesion
was
observed
in
the
anterior
portion
of
the
nasal
cavity
in
single
male
rats
of
Groups
2
and
3
and
in
a
Group
3
female
rat.
The
focal
inflamnation
in
the
two
male
rats
was
accompanied
by
squamous
metaplasia.
The
sections
of
nasal
turbinates
from
the
remaining
animals
were
considered
to
be
within,
normal
histologic
limits.

In
conclusion,
microscopic
evaluation
of
nasal
turbinate
sections
from
rats
exposed
to
PCL3
at
concentrations
of
0.5
and
3.0
ppm
failed
to
reveal
histomorphologic
alterations
attributed
to
compound
administration.
Focal
suppurative
inflamnation
noted
in
single
male
rats
of
Groups
2
and
3
and
in
a
Group
3
female
was
considered
to
be
a
spontaneous
disease
lesion
comparable
to
that
observed
in
a
control
male
rat
noted
on
the
initial
evaluation.
i
I
­
219
­
Standard
Key
t
o
lndividual
Histopathology
Findings
241­
141
SYMBOLS
APPEARING
OPPOSITE
'CODES"
SYMBOLS
PREFACING
NEOPLASTIC
FIffDINGS
H­
=
Histological
Comnent(
s)
B­
=
Primary,
Benign
Neoplasm
Present
f
o
r
t
h
i
s
Anima
1
H­
=
Primary,
Halignant
Neoplasm
N­
=
Metastatic
Neoplasm
I­
=
Locally
Invasive
Neoplasm
X­
=
O
t
h
e
r
Neoplasm
(See
Comment)

SYMBOLS
APPEARING
IN
THE
TABLE
MATRIX
.

Distribution
of
Findings
(n
=
severity
grade):

n
nM
nF
nD
Grades
f
o
r
1
=

2
=

3
=
+=
+n
=

+aa
=

u
=

­=
p
=

Pn
=
*=

A
=

R
=
H
=
PIN
=

HAN
=

SDS
=

000224
=
Not
Specified
=
Multifocal
=
Focal
=
Diffuse
Finding
Severity
or
Amount:

Minimal
4
=
Moderately
Severe
S
l
i
g
h
t
5
=
Severe
Moderate
Neoplastic
Findin­
g
Present
Multiple
Neoplasms
of
Same
Type
Present
(I
n
'
=
Number
Present)
Metastatic
o
r
Invasive
Neoplasm
from
Organ/
Tissue
Indicated
by
the
Abbreviation
'
a
a
'
,
(eg,
'
L
I
'
=
Liver)
Organ/
Tissue
Histologically
Unremarkable
(Tissues
w
i
t
h
dashes
present
f
o
r
a
l
l
f
i
n
d
i
n
g
s
also
histologically
unremarkable)
Finding
Not
Present
Finding
Present
Hultiple
Occurrences
o
f
Finding
Present
(I
n
1
=
Number
Present)
Tissue
Missing
Tissue
Autolytic
Tissue
Recut
Requested
Histological
Comment
Present.
f
o
r
t
h
i
s
Tissue
Permanent
Identi
f
i
cation
Number
Histology
Accession
Number
Sex/
Dose/
Screen
Non­
Protocol
Required
Tissue
Tissue
Not
i
n
Plane
of
Section
m
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0
a
a
n
a2
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ncn
nu
a
x
m
W
LLX
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el?.
2
0
3
O
Z
X
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au
e
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a
J
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an
t
mp:
0
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m
a
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c
z
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m
a
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c
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l=
l
111
h
h
­
P
w
N
9
u)
m
W
w
c
000231
MAZLEZON
LABORATORIES
AMERICA,
INC.

9200
LEESBURG
TURNPIKE.
VIENNA.
VlRGlNlA
2
2
1
80.
U.
S.
A.

RESEARCH
PROPOSAL
NO,
2881
SUBACUTE
INHALATION
TOXICITY
STUDY
OF
PHOSPHOROUS
TRI
CHLORIDE
(PCL3)
IN
RATS
MONSAKTO
COMPANY
ST.
LOUIS,
MISSOURI
I,
'
Study
11,
Purpose
­

111,
Test
Material
A,
­
Identification:

B,
Purity:

'
C.
Methods
of
Synthesis:

,
0.
Other:

IV.
Experimental
Design
A.
Animals:

1.
Species:

2.
Strain/
Source:

3.
Age
at
Initiation:

4.
Number/
Sex:

5.
Identification:
Subacute
Inhalation
Toxicity
Study
OF
PCL3
in
Rats
To
evaluate
the
subacute
toxicity
of
Phosphorous
Trichloride,
PCL3
following
exposure
by
the
inhalation
route.

PCL3
To
be
determined
by
the
sponsor,

Information
on
the
methods
of
synthesis,
stability,
as
well
as
data
on
composition
or
other
characteristics
which
define
the
test
material
are
on
file
with
the
sponsor.

This
study
may
be
submitted
to
a
U
S
.
regu­
latory
agency
and
will
be
conducted
accor­
ding
to
GLP
regulations,

Rat
Sprague­
Dawley
descended,
COBS/
Charl
es
River
Breeding
Laboratories,

6­
7
weeks
60
males
and
60
females
(Animals
selected
will
be
within
*
1.5
S.
D.
of
mean
weight
by
sex.
)

Individual
ear
tags
000232
'
IT
8
$%&&
k
C7031893­
5400.
TELEX
899436
CHAZLAES
WNAI.
CABLE
HAZLAES
W
A
S
H
DC
I
LAEOAATORIES
AMERICA,
INC.

9200
LEESSURG
TURNPIKE.
VIENNA.
VIRGlNlA,
227
60.
U.
S
A
­2
­

6.
Husbandry:

a.
Housing
b.
Food
c
.
Water
d.
Contaminants
e.
Environment
f.
Quarantine
7.
Randomization:

8.
Justification:
Individual
wire­
mesh
cages
when
in
and
when
out
of
the
chambers
Purina
Lab
Chow@
#5OO1,
ad
libitum
(except
during
exposuresr
Feed
will
have
been
analyzed
for
concentrations
of
speci­
fied
heavy
metals,
antibiotics,
aflatoxin,
pesticides,
and
nitrosamines
and
determined
to
contain
these
contaminants
at
or
below
accepted
levels.

Tap
water,
ad
libitum
(except
during
expo­
sures).
Thrwater
is
routinely
analyzed
on
a
retrospective
basis
for
specified
micro­
organisms,
pesticides,
heavy
metals,
alka­
linity,
and
halogens.

The
study
director
and/
or
the
sponsor
have
considered
possible
interfering
substances
potentially
present
in
animal
feed
and
water,
including
the
test
material
itself
or
possible
structurally
related
materials,
as
well
as
the
items
listed
in
"bit
and
"c"
above.
None
of
these
contaminants
are
reasonably
expected
to
be
present
in
animal
feed
or
water
at
levels
sufficient
to
inter­
fere
with
this
study.

Every
attempt
w
i
7
7
be
made
to
maintain
temperatures
a
t
700
2
4OF
with
a
rela­
tive
humidity
o
f
40­
60%.
A
12­
hour
light­
dark
cycle
will
be
maintained
by
an
auto­
matic
timer.
Exposures
will
be­
during
the
light
phase.
Cages
will
be
washed
weekly
and
chambers
cleaned
dai
ly.

Minimum
of
two
weeks.

Via
computerized
random
numbers
table.

Rats
have
historically
been
used
in
safety
evaluation
studies
designed
to
evaluate
possible
inhalation
effects.

000233
I
HAZLETON
LABORATORIES
AMERlC4
INC.

9200
LEESBURG
TURNPIKE.
VIENNA.
VIAGUWA
221
80.
US
A
­3
­

3.
Group
Designation
and
Exposure
Levels
Group
No.
No.
of
Animals
Concent
rations
Male
Female
PPm
­
1
(Air
Control)
15
15
2
(Low)
15
15
3
(Mid)
15
15
4
(High)
15
15
*
Exposure
levels
will
be
selected
following
consultation
based
on
the
LC50
and
corresponding
dose
response
curve
material.
with
the
sponsor,
for
the
test
C.
Exposure
Procedure:

1.
Exposure
Conditions:

Exposures
will
be
for
six
hours/
day,
f
i
v
e
days/
week,
f
o
r
four
weeks,
in
6­
m3
glass
and
stainless
steel
inhalation
chambers
operated
dynamically
at
an
airflow
o
f
'1000
liters
per
minute.
The
animals
will
be
individually
caged
without
food
and
water
in
stainless
steel
wire­
mesh
cages
f
o
r
whole
body
exposure.
The
animals'
position
in
the
chamber
will
be
systematically
rotated
f
o
l
­
lowing
daily
exposures.
The
chamber
will
be
exhausted
by
a
vacuum
pump
from
beneath
the
cages.
The
temperature
and
humidity
in
the
control
chamber
will
be
monitored
at
30­
rnin­
Ute
intervals;
targets
will
be
72
5
30F
and
30­
70%,
respectively.

2.
Compound
Generation:

Phosphorous
Trichloride,
PCL
wi
11
be
generated
as
a
vapor
by
bubb
7
ing
air
through,
or
sweeping
the
head
space
above
a
000234
I
LABORATORIES
AMERICA.
INC
9200
LEESBURG
TURNPIKE.
VIENNA.
VIRGINIA
22180.
US
A
­4
­

volume
of
the
fresh
test
compound,
replaced
daily,
in
a
glass
flask
followed
by
an
aerosol
trap,
prior
to
introduction
of
the
vapor
into
the
turret
top
of
the
inhalation
exposure
chamber.

3.
Exposure
Monitoring:

a.
Nominal
Concentration:

Nominal
concentrations
will
be
calculated
daily
by
dividing
the
total
weight
of
test
material
disseminated
into
the
exposure
chamber
atmosphere
by
the
total
volume
of
air
passed
through
the
chamber
during
generation.

b,
Analytical
Chamber
Concentration:
\
>?
;­
Tandem
Filter
(DM­
450)
or
Fibre
Glass
packed
.
­J
column
with
back­
up
Midget
lmpinger
samples
<
:
(using
0.0078M
NaOH
as
the
collection
b
Csolvent
and
eluent
for
filter
samples)
will
'
be
taken,
as
frequently
as
possible,
from
each
exposure
chamber
and
a
portion
of
the
sample
will
be
chemically
analyzed
for
total
inorganic
Phosphorus
and
Chloride.
The
remaining
portion
of
the
impinger
sample
will
be
forwarded
to
the
client
for
analysis.
In
addition,
once
daily,
three
(3).
hours
after
exposure
initiation,
a
chamber
sample
(using
either
an
evacuated
glass
flask
or
gas
tight
syringe)
will
be
taken
from
each
exposure
chamber
and
analyzed
by
Gas
Chromatography
f
o
r
potential
decomposition
products
of
the
test
material,
using
a
procedure
to
be
developed
at
HLA.
.­

c.
Particle
Size:
Once
weekly
during
exposures,
each
exposure
chamber
will'have
a
particle
size
determination
performed
using
an
Andersen
Mini­
Sampler
Cascade
impactor
with
back­
up
filter.
for
each
sample.
The
MMAD
and
ag
will
be
determined
000235
i­

I
.

HAZLEZON
LABORATORIES
AMERICA.
INC
9200
LEESSURG
TURNPIKE.
VIENNA,
VIRGINIA
221
€30.
U
5
A
­5
­

D.
Observation
of
Animals:

1,
Clinical
Observations:

Each
animal
will
be
observed
twice
daily
(pre­
and
post­
exposure)
for
mortality
or
moribundity,
Detailed
examinations
for
signs
of
interexposure
toxicity
will
be
conducted
each
week
at
weighing.

2,
Body
Weights
Body
weights
will
be
recorded
prior
to
exposure,
weekly
thereafter
and
on
the
morning
of
the
last
exposure
day.

3,
Ophthalmoscopic
Examination
Eye
examinations
will
be
conducted
on
all
animals
on
test
prior
to
study
initiation
and
at
termination.
Lids,
lacrimal
apparatus,
conjunctiva
will
be
examined
grossly;
cornea,
anterior
chamber,
lens,
vitreous
humor,
retina
and
optic
disc
wi7J
be
examined
by
indirect
ophthalmoscopy;
MydriacylQ
will
be
administered
to
induce
mydriasis,
A71
animals
examined
prior
to
initiation
o
f
exposure
which
are
considered
to
be
unsuitable
for
tbe
study
will
be
rep
1
aced
4,
Clinical
Pathology
(at
termination,
10
.

a,
Hemat
o
1
ogy
pre­
selected
anirnals/
sex/
group):

RBC,
WBC,
and
differential
leukocyte
counts;
hemoglobin
concentration
and
hematocrit,

b,
Clinical
Chemistry
'

Ca,
Na,
K,
P,
C1,
Mg,
SGOT,
SGPT,
alkaline
phosphatase,
total
bilirubin,
BUN,
albumin,
total
protein',
LDH
and
A/
G
ratio.

c
,
Urinalysis
Overnight
fasted
urine
samples
from
each
rat,
taken
just
prior
to
sacrifice,
will
be
analyzed
for:
appearance,
specific
gravity,
pH,
protein,
glucose,
ketones,
occult
blood,

.
*
I
":
F%
­k
+j
a,
Q00236
1
I
.

HAZLRCSN
LABORATORIES
AMERICA.
1NC
9200
LEESBUnG
TURNPIKE.
VIENNA.
VIRGINIA
22
180.
U.
S
A
­6
­

'
.
,:.
'f
E.
and
volume
with
microscopic
examination
o
f
sediment.
Urine
samples
will
be
frozen
and
saved
for
subsequent
shipment
to
sponsor
following
analysis.
These
samples
can
only
be
held
for
8
weeks
following
study
completion,

Termination:

I
.
Animals
That
Succumb:

Necropsies,
by
appropriately
trained
person­
nel
and
under
procedures
supervised
by
board­
certified
pathologists,
will
be
conducted
on
all
moribund
animals
and
on
all
animals
that
die.

2,
Sacrifice:
After
four
weeks
o
f
treatment,
all
surviving
animals
will
be
weighed
after
overnight
fast,
anesthetized,
and
exsanguinated.
Necropsies
will
be
conducted
on
each
animal
by
appropriately
trained
personnel
and
under
procedures
supervjsed
by
board­
certified
patho7
ogi
s
t
s
.

F.
Postmortem
Procedures:

1,
Gross
necropsy:
The
necropsy
will
include
examination
of:

­
The
external
surface
­
All
orifices
­
Cranial
cavity
­
Carcass
­
External
and
cut
surface
of
the
brain
and
­
The
thoracic,
abdominal
and
pelvic
cavities
­
The
cervical
tissues
and
organs
spinal
cord
and
their
viscera
Findings
will
be
recorded.
(trimmed
to
ipclude
a
consistent
length
of
trachea
to
permit
subsequent
perfusion),
liver,
kidneys,
brain,
heart
(excluding
major
vessels),
adrenals,
spleen
and
testes
will
be
weighed
and
organ/
tenninal
body
weight
and
organ/
brain
weight
ratios
will
be
calculated.
The
lungs
000237
I
MAZETON
LAEOR#
TORIES
AMERiC4
INC
9200
LEESSURG
TURNPIKE.
VIENNA.
VIRGINIA
22180,
U.
SA
­7
­

2.
Tissue
Preservation:

The
following
tissues
(when
present)
from
each
animal
will
be
preserved
in
10%
neutral
buffered
formalin
for
possible
future
histo­
pathological
examination
except
for
eyes
and
testes
which
will
.be
preserved
in
Bouin's
sol
ut
ion:

brain
(fore­,
mid,
hind)
p
it
u
i
t
ary
thoracic
spinal
cord
nasal
turbinates
eyes
(both)
sal
i
vary
g
1
ands
(mand
i
bu
1
ar)
stomach
trachea
thymus
esophagus
.heart
spleen
adrenal
s
pancreas
unusual
lesions
skin
mammary
gland
(females)
duodenum,
jejunum,
ileum
colon,
cecum
mesenteric
lymph
node
urinary
bladder
testes
with
epididymides
prost
ate
ovaries
uterus
femur
bone
marrow
(sternum)
lungs
(two
sections,
all
lobes)
seminal
vesicles
liver
(two
lobes)
kidneys
thyroid
(with
parathyroid)
skeletal
muscle
peripheral
nerve
>­
r;
;
3..

3,
Histopathologic
Examination:

Microscopic
examination
will
be
performed
on
all
tissues
listed
above
in
F.
2,
obtained
from
10
animals/
sex
in
Groups
1
and
4,
Addition­
ally,
microscopic
examination
will
be
perfor­
med
on
all
those
animals
that
die
or
are
sacrificed
moribund
prior
to
the
end
of
the
study,
as
well
as
on
a17
tissues
manifesting
gross
pathological
changes
in
the
control
and
high
dose
groups.
If
significant
differences
are
noted
in
the
tissues
of
the
high­
dose
animals,
corresponding
organs/
tissues
of
the
other
groups
will
be
examined,
at
extra
cost,
upon
approval
of
the
sponsor,

000238
,
..
..
­`
I
,.
..

HAZLRON
LABORATORIES
AMERICA,
INC
9200
LEESEURG
TURNPIKE.
VIENNA.
VIRGINIA
22180.
U.
5.
A
­8
­

V.
Final
Report
At
termination
of
the
study,
a
final
report
which
includes
the
following
information
will
be
submitted:

­
Experimental
Design
and
Methods
­
Results:

.
mortality
.
clinical
observations
(appearance,

.
hemato
1
ogy
clinical
Chemistry
.
urinalysis
body
weight
changes
.
organ
weight,
organ/
terminal
.body
weight,
organ/
brain
weight
ratios
.
gross
pathology
.
histopathology
behavior,
and
signs
of
toxic
and
pharmaco
log
ic
effect
)
I
.

­
Statistical
Evaluation:
By
analysis
o
f
variance
techniques,
inc
1
ud
ing
mu1
t
iple
comparisons
between
groups
as
appropri
ate)

.
body
weight
changes
hematology
means
­
clinical
chemistry
means
.
organ/
terminal
body
weight
and
organ/
brain
weight
ratios
­
Figure:
Body
Weight
Curves
­
Tables:

.
chamber
concentrations
.
mean
body
weight
changes
­
hematology
mean
data
(historical
control
.
c'ljnical
chemistry
mean
data
(historical
.
urinalysis
mean
data
.
incidences
of
gross
pathology
findings
.
histopathology
incidence
table
organ/
teminal
body
weights
and.
organ/
brain
weight
ratios
values
will
be
included)

control
values
will
be
included)

000239
I
HAZETON
LABORATORIES
AMERICA
INC
Sa00
LEESBURG
TURNPIKE.
VIENNA.
VIRGINIA
221
80.
U.
S
A
­9
­

­
Appendices:

.
individual
body
weights
'

.
individual
organ
weights
.
individual
hematology
findings
.
individual
clinical
chemistry
findings
.I
individual
histopathology
findings
PROTOCOL
APPROVAL:

000240
I
74
78
2
­e
­
_­
­a
DEPARTMENT
C
'JEDICINE
&
ENVIRONMENfAL
HEALTI;
SAMPLE
SUBMIss/
ON
STUDYNO.
h
L
­%z
­l
?.q
Monsanto
.
1
PLEASE
TYPE
OR
P
R
I
N
T
7719­
12­
2
~

1.
SAMPLE
IDENTIFICATION
PRODUCT
NAME(
S)
CHEMICAL
NAME
SAMPLE
SIZE
4
x
8
0
2
f'3osphorus
Trichlor
fde
I
Phosphorus
Trichloride
CP
NO.
CHEM.
ABSTRACTS
REG.
NO.
LOT
OR
I.
D.
NO.,
NOTE
BOOK
REF.

0
HOLD,
NOTIFY
PURITY
SAMPLE
DISPOSITION
0
DISCARD
RETURN
8EFO
RE
OISCAR
DI
NG
9s..
7
EMPl
RlCAL
FORMULA
:=­
I
I
.
CHEMICAL
AND
PHYSICAL
PROPERTIES
STRUCTURAL
FORMULA
(COMPOSITION
OF
MIXTURE)

MOLECULAR
WEIGHT
COLORPtiYSICAL
STATE
137.33
Colorless
liquid
c1
­
P
­
Cl
CI
t
­
SUBMlTTED
BY:
"'
(NaT
?~
ti??!.&%%%
3%
ne
Ext.
2120
.
G.
?bsuaarfcfi
"Plant
2/
17/
83
DMEH
CONTACT:
(Name.
Location.
Phone
NO..
Date)
­,
­,
.

A
2
.
f(­
J&<
&1i.
JQ.
L"
Tcmc,
n­
2­

~
I
.
.
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I
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I
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(2COC)
­­
SOLUBILITY:
WATER
I
ORGANIC
SOLVENTS
(SPECIFY)
I
OTHER
,
I
­
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.
"r
a
c
t
s
violently
I
Vapor
Density
4
.
­
PH
.
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HAZARDS
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FLAMMABLE
­0
EXPLOSIVE
0
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UNSTABLE
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LIGHT
0
UNSTABLE
TO
HEAT
UNSTABLE
TO
WATER
POLYMERIZES
READILY
0
HYGROSCOPIC
0
OTHER
(SPECIFY)

0
REACTS
WITH
NO
SPECIAL
PRECAUTIONS
­
­.
OTHER
PROPERTIES.
SPECIAL
REQUIREMENTS
(SPECIFY)
2
1:
the
presence
of
misture,
reacts
to
form
H,
PO,
an&
XCI
­­
I
l
l
.
TOXICITY
INFORMATION
­
NO
INFORMATION
AVAILABLE
8
ciaw,
k
­
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­
ORAL
LDSO
DERMAL
LD50
&'&
f
COG
­
SdT'G
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f
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ATTACHMENT
r­
,
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­OTHER
(SPECIFY)
EYEIRRITATION
(
U
G
b4&

SKIN
IRRITATION
SINGLE
VAPOR
INHALATION
­*
I
%
,
,­­

9
­
­.

'
A
Rr
:>..
!
\If
Phosphorus
trichloride
Fax­
On­
Demand:
Telephone:
(202)
401­
0527
Item
XXXX
PROPOSED1
:
05/
2002
PROPOSED
I:
05/
2002
United
States
Environmental
Protection
Agency
Office
of
Pollution
Prevention
and
Toxics
PHOSPHORUS
TRICHLORIDE
(CAS
Reg.
No.
007719­
12­
2)

PROPOSED
ACUTE
EXPOSUFtE
GUIDELINE
LEVELS
(AEGLs)

"PUBLIC
DRAFT"

Federal
Register
­
May
2002
000242
PROPOSED
1:
05/
2002
PHOSPHORUS
TRICHLORIDE
(CAS
Reg.
No.
007719­
12­
2)

PROPOSED
ACUTE
EXPOSURE
GUIDELINE
LEVELS
(AEGLs)

Oak
Ridge
National
Laboratory,
managed
by
UT­
Battelle,
LLC,
for
the
U.
S.
Dept.
of
Energy
under
contract
DE­
AC05­
000R22725.

000243
PHOSPHORUS
TRICHLORIDE
PREFACE
PROPOSED
1:
05/
2002
Under
the
authority
of
the
Federal
Advisory
Committee
Act
(FACA)
P.
L.
92­
463
of
1972,
the
National
Advisory
Committee
for
Acute
Exposure
Guideline
Levels
for
Hazardous
Substances
(NAC/
AEGL
Committee)
has
been
established
to
identifl,
review
and
interpret
relevant
toxicologic
and
other
scientific
data
and
develop
AEGLs
for
high
priority,
acutely
toxic
chemicals.

AEGLs
represent
threshold
exposure
limits
for
the
general
public
and
are
applicable
to
emergency
exposure
periods
ranging
from
10
minutes
to
8
hours.
AEGL­
2
and
AEGL­
3
levels,
and
AEGL­
1
levels
as
appropriate,
will
be
developed
for
each
of
five
exposure
periods
(10
and
30
minutes,
1
hour,
4
hours,
and
8
hours)
and
will
be
distinguished
by
varying
degrees
of
severity
of
toxic
effects.
It
is
believed
that
the
recommended
exposure
levels
are
applicable
to
the
general
population
including
infants
and
children,
and
other
individuals
who
may
be
sensitive
and
susceptible.
The
three
AEGLs
have
been
defined
as
follows:

AEGL­
1
is
the
airborne
concentration
(expressed
as
ppm
or
mg/
m3)
of
a
substance
above
which
it
is
predicted
that
the
general
population,
including
susceptible
individuals,
could
experience
notable
discomfort,
irritation,
or
certain
asymptomatic,
non­
sensory
effects.
However,
the
effects
are
not
disabling
and
are
transient
and
reversible
upon
cessation
of
exposure.

AEGL­
2
is
the
airborne
concentration
(expressed
as
ppm
or
mg/
m3)
of
a
substance
above
which
it
is
predicted
that
the
general
population,
including
susceptible
individuals,
could
experience
irreversible
or
other
serious,
long­
lasting
adverse
health
effects,
or
an
impaired
ability
to
escape.

AEGL­
3
is
the
airborne
concentration
(expressed
as
ppm
or
mg/
m3)
of
a
substance
above
which
it
is
predicted
that
the
general
population,
including
susceptible
individuals,
could
experience
life­
threatening
health
effects
or
death.

Airborne
concentrations
below
the
AEGL­
1
represent
exposure
levels
that
can
produce
mild
and
progressively
increasing
but
transient
and
nondisabling
odor,
taste,
and
sensory
irritation
or
certain
asymptomatic,
nonsensory
effects.
With
increasing
airborne
concentrations
above
each
AEGL,
there
is
a
progressive
increase
in
the
likelihood
of
occurrence
and
the
severity
of
effects
described
for
each
corresponding
AEGL.
Although
the
AEGL
values
represent
threshold
levels
for
the
general
public,
including
sensitive
subpopulations,
such
as
infants,
children,
the
elderly,
persons
with
asthma,
and
those
with
other
illnesses,
it
is
recognized
that
certain
individuals,
subject
to
unique
or
idiosyncratic
responses,
could
experience
the
effects
described
at
concentrations
below
the
corresponding
AEGL.

iii
PHOSPHORUS
TRICHLORIDE
TABLE
OF
CONTENTS
PROPOSED
1:
05/
2002
PREFACE
.........................................................................
iii
LISTOFAPPENDICES
..............................................................
v
LISTOFTABLES
...................................................................
v
EXECUTIVESUMMARY
............................................................
vi
1
.
INTRODUCTION
...........................................................
1
HUMANTOXICITYDATA
....................................................
2
2.1
AcuteLethali
ty
.........................................................
2
2.2
Nonlethal
Toxicity
......................................................
2
2.3
Epidemiologic
Studies
...................................................
4
2.4
Developmental/
Reproductive
Toxicity
......................................
4
2.6
Carcinogenicity
........................................................
4
2.4
Genotoxici
ty
...........................................................
4
2.7
Summary
.............................................................
4
3
.
ANIMALTOXICITYDATA
....................................................
4
3.1
AcuteLethali
ty
.........................................................
4
3.1.1
Rats
...........................................................
4
3.1.2
Guineapigs
.....................................................
5
3.1.3
Cats
...........................................................
5
3.2
Nonlethal
Toxicity
......................................................
5
3.2.1
Rats
............................................................
5
3.2.2
Guineapigs
.....................................................
6
3.2.3
Cats
...........................................................
6
3.3
DevelopmentalReproductive
Toxicity
......................................
6
3.4
Genotoxici
ty
...........................................................
6
3.5
Carcinogenicity
........................................................
6
3.6
Summary
.............................................................
7
4
.
SPECIALCONSIDERATIONS
..................................................
7
4.1
Metabolism
and
Disposition
..............................................
7
4.2
Mechanism
of
Toxicity
..................................................
7
4.3
Structure­
Activity
Relationships
...........................................
8
4.4
Other
Relevant
Information
...............................................
8
4.4.1
Species
Variability
...............................................
8
Concurrent
Exposure
Issues
........................................
8
4.4.2
iv
000245
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
092002
5
.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
1
.....................................
8
5.2
8
5.3
Derivation
of
AEGL­
1
...................................................
8
5.1
Summary
of
Human
Data
Relevant
to
AEGL­
1
...............................
8
Summary
of
Animal
Data
Relevant
to
AEGL­
1
...............................

6
.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
2
.....................................
9
6.1
Summary
of
Human
Data
Relevant
to
AEGL­
2
...............................
9
6.2
Summary
of
Animal
Data
Relevant
to
AEGL­
2
...............................
9
6.3
Derivation
of
AEGL­
2
..................................................
10
7
.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
3
....................................
11
7.1
Summary
of
Human
Data
Relevant
to
AEGL­
3
..............................
11
7.2
Summary
of
Animal
Data
Relevant
to
AEGL­
3
..............................
11
7.3
Derivation
of
AEGL­
3
..................................................
11
8
.
SUMMARY
OF
PROPOSED
AEGLS
...........................................
12
8.1
AEGL
Values
and
Toxicity
Endpoints
.....................................
12
8.2
Comparison
with
Other
Standards
and
Criteria
...............................
13
8.3
Data
Adequacy
and
Research
Needs
.......................................
15
9
.
REFERENCESCITED
........................................................
16
APPENDIX
A
(Derivation
of
AEGL
Values)
.............................................
18
APPENDIX
B
(Derivation
Summaries
for
Phosphorus
Trichloride
AEGL
Values)
...............
24
LIST
OF
TABLES
TABLE
1
.
TABLE
2
.
TABLE
3
.
Physical
and
Chemical
Data
for
Phosphorus
Trichloride
........................
Acute
Lethality
of
Phosphorus
Trichloride
in
Laboratory
Species
.................
AEGL­
1
for
Phosphorus
Trichloride
........................................
9
TABLE
4
.
AEGL­
2
for
Phosphorus
Trichloride
.......................................
10
TABLE
5
.
AEGL­
3
for
Phosphorus
Trichloride
.......................................
12
TABLE
6
.
Extant
Standards
and
Guidelines
for
Phosphorus
Trichloride
...................
13
1
7
V
000246
PHOSPHORUS
TRICHLORIDE
EXECUTIVE
SUMMARY
PROPOSED
1:
0512002
Phosphorus
trichloride
(CAS
no.
007719­
12­
2)
is
a
colorless,
clear
fuming
liquid
with
a
pungent,
irritating
odor.
In
the
presence
of
water,
the
chemical
decomposes
rapidly
in
a
highly
exothermic
reaction
to
phosphonic
acid,
hydrogen
chloride,
and
pyrophosphonic
acids.

No
acute
lethality
data
are
available
in
humans.
Qualitative
data
regarding
human
exposures
indicate
signs
and
symptoms
of
exposure
consistent
with
a
highly
irritating
chemical;
ocular
and
dermal
irritation,
respiratory
tract
irritation,
shortness
of
breath,
and
nausea.

Lethality
data
in
animals
are
available
for
rats,
cats,
and
guinea
pigs.
Cursory
studies
conducted
nearly
one
hundred
years
ago
in
Germany
provided
preliminary
data
on
lethal
and
nonlethal
effects
in
cats
and
guinea
pigs
following
various
treatment
regimens
with
inhaled
phosphorus
trichloride.
Although
results
of
the
studies
indicated
the
respiratory
tract
to
a
be
a
critical
target,
the
methods
and
results
of
these
studies
were
not
verifiable.
Weeks
et
al.
(1964)
reported
4­
hr
LC,,
values
of
104.5
ppm
and
50.1
ppm
for
rats
and
guinea
pigs,
respectively.
An
unpublished
study
by
Hazleton
Laboratories
(1983)
identified
a
NOAEL
of
3.4
ppm
and
a
LOAEL
(histopathologic
changes
in
the
respiratory
tract)
of
1
1
ppm
following
repeated
exposure
(6
hrs/
day,
5
daydweek
for
four
weeks)
of
rats.
There
are
no
data
regarding
reproductive/
developmental
toxicity,
genotoxicity
,
or
carcinogenicity
of
phosphorus
trichloride.
Definitive
data
regarding
the
mechanism
of
action
of
phosphorus
trichloride
are
unavailable.
Decomposition
products
(hydrogen
chloride,
phosphonic
acid,
and
pyrophosphonic
acids)
are
responsible,
at
least
in
part,
for
the
contact
irritation
reported
by
humans,
and
the
irritation
and
tissue
damage
observed
in
animal
species.

The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
C"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5.
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
andn
=
1
when
extrapolating
to
longer
time
points
using
the
C"
x
t
=
k
equation.
For
10­
minute
AEGL­
3
values
were
set
at
equivalence
to
the
30­
minute
values
due
to
uncertainties
in
extrapolating
from
the
experimental
exposure
durations
of
4
hours
and
greater.

Quantitative
data
consistent
with
AEGL
1
effects
were
unavailable.
Occupational
exposures
of
humans
to
1.8­
3.6
ppm
for
2­
6
hours
and
exposure
of
rats
to
3.4
ppm
for
6
hourdday,
5
daydweek
for
4
weeks
were
without
notable
effect.
These
data
can
be
considered
a
NOAEL
for
AEGL­
1
effects.
Because
they
were
derived
from
controlled
experiments,
the
AEGL­
1
values
were
based
upon
the
Hazleton
Laboratories
(1983)
report.
These
data
as
well
as
the
AEGL­
1
values
are
supported
by
the
human
experience
data
reported
by
Sassi
(1952).
The
interspecies
uncertainty
factor
was
limited
to
3
because
of
the
concordance
of
the
animal
data
with
the
human
experience
and
because
the
most
sensitive
species
tested
(guinea
pig)
was
only
about
2­
fold
more
sensitive.
The
intraspecies
uncertainty
factor
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
Additional
reduction
of
the
AEGL­
1
values
would
be
inconsistent
with
available
human
and
animal
data
.

Information
consistent
with
AEGL­
2
effects
were
limited
to
an
occupational
exposure
report
and
a
multiple
exposure
study
with
rats.
For
occupational
exposures,
there
was
notable
irritation
following
2­
6
vi
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
30­
min
hours
of
exposure
to
approximately
14­
27
ppm
phosphorus
trichloride
and
more
severe
but
reversible
irritation
following
exposures
of
1­
8
weeks.
Reports
providing
qualitative
information
but
no
exposure
terms
affirmed
the
potential
for
respiratory
tract
irritation
following
acute
exposures
to
phosphorus
trichloride.
Data
for
rats
showed
upper
respiratory
tract
involvement
following
multiple
exposures
over
4
weeks
to
11
ppm
but
not
to
3.4
ppm
(Hazleton
Laboratories,
1983).
For
development
of
AEGL­
2
values,
the
1
1
ppm
exposure
in
rats
was
considered
a
NOAEL
for
AEGL­
2
effects.
Uncertainty
factor
application
was
the
same
as
for
the
AEGL­
1
tier.

1­
hour
AEGL­
3
values
were
developed
based
upon
a
3­
fold
reduction
of
the
4­
hr
LC,,
(Weeks
et
al.,
1964)
as
an
estimate
of
the
lethality
threshold
(50.1
ppm/
3
=
16.7
ppm).
A
total
uncertainty
factor
adjustment
of
10
was
used
to
develop
the
AEGL­
3
values.
Animal
data
indicated
some
variability
in
the
toxic
response
to
phosphorus
trichloride
with
guinea
pigs
being
the
more
sensitive
among
the
species
tested.
Therefore,
uncertainty
adjustment
regarding
interspecies
variability
was
limited
to
3.
To
account
for
intraspecies
variability,
a
factor
of
3
was
applied.
The
uncertainty
of
intraspecies
variability
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
The
total
uncertainty
factor
of
10
may
be
justified
by
human
exposure
data
showing
that
repeated
2
to
6­
hour
exposures
of
up
to
27
ppm
were
without
life­
threatening
consequences.
Furthermore,
the
results
of
the
Hazleton
Laboratories
(1
983)
study
showed
no
fatalities
in
rats
following
multiple
6­
hour
exposures
to
11
ppm.
The
AEGL
values
for
phosphorus
trichloride
are
presented
in
the
table
below.

4­
hour
Classification
AEGL­
1
(Nondisabling)

AEGL­
2
(Disabling)

AEGL­
3
(Lethal)

a
Based
upon
anir
References
8­
hour
PROPOS
10­
min
0.78
ppm
2.5
ppm
0.78
ppm
0.62
ppm
2.0
ppm
2.5
ppm
7.0
ppm
0.39
ppm
1
data,
letha
0.26
ppm
1.3
ppm
0.83
ppm
7.0
ppm
5.6
ppm
ty
may
be
delayed.
3.5
ppm
1.8
ppm
1RIDE
EndDoint
(Reference)

~~~~

NOAEL
of
3.4
ppm
in
rats
exposed
6
hrdday,
5
daystweek
for
4
weeks
(Hazleton
Laboratories,
1983)

NOAEL
for
AEGL­
2
tier
effects;
based
upon
respiratory
tract
histopathology
in
rats
exposed
6
hrs/
day,
5
daystweek
for
4
weeks
(Hazleton
Laboratories,
1983)

Estimated
lethality
threshold
based
upon
3­
fold
reduction
of
guinea
pig
4­
hr
LCso
(50.1
ppd3
=
16.7
ppm)
(Weeks
et
al..
1964Y
Hazleton
Laboratories.
1983.
Subacute
inhalation
toxicity
study
in
rats
­
phosphorus
trichloride.
Final
Report.
Project
No.
241­
141.
Hmleton
Laboratories
America,
Inc.
Unpublished.

Weeks,
M.
H.,
Mussleman,
N.
P.,
Yevich,
P.
P.,
Jacobson,
K.
H.,
Oberst,
F.
W.
1964.
Acute
vapor
toxicity
of
phosphorus
oxychloride,
phosphorus
trichloride
andmethyl
phosphonic
dichloride.
Arner.
Ind.
Hyg.
J.
25:
470­
475.

vii
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
1.
INTRODUCTION
Phosphorus
trichloride
(CAS
No.
007719­
12­
2)
is
a
colorless,
clear,
fuming
liquid
with
a
pungent,
irritating
odor
(Fee
et
al.,
1996).
Odor
threshold
information
is
unavailable
for
this
chemical.
The
primary
use
of
phosphorus
trichloride
is
for
the
production
of
phosphonic
acid
which,
in
turn,
is
used
in
the
production
of
the
herbicide,
glyophosphate.
Phosphorus
trichloride
decomposes
rapidly
in
water
in
highly
exothermic
reactions.
It
may
also
decompose
in
moist
air
to
hydrochloric
acid
and
hydrated
phosphoric
acid.
The
reaction
products
include
phosphonic
acid,
hydrogen
chloride,
pyrophosphonic
acids,
depending
on
the
mole
ratio
of
water
and
phosphorus
trichloride
(Fee
et
al.,
1996).
If
the
mole
ratio
of
water
and
phosphorus
trichloride
is
greater
than
three,
the
following
reaction
will
occur.

PCl,
+
3
H,
O
­+
H,
PO,
+3
HCl
If
the
mole
ratio
is
2.5
to
3,
reaction
products
will
be
a
mixture
of
phosphonic
acid
and
pyrophosphonic
acids.

0
0
0
II
II
II
3PCl,
+
SH,
O
­+
9HCl
+HPOPH
+"
OH
I
I
I
HO
OH
OH
TABLE
1.
PHYSICAL
AND
CHEMICAL
DATA
FOR
PHOSPHORUS
TRICHLORIDE
I
I
Fee
et
al.,
1996;
NIOSH,

I
1994;
RTECS.
1998
Synonyms
Phosphorus
chloride,
trichlorophosphine
CAS
Registry
No.
007719­
12­
2
Budavari
et
a1.,
1989
I
I
Chemical
formula
PC13
Budavari
et
al.,
1989
Molecular
weight
137.33
Budavari
et
al.,
1989
Physical
state
liquid
Budavari
et
a1.,
1989
Vapor
pressure
100mmHg@
21"
C
ACGIH,
1991
Density
1.574
Budavari
et
al.,
1989
Boiling/
melting
point
76"
C/­
112"
C
Budavari
et
a1.,
1989
I
I
Solubility
decomposes
in
water
and
alcohol
Fee
et
al.,
1996
Conversion
factors
in
1
ppm
=
5.6
mg/
m3
Beliles
and
Beliles,
1993
1
00024
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2.
HUMAN
TOXICITY
DATA
2.1
Acute
Lethality
No
acute
lethality
exposure­
response
data
or
case
reports
are
currently
available.

2.2
Nonlethal
Toxicity
Sassi
(1952)
summarized
twenty
cases
of
acute
(2­
6
hours)
or
"subacute"
(1­
8
weeks
of
work)
exposures
of
workers
to
phosphorus
trichloride.
The
concentration
of
phosphorus
trichloride
in
the
workrooms
ranged
from
10­
20
mg/
m3
(­
1.8­
3.6
ppm)
under
normal
conditions
to
80­
150
mg/
m3
(­
14­
27
ppm)
during
periods
when
the
plant
was
"out
of
order".
The
method
by
which
the
concentrations
were
determined
was
not
stated
in
the
translated
abstract.
For
the
acute
exposures,
workers
experienced
a
burning
sensation
in
the
eyes
and
throat,
photophobia,
chest
tightness,
dry
cough,
and
slight
bronchitis
which
occurred
within
2­
6
hours
of
exposure.
For
the
"subacute"
exposures,
pharyngeal
irritation,
coughing,
catarrh,
dyspnea,
and
asthmatic
bronchitis
occur
at
1­
8
weeks
of
exposure.
Slight
increases
in
body
temperature
and
moderate
leucocytosis
with
neutrophilia
were
also
reported
for
both
exposures.
Signs
and
symptoms
reportedly
resolved
in
three
to
six
days
for
the
acute
exposures
and
10­
15
days
for
the
subacute
exposures.

exposed
to
phosphorus
trichloride
released
in
a
railroad
accident
in
1980.
The
report
indicated
that
the
phosphorus
trichloride
reacted
with
water
used
to
disperse
the
spillage
and
with
air
moisture
that
resulted
in
the
release
of
phosphoric
and
hydrochloric
acids
and
phosphorus
oxides.
No
information
was
provided
regarding
weather
conditions
(e.
g.,
wind,
temperature,
humidity)
at
the
time
of
the
accident.
Signs
and
symptoms
were
characteristic
of
exposure
to
irritants
and
included
burning
eyes
(86%),
shortness
of
breath
(59%),
throat
irritation
(59%),
lacrimation
(59%),
headache
(48%),
nausea
(48%),
burning
sensation
on
the
skin
(44%),
and
sputum
production
(41%).
Additional
effects
occurring
in
33%
or
less
of
the
patients
included
chest
pains,
wheezing,
skin
rash,
blurred
vision,
vomiting,
and
abdominal
pain.
Lactate
dehydrogenase
was
mildly
elevated
and
serum
bilirubin
and/
or
serum
transaminases
were
elevated
in
three
individuals.
Results
of
pulmonary
function
tests
showed
greater
severity
of
effect
with
decreasing
distance
from
the
release
site.
At
two
months,
86%
of
the
individuals
who
were
within
1/
16
mile
were
hypoxemic
while
only
50%
of
those
1/
16
to
1/
8
mile
distance
were
hypoxemic.
There
were
no
exposure
durations
provided
(probably
>
1.5
hours
as
described
below)
and
no
exposure
concentrations
were
measured
or
estimated.
Wason
et
al.
(1984)
reported
in
more
detail
on
the
railroad
accident
involving
spillage
of
phosphorus
trichloride.
The
report
focused
on
seventeen
individuals
(16
men
and
one
woman,
ages
21­
59
years),
seven
of
whom
were
requested
to
return
for
follow­
up
study
after
the
initial
medical
examination.
Signs
and
symptoms
of
exposure
included
eye,
skin
and
throat
irritation,
nausea,
vomiting,
blurred
vision,
headache,
and
various
effects
associated
with
respiration
and
ventilation
(e.
g.,
wheezing,
cough,
chest
pain,
dyspnea,
sputum
production).
Chest
X­
rays
of
all
subjects
were
normal
and
there
was
no
evidence
of
hepatic
toxicity.
Spirometry
tests
revealed
that
the
subjects
(10
of
17)
who
were
closest
(within
110
yards)
to
the
accident
site
had
a
significant
decrease
in
vital
capacity,
maximal
breathing
capacity,
FEV,,
and
maximal
ventilatory
flow
rate
at
25%
of
vital
capacity.
An
improvement
in
the
ventilatory
changes
was
seen
one
month
later.
Subjects
closer
to
the
release
site
appeared
to
exhibit
signs
and
symptoms
of
greater
severity.
It
was
also
found
that
patients
that
were
exposed
for
less
than
one
and
a
half
hours
had
An
abstract
by
Wason
et
al.
(1982)
provided
information
on
an
assessment
of
27
individuals
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significantly
(p=
0.02)
greater
maximal
expiratory
flow
rates
at
25%
of
vital
capacity
than
did
those
individuals
exposed
for
longer
periods.
Water
was
used
to
disperse
the
spilled
phosphorus
trichloride
and,
as
noted
in
the
report,
the
actual
exposure
most
likely
involved
phosphonic
acid
and
hydrochloric
acid
more
so
than
phosphorus
trichloride.
Eight
subjects
were
exposed
for
less
than
one
and
a
half.
hours
and
nine
were
exposed
longer
(duration
not
specified).
Pulmonary
function
tests
in
the
seven
follow­
up
patients
one
month
after
the
accident
revealed
significant
improvements
in
vital
capacity,
FEVI,
peak
expiratory
flow
rate,
and
maximal
expiratory
flow
rate
at
50%
vital
capacity.
Although
this
report
provides
information
regarding
the
nonlethal
effects
in
humans
following
exposure
to
phosphorus
trichloride,
there
were
no
data
on
the
exposure
concentrations
and
it
is
uncertain
as
to
the
precise
chemicals
(i.
e.,
phosphorus
trichloride
and/
or
its
degradation
products)
to
which
the
people
were
exposed.
A
NIOSH
health
hazard
evaluation
of
workers
at
the
FMC
plant
in
Nitro,
West
Virginia
revealed
that
those
with
known
repeated
exposures
to
phosphorus
oxychloride
and/
or
phosphorus
trichloride
experienced
a
significantly
higher
(p<
O.
OO
1)
prevalence
(65%)
of
occasional
respiratory
symptoms
(chest
tightness,
wheezing,
difficulty
breathing)
compared
to
unexposed
workers
(5%)
(Tharr
and
Singal,
1980).
However,
no
correlation
was
found
between
results
of
pulmonary
function
tests
on
the
workers
and
exposure
to
these
chemicals.
The
study
utilized
37
exposed
workers
and
22
unexposed
workers.
Most
air
samples
were
below
detection
limits
although
one
employee
(with
respiratory
protection
of
a
chlorine
gas
mask)
was
exposed
to
6
mg
phosphorus
trichloride/
m3
(1
ppm)
for
one
hour
during
a
truck­
loading
operation
(no
effects
were
reported
for
this
individual).
A
follow­
up
study
conducted
by
NIOSH
on
26
of
the
exposed
workers
and
1
1
of
the
unexposed
workers
from
the
aforementioned
FMC
Corp.
group
revealed
that
half
of
the
exposed
workers
reported
significantly
(p<
0.002)
more
episodes
of
respiratory
effects
(wheezing,
breathlessness,
and
chest
tightness)
compared
to
the
unexposed
workers
who
reported
no
such
effects
(Moody,
198
1).
Results
of
pulmonary
function
tests
did
not
reveal
significant
findings
regarding
effects
of
phosphorus
trichloride
(or
phosphorus
oxychloride)
exposure.
No
significant
difference
in
pulmonary
function
(FEV,)
was
found
in
the
exposed
workers
vs
the
unexposed
workers
over
a
two­
year
period.
The
small
sample
size,
however,
reduces
the
power
of
the
study
to
detect
such
changes
and,
therefore,
compromises
the
apparent
negative
finding.
Although
lacking
exposure
terms,
there
is
information
regarding
accidental
releases
of
phosphorus
trichloride
in
Illinois
(pers.
comm.).
Two
significant
releases
of
phosphorus
trichloride
occurred
in
1988
from
a
chemical
plant
in
Sauget,
Illinois.
The
first,
on
April
17,
resulted
from
overfilling
a
railroad
tanker,
with
an
estimated
6,000­
12,000
pounds
released
in
the
railroad
yard.
The
plume
caused
the
evacuation
of
approximately
22
square
blocks,
and
4
17
citizens
of
neighboring
Rush
City
and
East
St.
Louis,
Illinois
reported
to
area
hospitals
for
treatment.
Two
of
these
citizens
were
admitted
overnight
and
subsequently
released.
Eye
and
respiratory
irritation
were
the
main
symptoms
reported.
The
second
incident
resulted
from
failure
of
a
rupture
disk
during
start­
up
procedures
at
the
plant
on
July
3
I.
It
was
calculated
that
no
more
than
50
pounds
of
phosphorus
trichloride
were
released
from
the
plant,
and
the
plant's
security
and
industrial
hygiene
personnel
were
able
to
visually
track
and
bound
the
plume
that
moved
into
Rush
City.
Their
reports
indicated
that
the
plume
traveled
approximately
two
miles
before
dissipating.
This
plume
caused
244
citizens
to
report
to
area
hospitals
for
treatment.
Eight
of
these
citizens
were
admitted;
seven
were
kept
overnight
and
released,
while
the
eighth
was
kept
for
three
days
before
release.
This
patient's
history
of
asthma
contributed
to
the
severity
of
effects,
and
the
asthma
was
also
aggravated
by
the
exposure
to
the
phosphorus
trichloride.
The
main
complaints
of
the
citizens
were
eye,
nose,
and
throat
irritation.
No
measurements
of
airborne
concentrations
were
made
during
either
incident.

3
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2.3
Epidemiologic
Studies
No
epidemiologic
studies
of
phosphorus
trichloride
toxicity
are
currently
available.

2.4
DevelopmentaVReproductive
Toxicity
Data
regarding
the
reproductive/
developmental
toxicity
of
phosphorus
trichloride
in
humans
are
not
available.

2.5
Genotoxicity
No
human
genotoxicity
data
for
phosphorus
trichloride
are
currently
available.

2.6
Carcinogenicity
Information
regarding
the
potential
carcinogenicity
of
phosphorus
trichloride
in
humans
is
not
available.

2.7
Summary
There
are
no
data
regarding
lethal
exposures
of
humans
to
phosphorus
trichloride
but
some
information
on
nonlethal
exposures
is
available.
Workers
exposed
to
phosphorus
trichloride
following
a
railroad
car
spill
exhibited
signs
and
symptoms
consistent
with
exposure
to
a
highly
irritating
chemical.
Although
the
reports
of
this
accident
describe
qualitatively
the
effects
of
exposure,
there
are
no
quantitative
exposure­
response
terms.
Pulmonary
function
deficits
(e.
g.,
vital
capacity,
FEV,,
peak
expiratory
flow
rate,
maximal
expiratory
flow
rate
at
50%
vital
capacity)
that
correlated
with
distance
from
the.
release
showed
improvement
at
one
month
following
the
exposure.
The
effects
reported
could
be
attributed
to
phosphorus
trichloride
decomposition
products
(phosphonic
acid
and
hydrogen
chloride)
as
well
as
the
parent
compound.
In
an
occupational
exposure
setting,
workers
experienced
a
burning
sensation
in
the
eyes
and
throat,
photophobia,
chest
tightness,
dry
cough,
and
slight
bronchitis
following
2­
6
hours
of
exposure
to
approximately
14­
27
ppm
phosphorus
trichloride.
Exposure
of
workers
to
these
levels
for
1­
8
weeks
resulted
in
pharyngeal
irritation,
coughing,
catarrh,
dyspnea,
and
asthmatic
bronchitis.
Increases
in
body
temperature
and
moderate
leucocytosis
with
neutrophilia
were
also
reported
for
both
exposure
durations,
but
all
signs
and
symptoms
resolved
upon
removal
from
the
exposure.

3.
ANIMAL
TOXICITY
DATA
3.1
Acute
Lethality
3.1.1
Rats
Weeks
et
al.
(1964)
reported
on
the
acute
lethality
of
phosphorus
trichloride
in
female
rats
exposed
for
four
hours
to
an
atmosphere
of
phosphorus
trichloride
generated
by
passing
nitrogen
gas
through
the
liquid
test
material.
Chemical
analysis
was
used
to
determine
the
amount
of
the
test
material
in
the
exposure
chamber.
The
rats
were
observed
for
14
days
after
removal
from
exposure.
The
rats
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were
restless
and
exhibited
labored
breathing
during
the
exposure.
During
the
exposure,
the
eyes
were
closed
and
there
was
considerable
porphyrin
secretion
around
the
eyes.
Deaths
occurred
over
a
period
of
ten
days
indicating,
under
the
conditions
of
this
experiment,
a
notable
latency
period
in
the
lethal
response.
The
nostrils
and
paws
of
the
exposed
rats
exhibited
swelling,
edema,
discoloration
and
subsequent
sloughing
of
tissues
that
was
consistent
with
the
activity
of
a
corrosive
agent.
Microscopic
examination
revealed
necrosis
of
epithelium
and
supporting
structures
in
the
nostrils
but
pulmonary
damage
was
considered
to
be
negligible.
The
investigators
noted
that
the
primary
site
of
damage
appeared
to
be
the
kidneys
and
was
characterized
by
nephrosis
of
tubules
in
the
cortico­
medullary
region.
A
4­
hr
LCso
of
104.3
ppm
was
calculated
and
reported
by
the
investigators.
The
exposure
concentrations
tested
to
obtain
this
value
were
not
reported
and,
therefore,
there
was
no
information
regarding
the
exposure­
response
relationship.

3.1.2
Guinea
pigs
Weeks
et
al.
(1
964)
also
examined
the
lethal
response
of
guinea
pigs
exposed
for
four
hours
to
phosphorus
trichloride.
The
experimental
protocol
was
as
described
for
the
experiments
with
rats
(Section
3.1.1).
Based
upon
the
published
report,
the
response
of
guinea
pigs
was
similar
to
that
of
rats;
restlessness,
signs
of
ocular
and
nasopharyngeal
irritation,
and
renal
damage.
With
the
exception
of
the
4­
hr
LC,,
of
50.1
ppm,
no
additional
exposure­
response
data
were
provided.

pigs
exposed
to
623
ppm
phosphorus
trichloride
died
shortly
after
3
hours
of
exposure.
Results
of
early
inhalation
exposure
experiments
reported
by
Butjagin
(1904)
showed
that
guinea
3.1.3
Cats
Butjagin
(1904)
reported
that
test
animals
(guinea
pigs
and
cats)
died
shortly
after
3­
hour
exposure
to
623
ppm.
In
another
experiment,
one
cat
exposed
to
694
ppm
died
after
306
minutes.

3.2
Nonlethal
Toxicity
3.2.1
Rats
Although
the
Weeks
et
al.
(1964)
study
reported
on
lethality
in
rats
exposed
to
phosphorus
trichloride,
no
information
was
provided
regarding
nonlethal
effects.

In
an
unpublished
study
conducted
for
the
Monsanto
Company
(Hazleton
Laboratories,
1983),
groups
of
15
Sprague­
Dawley
rats
(1
5/
sex/
group)
were
exposed
to
phosphorus
trichloride
vapor/
aerosol
for
6
hourdday,
5
daydweek
for
four
weeks.
Over
the
four­
week
period,
nominal
exposure
concentrations
were
0.5,3.0,
or
10.0
ppm
and
analytical
concentrations
were
0.49,3.37,
and
10.96
ppm.
The
test
atmosphere
was
generated
by
passing
air
(200­
990
cc/
minute
depending
upon
the
test
concentration
group)
over
the
headspace
above
a
non­
specified
volume
of
phosphorus
trichloride
in
a
flask.
The
vapor
was
then
carried
to
the
test
chambers
via
Teflon@
tubing.
Sample
concentrations
were
determined
three
times
per
day
by
collecting
chamber
samples
in
impingers
containing
20
mL
of
sodium
hydroxide.
The
samples
were
subsequently
analyzed
in
a
chloride
meter
and
expressed
as
ppm
phosphorus
trichloride.
Over
the
4­
week
exposure
period,
concentration
excursions
deviated
from
target
values
by
­2.0,
+12.3,
and
+9.6%
for
the
low,
medium,
and
high­
dose
groups,
respectively.
A
control
group
was
exposed
to
filtered
air
under
the
same
conditions.
No
rat
died
during
the
exposure
period
and
5
000253
PHOSPHORUS
TRICHLORIDE
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1
2
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
3'
no
treatment­
related
adverse
effects
were
observed.
All
rats
were
sacrificed
and
necropsied
on
day
29.
Histological
alterations
in
the
maxillo­
and
nasoturbinates
and
in
the
lateral
wall
of
the
nasal
cavity
were
observed
in
seven
male
and
four
females
of
the
high­
dose
group;
the
remaining
high­
dose
rats
exhibited
no
remarkable
findings
in
the
nasal
cavities
and
turbinates.
Squamous
metaplasia
of
the
respiratory
epithelium
was
also
present
in
six
males
and
four
females
of
the
high­
dose
group.
There
were
no
treatment­
related
effects
on
hematologic
or
biochemical
parameters,
and
no
ophthalmologic
effects
or
body
weighuorgan
weight
changes
were
observed.
Under
the
conditions
of
this
study,
3.4
ppm
was
considered
a
No­
Observed­
Adverse
Effect
Level
(NOAEL)
in
rats.

3.2.2
Guinea
Pigs
In
experiments
reported
by
Butjagin
(1904),
guinea
pigs
were
exposed
to
phosphorus
trichloride
at
various
concentrations
for
different
durations
(1
­
6
hours).
Only
minor
effects
(restlessness,
salivary
and
nasal
secretions,
coughing,
irregular
respiration)
were
observed
following
6­
hour
exposure
to
0.7
1
ppm
or
1­
hour
exposure
to
1.78
to
5.36
ppm.
In
the
report
summary,
it
was
also
noted
that
exposures
of
50­
90
ppm
for
one
hour
produced
severe
signs
of
toxicity.
The
phosphorus
trichloride
concentrations
were
determined
by
measurement
of
chlorine.
It
appears
that
only
1
to
3
animals
were
used
for
any
given
exposure
and,
for
some
experiments,
the
same
animals
were
used.

3.2.3
Cats
Butjagin
(1904)
also
conducted
experiments
with
adult
cats
(2.1­
4.0
kg)
exposed
to
phosphorus
trichloride
as
previously
described
for
guinea
pigs.
The
results
were
similar
to
those
reported
for
the
guinea
pigs;
6­
hour
exposure
to
0.71
ppm
or
1­
hour
exposure
to
1.78
to
5.36
ppm
produced
signs
of
restlessness
and
nasopharyngeal
irritation.
Six­
hour
exposures
to
concentrations
of
135
to
303
ppm
rapidly
produced
signs
of
severe
irritation
(salivary,
nasal,
and
ocular
secretions,
breathing
through
the
mouth,
irregular
and
severely
labored
respiration).
Histological
examination
at
six
to
seven
days
after
exposure
revealed
severely
damaged
nasal
septum
and
bronchioles,
and
pulmonary
edema.
Inasmuch
as
these
animals
were
terminated
for
necropsy,
it
is
likely
(based
upon
the
findings)
that
they
may
not
have
survived.
In
summary,
the
study
author
reported
that
one­
hour
exposure
to
50­
90
gpm
resulted
in
severe
signs
of
toxicity.
It
appears
that
for
at
least
some
of
the
experiments,
the
same
cats
were
used.

3.3
DeveloprnentaVReproductive
Toxicity
No
data
are
available
regarding
the
developmentalheproductive
toxicity
of
phosphorus
trichloride
in
animals.

3.4
Genotoxicity
No
data
are
currently
available
regarding
the
genotoxicity
of
phosphorus
trichloride.

3.5
Carcinogenicity
No
data
are
available
regarding
the
carcinogenic
potential
of
phosphorus
trichloride
in
animals.

6
PHOSPHORUS
TRICHLORIDE
Species
Lethality
Value
Reference
I
Rat
4­
hr
LC,,
:
104.3
ppm
Weeks
et
al.,
1964
Cat
lethality
at
306
min,
694
ppm
Butjagin,
1904
Cat
lethality
at
3
hours,
623
ppm
Butjagin,
1904
Guinea
pig
4­
hr
LCso
:
50.1
ppm
Weeks
et
a1.,
1964
Guinea
pig
lethality
at
3
hours,
623
ppm
Butjagin,
1904
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2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
3.6
Summary
of
Toxicity
Data
In
Animals
Definitive
quantitative
exposure­
response
toxicity
data
in
animals
were
limited.
Median
lethal
exposure
concentrations
for
rats
and
guinea
pigs
are
available
and
shown
in
Table
2.
A
report
by
Weeks
et
al.
(1964)
provided
an
adequate
description
of
experimental
protocol
and
4­
hr
LC50
value
for
rats
(4­
hr
LC5,=
1o4.3
ppm)
and
guinea
pigs
(4­
hr
LCs0=
50.1
ppm).
Additional
data
obtained
from
limited
numbers
of
cats
and
guinea
pigs
exposed
to
various
concentrations
of
phosphorus
trichloride
for
varying
durations
described
both
lethal
and
nonlethal
responses
(Butjagin,
1904).
An
unpublished
study
by
Hazleton
Laboratories
(1983)
showed
that
multiple
6­
hourlday
exposures
of
male
and
female
rats
to
phosphorus
trichloride
at
11
ppm
over
four
weeks
produced
only
histologic
changes
in
the
nasal
turbinates
while
exposure
to
3.4
ppm
failed
to
produce
any
notable
effects.
The
available
information
affirms
that
exposure
to
vapors
of
phosphorus
trichloride
may
produce
dermal,
ocular,
and
nasopharyngeal
irritation
as
well
as
pulmonary
and
renal
damage.
Additionally,
based
upon
limited
data
in
rats,
cats
and
guinea
pigs,
there
appears
to
be
latency
period
in
the
lethal
response
to
phosphorus
trichloride.

I
TABLE
2.
ACUTE
LETHALITY
OF
PHOSPHORUS
TRICHLORIDE
IN
LABORATORY
SPECIES
I
4.
SPECIAL
CONSIDERATIONS
4.1
Metabolism
and
Disposition
Data
on
the
metabolism
and
disposition
of
phosphorus
trichloride
are
not
currently
available.

4.2
Mechanism
of
Toxicity
The
mechanism
of
toxicity
of
phosphorus
trichloride
is
currently
unknown.
The
lethal
toxicity
of
phosphorus
trichloride
does
not,
however,
appear
to
be
explained
solely
by
the
activity
of
the
irritant
degradation
products
(hydrogen
chloride
and
phosphonic
acid).
The
rapid
exothermic
reaction
in
the
presence
of
water
may
contribute
to
localized
tissue
damage
and
also
explain,
in
part,
the
greater
toxicity
of
phosphorus
trichloride
relative
to
hydrogen
chloride
and
phosphonic
acid.

000255
7
PHOSPHORUS
TRICHLORIDE
PROPOSED
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2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
4.3
Structure­
Activity
Relationships
Barbee
et
al.
(1995)
conducted
an
acute
toxicity
study
of
oxalyl
chloride
(COCl),
in
which
groups
of
10
rats
were
exposed
for
one
hour
to
0,462,866,1232,1694,
or
2233
ppm.
The
1­
hr
LC,,
was
found
to
be
1840
ppm.

oxychloride
following
acute
inhalation
exposures
(Weeks
et
al.,
1964;
ACGIH,
199
1)
and
also
undergoes
rapid
hydrolysis
to
phosphonic
acid
and
hydrogen
chloride.
Phosphorus
trichloride
produces
many
of
the
same
signs
and
symptoms
as
does
phosphorus
4.4
Other
Relevant
Information
4.4.1
Species
Variability
Data
are
insufficient
to
reliably
describe
species
variability
in
the
toxic
response
to
inhaled
phosphorus
trichloride.

4.4.2
Concurrent
Exposure
Issues
No
concurrent
exposure
issues
of
special
concern
have
been
identified
that
could
be
directly
incorporated
in
the
development
of
AEGL
values
for
phosphorus
trichloride.

5.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
1
5.1
Summary
of
Human
Data
Relevant
to
AEGEl
Quantitative
human
data
consistent
with
AEGL
1
effects
were
not
available.
Information
regarding
human
exposures
to
phosphorus
trichloride
indicate
acute
exposures
result
in
dermal
and
ocular
irritation,
irritation
of
the
respiratory
tract,
headache,
nausea,
and
shortness
of
breath.

5.2
Summary
of
Animal
Data
Relevant
to
AEGL­
1
The
only
animal
data
available
that
were
consistent
with
AEGL­
1
severity
effects
were
those
provided
in
the
report
by
Butjagin
(1904).
In
this
study,
cats
and
guinea
pigs
exposed
to
phosphorus
trichloride
concentrations
of
0.71
to
1.78
ppm
for
up
to
six
hours
exhibited
restlessness,
salivary
and
nasal
secretions,
coughing,
and
irregular
respiration.
Hazleton
Laboratories
(1
983)
reported
a
NOAEL
of
3.4
ppm
for
rats
following
multiple
6­
hr/
day
exposures.
This
was
bounded
by
a
NOEL
of
0.5
ppm
and
LOAEL
(1
1
ppm).

5.3
Derivation
of
AEGEl
Data
consistent
with
AEGL­
1
effects
come
from
an
older
study
in
cats
and
guinea
pigs
(Butjagin,
1904).
There
are
no
odor
threshold
data
and
no
quantitative
data
in
humans.
Because
of
the
uncertainties
regarding
exposure
atmosphere
measurements
from
a
study
conducted
almost
100
years
ago
and
the
fact
that
individual
test
animals
may
have
been
exposed
to
multiple
exposure
regimens,
the
data
from
Butjagin
(1
904)
were
not
used
in
the
development
of
AEGL­
1
values.
Data
from
the
Hazleton
Laboratories
study
suggested
that
an
exposure
above
0.5
ppm
may
be
consistent
with
AEGL­
1
effects
as
8
0002s.
G
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
AEGL
Level
AEGL­
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
0­
min
30­
min
1
­hr
4­
hr
8­
hr
0.78
ppm
0.78
ppm
0.62
ppm
0.39
ppm
0.26
ppm
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
multiple
6­
hour
exposures
to
this
concentration
over
a
four­
week
period
were
without
effect.
The
Hazleton
Laboratories
study
identified
3.4
ppm
as
a
NOAEL
for
rats
receiving
multiple
6­
hour
exposures
over
a
period
of
4
weeks.
Sassi
(1952)
reported
that
occupational
exposures
of
1.8
to
3.6
ppm
for
2
to
6
hours
were
without
notable
effect.
In
lieu
of
additional
data.
the
experimentally
determined
NOAEL
3.4
ppm
was
considered
a
NOAEL
for
development
of
AEGL­
1
values.
Data
for
humans
and
animals
indicate
some
variability
in
the
toxic
response
to
phosphorus
trichloride.
However,
upon
comparison
to
human
data
(albeit
limited),
rodents
appear
to
be
somewhat
more
sensitive
to
the
respiratory
effects
of
phosphorus
trichloride.
Therefore,
uncertainty
adjustment
regarding
interspecies
variability
was
limited
to
3.
To
account
for
intraspecies
variability,
a
factor
of
3
was
applied.
The
uncertainty
of
intraspecies
variability
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
The
attenuated
uncertainty
factors
may
be
justified
by
the
limited
human
exposure
data
(Sassi,
1952)
suggesting
that
humans
could
experience
2
to
6­
hour
exposures
of
up
to
3.6
ppm
with
no
apparent
effect
and
the
fact
that
AEGL­
1
development
is
based
upon
an
exposure
that
was
without
a
discernible
effect.
The
AEGL­
1
values
for
phosphorus
trichloride
are
shown
in
Table
3
and
their
derivations
shown
in
Appendix
A.

TABLE
3.
AEGL­
1
VALUES
FOR
PHOSPHORUS
TRICHLORIDE
6.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
2
6.1
Summary
of
Human
Data
Relevant
to
AEGL­
2
Quantitative
exposure­
response
data
in
humans
are
not
available
for
development
of
AEGL­
2
values
for
phosphorus
trichloride.
Information
regarding
the
human
experience
is
limited
to
qualitative
notations
regarding
signs
and
symptoms
(ocular,
dermal,
and
respiratory
tract
irritation,
and
ventilatory
effects).
The
information
in
these
reports
suggest
that
acute
exposure
to
phosphorus
trichloride
could
cause
irritation
severe
enough
to
impair
egress
from
a
contaminated
area.
Sassi
(1
953)
reported
that
workers
experienced
a
burning
sensation
in
the
eyes
and
throat,
photophobia,
chest
tightness,
dry
cough,
and
slight
bronchitis
following
2­
6
hours
of
exposure
to
approximately
14­
27
ppm
phosphorus
trichloride.
Although
these
effects
could
possibly
impair
escape,
thereby
by
qualifying
as
being
consistent
with
AEGL­
2
tier
effects,
the
method(
s)
by
which
the
exposure
concentrations
were
determined
was
not
reported.
Exposure
concentrations
were
not
provided
in
other
reports
(with
the
exception
of
the
anecdotal
data
by
Tharr
and
Singal,
1980)
and
information
on
exposure
duration
was
limited.

6.2
Summary
of
Animal
Data
Relevant
to
AEGL­
2
Quantitative
data
in
animals
regarding
effect
severity
consistent
with
AEGL­
2
were
limited
to
data
on
guinea
pigs
and
cats
reported
by
Butjagin
(1904).
The
robustness
of
these
data
are,
however,

9
000257
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
0572002
AEGL
Level
AEGL­
2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
1
0­
min
30­
min
1­
hr
4­
hr
8­
hr
2.5
ppm
2
5
ppm
2.0
ppm
1.3
ppm
0.83
ppm
limited
due
to
the
small
numbers
of
animals
in
each
experiment
(Le.,
1
­
3)
and
the
fact
that
some
of
the
animals
were
apparently
used
in
more
than
one
experiment.
This
becomes
a
significant
concern
considering
the
additive
nature
of
irritationhissue
damage
and
the
possible
latency
in
activity
for
some
adverse
effects
of
phosphorus
trichloride
(e.
g.,
pulmonary
damage
and
renal
toxicity).
Consistent
with
human
acute
exposure
reports,
the
predominant
response
by
animals
is
characterized
by
ocular,
nasopharyngeal,
and
pulmonary
irritation
and
subsequent
tissue
damage.
Animal
data
are
not
sufficient
to
provide
a
meaningful
exposure­
response
relationship.
The
responses
of
cats
and
guinea
pigs
in
the
Butjagin
study
were
reportedly
more
severe
at
higher
concentrations
and
occurred
more
quickly.
In
the
Butjagin
(1904)
report,
cats
and
guinea
pigs
exposed
to
5.36
ppm
for
one
hour
exhibited
restlessness,
signs
of
nasopharyngeal
irritation,
and
irregular
respiration.
A
6­
hour
exposure
of
cats
to
concentrations
of
135
to
303
ppm
resulted
in
signs
of
severe
irritation
and
respiratory
distress.
Histological
examination
of
the
cats
exposed
to
135
to
303
ppm
revealed
perforated
nasal
septa,
bronchial
damage,
and
pulmonary
edema.
Additionally,
Weeks
et
al.
(1964)
noted
renal
damage
in
rats
exposed
to
lethal
concentrations
of
phosphorus
trichloride.
However,
exposure­
response
data
were
not
provided
regarding
this
effect.
The
Hazleton
Laboratories
study
(1983)
in
rats
showed
that
multiple
6­
hour
exposures
to
1
1
ppm
over
a
four­
week
period
produced
histologic
alterations
in
the
nasal
turbinates
but
no
effects
on
ophthalmologic
hematologic
or
biochemical
parameters,
and
no
overt
signs
of
toxicity.
Because
the
nasal
lesions
were
the
result
of
multiple
exposures
(5
daydweek)
over
four
weeks
and
not
of
a
severity
consistent
with
the
AEGL­
2
tier,
a
threshold
for
AEGL­
2
effects
in
rats
is
likely
at
an
undetermined
concentration
above
11
ppm
for
a
single
six­
hour
exposure.

6.3
Derivation
of
AEGL­
2
Data
upon
which
to
base
AEGL­
2
development
are
limited.
Sassi
(1953)
reported
on
occupational
exposures
of
2­
6
hour
durations
to
concentrations
of
14­
27
ppm
that
produced
effects
that
could
be
considered
only
marginally
consistent
with
AEGL­
2.
As
previously
noted,
the
animal
data
reported
by
Butjagin
(1904)
are
deficient
for
the
purpose
of
AEGL
development.
Although
the
results
from
the
Hazleton
Laboratories
(1
983)
study
in
rats
exposed
to
for
6
hours/
day,
5
daydweek
for
four
weeks
did
not
define
a
response
consistent
with
AEGL­
2
severity,
the
11
ppm
exposure
that
resulted
in
histopathologic
alterations
in
the
respiratory
tract
may
be
considered
a
NOAEL
for
AEGL­
2
severity
effects.
Uncertainty
factor
application
and
time
scaling
were
as
described
for
AEGL­
1.
Data
from
available
reports
suggest
that
humans
are
not
especially
sensitive
to
the
effects
of
phosphorus
trichloride
when
compared
to
laboratory
animals.
As
such
further
reduction
of
AEGL
values
by
the
application
of
greater
uncertainty
factors
dose
not
appear
warranted.
The
AEGL­
2
values
for
phosphorus
trichloride
are
shown
in
Table
4
and
their
derivation
outlined
in
Appendix
A.

36
I
I
­~~

TABLE
4.
AEGL­
2
VALUES
FOR
PHOSPHORUS
TRICHLORIDE
II
37
3s
39
40
10
00025&
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
OY2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
7.
DATA
ANALYSIS
AND
PROPOSED
AEGL­
3
7.1
Summary
of
Human
Data
Relevant
to
AEGL­
3
Quantitative
data
are
not
available
regarding
lethality
in
humans
exposed
to
phosphorus
trichloride.

7.2
Summary
of
Animal
Data
Relevant
to
AEGL­
3
Weeks
et
al.
(1964)
provided
4­
hr
LC,,
values
of
104.3
ppm
and
50.1
ppm,
respectively,
for
rats
and
guinea
pigs.
In
early
experiments
by
Butjagin
(1904),
guinea
pigs
and
cats
exposed
to
623
ppm
phosphorus
trichloride
died
within
three
hours,
and
a
cat
exposed
to
694
ppm
died
after
306
minutes
of
exposure.
In
the
absence
of
any
additional
quantitative
data,
the
median
lethality
values
derived
by
Weeks
et
al.
may
be
considered
as
a
basis
for
AEGL­
3
development
and
also
serve
to
a
limited
extent
as
an
index
of
species
variability.
Because
the
exposure­
response
data
used
to
derive
the
median
lethality
values
were
not
provided,
it
is
not
possible
to
determine
the
exposure­
response
relationship.

7.3
Derivation
of
AEGL­
3
Because
the
median
lethality
values
provided
by
Weeks
et
al.
(1964)
represent
the
only
quantitatively
determined
estimates
regarding
the
lethal
response
to
acute
inhalation
of
phosphorus
trichloride,
they
may
be
considered
as
the
basis
for
AEGL3
development.
The
4­
hr
LCso
values
for
rats
(104.3
ppm)
and
guinea
pigs
(50.1
ppm)
suggest
a
species
variability.
In
the
absence
of
exposure­
response
data,
the
lethality
threshold
was
estimated
as
a
3­
fold
reduction
of
the
rat
4­
hr
LC50
(104.3
ppmI3
=
34.8
ppm).

be
described
by
c"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5.
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
C"
x
t
=
k
equation.
Because
of
the
uncertainty
in
extrapolating
from
a
4­
hour
exposure
to
a
10­
minute
exposure,
the
latter
was
set
equal
to
the
30­
minute
AEGL­
3.
A
total
uncertainty
factor
adjustment
of
10
was
used
to
develop
the
AEGL­
3
values.
Data
for
humans
and
animals
indicate
some
variability
in
the
toxic
response
to
phosphorus
trichloride
with
guinea
pigs
being
the
more
sensitive
(­
2­
fold)
among
the
laboratory
animals.
Limited
data
regarding
human
exposures
showed
that
2
to
6­
hour
exposures
to
14­
27
ppm
were
not
life­
threatening
(Sassi,
1952).
Therefore,
uncertainty
adjustment
regarding
interspecies
variability
was
limited
to
3.
To
account
for
intraspecies
variability,
a
factor
of
3
was
applied.
The
uncertainty
of
intraspecies
variability
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
The
attenuated
uncertainty
factors
may
be
further
justified
by
limited
human
exposure
data
(Sassi,
1952)
suggesting
that
humans
could
experience
repeated
exposures
of
up
to
27
ppm
without
life­
threatening
consequences.
The
resulting
AEGL­
3
values
are
presented
in
Table
5
and
their
derivation
is
shown
in
Appendix
A.
Because
the
lethal
response
in
guinea
pigs
and
rats
was
delayed
up
to
10
days,
note
of
possible
delayed
response
has
been
made
regarding
AEGL­
3
values.
The
concentration­
time
relationship
for
many
irritant
and
systemically
acting
vapors
and
gases
may
11
000253
PHOSPHORUS
TRICHLORIDE
AEGL
Level
AEGL­
3"
PROPOSED
1:
05/
2002
1
0­
min
30­
min
1­
hr
4­
hr
8­
hr
7
PPm
3.3
ppm
2.7
ppm
1.7
ppm
0.84
ppm
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
8.
SUMMARY
OF
PROPOSED
AEGLS
8.1
AEGL
Values
and
Toxicity
Endpoints
The
AEGL­
1
values
are
based
upon
a
NOAEL
an
laboratory
study
in
which
rats
received
multiple
exposures
over
a
period
of
four
weeks.
Although
a
conservative
assumption,
the
use
of
a
NOAEL
in
the
development
of
the
AEGL­
1
values
may
be
justified
by
the
relative
paucity
of
definitive
exposure­
response
data.
and
the
fact
that
limited
information
regarding
the
human
experience
indicates
that
2
to
6­
hour
exposures
to
1.8­
3.6
ppm
was
without
effect.
The
AEGL­
2
values
were
based
on
histopathologic
alterations
detected
in
the
respiratory
tract
of
rats
following
multiple
exposures
over
four
weeks.
The
effects
on
the
respiratory
tract
were
consistent
with
mode
of
action
of
phosphorus
trichloride
and,
therefore,
were
considered
a
NOAEL
for
the
AEGL­
2
tier
effect
level
(Le.,
the
effects
were
neither
disabling
nor
irreversible).
Information
regarding
the
human
experience
suggests
that
2
to
6­
hour
exposures
to
1.8­
3.6
ppm
were
without
effect
and
that
exposure
to
14­
27
ppm
resulted
in
irritation
of
the
eyes
and
upper
respiratory
tract,
photophobia,
chest
tightness,
and
bronchitis.
Therefore,
further
reduction
of
the
AEGL­
2
values
does
not
appear
to
be
warranted.
The
AEGL­
3
values
were
developed
based
upon
lethality
data
in
laboratory
species.
The
AEGL­
3
values
were
developed
based
upon
a
4­
hr
LCs0
value
for
rats
provided
in
a
study
by
Weeks
et
al.,
1964.
Data
pertaining
to
the
human
experience
also
indicate
respiratory
involvement
as
a
critical
effect.

12
000260
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
8.2
Comparison
with
Other
Standards
and
Criteria
Existing
standards
and
criteria
for
phosphorus
trichloride
are
presented
in
Table
6.

TABLE
6.
Extant
Standards
and
Guidelines
for
Phosphorus
Trichloride
Guideline
rR:
Not
recommended.
Numeric
values
for
AEGL­
1
and
AEGL­
2
are
not
recommended
due
to
the
lack
of
availab
data.
Absence
of
these
values
does
not
imply
that
exposure
below
the
AEGL­
3
is
without
adverse
effects.

13
000252.
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
a
ERPG
(Emergency
Response
Planning
Guidelines,
American
Industrial
Hygiene
Association)
(AIHA
,
1994)
The
ERPG­
1
is
the
maximum
airborne
concentration
below
which
it
is
believed
nearly
all
individuals
could
be
exposed
for
up
to
one
hour
without
experiencing
other
than
mild,
transient
adverse
health
effects
or
without
perceiving
a
clearly
defined
objectionable
odor.
The
ERPG­
2
is
the
maximum
airborne
concentration
below
which
it
is
believed
nearly
all
individuals
could
be
exposed
for
up
to
one
hour
without
experiencing
or
developing
irreversible
or
other
serious
health
effects
or
symptoms
that
could
impair
an
individual's
ability
to
take
protective
action.
The
ERPG­
3
is
the
maximum
airborne
concentration
below
which
it
is
believed
nearly
all
individuals
could
be
exposed
for
up
to
one
hour
without
experiencing
or
developing
life­
threatening
health
effects.
As
of
2001,
phosphorus
trichloride
values
are
categorized
as
under
Ballot,
Review,
and
Consideration.

EEGL
(Emergency
Exposure
Guidance
Levels,
National
Research
Council)
(NRC,
1985)
is
the
concentration
of
contaminants
that
can
cause
discomfort
or
other
evidence
of
irritation
or
intoxication
in
or
around
the
workplace,
but
avoids
death,
other
severe
acute
effects
and
long­
term
or
chronic
injury.

OSHA
PEL­
TWA
(Occupational
Health
and
Safety
Administration,
Permissible
Exposure
Limits
­
Time
Weighted
Average)
(OSHA,
1993)
is
defined
analogous
to
the
ACGM­
TLV­
TWA,
but
is
for
exposures
of
no
more
than
10
hourdday,
40
hourdweek.

OSHA
PEL­
STEL
(Permissible
Exposure
Limits
­
Short
Term
Exposure
Limit)
(OSHA,
1993)
is
defined
analogous
to
the
ACGIH­
TLV­
STEL.

e
IDLH
(Immediately
Dangerous
to
Life
and
Health,
National
Institute
of
Occupational
Safety
and
Health)
(NIOSH,
1996)
represents
the
maximum
concentration
from
which
one
could
escape
within
30
minutes
without
any
escape­
impairing
symptoms,
or
any
irreversible
health
effects.

NIOSH
REL­
TWA
(National
Institute
of
Occupational
Safety
and
Health,
Recommended
Exposure
Limits
­
Time
Weighted
Average)
(NIOSH,
1999)
is
defined
analogous
to
the
ACGIH­
TLV­
TWA.

NIOSH
REL­
STEL
(Recommended
Exposure
Limits
­
Short
Term
Exposure
Limit)
(NIOSH,
1999)
is
defined
analogous
to
the
ACGIH­
TLV­
STEL.

ACGIH
TLV­
TWA
(American
Conference
of
Governmental
Industrial
Hygienists,
Threshold
Limit
,

Value
­
Time
Weighted
Average)
(ACGIH,
1997)
is
the
time­
weighted
average
concentration
for
a
normal
8­
hour
workday
and
a
40­
hour
work
week,
to
which
nearly
all
workers
may
be
repeatedly
exposed,
day
after
day,
without
adverse
effect.

ACGIH
TLV­
STEL
(Threshold
Limit
Value
­
Short
Term
Exposure
Limit)
(ACGIH,
1997)
is
defined
as
a
15­
minute
TWA
exposure
which
should
not
be
exceeded
at
any
time
during
the
workday
even
if
the
8­
hour
TWA
is
within
the
TLV­
TWA.
Exposures
above
the
TLV­
TWA
up
to
the
STEL
should
not
be
longer
than
15
minutes
and
should
not
occur
more
than
4
times
per
day.
There
should
be
at
least
60
minutes
between
successive
exposures
in
this
range.

j
MAK
(Maximale
Arbeitsplatzkonzentration
[Maximum
Workplace
Concentration],
Deutsche
Forschungs­
gemeinschaft
[German
Research
Association],
Germany)
(DFG,
1999)
is
defined
analogous
to
the
ACGIH­
TLV­
TWA.

14
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
MAK
Spitzenbegrenzung
(Kategorie
II,
2)
[Peak
Limit
Category
II,
2]
(DFG,
1999)
constitutes
the
maximum
average
concentration
to
which
workers
can
be
exposed
for
a
period
up
to
30
minutes,
with
no
more
than
2
exposure
periods
per
work
shift;
total
exposure
may
not
exceed
8­
hour
MAK.

Einsatztoleranzwert
[Action
Tolerance
Levels]
(Vereinigung
zur
Fgrderung
des
deutschen
Brandschutzes
e.
V.
[Federation
for
the
Advancement
of
German
Fire
Prevention])
constitutes
a
concentration
to
which
unprotected
firemen
and
the
general
population
can
be
exposed
to
for
up
to
4
hours
without
any
health
risks.

j
MAC
(Maximaal
Aanvaarde
Concentratie
[Maximum
Accepted
Concentration])
(SDU
Uitgevers
[under
the
auspices
of
the
Ministry
of
Social
Affairs
and
Employment],
The
Hague,
The
Netherlands
2000)
is
defined
analgous
to
the
ACGIH­
TLV­
TWA
8.3
data
creates
substantial
uncertainty
regarding
the
exposure­
response
relationship
for
the
toxic
response
to
this
chemical.
Although
qualitative
data
are
available
regarding
the
acute
inhalation
toxicity
of
phosphorus
trichloride
in
humans,
quantitative
exposure­
response
data
are
lacking.
Quantitative
exposure­
response
data
are
severely
limited
for
nonlethal
responses
in
animals.
These
deficiencies
result
in
an
incomplete
picture
of
the
exposure
concentration­
response
curve
and
exposure
duration­
response
for
phosphorus
trichloride.
Additional
data
are
also
needed
regarding
the
mechanism
of
action,
possible
systemic
effects
(e.
g.,
renal
toxicity),
and
latency
in
the
toxic
responses
(e.
g.,
pulmonary
damage)
following
acute
inhalation
exposure
to
phosphorus
trichloride.
Data
Adequacy
and
Research
Needs
The
overall
robustness
of
the
data
base
for
phosphorus
trichloride
toxicity
is
poor.
The
lack
of
15
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
9.
REFERENCES
CITED
ACGIH
(American
Conference
of
Governmental
Hygienists).
1991.
Documentation
of
the
Threshold
Limit
Values
and
Biological
Exposure
Indices.
6th
ed.
ACGIH,
Cinc.,
OH.
pp.
1261­
1262.

ACGIH
(American
Conference
of
Governmental
Hygienists).
1997.
Threshold
Limit
Values
for
Chemical
Substances
and
Physical
Agents
and
Biological
Exposure
Indices.
ACGIH.

AIHA
(American
Industrial
Hygiene
Association).
1999.
The
AIHA
1999
Emergency
Response
Planning
Guideline
and
Workplace
Environmental
Exposure
Level
Guides
Handbook.
Amer.
Industrial
Hygiene
ASSOC.,
Fairfax,
VA.

Barbee,
S.
J.,
Stone,
J.
J.,
Hilaski,
R.
J.
1995.
Acute
inhalation
toxicology
of
oxalyl
chloride.
Am.
Ind.
Hyg.
J.
56:
74­
76.

Beliles,
R.
P.,
Beliles,
E.
M.
Phosphorus,
selenium,
tellurium,
and
sulfur.
In:
Clayton,
G.
D.,
Clayton,
F.
E.,
Eds.
Patty's
Industrial
Hygiene
and
Toxicologv.
Vol.
11.4th
ed.,
John
Wiley
&
Sons,
Inc.,
New
York.
pp.
790­
79
1.

Budavari,
S.,
O'Neil,
M.
J.,
Smith,
A.,
Heckelman,
P.
E.,
Kennedy,
J.
F.,
Eds.
1996.
Phosphorus
trichloride.
The
Merck
Index.
Merck
and
Co.,
Whitehouse,
NJ.

Butjagin,
P.
W.
1904.
Experimentelle
Studien
iiber
den
Einflufs
technisch
und
hygienisch
wichtiger
Gase
und
Dgimpfe
auf
den
Organismus.
Teil
XII.
Studien
iiber
phosphortrichlorid.
Archiv
f.
Hyg.
49:
307­
335.

Fee,
D.
C.,
Gard,
D.
R.,
Yang,
C­
H.
1996.
Phosphorus
compounds.
In:
Kirk­
Other
Encyclopedia
of
Chemical
Technology.
Pp.
761­
765.
Vol.
18.
John
Wiley
&
Sons,
New
York.

German
Research
Association
(Deutsche
Forschungsgemeinschaft).
1999.
List
of
MAK
and
BAT
Values
1999.
Commission
for
the
Investigation
of
Health
Hazards
of
Chemical
Compounds
in
the
Work
Area.
Report
No.
35.

Hazleton
Laboratories.
1983.
Subacute
inhalation
toxicity
study
in
rats
­
phosphorus
trichloride.
Final
Report.
Project
No.
24
1
­
14
1.
Hazleton
Laboratories
America,
Inc.
Unpublished.

HSDB
(Hazardous
Substances
Data
Bank).
1998.
On­
line
Moody,
P.
198
1.
Health
hazard
evaluation
Report
HETA
8
1­
089­
965
FMC
Corporation,
Nitro,
West
Virginia.
U.
S.
Dept.
Health
and
Human
Services,
Center
for
Disease
Control,
National
Institute
for
Occupational
Safety
and
Health,
Cincinnati,
OH.

NIOSH
(National
Institute
for
Occupational
Safety
and
Health).
1994.
Documentation
for
Immediately
Dangerous
to
Life
or
Health
Concentrations
(IDLHS).
National
Institute
for
Occupational
Safety
and
Health,
Cincinnati,
OH;
PB94
195047,
National
Technical
Information
Service,
Springfield,
VA.

NIOSH
(National
Institute
for
Occupational
Safety
and
Health).
1999.
NIOSH
Pocket
Guide
to
Chemical
Hazards.
NIOSH
Publication
94­
1
16,
U.
S.
Dept.
Health
and
Human
Services;
U.
S.
Government
Printing
Office,
Washington,
D.
C.

16
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
OSHA
(Occupational
Safety
and
Health
Administration).
1999.
Limits
for
Air
Contaminants.
Table
Z­
1.
Code
of
Federal
Regulations
29,
Part
1910.
Office
of
the
Federal
Register
National
Archives
and
Records
Administration.

RTECS
(Registry
of
Toxic
Effects
of
Chemical
Substances),
1998.
On­
line
retrieval.

Sassi,
C.
1952.
Occupational
poisoning
due
to
phosphorus
trichloride.
AMA
Arch.
Ind.
Hyg.
Occ.
Med.
7,
178.
(English
translation
of
abstract.)

ten
Berge,
W.
F.,
Zwart,
A.,
Appelman,
L.
M.
1986.
Concentration­
time
mortality
response
relationship
of
irritant
and
systemically
acting
vapours
and
gases.
J.
Hazard.
Materials
13:
301­
309.

Tharr,
D.
G.,
Singal,
M.
1980.
Health
hazard
evaluation
determination.
Report
No.
HHE­
78­
90­
739,
FMC
Corp.,
Specialty
Chemicals
Div.,
Nitro,
WV.
NTIS
Publ.
No.
PB­
83­
161­
190.

Wason,
S.,
Gomolin,
I.,
Gross,
P.,
Lovejoy,
F.
H.,
Jr.
1982.
Phosphorus
trichloride
exposure
­
a
follow­
up
study
of
27
exposed
patients.
Vet.
Human
Toxicol.
24:
275­
276.(
abstract)

Wason,
S.,
Gomolin,
I.,
Gross,
P.,
Mariam,
S.,
Lovejoy,
F.
H.
1984.
Phosphorus
trichloride
toxicity­
preliminary
report.
Amer.
J.
Med.
77:
1039­
1042.

Weeks,
M.
H.,
Mussleman,
N.
P.,
Yevich,
P.
P.,
Jacobson,
K.
H.,
Oberst,
F.
W.
1964.
Acute
vapor
toxicity
of
phosphorus
oxychloride,
phosphorus
trichloride
and
methyl
phosphonic
dichloride.
Amer.
Ind.
Hyg.
J.
25:
470­
475.

17
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
APPENDIX
A
DERIVATION
OF
AEGL
VALUES
18
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
Key
study:

Toxicity
endpoint:

Scaling:

Uncertainty
factors:

1
0­
min
AEGL­
1
30­
min
AEGL­
1
1
­hr
AEGL­
1
4­
hr
AEGL­
1
8­
hr
AEGL­
1
DERIVATION
OF
AEGL­
1
VALUES
Hazleton
Laboratories,
1983
NOAEL
of
3.4
ppm
for
rats
following
multiple
exposure
at
6
hrs/
day,
5
days/
week
for
4
weeks.

The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
c"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5
(ten
Berge
et
al.,
1986).
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
c"
x
t
=
k
equation.
(3.4
ppm)
'
x
6
hrs
=
20.4
ppm
.
hrs
(n
=
1)
(3.4
~p
m
)~
x
6
hrs
=
235.8
ppm3
hrs
(n
=
3)

Interspecies
UF
=
3;
the
attenuation
of
this
uncertainty
factor
is
justified
by
the
fact
that
the
guinea
pig
appears
to
be
the
most
sensitive
species
tested
and
because
limited
human
exposure
data
(Sassi,
1952)
indicate
that
humans
have
experienced
routine
occupational
exposures
of
up
to
3.6
ppm
without
effect.
Intraspecies
UF
=
3;
contact
irritation
and
subsequent
tissue
damage
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociaton
and
direct
corrosive
action
of
these
components
on
epithelial
surfaces.
Additional
application
of
uncertainty
factor
adjustment
would
provide
AEGL­
3
values
that
are
inconsistent
with
limited
data
on
human
exposures.

The
10­
minute
AEGL­
1,
was
set
equivalent
to
the
30­
minute
value
due
to
uncertainties
in
extrapolating
from
the
6­
hour
experimental
exposure
duration.

C3
x
0.5
hr
=
235.8
ppm3
.hr
C
=7.78ppm
30­
min
AEGL­
1
=
7.78
ppm/
lO
=
0.78
ppm
(4.4
mg/
m3)

C3
x
1
hr
=
235.8
ppm3.
hr
C
=6.18ppm
1­
hr
AEGL­
1
=
6.18
ppm/
lO
=
0.62
ppm
(3.5
mg/
m')

C3
x
4
hrs
=
235.8
ppm3*
hr
C
=3.89ppm
4­
hr
AEGL­
1
=
3.89
ppm/
lO
=
0.39
ppm
(2.2
mg/
m3)

C'
x
8
hrs
=
20.4
ppmehr
C
=
2.55
ppm
8­
hr
AEGL­
1
=
2.55
ppm/
l0
=
0.26
ppm
(1.5
mg/
m3)

19
000267
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
0512002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
Key
study:

Toxicity
endpoint:

Scaling:

Uncertainty
factors:

1
0­
min
AEGL­
2
30­
min
AEGL­
2
DERIVATION
OF
AEGL­
2
Hazleton
Laboratories,
1983
LOAEL
of
11
ppm
for
respiratory
tract
histopathologic
changes
in
rats
following
multiple
exposure
at
6
hrslday,
5
days/
week
for
4
weeks.

The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
C
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5
(ten
Berge
et
al.,
1986).
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
C
x
t
=
k
equation.
(11ppm)
'x6hrs
=66ppm*
hrs(
n=
1)
(1
1
ppm)
'
x
6
hrs
=
7986
ppm'
hrs
(n
=
3)

Interspecies
UF
=
3;
the
attenuation
of
this
uncertainty
factor
is
justified
by
the
fact
that
the
guinea
pig
appears
to
be
the
most
sensitive
species
tested
and
because
limited
human
exposure
data
(Sassi,
1952)
indicate
that
humans
have
experienced
routine
occupational
exposures
of
up
to
3.6
ppm
without
effect.
Intraspecies
UF
=
3;
contact
irritation
and
subsequent
tissue
damage
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociaton
and
direct
corrosive
action
of
these
components
on
epithelial
surfaces.
Adjustments
using
a
greater
level
of
uncertainty
uncertainty
would
provide
AEGL­
2
values
that
are
inconsistent
with
limited
data
on
human
exposures.

The
10­
minute
AEGL­
2,
was
set
equivalent
to
the
30­
minute
value
(2.5
ppm)
due
to
uncertainties
in
extrapolating
from
the
6­
hour
experimental
exposure
duration
to
a
10­
minute
duration.

C3
x
0.5
hr
=
7986
ppm3
.hr
C
=25.2ppm
30­
min
AEGL­
2
=
25.2
ppm/
l0
=
2.5
ppm
(14
mg/
m3)

1
­hr
AEGL­
2
C3
x
1
hr
=
7986
ppm3.
hr
C
=20.0ppm
1­
hr
AEGL­
2
=
20.0
ppm/
lO
=
2.0
ppm
(1
1
mg/
m3)

4­
hr
AEGL­
2
C3
x
4
hrs
=
7986
ppm3.
hr
C
=
12.6
ppm
4­
hr
AEGL­
2
=
12.6
ppm/
lO
=
1.3
ppm
(7.3
mglm')

20
PHOSPHORUS
TRICHLORIDE
1
8­
hr
AEGL­
2
2
3
4
C'
x
8
hrs
=
66
ppm­
hr
C
=8.25ppm
8­
hr
AEGL­
2
=
8.25
p
p
d
l
0
=
0.83
ppm
(4.6
mg/
m3)

21
PROPOSED
1:
05/
2002
000269
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
Key
study:

Toxicity
endpoint:

Scaling:

Uncertainty
factors:

1
O­
min
AEGL­
3
30­
min
AEGL­
3
DERIVATION
OF
AEGL­
3
Weeks
et
al.
1964
Lethality
threshold
estimated
as
3­
fold
reduction
in
the
4­
hr
LC5,
for
rats
(104.3
ppm/
3
=
34.8
ppm);
delayed
response
possible.

The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
c"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5
(ten
Berge
et
al.,
1986).
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
c"
x
t
=
k
equation.
(34.8
pprn)
'
x
4
hrs
=
139.2
ppm
hrs
(n
=
1)
(34.8
~p
m
)~
x
4
hrs
=
168,576.8
ppm3
*
hrs
(n
=
3)

Interspecies
UF
=
3;
the
attenuation
of
this
uncertainty
factor
is
justified
by
the
fact
that
the
guinea
pig
appears
to
be
the
most
sensitive
species
tested
and
because
limited
human
exposure
data
(SassiJ952)
indicate
that
humans
have
experienced
exposures
of
up
to
27
ppm
without
life­
threatening
consequences
Intraspecies
UF
=
3;
contact
irritation
and
subsequent
tissue
damage
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociaton
and
direct
corrosive
action
of
these
components
on
epithelial
surfaces.
Additional
application
of
uncertainty
factor
adjustment
would
provide
AEGL­
3
values
that
are
not
consistent
with
limited
data
on
human
exposures
or
with
the
results
of
repeated
exposures
in
rats
wherein
exposure
to
1
lppm
6
hrs/
day,
5
daydweek
for
4
weeks
showed
only
histologic
changes
in
the
upper
respiratory
tract
and
no
overt
signs
of
toxicity
Due
to
uncertainties
in
extrapolating
from
a
4­
hour
to
10­
minute
exposure,
the
10­
minute
AEGL­
3
is
set
equivalent
to
the
30­
minute
value
(7.0
ppm).

C3
x
0.5
hr
=
168,576.8
ppm3
.hr
C
=69.6ppm
30­
min
AEGL­
3
=
69.6
ppm/
lO
=
7.0
ppm
(39
mg/
m3)

l­
hr
AEGL­
3
C3
x
1
hr
=
168,576.8
ppm3.
hr
C
=55.2ppm
l­
hr
AEGL­
3
=
55.2
ppm/
lO
=
5.6
ppm
(3
1
mg/
m3)

4­
hr
AEGL­
3
C3
x
4
hrs
=
168,576.8
ppm3.
hr
C
=34.8ppm
4­
hr
AEGL­
3
=
34.8
ppm/
lO
=
3.5
ppm
(20
mg/
m3)

22
PHOSPHORUS
TRICHLORIDE
1
8­
hr
AEGL­
3
2
3
4
C'
x
8
hrs
=
139.2
ppm­
hr
C
=
17.4ppm
8­
hr
AEGL­
3
=
17.4
ppm/
lO
=
1.8
ppm
(10
mg/
m3)
PROPOSED
1:
05/
2002
23
000271
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
APPENDIX
B
DERIVATION
SUMMARY
FOR
PHOSPHORUS
TRICHLORIDE
AEGL
VALUES
000272
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
85/
2002
10
minutes
30
minutes
0.78
ppm
0.78
ppm
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
1
hour
4
hours
8
hours
0.62
ppm
0.39
ppm
0.26
ppm
ACUTE
EXPOSURE
GUIDELINES
FOR
PHOSPHORUS
TRICHLORIDE
(CAS
NO.
7719­
12­
2)

Reference:
Hazleton
Laboratories,
1983
Test
SpecieslStrainINumber:
Sprague­
Dawley
rats;
1
5/
sex/
group
Exposure
RoutelConcentrationsDurations:
Inhalation
exposure
(whole­
body)
to
0,0.5,3.0,
or
10.0
ppm
(nominal)
for
6
hrslday,
5
dayslweek
for
4
weeks
Toxicity
Endpoint:
No
effects
noted
at
3.4
ppm
(analytical)
following
multiple
exposure
of
rats
over
4
weeks
Time
Scaling:
The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
C"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5.
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
C"
x
t
=
k
equation.
For
10­
minute
AEGL­
1,
values
were
set
at
equivalence
to
the
30­
minute
values
due
to
uncertainties
in
extrapolating
from
the
experimental
exposure
durations
of
4
hours
or
greater.

ConcentratiodTime
Selectionkitionale:
In
the
absence
of
exposure­
response
data
specific
for
AEGL­
1
effects,
the
exposure
to
3.4
ppm
at
6
hrdday,
5
dayslweek
for
4
weeks
was
selected
as
a
conservative
basis
for
AEGL
development.

Uncertainty
FactorsIRationale:
Total
uncertainty
application
of
10.
The
interspecies
uncertainty
factor
was
limited
to
3
because
of
the
concordance
of
the
animal
data
with
the
human
experience
and
because
the
most
sensitive
species
tested
(guinea
pig)
was
only
about
2­
fold
more
sensitive.
The
intraspecies
uncertainty
factor
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
Furthermore,
the
AEGL­
1
is
based
upon
a
conservative
assumption
and
additional
reduction
of
the
AEGL­
1
values
would
be
inconsistent
with
available
human
and
animal
data.

Modifying
Factor:
Not
applicable
Animal­
to­
Human
Dosimetric
Adjustments:
Not
applicable
Data
Quality
and
Support
of
the
AEGL
Values:
Neither
human
nor
animal
quantitative
exposure­
response
data
are
available
regarding
effects
consistent
with
AEGL­
1
definition..
The
3.4
ppm
exposure
of
rats
over
4
weeks
was
selected
as
a
NOAEL
for
AEGL­
1.
Although
likely
to
be
a
conservative
basis
for
developing
AEGL­
1
values,
it
may
be
justified
due
to
the
relative
paucity
of
data
on
the
toxic
response
to
this
chemical.
PHOSPHORUS
TRICHLORIDE
1
26
PROPOSED
1:
05/
2002
000274
1
2
3
4
5
6
7
8
9
10
1
1
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
10
minutes
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
ACUTE
EXPOSURE
GUIDELINES
FOR
PHOSPHORUS
TRICHLORIDE
(CAS
NO.
7719­
12­
2)

30­
minutes
I
1
hour
I
4
hours
I
8
hours
2.5
ppm
2.5
ppm
2.0
ppm
1.3
ppm
0.83
ppm
I
I
I
~

Test
Species/
Strain/
Number:
Sprague­
Dawley
rats;
1
5/
sex/
group
Exposure
Route/
Concentrations/
Durations:
Inhalation
exposure
(whole­
body)
to
0,0.5,3.0,
or
10.0
ppm
(nominal)
for
6
hrsfday,
5
daydweek
for
4
weeks
Toxicity
Endpoint:
Histopathologic
alterations
in
respiratory
tract
in
rats
exposed
to
11
ppm
(analytical),
6
hrs/
day,
5
daysfweek
for
4
weeks.
There
were
no
concurrent
hematologic
or
biochemical
alterations
indicative
of
a
toxic
response,
and
there
were
no
ophthalmologic
effects.

Time
Scaling:
The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
C"
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5.
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
C"
x
t
=
k
equation.
For
10­
minute
AEGL­
2,
values
were
set
at
equivalence
to
the
30­
minute
values
due
to
uncertainties
in
extrapolating
from
the
experimental
exposure
durations
of
4
hours
or
greater.

Concentration/
Time
SelectiodRationale:
The
multiple
exposure
of
rats
to
11
ppm
over
4
weeks
was
considered
a
conservative
estimate
and
NOAEL
for
AEGL­
2
effects
(i.
e.,
the
effects
were
neither
disabling
nor
irreversible).

Uncertainty
Factors/
Rationale:
Total
uncertainty
application
of
10.
The
interspecies
uncertainty
factor
was
limited
to
3
because
of
the
concordance
of
the
animal
data
with
the
human
experience
and
because
the
most
sensitive
species
tested
(guinea
pig)
was
only
about
2­
fold
more
sensitive.
The
intraspecies
uncertainty
factor
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation.
Furthermore,
the
AEGL­
2
is
based
upon
a
histopathologic
changes
in
the
respiratory
tract
which
were
not
necessarily
irreversible
or
disabling.
Additional
reduction
of
the
AEGL­
2
values
would
be
inconsistent
with
available
human
and
animal
data.

Modifying
Factor:
Not
Applicable
Animal­
to­
Human
Dosimetric
Adjustments:
Not
applicable
27
000275
6
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
092002
Data
Quality
and
Support
of
the
AEGL
Values:
Limited
information
regarding
the
human
experience
indicated
that
2
to
6­
hour
exposures
to
1.8­
3.6
ppm
were
without
effect
and
that
exposure
to
14­
27
ppm
irritation
of
the
eyes
and
upper
respiratory
tract,
photophobia,
chest
tightness,
and
bronchitis.
Because
the
effects
were
neither
disabling
nor
irreversible,
the
endpoint
used
for
AEGL­
2
development
is
considered
a
NOAEL
for
AEGL­
2
effects.

28
000276
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
092002
1
2
3
4
5
6
7
S
9
10
11
12
13
14
15
16
17
`1
s
19
20
21
22
23
24
25
26
27
2s
29
30
31
32
33
34
35
36
37
3s
39
40
ACUTE
EXPOSURE
GUIDELINES
FOR
PHOSPHORUS
TRICHLORIDE
(CAS
NO.
7719­
12­
2)

AEGL­
3
VALUES
10
minutes
30
minutes
1
hour
4
hours
8
hours
3.3
ppm
3.3
ppm
2.7
ppm
1.7
ppm
0.84
ppm
Reference:
Weeks,
M.
H.,
Mussleman,
N.
P.,
Yevich,
P.
P.,
Jacobson,
K.
H.,
Oberst,
F.
W.
1964.
Acute
vapor
toxicity
of
phosphorus
oxychloride,
phosphorus
trichloride
and
methyl
phosphonic
dichloride.
Amer.
Ind.
Hyg.
J.
25:
470­
475.

Test
Species/
Strain/
Number:
female
rats
and
guinea
pigdstrain
not
specified20
per
group
Exposure
Route/
Concentrations/
Durations:
inhalatiordmedian
lethal
concentrations
derived
but
exposure
concentrations
not
specified4
hrs
Toxicity
Endpoint:
guinea
pig
4­
hr
LC,,
of
50.1
ppm
Time
Scaling:
The
concentration­
time
relationship
for
may
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
C`
x
t
=
k
,
where
the
exponent
n
ranges
from
0.8
to
3.5.
Due
to
the
limited
toxicity
data
for
this
chemical,
an
empirical
derivation
of
n
was
not
possible.
In
the
absence
of
an
empirically
derived
exponent
(n),
and
to
obtain
conservative
and
protective
AEGL
values,
temporal
scaling
was
performed
using
n
=
3
when
extrapolating
to
shorter
time
points
and
n
=
1
when
extrapolating
to
longer
time
points
using
the
C`
x
t
=
k
equation.
(16.7
ppm)
'
x
4
hrs
=
66.8
ppm
hrs
(n
=
1
)
(16.7
~p
m
)~
x
4
hrs
=
18,629.85
ppm3
hrs
(n
=
3)

ConcentratiordTime
SelectiodRationale:
a
3­
fold
reduction
of
the
guinea
pig
4­
hr
LC,,
(50.1
ppm/
3
=
16.7
ppm)
was
used
as
an
estimate
of
the
lethality
threshold.

Uncertainty
FactodRationale:
Total
Uncertainty:
10
Interspecies
UF
=
3
Data
for
humans
and
animals
indicate
some
variability
in
the
toxic
response
to
phosphorus
trichloride
but
guinea
pigs
appear
to
be
the
more
sensitive
among
the
species
tested.
The
uncertainty
for
intraspecies
variability
was
limited
to
3
because
primary
effects
of
phosphorus
trichloride
(irritation
and
subsequent
tissue
damage)
appear
to
be
due,
in
part,
to
hydrogen
chloride
and
phosphonic
acid
resulting
from
chemical
dissociation
and
the
direct
corrosive
action
of
these
on
epithelial
tissue.
The
overall
uncertainty
factor
adjustment
of
10
may
be
justified
by
limited
human
exposure
data
suggesting
that
humans
could
experience
exposures
of
up
to
27
ppm
without
life­
threatening
consequences.
Furthermore,
the
results
of
a
study
in
rats
exposed
to
11
ppm
6
hrs/
day,
5
daystweek
for
4
weeks
showed
only
histologic
changes
in
the
upper
respiratory
tract
and
no
overt
signs
of
toxicity.
Intraspecies
UF
=
3
Modifying
Factor:
none
applied
Animal­
to­
Human
Dosimetric
Adjustments:
insufficient
data
29
000277
PHOSPHORUS
TRICHLORIDE
PROPOSED
1:
05/
2002
It
II
Data
Quality
and
Support
for
the
AEGL
Values:
Lethality
data
are
limited
to
two
species
and
quantitative
data
for
humans
are
limited.
However,
comparison
of
the
AEGL­
3
values
with
available
data
do
not
support
application
of
uncertainty
adjustment
greater
than
that
currently
applied.
Data
suitable
for
determining
exposure­
time
relationships
are
also
lacking
and
impact
on
temporal
extrapolation
efforts.
A
delayed
response
is
possible
as
demonstrated
in
the
Weeks
et
al.
(1964)
study
in
which
deaths
of
guinea
pigs
occurred
up
to
10
days
post
exposure.

I'
SI
30
