Document ID: EPA-HQ-OPPT-2002-0027-0001
Agency: epa
Document Type: Notice
Title: National Advisory Committee for Acute Exposure Guideline Levels (AEGLs) for Hazardous Substances; Proposed AEGL Values
Posted Date: 2003-07-18T04:00Z

42710
Federal
Register
/
Vol.
68,
No.
138
/
Friday,
July
18,
2003
/
Notices
2.
100
 
EUP
 
112.
Issuance.
Syngenta
Crop
Protection,
410
Swing
Road,
Greensboro,
NC
27419
 
8300.
This
EUP
allows
the
use
of
74
pounds
active
ingredient
of
the
insecticide
Lufenuron
around
125
structures
to
be
used
as
an
outdoor
in­
ground
termite
bait.
The
program
is
authorized
in
the
States
of
Alabama,
Arizona,
Arkansas,
California,
Florida,
Georgia,
Hawaii,
Indiana,
Kansas,
Kentucky,
Louisiana,
Maryland,
Mississippi,
Missouri,
Nebraska,
Nevada,
North
Carolina,
Ohio,
Oklahoma,
Pennsylvania,
South
Carolina,
Texas,
and
Virginia.
The
EUP
is
effective
from
April
3,
2003
to
April
3,
2006.
3.
100
 
EUP
 
113.
Issuance.
Syngenta
Crop
Protection,
410
Swing
Road,
Greensboro,
NC
27419
 
8300.
This
EUP
allows
the
use
of
1
pound
active
ingredient
of
the
insecticide
Lufenuron
around
25
structures
to
be
used
as
an
above
ground
termite
bait.
The
program
is
authorized
only
in
the
States
of
Arizona,
California,
Florida,
Georgia,
Hawaii,
Louisiana,
Ohio,
South
Carolina,
and
Texas.
The
EUP
is
effective
from
May
7,
2003
to
May
7,
2006.
4.
352
 
EUP
 
167.
Issuance.
E.
I.
Dupont
de
Nemours
and
Company,
P.
O.
Box
30,
Newark,
DE
19714.
This
EUP
allows
the
use
of
450
pounds
of
the
insecticide
Dupont
Avaunt,
containing
135
pounds
of
the
active
ingredient
indoxacarb
on
300
acres
of
peaches
to
evaluate
the
control
of
the
Oriental
fruit
moth
and
plum
curculio.
The
program
is
authorized
only
in
the
States
of
Georgia,
Michigan,
New
Jersey,
Pennsylvania,
South
Carolina,
and
West
Virginia.
The
EUP
is
effective
from
May
2,
2003
to
May
2,
2005.
5.
70341
 
EUP
 
2.
Issuance.
IPM
Technologies,
Inc.,
4134
North
Vancouver
Avenue
#
105,
Portland,
OR
97217.
This
EUP
allows
the
use
of
300
pounds
of
the
insecticide
Last
Call
PLR,
containing
18
pounds
of
the
active
ingredient
permethrin
and
4.8
pounds
of
a
pheromone
blend
on
68
acres
of
apples
to
evaluate
the
control
of
Pandemis
leafroller
moth.
The
program
is
authorized
only
in
the
State
of
Washington.
The
EUP
is
effective
from
May
15,
2003
to
May
14,
2004.
6.
70341
 
EUP
 
3.
Issuance.
IPM
Technologies,
Inc.,
4134
North
Vancouver
Avenue
#
105,
Portland,
OR
97217.
This
EUP
allows
the
use
of
300
pounds
of
the
insecticide
Last
Call
OBLR,
containing
18
pounds
of
the
active
ingredient
permethrin
and
4.8
pounds
of
a
pheromone
blend
on
68
acres
of
apples
to
evaluate
the
control
of
Oblique
banded
leafroller
moth.
The
program
is
authorized
only
in
the
State
of
Washington.
The
EUP
is
effective
from
May
15,
2003
to
May
14,
2004.
7.
71715
 
EUP
 
2.
Issuance.
Tonnie
L.
C.
Casey,
Kamehameha
Schools,
78
 
6831
Alii
Drive,
Suite
232,
Kailua­
Kona,
HI
96740.
This
EUP
allows
the
use
of
16,000
pounds
of
the
rodenticide
Eaton's
Bait
Pellet
Rodenticide
with
Fish
Flavorizer,
containing
80
pounds
of
the
active
ingredient
diphacinone
on
800
acres
of
forested
ranchland
to
evaluate
the
control
of
invasive
rodents
and
mongooses.
The
program
is
authorized
only
in
the
State
of
Hawaii.
The
EUP
is
effective
from
May
6,
2003
to
May
6,
2004.

Authority:
7
U.
S.
C.
136c.

List
of
Subjects
Environmental
protection,
Experimental
use
permits.

Dated:
July
1,
2003.
Debra
Edwards
Director,
Registration
Division,
Office
of
Pesticide
Programs.

[
FR
Doc.
03
 
18318
Filed
7
 
17
 
03;
8:
45
am]

BILLING
CODE
6560
 
50
 
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPPT
 
2002
 
0027;
FRL
 
7189
 
8]

National
Advisory
Committee
for
Acute
Exposure
Guideline
Levels
(
AEGLs)
for
Hazardous
Substances;
Proposed
AEGL
Values
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.

SUMMARY:
The
National
Advisory
Committee
for
Acute
Exposure
Guideline
Levels
for
Hazardous
Substances
(
NAC/
AEGL
Committee)
is
developing
AEGLs
on
an
ongoing
basis
to
provide
Federal,
State,
and
local
agencies
with
information
on
short­
term
exposures
to
hazardous
chemicals.
This
notice
provides
AEGL
values
and
executive
summaries
for
10
chemicals
for
public
review
and
comment.
Comments
are
welcome
on
both
the
AEGL
values
in
this
notice
and
the
technical
support
documents
placed
in
the
public
version
of
the
official
docket
for
these
10
chemicals.
DATES:
Comments,
identified
by
docket
ID
number
OPPT
 
2002
 
0027,
must
be
received
on
or
before
August
18,
2003.
ADDRESSES:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
FOR
FURTHER
INFORMATION
CONTACT:
For
general
information
contact:
Barbara
Cunningham,
Acting
Director,
Environmental
Assistance
Division
(
7408M),
Office
of
Pollution
Prevention
and
Toxics,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
202)
554
 
1404;
e­
mail
address:
TSCA­
Hotline@
epa.
gov.
For
technical
information
contact:
Paul
S.
Tobin,
Designated
Federal
Officer
(
DFO),
Office
of
Pollution
Prevention
and
Toxics
(
7406M),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
202)
564
 
8557;
e­
mail
address:
tobin.
paul@
epa.
gov.

SUPPLEMENTARY
INFORMATION:

I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
general
public
to
provide
an
opportunity
for
review
and
comment
on
``
Proposed''
AEGL
values
and
their
supporting
scientific
rationale.
This
action
may
be
of
particular
interest
to
anyone
who
may
be
affected
if
the
AEGL
values
are
adopted
by
government
agencies
for
emergency
planning,
prevention,
or
response
programs,
such
as
EPA's
Risk
Management
Program
under
the
Clean
Air
Act
and
Amendments
Section
112r.
It
is
possible
that
other
Federal
agencies
besides
EPA,
as
well
as
State
and
local
agencies
and
private
organizations,
may
adopt
the
AEGL
values
for
their
programs.
As
such,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
DFO
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

B.
How
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPPT
 
2002
 
0027.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
EPA
Docket
Center,
Rm.
B102­
Reading
Room,
EPA
West,
1301
Constitution
VerDate
Jan<
31>
2003
19:
43
Jul
17,
2003
Jkt
200001
PO
00000
Frm
00039
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
18JYN1.
SGM
18JYN1
OPPT­
2002­
0027­
0001
RECEIVED
OPPT
NCIC
2003
July
18
7:
36AM
42711
Federal
Register
/
Vol.
68,
No.
138
/
Friday,
July
18,
2003
/
Notices
Ave.,
NW.,
Washington,
DC.
The
EPA
Docket
Center
is
open
from
8:
30
a.
m.
to
4:
30
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
EPA
Docket
Center
Reading
Room
telephone
number
is
(
202)
566
 
1744
and
the
telephone
number
for
the
OPPT
Docket,
which
is
located
in
EPA
Docket
Center,
is
(
202)
566
 
0280.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
docket.
To
the
extent
feasible,
publicly
available
docket
materials
will
be
made
available
in
EPA's
electronic
public
docket.
When
a
document
is
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
document
is
available
for
viewing
in
EPA's
electronic
public
docket.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
docket
materials
through
EPA's
electronic
public
docket.
For
public
commenters,
it
is
important
to
note
that
EPA's
policy
is
that
public
comments,
whether
submitted
electronically
or
in
paper,
will
be
made
available
for
public
viewing
in
EPA's
electronic
public
docket
as
EPA
receives
them
and
without
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
comment
that
is
placed
in
EPA's
electronic
public
docket.
The
entire
printed
comment,
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
be
transferred
to
EPA's
electronic
public
docket.
Public
comments
that
are
mailed
or
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA's
electronic
public
docket.
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
placed
in
EPA's
electronic
public
docket
along
with
a
brief
description
written
by
the
docket
staff.

C.
How
and
To
Whom
Do
I
Submit
Comments?
You
may
submit
comments
electronically,
by
mail,
or
through
hand
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
the
close
of
the
comment
period
will
be
marked
``
late.''
EPA
is
not
required
to
consider
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
or
e­
mail
to
submit
CBI
or
information
protected
by
statute.
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
unit,
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
email
address
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
your
comment.
EPA's
policy
is
that
EPA
will
not
edit
your
comment,
and
any
identifying
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
comment.
i.
EPA
Dockets.
Your
use
of
EPA's
electronic
public
docket
to
submit
comments
to
EPA
electronically
is
EPA's
preferred
method
for
receiving
comments.
Go
directly
to
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/,
and
follow
the
online
instructions
for
submitting
comments.
Once
in
the
system,
select
``
search,''
and
then
key
in
docket
ID
number
OPPT
 
2002
 
0027.
The
system
is
an
``
anonymous
access''
system,
which
means
EPA
will
not
know
your
identity,
e­
mail
address,
or
other
contact
information
unless
you
provide
it
in
the
body
of
your
comment.
ii.
E­
mail.
Comments
may
be
sent
by
e­
mail
to
oppt.
ncic@
epa.
gov,
Attention:
Docket
ID
Number
OPPT
 
2002
 
0027.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
e­
mail
system
is
not
an
``
anonymous
access''
system.
If
you
send
an
e­
mail
comment
directly
to
the
docket
without
going
through
EPA's
electronic
public
docket,
EPA's
e­
mail
system
automatically
captures
your
email
address.
E­
mail
addresses
that
are
automatically
captured
by
EPA's
e­
mail
system
are
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
you
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
2.
By
mail.
Send
your
comments
to:
Document
Control
Office
(
7407M),
Office
of
Pollution
Prevention
and
Toxics
(
OPPT),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
 
0001.
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
OPPT
Document
Control
Office
(
DCO)
in
EPA
East
Building
Rm.
6428,
1201
Constitution
Ave.,
NW.,
Washington,
DC.
Attention:
Docket
ID
Number
OPPT
 
2002
 
0027.
The
DCO
is
open
from
8
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
telephone
number
for
the
DCO
is
(
202)
564
 
8930.

D.
How
Should
I
Submit
CBI
to
the
Agency?
Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
EPA's
electronic
public
docket
or
by
e­
mail.
You
may
claim
information
that
you
submit
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
on
disk
or
CD
ROM,
mark
the
outside
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18,
2003
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Notices
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA's
electronic
public
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
clearly
that
it
does
not
contain
CBI.
Information
not
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA's
electronic
public
docket
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
technical
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.

E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?

You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
document.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.

II.
Background
A.
What
Action
is
the
Agency
Taking?

EPA's
Office
of
Prevention,
Pesticides
and
Toxic
Substances
(
OPPTS)
provided
notice
in
the
Federal
Register
of
October
31,
1995
(
60
FR
55376)
(
FRL
 
4987
 
3)
of
the
establishment
of
the
NAC/
AEGL
Committee
with
the
stated
charter
objective
as
``
the
efficient
and
effective
development
of
AEGLs
and
the
preparation
of
supplementary
qualitative
information
on
the
hazardous
substances
for
federal,
state,
and
local
agencies
and
organizations
in
the
private
sector
concerned
with
[
chemical]
emergency
planning,
prevention,
and
response.''
The
NAC/
AEGL
Committee
is
a
discretionary
Federal
advisory
committee
formed
with
the
intent
to
develop
AEGLs
for
chemicals
through
the
combined
efforts
of
stakeholder
members
from
both
the
public
and
private
sectors
in
a
costeffective
approach
that
avoids
duplication
of
efforts
and
provides
uniform
values,
while
employing
the
most
scientifically
sound
methods
available.
An
initial
priority
list
of
85
chemicals
for
AEGL
development
was
published
in
the
Federal
Register
of
May
21,
1997
(
62
FR
27734)
(
FRL
 
5718
 
9).
This
list
is
intended
for
expansion
and
modification
as
priorities
of
the
stakeholder
member
organizations
are
further
developed.
While
the
development
of
AEGLs
for
chemicals
are
currently
not
statutorily
based,
at
lease
one
rulemaking
references
their
planned
adoption.
The
Clean
Air
Act
and
Amendments
Section
112(
r)
Risk
Management
Program
states,
``
EPA
recognizes
potential
limitations
associated
with
the
Emergency
Response
Planning
Guidelines
and
Level
of
Concern
and
is
working
with
other
agencies
to
develop
AEGLs.
When
these
values
have
been
developed
and
peer­
reviewed,
EPA
intends
to
adopt
them,
through
rulemaking,
as
the
toxic
endpoint
for
substances
under
this
rule
(
see
61
FR
31685).''
It
is
believed
that
other
Federal
and
State
agencies
and
private
organizations
will
also
adopt
AEGLs
for
chemical
emergency
programs
in
the
future.

B.
Characterization
of
the
AEGLs
The
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
AEGLs
have
been
defined
as
follows:
AEGL­
1
is
the
airborne
concentration
(
expressed
as
parts
per
million
(
ppm)
or
milligram/
meter
cubed
(
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,
nonsensory
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
could
produce
mild
and
progressively
increasing
odor,
taste,
and
sensory
irritation,
or
certain
non­
symptomatic,
non­
sensory
effects.
With
increasing
airborne
concentrations
above
each
AEGL
level,
there
is
a
progressive
increase
in
the
likelihood
of
occurrence
and
the
severity
of
effects
described
for
each
corresponding
AEGL
level.
Although
the
AEGL
values
represent
threshold
levels
for
the
general
public,
including
sensitive
subpopulations,
it
is
recognized
that
certain
individuals,
subject
to
unique
or
idiosyncratic
responses,
could
experience
the
effects
described
at
concentrations
below
the
corresponding
AEGL
level.

C.
Development
of
the
AEGLs
The
NAC/
AEGL
Committee
develops
the
AEGL
values
on
a
chemical­
bychemical
basis.
Relevant
data
and
information
are
gathered
from
all
known
sources
including
published
scientific
literature,
State
and
Federal
agency
publications,
private
industry,
public
data
bases,
and
individual
experts
in
both
the
public
and
private
sectors.
All
key
data
and
information
are
summarized
for
the
NAC/
AEGL
Committee
in
draft
form
by
Oak
Ridge
National
Laboratories
together
with
``
draft''
AEGL
values
prepared
in
conjunction
with
NAC/
AEGL
Committee
members.
Both
the
``
draft''
AEGLs
and
``
draft''
technical
support
documents
are
reviewed
and
revised
as
necessary
by
the
NAC/
AEGL
Committee
members
prior
to
formal
NAC/
AEGL
Committee
meetings.
Following
deliberations
on
the
AEGL
values
and
the
relevant
data
and
information
for
each
chemical,
the
NAC/
AEGL
Committee
attempts
to
reach
a
consensus.
Once
the
NAC/
AEGL
Committee
reaches
a
consensus,
the
values
are
considered
``
Proposed''
AEGLs.
The
Proposed
AEGL
values
and
the
accompanying
scientific
rationale
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/
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138
/
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July
18,
2003
/
Notices
for
their
development
are
the
subject
of
this
notice.
The
NAC/
AEGL
Committee
publishes
proposed
AEGL
values
and
the
accompanying
scientific
rationale
for
their
development
for
10
hazardous
substances.
These
values
represent
the
sixth
set
of
exposure
levels
proposed
and
published
by
the
NAC/
AEGL
Committee
EPA
published
the
first
``
Proposed''
AEGLs
for
12
chemicals
from
the
initial
priority
list
in
the
Federal
Register
of
October
30,
1997
(
62
FR
58840
 
58851)
(
FRL
 
5737
 
3);
for
10
chemicals
in
the
Federal
Register
of
March
15,
2000
(
65
FR
14186
 
14196)
(
FRL
 
6492
 
4);
for
14
chemicals
in
the
Federal
Register
of
June
23,
2000
(
65
FR
39263
 
39277)
(
FRL
 
659
 
2);
for
7
chemicals
in
the
Federal
Register
of
December
13,
2000
(
65
FR
77866
 
77874)
(
FRL
 
6752
 
5)
for
18
chemicals
in
the
Federal
Register
of
May
2,
2001
(
66
FR
21940
 
21964)
(
FRL
 
6776
 
3);
and
for
8
chemicals
in
the
Federal
Register
of
February
15,
2002
(
67
FR
7164
 
7176)
(
FRL
 
6815
 
8)
in
order
to
provide
an
opportunity
for
public
review
and
comment.
In
developing
the
proposed
AEGL
values,
the
Committee
has
followed
the
methodology
guidance
Guidelines
for
Developing
Community
Emergency
Exposure
Levels
for
Hazardous
Substances,
published
by
the
National
Research
Council
of
the
National
Academy
of
Sciences
(
NAS)
in
1993.
The
term
Community
Emergency
Exposure
Levels
(
CEELS)
is
synonymous
with
AEGLs
in
every
way.
The
NAC/
AEGL
Committee
has
adopted
the
term
Acute
Exposure
Guideline
Levels
to
better
connote
the
broad
application
of
the
values
to
the
population
defined
by
the
NAS
and
addressed
by
the
NAC/
AEGL
Committee.
The
NAC/
AEGL
Committee
invites
public
comment
on
the
proposed
AEGL
values
and
the
scientific
rationale
used
as
the
basis
for
their
development.
Following
public
review
and
comment,
the
NAC/
AEGL
Committee
will
reconvene
to
consider
relevant
comments,
data,
and
information
that
may
have
an
impact
on
the
NAC/
AEGL
Committee's
position
and
will
again
seek
consensus
for
the
establishment
of
Interim
AEGL
values.
Although
the
Interim
AEGL
values
will
be
available
to
Federal,
State,
and
local
agencies
and
to
organizations
in
the
private
sector
as
biological
reference
values,
it
is
intended
to
have
them
reviewed
by
a
subcommittee
of
the
NAS.
The
NAS
subcommittee
will
serve
as
a
peer
review
of
the
Interim
AEGLs
and
as
the
final
arbiter
in
the
resolution
of
issues
regarding
the
AEGL
values,
and
the
data
and
basic
methodology
used
for
setting
AEGLs.
Following
concurrence,
``
Final''
AEGL
values
will
be
published
under
the
auspices
of
the
NAS.

D.
Use
of
Human
Data
The
NAC/
AEGL
Program
is
working
to
ensure
that
emergency
responders
and
risk
managers
in
this
country
and
abroad
are
armed
with
vital
information
they
need
to
protect
the
public
and
themselves
from
harm
in
the
event
of
chemical
accidents
or
homeland
security
emergencies.
Because
of
the
serious
nature
of
chemical
emergency
situations,
it
is
essential
that
involved
personnel
have
access
to
the
most
comprehensive
and
realistic
assessments
of
human
health
hazards
posed
by
released
chemicals.
Under
estimation
of
human
health
hazard
would
not
be
protective,
while
over
estimation
might
suggest
a
larger
than
necessary
response
zone.
The
Department
of
Army
and
Federal
Emergency
Management
Agency
Chemical
Stockpile
Emergency
Preparedness
Program
(
CSEPP),
for
example,
has
adopted,
as
outlined
in
CSEPP
Policy
Paper
Number
20,
AEGLs
for
sulfur
mustard
and
nerve
agents
for
use
in
CSEPP
community
emergency
planning
and
response
activities
``
to
prevent
or
minimize
exposures
above
AEGL­
2,
above
which
some
temporary
but
potentially
escape­
impairing
effects
could
occur.''
Thus,
with
the
application
of
the
procedures
discussed
in
this
unit,
the
AEGL
Program
recognizes
the
importance
of
considering
all
available
domestic
and
international
test
data,
both
animal
and
human,
to
determine
threshold
levels
of
harm
for
a
range
of
exposure
scenarios
critical
to
those
at
the
front
line
in
defending
public
health.
The
process
for
development
of
AEGL
values
incorporates
essential
scientific
and
ethical
considerations
posed
by
the
possible
use
of
research
with
human
subjects.
All
human
studies
that
were
used
as
key
or
supporting
evidence
to
derive
AEGL
values
were
judged
acceptable
for
use
according
to
ethical
considerations
detailed
in
the
Standing
Operating
Procedures
for
Developing
Acute
Exposure
Guideline
Levels
for
Hazardous
Substances,
Subcommittee
on
Acute
Exposure
Guideline
Levels,
National
Research
Council,
National
Academy
Press,
2001,
p.
53.
The
SOP
states
``
The
NAC/
AEGL
Committee
is
dependent
upon
existing
clinical,
epidemiologic,
and
case
report
studies
published
in
the
literature
for
data
on
humans.
Many
of
these
studies
do
not
necessarily
follow
current
guidelines
on
ethical
standards
that
require
effective,
documented,
informed
consent
from
participating
human
subjects.
Further,
recent
studies
that
followed
such
guidelines
may
not
include
that
fact
in
the
publication.
Although
human
data
may
be
important
in
deriving
AEGL
values
that
protect
the
general
public,
utmost
care
must
be
exercised
to
ensure
first
of
all
that
such
data
have
been
developed
in
accordance
with
ethical
standards.
No
data
on
humans
known
to
be
obtained
through
force,
coercion,
misrepresentation,
or
any
other
such
means
will
be
used
in
the
development
of
AEGLs.
The
NAC/
AEGL
Committee
will
use
its
best
judgment
to
determine
whether
the
human
studies
were
ethically
conducted
and
whether
the
human
subjects
were
likely
to
have
provided
their
informed
consent.
Additionally,
human
data
from
epidemiologic
studies
and
chemical
accidents
may
be
used.
However,
in
all
instances
described
here,
only
human
data,
documents,
and
records
will
be
used
from
sources
that
are
publicly
available
or
if
the
information
is
recorded
by
the
investigator
in
such
a
manner
that
subjects
cannot
be
identified
directly
or
indirectly.
These
restrictions
on
the
use
of
human
data
are
consistent
with
the
`
Common
Rule'
published
in
the
Code
of
Federal
Regulations
(
Protection
of
Human
Subjects,
40
CFR
26,
2000).''
Additionally,
EPA
has
recently
asked
the
NAC/
AEGL
Committee
to
add
an
explicit
documentation
step
early
in
the
AEGL
development
process
that
the
studies
proposed
for
consideration
have
been
consistent
with
the
Program's
Standing
Operating
Procedures
(
SOPs).

III.
List
of
Chemicals
On
behalf
of
the
NAC/
AEGL
Committee,
EPA
is
providing
an
opportunity
for
public
comment
on
the
AEGLs
for
the
10
chemicals
identified
in
Table
1
of
this
unit.

A.
Proposed
AEGL
Chemical
Table
TABLE
1.
 
10
CHEMICALS
FOR
PROPOSED
AEGLS
CAS
No.
Chemical
name
75
 
86
 
5
Acetone
cyanohydrin
7664
 
41
 
7
Ammonia
7726
 
95
 
6
Bromine
79
 
11
 
8
Chloroacetic
acid
7782
 
41
 
4
Fluorine
70892
 
10
 
3
Jet
Fuel
8
78
 
93
 
3
Methyl
ethyl
ketone
10025
 
87
 
3
Phosphorus
oxychloride
7719
 
12
 
2
Phosphorus
trichloride
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Vol.
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Friday,
July
18,
2003
/
Notices
TABLE
1.
 
10
CHEMICALS
FOR
PROPOSED
AEGLS
 
Continued
CAS
No.
Chemical
name
1330
 
20
 
7
Xylenes
B.
Executive
Summaries
The
following
are
executive
summaries
from
the
chemical
specific
technical
support
documents
(
which
may
be
obtained
as
described
in
Unit
I.
B.
and
III.)
that
support
the
NAC/
AEGL
Committee's
development
of
AEGL
values
for
each
chemical
substance.
This
information
provides
the
following
information:
A
general
description
of
each
chemical,
including
its
properties
and
principle
uses;
a
summary
of
the
rationale
supporting
the
AEGL­
1,
2,
and
3
concentration
levels;
a
summary
table
of
the
AEGL
values;
and
a
listing
of
key
references
that
were
used
to
develop
the
AEGL
values.
More
extensive
toxicological
information
and
additional
references
for
each
chemical
may
be
found
in
the
complete
technical
support
documents.
Risk
managers
may
be
interested
to
review
the
complete
technical
support
document
for
a
chemical
when
deciding
issues
related
to
use
of
the
AEGL
values
within
various
programs.
1.
Acetone
cyanohydrin
 
i.
Description.
Acetone
cyanohydrin
is
a
colorless
to
yellowish
liquid
with
a
characteristic
bitter
almond
odor
due
to
the
presence
of
free
HCN.
The
major
use
of
acetone
cyanohydrin
is
in
the
production
of
a­
methacrylic
acid
and
its
esters;
the
latter
are
used
for
the
production
of
plexiglass.
Further
uses
of
acetone
cyanohydrin
are
in
the
production
of
acrylic
esters,
polyacrylic
plastics,
and
synthetic
resins
as
well
as
in
the
manufacture
of
insecticides,
pharmaceuticals,
fragances,
and
perfumes.
Acetone
cyanohydrin
decomposes
spontaneously
to
acetone
and
hydrogen
cyanide;
this
process
is
catalyzed
by
heat
and
contact
with
water
(
especially
under
alkaline
conditions).
Fatal
cases
and
life­
threatening
poisonings
in
workers
have
been
described
after
accidental
inhalation,
skin
contact,
and
oral
uptake.
Initial
symptoms
following
mild
exposure
to
acetone
cyanohydrin
are
predominantly
cardiac
palpitation,
headache,
weakness,
dizziness,
nausea,
vomiting,
and
nose,
eye,
throat,
and
skin
irritation.
The
systemic
toxicity
of
acetone
cyanohydrin
is
caused
by
free
cyanide
ions
and
is
primarily
due
to
complex
formation
with
the
iron
moiety
in
the
tissue
enzyme
ferri
cytochrome
c
oxidase
or
cytochrome
a3.
The
blockage
of
the
electron
transport
system
of
mitochondria
results
in
inhibition
of
oxygen
utilization
and
causes
tissue
hypoxia
and
cellular
and
tissue
destruction.
Four
studies
exposed
rats
repeatedly
to
acetone
cyanohydrin
concentrations
of
about
10,
30,
and
60
ppm
for
6
hours/
day,
5
days/
week
for
a
total
of
4
weeks
(
Monsanto
Co.,
1986a;
using
groups
of
10
male
and
10
female
rats),
10
weeks
(
Monsanto
Co.,
1982b;
using
groups
of
15
male
rats)
and
14
weeks
(
Monsanto
Co.,
1986b;
using
groups
of
15
male
and
15
female
rats)
or
for
6
hours/
day
for
21
days
(
Monsanto
Co.,
1982c;
using
groups
of
15
female
rats).
Death
was
observed
at
60
ppm
after
the
first
exposure
in
3
animals
of
the
Monsanto
Co.
(
1986a)
study,
but
not
in
subsequent
exposures
or
in
the
other
studies
at
a
similar
exposure
concentration.
Preceding
death,
respiratory
distress,
prostration,
convulsions,
and
tremors
were
observed.
In
all
studies,
exposure
to
60
and
30
ppm
caused
signs
of
irritation
(
red
nasal
discharge,
clear
nasal
discharge,
perioral
wetness,
encrustations)
during
the
first
and
subsequent
weeks
of
exposure.
At
10
ppm,
red
nasal
discharge
was
not
observed
in
one
study
(
Monsanto
Co.,
1986a);
its
incidence
was
not
increased
compared
to
control
group
in
two
studies
(
Monsanto
Co.,
1982b;
1982c)
and
increased
compared
to
the
control
group
in
the
fourth
study
(
Monsanto
Co.,
1986b).
No
other
effects
were
reported
in
these
four
studies.
The
AEGL­
1
was
based
on
a
repeated
exposure
study
in
rats
in
which
a
concentration
of
9.2
ppm
for
6
hours/
day,
5
days/
week
for
4
weeks
did
not
result
in
red
nasal
discharge
(
Monsanto
Co.,
1986a).
An
uncertainty
factor
of
3
was
applied
for
interspecies
variability
because
the
lowest­
observed­
effect­
level
(
LOEL)
for
irritation
in
humans
exposed
to
cyanide
at
the
workplace
is
about
6
 
10
ppm
cyanide
(
El
Ghawabi
et
al.,
1975),
which
is
a
factor
of
about
3
below
the
irritation
threshold
of
acetone
cyanohydrin
in
rats
(
about
30
ppm)
and
because
a
multiple
exposure
study
was
used
for
the
derivation
of
AEGL
values.
An
uncertainty
factor
of
3
was
applied
for
intraspecies
variability
because
decomposition
of
acetone
cyanohydrin
does
not
involve
enzyme­
catalyzed
steps
and
the
binding
to
evolutionary
conservative
iron­
containing
proteins/
enzymes,
i.
e.,
the
target
protein
cytochrome
c
oxidase,
is
unlikely
to
differ
substantially
between
individuals.
A
modifying
factor
of
2
was
applied
due
to
the
lack
of
more
adequate
and
supporting
data
for
the
derivation
of
AEGL­
1
values.
The
exposure
durationspecific
values
were
derived
by
time
scaling
according
to
the
dose­
response
regression
equation
Cn
x
t
=
k,
using
the
default
of
n
=
3
for
shorter
exposure
periods
and
n
=
1
for
longer
exposure
periods,
due
to
the
lack
of
suitable
experimental
data
for
deriving
the
concentration
exponent.
For
the
10­
minute
AEGL­
1
the
30­
minute
value
was
applied
because
the
derivation
of
AEGL
values
was
based
on
a
long
experimental
exposure
period
and
no
supporting
studies
using
short­
exposure
periods
were
available
for
characterizing
the
concentration­
time­
response
relationship.
The
AEGL­
2
was
based
on
a
repeated
exposure
study
in
rats
in
which
a
concentration
of
29.9
ppm
for
6
hours/
day,
5
days/
week
for
4
weeks
did
not
result
in
respiratory
distress
(
red
nasal
discharge
as
a
sign
of
irritation
was
observed
during
the
first
and
subsequent
weeks
of
exposure)
(
Monsanto
Co.,
1986a).
An
uncertainty
factor
of
3
was
applied
for
interspecies
variability
because
repeated
exposure
of
humans
at
the
workplace
to
cyanide
concentrations
only
about
3­
fold
lower
than
the
lethality
threshold
of
about
60
ppm
acetone
cyanohydrin
in
rats
did
not
lead
to
life­
threatening
or
irreversible
health
effects
and
because
a
multiple
exposure
study
was
used
for
the
derivation
of
AEGL
values.
An
uncertainty
factor
of
3
was
applied
for
intraspecies
variability
because
decomposition
of
acetone
cyanohydrin
does
not
involve
enzyme­
catalyzed
steps
and
the
binding
to
evolutionary
conservative
iron­
containing
proteins/
enzymes,
i.
e.,
the
target
protein
cytochrome
c
oxidase,
is
unlikely
to
differ
substantially
between
individuals.
The
exposure
duration­
specific
values
were
derived
by
time
scaling
according
to
the
dose­
response
regression
equation
Cn
x
t
=
k,
using
the
default
of
n
=
3
for
shorter
exposure
periods
and
n
=
1
for
longer
exposure
periods,
due
to
the
lack
of
suitable
experimental
data
for
deriving
the
concentration
exponent.
For
the
10­
minute
AEGL­
2
the
30­
minute
value
was
applied
because
the
derivation
of
AEGL
values
was
based
on
a
long
experimental
exposure
period
and
no
supporting
studies
using
shortexposure
periods
were
available
for
characterizing
the
concentration­
timeresponse
relationship.
For
the
derivation
of
AEGL­
3
values,
it
was
taken
into
account
that:
a.
Acetone
cyanohydrin
decomposes
spontaneously
into
hydrogen
cyanide
and
acetone,
b.
The
decomposition
of
acetone
cyanohydrin
is
accelerated
by
heat
and
water,

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No.
138
/
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July
18,
2003
/
Notices
c.
The
systemic
toxic
effects
of
acetone
cyanohydrin
are
caused
by
free
cyanide
ions,
and
d.
Hydrogen
cyanide
has
a
far
higher
vapor
pressure
than
acetone
cyanohydrin.
From
these
facts
it
was
concluded
that
with
every
exposure
to
acetone
cyanohydrin
a
concomitant
exposure
to
hydrogen
cyanide
will
occur.
It
therefore
seemed
reasonable
to
apply
the
AEGL­
3
values
(
on
a
ppm
basis)
derived
for
hydrogen
cyanide
to
acetone
cyanohydrin.
This
procedure
is
supported
by
a
close
similarity
of
acetone
cyanohydrin
and
hydrogen
cyanide
regarding
lethal
effects
in
rats
exposed
for
6
hours.
The
proposed
AEGL
values
are
listed
in
Table
2
of
this
unit.

TABLE
2.
 
SUMMARY
TABLE
OF
PROPOSED
AEGL
VALUES
FOR
ACETONE
CYANOHYDRINA
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
1.1
ppm
(
3.9
mg/
m3)
1.1
ppm
(
3.9
mg/
m3)
0.84
ppm
(
2.9
mg/
m3)
0.53
ppm
(
1.9
mg/
m3)
0.35
ppm
(
1.2
mg/
m3)
No
red
nasal
discharge
in
rats
(
Monsanto
Co.,
1986a)

AEGL­
2
(
Disabling)
6.8
ppm
(
24
mg/
m3)
6.8
ppm
(
24
mg/
m3)
5.4
ppm
(
19
mg/
m3)
3.4
ppm
(
12
mg/
m3)
2.2
ppm
(
7.7
mg/
m3)
No
respiratory
distress
in
rats
(
Monsanto
Co.,
1986a)

AEGL­
3
(
Lethal)
27
ppm
(
95
mg/
m3)
21
ppm
(
74
mg/
m3)
15
ppm
(
53
mg/
m3)
8.6
ppm
(
30
mg/
m3)
6.6
ppm
(
23
mg/
m3)
Application
of
AEGL­
3
values
for
hydrogen
cyanide
a
Cutaneous
absorption
may
occur;
direct
skin
contact
with
the
liquid
should
be
avoided;
fatal
intoxications
have
been
reported
upon
skin
contact.

ii.
References.
a.
El
Ghawabi
A.;
M.
Gaafar;
A.
El
Saharta;
S.
H.
Ahmed;
K.
K.
Malash;
and
R.
Fares.
1975.
Chronic
cyanide
exposure:
a
clinical
radioisotope
and
laboratory
study.
British
Journal
of
Industrial
Medicine.
32:
215
 
219.
b.
Monsanto
Co.
1982b.
Male
fertility
study
of
Sprague­
Dawley
rats
exposed
by
inhalation
route
to
acetone
cyanohydrin.
Monsanto
Co.
Report
No.
ML­
82­
144.
Monsanto
Co.,
St.
Louis,
MO,
USA.
c.
Monsanto
Co.
1982c.
Female
fertility
study
of
Sprague­
Dawley
rats
exposed
by
inhalation
route
to
acetone
cyanohydrin.
Monsanto
Co.
Report
No.
ML­
82­
125.
Monsanto
Co.,
St.
Louis,
MO,
USA.
d.
Monsanto
Co.
1986a.
One­
month
inhalation
toxicity
of
acetone
cyanohydrin
in
male
and
female
Sprague­
Dawley
rats
with
cover
letter
dated
04­
25­
86.
Report
No.
BN­
81­
178.
Monsanto
Co.,
St.
Louis,
MO,
USA.
e.
Monsanto
Co.
1986b.
Three­
month
inhalation
toxicity
of
acetone
cyanohydrin
in
male
and
female
Sprague­
Dawley
rats
with
cover
letter
dated
04­
25­
86.
Report
No.
ML­
82­
143.
Monsanto
Co.,
St.
Louis,
MO,
USA.
2.
Ammonia
 
i.
Description.
Ammonia
is
a
colorless,
corrosive,
alkaline
gas
that
has
a
very
pungent
odor.
The
odor
detection
level
ranges
from
5
 
53
ppm.
Ammonia
is
used
as
a
compressed
gas
and
in
aqueous
solutions.
It
also
is
used
as
a
household
cleaning
product,
in
fertilizers,
and
as
a
refrigerant.
Exposures
to
ammonia
occur
as
a
result
of
accidents
during
highway
and
railway
transportation,
by
releases
at
manufacturing
facilities,
and
from
farming
accidents.
Ammonia
is
very
soluble
in
water.
Because
of
its
exothermic
properties,
ammonia
forms
ammonium
hydroxide
and
produces
heat
when
it
contacts
moist
surfaces,
such
as
mucous
membranes.
The
corrosive
and
exothermic
properties
of
ammonia
can
result
in
immediate
damage
(
severe
irritation
and
burns)
to
eyes,
skin,
and
mucous
membranes
of
the
oral
cavity
and
respiratory
tract.
In
addition,
ammonia
is
effectively
scrubbed
in
the
nasopharyngeal
region
of
the
respiratory
tract
because
of
its
high
solubility
in
water.
The
data
for
deriving
AEGL
values
were
obtained
primarily
from
case
studies
of
accident
victims,
experimental
studies
in
humans,
and
experimental
studies
on
lethality
and
irritation
in
animals.
The
case
studies
were
of
limited
use
for
quantitative
evaluation,
but
the
experimental
studies
in
humans
and
animals
contained
quantitative
data
that
would
be
used
for
deriving
AEGL
values.
No
reliable
quantitative
lethality
data
were
available
for
humans
dying
as
a
result
of
exposure
to
ammonia.
One
case
study
reported
the
death
of
an
individual
exposed
to
a
high
but
unknown
concentrations
of
ammonia.
Other
case
studies
also
contained
no
exposure
estimates,
but
showed
that
high
concentrations
of
ammonia
cause
severe
damage
to
the
respiratory
tract,
particularly
in
the
tracheobronchial
and
pulmonary
regions.
Death,
however,
is
most
likely
to
occur
when
damage
causes
pulmonary
edema.
Non­
lethal,
irreversible,
or
long­
term
effects
occur
when
damage
progresses
to
the
tracheobronchial
region,
manifested
by
reduced
performance
on
pulmonary
function
tests,
bronchitis,
bronchiolitis,
emphysema,
and
bronchiectasis.
Nondisabling,
reversible
effects
are
manifested
by
irritation
to
the
eyes,
throat,
and
nasopharyngeal
region
of
the
respiratory
tract.
The
odor
of
ammonia
is
detected
by
humans
at
concentrations
>
5
ppm;
the
odor
is
highly
penetrating
at
50
ppm
(
10
minutes).
Experimental
studies
on
human
volunteers,
showed
that
slight
irritation
may
occur
at
30
ppm
(
10
minutes),
moderate
irritation
to
the
eyes,
nose,
throat,
and
chest
occurs
at
50
ppm
(
10
minutes
to
2
hours),
moderate
to
highly
intense
irritation
occurs
at
80
ppm
(
30
minutes
to
2
hours),
highly
intense
irritation
occurs
at
110
ppm
(
30
minutes
to
2
hours),
unbearable
irritation
occurs
at
140
ppm
(
30
minutes
to
2
hours),
and
excessive
lacrimation
and
irritation
at
500
ppm.
In
addition,
some
subjects
were
able
to
breathe
140
ppm
for
up
to
2
hours
or
500
ppm
for
30
minutes
without
suffering
long­
lasting
effects.
Reflex
glottis
closure,
a
response
to
irritant
vapors,
occurred
at
570
ppm
for
21­
to
30­
year­
old
subjects,
1,000
ppm
for
60­
year­
old
subjects,
and
1,790
ppm
for
86­
to
90­
year­
old
subjects.
Acute
lethality
studies
in
animals
showed
that
the
LC50
values
for
rats
ranged
from
40,300
ppm
for
a
10­
minute
exposure
to
7,338
and
16,600
ppm
for
60­
minute
exposures.
For
the
mouse,
LC50
values
were
21,430
ppm
for
a
30­
minute
exposure
(
almost
all
animals
died
in
less
than
13
minutes),
10,096
ppm
for
a
10­
minute
exposure,
and
4,230
and
4,837
ppm
for
60­
minute
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Vol.
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No.
138
/
Friday,
July
18,
2003
/
Notices
exposures.
Comparative
data
for
the
same
exposure
duration
show
that
mice
are
more
sensitive
than
rats
to
the
acute
toxic
effects
of
ammonia
(
10
minute
LC50
values
for
mice
and
rats,
are
10,096
ppm
and
40,300
ppm,
respectively).
The
lowest
lethal
concentrations
reported
was
1,000
ppm
for
the
cat.
However,
cats
were
exposed
via
an
endotracheal
tube,
which
probably
exacerbated
the
effects
in
the
tracheobronchial
region
by
bypassing
the
scrubbing
action
of
the
nasopharyngeal
region.
Rats
exposed
by
inhalation
to
lethal
concentrations
of
ammonia,
showed
signs
of
dyspnea,
irritation
to
the
eyes
and
nose,
and
hemorrhage
in
the
lungs.
Mice
exposed
to
lethal
concentrations
of
ammonia
showed
signs
of
irritation
to
the
eyes
and
nose,
along
with
tremors,
ataxia,
convulsions,
seizures,
and
pathologic
lesions
in
the
alveoli.
Cats
exposed
to
the
lowest
lethal
concentration
showed
evidence
of
severe
airway
damage,
bronchopneumonia,
bronchitis,
bronchiolitis,
and
emphysema.
Toxic
effects
at
non­
lethal
concentrations
in
mice
and
rats
consisted
of
mild
effects
on
respiratory
epithelium
of
the
nasal
cavity
(
mice
and
rats),
reduction
in
the
respiratory
rate
(
mice),
and
evidence
of
eye
irritation
(
rat).
The
RD50
(
concentration
causing
a
50%
reduction
in
respiratory
rate)
for
the
mouse
was
300
ppm
for
a
30­
minute
exposure.
The
AEGL
values
for
the
three
toxicity
levels
(
nondisabling,
disabling,
and
lethal)
were
derived
from
both
human
and
animal
data.
The
odor
of
ammonia
is
detected
by
humans
at
concentrations
ranging
from
5
to
53
ppm
and
data
showed
that
it
is
irritating
to
the
upper
respiratory
tract
of
humans
at
30
ppm.
The
AEGL­
1
value
of
25
ppm
is
based
the
concentration
slightly
below
the
lowest
concentration
showing
irritation
in
humans.
An
intraspecies
uncertainty
factor
of
1
was
applied,
because
25
ppm
is
below
the
concentration
causing
irritation;
however,
if
irritation
did
occur,
it
would
be
mild
or
only
slightly
noticeable,
confined
to
the
nasal
cavity
and
eyes
(
ammonia
is
efficiently
scrubbed),
and
would
not
be
expected
to
affect
asthmatic
or
other
sensitive
individuals
to
a
greater
degree
than
nonasthmatic
individuals.
Atopic
and
nonatopic
subjects
did
not
respond
differently
to
a
nasal
exposure
to
ammonia.
The
AEGL­
1
values
are
based
on
human
data;
therefore,
an
interspecies
uncertainty
factor
is
not
applicable.
Because
upper
respiratory
tract
irritation
at
low
ammonia
concentrations
is
not
expected
to
change
or
become
more
severe
with
duration
of
exposure,
except
for
adaptation,
the
same
value
of
25
ppm
is
applied
to
all
AEGL­
1
exposure
durations.
The
AEGL­
2
values
were
based
on
a
study
of
nonexpert
human
subjects
who
had
no
previous
exposure
to
ammonia
and
were
not
familiar
with
effects
of
ammonia.
At
least
one
of
eight
subjects
reported
nuisance
or
offensive
irritation
to
the
eyes
and
throat
during
exposure
to
110
ppm
of
ammonia
for
1
hour
(
Verberk,
1977).
The
effects
reported
were
less
serious
than
those
described
in
the
AEGL­
2
definition,
no
residual
effects
were
reported
after
termination
of
exposure,
and
pulmonary
function
was
not
affected
by
exposure.
At
the
next
highest
concentration,
some
of
the
subjects
reported
the
effects
to
be
unbearable
and
left
the
chamber
between
30
minutes
and
1
hour.
Their
responses
suggest
that
this
concentration
would
impair
escape.
An
intraspecies
uncertainty
factor
of
1
was
used
for
deriving
the
AEGL
2
values
because
the
responses
of
the
non­
expert
group
ranged
from
just
perceptible
to
offensive,
but
the
AEGL­
2
value
was
based
on
the
response
of
the
most
sensitive
individuals.
The
reported
effects
from
this
group
involved
primarily
the
upper
respiratory
tract
and
eyes
and
is
unlikely
to
affect
asthmatics
differently
from
the
most
sensitive
nonexpert
individuals.
In
addition,
atopic
subjects
responded
similarly
to
nonatopic
subjects
to
a
brief
nasal
exposure
to
ammonia,
and
exercising
subjects
showed
only
a
small
equivocal
decrease
in
pulmonary
function.
The
equation
Cn
H
t
=
k,
where
n
=
2,
was
used
to
extrapolate
to
5­,
10­,
and
30­
minute
exposure
durations.
This
equation
was
based
on
mouse
and
rat
lethality
data.
The
same
AEGL­
2
values
were
established
for
1­,
4­,
and
8­
hour
exposures,
because
the
responses
of
the
subjects
exposed
to
110
ppm
of
ammonia
were
similar
after
1­
and
2­
hour
exposures.
The
AEGL­
3
values
were
based
on
LC01
values
of
3,317
and
3,374
ppm
derived
by
probit
analysis
of
mouse
lethality
data
reported
by
Kapeghian
et
al.
(
1982)
and
MacEwen
and
Vernot
(
1972),
respectively.
An
uncertainty
factor
of
3
was
applied
to
account
for
intraspecies
variability
because
at
high
concentrations
of
ammonia,
severe
irritation
is
elicited
immediately
upon
contact
with
the
eyes
and
mucous
membranes
of
the
respiratory
tract
and
the
severity
of
effects
such
as
pulmonary
edema
and
damage
to
the
tracheobronchial
region
would
be
similar
in
asthmatics
and
nonasthmatics
There
is
no
reason
to
apply
a
larger
uncertainty
factor
to
protect
individuals
with
asthma
because
the
severe
damage
to
the
respiratory
tract
would
have
a
greater
and
longer­
lasting
consequence
than
that
of
asthma.
Another
reason
for
not
applying
a
larger
intraspecies
uncertainty
factor
to
protect
children
is
the
evidence
from
one
study
showing
that
a
child
recovered
from
an
accidental
exposure
to
ammonia,
whereas
the
mother
carrying
the
child
suffered
severe
permanent
damage
to
the
lungs.
An
interspecies
uncertainty
factor
or
1
was
applied
to
the
mouse
data,
because
the
mouse
was
the
most
sensitive
species
among
mammals.
In
addition,
applying
a
larger
uncertainty
factor
would
result
in
a
30­
minute
AEGL­
3
value
less
than
the
500
ppm
that
human
can
tolerate
for
30
minutes
without
lethal
or
long­
term
consequences.
The
equation,
Cn
H
t
=
k
(
where
n
=
2)
based
on
mouse
lethality
data,
was
used
to
extrapolate
to
different
exposure
durations
The
proposed
AEGL
values
are
listed
in
Table
3
of
this
unit.

TABLE
3.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
AMMONIA
[
PPM
(
MG/
M3)]

Classification
Exposure
duration
Endpoint
(
Reference)
5­
minutes
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
AEGL­
1
(
Nondisabling)
25
(
17)
25
(
17)
25
(
17)
25
(
17)
25
(
17)
25
(
17)
No­
observed­
adverse­
effectlevel
(
NOAEL)
for
irritation
(
MacEwen
et
al.,
1970);
Verberk,
1977
AEGL­
2
(
Disabling)
380
(
266)
270
(
189)
160
(
112)
110
(
77)
110
(
77)
110
(
77)
Irritation:
Eyes
and
throat;
urge
to
cough
(
Verberk,
1977)

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18JYN1.
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Federal
Register
/
Vol.
68,
No.
138
/
Friday,
July
18,
2003
/
Notices
TABLE
3.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
AMMONIA
[
PPM
(
MG/
M3)]
 
Continued
Classification
Exposure
duration
Endpoint
(
Reference)
5­
minutes
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
AEGL­
3
(
Lethal)
3,800
(
2,657)
2,700
(
1,890)
1,600
(
1,119)
1,100
(
769)
550
(
385)
390
(
273)
Lethality
(
Kapeghian
et
al.,
1982;
MacEwen
and
Vernot,
1972)

ii.
References.
a.
Kapeghian,
J.
C.;
Mincer,
H.
H.;
and
Hones,
A.
B.,
et
al.
1982.
Acute
inhalation
toxicity
of
ammonia
in
mice.
Bulletin
of
Environmental
Contamination
and
Toxicology.
29:
371
 
378.
b.
MacEwen,
J.
D.;
Theodore,
J;
and
Vernot,
E.
H.
1970.
Human
exposure
to
EEL
concentrations
of
monomethylhydrazine,
AMRL­
TR­
70­
102,
Paper
No
23.
Proceedings
of
the
1st
Annual
Conference
on
Environmental
Toxicology.
September
9
 
11,
1970.
Wright­
Patterson
AFB,
OH.
pp.
355
 
363.
c.
MacEwen,
J.
D.
and
Vernot,
E.
H.
1972.
Toxic
Hazards
Research
Unit
Annual
Technical
Report:
1972.
SysteMed
Report
No.
W­
72003,
AMRLTR
72­
62.
Sponsor:
Aerospace
Medical
Research
Laboratory,
Wright­
Patterson
AFB,
OH.
AD­
755­
358.
d.
Verberk,
M.
M.
1977.
Effects
of
ammonia
on
volunteers.
International
Archives
of
Occupational
and
Environmental
Health.
39:
73
 
81.
3.
Bromine
 
i.
Description.
The
halogen
bromine
(
Br2)
is
a
dark
reddishbrown
volatile
liquid
at
room
temperature.
Its
oxidizing
potential
lies
between
that
of
chlorine
and
iodine.
Bromine
is
used
as
a
water
disinfectant,
for
bleaching
fibers
and
silk,
and
in
the
manufacture
of
medicinal
bromine
compounds,
dyestuffs,
flame
retardants,
agricultural
chemicals,
inorganic
bromide
drilling
fluids,
and
gasoline
additives.
Bromine
is
a
skin,
eye,
and
respiratory
tract
irritant.
Inhalation
causes
respiratory
tract
irritation
and
pulmonary
edema.
Although
accidental
human
exposures
have
occurred,
concentrations
were
either
not
reported
or
were
judged
unreliable.
Aside
from
old
and
anecdotal
information,
the
data
base
is
limited
to
one
study
with
human
subjects
and
two
lethality
studies
with
the
mouse
as
the
test
species.
One
of
the
lethality
studies
(
Bitron
and
Aharonson
1978)
provided
data
sufficient
for
derivation
of
the
relationship
between
concentrations
that
result
in
lethality
(
LC50
values)
and
exposure
duration:
C2.2
x
t
=
k.
The
AEGL­
1
was
based
on
exposures
of
20
healthy
human
volunteers
to
concentrations
of
0.1
to
1.0
ppm
for
at
least
30
minutes
(
Rupp
and
Henschler
1967).
Eye
irritation,
but
not
nose
or
throat
irritation,
occurred
during
a
30­
minute
exposure
to
0.1
ppm.
At
concentrations
$
0.5
ppm,
there
was
a
stinging
and
burning
sensation
of
the
conjunctiva.
The
30­
minute
0.1
ppm
was
chosen
as
the
basis
for
the
AEGL­
1.
The
0.1
ppm
concentration
was
divided
by
an
intraspecies
uncertainty
factor
of
3
to
protect
susceptible
individuals.
An
intraspecies
uncertainty
factor
of
3
was
considered
sufficient
because
workers
have
been
occupationally
exposed
to
1
ppm
with
no
symptoms
other
than
``
excess
irritation''
(
Elkins
1959).
Furthermore,
effects
at
this
low
concentration
appear
to
be
limited
to
the
eyes
and
upper
respiratory
tract;
there
was
no
penetration
to
the
lower
respiratory
tract.
The
resulting
30­
minute
AEGL­
1
value
of
0.03
ppm
was
time­
scaled
to
the
other
AEGL
exposure
durations
using
the
C2.2
x
t
=
k
relationship
derived
from
the
mouse
lethality
study.
The
AEGL­
2
was
based
on
the
concentration
of
1
ppm
for
30
minutes
which
the
volunteers
in
the
above
study
(
Rupp
and
Henschler
1967)
found
irritating
(
stinging
and
burning
sensation
of
the
conjunctiva;
nose
and
throat
irritation).
The
30­
minute
1
ppm
value
was
divided
by
an
intraspecies
uncertainty
factor
of
3
to
protect
susceptible
individuals
and
time
scaled
to
the
other
AEGL­
2
exposure
durations
using
the
concentration­
exposure
duration
relationship
from
the
mouse
lethality
study
of
C2.2
x
t
=
k.
An
intraspecies
uncertainty
factor
of
3
was
considered
sufficient
as
the
symptoms
may
be
below
those
defining
an
AEGL­
2.
However,
no
reliable
studies
with
exposures
to
higher
concentrations
were
located.
Both
lethality
studies
with
the
mouse
described
the
inhalation
toxicity
of
chlorine
and
bromine.
However,
both
studies
reported
lower
LC50
values
for
chlorine
than
those
reported
in
more
recent
well­
conducted
studies.
Nevertheless,
the
study
that
reported
the
lower
lethal
concentrations
for
chlorine
was
used
for
derivation
of
the
AEGL­
3
values
for
bromine
(
Schlagbauer
and
Henschler
1967).
The
data
in
this
study
showed
a
clear
concentration­
response
relationship;
the
exposure
duration
was
30
minutes.
Using
probit
analysis,
a
30­
minute
LC50
value
of
204
ppm
and
a
30­
minute
LC01
of
116
ppm
were
calculated.
The
30­
minute
LC01
of
116
ppm
was
used
as
the
basis
for
calculation
of
AEGL­
3
values.
The
116
ppm
LC01
was
divided
by
a
combined
uncertainty
factor
of
10
(
3
for
interspecies
differences
[
the
mouse
was
the
most
sensitive
species
for
lethal
effects
in
tests
with
other
halogens]
and
3
for
intraspecies
differences
[
at
high
concentrations
bromine
is
corrosive
to
the
mucous
membranes
of
the
respiratory
system;
effects
are
not
expected
to
differ
greatly
among
individuals])
and
scaled
across
time
using
the
relationship
C2.2
x
t
=
k,
derived
from
the
same
study.
The
proposed
AEGL
values
are
listed
in
Table
4
of
this
unit.

TABLE
4.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
BROMINE
[
PPM
(
MG/
M3)]

Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
0.055
(
0.36)
0.033
(
0.22)
0.024
(
0.16)
0.013
(
0.09)
0.0095
(
0.06)
Rupp
and
Henschler
1967
AEGL­
2
(
Disabling)
0.55
(
3.6)
0.33
(
2.1)
0.24
(
1.6)
0.13
(
0.85)
0.095
(
0.62)
Rupp
and
Henschler
1967
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18JYN1.
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18JYN1
42718
Federal
Register
/
Vol.
68,
No.
138
/
Friday,
July
18,
2003
/
Notices
TABLE
4.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
BROMINE
[
PPM
(
MG/
M3)]
 
Continued
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
3
(
Lethal)
19
(
124)
12
(
78)
8.5
(
55)
4.5
(
29)
3.2
(
21)
Schlagbauer
and
Henschler
1967
ii.
References.
a.
Bitron,
M.
D.
and
E.
F.
Aharonson.
1978.
Delayed
mortality
of
mice
following
inhalation
of
acute
doses
of
CH2,
SO2,
Cl2,
and
Br2.
American
Industrial
Hygiene
Association
Journal.
39:
129
 
138.
b.
Elkins,
H.
B.
1959.
Inorganic
compounds:
Bromine.
Chemistry
of
Industrial
Toxicology.
John
Wiley
&
Sons,
New
York.
p.
89.
c.
Rupp,
H.
and
D.
Henschler.
1967.
Effects
of
low
chlorine
and
bromine
concentrations
in
man.
Internationales
Archiv
fuer
Gewerbepathologie
und
Gewerbehygiene.
23:
79
 
90.
d.
Schlagbauer,
M.
and
D.
Henschler.
1967.
Inhalation
toxicity
of
chlorine
and
bromine
with
single
and
repeated
exposures.
Internationales
Archiv
fuer
Gewerbepathologie
und
Gewerbehygiene.
23:
91
 
98.
4.
Chloroacetic
acid
 
i.
Description.
Monochloroacetic
acid
(
MCAA)
is
a
colorless
crystalline
material,
which
is
highly
soluble
in
water
and
soluble
in
organic
solvents.
Its
vapor
pressure
at
room
temperature
is
moderate
with
reported
values
between
0.2
hPa
(
crystalline
substance)
and
10
hPa
(
solution
in
water).
MCAA
has
a
pungent
odor.
MCAA
is
produced
by
chlorination
of
acetic
acid
or
hydrolysis
of
trichloroethene
using
sulfuric
acid.
The
world
production
capacity
was
estimated
at
362,500
tons/
year
in
1987.
MCAA
or
its
sodium
salt,
sodium
monochloroacetate,
are
used
primarily
in
the
industrial
production
of
carboxymethylcellulose,
herbicides,
thioglycolic
acid
as
well
as
in
the
production
plastics,
pharmaceuticals,
flavors,
cosmetics,
and
other
organic
chemicals.
MCAA
is
an
acid
(
pKa
2.85)
and
therefore
can
cause
eye
and
skin
irritation
upon
contact
with
a
diluted
MCAA
solution
and
skin
corrosion
and
conjunctival
burns
upon
contact
with
more
concentrated
solutions.
The
systemic
toxicity
of
MCAA
is
caused
by
inhibition
of
enzymes
of
the
glycolytic
pathway
and
the
tricarboxylic
acid
cycle.
This
metabolic
blockage
damages
organs
with
a
high
energy­
demand,
such
as
heart,
central
nervous
system
(
CNS),
and
muscles,
and
leads
to
metabolic
acidosis
due
to
the
accumulation
of
lactic
acid
and
citric
acid
in
the
body.
No
studies
are
available
reporting
severe
toxic
effects
in
humans
after
inhalation
exposure
to
MCAA.
Mortality
was
reported
in
a
child
after
oral
uptake
of
5
 
6
ml
of
an
80%
MCAA
solution
(
Rogers,
1995).
Several
lethal
accidents
have
been
reported,
in
which
workers
were
dermally
exposed
to
hot,
liquid
MCAA.
An
inadequately
described
study
reported
an
irritation
threshold
of
1.48
ppm
(
Maksimov
and
Dubinina,
1974);
no
respiratory
tract
irritation,
effects
on
lung
function
parameters
or
irritation
of
skin
and
mucous
membranes
were
reported
for
>
33
workers
potentially
exposed
to
MCAA
concentrations
between
<
0.13
ppm
for
3
hours
and
0.31
ppm
for
7
hours
(
Clariant
GmbH,
2000).
The
only
animal
study
reporting
lethal
effects
after
inhalation
exposure
was
an
inadequately
described
study
in
which
a
LC50
of
46.8
ppm
for
4
hours
was
reported
for
rats
(
Maksimov
and
Dubinina,
1974).
Several
studies
report
lethal
effects
after
oral
exposure
with
LD50
values
mostly
between
50
 
200
mg/
kilogram
(
kg)
for
rats,
mice
and
guinea
pigs.
In
a
single
inhalation
experiment
on
rats,
eye
squint
and
slight
lethargy
were
observed
during
exposure
to
an
analytical
concentration
of
66
ppm
for
1
hour
(
Dow
Chemical
Co.,
1987).
In
an
inadequately
reported
study,
an
irritation
threshold
in
rats
of
6.16
ppm
and
a
no­
observed­
effect­
level
(
NOEL)
for
histological
changes
in
the
respiratory
tract
in
rats
and
guinea
pigs
of
1.5
ppm
after
4
months
have
been
reported
(
Maksimov
and
Dubinina,
1974).
No
relevant
studies
of
adequate
quality
were
available
for
the
derivation
of
the
AEGL­
1.
Therefore,
due
to
insufficient
data,
AEGL­
1
values
were
not
derived.
The
AEGL­
2
was
based
on
a
single
inhalation
study
in
rats
(
Dow
Chemical
Co.,
1987)
in
which
eye
squint
and
lethargy
were
observed
in
rats
exposure
to
66
ppm
for
1
hour.
A
total
uncertainty
factor
of
10
was
used.
A
factor
of
3
was
applied
for
interspecies
variability
because
the
effect
level
was
considered
below
that
of
an
AEGL­
2
and
because
the
available
data
do
not
point
at
a
large
interspecies
variability
for
more
severe
(
lethal)
effects.
A
factor
of
3
was
applied
for
intraspecies
variability
because
a
higher
factor
was
not
considered
adequate
on
the
basis
of
a
comparison
with
human
data
for
oral
exposure.
The
other
exposure
durationspecific
values
were
derived
by
time
scaling
according
to
the
dose­
response
regression
equation
Cn
x
t
=
k,
using
the
default
of
n
=
3
for
shorter
exposure
periods
and
n=
1
for
longer
exposure
periods,
due
to
the
lack
of
suitable
experimental
data
for
deriving
the
concentration
exponent.
No
relevant
studies
of
adequate
quality
were
available
for
the
derivation
of
the
AEGL­
3
value.
Therefore,
due
to
insufficient
data
and
the
uncertainties
of
a
route­
to­
route
extrapolation,
AEGL­
3
values
were
not
derived.
The
proposed
AEGL
values
are
listed
in
Table
5
of
this
unit.

TABLE
5.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
MONOCHLOROACETIC
ACID
A
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
Insufficient
data
(
I.
D.)
I.
D.
I.
D.
I.
D.
I.
D.
I.
D.

AEGL­
2
(
Disabling)
12
ppm
(
47
mg/
m3)
8.3
ppm
(
33
mg/
m3)
6.6
ppm
(
26
mg/
m3)
1.7
ppm
(
6.7
mg/
m3)
0.83
ppm
(
3.3
mg/
m3)
Eye
squint
and
lethargy
in
rats
(
Dow
Chemical
Co.,
1987)

AEGL­
3
(
Lethal)
I.
D.
I.
D.
I.
D.
I.
D.
I.
D.
I.
D.

a
Skin
contact
with
molten
MCAA
or
MCAA
solutions
should
be
avoided;
dermal
penetration
is
rapid
and
fatal
intoxications
have
been
observed
when
10%
or
more
of
the
body
surface
was
involved.

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18,
2003
/
Notices
ii.
References.
a.
Clariant
GmbH,
2000.
Unpublished.
Letter
of
Dr.
Kreiling
dated
23.08.2000.
Dow
Chemical
Co.,
1987.
Monochloroacetic
acid:
an
acute
vapor
inhalation
limit
study
with
Fischer
344
rats.
Unpublished
Report,
Dow
Chemical
Company,
Midland,
USA.
b.
Maksimov,
G.
G.
and
O.
N.
Dubinina,
1974.
Materials
of
experimental
substantiation
of
maximally
permissible
concentration
of
monochloroacetic
acid
in
the
air
of
production
area.
Gigiena
Truda
i
Professional
nye
Zabolevarija.
9:
32
 
35.
c.
Rogers
D.
R.
1995.
Accidental
fatal
monochloroacetic
acid
poisoning.
American
Journal
of
Forensic
Medicine
and
Pathology.
16:
115
 
116.
5.
Fluorine
 
i.
Description.
Fluorine
is
a
reactive,
highly
irritating
and
corrosive
gas
used
in
the
nuclear
energy
industry,
as
an
oxidizer
of
liquid
rocket
fuels,
and
in
the
manufacture
of
various
fluorides
and
fluorocarbons.
Fluorine
is
a
severe
irritant
to
the
eyes,
mucous
membranes,
lungs,
and
skin;
the
eyes
and
the
respiratory
tract
are
the
target
organ/
tissues
of
an
acute
inhalation
exposure.
Death
is
due
to
pulmonary
edema.
Data
on
irritant
effects
in
humans
and
lethal
and
sublethal
effects
in
five
species
of
mammals
(
dog,
rat,
mouse,
guinea
pig,
and
rabbit)
were
available
for
development
of
AEGL
values.
Regression
analyses
of
the
concentration­
exposure
durations
(
for
the
fixed
endpoint
of
mortality)
for
all
of
the
animal
species
reported
in
the
key
study
(
Keplinger
and
Suissa
1968)
determined
that
the
relationship
between
concentration
and
time
is
Cn
x
t
=
k,
where
n
=
approximately
2
(
actual
value
of
n
for
the
most
sensitive
species
in
irritation
and
lethality
studies,
the
mouse,
is
1.77).
This
concentration
exposure
duration
relationship
was
applied
both
the
AEGL­
2
and
AEGL­
3
levels
because
the
irritant
and
corrosive
action
of
fluorine
on
the
respiratory
tissues
differs
by
only
a
matter
of
degree
for
these
AEGL
levels:
a.
Respiratory
irritation
with
edema
resulting
in
mild,
reversible
lung
congestion,
and
b.
Severe
respiratory
irritation
resulting
in
severe
lung
congestion.
Although
the
data
base
for
fluorine
is
small,
the
data
from
the
key
study,
augmented
with
data
from
several
other
studies,
were
considered
adequate
for
derivation
of
the
three
AEGL
classifications
for
four
time
periods.
The
AEGL­
1
was
based
on
the
observation
that
human
volunteers
could
tolerate
exposure
to
10
ppm
for
15
minutes
without
irritant
effects
(
Keplinger
and
Suissa
1968).
Although
this
value
is
below
the
definition
of
an
AEGL­
1
(
notable
discomfort),
it
provides
the
longest
exposure
duration
for
which
no
irritation
in
humans
was
reported.
An
intraspecies
uncertainty
factor
of
3
was
applied
because
fluorine
is
highly
corrosive
to
the
tissues
of
the
respiratory
tract
and
effects
are
not
expected
to
vary
greatly
among
individuals,
including
susceptible
individuals.
Although
no
data
on
asthmatics
were
found,
the
uncertainty
factor
of
3
was
considered
adequate
to
protect
this
sensitive
subpopulation
because
the
value
was
a
NOAEL
and
because
shorter­
term,
repeated
exposures
produced
no
substantially
greater
effects
in
healthy
individuals.
The
value
is
supported
by
a
second
study
in
which
volunteers
``
tolerated''
exposure
to
10
ppm
for
an
undefined
period
of
time.
Furthermore,
occupational
exposure
concentrations
for
healthy
adults
have
ranged
up
to
17
ppm,
albeit
for
short,
undefined
periods
of
time
(
Lyon
1962).
A
modifying
factor
of
2
was
applied
based
on
a
limited
data
base.
The
resulting
value
of
1.7
ppm
was
used
across
all
AEGL­
1
exposure
durations
because
at
mildly
irritating
concentrations
there
is
accommodation
to
irritating
gases.
As
noted,
this
value
is
supported
by
limited
workplace
monitoring
data:
Workers
exposed
to
fluorine
at
average
yearly
concentrations
up
to
1.2
ppm
(
range,
0.0
 
17
ppm)
over
a
4­
year
period
reported
fewer
incidences
of
respiratory
complaints
or
diseases
than
a
similar
group
of
nonexposed
workers
(
Lyon
1962).
The
workers
are
assumed
to
encompass
a
small
range
of
sensitivity;
the
additional
intraspecies
uncertainty
factor
of
3
was
considered
sufficient
to
protect
sensitive
individuals.
Mild
lung
congestion
was
selected
as
the
threshold
for
irreversible,
longlasting
effects
as
defined
by
the
AEGL­
2.
The
AEGL­
2
was
based
on
an
animal
study
in
which
mild
lung
congestion
was
observed
in
mice
at
67
ppm
for
30
minutes
and
30
ppm
for
60
minutes
(
Keplinger
and
Suissa
1968).
Effects
were
slightly
less
serious
in
three
other
species.
Although
concentrations
causing
irritant
effects
or
lethality
for
three
other
species
for
the
same
time
periods
suggested
similar
species
sensitivity,
the
mouse
data,
because
of
slightly
lower
values,
were
chosen
as
the
basis
for
developing
the
AEGL­
2
and
AEGL­
3.
Because
similar
sensitivity
was
observed
among
five
species
in
the
key
study,
no
uncertainty
factor
for
interspecies
variability
was
applied.
Fluorine
is
a
highly
corrosive
gas
that
reacts
directly
with
the
tissues
of
the
respiratory
tract,
with
no
pharmacokinetic
component
involved
in
the
toxicity;
therefore,
there
is
likely
to
be
little
difference
among
individuals
in
response
to
fluorine
at
concentrations
that
define
the
AEGL­
2.
The
30­
and
60­
minute
values
for
the
mouse
were
divided
by
an
intraspecies
uncertainty
factor
of
3
to
protect
sensitive
individuals,
since
effects
are
not
likely
to
differ
greatly
among
individuals,
and
by
a
modifying
factor
of
2,
based
on
a
limited
data
base.
The
30­
minute
value
was
used
for
the
10­
and
30­
minute
AEGL­
2
and
the
60­
minute
value
was
used
for
the
60­
minute
AEGL­
2.
The
4­
hour
AEGL­
2
value
was
scaled
from
the
60­
minute
value
based
on
the
C1.77
x
t
=
k
relationship.
The
value
of
n
was
derived
from
regression
analysis
of
the
mouse
lethality
data
in
the
key
study.
The
8­
hour­
AEGL­
2
value
was
set
equal
to
the
4­
hour
value
because
at
low
concentrations
the
hygroscopic
fluorine
would
react
with
and/
or
be
scrubbed
by
the
nasal
passages
and
because
at
low
concentrations
there
is
accommodation
to
irritant
gases.
The
10­
and
3­
minute
AEGL­
2
values
are
supported
by
studies
in
which
human
volunteers
found
shortterm
exposures
to
15
 
25
ppm
irritating
to
the
eyes,
nose,
and
throat
(
Rickey
1959;
Keplinger
and
Suissa
1968).
The
AEGL­
3
values
were
derived
from
the
highest
exposures
that
resulted
in
no
deaths
in
five
species
over
four
exposure
durations
(
13
tests)
for
up
to
45
days
post
exposure,
but
did
produce
severe
lung
congestion
in
the
mouse
(
Keplinger
and
Suissa
1968).
Severe
lung
congestion
in
the
sensitive
mouse
was
considered
the
threshold
for
lethality
as
defined
by
the
AEGL­
3.
For
the
mouse,
the
60­
minute
value
was
75
ppm.
Because
of
the
similar
species
sensitivity
in
the
key
study,
based
on
both
irritant
effects
and
lethality,
no
uncertainty
factor
for
interspecies
variability
was
applied.
The
values
were
divided
by
an
uncertainty
factor
of
3
to
protect
sensitive
individuals
(
fluorine
is
a
highly
reactive,
corrosive
gas
whose
effect
on
respiratory
tract
tissues
is
not
expected
to
differ
greatly
among
individuals)
and
by
a
modifying
factor
of
2,
based
on
a
limited
data
base.
Using
the
60­
minute
value
of
75
ppm,
AEGL­
3
values
for
the
other
exposure
times
were
calculated
based
on
the
C1.77
x
t
=
k
relationship.
The
value
of
n
was
derived
from
regression
analysis
of
the
mouse
lethality
data
in
the
key
study.
The
8­
hour
value
was
set
equal
to
the
4­
hour
value
because
fluorine
would
react
with
or
be
scrubbed
by
the
nasal
passages
at
fairly
low
concentrations.
The
safety
of
setting
the
8­
hour
value
equal
to
the
4­
hour
value
is
supported
by
another
study
in
which
a
7­
hour
experimental
exposure
concentrations
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18,
2003
/
Notices
resulting
in
an
overall
60%
mortality
for
four
species
(
Eriksen
1945;
Stokinger
1949)
is
higher
than
the
extrapolated
7­
hour
values
for
the
mouse
and
rat
based
on
the
Keplinger
and
Suissa
study.
The
proposed
AEGL
values
are
listed
in
Table
6
of
this
unit.

TABLE
6.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
FLUORINE
[
PPM
(
MG/
M3)]

Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1a,
b
(
Nondisabling)
1.7
(
2.6)
1.7
(
2.6)
1.7
(
2.6)
1.7
(
2.6)
1.7
(
2.6)
No
irritant
effects
 
humans
(
Keplinger
and
Suissa
1968)

AEGL­
2
(
Disabling)
20
(
31)
11
(
17)
5.0
(
7.8)
2.3
(
3.6)
2.3
(
3.6)
Mild
lung
congestion
 
mice
(
Keplinger
and
Suissa
1968)

AEGL­
3c
(
Lethal)
36
(
56)
19
(
29)
13
(
20)
5.7
(
8.8)
5.7
(
8.8)
Severe
lung
congestion
 
mice
(
Keplinger
and
Suissa
1968)

aThe
characteristic,
pungent
odor
of
fluorine
will
be
noticeable
at
this
concentration.
bThe
same
value
was
used
across
all
time
periods
because
at
low
concentrations
there
is
accommodation
to
irritant
gases.
c30­
Minute
and
1­
hour
values
are
based
on
separate
data
points.

ii.
References.
a.
Eriksen,
N.
1945.
A
Study
of
the
Lethal
Effect
of
the
Inhalation
of
Gaseous
Fluorine
(
F2)
at
Concentrations
from
100
ppm
to
10,000
ppm.
DOE/
EV/
03490­
T3,
United
States
Atomic
Energy
Commission.
Pharmacology
Report
435.
University
of
Rochester,
Rochester,
NY.
b.
Keplinger,
M.
L.
and
L.
W.
Suissa.
1968.
Toxicity
of
fluorine
short­
term
inhalation.
American
Industrial
Hygiene
Association
Journal.
29:
10
 
18.
c.
Lyon,
J.
S.
1962.
Observations
on
personnel
working
with
fluorine
at
a
gaseous
diffusion
plant.
Journal
of
Occupational
Medicine.
4:
199
 
201.
d.
Rickey,
R.
P.
1959.
Decontamination
of
Large
Liquid
Fluorine
Spills.
AFFTCTR
59­
31,
U.
S.
Air
Force,
Air
Research
and
Development
Command,
Air
Force
Flight
Test
Center,
Edwards
Air
Force
Base,
CA;
AD­
228
 
033,
Defense
Technical
Information
Center,
Ft.
Belvoir,
VA.
e.
Stokinger,
H.
E.
1949.
Toxicity
following
inhalation
of
fluorine
and
hydrogen
fluoride,
Chapter
17.
Pharmacology
and
Toxicology
of
Uranium
Compounds.
C.
Voegtlin
and
H.
C.
Hodge,
eds.
McGraw­
Hill
Book
Company,
New
York.
6.
Jet
Fuel
8
 
i.
Description.
Jet
propellant
(
JP)
fuels,
used
in
military
and
civilian
aircraft,
are
complex
mixtures
of
aliphatic
and
aromatic
hydrocarbons
made
by
blending
various
distillate
stocks
of
petroleum.
The
primary
military
fuel
for
land­
based
military
aircraft
is
JP­
8;
JP­
5
was
developed
by
the
U.
S.
Navy
for
shipboard
service.
The
composition
of
these
two
fuels
is
basically
that
of
kerosene
(
with
additives)
and
they
have
similar
chemical
and
physical
characteristics.
Worldwide,
approximately
60
billion
gallons
of
military
JP­
8
and
the
equivalent
commercial
Jet
A
and
Jet
A­
1
are
consumed
on
an
annual
basis.
The
military
jet
fuels
contain
additives
that
are
not
contained
in
commercial
jet
fuels.
Civilian
and
military
personnel
may
be
exposed
to
jet
fuels
during
fuel
production,
aircraft
fueling
operations,
aircraft
maintenance
operations,
and
accidental
spills
or
pipeline
leaks.
Although
several
jet
fuels
are
discussed
in
this
document
(
JP­
4,
JP­
5,
JP­
7,
and
JP­
8),
the
discussion
focuses
on
the
toxicity
of
JP­
8
with
some
attention
to
the
chemically
similar
JP­
5.
These
two
fuels
have
a
similar
composition
and
appear
to
have
similar
toxicities.
Monitoring
data
indicate
that
exposures
to
JP­
4
which
has
a
higher
vapor
pressure
than
JP­
8
and
JP­
5
were
higher
than
to
the
presently
used
JP­
8
and
JP­
5.
Data
were
located
on
acute
sensory
and
systemic
effects
of
JP­
8
and
JP­
5
to
mice
and
rats;
subchronic
studies
addressed
systemic
effects,
particularly
effects
on
the
lungs.
For
all
fuels,
tests
of
eye
irritation
were
generally
negative,
whereas
mild
skin
irritation
occurred
for
some
fuels.
Several
short­
term
and
repeated
exposure
studies
addressed
the
particular
issue
of
the
toxicity
of
aerosols.
Exposure
to
aerosols
of
jet
fuels
induces
more
toxic
effects
than
exposure
to
vapors,
with
the
lungs
and
immune
system
identified
as
the
target
organs.
Animal
studies
also
addressed
neurotoxicity,
developmental/
reproductive
effects,
and
carcinogenicity.
These
fuels
are
generally
not
considered
genotoxic
or
carcinogenic
and,
in
a
preliminary
study,
JP­
8
failed
to
cause
spermatotoxic
effects
in
humans.
A
nephropathy
and
resulting
carcinogenic
effect,
unique
to
male
rats
exposed
to
hydrocarbons,
is
not
relevant
to
humans.
No
information
relevant
to
time
scaling
was
available.
The
AEGL­
1
is
based
on
the
sensory
irritation
study
of
Whitman
et
al.
(
2001),
specifically
the
RD50
(
the
concentration
that
reduces
the
respiratory
rate
by
50%)
for
JP­
8
of
2,876
mg/
m3
vapor
plus
aerosol.
The
RD50
test
is
a
standard
test
for
estimating
sensory
irritancy
of
airborne
chemicals
(
ASTM
E981
 
84).
In
the
key
study,
male
Swiss­
Webster
mice
were
exposed
for
30
minutes
to
681;
1,090;
1,837;
or
3,565
mg/
m3.
JP­
8
is
not
a
primary
irritant
and
reductions
in
the
respiratory
rate
did
not
occur
within
10
minutes
at
the
lower
concentrations.
However,
reductions
in
the
respiratory
rate
within
the
30­
minute
exposure
durations
were
concentrationdependent
and
allowed
calculation
of
an
RD50.
Based
on
the
correlation
between
RD50
data
and
sensory
irritancy
levels
for
numerous
chemicals,
a
0.1­
fold
reduction
of
the
RD50
results
in
a
concentration
that
elicits
some
sensory
irritation
in
humans
but
that
can
be
tolerated
for
hours
to
days
(
Alarie
1981).
Using
this
reasoning,
the
resulting
concentration
of
290
mg/
m3
can
be
tolerated
over
all
AEGL­
1
exposure
durations.
The
290
mg/
m3
value
is
supported
by
the
lack
of
adverse
health
effects
in
animal
studies
with
repeated
exposures
to
1,000
mg/
m3
of
JP­
8
vapor
(
continuous
exposures
up
to
90
days)
(
Mattie
et
al.
1991;
Briggs
2001;
Rossi
et
al.
2001).
Dividing
the
1,000
mg/
m3
value
by
an
interspecies
uncertainty
factor
of
1
(
no
species
differences
were
observed
in
multiple
studies
with
rats
and
mice
and
the
exposures
were
repeated)
and
an
intraspecies
uncertainty
factor
of
3
(
to
account
for
potential
differences
in
human
susceptibilities
to
sensory
irritation)
results
in
330
mg/
m3,
a
value
similar
to
that
derived
from
the
RD50
study.
The
repeated
nature
of
the
support
studies
also
supports
the
use
of
a
single
value
for
all
exposure
durations.
The
AEGL­
2
is
based
on
several
studies
with
rodents
(
rats
and
mice)
that
indicate
that
exposure
to
1,100
mg/
m3
of
JP­
8
would
not
elicit
adverse
health
effects
but
may
be
the
threshold
for
such
effects.
The
shorter­
term
studies
(
30
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Notices
minutes
to
4
hours)
with
exposures
to
3,430
 
5,000
mg/
m3
of
JP­
8
or
JP­
5
in
the
vapor/
aerosol
form
(
MacEwen
and
Vernot
1985;
Wolfe
et
al.
1996;
Whitman
et
al.
2001)
with
support
from
the
studies
using
repeated
exposures
to
1,000
mg/
m3
(
Mattie
et
al.
1991;
Briggs
2001;
Rossi
et
al.
2001)
were
used
as
the
basis
for
the
AEGL­
2.
No
uncertainty
factors
were
applied
to
the
1,000
mg/
m3
concentration
because
there
were
no
adverse
effects
and
the
exposures
were
repeated
for
up
to
90
days.
The
higher
concentrations
of
JP­
8,
3430
and
4,440
mg/
m3,
and
of
JP­
5,
5,000
mg/
m3,
were
divided
by
an
interspecies
factor
of
1
(
there
were
no
species
differences)
and
by
an
intraspecies
uncertainty
factor
of
3
to
protect
potentially
sensitive
individuals.
An
intraspecies
uncertainty
factor
of
3
is
considered
adequate
because
the
thresholds
for
both
sensory
irritation
and
central
nervous
system
depression
to
solvents
do
not
generally
differ
by
more
than
3­
fold.
The
resulting
value
is
1,100
mg/
m3
(
1,100
 
1,700
mg/
m3),
approximately
the
same
concentration
as
in
the
no­
adverse­
effect
repeated
exposure
studies.
No
information
was
available
for
time
scaling.
Central
nervous
system
depression
is
a
concentration­
related
effect.
Therefore,
the
1,100
mg/
m3
value
was
used
for
the
4­
hour
and
shorter
time
period.
But,
because
the
exposures
to
1,000
mg/
m3
were
repeated
for
up
to
90
days,
the
1,100
mg/
m3
value
can
also
be
used
for
the
longest
AEGL
exposure
duration
of
8
hours.
The
fact
that
the
exposures
in
most
of
these
studies,
especially
at
the
higher
concentrations,
were
to
both
the
vapor
and
the
more
toxic
aerosol
supports
the
appropriateness
of
the
derived
value.
It
should
be
noted
that,
because
of
its
relatively
low
vapor
pressure,
JP­
8
might
not
attain
a
sustained
vapor
concentration
high
enough
to
cause
death.
In
a
laboratory
study
reported
by
Wolfe
et
al.
(
1996),
the
highest
vapor
concentration
of
JP­
8
that
could
be
attained
was
3,430
mg/
m3.
The
highest
vapor/
aerosol
concentration
that
could
be
attained
was
4,440
mg/
m3.
The
highest
vapor/
aerosol
attainable
under
ambient
concentrations
has
been
estimated
at
700
mg/
m3.
However,
higher
concentrations
might
be
attained
in
closed
spaces
at
high
temperatures.
A
concentration
of
500
mg/
m3
is
assumed
to
be
the
upper
bound
for
a
stable
cloud
of
inhalable
dust
(
and
aerosols).
Based
on
the
likelihood
that
lethal
concentrations
of
JP­
8
cannot
be
sustained
under
ambient
conditions,
an
AEGL­
3
was
not
determined.
The
proposed
AEGL
values
are
listed
in
Table
7
of
this
unit.

TABLE
7.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
JP­
8
(
MG/
M3)
A,
B
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
290
290
290
290
290
Slight
sensory
irritation
in
humans
(
mouse
RD50
test)
(
Whitman
et
al.
2001)

AEGL­
2
(
Disabling)
1,100
1,100
1,100
1,100
1,100
No
clinical
signs
during
repeated
exposures
to
1,000
mg/
m3
 
rats
and
mice
(
Mattie
et
al.
1991;
Briggs
2001;
Rossi
et
al.
2001);
sensory
irritation
at
>
3,430
mg/
m3
 
rats
and
mice
(
Wolfe
et
al.
1996;
Whitman
et
al.
2001)

AEGL­
3
(
Lethal)
Not
determined
Not
determined
Not
determined
Not
determined
Not
determined
cNo
data
a
The
values
apply
to
JP­
8
vapor
or
vapor/
aerosol
and
not
to
the
pure
aerosol.
b
The
values
apply
to
JP­
8
vapor
and
not
to
JP­
8+
100.
c
A
lethal
concentration
was
not
attained
in
the
available
toxicity
studies;
the
low
vapor
pressure
of
JP­
8
may
preclude
attainment
of
a
lethal
concentration.

ii.
References.
a.
Alarie,
Y.
1981.
Dose­
response
analysis
in
animal
studies:
prediction
of
human
responses.
Environmental
Health
Perspectives.
42:
9
 
13.
b.
Briggs,
G.
B.
2001.
Evaluation
of
military
fuel
potential
to
produce
male
reproductive
toxicity.
Presented
at
the
International
Conference
on
the
Environmental
Health
and
Safety
of
Jet
Fuel
held
in
San
Antonio,
TX,
August
8
 
11,
2001.
c.
MacEwen,
J.
D.
and
E.
H.
Vernot.
1985.
Investigation
of
the
1­
hour
emergency
exposure
limit
of
JP­
5.
In
Toxic
Hazards
Research
Unit
Annual
Report,
Report
No.
AAMRL­
TR­
85­
058;
Aerospace
Medical
Research
Laboratory,
Wright­
Patterson
Air
Force
Base,
OH.
pp.
137
 
144.
Available
from
Defense
Technical
information
Center,
Doc.
No.
AD­
A161558.
d.
Mattie,
D.
R.;
C.
L.
Alden;
T.
K.
Newell;
C.
L.
Gaworski;
and
C.
D.
Flemming.
1991.
A
90­
day
continuous
vapor
inhalation
toxicity
study
of
JP­
8
jet
fuel
followed
by
20
or
21
months
of
recovery
in
Fischer
344
rats
and
C57BL/
6
mice.
Toxicologic
Pathology.
19:
77
 
87.
e.
Rossi,
J.,
III;
A.
F.
Nordholm;
R.
L
Carpenter;
G.
D.
Ritchie;
and
W.
Malcomb.
2001.
Effects
of
repeated
exposure
of
rats
to
JP­
5
or
JP­
8
jet
fuel
vapor
on
neurobehavioral
capacity
and
neurotransmitter
levels.
Journal
of
Toxicology
and
Environmental
Health.
Part
A
63:
397
 
428.
f.
Whitman,
F.
T.;
J.
J.
Freeman;
G.
W.
Trimmer;
J.
L.
Martin;
E.
J.
Febbo;
W.
J.
Bover;
and
R.
L.
Harris.
2001.
Sensory
Irritation
Study
in
Mice.
Final
Report,
Project
No.
162951,
ExxonMobil
Biomedical
Sciences,
Inc.,
Annandale,
NJ.
g.
Wolfe,
R.
E.;
E.
R.
Kinkead;
M.
L.
Feldmann;
H.
F.
Leahy;
W.
W.
Jederberg;
K.
R.
Still;
and
D.
R.
Mattie.
1996.
Acute
toxicity
evaluation
of
JP­
8
jet
fuel
containing
additives.
AL/
OE­
TR­
1996­
0136,
NMRI­
94­
114,
Armstrong
Laboratory,
Occupational
and
Environmental
Health
Directorate,
Toxicology
Division,
Wright­
Patterson
AFB,
OH.
7.
Methyl
ethyl
ketone
 
i.
Description.
Methyl
ethyl
ketone
(
MEK)
is
a
volatile
solvent
with
a
sweet/
sharp
acetone­
like
odor.
MEK
is
widely
used
as
a
solvent
in
common
household
products
such
as
inks,
paints,
cleaning
fluids,
varnishes,
and
glues.
In
most
industrial
applications
it
is
used
as
a
component
of
a
mixture
of
organic
solvents.
It
has
also
been
detected
in
a
wide
variety
of
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natural
products
and
may
be
a
minor
product
of
normal
mammalian
metabolism.
In
1999,
U.
S.
production
capacity
was
675
million
pounds.
The
inhalation
toxicity
of
MEK
is
low.
Low
concentrations
are
only
mildly
irritating.
At
high
concentrations
MEK
causes
a
narcotic
effect
on
the
central
nervous
system
as
evidenced
by
neurobehavioral
effects
in
animals.
MEK
is
not
teratogenic,
but
at
high
concentrations
is
mildly
fetotoxic
to
rats
and
mice.
Data
on
human
exposures
were
available
from
clinical
studies
and
workplace
monitoring.
Animal
studies
with
a
variety
of
species
(
baboon,
rat,
mouse,
and
guinea
pig)
addressed
irritation,
neurotoxicity,
developmental
toxicity,
chronic
toxicity/
carcinogenicity,
and
lethality.
Exposure
durations
ranged
from
acute
to
chronic.
Genotoxicity
was
also
addressed.
Two
studies
with
human
volunteers
exposed
to
100,
200,
or
350
ppm
were
evaluated
for
the
AEGL­
1;
the
exposure
times
were
5
minutes
(
Nelson
et
al.
1943)
and
4
hours
(
Dick
et
al.
1992).
Although
a
concentration
of
200
ppm
was
judged
unobjectionable
in
both
studies,
slight
nose
and
throat
irritation
were
noted
at
100
ppm
in
the
Nelson
et
al.
(
1943)
study.
Therefore,
100
ppm
was
selected
as
the
threshold
for
sensory
irritation.
The
safety
of
this
value
is
supported
by
numerous
clinical
studies
in
which
volunteers
were
routinely
exposed
to
200
 
400
ppm
for
up
to
4
hours
without
reports
of
irritation
or
changes
in
neurobehavioral
parameters.
Because
this
is
a
threshold
value
and
slight
irritation
should
not
increase
in
intensity
with
time,
an
intraspecies
uncertainty
factor
of
1
was
applied.
Because
accommodation
to
slight
irritation
occurs,
the
100
ppm
concentration
was
used
across
all
AEGL­
1
exposure
durations.
Furthermore,
MEK
is
rapidly
metabolized
and
will
not
accumulate
in
the
blood
or
in
the
body
which
further
supports
using
the
same
value
for
all
the
time
intervals.
The
AEGL­
2
was
based
on
the
chronic
study
of
Cavender
et
al.
(
1983)
in
which
rats
were
exposed
to
5,000
ppm
for
5
days/
week
for
90
days.
No
lesions
were
reported
in
this
study,
but
the
concentration
is
close
to
the
threshold
for
neurotoxicity
as
evidenced
by
somnolence
in
another
repeated
exposure
study
in
which
rats
were
exposed
to
6,000
ppm
for
several
weeks
(
Altenkirch
et
al.
1978).
Because
this
was
a
no­
effect
repeated­
exposure
study,
no
interspecies
uncertainty
factor
was
applied.
Because
the
threshold
for
narcosis
differs
by
no
more
than
2­
to
3­
fold
among
the
general
population,
an
intraspecies
uncertainty
factor
of
3
was
applied
to
protect
sensitive
individuals.
Because
the
threshold
for
narcosis
is
concentration
dependent,
the
resulting
1,700
ppm
concentration
was
applied
across
all
AEGL­
2
exposure
durations.
The
AEGL­
3
values
were
based
on
two
different
studies.
The
10­
and
30­
minute
values
were
based
on
a
study
with
mice
in
which
a
30­
minute
exposure
to
31,426
ppm
was
projected
to
reduce
the
respiratory
rate
by
50%;
there
were
no
deaths
at
the
highest
tested
concentration
of
26,416
ppm
(
Hansen
et
al.
1992).
Because
a
30­
minute
exposure
of
rats
to
3
times
this
concentration
(
92,239
ppm)
also
resulted
in
no
deaths
(
Klimisch
1988),
the
31,426
ppm
value
was
adjusted
by
an
interspecies
uncertainty
factor
of
1.
Because
the
threshold
for
narcosis
differs
by
no
more
than
2­
to
3­
fold
among
the
general
population,
an
intraspecies
uncertainty
factor
of
3
was
applied
to
protect
sensitive
individuals.
The
resulting
value
of
10,000
ppm
was
used
for
the
10­
minute
and
30­
minute
AEGL­
3
exposure
durations.
The
longerterm
values
were
based
on
an
MLE01
of
7,500
ppm
calculated
by
Fowles
et
al.
(
1999)
from
a
4­
hour
study
with
rats
exposed
to
several
concentrations
for
4
hours
(
La
Belle
and
Brieger
1955).
In
this
study
the
4­
hour
LC50
was
11,700
ppm
and
the
highest
concentration
resulting
in
no
deaths
was
7,850
ppm
for
4
hours.
The
7,500
ppm
concentration
was
divided
by
an
intraspecies
uncertainty
factor
of
3.
The
resulting
value
of
2,500
ppm
was
used
for
both
the
4­
hour
and
8­
hour
AEGL­
3
values
because
MEK
would
reach
equilibrium
in
the
body
prior
to
this
time
period.
The
4­
hour
2,500
ppm
value
was
time
scaled
to
the
1
hour
time
using
the
default
n
value
of
3
for
scaling
to
shorter
time
intervals.
The
proposed
AEGL
values
are
listed
in
Table
8
of
this
unit.

TABLE
8.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
METHYL
ETHYL
KETONE
[
PPM
(
MG/
M3)]

Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
100
(
293)
100
(
293)
100
(
293)
100
(
293)
100
(
293)
Threshold
for
sensory
irritation
in
humans
(
Nelson
et
al.
1943)

AEGL­
2
(
Disabling)
1,700
(
4,980)
1,700
(
4,980)
1,700
(
4,980)
1,700
(
4,980)
1,700
(
4,980)
Threshold
for
narcosis
 
rats
(
Cavender
et
al.
1983)

AEGL­
3(
Lethal)
10,000a,
b
(
29,300)
10,000
(
29,300)
4,000c
(
11,720)
2,500
(
7,325)
2,500
(
7,325)
Threshold
for
lethality
 
mouse
(
Hansen
et
al.
1992;
La
Belle
and
Brieger
1955)

aBased
on
Hansen
et
al.
(
1992).
bThis
value
is
more
than
one­
half
of
the
lower
explosive
limit
of
18,000
ppm.
cBased
on
La
Belle
and
Brieger
(
1955).

ii.
References.
a.
Altenkirch,
H.;
G.
Stoltenburg;
and
H.
M.
Wagner.
1978.
Experimental
studies
on
hydrocarbon
neuropathies
induced
by
methyl­
ethylketone
(
MEK).
Journal
of
Neurology.
219:
159
 
170.
b.
Cavender,
F.
L;
H.
W.
Casey;
H.
Salem;
J.
A.
Swenberg;
and
E.
J.
Gralla.
1983.
A
90­
day
vapor
inhalation
toxicity
study
of
methyl
ethyl
ketone.
Fundamental
and
Applied
Toxicology.
3:
264
 
270.
c.
Dick,
R.
B.;
E.
F.
Krieg,
Jr.;
J.
Setzer;
and
B.
Taylor.
1992.
Neurobehavioral
effects
from
acute
exposures
to
methyl
isobutyl
ketone
and
methyl
ethyl
ketone.
Fundamental
and
Applied
Toxicology.
19:
453
 
473.
d.
Fowles,
J.
R.;
G.
V.
Alexeeff;
and
D.
Dodge.
1999.
The
use
of
the
benchmark
dose
methodology
with
acute
inhalation
lethality
data.
Regulatory
Toxicology
and
Pharmacology.
29:
262
 
278.
e.
Hansen,
L.
F.;
A.
Knudsen;
and
G.
D.
Nielsen.
1992.
Sensory
irritation
effects
of
methyl
ethyl
ketone
and
its
receptor
activation
mechanism.
Pharmacology
&
Toxicology.
71:
201
 
208.
f.
Klimisch,
H.
1988.
The
inhalation
hazard
test;
principle
and
method.
Archives
of
Toxicology.
61:
411
 
416.
g.
La
Belle,
C.
and
H.
Brieger.
1955.
The
vapor
toxicity
of
a
composite
solvent
and
its
principal
components.

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Notices
Archives
of
Industrial
Health.
12:
623
 
627.
h.
Nelson,
K.
W.;
J.
F.
Ege,
Jr.;
M.
Ross;
L.
E.
Woodman;
and
L.
Silverman.
1943.
Sensory
response
to
certain
industrial
solvent
vapors.
Journal
of
Industrial
Hygiene
and
Toxicology.
25:
282
 
285.
8.
Phosphorus
oxychloride
 
i.
Description.
Phosphorus
oxychloride
(
CAS
No.
10025
 
87
 
3),
a
colorless
fuming
liquid
with
a
pungent
odor,
is
stable
to
above
300
°
C
but
is
highly
reactive
with
water
yielding
phosphoric
acid
and
hydrogen
chloride.
It
is
used
in
the
manufacture
of
plasticizers,
hydraulic
fluids,
gasoline
additives,
fire
retarding
agents,
and
in
the
manufacture
of
alkyl
and
aryl
orthophosphate
triesters.
Information
regarding
exposure
of
humans
to
phosphorus
oxychloride
are
limited
to
qualitative
reports
that
indicate
notable
dermal,
ocular,
pharyngeal
and
pulmonary
irritation
following
acute
and
subchronic
(
intermittent)
exposures.
Most
reports
lacked
exposure
terms
although
one
report
of
occupational
exposures
indicated
that
air
concentrations
of
phosphorus
oxychloride
ranged
from
1.6
to
11.2
ppm.
The
effects
often
persisted
after
cessation
of
exposure,
especially
in
those
individuals
experiencing
more
severe
effects.
Neither
odor
detection
data
nor
lethality
data
are
available
for
humans.
Quantitative
data
in
animals
are
limited
to
reports
of
lethality.
These
data
include
a
4­
hour
LC50
for
rata
(
44.4
ppm)
and
guinea
pigs
(
52.5
ppm),
and
an
unverified
4­
hour
LC50
of
32
ppm
for
rats.
A
5
 
15
minute
exposure
of
rats
and
guinea
pigs
to
0.96
ppm
phosphorus
oxychloride
was
noted
as
a
``
threshold
response''
in
a
Russian
report.
A
brief
report
from
industry
indicated
immediate
adverse
responses
(
at
2
minutes)
and
death
(
18
minutes)
following
exposure
to
a
very
high
concentration
(
25,462
ppm).
The
available
studies
affirm
the
extreme
irritation
properties
of
phosphorus
oxychloride,
although
the
exposures
described
also
resulted
in
lethality.
No
information
was
available
regarding
reproductive/
developmental
toxicity,
genotoxicity,
or
carcinogenicity.
There
are
no
definitive
data
regarding
the
metabolism
or
precise
mechanism
of
action
of
phosphorus
oxychloride
toxicity.
Based
upon
the
limited
human
and
animal
toxicity
data,
and
the
chemical
properties
of
phosphorus
oxychloride,
it
may
be
assumed
that
the
primary
effect
involves
damage
to
epithelial
tissue
and,
for
respiratory
effects,
subsequent
pulmonary
edema.
The
lethal
potency
of
phosphorus
oxychloride,
however,
does
not
appear
to
be
explained
simply
by
the
activity
of
its
degradation
products
(
phosphoric
acid
and
hydrogen
chloride).
In
the
absence
of
odor
detection
data
and
quantitative
data
pertaining
to
effects
consistent
with
AEGL­
1
definition,
AEGL­
1
values
were
not
developed.
Exposure­
response
data
pertaining
to
AEGL­
2
level
effects
were
unavailable
and,
therefore
no
AEGL­
2
values
were
developed.
Because
of
the
lack
of
exposure­
response
data
for
any
effects,
estimating
AEGL­
2
values
by
a
reduction
in
AEGL­
3
values
was
considered
tenuous
and
difficult
to
justify.
AEGL­
3
values
were
developed
using
an
estimate
of
the
lethality
threshold
based
upon
the
4­
hour
LC50
of
48.4
ppm
in
rats
that
was
reported
by
Weeks
et
al.
(
1964).
Although
exposure­
response
data
were
unavailable,
the
lethality
threshold
was
estimated
a
one
third
of
the
4­
hour
LC50
(
i.
e.,
48.4
ppm/
3
=
16.1
ppm).
Due
to
uncertainties
regarding
species
variability
in
the
lethal
response
to
phosphorus
oxychloride
and
the
lack
of
lethality
data
in
humans,
an
order­
ofmagnitude
uncertainty
adjustment
was
applied
for
interspecies
variability.
Contact
irritation
resulting
in
damage
to
epithelial
tissue
appears
to
be
involved
in
the
toxic
response
to
phosphorus
oxychloride.
It
is
likely
that
this
response
is
a
function
of
the
extreme
reactivity
of
phosphorus
oxychloride
with
tissues
(
e.
g.,
pulmonary
epithelium)
and
not
likely
to
vary
greatly
among
individuals.
The
uncertainty
adjustment
for
intraspecies
variability,
therefore,
was
limited
to
3.
The
concentration
exposure
time
relationship
for
many
irritant
and
systemically
acting
vapors
and
gases
may
be
described
by
Cn
x
t
=
k,
where
the
exponent,
n,
ranges
from
0.8
to
3.5.
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
Cn
x
t
=
k
equation.
The
range
of
interspecies
variability
remains
uncertain
due
to
limited
animal
data
and
the
absence
of
quantitative
exposure­
response
data
for
humans.
The
absence
of
exposure­
response
data
for
non­
lethal
effects
in
animals
or
humans
is
a
significant
data
deficiency.
The
proposed
AEGL
values
are
listed
in
Table
9
of
this
unit.

TABLE
9.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
PHOSPHORUS
OXYCHLORIDE
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
NR
NR
NR
NR
NR
Data
unavailable
for
development
AEGL­
2
(
Disabling)
NR
NR
NR
NR
NR
Data
unavailable
for
development
AEGL­
3
(
Lethal)
1.1
ppm
(
6.9
mg/
m3)
1.1
ppm
(
6.9
mg/
m3)
0.85
ppm
(
5.3
mg/
m3)
0.54
ppm
(
3.4
mg/
m3)
0.27
ppm
(
1.7
mg/
m3)
Weeks
et
al.,
(
1964).
Estimate
of
lethality
threshold
in
rats
(
16.1
ppm)
based
upon
3­
fold
reduction
in
4­
hour
LC50
of
48.4
ppm.

NR:
Not
recommended.
Numeric
values
for
AEGL­
1and
AEGL­
2
are
not
recommended
due
to
the
lack
of
available
data
Absence
of
AEGL­
1
and
AEGL­
2
values
does
not
imply
that
exposure
below
the
AEGL­
3
is
without
effect.

ii.
References.
Weeks,
M.
H.;
Mussleman,
N.
P.;
Yevich,
P.
P.;
Jacobson,
K.
H.;
and
Oberst,
F.
W.
1964.
Acute
vapor
toxicity
of
phosphorus
oxychloride,
phosphorus
trichloride
and
methyl
phosphonic
dichloride.
Industrial
Hygiene
Journal.
25:
470
 
475.
9.
Phosphorus
trichloride
 
i.
Description.
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.

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18,
2003
/
Notices
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
100
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
hour
LC50
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
11
ppm
following
repeated
exposure
(
6
hours/
day,
5
days/
week
for
4
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
Cn
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
Cn
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
hours/
day,
5
days/
week
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
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
11
ppm
exposure
in
rats
was
considered
a
NOAEL
for
AEGL­
2
effects.
Uncertainty
factor
application
was
the
same
as
for
the
AEGL­
1
tier.
AEGL­
3
values
were
developed
based
upon
a
3­
fold
reduction
of
the
4­
hour
LC50
(
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
(
1983)
study
showed
no
fatalities
in
rats
following
multiple
6­
hour
exposures
to
11
ppm.
The
proposed
AEGL
values
are
listed
in
Table
10
of
this
unit.

TABLE
10.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
PHOSPHORUS
TRICHLORIDE
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
0.78
ppm
0.78
ppm
0.62
ppm
0.39
ppm
0.26
ppm
NOAEL
of
3.4
ppm
in
rats
exposed
6
hours/
day,
5
days/
week
for
4
weeks
(
Hazleton
Laboratories,
1983)

AEGL­
2
(
Disabling)
2.5
ppm
2.5
ppm
2.0
ppm
1.3
ppm
0.83
ppm
NOAEL
for
AEGL­
2
tier
effects;
based
upon
respiratory
tract
histopathology
in
rats
exposed
6
hours/
day,
5
days/
week
for
4
weeks
(
Hazleton
Laboratories
1983)

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Notices
TABLE
10.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
PHOSPHORUS
TRICHLORIDE
 
Continued
Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
3
(
Lethal)
7.0
ppm
7.0
ppm
5.6
ppm
3.5
ppm
1.8
ppm
Estimated
lethality
threshold
based
upon
3­
fold
reduction
of
guinea
pig
4­
hour
LC50
(
50.1
ppm/
3
=
16.7
ppm)
(
Weeks
et
al.,
1964)
a
aBased
upon
animal
data,
lethality
may
be
delayed.

ii.
References.
a.
Hazleton
Laboratories.
1983.
Subacute
inhalation
toxicity
study
in
rats
 
phosphorus
trichloride.
Final
Report.
Project
No.
241
 
141.
Hazleton
Laboratories
America,
Inc.
Unpublished.
b.
Weeks,
M.
H.;
Mussleman,
N.
P.;
Yevich,
P.
P.;
Jacobson,
K.
H.;
and
Oberst,
F.
W.
1964.
Acute
vapor
toxicity
of
phosphorus
oxychloride,
phosphorus
trichloride
and
methyl
phosphonic
dichloride.
American
Industrial
Hygiene
Journal.
25:
470
 
475.
10.
Xylenes
 
i.
Description.
Xylene
is
found
in
a
number
of
consumer
products,
including
solvents,
paints,
or
coatings,
and
as
a
blend
in
gasoline.
Mixed
xylenes
are
comprised
of
3
isomers:
M­
xylene,
o­
xylene,
and
pxylene
with
the
m­
isomer
predominating.
Ethyl
benzene
is
also
present
in
the
technical
product
formulation.
Absorbed
xylene
is
rapidly
metabolized
and
is
excreted
almost
exclusively
in
the
urine
as
methylhippuric
acid
isomers
in
humans
and
as
methylhippuric
acid
isomers
and
toluic
acid
glucuronides
in
animals.
In
both
humans
and
animals,
xylene
causes
irritation
and
effects
the
central
nervous
system
following
acute
inhalation
exposure.
No
consistent
developmental
or
reproductive
effects
were
observed
in
the
studies
found
in
the
available
literature.
Commercial
xylene
and
all
3
isomers
have
generally
tested
negative
for
genotoxicity.
Xylenes
are
currently
not
classifiable
as
to
its
carcinogenicity
by
the
International
Agency
on
Research
for
Cancer
(
IARC)
or
the
EPA
because
of
inadequate
evidence.
The
AEGL­
1
is
based
upon
slight
eye
irritation
noted
during
a
30­
minute
exposure
to
400
ppm
mixed
xylenes
(
Hastings
et
al.,
1986).
An
interspecies
uncertainty
factor
was
not
applied
because
the
key
study
used
human
data.
An
intraspecies
uncertainty
factor
of
3
was
applied
because
the
toxic
effect
(
slight
irritation)
was
less
severe
than
that
defined
for
the
AEGL­
1
tier
(
notable
discomfort).
The
resulting
value
of
130
ppm
is
supported
by
several
other
studies,
including:
A
150
ppm
p­
xylene
exposure
resulting
in
eye
irritation
in
a
contact
lens
wearer
(
Hake
et
al.,
1981);
a
15­
minute
exposure
to
230
ppm
mixed
xylenes
resulting
in
mild
eye
irritation
and
dizziness
in
one
individual;
and
a
3­
hour
exposure
to
200
ppm
m­
or
pxylene
(
Ogata
et
al.,
1970),
a
4­
hour
exposure
to
200
ppm
m­
xylene
(
Savolainen
et
al.,
1981),
and
a
5.5
hour
exposure
to
200
ppm
m­
xylene
(
Laine
et
al.,
1993)
all
representing
no­
effect
levels.
The
AEGL­
2
is
based
upon
poor
coordination
resulting
when
rats
were
exposed
to
1,300
ppm
mixed
xylenes
for
4
hours
(
Carpenter
et
al.,
1975).
This
concentration
represents
the
threshold
for
reversible
equilibrium
disturbances.
This
concentration
and
endpoint
are
consistent
with
the
preponderance
of
available
data
for
4­
hour
exposures
in
rats:
The
EC50
for
decreased
rotarod
performance
was
1982
ppm
(
Korsak
et
al.,
1993);
the
minimum
narcotic
concentrations
for
m­,
o­,
and
p­
xylene
ranged
from
1,940
 
2,180
ppm
(
Molna
´
r
et
al.,
1986);
and
exposure
to
1,600
ppm
p­
xylene
resulted
in
hyperactivity,
fine
tremor,
and
unsteadiness
(
Bushnell,
1989),
induced
flavor
aversion
(
Bushnell
and
Peele,
1988),
and
caused
changes
in
the
flash
evoked
potential
suggestive
of
increased
arousal
(
Dyer
et
al.,
1988).
In
dogs,
exposure
to
1,200
ppm
for
4
hours
represented
a
threshold
for
eye
irritation
(
Carpenter
et
al.,
1975).
An
interspecies
uncertainty
factor
of
1
was
applied
because
rats
receive
a
greater
systemic
dose
of
inhaled
xylene
as
compared
to
humans.
An
intraspecies
uncertainty
factor
of
3
was
applied
because
the
minimum
alveolar
concentration
(
MAC)
for
volatile
anesthetics
should
not
vary
by
more
than
a
factor
of
2
 
3­
fold
among
humans.
A
3­
fold
factor
is
also
adequate
to
account
for
moderate
physical
activity
during
exposure,
which
would
result
in
greater
uptake
of
the
chemical.
The
AEGL­
3
derivation
is
based
upon
prostration
occurring
in
all
10
rats
exposed
for
4
hours
to
2,800
ppm
mixed
xylenes,
with
recovery
occurring
within
1
hour
of
exposure
(
Carpenter
et
al.,
1975).
Although
coordination
initially
remained
poor,
it
returned
to
normal
the
following
day.
This
concentration
also
represents
a
no­
effect
level
for
lethality.
An
interspecies
uncertainty
factor
of
1
was
applied
because
rats
receive
a
greater
systemic
dose
of
inhaled
xylene
as
compared
to
humans.
An
intraspecies
uncertainty
factor
of
3
was
applied
because
the
MAC
for
volatile
anesthetics
should
not
vary
by
more
than
a
factor
of
2
 
3­
fold
among
humans.
A
3­
fold
factor
is
also
adequate
to
account
for
moderate
physical
activity
during
exposure,
which
would
result
in
greater
uptake
of
the
chemical.
The
two
primary
effects
of
concern
for
xylene
are
those
of
irritation
and
central
nervous
system
effects.
Irritation
is
considered
a
threshold
effect
and
therefore
should
not
vary
over
time.
The
AEGL­
1
value
based
on
irritation
is
therefore
not
scaled
across
time,
but
rather
the
threshold
value
is
applied
to
all
times.
Data
indicate
that
once
steady
state
is
reached,
concentration,
not
duration,
is
the
prime
determinant
in
xyleneinduced
central
nervous
system
toxicity.
Pharmacokinetic
modeling
in
both
humans
and
rats
indicate
that
venous
blood
concentrations
rapidly
increase
during
the
first
15
minutes
of
exposure,
followed
by
minimal
increases
in
blood
concentrations
with
continuing
exposure
(
i.
e.,
increases
follow
a
hyperbolic
curve).
Likewise,
available
human
data
indicate
that
once
the
initial
increase
in
blood
xylene
concentration
is
reached,
blood
concentrations
level
off
with
increasing
exposure
duration.
Conversely,
available
human
and
animal
data
demonstrate
that
increasing
exposure
concentrations
correlate
with
increases
in
venous
blood
xylene
concentrations.
Therefore,
the
AEGL
2­
and
­
3
values
are
set
equal
across
time
once
steady
state
is
approached
(
starting
at
approximately
1
hour),
while
pharmacokinetic
modeling
was
used
to
extrapolate
to
exposure
durations
of
10­
and
30­
minutes.
The
AEGL
values
should
be
protective
of
human
health.
The
AEGL­
1
values
are
consistent
with
other
human
studies,
and
represent
a
value
consistent
with
exposure
concentrations
that
might
result
in
mild
eye
irritation.
The
AEGL­
2
levels
are
protective,
especially
when
considering
numerous
human
studies
investigating
the
effects
of
exposure
to
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/
Notices
200
ppm
xylene
with
20­
minute
peak
exposures
to
400
ppm,
in
some
cases
additionally
combining
peak
exposures
with
physical
exercise
resulting
in
greater
uptake
of
the
chemical,
and
finding
only
minimal
central
nervous
system
effects.
The
difficultly
in
defining
an
AEGL­
2
level
for
xylene
comes
from
its
``
all­
or­
nothing''
continuum
of
toxicity:
Toxicity
ranges
from
mild
irritation
to
narcosis,
with
little
happening
in
between.
The
AEGL­
3
levels
represent
the
threshold
for
narcosis,
and
are
protective
as
supported
by
human
data
demonstrating
that
exposure
to
690
ppm
for
15
minutes
resulted
in
lightheadedness/
dizziness
and
a
30
minute
exposure
to
700
ppm
resulted
in
nausea,
vomiting,
dizziness,
or
vertigo.
The
proposed
AEGL
values
are
listed
in
Table
11
of
this
unit.

TABLE
11.
 
SUMMARY
OF
PROPOSED
AEGL
VALUES
FOR
XYLENES
[
PPM
(
MG/
M3)]

Classification
10­
minutes
30­
minutes
1­
hour
4­
hours
8­
hours
Endpoint
(
Reference)

AEGL­
1
(
Nondisabling)
130
(
560)
130
(
560)
130
(
560)
130
(
560)
130
(
560)
Eye
irritation
in
human
volunteers
exposed
to
400
ppm
mixed
xylenes
for
30
minutes
(
Hastings
et
al.,
1986)

AEGL­
2
(
Disabling)
990
(
4,300)
480
(
2,100)
430
(
1,900)
430
(
1,900)
430
(
1,900)
Rats
exposed
to
1,300
ppm
mixed
xylenes
for
4
hours
exhibited
poor
coordination
(
Carpenter
et
al.,
1975)

AEGL­
3
(
Lethal)
2,100
(
9,100)
1,000
(
4,300)
930
(
4,000)
930
(
4,000)
930
(
4,000)
Rats
exposed
to
2,800
ppm
for
4
hours
exhibited
prostration
followed
by
a
full
recovery
(
Carpenter
et
al.,
1975)

ii.
References.
a.
Bushnell,
P.
J.
1989.
Behavioral
effects
of
acute
p­
xylene
inhalation
in
rats:
Autoshaping,
motor
activity,
and
reversal
learning.
Neurotoxicology
and
Teratology.
10:
569
 
577.
b.
Bushnell,
P.
J.
and
Peele,
D.
B.
1988.
Conditioned
flavor
aversion
induced
by
inhaled
p­
xylene
in
rats.
Neurotoxicology
and
Teratology.
10:
273
 
277.
c.
Carpenter,
C.
P.;
Kinkead,
E.
R.;
Geary,
D.
L.
Jr.;
Sullivan,
L.
J.;
and
King,
J.
M.
1975b.
Petroleum
hydrocarbon
toxicity
studies.
V.
Animal
and
human
response
to
vapors
of
mixed
xylene.
Toxicology
and
Applied
Pharmacology.
33:
543
 
58.
d.
Dyer,
R.
S.;
Bercegeay,
M.
S.;
and
Mayo,
L.
M.
1988.
Acute
exposures
to
pxylene
and
toluene
alter
visual
information
processing.
Neurotoxicology
and
Teratology.
10:
147
 
153.
e.
Hake,
C.
R.
L.;
Stewart,
R.
D.;
and
Wu,
A.,
et
al.
1981.
p­
Xylene:
Development
of
a
biological
standard
for
the
industrial
worker.
Report
to
the
National
Institute
for
Occupational
Safety
and
Health,
Cincinnati,
OH,
by
the
Medical
College
of
Wisconsin,
Inc.,
Milwaukee,
WI.
PB82­
152844.
f.
Hastings,
L.;
Cooper,
G.
P.;
and
Burg,
W.
1986.
Human
sensory
response
to
selected
petroleum
hydrocarbons.
In:
MacFarland,
H.
N.
ed.
Advances
in
Modern
Environmental
Toxicology.
Vol.
VI.
Applied
Toxicology
of
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1993.
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6:
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1993.
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65:
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A
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;
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1986.
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during
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to
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1970.
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98.

IV.
Next
Steps
The
NAC/
AEGL
Committee
plans
to
publish
``
Proposed''
AEGL
values
for
five­
exposure
periods
for
other
chemicals
on
the
priority
list
of
85
in
groups
of
approximately
10
to
20
chemicals
in
future
Federal
Register
notices
during
the
calendar
year
2003.
The
NAC/
AEGL
Committee
will
review
and
consider
all
public
comments
received
on
this
notice,
with
revisions
to
the
``
Proposed''
AEGL
values
as
appropriate.
The
resulting
AEGL
values
will
be
established
as
``
Interim''
AEGLs
and
will
be
forwarded
to
the
National
Research
Council,
National
Academy
of
Sciences
(
NRC/
NAS),
for
review
and
comment.
The
``
Final''
AEGLs
will
be
published
under
the
auspices
of
the
NRC/
NAS
following
concurrence
on
the
values
and
the
scientific
rationale
used
in
their
development.

List
of
Subjects
Environmental
protection,
Hazardous
chemicals,
Worker
protection.

Dated:
July
7,
2003.

Susan
B.
Hazen,

Acting
Assistant
Administrator
for
Prevention,
Pesticides
and
Toxic
Substances.

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