Document ID: EPA-HQ-OPPT-2004-0111-0008
Agency: epa
Document Type: Proposed Rule
Title: Occupational Exposure to 2-Methoxyethanol, 2-Ethoxyethanol and their Acetates (Glycol Ethers)
Posted Date: 2004-10-05T04:00Z

[
page
15526]

DEPARTMENT
OF
LABOR
29
CFR
Part
1910
Docket
No.
H­
044
Occupational
Exposure
to
2­
Methoxyethanol,
2­
Ethoxyethanol
and
Their
Acetates
(
Glycol
Ethers)

AGENCY:
Occupational
Safety
and
Health
Administration
(
OSHA),
Labor
ACTION:
Proposed
rule
and
notice
of
hearing
SUMMARY:
The
Occupational
Safety
and
Health
Administration
(
OSHA)
proposes
to
amend
its
existing
regulation
for
occupational
exposure
to
2­
Methoxyethanol
(
2­
ME),
2­
Ethoxyethanol
(
2­
EE)
and
their
acetates
(
2­
MEA,
2­
EEA)
("
Glycol
Ethers"),
contained
in
29
CFR
1910.1000
Table
Z­
1,
and
to
be
codified
as
new
section
29
CFR
1910.1031.
The
Assistant
Secretary
has
determined,
based
on
a
review
and
evaluation
of
studies
conducted
on
the
health
effects
of
these
glycol
ethers,
that
the
current
permissible
exposure
limits
(
PELs)
do
not
adequately
protect
employees
from
significant
risks
of
adverse
health
effects,
specifically
reproductive
and
developmental
health
effects
To
eliminate
these
significant
risks
of
adverse
health
effects,
OSHA
is
proposing
for
general,
maritime,
agriculture
and
construction
industries
to
reduce
the
existing
8­
hour
time
weighted
average
(
TWA)
PELs
for
2­
ME
and
2­
MEA
to
0.1
ppm
and
for
2­
EE
and
2­
EEA
to
0.5
ppm
OSHA
proposes
excursion
limits
(
ELs)
for
these
glycol
ethers
of
five
times
the
proposed
PELs.
OSHA
also
proposes
to
set
Action
Levels
(
ALs)
for
these
glycol
ethers
of
one­
half
the
proposed
PELs,
measured
as
an
8­
hour
TWA,
to
encourage
lower
exposure
for
employees
while
reducing
administrative
burdens
on
employers.
In
addition,
OSHA
proposes
that
no
employee
shall
be
exposed
to
these
glycol
ethers
through
dermal
contact
OSHA
proposes
to
require
certain
ancillary
provisions
for
employee
protection
such
as
preferred
methods
to
control
exposure,
employee
exposure
monitoring,
medical
surveillance,
recordkeeping,
regulated
areas,
emergency
procedures,
hazard
communication,
and
personal
protective
equipment
DATES:
Written
comments
on
the
proposed
standard
must
be
postmarked
on
or
before
June
7,
1993.
Notices
of
Intention
to
Appear
at
the
informal
public
hearings
on
the
proposed
standard
must
be
postmarked
by
June
7,
1993.
Parties
who
request
more
than
10
minutes
for
their
presentations
at
the
informal
public
hearing
and
parties
who
submit
documentary
evidence
at
the
hearing
must
submit
the
full
text
of
their
testimony
and
all
documentary
evidence
no
later
than
June
28,
1993.
The
informal
rulemaking
hearing
is
scheduled
to
begin
on
July
20,
1993
ADDRESSES:
Written
comments
should
be
submitted
to
the
Docket
Officer,
Docket
No.
H­
044,
Room
N­
2625,
U.
S.
Department
of
Labor,
200
Constitution
Avenue,
N.
W.,
Washington,
DC
20210
Notices
of
Intention
to
Appear
at
the
informal
rulemaking
hearing,
testimony,
and
documentary
evidence
are
to
be
sent
to
Tom
Hall,
OSHA
Division
of
Consumer
Affairs,
Docket
No.
H­
044,
Room
N­
3662,
U.
S.
Department
of
Labor,
200
Constitution
Avenue,
N.
W.,
Washington,
DC
20210
FOR
FURTHER
INFORMATION
CONTACT:
Mr.
James
F.
Foster,
OSHA,
U.
S.
Department
of
Labor,
Office
of
Public
Affairs,
Room
N­
3647,
200
Constitution
Avenue,
N.
W.,
Washington
,
DC
20210.
Telephone
(
202)
219­
8151.

SUPPLEMENTARY
INFORMATION:

I.
Introduction
Table
of
Contents
I.
Introduction
II.
Pertinent
Legal
Authority
III.
History
of
the
Regulation
IV.
Chemical
Identification,
Production,
and
Use
of
Ethylene
Glycol
Ethers
V.
Health
Effects
A.
Introduction
B.
Metabolism/
Metabolic­
Related
Health
Effects
C.
Acute
Toxicity
D.
Background
Discussion
on
Reproductive
and
Developmental
Toxicology
E.
Effects
in
Animals
1.
Male
Reproductive
Effects
2.
Maternal/
Developmental
Effects
3.
Blood
Effects
F.
Adverse
Effects
in
Humans
G.
Mutagenicity
H.
Conclusions
I.
Health
Effects
of
Other
Glycol
Ethers
VI.
Risk
Assessment
VII.
Significance
of
Risk
VIII.
Summary
of
the
Regulatory
Impact
Analyses
and
Regulatory
Flexibility
Analysis
IX.
Environmental
Impact
X.
Summary
and
Explanation
of
the
Proposed
Standard
XI.
Clearance
of
Information
Collection
Requirements
XII.
Public
Participation
­
Notice
of
Hearings
XIII.
Authority
and
Signature
XIV.
Proposed
Standard
and
Appendices
A.
Issues
Comment
is
requested
on
all
relevant
issues,
including
health
effects,
risk
assessment,
technological
and
economic
feasibility
and
provisions
that
should
be
included
in
a
final
glycol
ethers
standard
OSHA
is
especially
interested
in
answers,
supported
by
evidence
and
reasons,
to
the
following
questions
1.
Do
OSHA's
proposed
TWA
permissible
exposure
limits
(
PELs)
of
0.1
ppm
for
2­
ME
and
2­
MEA
and
0.5
ppm
for
2­
EE
and
2­
EEA
adequately
protect
employees
from
significant
risk
of
adverse
health
effects?
If
not,
what
TWA
permissible
exposure
limits
would
be
more
appropriate
or
would
more
adequately
protect
employees
from
health
risks?
Please
provide
data
and
evidence
to
support
your
response
2.
In
addition
to
the
proposed
TWA
PELs
and
action
levels,
OSHA
has
proposed
Excursion
Limits
(
ELs)
of
0.5
ppm
for
2­
ME
and
2­
MEA
and
2.5
ppm
for
2­
EE
and
2­
EEA.
In
the
preamble
to
this
proposal
OSHA
has
also
explained
the
various
reasons
for
establishing
ELs
for
the
glycol
ethers
included
in
this
proposal.
OSHA
requests
comment
on
this
provision.
Please
provide
data
and
evidence
to
support
your
response
3.
In
addition
to
the
PELs
for
airborne
exposure
to
glycol
ethers,
OSHA
is
also
proposing
that
employers
ensure
that
no
employee
is
exposed
to
glycol
ethers
through
dermal
contact.
OSHA
requests
comment
on
this
provision.
In
particular:

a.
Are
there
methods
to
measure
dermal
exposure
that
could
be
routinely
used
to
monitor
worker
exposure
to
glycol
ethers?

b.
For
employers
whose
employees
are
exposed
to
glycol
ethers,
what
methods
do
you
use
to
protect
employees
from
dermal
contact
with
glycol
ethers?

c.
What
do
these
methods
cost?

4.
OSHA
has
limited
the
scope
of
this
proposal
to
the
four
glycol
ethers
referred
to
OSHA
by
EPA.
OSHA
requests
comment
about
whether
the
proposed
scope
of
this
rulemaking
is
appropriate.
OSHA
also
requests
comment
about
whether
the
scope
of
this
proposed
standard
should
be
expanded
to
cover
other
ethylene
glycol
ethers
and/
or
other
propylene
glycol
ethers.
Should
there
be
separate
rulemaking
undertaken
to
cover
other
glycol
ethers
not
included
in
this
proposal?
If
so,
what
data
and
evidence
are
available
to
indicate
that
exposure
to
these
other
glycol
ethers
present
a
risk
to
employees?

5.
In
making
its
risk
assessment,
OSHA
relied
upon
the
NOEL­
Uncertainty
Factor
approach
to
describe
and
calculate
the
risks
associated
with
occupational
exposure
to
glycol
ethers.
OSHA
requests
comment
on
whether
this
approach
is
appropriate
for
making
a
risk
assessment
regarding
reproductive/
developmental
health
effects
[
page
15527]

a.
OSHA
requests
comment
on
whether
there
are
more
appropriate
models
for
describing
or
calculating
the
risks
of
adverse
reproductive/
developmental
effects
among
exposed
workers.
Are
there
scientifically
valid
quantitative
models
that
would
be
more
appropriate
for
assessing
risk
of
reproductive/
developmental
health
effects?

b.
OSHA
has
used
an
Uncertainty
Factor
of
100
to
determine
a
level
below
which
humans
are
unlikely
to
experience
significant
risk
of
adverse
reproductive/
developmental
effects
similar
to
those
observed
in
animals.
Is
an
Uncertainty
Factor
of
100
appropriate
in
this
circumstance?
Would
an
alternative
Uncertainty
Factor
be
more
appropriate?
Please
provide
data
and
evidence
to
support
your
response.
(
Please
see
Section
VI
of
this
section
for
more
detailed
questions
on
risk
assessment.)

6.
Paragraph
(
g)
of
the
proposed
standard
would
require
that
supplied
air
respirators
be
used
in
those
limited
situations
where
the
TWA
and/
or
EL
permissible
exposure
limits
are
not
capable
of
being
achieved
solely
by
means
of
engineering
and
work
practice
controls.
The
requirement
that
respiratory
protection
be
limited
to
supplied
air
respiratory
protection
is
based
on
the
fact
that
glycol
ethers
have
poor
warning
properties
at
the
proposed
PELs.
OSHA
requests
comment
on
this
provision.
OSHA
also
requests
comment
on
the
following:

a.
Would
the
proposed
requirement
of
supplied
air
respirators
provide
adequate
protection
or
are
there
other
kinds
of
respiratory
protection
that
would
be
more
appropriate
and
provide
more
protection?

b.
Are
there
situations
in
which
organic
vapor
cartridges
or
canisters
could
be
used
to
adequately
reduce
exposures
to
or
below
the
PELs?
Do
these
other
methods
have
adequate
warning
of
potential
breakthrough?
Please
provide
evidence
to
support
your
response
c.
Are
there
any
end­
of­
service­
life
indicators
for
the
glycol
ethers
covered
by
this
rulemaking?

d.
For
those
employers
whose
employees
are
exposed
to
glycol
ethers,
what
respiratory
protection
is
provided
to
employees
who
are
exposed
above
the
PELs?
How
and
why
was
the
particular
type
of
respiratory
protection
selected?

e.
What
is
the
cost
of
the
respiratory
protection
program?

7.
The
proposed
standard
would
require
that
employers
provide
appropriate
personal
protective
equipment
(
e.
g.
coveralls,
gloves,
eye
shields)
to
prevent
exposure
through
dermal
or
eye
contact
in
those
limited
situations
where
elimination
of
such
contact
is
not
capable
of
being
achieved
solely
by
means
of
engineering
and
work
practice
controls.
OSHA
requests
comment
on
this
provision.
OSHA
also
requests
information
on
the
following:
a.
OSHA
is
aware
that
some
exposures
to
glycol
ethers
may
be
intermittent
or
of
short
duration.
In
these
situations
the
breakthrough
time
of
protective
clothing
or
gloves
may
not
be
exceeded
during
a
single
use.
OSHA
requests
comment
on
whether
the
clothing
or
gloves
should
be
allowed
to
be
reused?
If
so,
in
what
situations
would
reuse
be
appropriate
or
to
what
situations
should
reuse
be
limited?

b.
For
employers
whose
employees
are
exposed
to
glycol
ethers,
what
kind
of
personal
protective
equipment
is
provided
and
in
what
situations?
Please
explain,
based
on
the
specific
situation,
how
and
why
use
of
such
equipment
was
determined.
Do
employees
reuse
protective
clothing
and
gloves?

c.
For
employers
whose
employees
are
exposed
to
glycol
ethers,
what
is
the
cost
of
the
personal
protective
equipment
that
is
provided?

8.
A
number
of
provisions
have
been
proposed
to
prevent
exposure
of
employees
through
off­
gassing
from
and/
or
contact
with
glycol
ethers
from
contaminated
personal
protective
equipment.
OSHA
requests
information
on
problems
associated
with
off­
gassing
and/
or
contact
in
the
storage,
handling,
and
disposal
of
contaminated
equipment
(
particularly
at
the
action
levels
that
have
been
proposed).
Should
specific
change
rooms
and
showers
be
required?

9.
Specific
clean­
up
procedures
have
not
been
required
in
the
proposal.
OSHA
requests
information
on
whether
specific
procedures
and
practices
should
be
required
and,
if
so,
what
procedures
are
necessary.
Is
peroxide
formation
a
problem
with
these
compounds?

10.
Paragraph
(
d)(
2)
of
the
proposed
standard
provides
that
initial
exposure
monitoring
would
be
required
for
all
employees
who
are
or
may
be
exposed
to
glycol
ethers.
OSHA
requests
comment
on
this
provision
a.
For
employers
whose
employees
are
exposed
to
glycol
ethers,
please
describe
your
monitoring
program
and
the
basis
for
performing
initial
monitoring
b.
What
are
the
cost
of
your
monitoring
program?

11.
Monitoring
would
be
permitted
to
be
discontinued
if
initial
monitoring
results
show
exposure
levels
to
be
below
the
action
level
and
at
or
below
the
excursion
limits.
Should
the
Agency
require
a
second
sample,
taken
at
least
seven
days
later,
to
confirm
the
initial
monitoring
results
before
permitting
discontinuance
of
monitoring
for
that
employee,
as
has
been
required
for
discontinuance
of
periodic
monitoring?

12.
In
the
medical
surveillance
provisions
of
the
proposed
standard
OSHA
has
not
proposed
a
requirement
for
any
specific
tests
for
the
detection
of
the
early
onset
of
adverse
reproductive
or
developmental
effects.
OSHA
requests
information
about
whether
there
are
any
medical
tests
which
can
be
routinely
used
to
detect
such
effects?
If
so,
what
are
these
tests
and
with
what
frequency
should
they
be
required?
Please
provide
data
and
evidence
to
support
your
response
13.
The
medical
surveillance
provisions
of
the
proposed
standard
would
require
that
counseling
or
tests,
which
are
requested
by
the
employee
and
deemed
appropriate
by
the
examining
physician,
be
made
available
to
employees
exposed
to
glycol
ethers
who
are
having
difficulty
conceiving
a
child
or
who
have
concerns
about
their
ability
to
conceive
a
healthy
child.
Are
these
requirements
adequate
and
appropriate?
If
not,
what
other
provisions
should
be
added?
For
those
employers
whose
employees
are
exposed
to
glycol
ethers,
OSHA
also
requests
information
on
the
following:

a.
Is
medical
surveillance
being
provided
to
exposed
employees?

b.
What
exposure
levels
or
other
factors
trigger
medical
surveillance?

c.
What
tests
and
counseling
are
included
in
the
medical
surveillance
program?

d.
What
provisions
are
included
in
the
medical
surveillance
program
to
address
reproductive/
developmental
health
effects
resulting
from
exposure
to
glycol
ethers?

e.
What
benefits
have
been
achieved
from
the
medical
surveillance
program?

f.
What
are
the
costs
of
the
medical
surveillance
program?

14.
Under
the
recordkeeping
provisions,
OSHA
proposes
that
medical
records
be
maintained
for
at
least
the
duration
of
employment
plus
30
years.
Is
this
recordkeeping
provision
adequate?
If
not,
what
other
provisions
would
provide
more
protection
and
be
more
appropriate?
For
those
employers
whose
employees
are
exposed
to
glycol
ethers,
what
is
the
current
policy
regarding
maintenance
of
medical
records?

15.
Data
and
evidence
presented
to
OSHA
in
response
to
the
ANPR
indicate
that
a
number
of
industry
sectors
are
substituting
away
from
manufacture
and
use
of
the
glycol
ethers
covered
under
[
page
15528]

this
proposal.

The
major
substitutes
are
2­
Butoxyethanol,
propylene
glycol
monomethyl
ether,
propylene
glycol
monomethyl
ether
acetate
and
ethylene
glycol
monopropyl
ether.
OSHA
requests
comment
on
the
following:

a.
Where
and
how
are
these
substitutes
being
used
and
to
what
degree
have
substitutes
replaced
the
glycol
ethers
covered
by
this
proposal?

b.
What
other
substitutes
are
being
used
in
place
of
the
glycol
ethers
covered
by
this
proposal?

c.
What
are
the
current
employee
exposure
levels
for
the
substitutes?
d.
Are
there
known
hazards
and
health
risks
associated
with
these
substitutes?

e.
For
employers
who
have
substituted,
wholly
or
partially,
away
from
the
glycol
ethers
covered
by
this
proposal,
why
was
substitution
undertaken?

f.
What
results,
positive
and
negative,
have
been
documented
as
a
result
of
substitution
(
e.
g.,
changes
in
productivity
and/
or
production
efficiency;
changes
in
product
quality;
changes
in
employee
absenteeism,
medical
expenses,
worker
compensation
payments,
insurance
premiums;
effects
on
compliance
with
environmental
regulations)?

g.
What
were
the
costs
of
substitution?

16.
For
employers
that
currently
manufacture
or
use
glycol
ethers
covered
by
this
proposal,
OSHA
requests
the
following
information
regarding
substitution:

a.
Are
there
substitutes
for
glycol
ethers
available
for
your
business?

b.
If
you
are
planning
to
substitute,
what
plans
and
timeline
do
you
have
for
replacing
glycol
ethers
with
substitute
chemicals?

c.
What
percentage
of
production
has
been
substituted
and
what
percentage
still
can
be
substituted
away
from
glycol
ethers?
What
factors
prevent
complete
substitution
away
from
glycol
ethers?

d.
What
will
be
the
projected
costs
of
substitution?

17.
OSHA
requests
the
following
information
from
employers
involved
in
glycol
ether
operations:

a.
Job
categories
for
each
operation
or
process
in
which
employees
are
potentially
exposed
to
glycol
ethers
b.
The
number
of
employees
in
each
of
those
job
categories
c.
A
brief
description
of
each
of
those
operations,
job
categories
and
production
techniques
d.
A
brief
description
of
the
engineering
and
work
practice
controls
associated
with
each
of
those
operations
e.
Raw
exposure
data,
annotated
if
possible,
associated
with
the
operations
described
above
f.
The
Standard
Industrial
Classification
(
SIC)
codes
of
the
establishment(
s)
18.
In
each
job
category
where
employees
are
potentially
exposed
to
glycol
ethers,
please
provide
the
following
information
regarding
employee
exposure
levels:

a.
The
last
two
years
of
raw
air
monitoring
results,
annotated
if
possible,
expressed
as
an
8­
hour
time
weighted
average
for
all
employees
who
are
exposed
to
glycol
ethers
and
the
dates
of
all
raw
air
monitoring
data
b.
The
duration
and
frequency
of
exposure
for
those
employees
c.
The
job
tasks
or
duties
being
performed
at
the
time
of
monitoring
d.
The
engineering
and
work
practice
controls
in
place
at
the
time
of
monitoring
e.
The
method
of
monitoring
used
to
measure
these
exposures
f.
To
the
extent
that
representative
sampling
is
used,
clearly
indicate
which
employees
within
each
job
category
were
monitored,
the
corresponding
results
and
which
employees
were
represented
by
the
sampling
results.
Please
discuss
your
representative
sampling
strategy
and
why
representative
sampling
was
used
19.
Please
provide
information
on
any
job
category
and
employee
whose
exposure
to
glycol
ethers
is
so
varied,
intermittent,
or
of
such
short
duration,
etc.,
that
the
raw
air
monitoring
data
provided
in
response
to
the
previous
question
do
not
adequately
portray
the
nature
of
the
exposures.
Please
explain
your
response
and
indicate
peak
levels,
duration
and
frequency
of
exposures
for
employees
in
those
job
categories
20.
OSHA
requests
the
following
information
regarding
engineering
and
work
practice
controls:

a.
For
employers
whose
employees
are
exposed
to
glycol
ethers,
are
the
proposed
PELs
currently
being
achieved
in
your
facilities
in
most
operations
most
of
the
time
by
means
of
engineering
and
work
practice
controls?

b.
In
what
operations
are
the
proposed
PELs
being
achieved
most
of
the
time
by
means
of
engineering
and
work
practice
controls?
What
engineering
and
work
practice
controls
have
been
implemented
in
those
operations?

c.
For
all
operations
in
your
facilities,
what
engineering
and
work
practice
controls
have
been
implemented?

d.
What
additional
engineering
and
work
practice
controls
could
be
implemented
in
each
operation
where
exposure
levels
are
currently
above
the
proposed
PELs
to
further
reduce
exposure
levels?

e.
When
these
additional
controls
are
implemented,
to
what
levels
can
exposure
levels
be
expected
to
be
reduced?
f.
What
are
the
costs
and
time
needed
to
develop,
install
and/
or
implement
additional
controls?

g.
Are
there
any
processes
or
operations
in
which
it
is
not
reasonably
possible
to
implement
engineering
and
work
practice
controls
within
six
months
to
one
year
to
achieve
the
proposed
PELs?
If
so,
would
allowing
additional
time
for
employers
to
come
into
compliance
with
paragraph
(
f)
make
compliance
reasonably
possible?
How
much
time
would
be
necessary?

21.
In
operations
where
air
exposure
levels
are
above
the
proposed
PELs,
to
what
extent
can
these
operations
and
processes
be
automated
and
enclosed
or
remotely
controlled?
To
what
extent
can
quality
control
sampling
be
remotely
controlled?
Are
there
any
restrictions
on
the
use
of
automated
or
remote
control
techniques?

22.
What
are
the
benefits,
other
than
reducing
employee
exposures
to
glycol
ethers,
that
can
be
derived
from
implementing
engineering
and
work
practice
controls
(
e.
g.,
reduced
exposure
to
other
contaminants;
compliance
with
environmental
regulations;
increased
productivity
and/
or
production
efficiency;
product
improvement;
reduced
absenteeism;
reduction
in
medical
expenses,
insurance
premiums
and
worker
compensation
payments,
etc.)?

23.
Are
engineering
control
technologies
that
have
proven
effective
in
industries
not
covered
by
this
notice
applicable
or
transferrable
to
the
chemicals
covered
by
this
proposal?
Please
explain
and
provide
evidence
to
support
the
nature
and
extent
of
compatibility
or
applicability
24.
OSHA
requests
information
on
whether
there
are
any
limited
unique
conditions
or
job
tasks
in
glycol
ether
manufacture
or
use
where
engineering
and
work
practice
controls
are
not
available
or
are
not
capable
of
reducing
exposure
levels
to
or
below
the
proposed
PELs
most
of
the
time.
Please
provide
data
and
evidence
to
support
your
response
25.
In
the
Preliminary
Regulatory
Impact
Analysis
OSHA
has
estimated
benefits
by
extrapolating
from
the
NOEL­
Uncertainty
Factor
approach.
OSHA
requests
comment
on
its
methodology
in
using
the
Uncertainty
Factor
approach
to
project
benefits.
OSHA
also
requests
comment
on
whether
there
are
alternative
methods,
either
quantitative
or
qualitative,
for
projecting
benefits
associated
with
a
reduction
in
exposure
to
glycol
ethers
26.
In
order
to
perform
the
economic
feasibility
analysis
for
the
final
rule,

[
page
15529]

OSHA
requests
employers
and
interested
parties
submit
the
following
information
from
the
last
five
years
on
your
company
and/
or
industry
sector:
a.
Profits,
sales
and
the
percentage
of
each
which
are
related
to
the
glycol
ethers
covered
by
this
proposal
b.
Total
annual
volume
and
dollar
value
of
production
for
your
company
and/
or
industry
sector.
What
percentages
are
related
to
the
glycol
ethers
covered
by
this
proposal?

c.
Annual
labor
turnover
rate
of
your
company
and/
or
industry
sector
for
jobs
involving
exposure
to
the
glycol
ethers
covered
by
this
proposal
27.
For
performing
an
economic
feasibility
analysis
,
OSHA
also
requests
the
following:

a.
A
financial
and
economic
profile
of
your
company
and/
or
industry
sector
b.
A
profile
of
your
financial
position
in
the
market
and
your
market
share
in
producing
glycol
ethers
or
producing
products
utilizing
glycol
ethers
c.
The
number
of
facilities
in
your
industry
sector
28.
What
is
the
age,
production
capacity
and
estimated
remaining
life
of
your
plant
and
equipment?

29.
Will
major
renovation
or
reconstruction
of
your
company
be
required
to
bring
air
monitoring
results
into
compliance
with
the
proposed
standard?
If
so,
please
provide
costs
and
time
necessary
for
renovation
and/
or
reconstruction
30.
The
Agency
has
prepared
a
draft
Regulatory
Flexibility
Analysis
analyzing
the
impacts
of
the
proposed
standard
on
the
small
businesses
which
OSHA
believes
may
be
affected.
The
following
information
is
requested
for
small
businesses
in
addition
to
the
information
OSHA
has
gathered
(
a)
What
kinds
of
small
businesses
or
organizations
and
how
many
of
them
would
be
affected
by
regulating
exposures?

(
b)
Which,
if
any,
federal
rules
may
duplicate,
overlap,
or
conflict
with
an
OSHA
regulation
concerning
glycol
ethers?

(
c)
Will
difficulties
be
encountered
by
small
entities
when
attempting
to
comply
with
requirements
of
the
proposed
standard?
Can
some
of
the
requirements
be
deleted
or
simplified
for
small
entities,
while
still
achieving
comparable
protection
for
the
health
of
employees
of
small
entities?

(
d)
What
timetable
would
be
appropriate
to
allow
small
entities
sufficient
time
to
comply?
31.
The
National
Environmental
Policy
Act
(
NEPA)
of
1969
(
42
U.
S.
C.
4321
et
seq.)
requires
that
each
Federal
agency
consider
the
environmental
impact
of
major
actions
significantly
affecting
the
quality
of
the
human
environment.
Any
person
having
information,
data
or
comments
pertaining
to
possible
environmental
impacts
is
invited
to
submit
them
along
with
accompanying
documentation
to
OSHA.
Such
impacts
might
include:

(
a)
Any
positive
or
negative
environmental
effects
that
could
result
should
a
standard
be
adopted;

(
b)
Beneficial
or
adverse
relationships
between
the
human
environment
and
productivity;

(
c)
Any
irreversible
commitments
of
natural
resources
which
could
be
involved
should
a
standard
be
implemented;
and
(
d)
Estimates
of
the
degree
of
reduction
of
glycol
ethers
in
the
environment
by
the
proposed
standard
and
alternatives
In
particular,
consideration
should
be
given
to
the
potential
direct
or
indirect
impacts
of
any
action,
or
alternative
actions,
on
water
and
air
pollution,
energy
usage,
solid
waste
disposal,
or
land
use
B.
Federalism
This
proposed
standard
has
been
reviewed
in
accordance
with
Executive
Order
12612,
52
FR
41685
(
October
30,
1987),
regarding
Federalism.
This
Order
requires
that
agencies,
to
the
extent
possible,
refrain
from
limiting
state
policy
options,
consult
with
States
prior
to
taking
any
actions
that
would
restrict
State
policy
options,
and
take
such
actions
only
when
there
is
clear
constitutional
authority
and
the
presence
of
a
problem
of
national
scope.
The
Order
provides
for
preemption
of
State
law
only
if
there
is
a
clear
Congressional
intent
for
the
agency
to
do
so.
Any
such
preemption
is
to
be
limited
to
the
extent
possible
Section
18
of
the
Occupational
Safety
and
Health
Act
(
OSH
Act),
expresses
Congress'
clear
intent
to
preempt
State
laws
with
respect
to
which
Federal
OSHA
has
promulgated
occupational
safety
or
health
standards.
Under
the
OSH
Act
a
State
can
avoid
preemption
only
if
it
submits,
and
obtains
Federal
approval
of,
a
plan
for
the
development
of
such
standards
and
their
enforcement.
Occupational
safety
and
health
standards
developed
by
such
Plan­
States
must,
among
other
things,
be
at
least
as
effective
as
the
Federal
standards
in
providing
safe
and
healthful
employment
and
places
of
employment
Since
these
materials
are
present
in
workplaces
in
every
state
of
the
Union,
the
occupational
hazard
of
glycol
ethers
is
a
national
problem
The
Federally
proposed
glycol
ether
standard
is
drafted
so
that
employees
in
every
State
would
be
protected
by
the
standard.
To
the
extent
that
there
are
any
State
or
regional
peculiarities,
States
with
occupational
safety
and
health
plans
approved
under
Section
18
of
the
OSH
Act
would
be
able
to
develop
their
own
State
standards
to
deal
with
any
special
problems
In
short,
there
is
a
clear
national
problem
related
to
occupational
safety
and
health
for
employees
exposed
to
glycol
ethers.
Those
States
which
have
elected
to
participate
under
Section
18
of
the
OSH
Act
would
not
be
preempted
by
this
proposed
regulation
State
comments
are
invited
on
this
proposal
and
will
be
fully
considered
prior
to
promulgation
of
a
final
rule
C.
State
Plans
Revisions
The
23
states
and
2
territories
which
operate
their
own
Federally­
approved
occupational
safety
and
health
plans
must
adopt
a
comparable
standard
within
six
months
of
the
publication
date
of
a
final
standard.
These
States
include:
Alaska,
Arizona,
California,
Connecticut
(
for
State
and
local
government
employees
only),
Hawaii,
Indiana,
Iowa,
Kentucky,
Maryland,
Michigan,
Minnesota,
Nevada,
New
Mexico,
New
York
(
for
State
and
local
government
employees
only),
North
Carolina,
Oregon,
Puerto
Rico,
South
Carolina,
Tennessee,
Utah,
Vermont,
Virginia,
Virgin
Islands,
Washington,
Wyoming.
Until
such
time
as
a
state
or
territorial
standard
is
promulgated,
Federal
OSHA
will
provide
interim
enforcement
assistance,
as
appropriate
II.
Pertinent
Legal
Authority
This
proposed
standard
and
the
issuance
of
a
final
standard
are
authorized
primarily
by
sections
4(
b)(
2),
6(
b),
8(
c)
and
8(
g)(
2)
of
the
Occupational
Safety
and
Health
Act
of
1970
(
the
Act)
(
29
U.
S.
C.
653(
b)(
2),
655(
b).,
657(
c),
657(
g)(
2))

Section
6(
b)(
5)
governs
the
issuance
of
occupational
safety
and
health
standards
dealing
with
toxic
materials
or
harmful
physical
agents.
Section
6(
b)(
5)
provides:
The
Secretary,
in
promulgating
standards
dealing
with
toxic
materials,
or
harmful
physical
agents
under
this
subsection,
shall
set
the
standard
which
most
adequately
assures,
to
the
extent
feasible,
on
the
basis
of
the
best
available
evidence,
that
no
employee
will
suffer
material
impairment
of
health
or
functional
capacity
even
if
such
employee
has
regular
exposure
to
the
hazard
dealt
with
by
such
standard
for
the
period
of
his
working
life.
Development
of
standards
under
this
subsection
shall
be
based
upon
research,
demonstrations,
experiments,
and
such
other
[
page
15530]

information
as
may
be
appropriate.
In
addition
to
the
attainment
of
the
highest
degree
of
health
and
safety
protection
for
the
employee,
other
considerations
shall
be
the
latest
available
scientific
data
in
the
field,
the
feasibility
of
standards,
and
experience
gained
under
this
and
other
health
and
safety
laws
Section
3(
8)
of
the
Act
defines
an
occupational
safety
and
health
standard
as
:
a
standard
which
requires
conditions,
or
the
adoption
or
use
of
one
or
more
practices,
means,
methods,
operations,
or
processes,
reasonably
necessary
or
appropriate
to
provide
safe
or
healthful
employment
and
places
of
employment
Under
section
6(
b)(
7)
of
the
Act,
standards
must,
where
appropriate,
include
provisions
for
labels
or
other
appropriate
forms
of
warning
to
apprise
employees
of
hazards,
suitable
protective
equipment,
exposure
control
procedures,
monitoring
and
measuring
of
employee
exposure,
employee
access
to
the
results
of
monitoring,
medical
examinations
or
other
tests,
at
no
cost
to
employees,
to
determine
whether
the
health
of
employees
is
adversely
affected
by
such
exposure,
and
training
and
education.
In
addition,
Section
8(
c)(
3)
of
the
Act
empowers
the
Secretary
to
promulgate
standards
prescribing
recordkeeping
requirements
where
necessary
or
appropriate
for
enforcement
of
the
Act
or
for
developing
information
regarding
the
causes
and
prevention
of
occupational
accidents
and
illnesses
The
Supreme
Court
has
held
that
under
the
Act
the
Secretary,
before
issuing
a
new
standard,
must
determine
that
it
is
reasonably
necessary
and
appropriate
to
remedy
a
significant
risk
of
material
health
impairment.
Industrial
Union
Department
v.
American
Petroleum
Institute,
448
U.
S.
607,
642
(
1980).
The
Court
stated
that
"
before
he
can
promulgate
any
permanent
health
or
safety
standard,
the
Secretary
is
required
to
make
a
threshold
finding
that
a
place
of
employment
is
unsafe
in
the
sense
that
significant
risks
are
present
and
can
be
eliminated
or
lessened
by
a
change
in
practices."
Id.,
at
642,
644,
n.
49
The
Court
indicated,
however,
that
the
significant
risk
determination
is
"
not
a
mathematical
straightjacket."
Id.,
at
655.
"
OSHA
is
not
required
to
support
its
finding
that
a
significant
risk
exists
with
anything
approaching
scientific
certainty."
Id.,
at
656.
Rather,
the
Court
stated
that
"
a
reviewing
court
[
is]
to
give
OSHA
some
leeway
where
its
findings
must
be
made
of
the
frontiers
of
scientific
knowledge."
Id.,
at
656.
The
Court
also
stated
that
while
the
"
Agency
must
support
its
findings
that
a
certain
level
of
risk
exists
with
substantial
evidence,
we
recognize
that
its
determination
that
a
particular
level
of
risk
is
'
significant'
will
be
based
largely
on
policy
considerations."
Id.,
at
655­
56,
n.
62
After
OSHA
has
determined
that
a
significant
risk
exists
and
that
such
a
risk
can
be
reduced
or
eliminated,
it
must
set
a
standard
"
which
most
adequately
assures,
to
the
extent
feasible
on
the
basis
of
the
best
available
evidence,
that
no
employee
will
suffer
material
impairment
of
health."
(
Section
6(
b)(
5)).
The
Supreme
Court
has
interpreted
this
section
to
mean
that
OSHA
must
enact
the
most
protective
standard
possible
to
eliminate
a
significant
risk
of
material
health
impairment,
subject
to
the
constraints
of
technological
and
economic
feasibility.
American
Textile
Manufacturers
Institute
v.
Donovan,
452
U.
S.
490,
509
(
1981).
The
Court
held
that
"
cost­
benefit
analysis
by
OSHA
is
not
required
by
the
statute
because
feasibility
analysis
is."
Id
Section
4(
b)(
2)
of
the
Act
provides
that
standards
issued
under
OSHA
apply
to
construction
and
maritime
employment
where
the
Secretary
determines
these
standards
to
be
more
effective
than
existing
standards
which
would
otherwise
apply
to
that
employment.
(
OSHA
has
proposed
the
addition
of
new
paragraph
(
n)
to
29
CFR
1910.19,
which
would
apply
the
proposed
glycol
ethers
standard
to
construction
and
maritime
employment,
in
addition
to
its
coverage
of
general
industry)
Authority
to
issue
this
proposed
standard
is
further
supported
by
the
general
rulemaking
authority
found
in
section
8(
g)
of
the
Act
Section
8(
g)(
2)
empowers
the
Secretary
to
"
prescribe
such
rules
and
regulations
as
he
may
deem
necessary
to
carry
out
[
his]
responsibilities
under
the
Act."
The
Secretary's
responsibilities
under
the
Act
are
defined
largely
by
its
enumerated
purposes
(
section
2(
b)),
which
include:

Encouraging
employers
and
employees
in
their
efforts
to
reduce
the
number
of
occupational
safety
and
health
hazards
at
their
places
of
employment,
and
to
stimulate
employers
and
employees
to
institute
new
and
to
perfect
existing
programs
for
providing
safe
and
healthful
working
conditions;

Building
upon
advances
already
made
through
employer
and
employee
initiative
for
providing
safe
and
healthful
working
conditions;

Developing
innovative
methods,
techniques,
and
approaches
for
dealing
with
occupational
safety
and
health
problems;

Exploring
ways
to
discover
latent
diseases,
establishing
causal
connections
between
diseases
and
work
in
environmental
conditions;

Providing
for
the
developing
and
promulgation
of
occupational
safety
and
health
standards;

Providing
for
appropriate
reporting
procedures
with
respect
to
occupational
safety
and
health
which
procedures
will
help
achieve
the
objectives
of
this
Act
and
accurately
describe
the
nature
of
the
occupational
safety
and
health
problems;

Encouraging
joint
labor­
management
efforts
to
reduce
injuries
and
disease
arising
out
of
employment
Because
the
proposed
glycol
ethers
standard
is
reasonably
related
to
these
statutory
goals
and
because
the
Agency's
preliminary
judgement
is
that
the
evidence
satisfies
the
statutory
requirements
and
that
the
proposed
standard
is
feasible
and
substantially
reduces
significant
risk
of
adverse
health
effects,
especially
reproductive
and
developmental
health
effects,
the
Secretary
preliminarily
finds
that
the
proposed
standard
is
necessary
and
appropriate
to
carry
out
the
Agency's
responsibilities
under
the
Act
III.
History
of
the
Regulation
OSHA's
current
Permissible
Exposure
Limits
(
PELs)
for
2­
ME,
2­
MEA,
2­
EE,
and
2­
EEA
are
25
ppm,
25
ppm,
200
ppm,
and
100
ppm,
respectively.
All
are
time
weighted
averages
(
TWAs)
for
an
8­
hour
workshift
(
29
CFR
1910.1000,
Table
Z­
1­
A).
In
the
Z­
1­
A
Table,
2­
ME,
2­
MEA,
2­
EE,
and
2­
EEA
are
listed
under
the
names
Methyl
Cellosolve,
Methyl
Cellosolve
Acetate,
2­
Ethoxyethanol,
and
2­
Ethoxyethanol
Acetate,
respectively.
The
OSHA
standards
bear
a
skin
notation,
indicating
the
potential
contribution
to
the
overall
exposure
by
the
cutaneous
route,
including
mucous
membranes
and
eye,
either
by
airborne
or
more
particularly,
by
direct
contact
with
the
substance
The
current
standards
were
adopted
in
1971
pursuant
to
section
6(
a)
of
the
Occupational
Safety
and
Health
Act
of
1970
(
29
U.
S.
C.
655).
The
source
of
these
standards
was
the
American
Conference
of
Governmental
Industrial
Hygienists
(
ACGIH)
and
they
are
based
primarily
on
blood,
kidney,
liver
and
central
nervous
system
toxicity
In
the
late
1970'
s,
many
studies
began
to
be
published
regarding
adverse
effects,
including
testicular
atrophy,
infertility,
fetotoxicity,
and
fetal
malformations
in
laboratory
animals
exposed
to
glycol
ethers.
In
response
to
these
findings,
the
ACGIH,
in
its
notice
of
Intended
Changes
(
for
1982),

[
page
15531]

proposed
TWAs
of
5
ppm
for
2­
ME,
2­
EE
and
their
acetates
which
were
subsequently
adopted
in
1984.
Likewise,
on
May
2,
1983,
NIOSH
published
a
Current
Intelligence
Bulletin
recommending
that
2­
ME
and
2­
EE
be
regarded
in
the
workplace
as
having
the
potential
to
cause
adverse
reproductive
effects
in
male
and
female
workers
and
embryotoxic
effects,
including
teratogenesis,
in
the
offspring
of
the
exposed
pregnant
females
and
urged
employers
to
reduce
exposures
to
the
lowest
extent
possible
(
Ex.
5­
001)

On
January
24,
1984,
EPA
published
an
Advance
Notice
of
Proposed
Rulemaking
(
ANPR)
in
which
they
announced
their
intention
to
regulate
2­
ME,
2­
EE
and
their
acetates
(
49
FR
2921).
EPA
was
concerned
about
the
toxicity
of
these
chemicals
due
to
evidence
of
human
exposure
to
concentrations
above
levels
currently
recommended
by
the
ACGIH,
and
the
potential
for
significant
numbers
of
individuals
to
become
exposed.
After
consideration
of
the
record
developed
in
connection
with
its
ANPR,
EPA
determined
that
the
risks
associated
with
exposure
to
2­
ME,
2­
EE
and
their
acetates
could
be
sufficiently
reduced
by
action
taken
under
the
OSH
Act.
Following
these
findings,
EPA,
in
accordance
with
section
9(
a)
of
TSCA,
on
May
20,
1986,
referred
2­
ME,
2­
EE
and
their
acetates
to
OSHA
to
give
this
Agency
an
opportunity
to
regulate
the
chemicals
under
the
OSH
Act(
51
FR
18488).
EPA
requested
OSHA
to
determine
whether
the
risks
described
in
the
EPA
report
could
be
prevented
or
reduced
to
a
sufficient
extent
by
action
taken
under
the
OSH
Act.
If
such
a
determination
was
made
then
OSHA
was
requested
to
issue
a
notice
declaring
whether
the
manufacture
and
use
described
in
the
EPA
report
presented
the
risk
therein
described.
EPA
requested
OSHA
to
respond
within
180
days
On
December
11,
1986,
OSHA
published
a
notice
(
51
FR
42257)
responding
to
the
EPA
referral
report
by
making
a
preliminary
determination
that
a
revised
OSHA
standard
limiting
occupational
exposure
to
2­
ME,
2­
EE
and
their
acetates
could
prevent
or
reduce
the
risks
due
to
exposure
to
a
sufficient
extent
and
that
such
a
risk
had
been
accurately
described
by
EPA
in
the
report
On
April
2,
1987,
OSHA
decided
it
would
proceed
with
permanent
rulemaking
to
reduce
exposure
to
2­
ME,
2­
EE
and
their
acetates
and
published
an
ANPR
(
52
FR
10586).
OSHA
based
its
decision
on
the
determination
that
the
existing
standards
did
not
adequately
address
the
adverse
health
effects
associated
with
2­
ME,
2­
EE
and
their
acetates.
OSHA
solicited
information
and
comments
regarding
the
hazards
of
exposures
to
the
chemicals,
control
methods
for
reducing
these
hazards
and
the
costs
of
controlling
exposures
In
September
of
1991,
NIOSH
published
a
Criteria
for
a
Recommended
Standard
for
Ethylene
Glycol
Monomethyl
Ether,
Ethylene
Glycol
Monoethyl
Ether,
and
Their
Acetates
(
i.
e.,
2­
ME,
2­
EE
and
their
acetates)
(
Ex.
5­
154).
In
this
document
NIOSH
recommended
worker
exposures
to
2­
ME
and
its
acetate,
2­
MEA,
be
limited
to
0.1
ppm
as
time
weighted
average
for
up
to
10
hours/
day
during
a
40
hour
workweek
(
10­
hr
TWA)
and
that
worker
exposure
to
2­
EE
and
its
acetate,
2­
EEA,
be
limited
to
0.5
ppm
as
a
10­
hr
TWA.
NIOSH
also
recommended
that
dermal
contact
to
2­
ME,
2­
EE
and
their
acetates
be
prohibited.
In
addition
to
these
recommended
exposure
limits,
NIOSH
also
recommended
various
industrial
hygiene
provisions
including
exposure
monitoring,
medical
monitoring,
protective
clothing
and
equipment,
engineering
controls
and
work
practices
and
hazard
communication.
The
provisions
of
this
recommended
standard
were
based
primarily
on
adverse
reproductive,
developmental
and
blood
effects
IV.
Chemical
Identification,
Production
and
Use
of
Ethylene
Glycol
Ethers
The
chemicals,
2­
Methoxyethanol
(
2­
ME),
2­
Methoxyethanol
acetate
(
2­
MEA),
2­
Ethoxyethanol
(
2­
EE),
and
2­
Ethoxyethanol
acetate
(
2­
EEA)
are
members
of
a
class
of
chemicals
known
as
ethylene
glycol
ethers
which
are,
in
turn,
members
of
a
broader
class
of
chemicals
known
as
glycol
ethers.
In
this
document
the
terms
ethylene
glycol
ethers
or
glycol
ethers
will
refer
only
to
2­
ME,
2­
MEA,
2­
EE
and
2­
EEA.
The
respective
Chemical
Abstract
Service
(
CAS)
Registry
numbers
for
the
subject
ethylene
glycol
ethers
are
109­
86­
4,
110­
49­
6,
110­
80­
5,
111­
15­
9.
All
four
compounds
are
colorless,
flammable
liquids
which
are
compatible
with
a
broad
range
of
resins
and
are
miscible
in
both
organic
solvents
and
water.
They
have
relatively
low
vapor
pressures,
high
boiling
points,
low
evaporation
rates
and
high
flash
points.
At
room
temperature
and
atmospheric
pressure,
these
compounds
are
highly
reactive
in
the
presence
of
strong
oxidizers;
2­
MEA
and
2­
EEA
are
also
highly
reactive
in
the
presence
of
nitrates
and
strong
acids.
Decomposition
products
during
combustion
include
toxic
gases
and
vapors
such
as
carbon
monoxide
2­
ME,
chemical
formula
CH(
3)
OCH(
2)
CH(
2)
OH,
has
a
molecular
weight
of
76.1,
a
boiling
point
at
760mm
Hg
of
124
C,
a
vapor
pressure
at
20
C
of
6mm
Hg,
a
flash
point
of
42
C
and
possesses
a
mild
non­
residual
odor.
2­
MEA,
chemical
formula
CH(
3)
COOCH(
2)
OCH(
3),
has
a
molecular
weight
of
118,
a
boiling
point
of
145
C
,
a
vapor
pressure
of
2mm
Hg,
a
flash
point
of
44
C
and
possesses
a
mild
ether­
like
odor.
2­
EE,
chemical
formula
C(
2)
H(
5)
OCH(
2)
CH(
2)
OH,
has
a
molecular
weight
of
90.1.,
a
boiling
point
of
135
C,
a
vapor
pressure
of
4mm
Hg,
a
flash
point
of
49
C
and
possesses
a
sweetish
odor
with
odor.
2­
EEA
has
chemical
formula
C(
2)
H(
5)
OCH(
2)
OCOCH(
3),
a
molecular
weight
of
132,
a
boiling
point
of
156
C,
a
vapor
pressure
of
2mm
Hg,
a
flash
point
of
47
C
and
possesses
a
mild
non­
residual
odor.
The
odor
thresholds
of
these
compounds
are
discussed
in
the
Respiratory
Protection
portion
of
this
document
Ethylene
glycol
ethers
are
produced
by
the
ethoxylation
of
ethylene
oxide
with
preheated
anhydrous
alcohol.
Methyl
alcohol
produces
ethylene
glycol
monomethyl
ether
(
2­
ME)
and
ethyl
alcohol
produces
ethylene
glycol
monoethyl
ether
(
2­
EE).
The
corresponding
acetates,
2­
MEA
and
2­
EEA,
are
produced
by
the
esterification
of
2­
ME
and
2­
EE
with
acetic
acid
Due
to
their
physical
characteristics,
ethylene
glycol
ethers
are
useful
in
a
wide
variety
of
applications,
particularly
as
solvents.
In
general,
these
ethers
are
used
extensively
in
the
formulation
of
paints
and
coatings,
commercial
printing
inks,
industrial
solvents,
and
cleaners.
They
are
also
used
as
chemical
intermediates
in
the
production
of
plastisizers,
as
de­
icing
additives
in
jet
fuels,
and
in
electronics
manufacturing
After
manufacture
of
glycol
ethers
for
export
(
45%
of
total
sales),
the
utilization
of
these
compounds
as
chemical
intermediates
accounts
for
the
largest
percentage
(
24%)
of
their
sales
(
PEI
report,
Ex.
5­
164).
For
example,
the
manufacture
of
2­
EEA
is
the
largest
single
use
of
2­
EE
while
2­
ME
is
used
in
the
production
of
2­
MEA.
Both
2­
ME
and
2­
EE
are
also
used
to
produce
a
variety
of
plastisizers
for
use
in
such
products
as
35
mm
film,
insulation
for
high
voltage
wires,
and
high
flash
coatings
Another
principal
area
of
use
(
15%
of
total
sales)
of
the
four
glycol
ethers
is
in
the
formulation
of
paints
and
coatings
(
e.
g.,
primers,
varnishes,
stains,
etc.).
These
paints
and
coatings
are
utilized
in
original
equipment
manufacture
(
OEM)
of
items
such
as
automobiles
and
trucks,
machinery
and
equipment,
metal
cans,

[
page
15532]

metal
furniture
and
appliances,
and
in
coil
coatings.
They
are
also
found
in
auto
refinishing
and
maintenance
painting
formulations.
In
addition,
all
four
glycol
ethers
are
used
in
a
variety
of
special
coating
applications
ranging
from
fingernail
polish
to
wood
stains
The
electronics
industry
employs
glycol
ethers
in
the
manufacture
of
semiconductors
and
circuit
boards.
Glycol
ethers
are
a
component
of
the
photoresist
used
in
the
photolithography
of
semiconductor
circuit
designs
in
addition
to
being
utilized
in
coating/
lamination
resins
of
circuit
boards.
Products
used
in
the
marking,
bonding,
and
labeling
of
circuit
boards
may
also
contain
ethylene
glycol
ethers
Substantial
quantities
of
2­
ME
are
used
as
de­
icing
additive
in
jet
fuel.
Since
commercial
jets
have
in­
line
de­
icers,
this
market
is
principally
military.
However,
some
general
aviation
jet
fuel
also
requires
de­
icing
additive
Comparable
to
glycol
ether's
use
in
paint
and
coatings
is
their
role
as
solvents
in
the
formulation
of
commercial
printing
inks,
particularly
those
used
in
silk
screen,
flexographic,
and
gravure
printing.
Ethylene
glycol
ethers
are
also
found
in
formulations
used
in
textile
dyeing
and
printing.
In
addition
to
being
a
component
of
the
ink
itself,
glycol
ethers
are
used
in
solvents
and
machinery
cleaners
for
the
commercial
printing
industry
While
the
above
uses
account
for
the
vast
bulk
of
glycol
ether
consumption,
they
have
also
been
reported
to
be
utilized
in
a
number
of
diverse
cleaning
solvents,
as
solvent
in
adhesive,
in
leather
dying/
tanning,
and
in
the
manufacturing
of
pharmaceuticals
V.
Health
Effects
A.
Introduction
The
experimental
studies
in
animals
clearly
demonstrate
that
2­
ME
and
2­
EE
induce
adverse
reproductive,
developmental
and
hematological
effects.
Several
species
(
e.
g.,
rats,
rabbits
and
mice)
exposed
through
several
routes
of
exposure
(
e.
g.,
oral,
dermal,
and
inhalation)
have
consistently
shown
similar
effects
after
exposure
to
these
ethylene
glycol
ethers.
Exposed
males
have
exhibited
testicular
degeneration,
disrupted
spermatogenesis
and
reduced
fertility.
Females
exposed
during
gestation
have
shown
signs
of
maternal
toxicity
as
well
as
increased
incidence
of
resorptions.
Offspring
from
these
exposed
females
have
exhibited
a
variety
of
teratogenic
effects
including
cardiac,
skeletal
and
visceral
malformations.
In
addition
new
born
pups
have
exhibited
behavioral
and
neurochemical
alterations.
Adverse
blood
effects
have
also
been
observed
after
exposure.
These
effects
include
decreases
in
red
blood
cells,
white
blood
cells,
hemoglobin
concentrations
and
hematocrit
Although
less
extensive,
the
animal
data
has
also
shown
that
the
acetates,
2­
MEA
and
2­
EEA,
induce
adverse
reproductive
and
developmental
and
hematological
effects
similar
to
those
observed
among
their
parent
glycol
ethers.
These
studies
confirm
the
findings
of
metabolic
studies
which
indicate
that
2­
ME,
2­
EE
and
their
acetates
follow
similar
metabolic
pathways,
producing
similar
metabolites,
which
are
the
active
agents
most
likely
responsible
for
the
observed
effects
Consistent
with
these
experimental
results
is
human
evidence
of
reproductive
and
hematological
effects.
Workers
exposed
to
2­
ME
and
2­
EE
have
exhibited
decreased
sperm
counts,
testicular
atrophy
and
decreased
red
and
white
blood
cell
counts.
Little
data
has
been
reported
on
the
reproductive,
maternal
or
developmental
effects
for
women
exposed
to
glycol
ethers.
However,
the
lack
of
data
in
this
area
may
be
due,
in
most
part,
to
the
difficulty
in
conducting
analyses
for
these
types
of
adverse
effects.
Although
workers
in
some
instances
were
exposed
to
multiple
substances,
making
it
difficult
to
ascribe
exposure
to
a
particular
glycol
ether
to
an
observed
effect,
the
human
evidence
is,
nevertheless,
consistent
with
and
supportive
of
the
animal
evidence
which
indicates
that
these
substances
will
induce
adverse
reproductive
and
developmental
effects
B.
Metabolism/
Metabolic­
Related
Health
Effects
The
ethylene
glycol
ethers,
2­
ME
and
2­
EE,
are
metabolized
to
their
corresponding
acetic
acids,
methoxyacetic
acid
(
MAA)
and
ethoxyacetic
acid
(
EAA),
by
an
alcohol
dehydrogenase
(
ADH)
mediated
pathway.
Animal
studies
conducted
with
MAA
have
shown
that
it
is
the
metabolite,
rather
than
the
parent
glycol
ether,
which
is
responsible
for
inducing
adverse
reproductive
and
developmental
effects.
2­
MEA
and
2­
EEA
are
also
metabolized
by
the
ADH
pathway
to
MAA
and
EAA.
Because
these
two
acetates
are
metabolized
to
the
same
primary
metabolites
as
their
corresponding
parent
glycol
ethers,
it
is
assumed
that
they
will
induce
similar
adverse
reproductive
and
developmental
effects.
Studies
in
male
and
female
volunteers
confirm
that
the
ADH
pathway
is
also
the
primary
route
of
metabolism
in
humans.
However
these
studies
also
indicate
that
the
retention
and
biological
half
life
of
the
active
metabolite
is
longer
in
humans
than
in
animals
Miller
et
al.
(
Ex.
4­
131)
identified
MAA
as
the
primary
metabolite
of
2­
ME
by
radiogaschromatography
mass
spectrometry
analysis.
The
investigators
recovered
50­
60%
of
the
administered
14C
from
urine
of
rats
within
48
hours
after
a
single
oral
dose
of
[
14C]
2­
ME.
Expired
14CO2
was
the
only
other
significant
route
of
elimination
(
12%).
Thus,
urine
was
established
as
the
major
vehicle
of
elimination
of
14C
after
a
single
oral
dose
of
[
14C]
2­
ME.
Urine
collected
was
then
analyzed
by
radiogas­
chromatography/
mass
spectrometry.
Analysis
revealed
the
primary
component
as
methoxyacetic
acid.
Based
on
these
findings
Miller
et
al.
concluded
that
2­
ME
is
first
oxidized
to
methoxyacetaldehyde
by
ADH
and
then
further
oxidized
to
MAA
by
aldehyde
dehydrogenase
Evidence
also
indicates
that
MAA
is
the
ultimate
toxin
responsible
for
the
observed
adverse
reproductive
and
developmental
effects.
Brown
et
al.
(
Ex.
4­
102)
gave
single
injections
of
244
mg
MAA/
kg
to
pregnant
rats
on
days
8,
10,
12
or
14
of
gestation.
Exposure
to
MAA
induced
significant
increases
in
the
incidence
of
embryo­
fetal
mortality,
decreases
in
fetal
weight,
and
increases
in
structural
malformations
(
e.
g.,
skeletal
malformations,
hydrocephalus
and
urogenital
abnormalities).
Similarly
Miller
et
al.
(
Ex.
4­
133)
found
that
the
administration
of
MAA
daily
for
two
weeks
by
gavage
to
rats
resulted
in
severe
degeneration
of
testicular
germinal
epithelium
and
hematological
abnormalities.
For
example
significant
decreases
in
testicular
weight
and
in
red
blood
cell
counts
were
observed
at
300
and
100
mg
MAA/
kg.
These
toxicological
effects
were
remarkably
similar
to
those
observed
following
administration
of
2­
ME.
The
authors
concluded
that
the
adverse
health
effects
of
2­
ME
are
probably
the
result
of
in
vivo
activation
of
2­
ME
to
MAA,
and
that
MAA
is
the
proximate
toxin
following
administration
of
2­
ME.
The
findings
of
Ritter
et
al.
(
Ex.
4­
143),
Yonemoto
(
Ex.
4­
192)
and
Foster
et
al.
(
Ex.
5­
052)
are
consistent
with
this
view
In
addition
to
their
studies
on
the
teratogenicity
of
MAA,
Ritter
al.
(
Ex.
4­
143)
also
investigated
the
effects
of
the
co­
administration
of
2­
ME
and
4­
Methylpyrazole.
4­
Methylprazole(
4­
MP)
is
an
inhibitor
of
alcohol
dehydrogenase(
ADH)
and
thus
may
block
metabolism
occurring
by
an
ADH
pathway.
In
this
study
it
was
observed
[
page
15533]

that
embryotoxicity
(
i.
e.,
the
number
of
dead,
resorbed
and
malformed
fetuses)
following
co­
administration
of
the
two
substance
was
16.8%,
as
compared
to
100%
for
the
same
dose
and
the
same
route
of
2­
ME
alone.
The
observation
that
the
co­
administration
of
4­
MP
provided
significant
protection
against
the
embryotoxic
of
2­
ME
is
consistent
with
the
hypothesis
that
metabolism
of
2­
ME
occurs
via
the
alcohol
dehydrogenase(
ADH)
pathway
and
that
it
is
the
primary
metabolite
that
is
most
likely
the
active
agent
in
the
induction
of
adverse
effects
Similar
findings
have
been
reported
by
Sleet
et
al
(
Ex.
5­
118).
In
this
study
pregnant
mice
were
exposed
to
either
2­
ME
(
1.3
to
1.6
mmole/
kg)
or
MAA
(
1.1
to
1.7
mmole/
kg)
by
gavage
on
day
11
of
gestation.
2­
ME
and
MAA
were
found
to
be
equally
potent
in
producing
significant
increases
in
the
incidence
of
paw
malformations
(
e.
g.,
webbed,
missing
or
additional
digits).
The
co­
administration
of
4­
Methyl
Pyrazole
was
found
to
reduce
the
teratogenic
potency
of
2­
ME.
For
example,
the
incidence
of
malformations
induced
by
4.6
mmole/
kg
2­
ME
was
reduced
from
94%
to
59%
when
4­
MP
was
administered
at
a
dose
of
0.12
mmole/
kg.
The
incidence
of
malformations
was
reduced
to
0%
when
4­
MP
was
administered
at
a
dose
of
1.2
mmole/
kg.
These
data
further
indicate
the
role
of
metabolism
in
inducing
teratogenic
effects
and
strongly
points
to
MAA
as
the
active
agent
Similar
to
the
metabolic
studies
on
2­
ME,
the
evidence
also
indicates
that
the
primary
metabolite
of
2­
EE
is
also
an
alkoxyacetic
acid;
in
this
case
ethoxyacetic
acid
(
EAA).
Cheever
et
al.
(
Ex.
5­
089)
gave
single
oral
doses
of
230
mg
2­
EE/
kg
body
weight.
The
major
metabolites
detected
in
the
urine
were
EAA
and
N­
ethoxyacetyl
glycine.
EAA
was
also
detected
in
the
rat
testes.
The
authors
concluded
that
the
most
probable
route
of
metabolism
was
the
oxidation
of
2­
EE
through
ADH
to
EAA
with
some
subsequent
conjugation
of
EAA
to
glycine
to
form
N­
ethoxyacetyl
glycine
Similar
to
the
findings
in
animal
studies,
experimental
studies
using
male
and
female
volunteers,
have
shown
alkoxyacetic
acids
to
be
the
primary
metabolites
in
humans.
In
a
series
of
experiments
Groeseneken
et
al.
(
Exs.
5­
112,
5­
113,
and
5­
114)
exposed
10
male
volunteers
by
inhalation
to
2.7,
5.4
or
10.8
ppm
2­
EE
for
4
hours,
both
at
rest
and
during
physical
exercise.
Consistent
with
findings
in
animal
studies,
EAA
was
found
to
be
the
major
urinary
metabolite.
However
the
biological
half
life
in
humans
was
found
to
be
approximately
21­
24
hours
compared
to
the
biological
half
life
of
8­
12
hours
reported
in
animals.
It
was
also
observed
that
EAA
excretion
increased
with
increasing
dose
and/
or
physical
activity.
Due
to
the
long
half
life,
the
authors
stated
that
EAA
will
not
be
cleared
from
the
urine
by
the
next
morning
following
exposure
and
accumulation
of
the
metabolite
may
be
expected
through
repetitive
exposures.
Thus
EAA
may
build
up
in
the
body
over
the
course
of
the
workweek
In
a
similar
study
Groeseneken
et
al.
(
Ex.
5­
115)
exposed
10
male
volunteers
by
inhalation
to
2­
EEA.
Five
volunteers
were
exposed
at
rest
to
2.6,
5.2
and
9.3
ppm
2­
EEA
and
5
were
exposed
to
5.2
ppm
2­
EEA
during
physical
exercise.
Again,
EAA
was
detected
as
the
major
metabolite
with
a
biological
half
life
of
approximately
23
hours.
It
was
observed
that
the
metabolism
of
2­
EEA
followed
the
same
time
course
as
2­
EE
(
Ex.
5­
112)
and
that
for
equivalent
doses
of
2­
EE
and
2­
EEA,
equivalent
amounts
of
EAA
were
excreted.
The
authors
concluded
that
2­
EEA
is
first
converted
to
2­
EE
by
esterases
and
then
to
EAA
by
an
ADH
mediated
pathway.
Similarly
it
was
found
that
EAA
is
not
cleared
from
urine
by
the
next
morning
and
thus
may
build
up
over
the
work
week
following
repetitive
exposures
In
field
study
of
workers,
Veulemans
et
al.
(
Ex.
5­
114)
studied
the
urinary
excretion
of
EAA
for
a
group
of
5
female
silk
screen
operators
who
were
exposed,
by
inhalation,
to
mixtures
of
2­
EE
and
2­
EEA
at
approximately
5.6
and
5
ppm,
respectively.
In
this
study
the
women
were
monitored
for
5
days
during
a
normal
production
period.
They
were
also
monitored
during
another
7
day
period
after
a
12
day
production
stop.
Similar
to
the
experimental
studies
among
human
volunteers,
EAA
was
detected
in
the
urine
as
the
major
metabolite
during
the
5
days
of
production
and
was
also
found
to
accumulate
during
the
workweek.
The
authors
also
reported
that
even
after
12
days
of
non­
exposure,
traces
of
EAA
were
still
detectable
in
the
urine.
The
authors
stated
that
these
findings
confirmed
the
earlier
short
term
studies
by
Groeseneken
(
Exs.
5­
112
and
5­
115)
and
suggested
that
the
biological
half
life
of
EAA
may
even
be
greater
than
24
hours.
Moreover
they
added
that
from
a
toxicological
point
of
view,
"
it
would
certainly
warrant
extra
caution
in
the
extrapolation
of
experimental
data
from
laboratory
animals
to
man,
since
comparable
accumulation
effects
apparently
are
not
found
in
all
species."

To
further
investigate
the
metabolic
differences
between
rats
and
humans,
Groeseneken
et
al.
(
Ex.
5­
137)
compared
the
urinary
excretion
of
EEA
in
man
and
rat.
In
this
study
rats
were
orally
exposed
to
2­
EE
at
low
doses
comparable
to
the
inhalation
doses
used
on
male
volunteers
in
previous
experimental
studies(
Ex.
5­
112).
The
authors
stated
that
oral
doses
were
used
in
rats
due
to
the
lack
of
animal
data
necessary
to
calculate
respiratory
uptake
of
2­
EE
(
e.
g.,
2­
EE
pulmonary
retention
and
respiratory
minute
volume).
Data
for
calculating
respiratory
uptake
were
available
in
human
studies.
It
was
assumed
that
metabolism
was
independent
of
the
route
of
administration.
Groups
of
five
rats
were
exposed
to
single
oral
doses
of
0.5
mg/
kg,
1
mg/
kg,
5
mg/
kg,
10
mg/
kg,
50
mg/
kg
or
100
mg/
kg
2­
EE.
Exposure
levels
of
0.5
mg/
kg
and
1
mg/
kg
were
noted
by
the
authors
to
be
equivalent
to
human
exposures
of
5.4
ppm
or
10.8
ppm
2­
EE
used
in
the
human
experimental
studies.
After
a
correction
for
body
weight
on
urinary
excretion,
results
from
these
studies
showed
that,
for
humans,
the
maximal
excretion
rate
of
the
primary
metabolite,
EEA,
declined
at
a
slower
rate
(
48
hours
after
exposure)
than
in
rats
(
12
hours
after
exposure)
at
equivalent
doses.
In
addition
the
half
life
for
EEA
in
humans
was
calculated
at
42
hours
compared
to
7.2
hours
for
rats:
almost
6
times
higher
for
man.
The
authors
suggested
that
these
findings
could
have
important
consequences
for
the
toxicity
of
2­
EE
in
man
as
the
toxic
properties
of
2­
EE
have
been
associated
with
the
alkoxyacetic
acid
metabolite,
EEA.
Romer
et
al.
(
Ex.
5­
033)
have
also
shown
that
the
coadministration
of
ethanol
with
2­
ME
and
2­
EE
prolonged
the
retention
of
2­
ME
and
2­
EE
in
the
blood.
In
this
study
rats
were
pretreated
with
ethanol
and
then
exposed
by
inhalation
to
1600
ppm
2­
ME
or
420
ppm
2­
EE
or
ip­
administration
to
5
ml/
kg
body
weight
2­
ME
or
2­
EE).
In
both
cases
it
was
observed
that
degradation
of
2­
ME
and
2­
EE
was
almost
completely
inhibited
when
rats
were
pretreated
with
ethanol.
Only
after
the
elimination
of
ethanol
was
complete,
did
the
blood
levels
of
2­
ME
and
2­
EE
begin
to
decrease.
The
authors
concluded
that
ethanol,
which
is
also
metabolized
by
the
alcohol
dehydrogenase
(
ADH)
pathway,
must
have
a
higher
affinity
for
ADH
enzymes
than
2­
ME
or
2­
EE.
Because
of
its
higher
affinity,
ethanol
is
preferentially
metabolized.
The
authors
suggested
that
blood
levels
of
2­
ME
and
2­
EE
may
persist
in
workers
who
use
2­
ME
or
2­
EE
in
combination
with
alcoholic
consumption.
This
persistence
of
2­
ME
and
2­
EE
in
the
blood
could
result
in
an
enhanced
health
risk.

[
page
15534]

C.
Acute
Toxicity
The
acute
toxicity
of
ethylene
glycol
ethers
have
been
shown
in
several
animal
species
(
e.
g.,
mice,
rats,
rabbits,
guinea
pigs
and
cats)
by
various
routes
of
administration
(
e.
g.,
oral,
injection,
dermal
and
inhalation).
Smyth
et
al.
(
Ex.
5­
138)
examined
the
single
dose
toxicity
of
a
variety
of
compounds,
including
2­
ME,
2­
EE,
2­
MEA
and
2­
EEA.
In
this
study
rats
and
guinea
pigs
were
exposed
through
oral
administration
to
varying
concentrations
in
order
to
determine
the
lethal
dose
(
LD50)
of
the
various
compounds.
In
rats,
the
LD50
identified
for
2­
ME,
2­
MEA,
2­
EE
and
2­
EEA
were
respectively
2460
mg/
kg,
3920
mg/
kg,
3000
mg/
kg
and
5100
mg/
kg
body
weight.
In
guinea
pigs
the
LD50'
s
for
these
same
4
compounds
were
0.95,
1.25,
1.4
and
1.91
mg/
kg
body
weight,
respectively.
The
authors
noted
that
these
compounds
induced
narcosis
but
only
at
exposures
at
or
above
the
LD50.
Pathological
examination
revealed
the
primary
effect
was
kidney
damage
Reviews
of
the
data
also
report
relatively
high
lethal
doses
(
LD50)
and
lethal
concentrations
(
LC50)
(
Exs.
5­
134,
5­
046
and
5­
140).
For
example,
the
LC50'
s
observed
in
mice
exposed
for
7
hours
to
2­
EE
and
2­
ME
were
1820
ppm
and
1480
ppm,
respectively.
A
LC50
of
7000
ppm
was
observed
among
rats
exposed
to
2­
MEA
for
4
hours.
For
2­
EEA,
a
LC50
of
4000
ppm
was
reported
for
cats
exposed
from
4
to
6
hours.
In
most
cases
deaths
were
attributed
to
lung
and
kidney
damage.
Pathological
examination
revealed
lung
edema,
slight
liver
damage
and
marked
kidney
injury.
Prior
to
death
animals
exhibited
difficulty
in
breathing,
sleepiness,
weakness
and
loss
of
muscular
coordination
Little
evidence
is
available
on
acute
toxicity
in
humans.
Most
of
the
available
evidence
is
limited
to
case
studies
of
accidental
poisonings
where
glycol
ethers
have
been
ingested
(
Ex.
5­
134,
pp.
21­
24).
For
example,
two
men
hospitalized
after
drinking
100
ml
of
2­
ME,
exhibited
signs
of
confusion,
disorientation,
and
progressive
muscular
weakness.
They
also
suffered
from
hyperventilation,
tachycardia
and
moderate
renal
failure.
Similarly
a
woman
who
drank
40
ml
of
2­
EE
exhibited
renal
failure
and
adverse
central
nervous
system
effects
(
e.
g.,
vertigo
and
unconsciousness).
Other
effects
observed
among
humans
after
acute
exposures
include
irritation
of
the
eyes
and
mucous
membranes
including
the
respiratory
system
D.
Background
Discussion
On
Reproductive
And
Developmental
Toxicity
Reproductive
and
developmental
effects
are
the
primary
health
concerns
associated
with
exposure
to
ethylene
glycol
ethers.
The
term
reproductive
effects
refers
to
effects
on
the
male
and
female
reproductive
systems
and
the
term
developmental
effects
refers
to
effects
on
the
developing
organism.
Various
terms
have
been
used
in
the
field
of
reproductive
and
developmental
toxicology,
many
of
which
are
ambiguous
and
open
to
different
interpretations.
In
order
to
provide
guidance
and
assistance
in
assessing
reproductive
and
developmental
risks,
the
EPA
has
published
proposed
guidelines
on
assessing
female
and
male
reproductive
toxicity
(
Exs.
5­
122
and
5­
123)
and
developmental
toxicity
(
Exs.
5­
106,
5­
153).
These
guidelines
discuss
many
of
the
critical
issues
in
reproductive
and
developmental
toxicology.
Much
of
the
terminology
in
the
following
discussion
is
adopted
and
modified
from
the
EPA
guidelines
Male
reproductive
toxicity
is
generally
defined
as
the
occurrence
of
adverse
effects
on
the
male
reproductive
system
that
may
result
from
exposure
to
chemical,
biological,
or
physical
agents
The
toxicity
may
be
expressed
as
alterations
to
the
male
reproductive
organs
and/
or
related
endocrine
system.
For
example
toxic
exposures
may
interfere
with
spermatogenesis
(
the
production
of
sperm),
resulting
in
adverse
effects
in
number,
morphology
(
e.
g.,
size
and
shape),
or
function
(
e.
g.,
motility)
of
sperm.
These
effects
in
turn
may
adversely
affect
fertility.
The
process
of
spermatogenesis
is
a
cyclical
process
marked
by
distinct
stages
that
may
be
sensitive
to
toxic
agents.
In
this
process
germ
cells
(
spermatogonia)
differentiate
into
primary
spermatocytes
then
to
secondary
spermatocytes,
to
spermatids
and
finally
into
spermatozoa
Men
produce
sperm
continually
from
puberty
throughout
life
and
thus
the
risk
of
disrupted
spermatogenesis
is
of
concern
for
the
entire
adult
life
of
a
man.
Reproductive
toxicity
may
also
include
dysfunction
in
sexual
behavior
or
processes
which
are
integral
to
reproductive
success
Female
reproductive
toxicity
is
generally
defined
as
the
occurrence
of
adverse
effects
on
the
female
reproductive
system
that
may
result
from
exposure
to
chemical,
biological,
or
physical
agents
This
toxicity
includes
adverse
effects
in
sexual
behavior,
onset
of
puberty,
ovulation,
menstrual
cycling,
fertility,
gestation,
parturition,
lactation,
or
premature
reproductive
senescence(
the
loss
of
reproductive
capability
associated
with
aging)

Developmental
toxicity
is
defined
as
adverse
effects
on
the
developing
organism
that
may
result
from
exposure
prior
to
conception
(
either
parent),
during
prenatal
development,
or
postnatally
to
the
time
of
sexual
maturation.
Developmental
effects
induced
by
exposures
prior
to
conception
may
occur,
for
example,
when
mutations
are
chemically
induced
in
sperm.
If
the
mutated
sperm
fertilizes
an
egg,
adverse
developmental
effects
may
be
manifested
in
developing
fetuses.
Mutations
may
also
be
induced
in
the
eggs.
Such
effects
are
often
referred
to
as
dominant
lethal
effects
The
major
manifestations
of
developmental
toxicity
include:
(
1)
death
of
the
developing
organism,
(
2)
structural
abnormality,
(
3)
altered
growth,
and
(
4)
functional
deficiency.
Structural
abnormalities
include
malformations
and
variations.
As
stated
in
the
EPA
Guidelines,
a
malformation
is
usually
defined
as
a
permanent
structural
change
that
may
adversely
affect
survival,
development,
or
function.
These
types
of
effects
are
often
referred
to
as
teratogenic
effects.
The
term
variation
is
used
to
indicate
a
divergence
or
a
change
in
structure
which
is
beyond
the
range
of
what
is
generally
considered
to
be
normal
development.
This
divergence
may
not
adversely
affect
survival,
or
health.
However
as
noted
by
EPA
in
its
guidelines,
distinguishing
between
variations
and
malformations
is
difficult
since
there
exists
a
continuum
of
responses
from
the
normal
to
the
extreme
deviant.
There
is
no
generally
accepted
classification
of
malformations
and
variations.
Other
terminology
that
is
often
used,
but
no
better
defined,
includes
anomalies,
deformations,
and
aberrations
Altered
growth
is
an
alteration
in
offspring
organ
or
body
weight
or
size.
Altered
growth
can
be
induced
at
any
stage
of
development,
may
be
reversible,
or
may
result
in
a
permanent
change
Functional
deficiency
includes
alterations
in
the
functional
competence
of
an
organ
or
a
variety
of
organ
systems.
This
functional
deficiency
may
be
expressed
as
behavioral
abnormalities.
Such
effects
may
often
not
be
apparent
at
birth
but
may
instead
be
noted
during
postnatal
development.
Similarly,
exposure
during
development
may
lead
to
adverse
reproductive
functioning.
For
example,
a
female's
entire
complement
of
oocytes
(
eggs)
are
formed
during
gestation,
as
opposed
to
males
who
produce
spermatocytes
[
page
15535]

continually
throughout
their
adult
life.
Thus
toxic
insults
during
gestation
may
adversely
effect
oogenesis
(
the
formation
of
eggs)
.
However
because
structural
and
functional
maturity
of
eggs
does
not
occur
until
puberty,
adverse
effects
may
not
be
manifested
until
females
reach
reproductive
maturity
One
of
the
critical
phases
in
development,
is
the
period
of
gestation
referred
to
as
organogenesis.
During
this
phase
of
gestation,
embryonic
cells
migrate
and
associate
into
tissues
and
organ
rudiments
and
establish
the
basic
organizational
patterns
of
organ
systems.
Because
this
is
a
period
marked
by
rapid
cell
proliferation
and
organ
development
it
is
vulnerable
to
the
induction
of
structural
defects.
It
is
generally
assumed
that
a
single
exposure,
of
sufficient
dose,
during
such
critical
periods
of
development,
may
be
sufficient
to
produce
an
adverse
developmental
effect.
Thus
repeated
exposures
may
not
be
necessary
to
induce
developmental
toxicity.
However
developing
organisms
are
also
known
to
have
the
capacity
to
compensate
for
or
to
repair
certain
amounts
of
damage
at
the
cellular,
tissue
or
organ
level.
Thus
it
is
also
generally
assumed
that
there
may
be
thresholds
for
developmental
toxins
The
level
of
concern
for
a
developmental
toxic
effect
is
related
to
several
issues,
including
the
relative
toxicity
of
an
agent
to
the
offspring
versus
the
adult
animal
and
the
long­
term
consequences
of
findings
in
the
fetus
or
neonate.
The
developing
organism
is
dependent
on
the
maternal
animal
to
provide
nutrients
and
to
maintain
a
protective
environment
in
which
the
conceptus
can
grow
and
develop
Thus
any
agent
which
adversely
affects
the
maternal
animal
may
have
the
potential
to
adversely
affect
the
offspring.
However
it
is
often
difficult
to
differentiate
between
effects
which
are
a
result
of
stress
to
the
maternal
animal
and
effects
which
are
solely
a
result
of
the
sensitivity
of
the
developing
organism.
Those
agents
which
produce
developmental
toxicity
at
a
dose
that
is
not
toxic
to
the
maternal
animal
are
of
the
greatest
concern
because
the
developing
organism
appears
to
be
more
sensitive
than
the
adult.
The
adult/
developmental
toxicity
ratio
(
A/
D
Ratio)
was
introduced
to
account
or
describe
the
differential
susceptibility
between
the
maternal
animal
and
the
developing
organism
(
Exs.
4­
147
and
5­
106).
This
ratio
is
calculated
by
dividing
the
Lowest
Observed
Effect
Level
(
LOEL)
in
the
maternal
animal
by
the
LOEL
observed
for
the
developing
organism.
A/
D
ratios
greater
than
1
suggest
that
the
developing
organism
is
more
sensitive
to
a
chemical
insult
than
the
mother
and
is
therefore
of
greater
concern.
However,
there
is
no
consensus
on
the
predictive
value
of
the
A/
D
ratio
(
Exs.
5­
098
and
5­
099).
One
reason
is
that
the
A/
D
ratio
can
be
influenced
by
the
design
of
the
underlying
bioassay
(
e.
g.,
the
spacing
of
doses
chosen
for
study).
Secondly,
the
maternaldevelopmental
relationship
may
be
misrepresented
if
insensitive
developmental
endpoints
are
compared
to
sensitive
maternal
endpoints
or
vice­
versa.
In
these
cases
the
power
of
the
experimental
study
may
influence
the
level
at
which
an
effect
is
observed
and
thus
influence
the
calculation
of
the
A/
D
ratio.
Thus,
developmental
effects
which
are
produced
only
at
maternally
toxic
doses
cannot
be
discounted
as
being
secondary
to
maternal
toxicity.
Current
information
is
inadequate
to
assume
that
developmental
effects
at
maternally
toxic
doses
result
only
from
the
maternal
toxicity.
Rather,
when
the
lowest
observed
effect
level
is
the
same
for
the
adult
and
the
developing
organism,
it
may
simply
indicate
that
both
are
sensitive
to
that
dose
level.
Moreover,
the
maternal
effects
may
be
reversible
while
effects
on
the
offspring
may
be
permanent.
These
are
important
considerations
for
agents
to
which
humans
may
be
exposed
at
minimally
toxic
levels
in
the
workplace
Most
of
the
evidence
on
the
reproductive
and
developmental
toxicity
of
the
four
subject
glycol
ethers,
as
will
be
discussed
later,
is
limited
to
data
from
experimental
studies
in
mice,
rats
and
rabbits.
This,
in
major
part,
is
due
to
the
difficulty
in
conducting
epidemiological
analyses
to
detect
adverse
reproductive
and/
or
developmental
outcomes.
For
example,
many
outcomes
such
as
early
embryonic
loss,
spontaneous
abortions,
or
reproductive
capacity
of
offspring
are
not
easily
observed
in
humans.
Epidemiological
analysis
is
also
complicated
by
the
fact
that,
because
there
is
a
wide
spectrum
of
inter­
related
effects,
different
types
of
effects
may
occur
at
different
exposure
levels.
Thus
multiple
endpoints
may
result
from
a
single
toxicant.
Some
reproductive
outcomes
are
rare
and
thus
a
large
number
of
births
are
required
to
give
the
study
enough
power
to
detect
a
possible
effect.
For
example,
it
has
been
estimated
that
to
detect
a
two
fold
increase
in
spontaneous
abortions
a
sample
size
of
322
pregnancies
(
161
exposed
and
161
controls)
would
be
required
(
Ex.
5­
135,
p.
167).
More
rare
outcomes
such
as
severe
mental
retardation,
neural
tube
defects
and
chromosomal
abnormalities
would
require
samples
sizes
of
1819,
8986
and
17,907
live
births
respectively,
to
detect
a
two
fold
increase.
Large
populations
of
workers
would
be
required
to
observe
this
many
pregnancies
or
live
births.
Adequate
sample
sizes
may
be
difficult
to
obtain
due
to
factors
such
as
marital
status,
education,
age,
use
of
birth
control
or
prior
reproductive
history.
These
factors
may
affect
couples'
ability
or
attempts
to
have
children
and
thus
affect
the
number
of
outcomes
available
for
study
Because
adequate
human
data
are
rarely
available
for
reproductive
or
developmental
outcomes,
animal
studies
have
been
used
and
are
generally
considered
to
be
useful
in
the
prediction
of
reproductive/
developmental
toxicity
for
humans.
A
basic
tenet
of
toxicology
is
that
if
an
agent
produces
adverse
effects
in
experimental
animals,
this
agent
may
pose
potential
hazards
to
humans.
This
tenet
is
supported
by
reviews
of
studies
in
both
humans
and
experimental
animals
on
the
reproductive
effects
of
selected
agents
which
have
shown
parallels
among
the
adverse
effect
observed
in
animal
experiments
and
effects
reported
in
humans
(
Exs.
4­
103,
p.
96
and
5­
135,
pp.
169­
170).
For
example,
disturbances
in
estrous
cycles
in
rats
were
observed
after
exposure
to
benzene
and
menstrual
disorders
were
reported
among
humans
exposed
to
benzene.
DBCP
induced
testicular
atrophy
and
decreased
fertility
in
rats
and
has
also
been
associated
with
similar
effects
in
men.
EDB
has
caused
sterility
in
rats
and
reduced
fertility
in
men.
Similar
concordance
of
effects
have
been
observed
with
other
agents
such
as
carbon
disulfide,
arsenic,
lead,
alcohol
and
vinyl
chloride
While
there
are
parallels
in
observed
effects
between
experimental
animals
and
humans,
it
is
not
necessarily
assumed
that
there
is
site
concordance
of
effects
seen
in
animals
and
effects
potentially
occurring
in
humans.
That
is,
effects
observed
in
experimental
animals
may
not
exactly
be
the
same
as
those
which
may
occur
in
humans.
For
example
within
the
period
of
organogenesis,
different
organ
systems
may
form
at
different
times.
In
addition
an
individual
organ
system
may
have
a
narrow
time
span
when
it
is
vulnerable.
Furthermore,
the
time
during
organogenesis
when
a
particular
organ
system
develops
may
vary
across
species.
Therefore,
exposures
occurring
in
different
developing
systems
or
even
in
similar
systems,
but
at
different
times,
may
result
in
different
types
of
adverse
developmental
effects.
Thus
although
a
particular
adverse
effect
may
not
be
observed
in
humans,

[
page
15536]

the
presence
of
the
effect
in
experimental
animals
indicates
the
potential
of
an
agent
to
perturb
development
and
therefore
is
an
outcome
of
concern
for
human
development
E.
Effects
In
Animals
Experimental
studies
in
rats,
rabbits,
mice
and
monkeys
through
inhalation,
dermal
and
oral
exposure,
have
shown
clearly
and
consistently
that
2­
ME,
2­
EE
and
their
acetates
cause
adverse
hematologic,
reproductive
and
developmental
effects.
These
effects
include
decreased
white
and
red
blood
cell
counts,
decreased
hemoglobin
concentrations,
decreased
fertility,
decreased
sperm
count,
decreased
testes
size
and
weight,
early
embryonic
death,
fetal
malformations,
delayed
development
and
behavioral
and
neurochemical
alterations
1.
Male
Reproductive
Toxicity
a.
2­
ME.
2­
ME
was
shown
to
induce
testicular
degeneration
in
rats
by
Rao
et
al.(
Ex.
4­
142).
In
this
study
male
rats
were
exposed,
by
inhalation,
to
0,
30,
100
or
300
ppm
2­
ME,
6
hours/
day
for
13
weeks.
These
rats
were
then
bred
with
unexposed
females
to
evaluate
male
reproductive
function
and
dominant
lethality.
Dominant
lethal
tests
are
conducted
to
detect
mutagenic
effects
in
the
spermatogenic
process
which
may
lead
to
fetal
effects
on
the
embryo/
fetus.
Male
rats
exposed
to
300
ppm
exhibited
significant
decreases
in
testes
size
and
atrophy
of
the
seminiferous
tubules.
Only
4
of
20
unexposed
females
mated
to
this
group
of
exposed
males
were
successfully
inseminated
and
all
4
pregnancies
ended
in
resorptions.
The
authors
stated
that
at
300
ppm
there
was
a
complete
suppression
of
fertility
which
they
attributed
to
an
interference
in
spermatogenesis.
No
significant
decreases
in
fertility
were
reported
for
males
exposed
to
100
or
30
ppm
2­
ME.
Because
no
litters
were
produced
in
the
300
ppm
exposure
group,
the
authors
stated
that
dominant
lethality
could
not
be
assessed.
However
the
authors
did
not
address
the
issue
as
to
whether
the
resorptions
observed
in
the
300
ppm
group
may
have
been
a
possible
dominant
lethal
effect.
Among
the
litters
from
rats
exposed
to
30
and
100
ppm
there
were
no
significant
increases
in
pre­
implantation
loss
or
resorption
rate
compared
to
controls.
The
authors
thus
concluded
that
there
was
no
dominant
lethal
effect
from
exposure
at
these
doses.
The
authors
did
note
that
there
was
a
significant
increase
in
the
resorption
rate
at
30
ppm
.
However
because
this
effect
was
not
observed
at
100
ppm,
it
was
not
considered
to
be
treatment
related.
Thus
the
NOEL
for
this
study
was
identified
as
100
ppm
In
this
same
study
by
Rao
et
al.,
male
rats
exposed
at
300
ppm
were
additionally
bred
with
unexposed
females
13
and
19
weeks
after
exposure
was
terminated.
Fifty
percent
of
the
males
sired
litters
with
viable
implantations.
Rats
bred
13
weeks
post
exposure
had
regained
55%
fertility.
Rats
bred
19
weeks
post
exposure
had
regained
50%
fertility.
These
results
suggest
that
adverse
effects
on
fertility
may
be
partially
reversible
after
exposure
is
stopped.
However
these
results
also
indicate
that
recovery
may
not
be
complete
as
50%
of
the
exposed
males
still
showed
signs
of
reduced
fertility
Testicular
degeneration
was
also
observed
in
a
study
by
Miller
et
al.
(
Ex.
5­
023,
see
also
Ex.
4­
045)
where
both
rats
and
rabbits
were
exposed
to
0,
30,
100,
or
300
ppm
2­
ME
for
6
hours/
day,
5
days/
week
for
13
weeks.
Rats
exposed
to
300
ppm
exhibited
significant
decreases
in
testes
weight
as
a
result
of
degeneration
of
the
germinal
epithelium
of
the
seminiferous
tubules.
The
authors
reported
that
rats
exposed
to
300
ppm
showed
reduced
numbers
of
spermatozoa
and
degenerating
spermatozoa
in
the
epididymis.
However
the
authors
did
not
state
whether
these
were
significant
reductions.
No
treatment
related
effects
were
observed
among
rats
exposed
to
30
or
100
ppm
2­
ME.
A
more
sensitive
response
was
observed
among
the
exposed
rabbits
which
exhibited
testicular
effects
at
300,
100
and
30
ppm.
All
male
rabbits
exposed
to
300
ppm
had
small
and
flaccid
testes.
Significant
but
less
severe
decreases
in
testes
size
were
observed
in
rabbits
exposed
at
100
and
30
ppm.
Histological
examination
of
the
rabbits
revealed
that
the
testicular
effects
were
related
to
atrophy
of
the
seminiferous
tubules.
The
effects
observed
in
rabbits
at
30
ppm
were
questioned
by
the
authors
as
they
noted
that
only
a
small
percentage
of
the
animals
(
1
of
5
rabbits)
were
effected
and
rabbits
exposed
to
30
ppm
in
a
subsequent
study
(
Ex.
5­
057)
showed
no
adverse
testicular
response
2­
ME
has
also
been
shown
to
induce
adverse
testicular
effects
in
shorter
term
tests.
In
an
inhalation
study
by
Doe
et
al.(
Ex.
4­
111)
male
rats
were
exposed
to
100
or
300
ppm
2­
ME,
6
hours/
day
for
10
consecutive
days.
Adverse
testicular
effects
were
only
observed
among
rats
exposed
at
300
ppm.
In
these
animals
the
testes
were
significantly
decreased
in
both
size
and
weight.
Histological
examination
of
the
testes
revealed
atrophy
of
the
seminiferous
tubules
and
degeneration
of
the
primary
spermatocytes.
No
significant
adverse
effects
were
observed
among
rats
exposed
at
100
ppm,
and
thus
this
level
was
identified
as
the
NOEL
Similarly
adverse
effects
were
produced
in
a
short
term
(
9­
day)
inhalation
test
conducted
by
Miller
et
al.
(
Ex.
4­
132).
Male
rats
and
mice
were
exposed
6
hours/
day
to
0,
100,
300
or
1000
ppm
2­
ME.
Severe
testicular
degeneration
was
observed
in
both
rats
and
mice
exposed
at
1000
ppm.
Histopathological
examination
revealed
a
degeneration
and
necrosis
of
all
spermatogenic
elements
as
well
as
a
cessation
of
spermatogenesis.
Similar
but
less
severe
testicular
effects
were
observed
in
the
300
ppm
exposure
groups.
However
theese
effects
were
not
statistically
significantly
different
from
control
groups.
No
treatment
related
changes
were
observed
in
the
100
ppm
exposed
animals
2­
ME
also
induces
adverse
testicular
effects
when
administered
orally.
For
example,
Nagano
et
al.
(
Ex.
4­
135)
exposed
male
mice
to
62.5,
125,
250,
500,
1000,
or
2000
mg
2­
ME/
kg
body
weight,
5
days
a
week
for
5
weeks.
In
the
high
dose
group
4
out
of
5
mice
died
before
examination.
Significant
decreases
in
testes
weight
were
observed
for
the
1000,
500,
and
250
mg/
kg
dose
groups
as
a
result
of
seminiferous
tubule
atrophy.
The
authors
noted
that
the
degree
of
changes
in
atrophy
were
related
to
increases
in
dosage
thus
implying
the
presence
of
a
dose­
response
relationship.
For
example
histopathological
examination
showed
that
at
1000
mg/
kg
no
germ
cells
were
present.
At
500
mg/
kg
only
small
numbers
of
spermatozoa,
spermatocytes
and
spermatids
were
present
Similar
effects
were
observed
by
Foster
et
al.(
Ex.
4­
119)
where
male
rats
were
exposed
orally
to
50,
100,
250
or
500
mg
2­
ME/
kg
body
weight
for
11
days.
A
significant
degeneration
of
the
testes
was
observed
in
the
100,
250
and
500
mg/
kg
dose
groups.
A
single
dose
exposure
to
100
mg/
kg
2­
ME
resulted
in
testicular
damage
within
24
hours
of
exposure.
In
this
study
meiotic
cells
of
the
testes
were
identified
as
the
primary
site
of
testicular
damage.
Primary
spermatocytes
were
damaged
initially.
Prolonged
exposure
damaged
late
spermatocytes
and
led
to
a
depletion
of
the
spermatid
population.
Results
of
this
study
indicated
that
testicular
damage
may
be
partially
reversible.
After
exposure
was
stopped,
testes
weight
returned
to
control
values
and
spermatogenesis
resumed.
However
some
animals
exposed
at
high
doses
still
exhibited
a
small
proportion
of
atrophied
seminiferous
tubules.
Thus
the
authors
concluded
that
prolonged
[
page
15537]

high
exposure
may
prevent
total
recovery
of
testicular
function
Adverse
effects
in
spermatogenesis
and
mating
performance
were
observed
in
short
term
tests
conducted
by
Chapin
(
Ex.
5­
007).
In
the
first
phase
of
this
study
male
rats
were
exposed
to
0,
50,
100
or
200
mg
2­
ME/
kg
body
weight
for
5
days
and
then
mated
with
untreated
females
for
8
weeks.
Significant
decreases
in
the
percentage
of
pregnancies
and
the
number
of
live
fetuses
were
observed
among
females
mated
with
males
from
the
200
and
100
mg/
kg
dose
groups.
No
significant
effects
were
observed
among
females
mated
with
50
mg/
kg
dosed
males.
Females
mated
to
rats
exposed
at
200
mg/
kg
exhibited
an
increase
in
the
incidence
of
resorptions
but
only
at
weeks
5
and
6.
No
increases
in
resorption
rates
were
observed
among
any
other
group
Significant
increases
in
preimplantation
losses
were
observed
among
females
mated
with
males
exposed
to
200
and
100
mg/
kg.
The
authors
noted
that
the
decrease
in
litter
size
is
a
possible
indication
of
a
dominant
lethal
effect.
However
because
there
was
no
significant
increase
in
the
number
of
dead
fetuses
and
only
a
slightly
significant
increase
in
resorptions
at
weeks
5
and
6
of
the
high
dose
group,
the
authors
stated
that
the
decrease
in
litter
size
was
probably
due
to
decreased
number
of
viable
sperm
number
rather
than
a
dominant
lethal
effect.
The
authors
added
that
this
conclusion
is
supported
by
the
evidence
of
pre­
implantation
loss
as
well
as
by
the
findings
of
others
researchers
(
e.
g.,
Rao
et
al.,
Ex.
4­
142)

In
the
second
phase
of
this
study
by
Chapin,
additional
groups
of
male
rats
were
exposed
similar
to
rats
in
the
first
phase
of
the
study
but
this
time
were
not
allowed
to
mate.
Rats
exposed
at
100
and
200
mg/
kg
showed
significant
sperm
count
reductions
throughout
the
study.
In
addition,
these
groups
showed
significant
decreases
in
the
percentage
of
motile
sperm
and
increases
in
the
frequency
of
abnormal
sperm
morphology.
A
reduction
in
sperm
counts
was
observed
in
the
50
mg/
kg
group
at
week
5
only.
In
this
group
sperm
motility
was
unaffected.
The
findings
of
this
study
also
indicated
that
as
dose
increased,
different
types
of
testicular
cells
were
affected.
For
example,
at
100
mg/
kg
only
spermatocytes
were
affected,
while
at
200
mg/
kg
the
later
stage
spermatids
and
spermatogonia
were
effected
In
a
subsequent
study
using
a
similar
protocol,
Chapin
et
al.(
Ex.
5­
006)
examined
testicular
recovery
from
2­
ME
treatment.
Again
male
rats
were
exposed
orally
to
0,
50,
100,
or
200
mg
2­
ME/
kg
body
weight
for
5
days
and
followed
for
8
weeks.
Rats
exposed
to
200
and
100
mg
2­
ME/
kg
exhibited
significant
signs
of
testicular
damage
including
abnormal
sperm
morphology,
delayed
spermatogenesis,
and
cell
death.
All
animals
exposed
to
200
mg
2­
ME/
kg
showed
significant
signs
of
testicular
toxicity
during
the
first
week
of
observation.
These
animals
exhibited
widespread
death
of
all
stages
of
spermatocytes
and
abnormal
sperm
morphology.
By
weeks
5­
8,
50%
of
the
tubules
appeared
normal
for
the
200
mg/
kg
exposed
groups.
Cell
death
and
abnormal
sperm
morphology
were
also
observed
at
100
mg/
kg.
Similarly
by
week
8
a
50%
recovery
was
noted.
In
the
50
mg/
kg
exposure
group,
changes
in
morphology
were
not
noted
until
week
4.
By
week
8
no
treatment
related
changes
were
observed
Similar
findings
have
been
reported
in
more
recent
studies
by
Anderson
et
al.(
Ex.
5­
100).
Male
mice
and
rats
were
exposed
to
single
doses
of
0,
500,
750,
1000
or
1500
mg
2­
ME/
kg
body
weight.
Selected
groups
were
additionally
mated
to
untreated
females
to
examine
dominant
lethality.
As
in
earlier
studies
increasing
doses
resulted
in
increased
levels
of
testicular
damage.
In
the
rat,
testes
weight
and
sperm
counts
were
significantly
reduced
at
all
dose
levels.
Abnormal
sperm
morphology
was
also
observed
among
treated
rats.
In
mice,
significant
decreases
in
testes
weight
and
sperm
count
were
observed
in
the
750
mg/
kg
group
at
week
3
and
in
the
500
and
1000
mg/
kg
groups
at
week
4.
In
the
dominant
lethal
studies
female
rats
mated
to
exposed
males,
exhibited
a
significant
reduction
in
the
number
of
implants.
No
statically
significant
increase
in
the
incidence
of
abnormalities
in
offspring
or
any
other
signs
of
dominant
lethality
were
observed
among
the
rat
offspring.
In
the
mice,
no
significant
decreases
in
fertility
or
signs
of
dominant
lethality
were
observed
b.
2­
MEA
Evidence
strongly
indicates
that
2­
MEA
will
induce
adverse
reproductive
effects
similar
to
its
parent
glycol
ether
2­
ME.
As
was
discussed
in
the
section
on
metabolism,
MAA
is
thought
to
be
the
primary
metabolite
of
2­
MEA.
Metabolic
studies
indicate
that
the
adverse
reproductive
effects
of
2­
ME
are
mediated
by
its
primary
metabolite
methoxyacetic
acid
(
MAA).
Therefore
it
is
likely
that
equal
doses
of
2­
MEA
would
induce
adverse
reproductive
effects
similar
to
2­
ME,
as
these
two
compounds
appear
to
follow
similar
metabolic
pathways
The
metabolic
data
are
supported
by
the
findings
of
testicular
degeneration
in
mice
by
Nagano
et
al.
(
Ex.
4­
135).
In
this
study,
male
mice
were
orally
exposed
to
62.5,
125,
250,
500,
1000,
or
2000
mg
2­
MEA/
kg
body
weight,
5
days/
week
for
5
weeks.
Significant
decreases
in
testicular
weight
were
observed
only
in
the
500
mg/
kg
dose
group.
Converting
this
dosage
to
mmole/
kg
the
authors
noted
that
on
an
equimolar
basis
2­
ME
and
2­
MEA
resulted
in
similar
effects
c.
2­
EE
Like
2­
ME,
2­
EE
has
also
been
shown
to
cause
male
reproductive
toxicity
in
laboratory
animals
although
2­
EE
has
not
been
tested
as
extensively.
For
example,
Barbee
and
Terrill
et
al.
(
Exs.
5­
084
and
4­
108)
exposed
male
rats
and
rabbits
by
inhalation
to
25,
100
or
400
ppm
of
2­
EE,
6
hours/
day,
5
days
a
week,
for
13
weeks.
In
rats
the
only
significant
effects
observed
were
decreased
pituitary
weights
at
400
ppm.
Pathological
examination
of
these
organs
did
not
reveal
any
lesion
indicative
of
a
treatment
related
effect.
Thus
the
authors
concluded
that
the
increased
pituitary
weight
was
not
likely
to
be
a
treatment
related
effect.
Rabbits
exhibited
a
significant
decrease
in
testes
weight
when
exposed
to
400
ppm.
Based
on
the
pathological
analyses
this
decreased
weight
was
attributed,
by
the
authors,
to
the
degeneration
of
the
seminiferous
tubules.
No
adverse
effects
were
observed
at
100
or
25
ppm.
From
these
findings
the
NOEL
for
reproductive
effects
in
male
rats
was
identified
as
400
ppm
while
the
NOEL
for
reproductive
effects
in
male
rabbits
was
100
ppm
2­
EE
also
induces
testicular
degeneration
after
oral
exposure.
For
example,
Nagano
et
al.
(
Ex.
4­
135)
exposed
male
mice
to
500,
1000,
2000,
or
4000
mg
2­
EE/
kg
body
weight,
5
days/
week
over
a
5
week
period.
At
4000
mg
2­
EE/
kg,
all
animals
died
before
examination.
Significant
decreases
in
testes
weights
were
observed
in
the
1000
and
2000
mg/
kg
exposure
groups.
Histopathological
examinations
revealed
dosage
related
degrees
of
seminiferous
atrophy
among
groups
exhibiting
a
significant
reduction
in
testes
weight.
For
example,
at
500
mg/
kg
no
significant
effects
on
the
testes
were
observed.
At
1000
mg/
kg
there
were
significant
reductions
in
the
testes
weight
and
a
corresponding
decrease
in
the
number
of
spermatozoa,
spermatids
and
spermatocytes.
At
2000
mg/
kg
there
were
also
a
significant
decrease
in
testes
weight
with
a
corresponding
decreae
in
spermatozoa
and
spermatids
had
completely
vanished
Similar
effects
were
observed
in
short
term
oral
studies
by
Foster
et
al.
(
Ex.
4­
119).
In
this
study
male
rats
were
exposed
to
250,
500
or
1000
mg
2­
EE
/
kg
body
weight
for
11
days.
Significant
decreases
in
testes
weight
were
[
page
15538]

observed
at
500
and
1000
mg/
kg
after
the
11th
day
of
exposure.
The
authors
noted
that
rats
appeared
to
be
slightly
more
sensitive
than
mice.
Histological
examination
of
the
testes
revealed
spermatocyte
degeneration
of
the
primary
and
secondary
spermatocytes.
No
significant
testicular
abnormalities
were
observed
at
250
mg/
kg.
The
NOEL
was
identified
as
250
mg/
kg
body
weight
d.
2­
EEA
As
in
the
case
of
2­
MEA,
evidence
strongly
indicates
that
2­
EEA
will
induce
adverse
reproductive
effects
similar
to
2­
EE.
As
discussed
earlier,
metabolic
studies
indicate
that
ethoxyacetic
acid
(
EAA)
is
the
primary
metabolite
of
both
2­
EE
and
2­
EEA
and
thus
2­
EEA
is
likely
to
produce
similar
effects
to
those
of
2­
EE.
This
evidence
is
supported
by
the
studies
of
Nagano
et
al.
(
Ex.
4­
135)
who
exposed
male
mice
to
500,
1000,
2000,
or
4000
mg
2­
EEA/
kg
body
weight,
5
days/
week,
for
5
weeks.
Significant
decreases
in
testicular
weight
were
observed
in
mice
exposed
to
1000,
2000
and
4000
mg/
kg
2­
EEA.
Histopathological
examinations
revealed
dose
related
changes
in
seminiferous
tubule
atrophy.
For
example
at
200
and
100
mg/
kg
the
exposed
groups
exhibited
a
significant
reduction
in
testes
weight
and
a
corresponding
reduction
in
the
number
of
spermatozoa,
spermatids
and
spermatocytes.
At
400
mg/
kg
there
was
also
a
significant
reduction
in
testes
weight
but
at
this
dose
the
spermatozoa
and
spermatids
had
completely
vanished.
Conversion
of
dosage
to
mmole/
kg
revealed
that
equimolar
doses
of
2­
EE
and
2­
EEA
induced
similar
effects.
Thus
the
authors
concluded
that
these
results
suggest
that
a
glycol
ether
and
its
corresponding
acetate
have
similar
toxic
potential
In
summary,
the
evidence
clearly
shows
that
2­
ME,
2­
EE
and
their
acetates
induce
adverse
male
reproductive
effects.
Both
through
inhalation
and
oral
exposure
of
these
compounds,
several
animal
species
have
exhibited
infertility
and
testicular
degeneration.
2.
Maternal/
Developmental
Effects
2­
ME
and
2­
EE
and
their
acetates
also
induce
adverse
developmental
and
maternal
effects.
Rats,
mice,
rabbits
and
monkeys
after
oral
and
dermal
exposures
to
these
compounds
have
exhibited
adverse
effects
including
decreased
maternal
weight
gain,
increased
lengths
of
gestation,
increased
resorptions,
fetal
malformations
and
delayed
development
a.
2­
ME
Hanley
et
al.
(
Exs.
4­
120,
4­
106,
and
4­
042a)
studied
the
effects
of
inhaled
2­
ME
on
fetal
development
in
rats,
mice
and
rabbits.
Pregnant
rats
were
exposed
to
0,
3,
10,
or
50
ppm
2­
ME
for
6
hours/
day
on
days
6
through
15
of
gestation.
Pregnant
mice
were
exposed
to
0,
10
or
50
ppm
for
6
hours/
day
on
days
6
through
15
of
gestation.
Pregnant
rabbits
were
exposed
to
0,
3,
10,
or
50
ppm
for
6
hours/
day
on
days
6
through
18
of
gestation.
Female
rats
exposed
to
50
ppm
exhibited
a
significant
decrease
in
maternal
body
weight
gain.
No
other
signs
of
maternal
toxicity
for
any
other
test
doses
were
noted.
A
significant
decreased
in
maternal
body
weight
gain
was
also
observed
in
mice
but
again
only
at
50
ppm.
The
only
statistically
significant
dose­
related
developmental
effects
in
rats
were
an
increased
incidence
of
lumbar
spurs
and
delayed
ossification
after
exposure
to
50
ppm
2­
ME.
In
mice
the
only
significant
dose
related
developmental
effects
observed
were
increased
incidence
of
lumbar
spurs
and
unilateral
testicular
hypoplasia
at
50
ppm.
No
statistically
significant
effects
were
observed
at
10
or
3
ppm
in
mice.
Rabbits
however
exhibited
a
more
sensitive
response
to
2­
ME
exposure.
At
50
ppm
significant
decreases
in
maternal
body
weight
gain
and
increases
in
maternal
liver
weight
were
observed.
At
50
ppm
rabbits
had
a
significant
increase
in
the
incidence
of
resorptions.
Fetuses
from
this
group
exhibited
a
significant
decrease
in
mean
fetal
body
weight
and
a
significant
increase
in
the
incidence
of
malformations
of
all
organ
systems
(
e.
g.,
joint
contracture,
shortness
and
absence
of
digits,
ventricular
septal
defects
of
the
heart,
missing
paw
bones
and
rib
malformations).
Despite
the
strong
effect
observed
at
50
ppm,
there
was
no
statistically
significant
increased
incidence
of
malformations
at
10
or
3
ppm
for
rabbits.
However
a
statistically
significant
increase
in
resorption
rate
was
observed
at
10
ppm.
The
authors
of
the
study
however
dismissed
this
effect
stating
that
the
observed
increase
was
a
result
of
an
unusually
low
concurrent
control
value
for
resorptions.
The
authors
stated
that
the
observed
increase
at
10
ppm
was
within
the
range
observed
among
historical
controls
Similar
results
were
observed
by
Doe
et
al.
(
Ex.
4­
111).
In
this
study
pregnant
rats
were
exposed
by
inhalation
to
0,
100
or
300
ppm
2­
ME
for
6
hours/
day
on
days
6
through
17
gestation.
Rats
exposed
to
300
ppm
exhibited
a
significant
decrease
in
maternal
body
weight
gains
and
failed
to
produce
any
litters.
Nine
of
the
20
rats
exposed
to
100
ppm
2­
ME
produced
litters,
but
the
gestation
period
was
significantly
increased
over
controls.
Exposure
to
100
ppm
also
induced
a
significant
reduction
in
the
total
numbers
of
pups,
the
proportion
of
pups
live
at
birth
and
the
proportion
of
pups
surviving
to
day
3
postpartum.
The
authors
stated
that
all
pups
from
the
100
ppm
group
were
normal
externally,
but
no
further
examination
of
the
pups
was
performed
to
determine
whether
or
not
there
was
any
other
evidence
of
a
developmental
effect.
Because
statistically
significant
effects
were
observed
at
both
of
the
tested
doses
a
NOEL
was
not
established
in
this
study
Inhalation
studies
by
Nelson
et
al.(
Ex.
4­
136)
examined
the
behavioral
and
neurochemical
effects
in
offspring
after
parental
exposure
to
2­
ME.
In
these
studies
both
male
and
female
rats
were
exposed
to
25
ppm
2­
ME.
Twenty­
five
ppm
was
chosen
as
a
test
level
as
this
dose
represented
the
current
allowable
limit
of
exposure
under
the
OSHA
standards.
Male
rats
were
exposed
for
7
hours/
day,
7
days/
week,
for
5
weeks.
These
rats
were
then
mated
with
untreated
females
which
were
allowed
to
deliver
their
young.
Separate
groups
of
pregnant
rats
were
exposed
7
hours/
day
on
days
7
through
13
or
days
14
through
20
gestation
and
were
also
allowed
to
deliver
their
young.
Behavioral
testing
to
evaluate
central
nervous
system
effects
(
i.
e
motor,
sensory
and
cognitive
functions)
were
conducted
on
offspring
from
both
groups
of
rats
and
the
brains
from
selected
offspring
were
analyzed
for
neurochemical
levels
(
e.
g.,
dopamine,
acetylcholine,
and
norepinephrine).
The
only
statistically
significant
effect
in
behavior
observed
was
the
difference
in
avoidance
conditioning
in
offspring
from
female
rats
exposed
on
days
7­
13
gestation.
In
the
neurochemical
analyses
offspring
from
both
the
paternally
and
maternally
exposed
rats
exhibited
significant
neurochemical
deviations
particularly
in
the
brainstem
and
cerebrum.
These
results
indicate
that
both
paternal
and
maternal
exposure
may
result
in
teratogenic
effects
on
the
offspring.
However
only
one
dose
was
used
in
this
study
and
thus
no
conclusions
about
dose­
response
effects
or
NOEL's
can
be
drawn
Studies
have
shown
that
oral
exposure
to
2­
ME
also
induces
adverse
developmental
effects.
Nagano
et
al.
(
Ex.
5­
026)
orally
exposed
pregnant
mice
to
31.25,
62.5,
125,
250,
500
or
1000
mg
2­
ME/
kg
body
weight
on
days
7
through
14
gestation.
A
significant
increase
in
the
incidence
of
dead
fetuses
was
observed
among
mice
exposed
to
250,
500
and
1000
mg/
kg
2­
ME.
There
were
also
significant
reductions
in
fetal
weight
among
fetuses
from
the
125
and
250
mg/
kg
dosed
groups.
At
250
mg/
kg
[
page
15539]

there
was
a
significant
increase
in
the
incidence
of
gross
malformations,
including
exencephaly,
umbilical
hernia
and
abnormal
fingers.
Increased
skeletal
malformations
including
fused
ribs,
fused
vertebrae,
spina
bifida,
syndactly
(
fused
fingers),
oligodactly
(
absence
of
fingers),
and
polydactly
(
extra
fingers)
were
observed
after
exposure
to
62.5,
125,
and
250
mg/
kg.
Delayed
ossification
was
observed
in
fetuses
from
all
dose
levels.
Thus
in
this
study
a
NOEL
was
not
established
Similarly,
Toraason
et
al.(
Ex.
5­
042)
exposed
pregnant
rats
by
gavage
to
0,
25,
50,
or
100
mg
2­
ME/
kg
body
weight
on
days
7
through
13
gestation.
At
day
20
of
gestation
fetuses
were
removed
for
electrocardiographic
(
EKG)
analysis
and
later
examined
for
physical
defects.
The
EKG
evaluation
involved
measuring
rhythm
variations
of
the
heart,
the
presence
or
absence
of
peaks
produced
by
EKG
output
(
i.
e.,
R,
QRS,
QT
and
R­
R
peaks).
All
fetuses
were
resorbed
at
100
mg/
kg
2­
ME
and
thus
no
EKG
analysis
was
possible
at
this
dose.
There
was
a
significant
increase
in
the
number
of
fetuses
with
abnormal
QRS's
from
both
the
25
and
50
mg/
kg
exposure
groups.
At
these
doses
no
other
EKG
characteristics
were
significantly
affected
by
2­
ME
exposure.
The
most
prevelant
cardiovascular
defect,
ventricular
septal
defect
and
ductus
arteriosis,
was
observed
in
fetuses
from
the
50
mg/
kg
exposure
group.
However
the
authors
concluded
that
the
abnormal
QRS's
did
not
appear
to
be
related
to
the
cardiovascular
malformation.
For
example
the
authors
noted
that
four
fetuses
with
abnormal
QRS's
had
heart
defects
but
4
fetuses
without
heart
malformations
also
had
abnormal
QRS's.
The
authors
attributed
the
abnormal
QRS's
to
a
delay
in
conduction.
Nevertheless
the
results
of
this
study
indicate
that
2­
ME
exposure
may
adversely
effect
fetal
heart
function
Adverse
developmental
effects
of
2­
ME
have
also
recently
been
reported
in
non­
human
primates.
Scott
et
al.(
Ex.
5­
125)
exposed
pregnant
monkeys
by
gavage
to
0,
12,
24
or
36
mg/
kg
body
weight,
on
days
20
to
45
of
gestation.
Signs
of
maternal
toxicity
including
a
reduction
in
maternal
body
weight
and
loss
of
appetite
were
observed
at
all
dose
levels.
At
the
highest
dose
(
36
mg/
kg)
all
pregnancies
ended
in
abortion.
Three
of
10
pregnancies
were
also
aborted
in
the
24
mg/
kg
dose
group
and
3
of
13
pregnancies
were
aborted
in
the
12
mg/
kg
dose
group.
Fetuses
were
removed
on
day
100
of
gestation
and
examined
for
abnormalities.
No
malformations
were
observed
among
any
of
the
fetuses
surviving
to
day
100
of
gestation
b.
2­
MEA
The
studies
discussed
above
clearly
show
that
2­
ME
induces
adverse
maternal
and
developmental
effects.
As
discussed
earlier,
metabolic
data
indicate
that
the
toxicity
of
2­
ME
is
mediated
by
its
primary
metabolite,
methoxyacetic
acid
(
MAA).
MAA
is
also
the
primary
metabolite
of
2­
MEA
and
thus
it
is
likely
that
2­
MEA
will
induce
similar
adverse
effects
to
2­
ME
c.
2­
EE
Similar
to
2­
ME,
2­
EE
has
also
induced
adverse
developmental
effects.
Doe
and
Tinston
et
al.
(
Exs.
5­
071,
4­
038,
4­
039
and
4­
105)
exposed
pregnant
rats,
by
inhalation,
to
0,
10,
50
or
250
ppm
2­
EE
for
7
hours/
day
on
days
6
through
15
gestation.
Pregnant
rabbits
were
exposed
to
0,
10,
50
or
175
ppm
2­
EE
for
7
hours/
day
on
days
6
through
18
gestation.
No
adverse
maternal
effects
were
observed
among
either
exposed
rats
or
rabbits.
Among
rats,
exposure
to
250
ppm
induced
a
significant
increase
in
late
interuterine
death
and
a
decrease
in
fetal
growth.
Fetuses
from
the
250
ppm
group
exhibited
significant
increases
in
skeletal
defects,
(
e.
g.,
partial
and/
or
nonossification
of
the
skull
and
the
thoracic
and
lumbar
vertebrae)
and
increases
in
sternebrae
abnormalities.
No
significant
adverse
effects
were
observed
in
the
50
or
10
ppm
exposed
groups.
In
the
high
dose
rabbits
(
175
ppm)
there
were
no
significant
increases
in
late
interuterine
death
or
decreases
in
fetal
growth.
The
only
statistically
significant
effect
observed
at
this
dose
was
an
increased
number
of
fetuses
with
extra
ribs.
As
neither
species
showed
any
significant
adverse
effects
at
50
ppm,
the
authors
stated
that
a
clear
no
effect
level
of
50
ppm
for
2­
EE
was
identified
in
this
study
Similar
findings
were
reported
by
Andrew
et
al.
(
Exs.
4­
065
and
5­
069)
who
exposed
pregnant
rabbits
by
inhalation
to
0,
160,
or
615
ppm
2­
EE
for
7
hours/
day
on
days
1­
18
gestation.
Rabbits
exposed
to
615
ppm
exhibited
maternal
toxicity
including
severe
anorexia,
reduced
weight
gain
and
an
increased
incidence
of
maternal
mortality
(
5
of
19
died).
Rabbits
exposed
to
160
ppm
exhibited
significant
reductions
in
food
consumption
and
maternal
body
weight
gain.
All
litters,
from
the
surviving
does,
in
the
615
ppm
exposure
group,
were
resorbed.
Resorptions
were
also
significantly
increased
in
the
160
ppm
exposure
group.
In
addition
there
was
a
significant
reduction
in
the
number
of
live
fetuses.
Fetuses
from
the
160
ppm
group
exhibited
a
significant
increase
in
malformations
including
cardiovascular
effects
(
e.
g.,
fused
aorta
and
pulmonary
artery),
renal
effects
(
e.
g.,
fused
kidneys)
and
skeletal
effects
(
e.
g.,
extra
and
malformed
ribs)

In
the
Andrew
study,
female
rats
were
also
exposed
to
2­
EE
by
inhalation
to
0,
150,
or
650
ppm
for
7
hours/
day,
5
days/
week
for
a
3
week
pregestational
period
followed
by
exposure
to
0,
200
or
760
ppm
2­
EE
during
days
1­
19
gestation.
Pregestational
exposure
had
no
effect
on
maternal
toxicity
or
the
establishment
of
pregnancy.
Significant
decreases
in
liver
weights
and
kidney
weights
were
observed
in
the
rats
exposed
to
760
ppm
during
gestation.
All
litters
in
the
760
ppm
exposure
group
were
resorbed.
The
number
of
resorptions
was
not
increased
in
the
200
ppm
exposure
group.
However
exposure
to
200
ppm
during
gestation
significantly
increased
the
incidence
of
cardiovascular
malformations,
and
skeletal
defects
(
e.
g.,
extra
ribs
and
vertebrae,
and
reduced
skeletal
ossification)
in
the
pups
Nelson
et
al.(
Ex.
4­
138)
examined
developmental
effects
in
the
behavior
of
offspring
from
rats
exposed
to
2­
EE.
Pregnant
rats
were
exposed
by
inhalation
to
100
ppm
2­
EE,
7
hours/
day
on
days
7­
13
or
days
14­
20
of
gestation.
Behavioral
tests
were
subsequently
conducted
on
offspring
from
the
control
and
exposed
groups
to
evaluate
CNS
function
(
e.
g.,
motor,
sensory
and
cognitive
functions).
Selected
offspring
were
also
used
for
neurochemical
analyses
(
e.
g.,
acetylcholine,
norepinephrine
and
dopamine
levels).
The
only
evidence
of
any
maternal
toxicity
was
a
significant
increase
in
the
duration
of
pregnancy
compared
to
controls.
Offspring
from
rats
exposed
on
days
7­
13
of
gestation
exhibited
impaired
performance
in
the
rotorod
and
open
field
test
and
marginal
superiority
in
the
avoidance
conditioning
test.
Offspring
from
the
14­
20
gestation
day
exposure
group
had
impaired
performance
in
the
running
wheel
and
avoidance
conditioning
tests.
Neurochemical
analyses
revealed
that
in
both
the
7­
13
and
14­
20
day
exposure
groups,
whole
brain
samples
from
offspring
showed
significantly
decreased
levels
of
norepinephrine.
In
the
7­
13
day
groups
the
cerebrum
and
cerebellum
had
significant
elevations
in
acetylcholine
and
dopamine.
Thus
the
results
of
this
study
indicate
that
at
100
ppm
2­
EE
can
induce
behavioral
and
neurochemical
alterations.
Because
only
one
dose
was
tested
the
study
was
not
able
to
evaluate
any
potential
doseresponse
trend
or
identify
a
NOEL
2­
EE
has
also
induced
adverse
developmental
effects
after
dermal
exposure.
Hardin
et
al.
(
Ex.
4­
121)
applied
0.25
ml
or
0.50
ml
2­
EE
[
page
15540]

dermally
four
times
daily
to
pregnant
rats
on
days
7­
16
gestation.
Rats
exposed
to
0.50
ml
2­
EE
exhibited
ataxia
(
loss
of
muscular
coordination)
and
reduced
body
weight
gain
during
the
later
days
of
exposure.
No
other
significant
signs
of
maternal
toxicity
were
noted.
All
fetuses
from
the
0.50
ml
exposure
group
were
resorbed.
There
was
also
a
significant
increase
in
the
numbers
of
resorptions
in
the
0.25
ml
exposure
group.
The
0.25
ml
group
also
exhibited
significantly
increased
incidence
of
cardiovascular
malformations
and
skeletal
defects
(
e.
g.,
incomplete
ossification,
extra
and
malformed
ribs
and
vertebrae).
The
results
of
this
study
indicate
that
skin
exposure
is
a
significant
route
of
exposure
for
inducing
teratogenic
effects
d.
2­
EEA
Inhalation,
dermal
and
oral
studies
have
clearly
shown
a
teratogenic
response
from
exposure
to
2­
EE.
As
discussed
earlier,
metabolic
studies
also
indicate
that
it
is
the
primary
metabolite,
EAA,
which
is
likely
to
be
the
active
agent.
EAA
is
also
the
primary
metabolite
of
2­
EEA
and
thus
it
is
likely
that
2­
EEA
will
induce
teratogenic
effects
similar
to
2­
EE.
Several
inhalation
studies
support
these
conclusions.
For
example,
Nelson
et
al.
(
Ex.
5­
091)
exposed
pregnant
rats
by
inhalation
to
0,
130,
390,
or
600
ppm
2­
EEA,
7
hours/
day,
on
days
7­
15
gestation.
At
600
ppm
rats
exhibited
a
significant
decrease
in
maternal
body
weight.
However
the
authors
attributed
this
reduction
in
maternal
weight
at
high
dose
to
be
due
to
resorptions.
They
thus
concluded
that
no
significant
signs
of
maternal
toxicity
were
observed.
All
fetuses
from
the
600
ppm
group
were
resorbed.
Resorptions
were
also
significantly
increased
in
the
390
ppm
exposure
group.
Fetuses
from
both
the
390
and
130
ppm
exposure
groups
exhibited
significant
decreases
in
weight,
as
well
as
significant
increases
in
visceral
malformations
(
e.
g.,
septal
defects
of
the
heart
and
umbilical
hernia)
and
skeletal
defects
(
e.
g.,
wavy
and
fused
ribs).
A
NOEL
was
not
established
for
this
study
Adverse
effects
were
also
reported
by
Doe
et
al.
(
Ex.
5­
071)
who
exposed
pregnant
rabbits
to
0,
25,
100
or
400
ppm
2­
EEA
for
6
hours/
day
on
days
6
through
18
of
gestation.
Maternal
toxicity
was
only
observed
among
the
400
ppm
exposed
rabbits.
In
this
group
rabbits
exhibited
significant
decreases
in
maternal
body
weight
gain
and
food
consumption.
Mean
live
fetal
weights
were
significantly
reduced
for
fetuses
from
both
the
400
and
100
ppm
exposure
groups.
Fetuses
from
the
400
ppm
exposure
group
exhibited
significant
increases
in
visceral
defects
(
e.
g.,
opaque/
empty
gall
bladders,
reduced/
pale
spleens)
and
skeletal
defects
(
e.
g.,
retarded
ossification).
Fetuses
from
the
100
ppm
group
also
showed
a
significantly
increased
incidence
of
partial
ossification.
The
only
significant
effect
observed
among
fetuses
from
the
low
dose
exposure
group
(
25
ppm)
was
an
extra
center
of
ossification
above
the
1st
sternebra.
However
because
significant
skeletal
defects
were
observed
only
at
400
and
25
ppm
the
authors
concluded
that
the
effects
at
25
ppm
were
probably
not
dose
related
and
thus
the
NOEL
for
this
study
was
25
ppm
More
recent
investigations
by
Tyl
et
al.
(
Ex.
5­
124)
have
further
confirmed
the
teratogenic
potential
of
2­
EEA.
In
this
inhalation
study
pregnant
rabbits
and
rats
were
exposed
to
0,
50,
100,
200
or
300
ppm
2­
EEA,
6
hours/
day
for
days
6­
15
(
rats)
or
days
6­
18
(
rabbits)
of
gestation.
Rabbits
exhibited
significant
decreases
in
maternal
weight
gain
at
300,
200
and
100
ppm
2­
EEA.
After
exposure
to
300
and
200
ppm
rabbits
also
exhibited
significant
decreases
in
gravid
uterine
weight
and
increases
in
absolute
liver
weight.
Rats
exposed
to
2­
EEA
exhibited
a
significant
decrease
in
maternal
weight
gain
and
food
consumption
at
300
and
200
ppm.
A
significant
decrease
in
absolute
liver
weight
was
observed
in
rats
at
100,
200
and
300
ppm.
A
significantly
increased
incidence
of
nonviable
implantations
was
observed
at
300
and
200
ppm
in
rabbits
and
at
300
ppm
in
rats.
Rabbits
also
exhibited
a
significant
increase
in
the
incidence
of
resorptions
after
exposure
to
300
ppm.
Significant
reductions
in
fetal
body
weight
per
litter
were
observed
only
among
rats
exposed
to
300
and
200
ppm
2­
EEA.
Examinations
of
rabbit
fetuses
revealed
a
significant
increase
in
the
incidence
of
skeletal,
cardiovascular
and
renal
effects
at
300
and
200
ppm.
Similarly
rats
exhibited
significant
increases
in
malformations
(
e.
g.,
cardiovascular,
renal
and
skeletal
effects)
at
both
200
and
300
ppm.
No
signs
of
maternal
or
fetal
toxicity
were
observed
at
50
ppm
for
either
species
and
thus
this
exposure
dose
was
identified
as
the
NOEL
for
this
study
Similar
to
findings
in
dermal
studies
on
2­
EE,
studies
on
2­
EEA
have
also
shown
that
dermal
exposure
induces
teratogenic
effects
similar
to
those
observed
in
inhalation
studies.
Hardin
et
al.
(
Ex.
5­
073)
dermally
exposed
pregnant
rats
to
0.35
ml
2­
EEA,
twice
daily
for
days
7
through
16
of
gestation.
Dermal
exposure
induced
significant
decreases
in
maternal
body
weight
gain,
significant
increases
in
the
incidence
of
dead
implants
per
litter
and
significant
increases
in
the
frequency
of
resorbed
litters.
Fetal
examination
revealed
a
significant
increase
in
the
incidence
of
cardiovascular
and
skeletal
defects
(
e.
g.,
reduced
ossification
and
mishaped
vertebrae).
Thus
the
findings
of
this
study
further
demonstrate
the
teratogenic
potential
of
2­
EEA.
In
addition
these
findings
indicate
that
dermal
exposure
may
be
a
significant
route
of
exposure
3.
Blood
Effects
In
addition
to
adverse
reproductive
and
developmental
effects,
the
animal
studies
provide
evidence
that
2­
ME,
2­
EE
and
their
acetates
also
induce
adverse
hematological
effects.
Various
studies
in
rats,
rabbits
and
mice
by
both
inhalation
and
oral
exposure
have
demonstrated
exposure
related
decreases
in
various
blood
parameters
including
white
blood
cell
counts
(
WBC),
hemoglobin
concentration
(
HGB),
platelet
count
and
red
blood
cell
count
(
RBC)
a.
2­
ME
and
2­
MEA
Miller
et
al.
(
Ex.
4­
132)
exposed
rats
and
mice
to
0,
100,
300
or
1000
ppm
2­
ME,
6
hours/
day
for
9
days.
At
1000
ppm
both
male
and
female
rats
exhibited
significant
decreases
in
WBCs,
RBCs,
HGB
and
packed
cell
volume.
Male
mice
showed
similar
significant
effects
at
1000
ppm
while
female
mice
showed
a
significant
decrease
in
WBC
only
at
1000
ppm.
WBC
was
also
decreased
at
300
ppm
for
male
rats
and
at
100
ppm
for
female
rats
In
a
similar
study,
Doe
et
al.
(
Ex.
4­
111)
exposed
male
rats
to
0,
100
or
300
ppm
2­
ME,
6
hours/
day
for
10
consecutive
days.
Exposures
at
300
ppm
resulted
in
significant
reductions
in
whole
blood
count,
red
blood
cell
count,
hemoglobin
concentration,
hematocrit
and
mean
cell
hemoglobin.
No
significant
blood
effects
were
observed
among
rats
exposed
to
100
ppm
Thirteen
week
inhalation
studies
by
Miller
et
al.
(
Ex.
5­
023)
support
the
authors'
earlier
findings
(
Ex.
4­
132)
of
adverse
blood
effects.
In
this
study
rats
and
rabbits
were
exposed
to
0,
30,
100
or
300
ppm
2­
ME
for
6
hours/
day,
5
days/
week
for
13
weeks.
Both
rats
and
rabbits,
male
and
female,
exposed
to
300
ppm
2­
ME
exhibited
significant
decreases
in
WBC,
platelet
counts,
packed
cell
volume,
and
HGB.
Rabbits
exposed
to
300
ppm
also
showed
a
significant
decrease
in
RBC.
No
adverse
effects
in
blood
were
observed
at
100
or
30
ppm
2­
ME
for
rats
or
rabbits
Similarly,
Hanley
et
al.
(
Ex.
4­
120)
exposed
pregnant
rats,
rabbits
and
mice
to
0,
3,
10
or
50
ppm
2­
ME
for
6
hours/
day
on
days
6­
15,
6­
18
and
6­
15
[
page
15541]

respectively.
Rats
exhibited
a
significant
decrease
in
HGB
and
packed
cell
volume
at
all
dose
levels
and
a
significant
decrease
in
RBC
at
50
ppm
only.
Neither
mice
nor
rabbits
showed
any
significant
dose
related
blood
effects
Oral
studies
in
mice
by
Nagano
et
al.
(
Exs.
5­
026
and
4­
135)
have
observed
significant
decreases
in
WBC
after
high
dose
exposure.
Pregnant
mice
exposed
during
days
7­
14
gestation
to
31.25,
62.5,
125,
250,
500
or
1000
mg
2­
ME/
kg
body
weight
showed
significantly
decreased
WBCs
at
1000
mg/
kg
(
5­
026).
Male
mice
exposed
at
12.5,
125,
250
500,
1000
or
2000
mg/
kg
over
a
five
week
period
also
exhibited
significant
decreases
in
WBC
at
500
mg/
kg
and
above
(
Ex.
4­
135).
Nagano
et
al.
also
exposed
male
mice
to
2­
MEA,
resulting
in
a
significant
decrease
in
WBC
at
1000
mg/
kg.
The
authors
noted
that
when
expressed
in
equimolar
doses,
the
dose­
effect
levels
are
similar
for
2­
ME
and
2­
MEA.
No
other
studies
have
investigated
the
hematological
effects
of
2­
MEA
b.
2­
EE
Barbee
et
al.(
Ex.
5­
084)
exposed
male
and
female,
rats
and
rabbits,
to
0,
25,
100
or
400
ppm
2­
EE,
6
hours/
day
for
5
days/
week
for
13
weeks.
Adverse
blood
effects
were
only
observed
among
male
and
female
rabbits
exposed
at
400
ppm.
These
rabbits
exhibited
a
significant
decrease
in
HGB,
hematocrit
and
RBC
In
their
teratology
studies
Doe
et
al.
(
Ex.
5­
071)
exposed
pregnant
rats
to
0,
10,
50
or
250
ppm
2­
EE,
6
hours/
day
on
days
6­
15
gestation
and
rabbits
to
0,
10,
50
or
175
ppm
2­
EE,
6
hours/
day
on
days
6­
18
gestation.
Rats
exposed
to
250
ppm
exhibited
a
decrease
in
HGB,
hematocrit
and
RBC.
It
is
not
stated
clearly
as
to
whether
or
not
these
effects
were
statistically
significant.
No
treatment
related
effects
were
observed
at
50
or
10
ppm.
No
adverse
blood
effects
were
observed
at
any
of
the
test
doses
for
rabbits
Nagano
et
al.
(
Ex.
4­
135)
exposed
male
mice
to
500,
1000,
2000
or
4000
mg
2­
EE/
kg
body
weight
5
days/
week
for
5
weeks.
Significant
decreases
in
WBC
were
observed
in
the
2000
and
4000
mg/
kg
exposure
groups
c.
2­
EEA
Tyl
et
al.
(
Ex.
5­
124)
exposed
pregnant
rats
and
rabbits
to
0,
50,
100,
200
or
300
ppm
2­
EEA
6
hours/
day
on
days
6­
15
and
days
6­
18
gestation,
respectively.
Rabbits
showed
significant
decreases
in
platelet
counts
at
200
and
300
ppm.
Rats
also
had
decreased
platelet
counts
at
200
and
300
ppm.
In
addition
rats
exhibited
a
significant
increase
in
WBC
at
200
and
300
ppm
and
a
decrease
in
RBC
at
100,
200,
and
300
ppm
exposure.
Barbee
et
al.
(
Ex.
5­
071)
also
exposed
pregnant
rabbits
to
2­
EEA
at
doses
of
0,
25,
100
or
400
ppm.
The
only
statistically
significant
effect
observed
was
a
decrease
in
HGB
at
400
ppm.
Oral
studies
by
Nagano
(
Ex.
4­
135)
exposed
mice
to
500,
1000,
2000,
or
4000
mg
2­
EEA/
kg
body
weight.
The
only
significant
effect
in
this
study
was
a
decrease
in
packed
cell
volume
in
mice
exposed
at
4000
mg/
kg
F.
Adverse
Health
Effects
In
Humans
Workers
exposed
to
2­
ME
and
2­
EE
have
exhibited
adverse
effects
on
the
hematologic
and
male
reproductive
systems.
Blood
effects
among
exposed
workers
include
bone
marrow
injury,
reduced
red
and
white
blood
cell
counts
and
anemia.
The
major
reproductive
effect
observed
among
exposed
workers
is
reduced
sperm
count.
OSHA
is
unaware
of
any
female
reproductive
or
developmental
toxicity
data
among
workers
exposed
to
glycol
ethers.
OSHA
believes
however
that
the
lack
of
data
in
this
area
is
due
in
major
part,
to
the
difficulty
in
structuring
and
conducting
analyses
to
detect
these
types
of
adverse
effects.
Thus,
although
the
human
data
are
limited,
there
is
positive
evidence
among
exposed
workers
and
this
evidence
supports
the
strong
body
of
evidence
observed
in
experimental
animals
1.
2­
ME
Ohi
and
Wegman
(
Ex.
4­
139)
reported
on
two
workers
in
a
textile
printing
plant
who
developed
clinical
manifestations
of
encephalopathy
(
brain
disease)
after
the
acetone
that
was
usually
used
in
a
hand
cleaning
operation
had
been
substituted
with
2­
ME.
Protective
gloves
were
not
worn.
In
addition
to
the
neurological
symptoms
of
encephalopathy,
both
workers
had
evidence
of
bone
marrow
injury.
One
had
pancytopenia
(
reduction
in
the
numbers
of
all
of
the
formed
elements
of
the
blood).
Air
samples
collected
during
the
washing
operation
averaged
8
ppm.
Although
no
estimate
was
made
of
the
magnitude
of
skin
absorption,
exposure
was
characterized
as
being
"
predominantly
dermal."
Thus
dermal
exposure
may
have
played
a
significant
part
in
the
observed
effects.
The
authors
noted
that
blood
counts
returned
to
normal
after
removal
from
exposure
indicating
that
blood
effects
may
be
reversible
Cohen
(
Ex.
5­
049)
presented
a
case
report
of
subjective
central
nervous
system
complaints
and
asymptomatic
hematopoietic
effects
following
inhalation
and
skin
exposure
to
2­
ME
in
a
microfilm
coating
and
mixing
operator.
The
worker's
job
in
this
case
report
entailed
mixing
chemicals,
often
while
standing
directly
over
open
1500
gallon
kettles
which
contained
33%
2­
ME.
2­
ME
was
also
used
in
the
manual
cleaning
of
the
kettles,
usually
done
without
gloves.
Breathing
zone
exposures
revealed
timeweighted
average
2­
ME
levels
of
18.2
ppm
to
57.8
ppm
(
average
being
approximately
35
ppm).
Small
quantities
of
methylethyl
ketone
(
MEK)
(
1­
5
ppm)
were
present.
During
a
periodic
examination
less
than
a
year
after
starting
his
job,
it
was
found
that
the
blood
indices
of
this
32­
year
old
worker,
which
had
previously
been
normal,
dropped.
His
white
blood
cell
(
WBC)
count,
red
blood
cell
(
RBC)
count,
hemoglobin,
hematocrit,
and
platlets
were
all
found
to
have
fallen
to
abnormally
low
levels.
The
worker
also
noted
an
increase
in
sleep
time,
increase
in
weight,
decrease
in
appetite,
increased
fatigue,
and
feelings
of
apathy.
When
the
worker
was
removed
from
skin
and
inhalation
exposure
to
2­
ME,
all
hematologic
parameters
returned
to
normal
Cook
et
al.
(
Ex.
5­
002)
conducted
a
cross­
sectional
study
among
male
manufacturing
and
processing
employees,
40
with
potential
exposure
to
2­
ME,
to
determine
if
anemia,
leukopenia
(
reduction
in
number
of
white
blood
cells),
or
sterility
were
present
and,
if
so,
if
they
were
more
prevalent
among
the
exposed
workers.
Manufacturing
of
2­
ME
was
by
a
continuous
enclosed
process.
In
a
separate
packaging
and
distribution
facility,
2­
ME
was
loaded
into
drums,
tank
cars,
or
rail
cars.
Drums
were
filled
automatically,
but
there
was
manual
capping.
TWA
air
samples
of
2­
ME
collected
in
the
packaging
and
distribution
facility
in
1980
indicated
personal
exposures
of
5
to
9
ppm
2­
ME
and
area
concentrations
of
4
to
20
ppm.
However,
because
of
the
potential
for
skin
contact
and
absorption,
continued
use
of
protective
gloves
was
recommended
to
avoid
skin
contact
during
sampling
and
maintenance.
Workers
exposed
to
2­
ME
were
also
potentially
exposed
to
2­
EE,
polyols
and
polyoxypropylene
glycols,
brake
fluids,
butylene
oxide,
and
polyglycols.
Complete
blood
counts
(
CBC),
hormone
levels
[
i.
e.,
Luteinizing
hormone
(
LH),
Follicle
Stimulating
hormone
(
FSH),
testosterone],
length
and
width
of
testis,
and
sperm
counts
were
evaluated
for
frequencies
of
abnormal
outcomes
and
percentage
differences
of
grouped
means
in
workers
exposed
to
2­
ME
and
in
the
unexposed
workers.
Hematologic
variables
in
40
exposed
and
25
controls
were
compared
to
determine
prevalence
of
anemia
and/
or
leukopenia.
Clinical
fertility
indices
for
a
subgroup
of
15
(
6
[
page
15542]

exposed,
9
control)
were
supplemented
by
medical
history
and
responses
to
the
question:
"
Looking
back,
do
you
feel
you
have
had
any
trouble
having
children?"

Study
results
indicated
little
difference
between
exposed
and
controls.
The
only
difference
between
means
that
approached
statistical
significance
was
testicular
width
(
p=.
08);
however,
testicular
length
was
also
diminished
among
the
total
exposed
(
p=.
19).
The
authors
acknowledged
a
variety
of
chemical
exposures
for
both
study
groups.
They
also
suggested
the
likelihood
of
interobserver
bias,
given
that
one
physician
consistently
measured
lower
values
and
examined
appreciably
more
exposed
individuals
than
controls
2.
2­
EE
In
1984
NIOSH
conducted
a
Health
Hazard
Evaluation
of
possible
reproductive
effects
among
male
workers
exposed
to
2­
EE
at
Precision
Castparts
Corporation
(
Ex.
5­
003).
2­
EE
was
used
as
a
binder
in
the
preparation
of
ceramic
shells
used
to
cast
precision
metal
parts
from
wax
molds.
Approximately
80
male
workers
engaged
in
this
process
were
potentially
exposed
to
2­
EE.
Full
shift
breathing
zone
airborne
exposures
ranged
from
non­
detectable
to
23.8
ppm.
Because
of
the
potential
for
skin
exposure
to
2­
EE,
urine
measurements
of
ethoxyacetic
acid
(
EAA),
a
metabolite
of
2­
EE,
were
also
determined
Urine
excretion
of
EAA
ranged
from
non­
detectable
to
163
ug/
g
creatinine.
Blood
samples
analyzed
for
2­
EE
concentrations
did
not
reveal
any
detectable
levels
of
2­
EE
In
this
study
NIOSH
also
conducted
a
cross­
sectional
evaluation
of
semen
quality
(
sperm
concentration,
pH,
volume,
viability,
motility,
velocity
and
morphology)
among
37
men
exposed
to
2­
EE
in
this
plant.
The
evaluation
included
a
comparison
group
of
38
unexposed
men
from
elsewhere
in
the
plant.
A
questionnaire
to
determine
personal
habits,
medical
and
work
histories
and
a
brief
examination
of
the
genital
tract,
including
measurements
of
testicular
size,
were
also
administered
The
average
sperm
count
per
ejaculate
among
the
2­
EE
exposed
workers
was
significantly
lower
than
that
of
the
unexposed
group
(
113
v.
154
million
sperm
per
ejaculate;
(
p
<
0.05).
For
exposed
workers,
this
difference
was
statistically
highly
significant
(
p
<
0.001).
The
two
groups
did
not
differ
significantly
with
respect
to
other
semen
characteristics
or
testicular
size.
Consideration
of
the
other
factors
(
e.
g.,
abstinence,
sample
age,
subject's
age,
tobacco,
alcohol,
and
caffeine
use,
history
of
urogenital
disorders,
fever,
and
other
illness)
which
affect
semen
quality
did
not
alter
these
results.
However
the
authors
noted
that
the
average
sperm
concentrations
of
both
groups
were
lower
than
the
average
for
other
occupational
populations
studied
by
NIOSH.
Historical
control
sperm
concentration
is
70
million/
ml.
In
the
present
study
the
mean
sperm
concentration
of
the
unexposed
group
was
60
million/
ml
and
that
of
the
exposed
group
was
48
million/
ml
NIOSH
concluded
that
there
was
a
possible
effect
of
2­
EE
on
sperm
count
among
these
workers,
and
recommended
limiting
exposure
to
2­
EE
to
the
fullest
extent
feasible,
given
the
known
testicular
toxicity
in
animals
In
the
first
of
three
related
papers
Sparer,
Welch,
McManus
and
Cullen
(
Ex.
5­
103)
characterized
exposure
to
ethylene
glycol
ethers
in
a
group
of
shipyard
painters.
Painters
employed
at
the
shipyard
worked
in
four
crews:
shop
crew,
interior
crew,
tank
crew,
and
exterior
crew.
The
shop
crew
worked
in
the
paint
shop
where
they
formulated
and
mixed
paints
and
issued
respirators.
The
majority
of
men
in
the
shop
crew
had
worked
on
other
crews
in
the
past.
Interior,
exterior,
and
tank
crews
worked
on
the
boats.
Assignment
of
a
painter
to
a
crew
depended
on
the
stage
of
completion
of
the
boat.
Painters
may
have
been
assigned
to
one
crew
and
worked
overtime
on
another.
In
any
given
month
a
painter
may
have
worked
on
the
interior,
exterior,
and
tank
crews
Much
of
the
painting
performed
by
the
interior
crews
was
by
brush
application.
Tanks
were
primarily
spray
painted,
and
air­
supplied
respirators
were
always
worn
during
this
operation.
Half­
face
filter
respirators
with
organic
vapor
cartridges
and
paint
filters
were
worn
by
painters
whenever
they
sprayed
on
interior
jobs
and
were
available,
but
seemed
to
be
optional,
for
those
doing
brush
painting
One
hundred
and
two
air
samples
from
thirty­
six
painters
were
analyzed
for
2­
EE,
and
2­
ME.
2­
EE
was
detected
in
90
samples,
2­
ME
in
81.
For
2­
ME
the
mean
was
0.8
+/­
1.0
ppm;
median
0.44
ppm
and
the
range
0­
5.6
ppm.
The
mean
value
for
2­
EE
was
2.6
+/­
4.2
ppm;
the
median
1.2;
the
range
0
­
21.5
ppm.
The
mean
air
exposure
of
the
interior
crew
was
2.6
+/­
4.2
ppm
for
2­
EE
and
0.8
+/­
1.0
ppm
for
2­
ME.
Visible
paint
on
the
painters
indicated
that
60%
of
the
men
sampled
had
skin
contact.
Painters
who
were
using
paints
without
ethylene
glycol
ethers,
or
not
painting
at
all,
still
had
exposure
to
these
solvents
as
demonstrated
by
air
sampling
Sparer
and
Welch
et
al.
stated
that
although
these
sampling
observations
do
serve
to
help
characterize
the
exposure
of
these
painters
to
ethylene
glycol
ethers,
several
factors
suggest
that
these
measurements
may
underestimate
exposure.
A
NIOSH
investigation
of
2­
EE
exposures
reported
variable
results
in
recovering
analyte
from
field
samples
that
are
shipped
to
an
analytical
laboratory
and
stored
for
extended
periods.
Recovery
was
found
to
be
between
60%
and
100%
(
Ex.
5­
003).
The
painters
also
reported
that,
perhaps
because
of
the
sampling
in
progress,
work
on
the
study
days
was
much
slower
than
usual.
This
may
have
resulted
in
measured
values
lower
than
usual
levels
Welch
et
al.
(
Ex.
5­
104)
conducted
semen,
hematologic,
and
fertility
studies
for
the
entire
study
population,
94
painters
and
55
nonexposed
controls.
The
workers
supplied
information
on
demographic
characteristics,
medical
conditions,
personal
habits,
and
reproductive
history
and
underwent
a
physical
examination.
The
questionnaire
elicited
basic
demographic
information
and
information
about
medical
conditions
and
personal
habits
that
have
been
reported
to
effect
semen
parameters,
including
smoking,
alcohol
consumption,
caffeine
consumption,
medications,
radiotherapy
or
chemotherapy,
recent
febrile
illness,
past
history
of
mumps,
and
genitourinary
conditions.
Each
participant
was
asked
about
his
work
history
and
hobbies.
He
was
asked
if
he
and
his
wife
ever
had
difficulty
conceiving
a
child,
whether
he
ever
saw
a
physician
for
this
problem,
and
the
physician's
diagnosis
A
sample
of
blood
was
obtained
for
a
complete
blood
count
(
CBC),
and
for
determination
for
serum
follicular
stimulating
hormone
(
FSH),
luteinizing
hormone
(
LH)
and
testosterone.
Urine
samples
were
obtained
from
each
painter
at
the
beginning
and
end
of
each
sampling
period.
These
samples
were
frozen
and
transported
to
the
NIOSH
laboratories
for
analysis
for
the
alkoxyacetic
acid
metabolites
of
2­
ME
and
2­
EE
Semen
samples
were
collected
from
73
of
the
painters
and
40
controls
to
determine
whether
2­
EE
and
2­
ME
affects
the
reproductive
potential
of
exposed
men.
Semen
samples
were
analyzed
for
pH,
volume,
turbidity,
liquidity
,
viability,
sperm
density
and
count
per
ejaculate,
motility,
morphology
and
morphometry
The
proportion
of
men
with
a
sperm
density<
20
million/
cc
was
higher
in
the
exposed
group
than
in
the
unexposed
group,
13.5%
(
10
painters)
vs.
5%
(
2
controls)
(
p=
0.12).
The
authors
noted
[
page
15543]

that
the
proportion
found
in
the
controls,
5%,
was
in
agreement
with
population
surveys
of
sperm
density.
When
oligospermia
(
deficiency
in
number
of
sperm)
is
defined
as
a
sperm
count
per
ejaculate<
100
million,
33%
(
24
painters)
and
20%
(
18
controls)
were
oligospermic
(
p=
0.20).
The
rate
of
oligospermia
was
analyzed
separately
for
smokers
and
non­
smokers.
Among
the
non­
smokers,
the
exposed
group
had
a
higher
rate
of
oligospermia
(
p=
0.05).
When
smoking
was
controlled,
the
odds
ratio
calculated
for
a
decreased
count
per
ejaculate
among
the
painters
was
1.85,
with
a
95%
confidence
interval
of
0.6
­
5.6
Because
of
the
regular
rotation
of
painters
from
one
job
to
another
at
the
shipyard,
the
painters
could
not
be
classified
into
dose
groups.
Because
of
the
cyclical
nature
of
spermatogenesis
the
authors
stated
that
exposure
from
two
to
six
months
prior
to
semen
analysis
was
likely
to
have
produced
an
effect
at
the
time
of
the
study,
and
it
was
not
possible
to
determine
each
man's
job
and
exposure
at
that
time.
Therefore,
the
researchers
assumed
that
all
the
painters
had
the
same
exposure
Painters
were
also
exposed
to
two
other
substances
that
have
been
reported
in
the
past
to
affect
semen
quality,
lead
and
epichlorohydrin.
Lead
is
known
to
cause
a
depression
of
sperm
count
The
mean
lead
levels
of
the
45
men
who
had
been
monitored
for
lead
were
mostly
below
20
ug/
deciliter(
dl),
and
the
highest
single
level
in
any
individual
was
40
ug/
dl.
The
authors
stated
that
this
level
of
lead
exposure
has
not
been
documented
to
cause
a
depressed
count.
Epichlorohydrin
was
not
detected
in
air
sampling
during
the
study
The
authors
thus
concluded
that
exposure
to
the
ethylene
glycol
ethers
2­
EE
and
2­
ME
lowered
sperm
count
in
this
group
of
painters.
The
authors
pointed
out
that
this
finding
is
consistent
with
the
effect
seen
in
animal
studies.
Studies
in
several
species
show
that
these
glycol
ethers
cause
loss
of
germinal
epithelium
and
testicular
atrophy.
Cellular
studies
show
that
this
effect
occurs
by
inhibition
of
cell
division
in
the
early
pachytene
stage
of
spermatogenesis,
an
effect
that
would
be
expected
to
result
in
a
decreased
count
rather
than
an
effect
on
motility
or
morphology
Welch
and
Cullen
(
Ex.
5­
102)
undertook
a
cross­
sectional
clinical
appraisal
of
a
sample
of
painters
and
unexposed
workers
to
evaluate
the
relationship
between
measurements
of
peripheral
blood
of
the
workers
and
ethylene
glycol
ether
exposure.
The
study
of
hematologic
function
included
:
a
complete
blood
count,
a
manual
differential
count
of
200
cells,
and
a
manual
platelet
count.
In
addition,
each
subject's
past
medical
record
from
the
employer's
medical
department
was
requested,
including
routine
blood
counts
and
whole
blood
levels.
Complete
records
were
obtained
for
two­
thirds
of
the
subjects
The
authors
reported
that
the
only
other
compounds
known
to
be
toxic
to
bone
marrow
or
circulating
blood
cells
that
painters
at
the
shipyard
were
exposed
to,
in
addition
to
ethylene
glycol
ethers,
were
lead
and
benzene.
Lead
exposure
was
limited
to
abrasive
blasting
operations;
the
highest
lead
level
detected
during
brushing
or
cleaning
operations
was
10
ug/
m3.
Sampled
levels
during
blasting
were
as
high
as
11
mg/
m3.
Painters
engaged
in
blasting
use
air­
supplied
respirators
and
their
blood
lead
was
routinely
monitored.
Forty­
five
of
94
painters
were
categorized
by
the
employer
as
"
lead
exposed"
and
were
participating
in
the
routine
blood
testing;
only
nine
of
the
forty­
five
men
had
a
mean
lead
level
greater
than
15
ug/
dl,
and
only
two
had
a
mean
greater
than
20
ug/
dl,
with
the
highest
at
30
ug/
dl.
The
highest
single
value
was
40
ug/
dl
Paints
or
cleaning
solutions
containing
more
than
1%
benzene
have
not
been
used
in
the
shipyard
sine
1977.
Ten
air
samples
for
benzene
were
obtained
by
NIOSH
during
the
1978
survey;
levels
of
0.08
to
0.53
mg/
m3
were
detectable
in
eight
samples.
None
of
the
bulk
samples
of
paints
or
cleaning
solutions
in
the
current
industrial
hygiene
survey
revealed
any
benzene.
Mean
hemoglobin
levels
did
not
differ
between
the
painters
(
15.43
g/
dl
+
1.09
S.
D.)
and
controls
(
15.67
g/
dl
+
0.84);
p=
0.14
in
a
two­
tailed
test.
Additionally,
there
were
no
statistically
significant
correlations
between
hemoglobin
and
cumulative
exposure
measured
as
years
painting
at
the
shipyard
The
hemoglobin
data
were
rank
ordered
and
analyzed
by
the
Wilcoxon
rank
order
test.
There
was
no
significant
difference
in
rank
for
the
entire
group.
However,
when
only
those
study
subjects
in
the
lowest
quartile
for
hemoglobin
were
included
in
the
analysis,
the
majority
of
low
values
were
in
painters
(
p=
0.028)

Using
an
a
priori
standard
for
anemia
in
working
age
adult
males
of
less
than
14
grams
hemoglobin/
dl
blood,
nine
of
the
147
subjects
with
adequately
coded
data
were
below
this
cutoff;
all
nine
were
painters.
The
past
medical
records
of
the
shipyard
for
the
anemic
painters
were
reviewed;
complete
medical
records
were
available
on
7
of
the
9.
Normal
hemoglobins
were
noted
on
hire
in
four
of
the
seven
anemic
men
with
available
records.
In
a
fifth,
the
initial
hemoglobin
of
13.8
g/
dl
had
dropped
steadily
to
12
at
the
time
of
the
study.
For
the
two
men
for
whom
there
were
no
preemployment
blood
counts,
their
hemoglobins
were
compared
to
those
of
the
respondents
of
the
National
Health
and
Nutrition
Examination
Survey
of
the
same
age,
sex,
and
race,
and
found
to
be
less
than
the
10th
percentile.
In
the
remaining
two,
hemoglobins
were
13.1
and
13.7
g/
dl
on
hire,
comparable
to
those
found
during
the
study.
After
eliminating
these
two,
whose
values
did
not
change
since
first
employed,
the
rate
of
anemia
is
significantly
different
between
painters
and
controls
(
p=
0.04).
Two
of
the
anemic
painters
also
had
an
abnormal
semen
analysis;
one
was
oligospermic,
and
one
was
azoospermic(
lack
of
sperm)

Total
polymorphonuclear
leukocyte
(
PMN)
count
was
calculated
by
multiplying
the
total
white
count
by
the
percentage
PMNs
in
the
differential
count.
The
mean
values
did
not
differ
significantly
between
the
two
groups
(
painters,
4,602
cell/
ul
+
2,041
S.
D.;
controls,
4,650
+
1,771).
A
lower
limit
of
1,800
cells/
ul
was
used
to
define
"
normal"
and
"
abnormal"
groups
of
painters
and
controls.
The
lowest
total
counts
were
found
among
painters;
five,
or
3.4%
of
the
painters
had
values
below
1,800
cell/
ul,
whereas
none
of
the
controls
had
such
low
levels
(
p=
0.07)

The
authors
concluded
that
the
differences
in
hematologic
values
seen
between
the
groups
of
painters
and
the
unexposed
controls
is
significant
and
that
preexisting
host
factors
or
rates
of
participation
are
not
able
to
explain
their
results.
Welch
and
Cullen
concluded
that
an
analysis
of
other
exposures
demonstrates
that
the
difference
is
attributable
to
ethylene
glycol
ethers.
They
added
that
the
absence
of
a
significant
effect
on
the
group
as
a
whole
and
the
inability
to
detect
a
dose­
response
pattern,
make
strong
conclusions
unwarranted.
The
authors
called
for
further
research
on
hematologic
effects
of
these
compounds
in
human
populations
In
summary,
although
limited
in
part
by
confounding
exposures
to
other
solvents,
data
among
workers
exposed
to
2­
ME
and
2­
EE
have
exhibited
anemia,
reduced
white
and
red
blood
cell
counts,
bone
marrow
injury
and
reduced
sperm
counts.
In
some
cases
these
effects
were
observed
at
levels
which
were
reportedly
below
those
of
the
current
permissible
exposure
limits
for
2­
ME
and
2­
EE.
These
findings
support
the
strong
body
of
experimental
animal
evidence,
which
show,
in
[
page
15544]

several
species,
that
2­
ME
and
2­
EE
induce
adverse
hematologic,
reproductive
and
developmental
effects
G.
Mutagenicity
Studies
in
general
indicate
a
lack
of
mutagenic
potential
for
2­
ME
and
2­
EE.
Mutagenicity
is
the
ability
to
induce
genetic
mutation,
i.
e.,
a
change
in
the
genetic
material.
Mutations
may
give
rise
to
developmental
effects
in
cases
where
the
genetic
material
of
the
egg
or
the
sperm
has
been
changed
such
as
to
induce
abnormal
development
in
the
fetus.
(
Mutations
may
also
give
rise
to
cancer.
However,
there
are
substances
which
may
be
carcinogenic
which
are
not
mutagenic.
The
carcinogenicity
of
these
glycol
ethers
has
not
been
tested.)

2­
ME
and
2­
EE
have
been
tested
in
various
tests
including
Ames
tests,
unscheduled
DNA
synthesis(
UDS)
assays
in
human
embryo
fibroblasts,
sister
chromatid
exchange
(
SCE)
tests
in
hamster
ovary
cells,
cytogenic
analyses
in
rat
bone
marrow
cells,
dominant
lethal
tests
in
rats,
sperm
abnormality
tests
in
mice
and
sex
linked
recessive
(
SLR)
tests
in
fruit
flies.
(
Exs.
5­
022,
5­
056
and
5­
076)

Neither
2­
ME
nor
2­
EE
induced
effects
in
either
the
Ames
test
or
UDS
assays.
2­
EE
did
induce
chromosomal
abnormalities
in
SCE
tests.
The
authors
stated
that
the
positive
findings
in
2­
EE
are
in
contrast
to
the
general
negative
findings
in
most
mutagenic
assays.
Thus
the
authors
concluded
that
it
may
be
premature
to
classify
these
substances
as
mutagenic.
In
the
SLR
assays
2­
EE
was
found
to
be
negative
while
inconsistent
results
were
observed
for
2­
ME.
Positive
results
were
observed
for
2­
ME
in
the
sperm
abnormality
and
dominant
lethal
tests.
For
example,
2­
ME
induced
abnormal
sperm
head
morphology
and
a
reduction
in
male
rat
fertility.
While
the
dominant
lethal
test
showed
a
decrease
in
male
fertility,
the
authors
raised
the
possibility
that
the
reduction
in
fertility
could
also
be
attributed
to
reduced
sperm
number
rather
than
a
dominant
mutation
Thus,
the
majority
of
the
available
data
indicates
that
2­
ME
and
2­
EE
lack
mutagenic
potential.
However
the
presence
of
positive
findings
raise
the
possibility
that
these
substances
may
have
some
weak
mutagenic
potential.
No
mutagenicity
testing
has
been
conducted
with
2­
MEA
or
2­
EEA,
but
the
metabolic
data
discussed
earlier
suggest
that
all
four
compounds
are
metabolized
by
similar
pathways
and
are
thus
likely
to
induce
similar
effects.
Thus
the
results
observed
for
2­
ME
and
2­
EE
are
predictive
of
mutagenic
potential
in
their
respective
acetates
H.
Conclusions
Health
effects
data
from
experimental
animal
studies
clearly
and
consistently
show
that
2­
ME,
2­
EE
and
their
acetates
produce
dose
related
adverse
hematologic,
reproductive
and
developmental
effects.
These
effects
include
testicular
damage,
reduced
fertility,
maternal
toxicity,
early
embryonic
death,
external,
skeletal
and
visceral
malformations,
delayed
development,
and
adverse
effects
on
the
blood
Evidence
also
indicates
that
both
inhalation
and
dermal
exposures
are
significant
routes
of
exposure
for
glycol
ethers
and
the
induction
of
adverse
effects.
In
addition
persons
occupationally
exposed
to
2­
ME
and
2­
EE
through
inhalation
and
dermal
exposures
have
exhibited
adverse
reproductive
and
hematologic
effects.
Although
not
as
extensive,
in
major
part
due
to
methodological
limitations,
the
human
data
are
nevertheless
highly
consistent
with
and
supportive
of
the
strong
body
of
data
in
experimental
animals
showing
adverse
hematologic,
reproductive
and
developmental
effects
I.
Other
Glycol
Ethers
Past
research
on
the
health
effects
of
glycol
ether
compounds
has
primarily
been
concentrated
on
2­
ME
and
2­
EE
as
these
two
compounds
and
their
acetates
have
represented
a
major
percentage
of
the
industrial
use
of
glycol
ethers
Although
less
extensive
there
is
also
research
on
other
glycol
ether
compounds.
Much
of
the
concentration
in
this
area
has
been
on
substitutes
for
2­
ME
and
2­
EE
such
as
2­
Butoxyethanol
and
the
propylene
glycol
ethers
(
e.
g.,
propylene
glycol
monomethyl
ether
and
its
acetate)

1.
2­
Butoxyethanol
(
2­
BE)

In
a
series
of
experiments
Carpenter
et
al
(
Ex.
5­
146)
exposed
various
animal
species
(
e.
g.,
rats,
guinea
pigs
and
mice)
to
2­
BE
by
inhalation.
Groups
of
rats
and
guinea
pigs
were
exposed
for
7
hours/
day,
5
days/
week
for
30
days
at
doses
of
54,
107,
203,
314
or
432
ppm
(
rats)
and
doses
of
54,
107,
203
376,
or
494
ppm
(
guinea
pigs).
Significant
increases
in
osmotic
fragility
in
red
blood
cells
was
observed
in
rats
at
doses
of
107
ppm
2­
BE
and
higher.
Osmotic
fragility
was
also
observed
at
54
ppm
when
doses
were
administered
daily
for
30
days.
No
statistically
significant
evidence
of
osmotic
fragility
was
observed
among
the
guinea
pigs
at
any
of
the
doses
tested.
Mice
were
exposed
to
exposed
7
hours/
day
for
30,
60
or
90
days
to
100,
200
or
400
ppm.
No
controls
were
included.
Osmotic
fragility
was
observed
at
all
doses
tested
Hematologic
analyses
were
also
conducted
by
Tyl
et
al.(
Ex.
4­
152)
on
pregnant
rats
and
rabbits
exposed
to
2­
BE
by
inhalation.
Rabbits
and
rats
were
exposed
to
0,
25,
50,
100
or
200
ppm
2­
BE
on
days
6­
18
(
rabbits)
and
days
6­
15
(
rats)
of
gestation.
Red
blood
cell
counts,
hemoglobin
and
hematocrit
were
analyzed
in
blood
samples
from
both
pregnant
rats
and
rabbits.
In
rats
osmotic
fragility
of
red
blood
cells
were
not
detected
at
any
of
the
tested
doses.
However,
significant
reductions
in
red
blood
cell
count
and
mean
corpuscular
hemoglobin
concentration
were
observed
at
both
200
and
100
ppm.
Mean
cell
volume
and
hemoglobin
were
significantly
increased
at
200
and
100
ppm.
The
only
significantly
treatment
related
effects
observed
among
rabbits
were
increases
in
hemoglobin
content
and
hematocrit
at
100
ppm.
However
these
same
blood
effects
were
not
observed
at
200
ppm
Dodd
et
al.
(
Ex.
5­
050)
performed
acute,
9­
day
and
13
week
inhalation
studies
in
rats
to
investigate
the
toxicity
of
2­
BE.
In
the
acute
study
rats
were
exposed
for
4
hours
to
target
concentrations
of
200,
500
and
850
ppm
2­
BE.
The
acute
4
hour
LC50
was
486
ppm
for
males
and
450
ppm
for
females.
Rats
exposed
to
500
and
850
ppm
exhibited
loss
of
coordination.
Post
mortem
examinations
of
these
animals
revealed
red
stained
urine
and
kidney
damage.
Rats
exposed
to
200
ppm
appeared
normal.
In
the
9­
day
study
rats
were
exposed
6
hours/
day
to
0,
25,
100
and
250
ppm
2­
BE.
At
250
ppm
rats
exhibited
significant
decreases
in
red
blood
cell
count
and
hemoglobin
concentration.
SSignificant
effects
in
the
blood
were
also
observed
among
rats
in
the
100
ppm
exposure
group.
However
the
authors
stated
that
the
effects
were
less
profound.
No
statistically
significant
adverse
hematological
effects
were
observed
among
the
rats
exposed
to
25
ppm.
In
the
13
week
study,
rats
were
exposed
to
0,
5,
25
or
75
ppm
2­
BE,
6
hours/
day,
5
days
a
week
for
13
weeks.
At
75
ppm
female
rats
exhibited
significant
decreases
in
red
blood
cell
count
and
hemoglobin
concentration
and
increases
in
mean
corpuscular
hemaglobin
after
6
weeks
of
exposure.
However
by
the
end
of
the
study
these
decreases
had
either
lessened
or
returned
to
controls
levels.
Male
rats
exposed
at
75
ppm
showed
a
significant
decrease
only
in
red
blood
cell
count.
No
other
dose
related
effects
were
observed
among
male
or
female
rats.
In
particular
there
were
no
alterations
in
testes
weight
among
males
exposed
to
2­
BE,
nor
were
any
lesions
observed
[
page
15545]

which
would
have
been
indicative
of
a
testicular
effect.

A
similar
lack
of
testicular
effect
after
exposure
to
2­
BE
was
noted
by
Nagano
et
al.
(
Ex.
4­
135).
In
this
study
mice
were
orally
exposed
to
500,
1000,
or
2000
mg/
kg
body
weight
of
2­
BE,
5
days/
week
for
5
weeks.
Animals
exposed
at
2000
mg/
kg
died.
Decreases
in
red
blood
cell
count
were
observed
among
both
the
1000
and
500
mg/
kg
exposure
groups.
However
males
at
100
and
500
mg/
kg
2­
BE
did
not
exhibit
any
statistically
changes
in
testicular
weight.
This
observation
was
in
contrast
to
results
from
this
same
study
which
showed
marked
testicular
degeneration
after
exposure
to
2­
ME,
2­
EE
and
their
acetates
Doe
(
Ex.
4­
112)
studied
the
testicular
effects
of
single
high
dose
exposures
to
2­
BE,
in
addition
to
examining
the
effects
of
2­
ME
and
2­
EE.
Rats
were
exposed
for
3
hours
to
single
high
doses
of
2­
BE
(
800
ppm),
2­
ME
(
7500
ppm),
or
2­
EE
(
3500
ppm)
and
then
were
followed
for
14
days.
2­
ME
and
2­
EE
significantly
induced
testicular
atrophy
however
no
significant
reduction
in
testes
weight
were
seen
among
the
2­
BE
exposed
rats
Similar
comparative
analyses
were
performed
by
Foster
et
al
(
Ex.
5­
052).
However
in
this
study
the
metabolites
of
2­
BE,
2­
ME
and
2­
EE
were
administered
rather
than
the
parent
glycol
ethers.
Male
rats
were
exposed
by
gavage
to
single
oral
doses
of
butoxyacetic
acid
(
0,
174,
434
or
868
mg/
kg),
methoxyacetic
acid
(
0,
118,
296,
or
595
mg/
kg)
or
ethoxyacetic
acid
(
0,
137,
342,
or
684
mg/
kg).
No
statistically
significant
evidence
of
testicular
toxicity
was
observed
at
any
of
the
test
doses
for
butoxyacetic
acid
whereas
both
methoxy­
and
ethoxyacetic
acid
were
found
to
significantly
decrease
testicular
weight
(
at
all
doses
for
2­
ME
and
at
high
doses
only
for
2­
EE).
As
a
part
of
this
same
study
in
vitro
testicular
cell
cultures
were
exposed
to
the
above
metabolites
to
investigate
the
effects
on
testicular
germ
cells.
Adverse
effects
in
spermatocytes
were
observed
after
administration
of
methoxy­
and
ethoxyacetic
acids.
For
example,
MAA
and
EAA
produced
an
enhancement
of
germ
cell
loss
from
Sertoli
cell
cultures.
In
contrast
no
specific
effects
such
as
those
that
were
observed
after
administration
of
butoxyacetic
acid
The
developmental
effects
of
2­
BE
were
studied
by
Tyl
et
al
(
Ex.
4­
152).
Pregnant
rats
and
rabbits
were
exposed
to
either
0,
25,
50
100
or
200
ppm
2­
BE
for
6
hours/
day
on
days
6­
15
(
rats)
or
days
6­
18
(
rabbits)
of
gestation.
Signs
of
maternal
toxicity
were
observed
in
rats
at
100
and
200
ppm
(
e.
g.,
significant
reductions
in
body
weight,
food
consumption
and
absolute
and
relative
organ
weights).
A
significant
increase
in
the
number
of
resorbed
litters,
a
significant
decrease
in
the
number
of
viable
implantation
per
litter
and
a
significant
reduction
in
skeletal
ossification
were
also
observed
after
exposure
to
200
ppm
2­
BE.
No
significant
increases
in
the
incidence
of
malformations
were
observed
at
any
doses
among
the
rats
In
rabbits,
increases
in
resorptions
and
reduced
body
weight
gain
were
observed
at
200
ppm
however
these
effects
were
not
statistically
significant.
Significant
reductions
in
the
number
of
viable
implants
were
observed
at
200
ppm.
No
evidence
of
statistically
significantly
increased
incidences
of
malformations
were
found
among
any
of
the
exposed
rabbits.
The
authors
concluded
that
2­
BE
induced
maternal
and
fetotoxic
effects
but
not
teratogenic
effects
No
significant
increases
in
maternal
or
developmental
effects
of
2­
BE
were
observed
by
Nelson
et
al
(
Ex.
5­
091).
In
this
study
pregnant
rats
were
exposed
to
0,
150,
or
200
ppm
2­
BE
for
7
hours/
day
on
days
7­
15
gestation.
These
levels
were
chosen
as
earlier
findings
reported
death
at
doses
from
250
to
500
ppm
2­
BE.
The
only
significant
adverse
effect
observed
was
"
slight"
hematuria
among
the
maternal
animals
after
the
first
day
of
exposure.
Otherwise,
no
other
significant
maternal
or
developmental
adverse
effects
were
observed.
Effects
examined
included
resorptions,
fetal
weights
and
incidence
of
malformations.
These
findings
are
in
contrast
to
results
of
this
same
study
in
which
2­
ME
and
2­
EE
were
shown
to
induce
adverse
maternal
and
developmental
effects
Dermal
application
of
2­
BE
has
also
shown
a
similar
lack
of
maternal
or
developmental
effect.
Hardin
et
al
(
Ex.
5­
073)
exposed
pregnant
rats
by
dermal
application
to
0.35
mL
2­
BE,
four
times
daily
on
days
9­
13
of
gestation.
Deaths
occurred
through
the
third
and
seventh
days
of
exposure.
Only
one
of
the
11
rats
treated
survived.
Therefore,
tests
were
repeated
at
0.12
mL,
four
times
daily.
No
significant
adverse
maternal
or
developmental
effects
were
observed
at
this
exposure
dose
In
the
recent
final
Air
Contaminants
standard
(
54
FR
2332)
OSHA
revised
the
Permissible
Exposure
Limit
(
PEL)
for
2­
BE
from
50
ppm
to
25
ppm.
OSHA
concluded
that,
[
T]
he
former
PEL
of
50
ppm
was
insufficiently
protective
against
the
risk
of
2­
butoxyethanol's
irritant,
hematological,
and
other
potential
systemic
effects,
which
constitute
material
health
impairments.
The
limit
of
25
ppm
included
in
the
final
rule
will
reduce
this
significant
risk
to
a
level
below
that
at
which
these
toxic
effects
have
been
observed
in
animals
and
humans.
This
lower
limit
will
also
prevent
the
discomfort
experienced
by
workers
at
exposure
levels
of
40
ppm.
(
Air
Contaminants
Final
Rule,
54
FR
2554)

In
1990
NIOSH
published
a
Criteria
Document
for
2­
BE
and
its
acetate,
2­
BEA
(
Ex.
5­
145).
NIOSH
reported
that
data
from
animals
indicate
that
2­
BE
and
2­
BEA
do
not
cause
adverse
reproductive
or
development
effects.
However
they
report
that
the
animal
evidence
shows
that
these
substances
do
induce
marked
adverse
effects
on
the
blood.
Based
on
the
adverse
blood
effects
observed
in
animals,
NIOSH
recommended
occupational
exposure
limits
of
5
ppm
for
both
2­
BE
and
2­
BEA
2.
Propylene
Glycol
Ethers
The
production
of
propylene
glycol
ethers
is
analogous
to
that
of
ethylene
glycol
ethers.
Ethylene
glycol
ethers
are
made
by
reacting
ethylene
oxide
and
the
appropriate
alcohol.
Propylene
glycol
ethers
are
produced
by
reacting
propylene
oxide
with
the
appropriate
alcohol.
As
such
the
propylene
and
ethylene
glycol
ethers
are
structurally
analogous.
For
example,
ethylene
glycol
monomethyl
ether
(
2­
ME)
is
structurally
very
similar
to
propylene
glycol
monomethyl
ether.
However
despite
some
structural
similarities,
differences
in
toxicities
have
been
observed
between
the
two
general
types
of
compounds
For
example,
in
a
series
of
experimental
studies
Hanley
et
al.
(
Exs.
5­
068
and
4­
120)
compared
the
developmental
effects
of
2­
ME
and
propylene
glycol
monomethyl
ether
(
2­
PGME).
In
studies
on
2­
ME
(
Ex.
4­
120)
rats
and
rabbits
were
exposed
to
0,
3,
10,
or
50
ppm
2­
ME,
6
hours/
day
on
days
6­
15
and
days
6­
18
of
gestation
respectively.
In
rabbits,
exposure
at
50
ppm
2­
ME
resulted
in
a
significant
decrease
in
maternal
body
weight
gain,
a
significant
increase
in
resorption
rates
and
significant
increases
in
major
malformations.
Increased
resorption
rates
were
also
observed
at
10
ppm
compared
to
concurrent
controls,
but
because
the
resorption
rates
were
not
statistically
different
from
historical
control
values,
the
authors
did
not
consider
the
effects
to
be
dose
related.
Rats
did
not
show
any
signs
of
maternal
toxicity
after
exposure
to
50
ppm.
However
fetuses
from
this
exposure
group
exhibited
a
significant
increase
in
the
incidence
in
lumbar
spurs
and
delayed
ossification.
Neither
rats
nor
rabbits
had
any
other
significant
adverse
effects
at
10
or
3
ppm.
In
comparison,

[
page
15546]

Hanley
et
al.(
Ex.
5­
068)
exposed
rats
and
rabbits
to
0,
500,
1500
or
300
ppm
2­
PGME
to
similar
periods
of
gestation
for
6
hours/
day.
At
3000
ppm
both
rats
and
rabbits
exhibited
maternal
effects
including
central
nervous
system
depression
and
a
significant
decrease
in
body
weight
gain.
No
significant
maternal
effects
were
observed
at
1500
or
500
ppm
for
either
species.
Neither
rats
nor
rabbits
exhibited
any
significant
increase
in
resorption
rates
or
major
malformations
at
any
of
the
dose
levels
tested.
It
was
noted
by
the
authors
that
a
significant
increase
in
malformations
among
rat
fetuses
at
3000
ppm
was
observed
compared
to
concurrent
controls.
However
this
increase
was
similar
to
historical
control
values
and
thus
was
not
considered
to
be
dose
related.
The
only
significant
effect
observed,
delayed
sternebral
ossification,
was
observed
at
3000
ppm
in
rats.
This
result
was
interpreted
by
the
authors
to
be
an
indication
of
slight
fetotoxicity
Miller
et
al.
(
Ex.
5­
088)
also
compared
the
toxicities
of
2­
ME
and
2­
PGME
in
rats
and
rabbits.
Rats
and
rabbits
were
exposed
to
0,
30,
100
or
300
ppm
2­
ME
or
0,
300,
1000
or
5000
ppm
2­
PGME,
6
hours/
day
for
13
weeks.
Exposure
to
300
ppm
2­
ME
induced
testicular
degeneration,
decreased
sperm
count,
decreased
white
blood
cell
counts
and
decreased
hemoglobin
concentrations.
No
significant
effects
were
observed
among
the
100
or
30
ppm
exposure
groups.
In
contrast,
no
significant
effects
on
testes
weight
or
blood
were
observed
among
rats
or
rabbits
exposed
to
2­
PGME
at
any
dose
tested.
The
authors
attributed
the
difference
in
toxicity
to
differences
in
metabolism.
The
authors
noted
that
2­
ME
is
a
primary
alcohol
and
has
been
shown
to
be
metabolized
by
an
alcohol
dehydrogenase
mediated
pathway
to
methoxyacetic
acid.
In
addition
methoxyacetic
acid
is
considered
to
be
the
active
metabolite
in
the
induction
of
reproductive
and
developmental
toxicity.
In
contrast,
2­
PGME
is
a
secondary
alcohol
and
is
metabolized
by
microsomal
enzymes
to
propylene
glycol.
The
authors
concluded
that
this
difference
in
metabolism
is
most
likely
to
be
responsible
for
the
differing
toxicities
of
2­
ME
and
2­
PGME
However
Miller
et
al.
(
Ex.
5­
093)
have
also
noted
that
there
are
two
isomeric
forms
of
2­
PGME;
the
alpha
isomer
(
which
is
a
secondary
alcohol)
and
the
beta
isomer
(
which
is
a
primary
alcohol).
Because
of
their
differences
in
structure
the
two
isomers
are
metabolized
differently.
The
alpha
isomer
is
metabolized
by
microsomal
enzymes
to
propylene
glycol
and
the
beta
isomer
is
metabolized
by
the
alcohol/
aldehyde
dehydrogenase
pathway
to
2­
methoxypropionic
acid.
The
beta
isomer
follows
a
metabolic
pathway
similar
to
that
of
the
ethylene
glycol
ethers,
2­
ME
and
2­
EE,
which
are
also
primary
alcohol
glycol
ethers.
Thus
it
was
postulated
that
the
beta
isomer
may
have
toxic
properties
different
from
its
alpha
isomer
and
may
possibly
be
more
similar
to
ethylene
glycol
ethers.
These
conclusions
are
supported
by
studies
by
Merkle
et
al.
(
Ex.
5­
092)
on
the
pure
beta
isomer
of
2­
PGME
Acetate.
In
this
study
pregnant
rats
were
exposed
to
0,
110,
550
or
2700
ppm
2­
PGME
Acetate
and
pregnant
rabbits
were
exposed
to
0,
36,
145
or
550
ppm
2­
PGME
Acetate.
In
rats,
exposure
to
2700
ppm
resulted
in
a
significant
increase
in
the
number
of
litters
with
skeletal
anomalies
(
e.
g.,
dumbbell
shaped
notches
of
the
thoracic
vertebrae).
A
slight,
but
significant,
decrease
in
fetal
body
weight
was
also
noted
at
2700
ppm.
No
significant
effects
were
observed
at
the
lower
test
doses.
Rabbits
however
showed
a
more
sensitive
response.
At
550
ppm,
all
fetuses
exhibited
severe
malformations
(
e.
g.,
heart
defects
and
anomalies
of
the
paw
and
sternum).
No
significant
increases
in
malformations
were
observed
at
other
tested
doses.
It
was
concluded
from
these
results
that
the
beta
isomer
of
the
2­
PGME
Acetate
has
teratogenic
potential.
By
analogy,
the
beta
isomer
of
its
parent
glycol
ether,
2­
PGME
was
also
considered
to
have
teratogenic
potential
While
the
beta
isomers
of
the
propylene
glycol
ethers
appear
to
have
teratogenic
potential
Miller
et
al.
(
Ex.
5­
093)
also
note
in
their
metabolic
study
that
the
commercial
product
of
2­
PGME
is
usually
a
mixture
of
the
two
isomers,
with
the
alpha
isomer
accounting
for
up
to
95%
of
the
mixture.
In
its
comment
on
the
ANPR,
the
ARCO
Chemical
Company,
a
primary
producer
of
propylene
glycol
ethers,
has
also
stated
that
2­
PGME
and
its
acetate
routinely
contain
less
than
2%
of
the
beta
isomer
(
Ex.
7­
19).
These
types
of
commercial
products
were
used
by
Miller
et
al.
(
Ex.
5­
088)
and
Hanley
et
al.
(
Ex.
5­
068)
in
their
reproductive
and
developmental
studies
and
were
shown
to
have
a
low
degree
of
biological
activity
in
comparison
to
ethylene
glycol
ethers
3.
Ethylene
Glycol
Monopropyl
Ether
(
EGPE)

Katz
et
al.
(
Ex.
5­
085)
conducted
a
series
of
acute
and
subchronic
toxicity
tests
on
EGPE
and
its
acetate
EGPEA
in
rats.
In
single
dose
oral
studies
rats
were
exposed
to
1090,
2180,
4360,
8720
mg/
kg
(
EGPE&
EGPEA)
or
17,470
mg/
kg
(
EGPEA
only).
The
LD50
of
EGPE
and
EGPEA
were
observed
to
be
3089
and
9456
mg/
kg,
respectively.
Prior
to
death
animals
exhibited
weakness,
anorexia
and
hemoglobinuria.
In
single
inhalation
dose
studies
rats
were
exposed
to
target
concentrations
of
0,
250,
100
or
200
ppm
EGPE
and
0,
250,
500
or
100
pp,
EGPEA.
No
lethality
was
observed
at
any
dose,
therefore
the
LC50
was
concluded
to
be
greater
than
2132
ppm
for
EGPE
and
greater
than
934
ppm
for
EGPEA.
In
six
week
oral
studies
male
rats
were
exposed
to
0,
195,
390,
780
or
1560
mg/
kg
body
weight
EGPE
or
0,
1097,
2193,
or
4386
mg/
kg
EGPEA.
Adverse
blood
effects
(
e.
g.,
significant
decreases
in
hemoglobin
concentration
and
significant
increases
in
platelet
counts
and
nucleated
red
blood
cells)
were
observed
for
both
compounds
at
all
dose
levels.
However,
only
rats
exposed
to
EGPEA
at
4386
mg/
kg
exhibited
significant
decreases
in
testicular
weight.
Pathological
examinations
revealed
atrophy
of
the
seminiferous
tubules
and
degenerated
sperm.
In
the
two
week
inhalation
studies
both
male
and
female
rats
were
exposed
for
6
hours/
day
to
either
0,
100,
200,
400,
800
ppm
EGPE
or
0,
100,
200,
400
or
800
ppm
EGPEA.
Slight,
but
significant
changes
in
red
blood
cells
(
e.
g.,
decreased
count,
and
increased
corpuscular
volume)
were
observed
at
800
and
400
ppm
for
both
compounds.
Hemoglobinuria
was
observed
in
males
and
females
at
800
ppm
EGPE
and
males
only
at
400
ppm.
Both
males(
4
out
of
5)
and
females(
5
out
of
5)
exhibited
hemoglobinuria
after
exposure
to
400
and
200
ppm
EGPEA.
A
significant
increase
in
spleen
weights
were
observed
at
800
and
400
ppm
for
both
compounds.
No
significant
changes
in
testicular
weight
were
observed
for
either
compound.
Based
on
these
results
the
authors
concluded
that
the
NOELs
in
this
study
were
200
ppm
for
EGPE
and
100
EGPEA
Krasavage
and
Katz
(
Ex.
5­
070)
studied
the
developmental
toxicity
of
EGPEA.
In
this
study
pregnant
rats
were
exposed
to
100,
200,
400
or
800
ppm
EGPEA,
6
hours/
day
on
days
6­
15
gestation.
Exposure
to
800
and
400
ppm
resulted
in
decreases
in
mean
maternal
body
weight,
feed
intake,
and
red
blood
cell
counts.
Exposure
at
800
ppm
also
resulted
in
a
significant
increase
in
the
incidence
in
resorptions
and
a
significant
reduction
in
mean
fetal
body
weight.
No
significant
increases
in
theincidence
of
major
malformations
were
observed
among
fetuses
exposed
up
to
800
ppm.
The
authors
stated
that
a
significant
increases
in
the
incidence
of
minor
skeletal
effects
(
e.
g.,
wavy,

[
page
15547]

knobby,
fused
and
partially
ossified
ribs
and
decreased
ossification
of
the
skull)
were
observed
at
800
and
400
ppm.
A
significant
increase
in
rudimentary
ribs
was
observed
in
the
200,
400
and
800
ppm
exposure
groups.
The
authors
concluded
that
adverse
fetal
effects
occur
after
exposure
to
EGPEA.
However
they
stated
that
these
effects
occurred
only
after
doses
which
were
overtly
toxic
to
the
maternal
animal
(
i.
e.,
800
and
400
ppm)

4.
Di­
Ethylene
Glycol
Monomethyl
Ether
(
DEGME)

In
inhalation
studies
by
Miller
et
al.
(
Ex.
5­
058)
male
and
female
rats
were
exposed
to
0,
30,
100
or
216
ppm
DEGME,
6
hours/
day,
five
days/
week
for
13
weeks.
No
dose
related
significant
effects
were
observed
among
the
male
or
female
animals
for
any
of
the
doses
tested.
Based
on
the
lack
of
effects
the
authors
concluded
that
DEGME
is
unlikely
to
present
the
same
degree
of
hazard
as
its
structural
homolog
2­
ME
The
teratogenic
potential
of
DEGME
was
examined
by
Scortichini
et
al.
(
Ex.
5­
060).
In
this
study
pregnant
rabbits
were
exposed
by
dermal
application
to
0,
50,
250
or
750
mg/
kg
day
of
DEGME
on
days
6­
18
gestation.
Rabbits
exposed
at
750
mg/
kg
exhibited
a
significant
decrease
in
maternal
weight
gain
and
red
blood
cell
counts.
No
statistically
significant
maternal
effects
were
observed
at
250
or
50
mg/
kg/
day.
The
authors
noted
an
increase
in
resorptions
at
750
mg/
kg/
day,
although
this
effect
was
not
statistically
significantly
different
from
controls.
In
addition
no
statistically
significant
increases
in
major
malformations
were
observed
at
any
of
the
doses
tested.
A
significant
increase
in
minor
skeletal
defects
such
as
forelimb
flexure,
fused
ribs,
delayed
ossification,
forked
ribs
and
cervical
spurs
were
observed
among
litters
from
rabbits
exposed
to
250
and
750
mg/
kg
DEGME.
The
authors
considered
these
to
be
significant
signs
of
fetotoxicity
rather
than
teratogenicity
and
suggested
that
these
types
of
fetal
defects
might
be
associated
with
maternal
toxicity
5.
Ethylene
Glycol
Monophenyl
Ether
(
2­
Phenoxyethanol)

Scortichini
et
al
(
Ex.
5­
059)
have
also
examined
the
teratogenic
potential
of
2­
Phenoxyethanol.
Pregnant
rabbits
were
dermally
exposed
to
0,
300,
600
or
1000
mg/
kg/
day
of
2­
Phenoxyethanol
on
days
6­
18
gestation.
Nine
of
25
rabbits
died
after
exposure
to
1000
mg/
kg/
day
and
5
of
25
rabbits
died
after
exposure
to
600
mg/
kg/
day.
Death
was
attributed
to
intravascular
hemolysis.
The
animals
surviving
in
these
groups
showed
no
statistically
significant
treatment
related
effects.
In
addition
no
statistically
significant
signs
of
maternal
toxicity
were
observed
after
exposure
to
300
mg/
kg/
day.
Among
fetuses
examined,
there
were
no
statically
significant
increases
in
the
incidence
of
external,
visceral
or
skeletal
malformations
at
300
or
600
mg/
kg/
day.
(
Fetal
observations
were
not
available
at
1000
mg/
kg/
day
due
to
the
high
lethality
at
1000
mg/
kg.
Animals
were
sacrificed
with
no
further
observations.
In
addition,
no
other
reproductive
parameters
such
as
resorptions
or
fetal
body
measurements
were
adversely
affected
at
600
or
300
mg/
kg/
day.
Based
on
these
results
the
authors
concluded
that
doses
up
to
600
mg/
kg/
day
produced
no
significant
signs
of
developmental
toxicity
6.
Conclusions
The
available
data
for
other
glycol
ether
compounds
suggests
that
there
are
differential
toxicities
between
the
longer
chain
glycol
ethers
and
shorter
chain
glycol
ethers
such
as
2­
ME,
2­
EE
and
their
acetates.
For
example,
in
the
case
of
2­
butoxyethanol,
there
were
observations
of
adverse
hematological
effects
but
no
observations
of
adverse
reproductive
or
developmental
effects.
Similarly
for
propylene
glycol
ethers
there
was
little
evidence
of
any
reproductive
or
developmental
toxicity
except
in
the
case
of
the
beta
isomeric
forms
of
these
compounds.
There
are
scattered
reports
on
other
ethylene
glycol
ether
compounds
showing
adverse
hematological
effects
and,
in
some
cases,
slight
evidence
of
testicular
effects
and
minor
skeletal
defects.
In
some
studies
the
authors
have
suggested
that
defects
observed
in
some
of
the
fetuses
may
be
due
to
maternal
toxicity
rather
than
a
direct
effect
on
the
conceptus.
However,
as
discussed
earlier,
developmental
effects
observed
at
maternally
toxic
doses
do
not
necessarily
imply
that
the
developmental
effects
are
secondary
to
maternal
effects
In
general,
the
toxicities
of
these
compounds
appear
less
potent
than
those
of
shorter
chain
glycol
ethers.
The
results
from
toxicity
tests
on
other
glycol
ethers
strongly
contrast
with
the
evidence
observed
after
exposures
to
2­
ME
and
2­
EE.
The
evidence
on
2­
ME
and
2­
EE
clearly
and
consistently
show
reduced
sperm
count,
decreased
fertility,
testicular
degeneration,
early
fetal
death,
major
external,
visceral
and
skeletal
malformations,
delayed
development
and
functional
deficiency.
These
effects
have
been
observed
in
several
species
and
through
various
routes
of
exposure.
The
totality
and
consistency
of
the
evidence
on
2­
ME,
2­
EE
and
their
acetates
in
experimental
animals,
clearly
indicate
that
these
agents
are
potential
reproductive
and
developmental
toxins
in
humans.
However,
OSHA
reiterates
that
past
research
primarily
concentrated
on
2­
ME,
2­
EE
and
their
acetates.
The
lack
of
evidence
on
other
glycol
ethers
may
be
due,
in
part,
because
less
research
has
been
conducted
on
these
compounds.
Thus,
OSHA
requests
data
and
analyses
on
other
glycol
ethers
and
their
potential
reproductive
and
developmental
toxicity
VI.
Preliminary
Risk
Assessment
A.
Introduction
The
United
States
Supreme
Court,
in
the
"
benzene"
decision,
Industrial
Union
Department,
AFL­
CIO
v.
American
Petroleum
Institute,
448
U.
S.
607
(
1980),
has
ruled
that
the
OSH
Act
requires
that,
prior
to
the
issuance
of
a
new
standard,
a
determination
must
be
made,
based
on
substantial
evidence
in
the
record
considered
as
a
whole,
that
there
is
a
significant
risk
of
health
impairment
at
existing
permissible
exposure
limits
and
that
issuance
of
a
new
standard
will
significantly
reduce
or
eliminate
that
risk.
The
Court
stated
that
"
before
he
can
promulgate
any
permanent
health
or
safety
standard,
the
Secretary
is
required
to
make
a
threshold
finding
that
a
place
of
employment
is
unsafe
in
the
sense
that
significant
risks
are
present
and
can
be
eliminated
or
lessened
by
a
change
in
practices."
448
U.
S.
642.
The
Court
also
stated
"
that
the
Act
does
limit
the
Secretary's
power
to
require
the
elimination
of
significant
risks."
448
U.
S.
644
Although
the
Court
in
the
"
cotton
dust"
case,
American
Textile
Manufacturers
Institute
v.
Donovan,
452
U.
S.
490
(
1981),
rejected
the
use
of
cost­
benefit
analysis
in
setting
OSHA
standards,
it
reaffirmed
its
previous
position
in
"
benzene"
that
a
risk
assessment
is
not
only
appropriate,
but
also
required
to
identify
significant
health
risk
to
workers
and
to
determine
if
a
proposed
standard
will
achieve
a
reduction
in
that
risk.
Although
the
Court
did
not
require
OSHA
to
perform
a
quantitative
risk
assessment
in
every
case,
the
Court
implied,
and
OSHA
as
a
matter
of
policy
agrees,
that
assessments
should
be
put
into
quantitative
terms
to
the
extent
possible
The
extent
to
which
a
risk
assessment
may
be
put
in
quantitative
terms
is
limited
in
the
case
of
glycol
ethers.
This
is
not
because
there
are
no
data
suitable
for
assessing
the
risk.
On
the
contrary,
there
are
a
number
of
well
conducted
rodent
bioassays
which
clearly
demonstrate
the
adverse
health
effects
[
page
15548]

associated
with
exposure
to
glycol
ethers
(
see
the
discussion
of
health
effects
above).
The
problem
lies
in
the
fact
that
there
is
not
a
quantitative
model
for
extrapolating
the
risk
of
developmental
and
reproductive
effects
either
from
high
doses
to
low
doses
or
across
species,
that
is
generally
accepted
in
the
scientific
community.
Therefore,
unlike
other
risk
assessments
which
OSHA
has
prepared
in
the
past,
this
risk
assessment
will
be
far
more
qualitative
than
quantitative
and
will
closely
follow
the
guidelines
of
the
Environmental
Protection
Agency
for
assessing
the
risks
of
suspect
developmental
and
reproductive
toxicants
(
Ex.
5­
153)
to
determine
those
levels
of
occupational
exposure
to
the
glycol
ethers
below
which
significant
risk
of
adverse
health
outcomes
is
unlikely.
This
approach,
which
is
described
in
detail
in
the
following
sections,
is
one
that
has
been
generally
accepted
in
both
the
scientific
and
regulatory
communities
and
is
generally
accepted
as
the
best
methodology
for
assessing
the
risks
associated
with
reproductive
and
developmental
toxins
Risk
assessment
is
a
process
in
which
scientific
judgments
are
made
concerning
the
potential
for
toxicity
to
occur
in
humans.
Because
human
data
are
often
not
available,
the
risk
assessment
process
often
requires
the
use
of
models
to
extrapolate
experimental
data
to
humans.
These
models
may
be
quantitative
or
qualitative.
Quantitative
models
generally
involve
mathematical
descriptions
of
dose­
response
relationships
which
allow
one
to
calculate
numerical
estimates
of
potential
risk
for
a
given
exposure.
Qualitative
models,
on
the
other
hand,
rely
more
on
narrative
descriptions
of
dose­
response
relationships
to
describe
the
likelihood
of
an
adverse
effect
for
a
given
exposure.
However
both
approaches
are
based
on
scientific
judgments
and
scientifically
based
assumptions
about
dose
response
relationships
and
the
predictive
value
of
experimental
data
The
scientific
and
regulatory
communities
have
chosen
a
preference
for
quantitative
models
especially
in
the
case
of
carcinogens.
However
the
scientific
and
regulatory
communities
also
consider
qualitative
models
as
an
acceptable
means
of
extrapolating
animal
data
to
humans.
The
No
Observed
Effect
Level­
Uncertainty
Factor
(
NOEL­
UF)
approach,
described
herein,
is
such
a
qualitative
model
As
a
matter
of
policy,
OSHA
has
chosen
to
use
the
NOEL­
UF
approach
in
describing
the
risks
associated
with
exposure
to
glycol
ethers.
OSHA
has
chosen
to
use
this
qualitative
approach
because
it
is
the
most
generally
well
accepted
approach
for
assessing
the
risks
from
reproductive
and
developmental
toxins.
OSHA's
decision
to
use
the
NOEL­
UF
approach
is
based
on
agreement
in
the
scientific
community
that
this
approach
is
the
best
methodology
currently
available
for
assessing
reproductive
health
risks.
This
approach,
in
addition
to
its
general
acceptance
in
the
scientific
community,
is
also
the
methodology
that
has
been
consistently
used
by
both
EPA
and
FDA
to
assess
reproductive
health
risks
in
their
rulemaking
procedures.
As
such
it
represents
the
best
evidence
available
to
OSHA
for
making
its
risk
determinations.
However
while
this
is
a
policy
choice
it
should
be
kept
in
mind
that
OSHA's
decision
to
use
the
NOEL­
UF
approach
is
a
scientifically
informed
choice
that
is
supported
by
scientific
expertise
and
judgment.
The
selection
of
the
NOEL­
UF
approach,
as
well
as
the
steps
involved
in
the
process
(
e.
g.,
the
selection
of
the
size
of
uncertainty
factors
to
extrapolate
from
animals
to
humans)
are
choices
based
on
underlying
scientific
data
and
assumptions
to
account
for
certain
basic
scientific
uncertainties
and
are
not
choices
borne
solely
from
a
public
health
perspective
to
provide
a
safe
workplace
in
the
face
of
scientific
uncertainty
B.
Assessing
the
Risk
of
Developmental
and
Reproductive
Effects
Most
OSHA
risk
assessments
have
focused
on
the
risk
of
cancer
from
occupational
exposure
to
toxic
substances.
In
the
case
of
carcinogen
risk
assessment,
mathematical
models
are
fit
to
dose­
response
data,
and
the
fitted
models
are
used
to
make
predictions
of
risk
at
a
variety
of
doses.
Although
there
are
a
number
of
mathematical
models
available
to
fit
to
carcinogen
dose­
response
data,
within
the
risk
assessment
community
in
general,
and
the
regulatory
community
in
particular,
a
consensus
exists
as
to
which
are
the
"
best"
models
In
the
case
of
non­
carcinogen
risk
assessment,
no
such
generally
accepted
mathematical
models
exist
for
predicting
risks.
The
traditional
approach
to
assessing
the
risk
of
noncancer
effects
has
been
first
to
make
a
qualitative
determination
that
a
toxic
substance
poses
a
risk
of
inducing
an
adverse
effect
and
then
to
determine
the
level
of
exposure
below
which
that
adverse
effect
is
unlikely
to
be
induced
in
humans
using
an
uncertainty
or
safety
factor
approach
This
approach
is
relatively
simple.
It
is
most
often
applied
to
experimental
(
animal)
data,
but
it
can
be
applied
to
epidemiological
data
when
such
data
are
available.
The
first
step
in
this
approach
is
to
determine
whether
an
effect
occurs
in
each
exposure
group
at
a
rate
which
is
statistically
significantly
elevated
over
the
rate
at
which
the
effect
occurs
in
the
unexposed
or
control
group.
The
highest
exposure
level
which
does
not
induce
the
effect
at
a
statistically
significantly
elevated
rate
is
called
the
no
observed
effect
level
or
NOEL.
In
its
most
recent
guidelines
(
Ex.
5­
153),
the
EPA
uses
the
term
NOAEL
or
no
observed
adverse
effect
level
instead
of
NOEL,
to
make
clear
that
effects
being
considered
are
of
toxicological
significance.
For
purposes
of
this
document,
NOEL
is
synonomous
with
NOAEL.
The
lowest
exposure
level
which
does
induce
the
effect
at
a
statistically
significantly
elevated
rate
is
called
the
lowest
observed
effect
level
or
LOEL.
(
EPA
also
refers
to
this
level
as
the
LOAEL
or
Lowest
Observed
Adverse
Effect
Level.
Again,
for
purposes
of
this
document,
LOEL
and
LOAEL
are
synonomous.)
In
this
approach
the
NOEL
is
usually
the
value
of
interest,
but
a
substance
may
induce
an
effect
at
a
statistically
significantly
elevated
rate
at
each
exposure
level
under
study.
In
that
case,
the
LOEL
becomes
the
value
of
interest.
Determination
of
the
NOEL
and/
or
the
LOEL
is
the
purpose
of
this
first
step
The
next
step
in
this
approach
is
to
divide
the
NOEL
or,
in
the
absence
of
a
NOEL,
the
LOEL
by
an
uncertainty
factor.
Choice
of
the
uncertainty
factor
will
depend,
in
part,
upon
whether
one
uses
the
NOEL
or
the
LOEL,
and
this
is
discussed
at
greater
length
below.
The
value
NOEL
Uncertainty
Factor
is
termed
the
"
acceptable
daily
intake"
or
ADI
and
is
considered
to
represent
the
level
of
exposure
at
which
humans
are
unlikely
to
experience
an
adverse
effect.
(
OSHA
notes
that
for
purposes
of
this
document,
the
ADI
is
not
to
be
interpreted
as
a
regulatory
limit,
but
rather
as
a
health­
based
level
upon
which
regulatory
considerations
can
be
referenced.)

Although
this
approach
requires
only
two
steps,
each
step
introduces
uncertainty
as
to
whether
the
final
ADI
estimate
does
indeed
represent
an
exposure
level
below
which
an
adverse
effect
is
unlikely
to
be
induced.
Implicit
in
the
uncertainty
factor
approach
is
the
assumption
that
there
is
a
threshold
level
of
exposure
below
which
a
toxic
[
page
15549]

response
will
not
be
induced,
and
the
NOEL
is
an
estimate
of
that
threshold.
There
is
debate,
however,
as
to
whether
non­
cancer
effects,
in
particular
developmental
effects,
are
indeed
threshold
phenomena.
Brent,
for
example,
has
argued
that
teratogenesis
"
is
by
and
large
a
threshold
phenomena,
which
means
that
the
vast
majority
of
teratogenic
agents
have
a
'
no
effect'
dose."
(
Ex.
5­
126).
He
cites
thalidomide
as
an
example
of
a
developmental
toxin
which
if
administered
at
50
mg
during
the
critical
gestation
period
can
effect
a
majority
of
embryos
but
which
will
have
no
effect
on
the
development
of
embryos
administered
at
0.5
mg
during
the
same
period
Others,
however,
maintain
that
not
all
developmental
toxins
have
a
threshold.
Gaylor
et
al
argue
that
"
if
a
chemical
produces
a
malformation
by
different
mechanism
than
spontaneous
malformations,
then
there
is
a
possibility
for
a
threshold
dose.
However,
if
a
chemical
produces
a
malformation
by
augmenting
or
accelerating
an
already
existing
mechanism
that
produces
spontaneous
malformations,
then
no
population
threshold
can
exist"
(
Ex.
5­
128).
Rodricks
et
al
maintain
that
"
in
cases
in
which
the
mechanisms
of
toxic
or
carcinogenic
action
are
not
understood,
it
is
not
possible
to
establish
or
reject
the
threshold
hypothesis
or
no­
threshold
hypothesis,
at
least
with
the
degree
of
certainty
usually
sought
in
scientific
proof.
There
are
numerous
reasons
to
believe
that
thresholds
must
exist
.
.
.,
but
generalization
to
all
agents
and
all
effects
is
not
possible"
(
Ex.
5­
130)

In
its
comments
in
response
to
OSHA's
Advance
Notice
of
Proposed
Rulemaking
(
ANPR),
the
Chemical
Manufacturer's
Association
(
CMA)
argues
that
acceptance
of
the
existence
of
thresholds
is
central
to
evaluating
reproductive
and
developmental
risk
(
Ex.
7­
17).
CMA
bases
its
position
in
part
on
the
"
demonstrated
regenerative,
repair
and
regulation
abilities
of
an
embryo
and
fetus."
In
addition,
CMA
notes
that
fetuses
are
protected
by
maternal
placenta
and
the
metabolic
processes
of
the
pregnant
female
that
break
down,
excrete,
store,
or
otherwise
inactivate
chemicals
before
they
can
damage
the
embryo.
CMA
concludes
that
"
to
make
appropriate
decisions
about
potential
human
reproductive
risks,
OSHA
must
focus
its
attention
on
studies
that
determine
the
threshold
below
which
adverse
effects
on
the
adult
or
the
conceptus
will
not
occur"
(
Ex.
7­
17)
While
OSHA
believes
it
is
likely
that
most
chemically­
induced
developmental
effects
have
a
threshold,
it
would
seem
that
CMA
is
confusing
the
finding
of
a
NOEL
in
an
animal
bioassay
with
the
certainty
a
threshold
exists.
As
noted
by
Rodricks
et
al,
the
existence
of
a
NOEL
from
experimental
data
is
consistent
with
the
hypothesis
of
a
threshold
but
is
not
sufficient
to
prove
it
(
Ex.
5­
130).
Furthermore,
if
a
threshold
does
exist,
there
is
little
reason
to
believe
that
the
NOEL
is
indeed
the
threshold
as
CMA
implies.
The
exposure
level
at
which
no
effect
is
observed
is
not
only
a
function
of
the
potency
of
the
substance
under
test
but
also
a
function
of
the
experimental
design
of
a
study.
For
example,
an
exposure
level
which
is
not
tested
cannot
be
a
NOEL.
If
a
researcher
tests
a
substance
at
10,
25,
and
50
ppm,
then
the
NOEL
can
only
be
10,
25,
or
50
ppm.
As
noted
by
Rodricks
et
al,
"[
f]
or
practical
reasons,
only
a
few
doses
can
be
used
in
experimental
studies.
While
these
doses
may
fall
above
and
below
the
true
threshold
doses,
it
is
only
by
chance
that
any
will
precisely
match
the
true
threshold
doses
(
and
this
chance
is
very
small)."

The
exposure
level
found
to
be
the
NOEL
in
a
study,
(
and
the
exposure
level
found
to
be
the
LOEL
in
a
study),
will
depend
not
only
upon
the
exposure
levels
chosen
by
a
researcher
but
also
upon
the
numbers
of
animals
in
each
exposure
group.
This
is
because
exposure
group
size
is
an
important
factor
in
determining
whether
an
observed
excess
of
an
effect
is
statistically
significant.
For
example,
suppose
an
experiment
is
run,
and
an
effect
is
found
to
occur
in
20%
of
the
animals
in
the
unexposed
group.
If
there
are
15
animals
in
each
exposure
group,
then
60%
of
the
animals
exposed
at
some
level
X,
(
9
out
of
15),
must
experience
the
effect
in
order
to
find
that
level
X
is
the
LOEL
(
i.
e.
60%
is
the
lowest
rate
at
which
the
effect
can
occur
in
order
to
be
statistically
significantly
elevated
at
the
p=
0.05
level
over
the
20%
rate
in
the
unexposed
animals
using
a
Fisher's
Exact
Test).
If
level
X
induces
the
effect
in
only
8
of
the
15
exposed
animals,
then
the
rate
for
the
effect
in
this
exposure
group
will
not
be
statistically
significant
If,
in
the
example
above,
the
number
of
animals
in
each
exposure
group
were
larger,
then
the
proportion
of
exposed
animals
which
must
experience
the
effect
to
achieve
statistical
significance
over
the
20%
rate
in
the
unexposed
group
decreases.
Thus,
if
there
were
30
animals
in
each
exposure
group,
then
only
43.3%
of
the
animals
exposed
to
some
level
Y,
(
13
out
of
30),
must
experience
the
effect
in
order
to
find
that
level
Y
is
the
LOEL.
If
there
were
1000
animals
in
each
exposure
group,
then
only
23.2%
of
the
animals
exposed
to
some
level
Z,
(
232
out
of
1000),
must
experience
the
effect
in
order
to
find
that
level
Z
is
the
LOEL
It
is
clear
from
this
example
that
the
exposure
levels
determined
to
be
the
NOEL
and
LOEL
will
depend
on
study
group
size.
The
"
true"
NOEL
may
be
lower
than
the
NOEL
determined
for
a
particular
study,
but
the
study
may
not
be
sensitive
enough
to
detect
it.
Few
studies
employ
1000
animals
per
group
in
their
study
design,
and
thus
the
direction
of
uncertainty
due
to
sample
size
is
towards
overestimating
the
NOEL
and
LOEL;
a
response
rate
which
is
statistically
significant
for
a
small
number
of
study
animals
will
always
be
statistically
significant
for
any
larger
number
of
animals
Because
small
exposure
group
size
and
therefore
lack
of
statistical
power
can
lead
to
the
erroneous
conclusion
that
exposure
induces
no
effect,
the
NOEL
is
not
taken
by
itself
to
represent
the
"
acceptable
daily
intake"
(
ADI).
Instead,
the
NOEL
is
adjusted
by
an
uncertainty
factor
not
only
to
account
for
uncertainties
associated
with
the
experimental
design
but
also
to
account
for
uncertainties
associated
with
extrapolation
across
species
(
i.
e.
from
experimental
animals
to
humans)
and
to
account
for
the
variability
of
responses
within
a
human
population
(
i.
e.
intra­
species
variability)

In
their
chapter
on
risk
assessment
for
effects
other
than
cancer,
Rodricks
et
al
provide
a
brief
history
of
the
origins
of
the
uncertainty
factor
(
Ex.
5­
130).
Referring
to
uncertainty
factors
as
safety
factors,
these
authors
write:

The
safety
factor
approach
was
originated
by
Lehman
and
Fitzhugh
of
the
FDA
who
indicated
that
variability
in
sensitivity
to
chemicals
(
expressed
as
differences
in
dose
causing
similar
responses)
across
several
species
was
usually
in
the
range
of
two
or
threefold
and
did
not
appear
to
exceed
tenfold.
They
also
indicated
that
the
variability
among
extensively
outbred
individuals
and
individuals
of
all
ages
and
degrees
of
susceptibility
(
e.
g.,
persons
in
the
general
population)
appeared
also
to
be
less
than
one
order
of
magnitude.
They
consequently
founded
the
100­
fold
safety
factor
as
a
general
method
of
dealing
with
the
uncertainties
of
extrapolation.
This
incorporated
a
factor
of
10
when
extrapolating
from
animals
to
humans
and
an
additional
factor
of
10
to
account
for
differential
sensitivities
within
the
human
population.
When
this
100­
fold
safety
factor
is
applied
to
the
highest
experimental
animal
NOEL,
it
is
considered
to
approximate
a
NOEL
for
humans
in
the
general
population,
and
becomes
the
ADI.

[
page
15550]

Since
the
concept
of
uncertainty
factors
was
first
introduced,
it
has
been
modified
to
derive
an
ADI
from
data
of
varying
quality.
For
example,
the
FDA
has
expanded
the
original
100­
fold
uncertainty
factor
approach.
When
a
NOEL
is
derived
from
subchronic
animal
data
but
that
NOEL
has
been
identified
in
two
species,
then
the
FDA
recommends
an
uncertainty
factor
of
1000.
Here,
the
additional
factor
of
10
is
needed
to
account
for
the
added
uncertainty
in
estimating
a
chronic
ADI
from
subchronic
data.
When
a
NOEL
is
derived
from
subchronic
animal
data
but
that
NOEL
has
been
identified
in
only
one
species,
FDA
recommends
an
uncertainty
factor
of
2000.
The
additional
two­
fold
factor
is
intended
to
account
for
possible
interspecies
differences
(
Ex.
5­
130)

If
a
NOEL
can
not
be
identified
from
study
data,
that
is,
if
the
lowest
exposure
level
used
in
a
study
induces
an
effect
at
a
rate
statistically
significantly
greater
than
observed
among
the
unexposed
group,
then
the
uncertainty
factor
is
applied
to
the
LOEL
instead
of
the
NOEL
to
derive
the
ADI.
As
with
the
NOEL,
the
uncertainty
factor
applied
to
the
LOEL
is
used
to
account
for
the
uncertainties
and
variability
described
above,
but
EPA
recommends
that
an
additional
uncertainty
factor,
usually
between
one
and
10,
be
used
to
account
for
the
fact
that
no
NOEL
was
identified
from
the
data
(
Ex.
5­
131)
Although
the
selection
of
uncertainty
factors
in
the
multiples
of
ten
may
appear
to
be
arbitrary,
there
is
some
experimental
support
for
their
selection,
and
this
is
discussed
at
some
length
in
an
article
by
Dourson
and
Stara
(
Ex.
4­
113).
(
The
scientific
basis
underlying
the
selection
and
use
of
uncertainty
factors
is
further
discussed
in
OSHA
Exhibit
5­
155.)
In
addition,
these
choices
of
uncertainty
factors
as
well
as
the
entire
uncertainty
factor
approach
for
non­
cancer
health
effects
have
been
adopted
by
a
number
of
governmental
agencies
and
international
organizations
including
the
U.
S.
Environmental
Protection
Agency
(
EPA),
the
U.
S.,
Food
and
Drug
Administration
(
FDA),
the
Joint
Food
and
Agricultural
Organization
of
the
World
Health
Organization
(
FAO/
WHO),
and
the
National
Academy
of
Sciences
(
NAS).
The
uncertainty
factor
approach
for
regulating
occupational
exposure
to
glycol
ethers
is
supported
by
many
of
the
commentors
responding
to
OSHA's
ANPR
including
CMA
(
Ex.
7­
17),
DOW
Chemical
(
Ex.
7­
21),
and
Du
Pont
(
Ex.
7­
28),
among
others,
although
not
all
agree
on
the
value
of
the
uncertainty
factor
which
should
be
used
As
CMA
points
out
in
its
comments,
the
uncertainty
factor
approach
"
has
been
well
established
for
regulating
reproductive
risks"
(
Ex.
7­
17).
As
noted
above,
the
ADI
represents
an
exposure
level
below
which
an
adverse
effect
is
unlikely,
and
confidence
that
the
ADI
is
an
exposure
level
below
which
an
adverse
effect
is
unlikely
will
depend,
to
a
large
extent,
upon
the
quality
of
the
data
from
which
it
is
derived.
If
we
know
something
of
the
mechanism
which
induces
an
effect
and
if
we
know
that
that
mechanism
is
activated
when
exposure
exceeds
some
threshold
level,
then
our
confidence
that
an
adverse
effect
is
unlikely
at
exposures
levels
at
or
below
the
ADI
increases
further
C.
Assessment
of
the
Developmental
Risk
from
Exposures
to
Glycol
Ethers
1.
Introduction
According
to
the
EPA
Guidelines
for
Developmental
Toxicity
Risk
Assessment
(
Ex.
5­
153),
the
major
manifestations
of
developmental
toxicity
include
1)
death
of
the
developing
organism;
2)
malformations;
3)
altered
growth,
and
4)
functional
deficiency.
The
studies
used
by
OSHA
for
its
assessment
of
developmental
risk
from
glycol
ethers
employed
a
protocol
exposing
fetuses
in
utero
during
organogenesis,
the
phase
of
gestation
during
which
the
major
organ
systems
develop.
The
pregnant
dams
were
sacrificed
at
the
end
of
this
gestational
phase
and
prior
to
giving
birth.
Each
of
the
unborn
fetuses
was
then
examined.
Under
this
protocol
the
endpoints
of
interest
in
these
studies
are
the
first
three
of
the
outcomes
listed
above
The
endpoint
"
death
of
the
developing
organism"
includes
resorptions
and
intra­
uterine
deaths.
Pre­
implantation
loss
is
not
a
measure
of
developmental
toxicity
in
these
studies
because
the
pregnant
females
were
not
exposed
to
any
glycol
ether
until
after
implantation
had
occurred
A
malformation
is
usually
defined
as
a
permanent
structural
change
that
may
adversely
affect
survival,
development,
or
function.
A
malformation
is
different
than
a
variation
which
is
usually
defined
as
a
divergence
beyond
the
usual
range
of
structural
constitution
that
may
not
adversely
affect
survival
or
health.
It
is
not
always
possible,
however,
to
distinguish
between
variations
and
malformations
because,
as
noted
by
EPA
in
its
Guidelines,
"
there
exists
a
continuum
of
responses
from
the
normal
to
extreme
deviant."
Furthermore,
there
is
no
generally
accepted
classification
of
malformations.
Other
terminology
which
is
also
used
includes
anomalies,
deformations,
and
aberrations,
but,
as
EPA
points
out,
these
terms
are
no
better
defined.
Nonetheless,
these
effects
indicate
toxicity
to
the
developing
organism
when
associated
with
exposure
to
a
chemical
Altered
growth
is
defined
by
EPA
as
an
alteration
in
offspring
organ
or
body
weight
or
size.
This
endpoint
may
be
reversible
or
may
result
in
a
permanent
change
As
noted
by
the
Interagency
Regulatory
Liaison
Group
(
IRLG)
in
its
Workshop
on
Reproductive
Toxicity
Risk
Assessment,
"
the
developmental
toxicity
endpoints
encountered
in
experimental
animals
do
not
and
should
not
be
expected
necessarily
to
mimic
those
observed
in
humans
exposed
to
the
same
toxicant"
and
"
the
specific
agentrelated
endpoints
in
humans
are
not
always
reproduced
in
experimental
animals"
(
Ex.
5­
018).
All
substances
known
to
cause
developmental
effects
in
humans,
however,
have
also
been
found
to
induce
developmental
effects
in
animals
with
the
exception
of
the
coumarin
anticoagulants
which
have
not
been
studied
extensively
in
animals
(
Ex.
4­
147).
Schardein
has
compared
the
effects
of
all
"
known
or
possible"
teratogens
in
humans
with
the
teratogenic
responses
observed
in
laboratory
animals
exposed
to
these
substances
(
Ex.
4­
147).
Each
of
the
developmental
toxicants
he
looked
at
induced
some
developmental
effect
in
at
least
one
animal
species,
but
only
one
class
of
substances,
androgenic
hormones,
induced
the
same
effect
as
observed
in
humans
in
each
species
which
experienced
an
effect.
Androgenic
hormones
have
been
tested
in
fourteen
species,
and
only
one
species
tested,
sheep,
experienced
no
effect
The
more
common
result
in
cross­
species
testing
of
developmental
toxicants
can
be
found
in
the
case
of
thalidomide
which
was
found
to
induce
limb
defects
(
i.
e.
missing
limbs)
in
humans.
In
laboratory
animals,
the
drug
was
found
to
induce
developmental
effects
in
seventeen
species,
but
an
effect
concordant
to
the
effect
observed
in
humans
was
observed
in
only
nine
species.
Furthermore,
eight
of
these
nine
species,
the
rhesus
monkey,
the
marmoset,
the
baboon,
the
bonnet
monkey,
the
crab­
eating
monkey,
the
green
monkey,
the
Japanese
monkey,
and
the
stump­
tailed
monkey,
are
not
the
usual
animals
used
in
animal
bioassays.
The
rabbit
was
the
sole
rodent
species
to
exhibit
an
effect
concordant
to
the
effect
observed
in
humans
(
Ex.
4­
147)

The
IRLG
has
noted
that
there
is
"
no
evidence
that
any
particular
species
or
[
page
15551]

strain
more
consistently
predicts
human
susceptibility
to
animal
teratogens
than
any
other
species
or
strain
"(
Ex.
5­
018).
This
is
borne
out
by
Schardein
(
Ex.
4­
147).
He
found
that
the
rabbit,
which
experienced
an
effect
from
thalidomide
concordant
to
the
effect
induced
humans,
experienced
no
adverse
developmental
effects
from
alcohol
or
diethylstilbestrol
(
DES),
both
known
to
cause
birth
defects
in
humans.
The
mouse
experienced
effects
concordant
to
those
in
humans
for
a
number
of
substances
including
alcohol,
diethylstilbestrol,
and
antithyroid
compounds,
but
neither
aminopterin
nor
streptomycin,
substances
found
to
induce
developmental
effects
in
humans,
induced
any
developmental
effects
in
this
species.
Rats
experienced
adverse
developmental
effects
from
exposure
to
most
of
the
toxicants
considered
by
Schardein,
(
rats,
and
mice
were
the
most
commonly
used
animals
in
tests
of
the
toxicants
considered
by
Schardein),
but
the
effects
were
concordant
with
those
in
humans
in
only
little
more
than
half
the
substances
and
at
least
one
substance
considered
by
Schardein,
trimethadione,
induced
no
effect
in
this
species
The
response
to
a
developmental
toxicant
in
animal
bioassay
can
be
measured
in
a
number
of
ways.
One
of
these
is
the
number
of
fetuses
affected
per
number
of
fetuses
exposed.
This
shall
be
referred
to
as
the
"
fetus
measure
of
response".
While
this
measure
gives
some
indication
of
the
potency
of
a
developmental
toxicant,
it
treats
each
fetus
independently
of
all
other
fetuses
thereby
ignoring
the
"
litter
effect".
The
litter
effect
is
the
tendency
for
littermates
to
respond
more
like
each
other
than
like
animals
from
different
litters.
Furthermore,
the
fetus
measure
cannot
distinguish
between
the
case
where
all
litters
have
one
or
two
affected
fetuses
and
the
case
where
all
affected
fetuses
are
from
only
one
or
two
litters,
although
these
two
scenarios
have
different
implications
for
the
potency
of
a
developmental
toxicant
An
alternative
measure
of
response
is
number
of
litters
with
at
least
one
affected
fetus
per
total
number
of
litters
exposed,
referred
to
as
the
"
litter
measure
of
response".
This
measure
treats
the
litters
as
the
experimental
unit
because,
as
noted
by
EPA
in
its
Guidelines,
it
is
the
maternal
animal
and
not
the
conceptus
which
is
treated
during
gestation
(
Ex.
5­
153).
This
is
the
measure
of
response
favored
by
EPA
for
evaluating
the
potency
of
a
developmental
toxicant.
The
drawback
to
this
measure,
however,
is
that
it
gives
equal
weight
to
a
litter
with
one
affected
fetus
as
it
gives
to
a
litter
with
all
affected
fetuses
In
addition
to
both
of
these
measures,
a
third
measure
which
OSHA
has
considered
for
evaluating
response
in
animals
exposed
to
developmental
toxicants
is
average
number
of
fetuses
affected
per
affected
litter.
This
shall
be
referred
to
as
the
"
fetus/
litter
measure
of
response".
This
measure
provides
a
compliment
to
the
fetus
measure
of
response
and
the
litter
measure
of
response,
for,
whereas
the
former
indicates
only
the
number
of
fetuses
affected
and
the
latter
indicates
only
the
number
of
litters
affected,
the
fetus/
litter
measure
provides
an
indication
of
how
severe
an
effect
may
be
within
an
affected
litter.
For
example,
a
fetus/
litter
value
of
1.0
would
indicate
that
only
one
fetus
was
affected
in
each
of
the
affected
litters.
A
fetus/
litter
value
of
2.0
would
indicate
that
on
average,
two
fetuses
were
affected
in
each
of
the
litters
with
affected
fetuses.
Comparison
of
fetus/
litter
values
across
exposure
groups
would
allow
one
to
determine
whether
more
fetuses
were
affected
in
each
affected
litter
as
dose
increases.
The
limitation
of
this
measure,
however,
is
that
unlike
the
other
two
measures
discussed
above,
the
fetus/
litter
measure
of
response
has
utility
only
as
a
descriptive
measure
and
can
not
be
used
for
statistical
inference
because
the
statistical
distribution
of
this
measure
is
unknown
2.
Choice
of
Data
a.
2­
ME
OSHA
has
identified
three
well
conducted
animal
bioassays
for
2­
ME
which
are
suitable
for
assessing
the
risk
of
developmental
effects
from
occupational
exposure
to
this
glycol
ether
and
for
determining
the
acceptable
daily
intake
or
ADI.
(
As
noted
earlier
for
purposed
of
this
document,
the
ADI
is
not
a
regulatory
limit
but
rather
a
health­
based
level
which
describes
the
level
at
which
humans
are
unlikely
to
exhibit
effects
similar
to
those
obseved
in
experimental
data.)
These
studies
were
chosen
because
in
each
of
these
studies,
exposure
levels
were
documented,
the
routes
of
exposure
were
the
same
as
is
found
in
most
occupational
settings
(
i.
e.
inhalation),
concurrent
controls
were
used,
two
or
more
exposure
levels
of
the
test
substance
were
employed,
statistically
significant
excesses
of
developmental
[
page
15552]

effects
were
observed
in
exposed
groups,
and
individual
litter
data
were
available
Hanley
and
associates
of
the
Dow
Chemical
Company
conducted
three
animal
inhalation
bioassays
for
2­
ME
using
female
rats,
rabbits,
and
mice
(
Exs.
4­
042a
and
4­
106).
Groups
of
30
to
31
bred
Fisher
344
rats
and
20
to
30
bred
New
Zealand
white
rabbits
were
exposed
to
2­
ME
at
levels
of
3,
10,
or
50
ppm.
Groups
of
30
to
32
bred
CF­
1
mice
were
exposed
to
2­
ME
at
levels
of
10
or
50
ppm.
The
test
article
was
supplied
by
Dow
and
was
99.96%
pure.
Thirty
bred
rats,
30
bred
rabbits,
and
31
bred
mice
served
as
controls
The
female
rats
were
bred
one
to
one
with
male
rats
of
the
same
strain.
The
female
mice
were
bred
two
to
one
with
male
mice
of
the
same
strain
(
two
females
to
one
male),
and
the
rabbits
were
bred
through
artificial
insemination.
Animals
were
randomly
assigned
to
exposure
groups.
Exposure
occurred
six
hours
per
day
through
the
organogenesis
phase
of
gestation:
from
day
6
through
day
15
of
gestation
for
rats
and
mice
and
from
day
6
through
day
18
gestation
for
rabbits.
All
animals
were
given
food
and
water
ad
libitum
except
during
periods
of
exposure
and
were
observed
daily
throughout
the
experimental
period
for
indications
of
toxicity
and
adverse
effects
of
treatment
Animals
found
dead
or
moribund
during
the
course
of
the
study
were
submitted
for
gross
pathological
examination.
Surviving
mice
were
sacrificed
on
day
18
of
gestation,
surviving
rats
were
sacrificed
on
day
21
of
gestation,
and
surviving
rabbits
were
sacrificed
on
day
29
of
gestation.
Caesarean
sections
and
examinations
were
preformed
on
all
animals
to
determine:
(
1)
the
number
and
position
of
fetuses
in
utero;
(
2)
the
number
of
live
and
dead
fetuses;
(
3)
the
number
and
position
of
resorption
sites;
(
4)
the
sex,
and
body
weight,
and
crown­
rump
length
of
each
fetus;
and
(
5)
any
gross
external
alternations.
In
addition,
the
rats
and
the
rabbits
were
examined
for
number
of
corpora
lutea.
The
uteri
of
apparently
non­
pregnant
animals
were
stained
and
examined
for
evidence
of
implantation
sites
to
determine
whether
pregnancy
had
occurred.
One
half
of
each
litter
was
dissected
and
examined
for
soft
tissue
alternations.
All
fetuses
were
examined
for
skeletal
alternations
b.
2­
EE
OSHA
has
identified
two
well
conducted
animal
inhalation
bioassays
for
2­
EE
which
are
suitable
for
assessing
the
risk
of
developmental
effects
from
occupational
exposure
to
this
glycol
ether
and
for
determining
the
acceptable
daily
intake
or
ADI.
As
with
2­
ME,
both
of
these
studies
were
chosen
because
in
each,
exposure
levels
were
documented,
the
routes
of
exposure
were
the
same
as
is
found
in
most
occupational
settings
(
i.
e.
inhalation),
concurrent
controls
were
used,
two
or
more
exposure
levels
of
the
test
substance
were
employed,
statistically
significant
excesses
of
developmental
effects
were
observed
in
exposed
groups,
and
individual
litter
data
were
available
Tinston,
Doe
and
associates
of
Imperial
Chemical
Industries
PLC
conducted
two
animal
inhalation
studies
for
2­
EE
using
rats
and
rabbits
(
Exs.
4­
038
and
4­
039;
see
also
Ex.
5­
071).
These
studies
were
sponsored
by
the
Chemical
Manufacturer's
Association
(
CMA)
and
followed
a
protocol
similar
to
the
one
used
by
Hanley
et
al.
Groups
of
24
bred
rats
of
the
Alpk/
AP
(
Wistar­
derived)
strain
were
exposed
to
2­
EE
at
levels
of
10,
50,
or
250
ppm.
Groups
of
24
bred
Dutch
rabbits
were
exposed
to
2­
EE
at
levels
of
10,
50,
and
175
ppm.
The
test
article
was
supplied
by
Imperial
Chemical
Industries
and
was
more
than
99%
pure.
Twenty­
four
bred
rats
and
24
bred
rabbits
served
as
controls
The
female
rats
were
bred
one
to
one
with
male
rats
of
the
same
strain,
and
female
rabbits
were
bred
with
2
male
rabbits
of
the
same
strain.
Animals
were
randomly
assigned
to
exposure
groups.
Exposure
occurred
six
hours
per
day
throughout
the
organogenesis
phase
of
gestation:
from
day
6
through
day
15
of
gestation
for
the
rats
and
from
day
6
through
day
18
of
gestation
for
the
rabbits.
All
animals
were
given
food
and
water
ad
libitum
except
during
periods
of
exposure
and
were
observed
daily
for
their
clinical
condition
Terminal
sacrifice
of
the
animals
occurred
on
day
21
of
gestation
for
the
rats
and
day
29
of
gestation
for
the
rabbits.
After
sacrifice,
the
number
of
corpora
lutea
in
each
animal's
ovaries
was
counted.
The
uterus
of
each
animal
was
cut
open
and
the
number
of
implantations
as
well
as
the
number
of
early
and
late
intra­
uterine
deaths
was
determined.
An
intra­
uterine
death
was
judged
to
be
late
if
fetal
tissues
were
distinguishable.
Each
fetus
which
had
not
died
in
utero
was
removed
from
the
uterus.
These
fetuses
were
weighed
and
examined
for
gross
defects.
Half
of
the
rat
fetuses
and
all
of
the
rabbit
fetuses
were
examined
for
skeletal
defects.
All
fetuses
of
both
species
were
examined
for
external
and
visceral
defects
3.
Bioassay
Results
a.
2­
ME
In
measuring
the
incidence
of
effects
of
2­
ME
in
fetal
rats,
rabbits,
and
mice,
Hanley
et
al
grouped
the
effects
into
three
categories:
external
alterations,
soft
tissue
alterations,
and
skeletal
alterations.
Each
of
these
categories
of
defects
was
subdivided
further
into
major
defects
and
minor
defects.
The
study
authors
provided
no
explanation
as
to
the
criteria
used
to
subdivide
these
categories,
and
one
must
assume
it
was
professional
judgement
(
Exs.
4­
047
and
4­
106)

Table
VI­
A
presents
the
incidence
of
developmental
effects
in
fetal
rats
exposed
to
2­
ME.
Incidence
is
reported
using
each
of
the
measures
of
response
discussed
above
(
i.
e.
fetus,
litter
and
fetus/
litter).
The
only
effects
presented
in
this
discussion
are
those
which
occurred
in
any
exposed
group
at
a
rate
statistically
significantly
greater
than
the
rate
in
the
unexposed
group
at
the
p=
0.05
level
using
either
the
fetus
measure
of
response
or
the
litter
measure
of
response.
Statistical
significance
was
determined
using
Fisher's
Exact
Test
Table
VI­
A
Incidence
of
Developmental
Effects
Observed
in
Fisher
344
Rats
Exposed
to
2­
ME
Days
6
through
15
of
Gestation
(
1)

MINOR
SKELETAL
ALTERATIONS
­­
Control
3
ppm
10
ppm
50
ppm
Fetus
(
2)
4/
287
3/
283
6/
293
19/
307(
3)

Delayed
Ossification
Litters
(
4)
4/
29
3/
28
5/
28
13/
30(
5)

of
Centra
Fetus/
Litter
(
6)
1.00
1.00
1.20
1.46
Fetus
18/
287
13/
283
20/
293
57/
307(
3)

Rib
Spurs
Litters
12/
29
10/
28
13/
28
26/
30(
3)

Fetus/
Litter
1.50
1.30
1.54
2.19
Fetus
125/
287
142/
283
131/
293
97/
307(
3)

Delayed
Ossification
Litters
28/
29
27/
28
27/
28
28/
30
of
Sternebrae
Fetus/
Litter
4.46
5.26
4.85
3.40
1
­
Data
from
Hanley
et
al,
Ex.
4­
042a.

2
­
Incidence
is
number
of
fetuses
affected
divided
by
the
total
number
of
fetuses
3
­
Significantly
different
than
controls
at
the
p<
.01
level
4
­
Incidence
is
number
of
litters
with
at
least
one
fetus
affected
5
­
Significantly
different
than
controls
at
the
p<
.05
level
6
­
Average
number
of
affected
fetuses
per
affected
litter
Delayed
ossification
of
the
centra
and
rib
spurs
are
the
two
developmental
effects
which
occurred
at
a
rate
statistically
significantly
greater
in
an
exposed
group
than
in
the
controls.
Both
of
these
effects
were
classified
as
minor
skeletal
alterations.
Both
effects
were
elevated
for
the
50
ppm
group
only,
but
incidence
was
significant
at
the
p=
0.012
level
or
lower
regardless
of
measure
of
response,
and
the
fetus/
litter
measure
of
response
increases
with
dose.
Delayed
ossification
of
the
sternebra
was
significantly
reduced
for
the
50
ppm
group
when
measured
using
the
fetus
measure
of
response,
but
it
was
not
significant
using
the
litter
measure
of
response
and
the
fetus/
litter
measure
does
not
show
a
dose
related
trend.
The
authors
attribute
the
observed
deficit
of
delayed
ossification
of
the
sternebra
to
normal
variation
and
not
to
exposure
to
2­
ME
Table
VI­
B
presents
the
incidence
of
developmental
effects
in
fetal
rabbits
exposed
to
2­
ME.
The
same
measures
of
incidence
presented
for
the
rats
are
presented
for
the
rabbits,
and
the
same
statistical
criteria
were
used
for
inclusion
of
an
effect
in
the
table
[
page
15553]

Table
VI­
B
Incidence
of
Developmental
Effects
Observed
in
New
Zealand
White
Rabbits
Exposed
to
2­
ME
Days
6
through
18
of
Gestation
(
1)

Control
3
ppm
10
ppm
50
ppm
Resorptions:
Fetus(
2)
7/
180
14/
186
23/
210(
3)
46/
191(
3)

Litters(
4)
5/
23
10/
24
14/
24(
5)
16/
24(
3)

Fetus/
Litter(
6)
1.40
1.40
1.64
2.88
MAJOR
EXTERNAL
ALTERATIONS(
7)

Arthrogryposis:

Fetus
0/
173
1/
172
0/
187
54/
145(
3)

Litters
0/
23
1/
23
0/
24
15/
22(
3)

Fetus/
Litter
0.00
1.00
0.00
3.60
Anonychia:

Fetus
0/
173
0/
172
0/
187
14/
145(
3)

Litters
0/
23
0/
23
0/
24
6/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
2.33
Brachydactyly:

Fetus
0/
173
0/
172
0/
187
6/
145(
3)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
1.50
Ectrodactyly:

Fetus
0/
173
0/
172
0/
187
6/
145(
3)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
1.50
Omphalocele:

Fetus
0/
173
0/
172
0/
187
5/
145(
5)

Litters
0/
23
0/
23
0/
24
2/
22
Fetus/
Litter
0.00
0.00
0.00
2.50
Thinning
of
Adominal
Wall:

Fetus
0/
173
0/
172
0/
187
6/
145(
3)

Litters
0/
23
0/
23
0/
24
3/
22
Fetus/
Litter
0.00
0.00
0.00
2.00
Kinky
Tail:

Fetus
0/
173
0/
172
0/
187
4/
145(
5)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
1.00
MINOR
EXTERNAL
ALTERATIONS
Misalignment
of
Palatine
Rugae:

Fetus
0/
173
0/
174
0/
187
27/
145(
3)
Litters
0/
23
0/
23
0/
24
11/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
2.45
Narrowed
tip
of
Tail:

Fetus
0/
173
0/
172
0/
187
6/
145(
3)

Litters
0/
23
0/
23
0/
24
6/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
1.00
MAJOR
SOFT
TISSUE
ALTERATIONS
f
Coarctation
of
the
Aortic
Arch:

Fetus
0/
95
0/
93
0/
101
13/
80(
3)

Litters
0/
23
0/
23
0/
24
6/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
2.17
Ventricular
Septal
Defect:

Fetus
0/
95
0/
93
0/
101
34/
80(
3)

Litters
0/
23
0/
23
0/
24
15/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
2.27
Hypoplastic
Spleen:

Fetus
0/
95
0/
93
0/
101
25/
80(
3)

Litters
0/
23
0/
23
0/
24
13/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
1.92
Dilated
Renal
Pelvis:

Fetus
0/
95
1/
93
1/
101
28/
80(
3)

Litters
0/
23
1/
23
1/
24
14/
22(
3)

Fetus/
Litter
0.00
1.00
1.00
2.00
Patent
Ductus
Arteriosis:

Fetus
0/
95
1/
93
0/
101
5/
80(
5)

Litters
0/
23
1/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
1.00
0.00
1.25
Hypoplastic
Gall
Bladder:

Fetus
0/
95
0/
93
0/
101
4/
80(
5)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
1.00
Pale
Spleen:

Fetus
4/
95
2/
93
1/
101
30/
80(
3)

[
page
15554]
Litters
1/
23
1/
23
1/
24
16/
22(
3)

Fetus/
Litter
4.00
2.00
1.00
1.88
Dilated
Ureter:

Fetus
0/
95
0/
93
0/
101
7/
80(
3)

Litters
0/
23
0/
23
0/
24
6/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
1.17
Convoluted
Ureter:

Fetus
3/
95
2/
93
0/
101
12/
80(
3)

Litters
2/
23
2/
23
0/
24
8/
22(
5)

Fetus/
Litter
1.50
1.00
0.00
1.50
Paroavarian
Cyst:

Fetus
g
0/
48
1/
47
1/
53
9/
40(
3)

Litters
h
0/
23
1/
21
1/
24
8/
22(
3)

Fetus/
Litter
0.00
1.00
1.00
1.13
Testicular
Cyst:

Fetus
g
0/
47
0/
46
0/
48
5/
40(
5)

Litters
i
0/
22
0/
23
0/
23
3/
22
Fetus/
Litter
0.00
1.00
1.00
1.13
Shortened
Nasals,
Maxillae
and
Mandibles:

Fetus
0/
173
0/
172
0/
187
6/
145(
3)
Litters
0/
23
0/
23
0/
24
1/
22
Fetus/
Litter
0.00
0.00
0.00
6.00
MAJOR
SKELETAL
ALTERATIONS
e
Missing
Palange(
s):

Fetus
0/
173
0/
172
0/
187
7/
145(
3)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
1.75
Missing
Metacarpal(
s):

Fetus
0/
173
0/
172
0/
187
4/
145(
5)

Litters
0/
23
0/
23
0/
24
2/
22
Fetus/
Litter
0.00
0.00
0.00
2.00
Missing
Metatarsal(
s):

Fetus
0/
173
0/
172
0/
187
9/
145(
3)

Litters
0/
23
0/
23
0/
24
4/
22(
5)

Fetus/
Litter
0.00
0.00
0.00
2.25
Shortened
Ribs:

Fetus
0/
173
0/
172
0/
187
4/
145(
5)

Litters
0/
23
0/
23
0/
24
2/
22
Fetus/
Litter
0.00
0.00
0.00
2.00
Enlarged
Interparietals:

Fetus
0/
173
0/
172
0/
187
5/
145(
5)

Litters
0/
23
0/
23
0/
24
1/
22
Fetus/
Litter
0.00
0.00
0.00
5.00
Delayed
Ossification
of
the
Hyoid:

Fetus
1/
173
2/
172
2/
187
14/
145(
3)

Litters
1/
23
2/
23
2/
24
8/
22(
3)

Fetus/
Litter
1.00
1.00
1.00
1.75
Delayed
Ossification
of
the
Tarsals(
s):

Fetus
0/
173
3/
172
1/
187
17/
145(
3)

Litters
0/
23
3/
23
1/
24
8/
22(
3)

Fetus/
Litter
0.00
1.00
1.00
2.13
Extra
Lumbar
Ribs:

Fetus
0/
173
0/
172
0/
187
13/
145(
3)

Litters
0/
23
0/
23
0/
24
7/
22(
3)

Fetus/
Litter
0.00
0.00
0.00
1.86
Shortened
Lumbar
Ribs:

Fetus
0/
173
0/
172
0/
187
4/
145(
5)

Litters
0/
23
0/
23
0/
24
2/
22
Fetus/
Litter
0.00
0.00
0.00
1.86
Delayed
Ossification
of
the
Centra:

Fetus
4/
173
2/
172
0/
187
11/
145(
5)

Litters
4/
23
2/
23
0/
24
(
5)
8/
22
Fetus/
Litter
1.00
1.00
0.00
1.38
Delayed
Ossification
of
the
Sternebrae:

Fetus
82/
173
93/
172
123/
187(
3)
127/
145(
3)

Litters
23/
23
23/
23
24/
24
22/
22
Fetus/
Litter
3.57
4.04
5.13
5.77
Fused
Sternebrae:

Fetus
3/
173
2/
172
0/
187
11/
145(
5)

Litters
3/
23
2/
23
0/
24
8/
22
[
page
15555]
Fetus/
Litter
3.57
4.04
5.13
1.33
Sternebrae
­
Extra
Site
of
Ossification:
Fetus
0/
173
0/
172
0/
187
4/
145(
5)

Litters
0/
23
0/
23
0/
24
3/
22
Fetus/
Litter
3.57
4.04
5.13
1.33
1
­
Data
from
Hanley
et
al,
Ex.
4­
042a
2
­
Incidence
is
number
of
fetuses
affected
divided
by
the
total
number
of
fetuses
3
­
Significantly
different
than
controls
at
the
p<
.01
level.
4
­
Incidence
is
number
of
litters
with
at
least
one
fetus
affected
5
­
Significantly
different
than
controls
at
the
p<
.05
level.
6
­
Average
number
of
affected
fetuses
per
affected
litter.
7
­
Denominator
(
i.
e.
the
number
of
animals
at
risk)
is
adjusted
for
resorptions
8
­
Only
a
portion
of
fetuses
in
each
exposure
group
were
examined
for
soft
tissue
alterations.
9
­
Denominator
not
specified
by
study
authors.
Number
of
fetuses
at
risk
estimated
by
applying
male/
female
ratio
for
each
exposure
group
to
number
of
fetuses
examined
for
soft
tissue
alterations
10
­
Denominator
is
number
of
litters
with
at
least
one
female
fetus.
11
­
Denominator
is
number
of
litters
with
at
least
on
male
fetus.

Incidence
of
resorptions
was
statistically
significantly
increased
using
both
the
fetus
and
the
litter
measures
of
response
for
the
10
ppm
and
the
50
ppm
group.
The
fetus/
litter
measure
of
incidence
shows
a
dose
related
increase.
The
study
authors
note
that
although
resorptions
are
significantly
elevated
for
the
10
ppm
group,
the
observed
rate
for
fetuses
(
11%)
and
for
litters
(
58%)
are
comparable
to
the
historical
incidence
of
resorptions
observed
in
other
studies
in
the
same
laboratory
(
7%
to
15%
for
fetuses
and
38%
to
74%
for
litters).
They
attribute
the
finding
of
statistical
significance
of
resorptions
in
this
exposure
group
to
the
unusually
low
control
group
incidence
of
resorptions
(
4%
for
fetuses
and
22%
for
litters)
and
not
to
exposure
Major
external
alterations
in
rabbits
occurred
at
a
significant
excess
in
the
50
ppm
group
only.
Incidence
of
arthrogryposis
(
abnormal
flexure
of
the
forelimbs),
anonychia
(
absence
of
nails),
brachydactyly
(
short
digits),
ectrodactyly
(
absence
of
part
or
all
of
a
digit),
and
kinky
tail
occurred
at
a
statistically
significantly
elevated
rate
for
both
the
fetus
measure
of
response
and
the
litter
measure
of
response.
Incidence
of
omphalocele
(
protrusion
of
the
intestines
through
the
abdominal
wall),
and
thinning
of
the
abdominal
wall
was
significant
for
fetuses
but
not
for
litters
As
with
the
major
external
alterations,
the
minor
external
alterations,
misalignment
of
the
palatine
rugae
and
narrowed
tip
of
tail,
occurred
at
a
significant
excess
only
in
the
50
ppm
group.
Both
were
statistically
significant
using
both
the
fetus
and
the
litter
measure
of
response
What
is
most
striking
about
these
data
is
that
every
external
alteration
observed,
major
or
minor,
was
observed
only
in
the
50
ppm
group
except
for
one
fetus
in
the
3
ppm
group
observed
with
arthrogryposis.
The
almost
total
absence
of
background
incidence
of
these
effects
reduces
the
uncertainty
as
to
whether
the
response
in
the
50
ppm
group
could
be
attributed
to
chance
variation
rather
than
exposure
to
2­
ME
While
all
the
fetal
rabbits
were
examined
for
external
alterations,
only
half
were
examined
for
soft
tissue
alterations.
Thus,
the
study
had
less
power
to
detect
this
type
of
developmental
effect.
Nonetheless,
a
large
number
of
soft
tissue
alterations
were
observed
at
a
significant
excess
in
50
ppm
group.
Incidence
of
these
effects
was
not
significantly
elevated
over
controls
in
any
other
exposure
group.
The
major
soft
tissue
alterations
were
coarctation
of
the
aortic
arch,
ventricular
septal
defect,
hypoplastic
spleen,
and
dilated
renal
pelvis,
and
incidence
of
these
effects
in
the
50
ppm
group
were
statistically
significant
using
both
the
fetus
and
the
litter
measure
of
response
at
the
p=
0.009
level
or
lower.
All
but
one
minor
soft
tissue
alteration
occurred
at
a
statistically
significant
rate
in
the
50
ppm
group
using
both
measures
of
response
These
alterations
were
patent
ductus
arteriosis,
hypoplastic
gall
bladder,
pale
spleen,
dilated
ureter,
convoluted
ureter,
and
parovarian
cysts.
Testicular
cysts
were
statistically
significant
in
male
fetal
rabbits
in
the
50
ppm
group
using
the
fetus
measure
but
not
using
the
litter
measure.
Here
again,
the
almost
total
absence
of
any
of
these
effects
in
the
control
group,
the
3
ppm
group,
or
the
10
ppm
group
lends
further
support
to
2­
ME
as
the
cause
for
these
effects
in
the
50
ppm
group
All
fetuses
were
examined
for
skeletal
alterations,
yet
incidence
of
all
but
two
of
these
alterations
was
significantly
elevated
in
the
50
ppm
group
only.
The
major
skeletal
alterations
which
occurred
at
a
significantly
elevated
rate
in
this
group
using
both
measures
of
response
were
missing
phalanges
and
missing
metatarsal;
the
minor
skeletal
alterations
were
delayed
ossification
of
the
hyoid,
delayed
ossification
of
the
tarsals,
and
extra
lumbar
ribs.
Incidence
of
shortened
nasals,
maxillae
and
mandibles
and
shortened
ribs,
both
major
external
alterations,
were
significantly
elevated
in
the
50
ppm
group
also
but
only
when
measured
in
fetuses.
Likewise,
incidence
of
enlarged
interparietals,
shortened
lumbar
ribs,
delayed
ossification
of
the
centra,
fused
sternebra,
and
extra
site
of
sternebra
ossification,
all
minor
external
alterations,
were
significantly
elevated
in
the
50
ppm
group
but
again,
only
for
the
fetus
measure
of
response.
There
was
a
statistically
significant
deficit
of
delayed
ossification
of
the
centra
in
litters
in
the
10
ppm
group,
this
most
likely
is
attributable
to
chance
variation
and
not
to
exposure.
Delayed
ossification
of
the
sternebra
was
significantly
elevated
over
controls
in
fetuses
in
the
10
ppm
and
the
50
ppm
exposure
groups,
but
the
incidence
of
this
effect
measured
in
litters
at
both
exposure
levels
was
the
same
(
100%)
as
in
the
control
and
3
ppm
exposure
group
Exposure
to
2­
ME
did
not
have
as
strong
an
effect
in
fetal
mice
as
it
did
in
fetal
rabbits.
Table
VI­
C
presents
the
results
of
the
mouse
bioassay.
Criteria
for
inclusion
of
an
effect
in
the
table
in
the
same
as
was
used
for
both
rats
and
rabbits.
Only
one
effect,
extra
lumbar
ribs,
a
minor
skeletal
alteration,
was
significantly
elevated
using
both
the
fetus
and
the
litter
measure
of
response,
and
this
was
in
the
50
ppm
group.
[
page
15556]

Incidences
of
resorption,
hypoplastic
testicle,
and
extra
site
of
sternebra
ossification
in
the
50
ppm
group
were
significantly
elevated
over
controls
but
only
in
fetuses
and
not
in
litters.
Incidence
of
testicular
hemorrhage
and
delayed
ossification
of
the
sternebra
was
significantly
elevated
over
controls
in
the
10
ppm
group
and
the
50
ppm
using
the
fetus
measure
of
response,
but
incidence
of
these
effects
was
not
significant
when
response
was
measured
in
litters
Table
VI­
C
Incidence
of
Developmental
Effects
Observed
in
CF­
1
Mice
Exposed
to
2­
ME
days
6
through
15
of
Gestation
(
1)

Control
10
ppm
50
ppm
Resorptions:

Fetus
b
25/
342
25/
285
35/
286(
3)

Litters
c
16/
26
14/
23
18/
24
Fetus/
Litter
d
1.56
1.79
1.94
MINOR
SOFT
TISSUE
ALTERATIONS
e
Hypoplastic
Testicle:

Fetus
f
2/
86
3/
64
8/
66(
3)

Litters
g
2/
26
3/
23
6/
22
Fetus/
Litter
1.00
1.00
1.33
Testicular
Hemorrhage:

Fetus
f
2/
86
3/
64
8/
66(
3)

Litters
g
2/
26
3/
23
6/
22
Fetus/
Litter
1.00
1.00
1.33
MINOR
SKELETAL
ALTERATIONS
h
Extra
Lumbar
Rib:

Fetus
48/
317
49/
260
82/
251(
10)

Litters
14/
26
14/
23
21/
24(
3)

Fetus/
Litter
3.43
3.50
3.90
Delayed
Ossification
of
the
Sternebrae:

Fetus
76/
317
43/
260
(
3)
77/
251(
3)
Litters
18/
26
13/
23
21/
24
Fetus/
Litter
3.43
3.50
3.90
Sternebrae
­
Extra
Site
of
Ossification:

Fetus
21/
317
9/
260
8/
251(
3)

Litters
9/
26
6/
23
4/
24
Fetus/
Litter
3.43
3.50
3.90
________________________________________________________________________
___

1
­
Data
from
Hanley
et
al,
Ex.
4­
106.
2
­
Incidence
is
number
of
fetuses
affected
divided
by
the
total
number
of
fetuses
3
­
Significantly
different
than
controls
at
the
p<
.05
level.
4
­
Incidence
is
number
of
litters
with
at
least
one
fetus
affected
5
­
Average
number
of
affected
fetuses
per
affected
litter.
6
­
Only
a
portion
of
fetuses
in
each
exposure
group
were
examined
for
soft
tissue
alterations
7
­
Denominator
not
specified
by
study
authors.
Number
of
fetuses
at
risk
estimated
by
applying
male/
female
ratio
for
each
exposure
group
to
number
of
fetuses
examined
for
soft
tissue
alterations
8
­
Denominator
is
number
of
litters
with
at
least
on
male
fetus.
9
­
Denominator
(
i.
e.
the
number
of
animals
at
risk)
is
adjusted
for
resorptions
10
­
Significantly
different
than
controls
at
the
p<
.01
level
b.
2­
EE
In
their
studies
of
the
developmental
effects
of
2­
EE
on
fetal
rats
and
fetal
rabbits,
Tinston,
Doe
et
al,
(
Exs.
4­
038
and
4­
039;
see
also
Ex.
5­
071),
classified
effects
differently
than
Hanley
et
al.
Abnormalities
which
were
deemed
either
rare
or
lethal
or
both
were
classified
as
major
external
and
visceral
defects
or
major
skeletal
defects
while
those
defects
which
were
judged
to
be
small
changes
that
would
not
normally
impair
survival
and
that
occur
at
a
moderate
to
low
frequency
in
the
strain
were
classified
as
minor
external
and
visceral
defects
or
minor
skeletal
defects.
A
third
classification,
variant,
was
used
to
describe
those
defects
which
are
common
in
the
species
and
are
not
normally
deleterious
Another
difference
between
the
2­
EE
bioassays
and
the
2­
ME
bioassays
is
that
the
investigators
in
the
2­
EE
bioassays
considered
much
more
specific
effects
than
did
the
investigators
in
the
2­
ME
bioassays.
For
example,
Tinston
et
al
looked
at
the
degree
of
ossification
(
i.
e.
partially
ossified
or
not
ossified)
of
each
centrum
and
sternebra
in
each
fetus
examined.
Thus,
the
study
authors
report
the
incidence
of
partial
ossification
of
the
first
sternebra,
partial
ossification
of
the
second
sternebra,
and
so
forth.
In
the
2­
ME
bioassays,
on
the
other
hand,
Hanley
et
al
grouped
any
ossification
defect
of
any
sternebra
into
the
category
"
delayed
ossification
of
the
sternebra"
and
any
ossification
defect
of
any
centrum
into
the
category
"
delayed
ossification
of
the
centra."
The
different
approaches
for
measuring
the
incidence
of
effects
have
implications
for
the
inferences
which
can
be
drawn
from
analysis
of
the
study
results,
and
these
implications
will
be
discussed
in
the
next
section
Table
VI­
D
presents
the
incidence
of
developmental
effects
in
fetal
rats
exposed
to
2­
EE.
As
with
the
results
from
the
2­
ME
bioassays,
incidence
is
reported
using
the
fetus,
litter,
and
fetus/
litter
measures
of
response,
and
only
those
effects
which
occurred
in
any
exposed
group
at
a
statistically
significantly
greater
rate
than
in
control
using
either
the
fetus
or
the
litter
measure
of
response
are
included.

[
page
15557]

Again,
statistical
significance
was
determined
using
Fisher's
Exact
Test
with
a
critical
value
of
p=
0.05.

Table
VI­
D
Incidence
of
Developmental
Effects
Observed
in
Wistar
Rats
Exposed
to
2­
EE
days
6
through
15
of
Gestation
(
a)

Control
10
ppm
50
ppm
250
ppm
All
Intra­
uterine
Deaths:

Fetus
(
b)
16/
297
22/
277
12/
261
32/
266
**

Litters
(
c)
12/
23
15/
24
10/
22
12/
21
Fetus/
Litter
(
d)
1.33
1.47
1.20
2.67
Late
Intra­
uterine
Deaths:

Fetus
(
e)
3/
284
3/
258
2/
251
17/
251
**

Litters
2/
23
2/
24
2/
22
7/
21
*

Fetus/
Litter
1.50
1.50
1.00
2.43
MINOR
SKELETAL
ANOMALIES
(
f)
Skull
­
Partially
Ossified
Frontals:

Fetus
1/
147
0/
131
4/
129
14/
122
**

Litters
1/
23
0/
24
4/
22
7/
21
*

Fetus/
Litter
1.00
0.00
1.00
2.00
Skull
­
Partially
Ossified
Parietal:

Fetus
10/
147
1/
131
**
15/
129
35/
122
**

Litters
6/
23
1/
24
*
8/
22
17/
21
**

Fetus/
Litter
1.67
1.00
1.88
2.06
Skull
­
Partially
Ossified
Interparietal:

Fetus
26/
147
3/
131
**
24/
129
40/
122
**

Litters
10/
23
3/
24
*
12/
22
17/
21
*

Fetus/
Litter
2.60
1.00
2.00
2.35
Skull
­
Odontoid
Not
Ossified:

Fetus
26/
147
19/
131
32/
129
93/
122
**

Litters
13/
23
10/
24
16/
22
20/
21
**

Fetus/
Litter
2.00
1.90
2.00
4.65
Cervical
centrum
#
3
Not
Ossified:

Fetus
14/
147
21/
131
25/
129
*
115/
122
**

Litters
6/
23
9/
24
12/
22
*
21/
21
**

Fetus/
Litter
2.33
2.33
2.08
5.48
Cervical
Centrum
#
4
Not
Ossified:

Fetus
10/
147
7/
131
16/
129
109/
122
**

Litters
5/
23
4/
24
11/
22
*
21/
21
**

Fetus/
Litter
2.00
1.75
1.45
5.19
Cervical
Centrum
#
5
Not
Ossified:

Fetus
2/
147
5/
131
9/
129
*
98/
122
**

Litters
1/
23
3/
24
6/
22
*
21/
21
**
Fetus/
Litter
2.00
1.67
1.50
4.67
Cervical
Centrum
#
6
Not
Ossified:

Fetus
1/
147
2/
131
6/
129
*
84/
122
**

Litters
1/
23
2/
24
4/
22
20/
21
**

Fetus/
Litter
1.00
1.00
1.50
4.20
Cervical
Centrum
#
7
Not
Ossified:

Fetus
0/
147
0/
131
2/
129
26/
122
**

Litters
0/
23
0/
24
2/
22
10/
21
**

Fetus/
Litter
0.00
0.00
1.00
2.60
Thoracic
Centrum
#
8
Partially
Ossified:

Fetus
0/
147
0/
131
0/
129
6/
122
**

Litters
0/
23
0/
24
0/
22
6/
21
**

Fetus/
Litter
0.00
0.00
0.00
1.00
Thoracic
Centrum
#
9
Partially
Ossified:

Fetus
0/
147
1/
131
0/
129
7/
122
**

Litters
0/
23
1/
24
0/
22
5/
21
*

Fetus/
Litter
0.00
1.00
0.00
1.40
Thoracic
Centrum
#
10
Partially
Ossified:

Fetus
0/
147
0/
131
0/
129
18/
122
**

Litters
0/
23
0/
24
0/
22
12/
21
**

Fetus/
Litter
0.00
0.00
0.00
1.50
Thoracic
Centrum
#
11
Partially
Ossified:

Fetus
5/
147
0/
131
1/
129
19/
122
**

Litters
5/
23
0/
24
1/
22
10/
21
Fetus/
Litter
1.00
0.00
1.00
1.90
Thoracic
Centrum
#
12
Partially
Ossified:

Fetus
2/
147
1/
131
4/
129
17/
122
**
Litters
2/
23
1/
24
4/
22
10/
21
**

Fetus/
Litter
1.00
1.00
1.00
1.70
[
page
15558]

Thoracic
Centrum
#
13
Partially
Ossified:

Fetus
1/
147
2/
131
3/
129
12/
122
**

Litters
1/
23
2/
24
3/
22
8/
21
**

Fetus/
Litter
1.00
1.00
1.00
1.50
Lumbar
Centrum
#
1
Partially
Ossified:

Fetus
0/
147
0/
131
1/
129
9/
122
**

Litters
0/
23
0/
24
1/
22
6/
21
**

Fetus/
Litter
0.00
0.00
1.00
1.50
Lumbar
Traverse
Process
Partially
Ossified
­
4th
Right:

Fetus
0/
147
5/
131
1/
129
6/
122
**

Litters
0/
23
5/
24
1/
22
5/
21
*

Fetus/
Litter
0.00
1.00
1.00
1.20
Lumbar
Traverse
Process
Partially
Ossified
­
4th
Both:

Fetus
0/
147
3/
131
0/
129
4/
122
*

Litters
0/
23
2/
24
0/
22
3/
21
Fetus/
Litter
0.00
1.50
0.00
1.33
Sternebra
#
1
Partially
Ossified:

Fetus
4/
147
2/
131
4/
129
35/
122
**

Litters
3/
23
2/
24
4/
22
14/
21
**

Fetus/
Litter
1.33
1.00
1.00
2.50
Sternebra
#
2
Partially
Ossified:

Fetus
1/
147
2/
131
6/
129
*
10/
122
**

Litters
1/
23
2/
24
5/
22
7/
21
*

Fetus/
Litter
1.00
1.00
1.20
1.43
SKELETAL
VARIANTS
Sternebra
#
6
Partially
Ossified:

Fetus
0/
147
0/
131
1/
129
8/
122
**

Litters
0/
23
0/
24
1/
22
3/
21
Fetus/
Litter
0.00
0.00
1.00
2.67
Sternebra
#
4
Misaligned:

Fetus
1/
147
0/
131
4/
129
6/
122
*

Litters
1/
23
0/
24
4/
22
5/
21
Fetus/
Litter
1.00
0.00
1.00
1.20
Sternebra
#
5
Misaligned:

Fetus
1/
147
0/
131
2/
129
6/
122
*

Litters
1/
23
0/
24
2/
22
4/
21
Fetus/
Litter
1.00
0.00
1.00
1.50
Sternebra
#
1
Bipartite:

Fetus
0/
147
0/
131
0/
129
9/
122
**

Litters
0/
23
0/
24
0/
22
8/
21
**

Fetus/
Litter
0.00
0.00
0.00
1.13
Skull
­
Partially
Ossified
Occipitals:

Fetus
141/
147
113/
131
124/
129
122/
122
*

Litters
23/
23
23/
24
22/
22
21/
21
Fetus/
Litter
6.13
4.91
5.64
5.81
cervical
Centrum
#
1
Not
Ossified:

Fetus
28/
147
40/
131
*
48/
129
**
94/
122
**

Litters
13/
23
15/
24
17/
22
21/
21
**

Fetus/
Litter
2.15
2.67
2.82
4.48
Cervical
Centrum
#
2
Not
Ossified:

Fetus
52/
147
63/
131
*
80/
129
**
118/
122
**
Litters
17/
23
22/
24
21/
22
21/
21
*

Fetus/
Litter
3.06
2.86
3.81
5.62
Extra
(
14th)
Rib
­
Unilateral
Left
Short:

Fetus
5/
147
7/
131
4/
129
15/
122
**

Litters
5/
23
7/
24
3/
22
8/
21
Fetus/
Litter
1.00
1.00
1.33
1.88
Extra
(
14th)
Bilateral
Short:

Fetus
14/
147
12/
131
33/
129
**
75/
122**

Litters
10/
23
6/
24
15/
22
18/
21
**

Fetus/
Litter
1.40
2.00
2.22
4.17
Pelvic
Girdle
Moved
Posteriorly
­
27
Pre­
Sacral
Vertebrae
(
g):

Fetus
1/
147
3/
131
2/
129
15/
122
**

Litters
1/
23
2/
24
2/
22
7/
21
*

Fetus/
Litter
1.00
1.50
1.00
2.14
Both
Calcaneum
Not
Ossified:

Fetus
136/
147
115/
131
119/
129
122/
122
**

Litters
23/
23
24/
24
22/
22
21/
21
Fetus/
Litter
5.91
4.79
5.41
5.81
[
page
15559]

MINOR
EXTERNAL
AND
VISCERAL
DEFECTS
10
Renal
Pelvic
Dilation:

Fetus
19/
281
25/
255
22/
249
30/
234
*

Litters
12/
23
14/
24
12/
22
18/
21
*

Fetus/
Litter
1.58
1.79
1.83
1.67
Hydroureter:

Fetus
13/
281
6/
255
4/
249
*
10/
234
Litters
5/
23
6/
24
3/
22
5/
21
Fetus/
Litter
2.60
1.00
1.33
2.00
Limb
Malrotation:

Fetus
0/
281
9/
255
**
2/
249
3/
234
Litters
0/
23
4/
24
1/
22
2/
21
Fetus/
Litter
0.00
2.25
2.00
1.50
a
­
Data
from
Tinston,
Doe
et
al,
Exs.
4­
038.
See
also
Ex.
5­
071
b
­
Incidence
is
number
of
fetuses
affected
divided
by
the
total
number
of
fetuses
c
­
Incidence
is
number
of
litters
with
at
least
one
fetus
affected
d
­
Average
number
of
affected
fetuses
per
affected
litter
e
­
Denominator
(
i.
e.
the
number
of
animals
at
risk)
is
adjusted
for
early
intra­
uterine
deaths
f
­
Only
a
portion
of
fetuses
in
each
exposure
group
were
examined
for
soft
tissue
alterations
g
­
This
skeletal
defect
was
not
classified
as
either
a
minor
skeltal
anomalie
or
a
skeletal
variant
h
­
Denominator
(
i.
e.
the
number
of
animals
at
risk)
is
adjusted
for
all
intra­
uterine
deaths
*
­
Significantly
different
than
controls
at
the
p
<.
05
level
**
­
Significantly
different
than
controls
at
the
p
<.
01
level
A
significant
excess
of
late
intra­
uterine
deaths
occurred
in
the
250
ppm
group
using
both
the
fetus
and
the
litter
measures
of
response,
but
when
combined
with
early
intra­
uterine
deaths
(
i.
e.
all
intra­
uterine
deaths)
the
effect
is
significant
for
the
250
ppm
group
in
fetuses
only.
Early
intra­
uterine
deaths
considered
separately
were
not
found
to
be
related
to
exposure
Most
of
the
minor
skeletal
defects
which
occurred
at
a
significantly
elevated
rate
were
also
in
the
250
ppm
group.
The
effects
which
are
significant
using
both
measures
of
response
were
partially
ossified
frontals,
partially
ossified
parietals,
partially
ossified
interparietals,
odontoid
not
ossified,
third,
fourth,
fifth,
sixth,
and
seventh
cervical
centra
not
ossified,
eighth
ninth,
tenth,
eleventh,
twelfth,
and
thirteenth
thoracic
centra
partially
ossified,
first
lumbar
centrum
partially
ossified,
fourth
right
lumbar
traverse
process
partially
ossified,
and
first
and
second
sternebrae
partially
ossified.
One
minor
skeletal
defect,
fourth
right
lumbar
traverse
process
partially
ossified,
was
significant
for
fetuses
in
the
250
ppm
group
but
not
for
litters
Two
minor
skeletal
defects
were
significant
for
the
50
ppm
group
using
both
measures
of
response:
third
cervical
centrum
not
ossified
and
fifth
cervical
centrum
not
ossified.
The
minor
skeletal
defects
of
unossified
sixth
cervical
centrum
and
partially
ossified
second
sternebra
shows
a
significant
excess
in
this
exposure
group
but
only
for
fetuses.
The
incidence
of
unossified
fourth
cervical
centrum
was
significantly
elevated
over
controls
in
the
50
ppm
group
for
litters
but
not
for
fetuses
Two
minor
skeletal
defects
showed
a
significant
deficit
of
occurrence
in
the
10
ppm
group.
Using
both
the
fetus
and
the
litter
measure
of
response,
study
results
show
that
fetal
rats
exposed
to
10
ppm
of
2­
EE
were
significantly
less
likely
to
experience
partially
ossified
parietals
or
partially
ossified
interparietals
than
were
controls.
The
study
authors
offer
no
explanation
for
this,
but
given
the
large
number
of
effects
for
which
each
fetus
was
examined,
the
statistical
significance
of
this
deficit
can
easily
be
attributed
to
chance
variation
A
number
of
skeletal
variants
were
observed
to
be
associated
with
exposure
in
fetal
rats.
Those
which
were
found
to
be
statistically
significantly
elevated
over
controls
using
both
the
fetus
and
the
litter
measures
of
response,
bipartite
first
sternebra,
unossified
first
cervical
centrum,
and
extra
(
14th)
rib
­
bilateral
short,
were
found
only
in
the
250
ppm
group.
Interestingly,
incidence
of
unossified
first
and
second
cervical
centra
were
also
significantly
elevated
in
the
10
ppm
group
and
the
50
ppm
group
when
measured
in
fetuses
but
not
when
measured
in
litters.
The
fetus/
litter
measure
shows
a
dose­
related
trend
for
ossified
first
cervical
centrum
but
not
for
unossified
second
cervical
centrum.
The
effect
extra
(
14th)
rib
­
bilateral
short
showed
a
showed
a
significant
excess
in
50
ppm
fetuses
but
not
in
50
ppm
litters
There
were
an
additional
number
of
skeletal
variants
which
were
statistically
significant
in
the
250
ppm
group
but
only
when
response
was
measured
in
fetuses.
These
effects
were
partially
ossified
sixth
sternebra,
misaligned
fifth
sternebra,
partially
ossified
occipital
and
extra
(
14th)
rib
­
unilateral
(
left)
short,
and
although
these
effects
were
not
significant
when
measured
in
litters,
when
measured
in
fetuses
these
effects
were
significant
at
the
P=
0.035
level
or
lower
Three
minor
external
and
visceral
defects
were
found
to
be
statistically
significant.
Renal
pelvic
dilation
occurred
at
a
significantly
elevated
rate
in
fetuses
and
in
litters
in
the
250
ppm
group.
Incidence
of
hydroureter
was
significantly
reduced
in
the
50
ppm
fetuses
but
in
no
other
group
of
fetuses
and
in
no
group
of
litters.
Incidence
of
limb
malrotation
was
significantly
elevated
in
the
10
ppm
group
of
fetuses
but
in
no
other
group
of
fetuses
and
in
no
groups
of
litters
There
were
two
skeletal
defects
which
occurred
at
a
statistically
significant
rate
in
the
250
ppm
group
which
were
not
classified.
"
Pelvic
girdle
moved
posteriorly
(
27
pre­
sacral
vertebrae)"
was
not
categorized
as
either
a
major
or
minor
skeletal
defect
or
as
a
variant.
This
effect
was
significant
in
both
fetuses
and
litters.
Likewise,
"
both
calcaneum
not
ossified"
was
not
classified
as
either
a
major
or
minor
skeletal
defect
or
as
a
variant.
This
effect
was
significant
only
in
fetuses
in
the
250
ppm
group.
[
page
15560]

The
incidence
of
developmental
effects
in
fetal
rabbits
exposed
to
2­
EE
are
presented
in
Table
VI­
E.
As
for
fetal
rats,
three
measures
of
response
are
presented,
and
the
same
statistical
criteria
were
used
for
inclusion
of
an
effect
in
the
table
Table
VI­
E
Incidence
of
Developmental
Effects
Observed
in
Dutch
Rabbits
Exposed
to
2­
EE
days
6
through
18
of
Gestation
(
a)

MINOR
SKELETAL
DEFECTS
(
b)

Control
10
ppm
50
ppm
175
ppm
Skull
­
Partially
Ossified
Hyoid:

Fetus
(
c)
15/
136
32/
138
**
12/
96
28/
134
*

Litters
(
d)
8/
21
9/
20
5/
16
11/
22
Fetus/
Litter
(
e)
1.88
3.56
2.40
2.55
27
Pre­
sacral
Vertebrae:

Fetus
3/
136
7/
138
5/
96
31/
134
**

Litters
3/
21
4/
20
2/
16
10/
22
*

Fetus/
Litter
1.00
1.75
2.50
3.10
6th
Sternebra
Partially
Ossified:

Fetus
2/
136
1/
138
2/
96
8/
134
*

Litters
2/
21
1/
20
2/
16
6/
22
Fetus/
Litter
1.00
1.00
1.00
1.33
5th
Sternebra
Not
Ossified:

Fetus
9/
136
20/
138
*
9/
96
13/
134
Litters
5/
21
7/
20
6/
16
5/
22
Fetus/
Litter
1.80
2.86
1.00
2.00
Pelvic
Girdle
­
Pubes
Not
Ossified:

Fetus
0/
136
1/
138
1/
96
7/
134
*

Litters
0/
21
1/
20
1/
16
4/
22
Fetus/
Litter
0.00
1.00
1.00
1.75
Extra
(
13th)
Rib
­
Unilateral
Short:

Fetus
3/
136
7/
138
7/
96
15/
134
**

Litters
3/
21
6/
20
7/
16
10/
22
*

Fetus/
Litter
1.00
1.17
1.00
1.50
Extra
(
13th
Rib
­
Bilateral
Normal:

Fetus
10/
136
17/
138
7/
96
38/
134
**

Litters
5/
21
7/
20
3/
16
13/
22
*

Fetus/
Litter
2.00
2.43
2.33
2.92
Extra
(
13th)
Rib
­
Bilateral
One
Normal
One
Short:

Fetus
4/
136
5/
138
6/
96
16/
134
**

Litters
4/
21
4/
20
4/
16
9/
22
Fetus/
Litter
1.00
1.25
1.50
1.78
5th
Sternebra
Partially
Ossified:

Fetus
53/
136
61/
138
45/
96
53/
134
Litters
14/
21
20/
20
**
14/
16
18/
22
Fetus/
Litter
3.79
3.05
3.21
2.94
a
­
Data
from
Tinston,
Doe
et
al,
Exs.
4­
039.
See
also
Ex.
5­
071
b
­
Only
a
portion
of
fetuses
in
each
exposure
group
were
examined
for
soft
tissue
alterations
c
­
Incidence
is
number
of
fetuses
affected
divided
by
the
total
number
of
fetuses
d
­
Incidence
is
number
of
litters
with
at
least
one
fetus
affected
e
­
Average
number
of
affected
fetuses
per
affected
litter
*
­
Significantly
different
than
controls
at
the
p<
.05
level
**
­
Significantly
different
than
controls
at
the
p<
.01
level
Only
one
skeletal
defect,
27
pre­
sacral
vertebrae,
which
Tinston
et
al
classified
as
minor
in
rabbits,
was
statistically
significant
in
fetuses
and
litters
and
this
was
in
the
175
ppm
group.
Three
minor
skeletal
defects,
partially
ossified
hyoid,
partially
ossified
sixth
sternebra,
and
unossified
pubes,
were
significant
in
fetuses
in
the
175
ppm
group
but
not
in
litters.
The
defect
partially
ossified
hyoid
occurred
at
a
significantly
elevated
rate
in
10
ppm
fetuses
but
was
not
significant
in
this
group
when
measured
in
litters.
The
same
result
was
seen
for
the
defect
unossified
fifth
sternebra
which
was
significant
in
fetuses
in
the
10
ppm
group
but
not
in
litters
and
not
in
any
other
exposure
group
The
175
ppm
group
had
statistically
significant
excess
of
two
skeletal
variants
when
measured
in
fetuses
and
in
litters:
extra
(
13th)
rib
­
unilateral
short
and
extra
(
13th)
rib
­
bilateral
normal.
The
skeletal
variant
extra
(
13th)
rib
­
one
normal
and
one
short
was
significantly
elevated
in
fetuses
in
the
175
ppm
group
but
was
not
significant
in
litters
One
skeletal
variant
was
significantly
elevated
in
the
10
ppm
group.
This
variant
was
partially
ossified
fifth
sternebra.
Incidence
was
significant
only
when
measured
in
litters
but
not
when
measured
in
fetuses
and
was
not
significant
for
any
other
exposure
group
using
any
measure
of
response.
Incidence
of
partially
ossified
fifth
sternebra
does
not
show
a
dose­
related
trend
using
the
fetus/
litter
measure
of
response,
and
the
study
authors
attribute
the
observed
excess
to
coincidence
because
similar
increases
in
this
variant
were
not
observed
in
the
50
and
175
ppm
groups.

[
page
15561]

4.
Derivation
of
the
No
Observed
Effect
Level
a.
2­
ME
In
reviewing
Table
VI­
A,
VI­
B,
and
VI­
C,
it
is
clear
that
almost
all
effects
which
occurred
in
an
exposed
group
at
rates
statistically
significantly
elevated
over
controls
occurred
in
the
highest
dose
group,
the
50
ppm
2­
ME
dose
group,
in
each
species.
Only
one
effect,
resorptions,
was
statistically
significant
in
litters
at
a
dose
below
50
ppm,
but,
as
noted
by
the
study
authors,
the
rate
of
resorptions
in
exposed
rabbits
fell
well
within
the
range
of
historical
controls
It
is
apparent
from
these
data
that
10
ppm
is
the
no
observed
effect
level
(
NOEL)
in
each
of
the
species
studied
by
Hanley
et
al
despite
the
varying
sensitivity
of
each
of
the
species
to
2­
ME
Still,
the
question
arises
as
to
how
the
incidence
of
effects
can
or
should
be
combined
to
arrive
at
a
measure
of
overall
response
Intuitively,
one
would
have
greater
confidence
in
a
NOEL
derived
from
an
overall
measure
of
response
rather
than
one
derived
from
specific
effects
which
may
be
statistically
significant
due
to
chance
alone
OSHA
proposes
that
an
overall
measure
of
the
incidence
of
developmental
effects
be
arrived
at
by
pooling
the
incidence
of
effects
which
occurred
at
a
statistically
significant
excess
in
any
exposed
group
when
measured
in
litters.
The
Agency
has
chosen
litters
as
the
most
appropriate
unit
of
measure
for
a
number
of
reasons.
First,
as
noted
above,
it
is
the
pregnant
female
that
is
exposed
to
the
test
substance,
therefore
it
is
her
litter
which
is
the
affected
unit.
Because
dose
is
administered
to
the
fetus
through
the
pregnant
dam,
the
dose
each
fetus
receives
is
unknown
and
may
depend
upon
the
individual
sensitivity
of
the
mother
animal
to
the
test
substance.
Furthermore,
the
dose
the
fetus
does
receive
may
be
affected
by
the
number
of
littermates
in
utereo
Another
reason
for
prefering
the
litter
as
the
unit
of
measure
is
that
fetuses
in
a
litter
are
more
likely
to
respond
like
each
other
than
like
fetuses
from
other
litter
(
i.
e.
the
litter
effect).
Therefore,
if
an
effect
is
observed
in
some
number
of
fetuses,
but
all
affected
fetuses
come
from
only
one
or
two
litters,
then
it
is
possible
to
attribute
the
effect
to
exposure
when
in
fact
it
is
due
to
variation
among
the
mother
animals
The
use
of
litters
as
the
unit
of
measure
in
studies
of
developmental
effects
in
animals
is
recommended
by
the
EPA
in
its
Guidelines
(
Ex.
5­
153),
and
this
unit
of
measure
enjoys
wide
support
in
the
literature
(
see,
for
example,
Ex.
5­
018)

OSHA's
decision
to
include
in
an
overall
measure
of
response
only
those
effects
which
are
statistically
significant
when
considered
individually
is
based
on
its
belief
that
by
so
restricting
inclusion
of
an
effect
in
an
overall
measure
one
obtains
a
more
accurate
measure
of
overall
response.
Inclusion
of
effects
which
are
not
dose
related
and
are
attributable
solely
to
chance
dilutes
the
overall
measure
of
the
potency
of
a
developmental
toxicant
This
position
is
easily
illustrated.
Hanley
et
al
counted
all
the
rabbit
litters
in
the
control
and
exposed
groups
which
had
at
least
one
fetus
with
any
major
malformation.
The
incidence
of
major
malformations
was
found
to
be
6/
23
in
controls
(
26%),
4/
23
in
the
3
ppm
group
(
17%),
3/
24
in
the
10
ppm
group
(
13%)
and
20/
22
in
the
50
ppm
group
(
91%).
If
only
those
major
malformations
which
were
statistically
significant
in
exposed
litters
had
been
included,
the
overall
incidence
of
major
malformations
would
have
been
0/
23
in
the
control
group
(
0%),
2/
23
in
the
3
ppm
group
(
13%)
1/
24
in
the
10
ppm
group
(
4%)
and
20/
22
in
the
50
ppm
group
(
91%).
While
the
NOEL
is
10
ppm
regardless
of
how
the
overall
incidence
of
major
malformations
is
measured,
the
effect
attributable
to
exposure
at
50
ppm
is
clearer
and
starker
when
those
major
malformations
attributable
to
chance
are
excluded
Tables
VI­
F,
VI­
G,
and
VI­
H
present
the
overall
incidence
of
developmental
effects
in
rats,
rabbits,
and
mice,
respectively.
For
rabbits,
resorptions
were
not
included
in
the
overall
measure
of
response
because
the
rate
for
all
three
exposure
groups
(
42%
to
67%)
was
well
within
the
historical
range
reported
by
Hanley
et
al
(
mean
55%,
range
38%
to
74%)
and
only
the
rate
of
resorption
among
controls
(
22%)
was
outside
of
that
range.
The
tables
clearly
indicate
that
2­
ME
induces
developmental
effects
in
all
three
species
at
50
ppm
and
that
the
NOEL
for
all
three
species
in
these
studies
is
10
ppm
Table
VI­
F
Overall
Incidence
of
Developmental
Effects
Observed
in
Litters
of
Fisher
344
Rats
Exposed
to
2­
ME
Days
6
through
15
of
Gestation
(
a)

Control
3
ppm
10
ppm
50
ppm
Minor
Skeletal
Alterations(
b):

Litters
14/
29
12/
28
16/
28
27/
30
**

a
­
Data
from
Hanley
et
al,
Ex.
4­
042a
b
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
either
delayed
ossification
of
centra
or
rib
spurs;
the
denominator
is
the
number
of
litters
at
risk
**
­
Significantly
different
than
controls
at
the
p
<
.01
level
Table
VI­
G
Overall
Incidence
of
Developmental
Effects
Observed
in
Litters
of
New
Zealand
White
Rabbits
Exposed
to
2­
ME
Days
6
through
15
of
Gestation
(
a)

Control
3
ppm
10
ppm
50
ppm
Major
External
Alterations(
b)

Litters
0/
23
1/
23
0/
24
16/
22
**

Minor
External
Alterations(
c)

Litters
0/
23
0/
23
0/
24
15/
22
**

Major
Soft
Tissue
Alterations(
d)

Litters
0/
23
1/
23
1/
24
20/
22
**

Minor
Soft
Tissue
Alterations(
e)

Litters
3/
23
5/
23
2/
22
18/
22
**

Major
Skeletal
Alterations(
f)

Litters
0/
23
0/
23
0/
24
5/
22
*

[
page
15562]

Minor
Skeletal
Alterations(
g)
Litters
1/
23
4/
23
2/
24
13/
22
**

Any
Major
Alterations(
h)

Litters
0/
23
2/
23
1/
24
20/
22
**

Any
Minor
Alterations(
i)

Litters
4/
23
7/
23
4/
24
20/
22
**

Any
Alterations(
j)

Litters
4/
23
7/
23
5/
24
20/
22
**

a
­
Data
from
Hanley
et
al,
Ex.
4­
042a
b
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
major
external
alterations:
arthrogryposis,
anonychia,
brachydactyly,
ectrodactyly,
or
kinky
tail;
the
denominator
is
the
number
of
litters
at
risk
c
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
minor
external
alterations:
misalignment
of
the
palatine
rugae
or
narrowed
tip
of
tail;
the
denominator
is
the
number
of
litters
at
risk
d
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
major
soft
tissue
alterations:
coarctation
of
the
aortic
arch,
ventricular
septal
defect,
hypoplastic
spleen,
or
dilated
renal
pelvis;
the
denominator
is
the
number
of
litters
at
risk
e
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
minor
soft
tissue
alterations:
patent
ductus
arteriosis,
hypoplastic
gall
bladder,
pale
spleen,
dilated
ureter,
convoluted
ureter,
or
parovarian
cyst;
the
denominator
is
the
number
of
litters
at
risk
f
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
major
skeletal
alterations:
missing
phalange
or
missing
metatarsal;
the
denominator
is
the
number
of
litters
at
risk
g
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
minor
skeletal
alterations:
delayed
ossification
of
the
hyoid,
delayed
ossification
of
the
tarsal,
or
extra
lumbar
ribs;
the
denominator
is
the
number
of
litters
at
risk
h
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
major
external
alterations,
any
major
soft
tissue
alteration
or
any
major
skeletal
alterations
listed
above;
the
denominator
is
the
number
of
litters
at
risk
i
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
minor
external
alterations,
any
minor
soft
tissue
alteration
or
any
minor
skeletal
alterations
listed
above;
the
denominator
is
the
number
of
litters
at
risk
j
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
major
or
minor
external
alterations,
soft
tissue
alteration
or
skeletal
alterations
listed
above;
the
denominator
is
the
number
of
litters
at
risk
*
­
Significantly
different
than
controls
at
the
p
<
.05
level
**
­
Significantly
different
than
controls
at
the
p
<
.01
level
Table
VI­
H
Overall
Incidence
of
Developmental
Effects
Observed
in
Litters
of
CF­
1
mice
Exposed
to
2­
ME
days
6
through
15
of
Gestation
(
a)

Control
10
ppm
50
ppm
Minor
Skeletal
Alterations(
b)

Litters
14/
26
14/
23
21/
24
*

a
­
Data
from
Hanley
et
al,
Ex.
4­
106
b
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
extra
lumbar
ribs;
the
denominator
is
the
number
of
litters
at
risk
*
­
Significantly
different
than
controls
at
the
p<
.05
level
In
its
comments
to
OSHA's
ANPR,
Du
Pont
states
that
it
is
"
appropriate
to
look
at
all
adverse
effects,
but
not
to
accumulate
these
effects
into
one
endpoint"
(
Ex.
7­
28).
OSHA
seeks
additional
information
on
how
the
approach
suggested
by
Du
Pont
could
be
used
for
quantitative
risk
assessment.
Specifically,
it
is
unclear
how
different
NOELs
for
different
endpoints
from
the
same
study
would
be
treated.
In
addition,
OSHA
seeks
comment
on
whether
adverse
developmental
effects
should
be
combined,
and
if
so,
how
this
should
be
done
Given
that
the
NOEL
for
2­
ME
has
been
derived
from
animal
studies,
OSHA
believes
that
an
uncertainty
factor
of
100
is
appropriate
for
derivation
of
the
acceptable
daily
intake
(
ADI)
i.
e.
the
dose
at
which
humans
are
unlikely
to
exhibit
effects
similar
to
those
observed
in
animals.
An
uncertainty
factor
of
100
provides
a
factor
of
10
for
inter­
species
variability
and
a
factor
of
10
for
intra­
species
variability
(
i.
e.
individual
human
sensitivity
to
2­
ME).
Therefore,
based
on
the
studies
of
Hanley
et
al,
OSHA
estimates
the
ADI
to
be
10
ppm/
100
or
0.1
ppm.
That
is,
at
0.1
ppm
of
2­
ME,
humans
are
unlikey
to
exhibit
effects
similar
to
those
observed
in
animals
b.
2­
EE
Table
VI­
D
and
VI­
E
show
clearly
that
exposure
to
2­
EE
had
an
effect
on
developing
animals
although
the
results
of
the
2­
EE
bioassay
are
not
as
strong
as
those
from
the
2­
ME
bioassay.
While
most
of
the
developmental
effects
observed
in
the
2­
EE
bioassay
were
observed
in
the
high
dose
groups
for
both
rats
and
rabbits
(
250
ppm
and
175
ppm
respectively),
there
were
statistically
significant
effects
in
the
50
ppm
group
of
rats
and
the
10
ppm
group
of
rabbits.
Thus,
determination
of
the
NOEL
for
2­
EE
is
more
difficult
than
for
2­
ME
Table
VI­
I
presents
the
overall
incidence
of
developmental
effects
in
fetal
rats
exposed
to
2­
EE.
Only
those
effects
which
were
statistically
significant
when
measured
in
litters
are
included
in
the
overall
measure
of
incidence.

[
page
15563]

Table
VI­
I
Overall
Incidence
of
Developmental
Effects
Observed
in
Litters
of
Wistar
Rats
Exposed
to
2­
EE
Days
6
through
15
of
Gestation
(
a)

Control
10
ppm
50
ppm
250
ppm
Late
Intra­
Uterine
Deaths
(
b)

Litters
2/
23
2/
24
2/
22
7/
21
*

Minor
Skeletal
Defects
(
c)

Litters
17/
23
21/
24
20/
22
21/
21
*

Skeletal
Variants
(
d)

Litters
20/
23
23/
24
22/
22
21/
21
Minor
External
and
Visceral
Defects
(
a)

Litters
12/
23
14/
24
12/
22
18/
21
*

Unclassified
Defects
(
f)

Litters
1/
23
2/
24
2/
22
7/
21
*

Any
Death,
Defect
or
Variant
(
g)

Litters
23/
23
23/
24
22/
22
21/
21
a
­
Data
from
Tinston,
Doe
et
al,
Ex.
4­
038a
b
­
The
numerator
is
the
number
of
litters
with
at
least
one
late
intra­
uterine
death;
the
denominator
is
the
number
of
litters
at
risk
c
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
minor
skeletal
defects:
frontal
partially
ossified,
parietal
partially
ossified,
interparietal
partially
ossified,
odontoid
not
ossified,
third,
fourth,
fifth,
sixth
or
seventh
cervical
centrum
not
ossified,
eighth,
ninth,
tenth,
twelfth,
or
thirteenth
thoracic
centrum
partially
ossified,
first
lumbar
centrum
partially
ossified,
fourth
right
lumbar
traverse
process
partially
ossified,
or
first
or
second
sternebra
partially
ossified;
the
denominator
is
the
number
of
litters
at
risk
d
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
of
the
following
skeletal
variants:
first
sternebra
bipartite,
first
or
second
cervical
centrum
not
ossified,
or
extra
(
14th)
rib
bilaterally
short;
the
denominator
is
the
number
of
litters
at
risk
e
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
renal
pelvic
dilation;
the
denominator
is
the
number
of
litters
at
risk
f
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
a
posteriorly
moved
pelvic
girdle
(
27
pre­
sacral
vertebrae);
the
denominator
is
the
number
of
litters
at
risk.
The
defect
"
pelvic
girdle
moved
posteriorly"
was
not
classified
as
a
major
or
minor
external
and
visceral
defect,
a
major
or
minor
skeletal
defect,
or
a
skeletal
defect.
Thus
it
is
"
unclassified."
g
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
dying
late
in
utero
or
presenting
any
minor
skeletal
defect,
skeletal
variant,
minor
external
or
visceral
defect,
or
unclassified
defect
listed
above;
the
denominator
is
the
number
of
litters
at
risk
*
­
Significantly
different
than
controls
at
the
p<
.05
level
The
surprising
result
in
table
VI­
I
is
that
when
all
the
effects
are
combined,
it
would
appear
that
2­
EE
has
no
effect
on
developing
rats
despite
the
fact
that
there
is
a
significant
excess
of
late
intra­
uterine
deaths
in
the
250
ppm
group,
a
significant
excess
of
minor
skeletal
defects
in
the
250
ppm
group,
and
a
significant
excess
of
external
and
visceral
defects
in
the
250
ppm
group.
Furthermore,
Table
VI­
D
shows
that
there
were
twenty­
four
effects
that
were
significantly
elevated
in
the
250
ppm
group
in
both
litters
and
fetuses
The
reason
the
overall
incidence
of
effects
in
fetal
rats
exposed
to
2­
EE
is
not
significant
is
that
the
study
authors
looked
at
the
developmental
effects
in
such
minute
detail.
While
this
results
in
there
being
a
large
number
of
effects
which
are
statistically
significant
in
the
250
ppm
group
when
each
effect
is
considered
individually,
when
combined
the
incidence
of
these
effects
in
the
other
exposure
groups
dilutes
the
association
between
dose
and
response
Examination
of
the
data
reveals
that
the
incidence
of
non­
ossification
of
the
cervical
centra
is
one
effect
which
is
diluting
the
overall
dose­
response
relationship.
When
ossification
of
each
of
the
seven
cervical
centra
is
considered
individually,
it
is
clear
that
exposure
to
250
ppm
of
2­
EE
in
fetal
rats
results
in
non­
ossification
of
each
of
the
centrum.
Incidence
of
non­
ossification
of
each
of
the
centrum
in
the
250
ppm
group
is
statistically
significant
at
the
p=.
014
level
or
lower.
If
all
the
centra
were
combined
into
a
category
"
delayed
ossification
of
the
cervical
centra",
however,
this
effect
would
not
be
statistically
significant
when
measured
in
litters.
The
litter
incidence
of
delayed
ossification
of
any
cervical
centrum
is
19/
23
in
control
(
83%),
23/
24
in
the
10
ppm
group
(
96%),
21/
22
in
the
50
ppm
group
(
95%),
and
21/
21
in
the
250
ppm
group
(
100%).
Thus,
when
each
centrum
is
considered
individually,
there
is
clearly
a
dose­
related
effect
at
the
250
ppm
level,
but
when
the
centra
are
considered
together,
this
effect
disappears.
Because
of
the
high
background
incidence
of
the
effect
and
the
small
number
of
litters
in
each
group,
the
overall
incidence
of
developmental
effects
in
the
250
ppm
group
appears
to
be
unrelated
to
dose
OSHA
does
not
believe
that
there
is
no
developmental
effect
on
fetal
rats
exposed
to
2­
EE.
When
the
incidence
of
late
intra­
uterine
deaths
is
considered,
when
the
overall
incidence
of
minor
skeletal
defects
is
considered
and
when
the
overall
incidence
of
minor
external
and
visceral
defects
are
considered,
it
is
clear
that
exposure
to
250
ppm
of
2­
EE
results
in
detrimental
effects
on
the
developing
fetus.
No
such
effect
is
seen
at
50
ppm
or
lower,
and
therefore
OSHA
concludes
that
the
NOEL
for
2­
EE
is
50
ppm
in
rats
The
results
presented
in
Table
VI­
J
demonstrate
that
50
ppm
is
also
the
NOEL
for
fetal
rabbits
exposed
to
2­
EE.
The
overall
incidence
of
developmental
effects
is
statistically
significant
for
the
175
ppm
group
at
the
p=
0.004
level.
This
indicates
that
exposure
below
the
250
ppm
level,
the
level
observed
to
have
an
adverse
effect
on
developing
rats,
can
have
an
adverse
effect
on
developing
rabbits
Although
fewer
effects
were
observed
in
the
rabbit
at
175
ppm
than
in
the
rat
at
250
ppm,
dose­
related
adverse
effects
were
nonetheless
induced
at
the
175
ppm
level.

Table
VI­
J
Overall
Incidence
of
Developmental
Effects
Observed
in
Litters
of
Dutch
Rabbits
Exposed
to
2­
EE
Days
6
through
18
of
Gestation
(
a)

Control
10
ppm
50
ppm
175
ppm
Minor
Skeletal
Defects
(
b)

Litters
3/
21
4/
20
2/
16
10/
22
*

[
page
15564]
Skeletal
Variants
(
c)

Litters
7/
21
10/
20
9/
16
18/
22
**

Any
Defect
or
Variant
(
d)

Litters
8/
21
11/
20
9/
16
18/
22
**

a
­
Data
from
Tinston,
Doe
et
al,
Ex.
4­
039a
b
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
27
pre­
sacral
vertebrae;
the
denominator
is
the
number
of
litters
at
risk
c
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
an
extra
(
13th)
rib
unilaterally
short
or
bilaterally
normal;
the
denominator
is
the
number
of
litters
at
risk
d
­
The
numerator
is
the
number
of
litters
with
at
least
one
fetus
presenting
any
minor
skeletal
defect
or
skeletal
variant
listed
above;
the
denominator
is
the
number
of
litters
at
risk
*
­
Significantly
different
than
controls
at
the
p<
.05
level
**
­
Significantly
different
than
controls
at
the
p<
.01
level
Given,
as
with
2­
ME,
that
the
NOEL
for
2­
EE
has
been
derived
from
animal
studies,
OSHA
believes
that
an
uncertainty
factor
of
100
is
again
appropriate
for
derivation
of
the
ADI.
As
with
2­
ME,
an
uncertainty
factor
of
100
provides
a
factor
of
10
for
inter­
species
variability
and
a
factor
of
10
for
intra­
species
variability.
Therefore,
based
on
the
studies
by
Tinston
et
al,
OSHA
estimates
the
ADI
to
be
50
ppm/
100
or
0.5
ppm.
That
is,
at
0.5
ppm
of
2­
EE,
humans
are
unlikely
to
exhibit
adverse
effects
similar
to
those
observed
in
animals
5.
Alternative
Uncertainty
Factors
As
discussed
in
a
previous
section,
an
ADI
(
i.
e
the
levels
at
ewhich
humans
are
unlikely
to
exhibit
effects
similar
to
those
observed
in
humans)
is
derived
by
dividing
a
NOEL
by
an
uncertainty
factor.
To
derive
ADIs
for
glycol
ethers,
OSHA
has
used
an
uncertainty
factor
of
100;
a
factor
of
ten
to
account
for
inter­
species
variability
and
a
factor
of
10
to
account
for
intra­
species
variability.
Several
of
the
commentors
who
responded
to
OSHA's
ANPR
for
glycol
ethers
advocated
use
of
a
lower
uncertainty
factor
(
see,
for
example,
Kodak,
Ex.
7­
16,
and
Du
Pont,
Ex.
7­
28).
In
its
comments,
CMA
argues
that
an
uncertainty
factor
well
below
100
should
be
used
to
arrive
at
new
PELs
(
Ex.
7­
17).
While
CMA
presents
a
number
of
reasons
for
its
position,
OSHA
does
not
find
any
of
its
reasons
sufficiently
compelling
to
depart
from
the
traditional
uncertainty
factor
for
derivation
of
ADIs
across
species.
What
follows
here
is
a
brief
description
of
each
of
the
arguments
presented
by
CMA
and
OSHA's
response
to
these
arguments
To
begin,
CMA
states
that
lower
safety
factors
are
appropriate
with
high
quality
animal
studies.
OSHA
agrees
that
the
Hanley
et
al
studies
and
the
Tinston
et
al
studies
are
high
quality
studies,
but
the
Agency
does
not
see
how
the
quality
of
these
studies
reduces
either
inter­
species
variability
or
intra­
species
variability.
Both
types
of
variability
are
issues
in
determining
a
"
safe"
occupational
exposure
level
from
animal
data
even
when
such
studies
are
of
high
quality
CMA
argues
that
lower
safety
factors
are
appropriate
when
NOELs
have
been
established
in
more
than
one
species.
CMA
notes
that
not
only
have
NOELs
been
established
for
a
number
of
species
but
the
NOELs
and
the
observed
effects
have
also
been
quite
similar
across
species
While
OSHA
agrees
that
one
has
greater
confidence
in
a
NOEL
determined
in
more
than
one
species,
the
Agency
is
concerned
the
CMA
has
confused
the
finding
of
the
same
NOEL
in
more
than
one
species
with
the
finding
of
the
same
threshold
in
more
than
one
species.
The
exposure
levels
employed
by
Hanley
et
al
and
by
Tinston
et
al
were
almost
identical
in
each
of
the
species
tested.
In
the
case
of
2­
ME,
for
example,
rats
and
rabbits
were
exposed
at
identical
exposure
levels
and
mice
were
exposed
to
two
of
the
three
same
levels.
Given
this
similarity
of
exposure,
it
is
not
surprising
that
the
same
NOEL
was
identified
in
all
three
species.
One
cannot
conclude
from
this,
however,
that
the
exposure
threshold
for
developmental
effects
is
the
same
in
all
three
species.
Based
on
the
data
from
the
Hanley
et
al
bioassays,
for
example,
one
cannot
reject
a
hypothesis
that
the
"
true"
NOELs
might
be
40
ppm
for
mice,
25
ppm
for
rats,
and
10
ppm
for
rabbits.
The
exposure
levels
employed
do
not
allow
one
to
reject
this
hypothesis,
thus
one
cannot
conclude
there
is
no
inter­
species
variability
for
2­
ME.
The
same
is
true
for
2­
EE.
In
addition,
the
small
number
of
animals
used
in
each
of
these
bioassays,
(
no
study
used
more
than
30
animals
in
each
exposure
group
and
most
used
less),
limited
the
power
of
these
bioassays
to
detect
lower
NOELs.
For
these
reasons,
OSHA
cannot
support
the
use
of
a
lower
safety
factor
on
these
grounds
as
advocated
by
CMA
In
addition,
OSHA
does
not
agree
that
the
effects
observed
across
species
exposed
to
the
same
glycol
ethers
were
quite
as
similar
as
CMA
maintains.
In
the
case
of
2­
ME,
the
only
effects
observed
to
occur
at
a
statistically
significantly
greater
rate
in
the
high
dose
groups
of
rats
and
mice
were
minor
skeletal
defects.
In
high
dose
rabbits,
however,
the
effects
were
far
and
away
more
severe
including
major
external
alterations,
major
soft
tissue
alterations,
and
major
skeletal
alterations.
In
the
case
of
2­
EE,
it
is
difficult
to
compare
effects
across
species
because
of
differences
in
exposure
levels
used
for
the
high
dose
group
CMA 
s
third
reason
for
advocating
an
uncertainty
factor
well
below
100
is
that
data
on
inter­
species
metabolism
and
pharmacokinetics
can
be
employed
to
justify
this.
As
discussed
in
the
Health
Effects
section
of
this
preamble,
the
evidence
indicates
that
the
four
glycol
ethers
of
interest
here
are
most
likely
metabolized
via
the
alcohol
dehydrogenase
(
ADH)
pathway
in
both
animals
and
humans.
Although
all
species
seem
to
share
the
same
metabolic
pathway,
however,
there
is
also
evidence
that
the
species
do
not
metabolize
glycol
ethers
at
the
same
rate.
Groeseneken
et
al
found
that
the
biological
half­
life
of
2­
EE
in
humans
was
21
to
24
hours
compared
to
the
biological
half­
life
of
8
to
12
hours
reported
in
animals
(
Exs.
5­
112,
5­
113,
and
5­
114).
This
finding
led
the
study
authors
to
conclude
that
the
metabolites
of
2­
EE
will
not
be
cleared
from
the
urine
by
the
next
morning
following
exposure
and
accumulation
of
the
metabolites
may
be
expected
through
repetitive
exposures.
In
a
study
of
2­
EEA
in
humans,
Groesenken
et
al
found
[
page
15565]

similar
results
(
Ex.
5­
115),
and
these
results
were
confirmed
in
study
of
female
silk
screen
operators
exposed
to
2­
EE
and
2­
EEA
by
Veulemans
et
al
(
Ex.
5­
114).
The
finding
of
a
longer
biological
half­
life
for
2­
EE
and
2­
EEA
in
humans
prompted
Veulemans
et
al
to
note
that
"
it
would
certainly
warrant
extra
caution
in
the
extrapolation
of
experimental
data
from
laboratory
animals
to
man,
since
comparable
accumulation
effects
apparently
are
not
found
in
all
species."
Although
2­
EE
and
2­
EEA
are
the
only
glycol
ethers
which
have
been
studied
in
humans,
these
findings
raise
enough
questions
about
the
similarities
of
the
metabolism
and
pharmacokinetics
of
glycol
ethers
across
species
to
deter
the
Agency
from
reducing
the
uncertainty
factor
used
based
on
the
similarity
of
the
pharmacokinetics
and
metabolism
of
glycol
ethers
across
species
CMA's
fourth
argument
is
that
when
dose
is
expressed
in
the
correct
units
using
the
correct
cross­
species
scaling
factor,
then
a
lower
uncertainty
factor
can
be
used.
OSHA
intends
to
discuss
this
issue
later
in
this
section
in
its
review
of
the
risk
assessment
performed
by
Environ
et
al
(
Ex.
4­
016f).
The
Agency
does
agree
with
CMA
that
uncertainty
is
reduced
when
dose
is
expressed
in
the
correct
units,
but
the
Agency
is
not
as
confident
as
CMA
regarding
what
are
the
correct
units
CMA's
final
argument
for
supporting
a
lower
uncertainty
factor
is
that
lower
uncertainty
factors
should
be
used
because
exposure
is
occupational.
In
an
appendix
to
CMA's
comments,
E.
M.
Johnson
argues
that
the
10­
fold
factor
for
intra­
species
variability
can
be
reduced
when
the
exposed
population
is
less
diverse
than
the
total
population
as
in
the
case
of
workers
who
tend
to
be
healthier
and
more
homogeneous
than
the
general
population
(
Ex.
7­
17,
Appendix
A)

OSHA
cannot
agree
with
this
position
for
a
number
of
reasons.
First
of
all,
while
it
is
plausible
that
a
woman
who
is
a
worker
may
be
healthier
than
a
woman
who
is
not
a
worker,
CMA
presents
no
evidence
that
the
"
healthy
worker
effect"
is
conferred
upon
the
developing
fetus.
Furthermore,
a
fetus
has
two
parents
who
contribute
to
its
genetic
identity,
and
there
is
no
reason
to
assume
that
the
father
of
a
fetus
of
a
working
mother
is
also
a
"
healthy
worker".
Finally,
although
"
healthy
workers"
may
constitute
a
homogeneous
population,
it
does
not
follow
that
their
offspring
will
constitute
a
homogenous
population,
healthy
or
otherwise
Although
OSHA's
approach
of
using
an
uncertainty
factor
of
100
may
appear
conservative,
OSHA
believes
that
the
uncertainties
associated
with
deriving
an
ADI
for
occupational
exposure
to
glycol
ethers
require
the
use
of
this
factor.
Some
of
the
uncertainties
stem
from
the
qualitative
nature
of
the
uncertainty
factor
approach
as
outlined
earlier
in
this
risk
assessment
(
e.
g.
the
unlikelihood
that
an
exposure
level
used
in
a
bioassay
will
be
the
"
true"
threshold,
varying
susceptibilities
across
species,
etc.).
Other
uncertainties
stem
specifically
from
the
data
available
for
assessing
the
risk
from
glycol
ethers
as
noted
above
(
e.
g.
similar
exposure
levels
used
across
species,
possible
differences
in
metabolism
and
pharmacokinetics
across
species,
etc.).
For
these
reasons,
OSHA
has
used
an
uncertainty
factor
of
100.
The
Agency
seeks
comment
on
its
choice
of
uncertainty
factor
and
its
justification
for
this
choice.
The
Agency
seeks
detailed
reasons
for
either
accepting
or
rejecting
the
choice
of
a
100­
fold
uncertainty
factor
and
any
data
available
to
support
the
position
D
.
Assessment
of
the
Reproductive
Risk
from
Exposure
to
Glycol
Ethers
1.
Introduction
The
Interagency
Regulatory
Liaison
Group,
(
IRLG),
describes
reproductive
toxicity
as
dealing
with
"
the
effects
of
toxicants
on
adult
reproductive
function
and
development
of
the
offspring
which
may
be
produced
by
alteration
of
a
wide
range
of
processes
in
either
the
female
or
the
male."
As
noted
by
the
IRLG,
these
processes
include
"
those
associated
with
the
primary
and
accessory
sexual
organs
and
with
fertilization,
as
well
as
those
which
impact
more
indirectly
on
normal
reproductive
function;
e.
g.,
neuroendocrine
control,
general
physiological
and
psychological
health,
and
nutrition."
The
IRLG
continues,
"[
f]
ollowing
fertilization,
processes
associated
specifically
with
pregnancy
are
also
vulnerable;
e.
g.,
implantation,
placental
formation
and
function,
conceptal
development,
and
parturation
and
lactation"
(
Ex.
5­
018)
In
its
Proposed
Guidelines
for
Assessing
Male
Reproductive
Risk
(
Ex.
5­
123),
the
EPA
identifies
a
number
of
measures
which
may
be
evaluated
to
assess
the
reproductive
effects
of
exposure
of
males
to
a
potential
reproductive
toxicant.
In
animals,
these
include
body
weight;
weight
and
histopathology
of
the
testes,
epididymides,
seminal
vesicles,
prostate,
and
pituitary
gland;
mating
ratio
and
pregnancy
ratio;
and
pregnancy
outcomes
such
as
litter
size,
pre­
and
post­
implantation
loss,
the
ratio
of
live
to
dead
pups,
sex
ratios,
malformations,
birth
and
postnatal
weights,
and
survival.
Supplemental
end
points
of
male
reproductive
toxicity
may
be
identified
through
sperm
and
endocrine
evaluations.
EPA
points
out
that
while
these
measures
are
useful
for
evaluating
reproductive
risk
in
humans
as
well
as
animals,
many
of
these
measures
such
as
early
fetal
loss,
reproductive
capacity
of
the
offspring,
and
the
invasive
measures
of
reproductive
function
are
not
easily
observed
in
humans
The
most
feasible
measures
used
in
studies
of
reproductive
effects
in
human
males
are
semen
evaluations,
indirect
measures
of
fertility/
infertility,
and
certain
pregnancy
outcomes
such
as
fetal
loss,
birth
weight,
sex
ratio,
congenital
malformations,
postnatal
function,
and
neonatal
growth
and
survival
The
measures
recommended
by
EPA
for
evaluation
to
determine
reproductive
effects
in
female
laboratory
animals
include
capacity
to
conceive;
length
of
time
required
for
conception;
alterations
in
the
onset
of
puberty;
alterations
in
the
reproductive
cycle;
oocyte
toxicity;
premature
reproductive
senescence;
weight
and
histopathology
of
the
ovary,
the
uterus,
and
the
pituitary
gland;
and
the
pregnancy
outcomes
described
for
males
above.
In
human
females,
the
feasible
measures
of
reproductive
toxicity
are
the
measures
of
fertility
and
pregnancy
outcomes
(
Ex.
5­
122)

While
studies
of
human
populations
provide
the
strongest
evidence
of
the
reproductive
toxicity
of
a
substance,
such
studies
are
usually
limited
in
their
ability
to
detect
risk.
Like
epidemiological
studies
of
cancer
mortality
and
other
discrete
outcomes,
studies
of
reproductive
toxicity
in
human
populations
often
suffer
from
lack
of
statistical
power
(
usually
due
to
small
sample
size),
inexact
exposure
measurements,
and
an
inability
to
control
for
all
potential
confounding
factors.
Studies
of
reproductive
toxicity
in
human
populations,
however,
have
additional
limitations.
Assessment
of
reproductive
endpoints
is
often
dependent
upon
voluntary
participation
and
self­
reporting
of
outcomes
which,
in
turn,
may
be
influenced
by
privacy
considerations
and
religious
considerations.
In
addition,
there
are
fewer
endpoints
which
may
be
feasibly
measured
in
humans
than
may
be
measured
in
laboratory
animals.
Thus,
because
of
these
limitations,
reproductive
risks
are
usually
assessed
from
animal
studies
2.
2­
ME
A
number
of
studies
showing
reproductive
effects
in
male
animals
exposed
to
2­
ME
are
described
in
the
[
page
15566]

Health
Effects
section
of
this
preamble.
Results
from
studies
of
animals
exposed
to
2­
ME
through
inhalation
are
supported
by
the
results
from
studies
of
animals
exposed
to
2­
ME
through
ingestion
The
lowest
NOEL
observed
in
laboratory
animals
was
observed
in
a
study
of
New
Zealand
white
rabbits
by
Miller
et
al
of
the
Dow
Chemical
Company
(
Exs.
4­
045
and
5­
023).
Groups
of
five
male
rabbits
were
exposed
to
2­
ME
at
concentrations
of
30,
100,
or
300
ppm
through
inhalation
for
6
hours
per
day,
5
days
per
week,
for
13
weeks.
A
group
of
5
male
rabbits
served
as
controls.
Food
and
water
was
provided
to
the
animals
ad
libitum
except
during
periods
of
exposure
when
neither
was
available
Following
13
weeks
of
exposure,
all
surviving
animals
were
sacrificed.
Two
rabbits
in
the
300
ppm
group
died
during
the
exposure
phase
of
the
study.
The
cause
of
death
for
one
was
bronchopneumonia.
The
cause
of
death
for
the
second
was
unknown.
All
animals
were
given
a
complete
gross
pathological
exam,
and
a
histological
exam
was
performed
on
selected
tissues
from
each
animal
Reduced
testes
weight
was
observed
in
rabbits
in
the
300
ppm
and
100
ppm
exposure
groups,
and
although
this
effect
was
statistically
significant
for
the
300
ppm
group
only,
the
study
authors
attributed
the
observation
in
both
groups
to
exposure.
Gross
pathological
exam
showed
that
all
of
the
rabbits
in
the
300
ppm
group
had
very
small
and
flaccid
testes.
A
slight
to
moderate
decrease
in
testes
size
relative
to
the
control
animals
was
observed
in
4
out
of
5
of
the
rabbits
in
the
100
ppm
group
(
p=
0.024,
Fisher's
Exact
Test),
and
2
out
of
5
of
the
rabbits
in
the
30
ppm,
group
(
p
>
0.05).
Histopathologic
exam
confirmed
the
gross
pathological
observations.
A
dose­
related
increase
in
both
the
incidence
and
severity
of
testicular
degenerative
changes
was
seen
in
the
test
animals.
In
all
three
of
the
rabbits
on
the
300
ppm
group,
which
survived
through
the
end
of
the
study,
the
degeneration
was
diffuse
and
severe
with
virtually
every
tubule
affected.
In
the
three
rabbits
with
testicular
degeneration
in
the
100
ppm
group,
more
of
a
spectrum
of
effects
was
noted
in
that
within
the
same
testes,
some
tubules
were
relatively
normal
in
appearance
while
others
contained
no
germinal
elements
at
all.
In
the
30
ppm
group,
the
microscopic
degenerative
changes
were
apparent
in
the
testes
of
only
one
of
the
two
rabbits
observed
to
have
decreased
testes
size
in
the
gross
pathological
exam.
The
microscopic
degenerative
changes
observed
in
this
animal
were
an
excess
of
tubules
in
which
the
germinal
epithelium
was
thinner
than
normal,
with
a
complete
complement
of
germinal
stages
but
very
few
spermatozoa
Histopathologic
exam
of
the
epididymis
found
that
the
epididymal
sperm
content
generally
reflected
the
degree
of
testicular
damage
with
noticeable
decreases
in
those
cases
which
were
moderately
to
severely
affected.
Degenerating
spermatic
elements
were
commonly
observed,
but
secondary
changes
in
accessory
sex
glands
were
not
seen
Despite
the
small
number
of
animals
in
each
exposure
group,
a
significant
dose­
related
effect
was
observed.
Based
upon
the
outcome
of
decreased
testes
size,
one
of
the
outcomes
identified
by
EPA
as
an
adverse
reproductive
outcome,
the
NOEL
for
reproductive
effects
of
2­
ME
in
rabbits
is
30
ppm
Given
that
the
NOEL
for
reproductive
effects
from
2­
ME
has
been
derived
from
animal
studies,
OSHA
believes
that
an
uncertainty
factor
of
100
is
appropriate
for
derivation
of
the
ADI
as
was
the
case
for
the
assessment
of
developmental
risks
from
exposure
to
2­
ME.
Here
again,
an
uncertainty
factor
of
100
provides
a
factor
of
10
for
inter­
species
variability
and
a
factor
of
10
for
intra­
species
variability.
Therefore,
based
upon
this
study
Miller
et
al,
the
ADI
for
2­
ME
would
be
30/
100
or
0.3
ppm
on
the
basis
of
reproductive
risks.
The
ADI
for
2­
ME
based
on
developmental
risks
is
0.1
ppm,
somewhat
lower
than
the
ADI
based
on
reproductive
risks
but
the
two
ADIs
are
very
close.
Thus
an
ADI,
of
0.1
ppm
would
cover
both
reproductive
and
developmental
effects,
i.
e.
at
this
level
humans
are
unlikey
to
exhibit
adverse
effects
(
both
reproductive
and
developmental)
similar
to
those
observed
in
animals
3.
2­
EE
There
are
fewer
studies
of
the
reproductive
effects
of
2­
EE
in
the
literature
than
there
are
of
2­
ME,
but
like
2­
ME,
2­
EE
has
been
found
to
induce
adverse
reproductive
effects
in
laboratory
animals
This
was
the
finding
of
Terrill
et
al
who
conducted
a
study
for
the
Chemical
Manufacturers
Association
exposing
rabbits
to
2­
EE
(
Exs.
4­
108
and
5­
084).
Groups
of
ten
male
New
Zealand
white
rabbits
were
exposed
to
2­
EE
at
concentrations
of
25,
100,
and
400
ppm
through
inhalation
for
6
hours
per
day,
5
days
per
week,
for
13
weeks.
A
group
of
ten
male
rabbits
served
as
controls.
Food
and
water
was
provided
to
the
animals
ad
libitum
except
during
periods
of
exposure
when
neither
was
available
All
animals
survived
the
exposure
phase
of
the
study.
At
terminal
sacrifice,
all
animals
were
given
a
complete
gross
post
mortem
exam.
Animals
in
the
control
and
high
dose
groups
were
given
a
complete
histopathological
exam,
but
for
the
low
and
middle
dose
groups,
only
the
bone
marrow,
the
testes
with
epididymis,
the
kidneys,
the
liver,
the
lymph
nodes,
the
spleen,
the
thymus,
and
any
observed
gross
lesion
or
tissue
mass
were
examined
In
the
400
ppm
group,
there
was
a
statistically
significant
decrease
in
absolute
testes
weight
and
in
testes
weight
relative
to
body
weight.
Gross
postmortem
examination
revealed
that
in
three
of
the
ten
rabbits
from
this
group,
there
was
slight
focal
tubule
degeneration.
Based
upon
decreased
testes
weight,
the
NOEL
for
reproductive
effects
for
2­
EE
in
rabbits
is
100
ppm
Although
there
are
fewer
animal
studies
of
the
reproductive
effects
of
exposure
to
2­
EE
than
2­
ME,
the
results
of
the
animal
studies
are
supported
by
observation
in
human
populations.
In
a
study
of
male
workers
at
Precision
Castparts
Corporation,
NIOSH
reported
significantly
reduced
sperm
count
among
workers
exposed
to
2­
EE
compared
to
workers
with
no
such
exposure
(
Ex.
5­
003).
Welch
et
al
also
found
reduced
sperm
in
a
group
of
shipyard
painters
exposed
to
2­
EE,
but
theses
workers
were
also
exposed
to
2­
ME,
so
it
is
impossible
to
determine
whether
the
effect
was
due
to
2­
EE,
2­
ME,
or
both
glycol
ethers
(
Ex.
5­
104).
These
studies
are
discussed
in
greater
detail
in
the
Health
Effects
Section
of
this
preamble
Applying
an
uncertainty
factor
of
100
to
the
NOEL
of
100
ppm
reported
by
Terrill
et
al
in
their
study
of
New
Zealand
white
rabbits,
one
would
arrive
at
an
ADI
of
100/
100
or
1
ppm
for
2­
EE
basee
on
reproductive
risk.
Here
again,
however,
the
ADI
must
be
based
on
developmental
risks
as
well
as
reproductive
risks.
The
ADI
for
2­
EE
based
on
developmental
risks
is
0.5
ppm,
lower
than
the
ADI
based
reproductive
risks.
As
is
the
case
for
2­
ME,
for
2­
EE
the
ADI
based
on
reproductive
risks
is
very
close
to
the
ADI
based
on
developmental
risks.
At
an
ADI
of
0.5ppm
2­
EE
humans
are
unlikely
to
exhibit
effects
(
both
reproductive
and
developmental)
similar
to
those
observed
in
animals
E.
Assessment
of
Risk
from
Exposure
to
Glycol
Ether
Acetates
The
acetates
of
2­
ME
and
2­
EE,
2­
MEA
and
2­
EEA,
have
not
been
studied
[
page
15567]

as
extensively
as
have
the
parent
compounds.
As
noted
in
the
Health
Effects
section
of
this
preamble,
however,
the
acetates
have
been
shown
to
induce
adverse
reproductive,
developmental,
and
hematological
effects
in
animals
similar
to
those
induced
by
2­
ME
and
2­
EE.
Furthermore,
as
discussed
in
the
Health
Effects
section,
it
has
been
shown
that
2­
MEA
and
2­
EEA
are
metabolized
to
the
same
acetic
acids,
methoxyacetic
acid
(
MAA)
and
ethoxyacetic
acid
(
EEA)
respectively,
by
the
same
mediated
pathway,
an
alcohol
dehydrogenase
(
ADH)
mediated
pathway,
as
their
parent
compounds
Because
of
the
similarity
in
induced
effects
between
the
acetates
and
their
parent
compounds
and
because
of
the
similarity
in
metabolism
between
the
acetates
and
their
parent
compounds,
OSHA
proposes
that
the
ADIs
derived
for
the
acetates
be
the
same
as
for
their
parent
compounds.
That
is,
the
ADI
for
for
2­
MEA
is
0.1
ppm
and
the
ADI
for
2­
EEA.
is
0.5
ppm
There
is
some
experimental
evidence
to
support
OSHA's
proposal.
As
reproductive
toxicants,
the
acetates
have
been
shown
not
only
to
induce
similar
effects
as
their
parent
compounds,
but
also
to
induce
these
effects
at
equivalent
doses.
Nagano
et
al
found
that
male
mice
exposed
orally
to
2­
MEA
at
500
mg/
kg
of
body
weight
experienced
significant
decreases
in
testicular
weight.
When
this
dose
was
converted
to
mmole/
kg,
the
authors
found
that
on
an
equimolar
basis,
exposure
to
2­
ME
and
2­
MEA
resulted
in
similar
effects
(
Ex.
4­
135).
Likewise,
these
authors
found
that
on
an
equimolar
basis,
male
mice
exposed
to
2­
EE
and
male
mice
exposed
to
2­
EEA
experienced
similar
adverse
reproductive
outcomes
(
Ex.
4­
135)

The
acetate
2­
MEA
has
not
been
tested
for
its
potential
to
adversely
affect
reproductive
outcomes.
Only
limited
data
exist
on
2­
MEA,
according
to
CMA,
because
of
the
small
production
volume
of
this
acetate
(
Ex.
7­
17).
Nonetheless,
CMA
argues
that
although
detailed
evaluation
of
the
developmental
toxicity
of
2­
MEA
has
not
been
conducted
as
it
has
for
2­
ME,
"
the
NOELs
determined
for
2­
ME
can
be
reasonably
employed
for
assessing
this
compound.
The
likelihood
that
any
effect
it
may
cause
would
occur
through
human
metabolism
of
2­
MEA
to
2­
ME
and
then
to
the
active
metabolite
makes
it
reasonable
to
employ
the
NOELs
for
2­
ME
to
protect
humans
against
effects
of
2­
MEA"
(
Ex.
7­
17).
OSHA
concurs
with
CMA's
position
Unlike
2­
MEA,
2­
EEA
has
been
tested
to
determine
its
potential
as
a
developmental
toxicant.
Nelson
et
al
reported
a
statistically
significant
excess
of
developmental
effects
in
rats
exposed
to
2­
EEA
at
levels
as
low
as
130
ppm
(
Ex.
5­
091).
This
level
was
the
lowest
exposure
level
used
in
this
bioassay
therefore
no
NOEL
was
established
for
this
study.
Doe
et
al
exposed
pregnant
Dutch
rabbits
to
0,
25,
100,
or
400
ppm
of
2­
EEA,
and
the
fetuses
of
rabbits
exposed
to
levels
as
low
as
100
ppm
showed
a
dose­
related
increase
in
skeletal
defects
(
Ex.
5­
071).
Tyl
et
al
exposed
pregnant
Fischer
344
rats
and
pregnant
New
Zealand
white
rabbits
to
0,
50,
100,
200,
or
300
ppm
of
2­
EEA
(
Ex.
5­
124).
Here
again,
100
ppm
was
the
LOEL
for
developmental
effects
in
both
species.
This
level,
100
ppm,
is
OSHA's
current
PEL
for
2­
EEA.
Fifty
ppm
was
established
to
be
the
NOEL
for
both
the
rats
and
the
rabbits.
Because
Doe
et
al
and
Tyl
et
al
established
the
same
LOEL
in
two
separate
studies
and
in
two
different
species,
it
is
reasonable
to
use
the
NOEL
from
the
Tyl
et
al
study,
50
ppm
of
2­
EEA,
as
the
NOEL
for
calculating
the
ADI.
As
with
the
parent
compounds,
an
uncertainty
factor
of
100
is
appropriate,
and
this
would
lead
to
an
ADI
of
50
ppm/
100
or
0.5
ppm.
That
is,
at
an
ADI
of
0.5
ppm
2­
EEA,
humans
are
likely
to
exhibit
effects
similar
to
those
observed
in
humans
OSHA's
proposal
for
deriving
ADIs
for
the
acetates
at
the
same
level
as
those
for
the
parent
compound
also
has
support
from
a
number
of
commentors
who
responded
to
OSHA's
ANPR.
For
example,
NIOSH
wrote
that
a
separate
PEL
for
each
of
the
acetates
and
their
parent
compounds
"
should
not
be
necessary
because
of
the
similarities
in
the
adverse
effects,
the
similarity
in
route
of
exposure,
and
the
fact
that
in
many
situations,
several
of
the
ethers
and
their
acetates
are
used
simultaneously"
(
Ex.
7­
22).
Similarly,
Du
Pont
noted
that
"
2­
methoxyethanol
(
2­
ME)
and
its
acetate
(
2­
MEA)
and
the
[
sic]
2­
ethoxyethanol
(
2­
EE)
and
its
acetate
(
2­
EEA)
could
be
regulated
together
because
the
toxic
effects
of
these
glycol
ethers
and
their
respective
acetates
are
the
same"
(
Ex.
7­
28),
and
Kodak
proposed
the
same
PELs
for
2­
ME
and
2­
MEA
and
for
2­
EE
and
for
2­
EEA,
(
Ex.
7­
23),
although
the
levels
proposed
are
different
than
those
proposed
by
OSHA.
OSHA
seeks
comment
on
this
approach
to
deriving
ADIs
for
the
glycol
ether
acetates
F.
Other
Approaches
to
the
Assessment
of
Risk
for
Glycol
Ethers
1.
The
Crump
Risk
Assessment
Under
contract
to
OSHA,
K.
S.
Crump
and
Company
performed
a
risk
assessment
for
developmental
and
reproductive
effects
from
exposure
to
2­
ME,
2­
EE,
and
their
acetates
(
Ex.
5­
136).
The
data
used
for
this
analysis
were
from
the
studies
of
developmental
effects
of
exposure
to
2­
ME
by
Hanley
et
al
(
Exs.
4­
042a
and
4­
106)
and
to
2­
EE
by
Tinston,
Doe
et
al
(
Exs.
4­
038
and
4­
039;
see
also
Ex.
5­
071)
and
the
studies
of
reproductive
effects
of
exposure
to
2­
ME
by
Miller
et
al
(
Ex.
5­
057)
and
to
2­
EE
by
Terrill
et
al
(
Exs.
4­
108
and
5­
084).
At
the
time
Crump
performed
its
analysis,
no
data
were
available
on
the
developmental
effects
of
2­
EE
as
measured
in
litters.
Therefore,
Crump
limited
its
analysis
of
the
developmental
effects
of
2­
EE
exposure
to
responses
observed
in
fetuses.
No
analyses
were
done
on
data
from
studies
of
the
acetates.
Crump
noted
that
"
2­
MEA
and
2­
EEA
are
believed
to
be
quickly
hydrolized
to
their
corresponding
glycol
ether.
Furthermore,
evidence
suggests
that
from
that
point
on,
their
metabolism
and
distribution
proceed
in
the
same
manner
as
the
ether.
If
that
is
the
case,
a
mole
of
an
ether
will
yield
the
same
amounts
of
products
as
a
mole
of
the
corresponding
acetate.
Moreover,
a
given
air
concentration
in
ppm
contains
the
same
number
of
moles
(
1
ppm
is
about
41
micromoles
per
cubic
meter
at
standard
temperature
and
pressure),
for
all
chemicals.
Consequently,
in
the
absence
of
data
on
the
acetates
needed
for
risk
assessment,
it
is
reasonable
to
assume
that
the
acetates
and
their
corresponding
ethers
will
produce
the
same
risks
at
equal
air
concentrations,
in
ppm"
(
Ex.
5­
136)

The
goal
of
the
Crump
risk
assessment
was
to
develop
dose­
response
models
for
developmental
and
reproductive
effects.
Only
brief
descriptions
of
the
models
and
methods
used
by
Crump
are
presented
here,
and
the
reader
is
referred
to
the
Crump
report
(
Ex.
5­
136)
for
additional
details.
Two
approaches
were
taken
to
develop
these
models
for
the
outcomes
of
interest.
The
first
of
these
applied
methods
similar
to
those
applied
to
cancer
data,
but
the
dose­
response
models
considered
were
non­
linear
or
incorporated
a
threshold.
Four
models
employed
this
approach:
the
quantal
linear
regression
(
QLR)
model,
the
Weibull
model,
the
continuous
linear
regression
(
QCR)
model,
and
the
continuous
power
(
CP)
model.
The
QLR
and
Weibull
models
were
used
for
incidence
data
measured
in
fetuses,
and
[
page
15568]

therefore
do
not
take
litter
size
or
intra­
litter
correlation
(
i.
e.
the
litter
effect)
into
account.
The
QCR
and
CP
models
were
used
for
incidence
data
measured
in
litters,
and
they
account
for
the
litter
effect
but
not
for
litter
size.
The
QLR
and
QCR
models
assume
a
threshold
with
a
linear
response
above
the
threshold.
The
Weibull
and
CP
models
are
non­
threshold
models
but
can
be
non­
linear
if
indicated
by
the
data
The
second
approach
taken
by
Crump
was
to
consider
two
models
recently
developed
specifically
for
assessing
developmental
effects,
(
these
models
use
only
litter
data),
and
to
modify
these
for
the
analysis
of
the
glycol
ethers
data.
The
first
of
these
was
developed
by
Kodell
et
al.
This
model
uses
the
beta­
binomial
distribution
to
account
for
the
litter
effect
and
takes
into
account
the
effect
of
litter
size
on
the
probability
of
a
developmental
effect.
The
second
model
considered
by
Crump
was
originally
put
forth
by
Rai
and
Van
Ryzin.
This
model
takes
litter
size
into
account
but
does
not
account
for
the
litter
effect.
In
its
analysis,
Crump
used
two
special
cases
of
the
Kodell
model,
the
Kodell­
QLR
model
which
assumes
a
threshold
but
is
linear
above
the
threshold,
and
the
Kodell­
Weibull
model
which
assumes
no
threshold
but
can
be
non­
linear.
Only
one
case
of
the
Rai
and
Van
Ryzin
model
was
considered.
This
model
assumes
no
threshold
and
is
linear.
Crump
felt
the
shortcomings
of
the
Rai
and
Van
Ryzin
model
made
it
less
appropriate
for
assessing
risk
than
the
other
models
considered
Crump
applied
the
models
described
here
only
to
data
on
developmental
outcomes.
The
models
developed
for
use
with
litter
data
could
not
be
used
with
the
data
Crump
had
on
reproductive
outcomes
because
the
data
Crump
had
measured
these
outcomes
in
individual
animals
and
not
litters.
Likewise,
the
models
developed
for
use
with
litter
data
could
not
be
used
with
the
data
Crump
had
on
developmental
outcomes
from
2­
EE
exposure
because,
as
noted
above,
litter
data
for
these
effects
were
not
available
to
Crump
when
it
did
its
analysis.
The
models
developed
for
use
with
fetal
data
could
have
been
used
with
the
data
on
reproductive
outcomes,
but
Crump
did
not
use
these
models
to
analyze
the
data
on
reproductive
effects
because
of
the
small
number
of
animals
used
in
these
bioassays
Although
the
goal
of
the
Crump
risk
assessment
was
to
develop
dose­
response
models
for
the
outcomes
of
interest,
two
additional
approaches
for
determining
a
"
safe"
level
of
exposure
were
considered.
The
first
of
these
was
to
calculate
a
NOEL
using
a
nostatistical
significance­
of­
trend
or
NOSTASOT
approach.
In
this
approach,
tests
of
statistical
hypothesis
were
conducted
to
determine
whether
the
bioassay
data
provided
sufficient
statistical
evidence
to
conclude
that
a
dose­
related
trend
existed,
(
i.
e.
whether
response
increased
with
dose),
and
if
so,
to
determine
the
highest
dose
used
in
the
bioassay
such
that
there
was
no
statistical
evidence
of
a
dose­
related
trend
in
response
at
that
dose
or
at
lower
doses.
The
highest
dose
which
showed
no
statistical
evidence
of
a
dose­
related
trend
is
called
the
NOSTASOT
dose
and
is
considered
to
be
a
statistically
determined
NOEL.
This
approach
was
used
for
both
developmental
and
reproductive
outcomes
for
both
2­
ME
and
2­
EE
The
final
approach
considered
by
Crump
was
calculation
of
a
benchmark
dose
as
an
alternative
to
the
NOEL.
A
benchmark
dose
is
defined
as
the
statistical
95%
lower
confidence
limit
on
the
dose
corresponding
to
a
1%
increase
in
the
extra
risk.
The
dose
corresponding
to
a
1%
increase
in
extra
risk
was
estimated
using
both
the
QLR
model
and
Weibull
model,
but
only
the
lower
of
the
two
benchmark
doses
was
reported.
Crump
chose
to
use
only
these
two
models
to
estimate
the
benchmark
doses
because
these
two
models
were
the
only
two
used
to
analyze
all
of
the
data
on
adverse
reproductive
outcomes
for
both
2­
ME
and
2­
EE
The
NOSTASOT
dose
and
the
benchmark
dose
calculated
by
Crump
are
much
like
the
NOELs
calculated
by
OSHA
in
that
neither
of
these
doses
alone
represents
a
"
safe"
level
of
exposure.
Rather,
Crump
intended
an
uncertainty
factor
to
be
applied
to
either
of
these
doses,
although
Crump
did
not
recommend
a
particular
uncertainty
factor
in
his
report.
Crump
argues
that
either
is
preferable
to
a
NOEL
established
using
traditional
methods
because
they
make
use
of
all
of
the
dose­
response
data.
Crump
notes
that
NOELs
"
determined
by
comparing
treatment
groups
individually
to
the
control
group
.
have
low
power
because
they
involve
only
the
animals
in
two
of
the
treatment
groups,
when
in
fact
the
data
from
any
intermediate
doses
are
also
relevant.
Thus
a
common
result
is
that
the
trend
test
is
significant,
but
none
of
the
treated
groups
differ
significantly
from
the
control
group."

Results
of
the
Crump
analysis
are
presented
in
Tables
VI­
K
through
VI­
N.
Although
the
sources
of
the
data
used
by
Crump
were
the
same
as
those
used
by
OSHA,
the
adverse
outcomes
considered
and
the
specific
estimates
of
incidence
were
different.
These
data
are
presented
in
the
Crump
report
Table
VI­
K
shows
that
for
2­
ME,
NOELs
established
using
the
NOSTASOT
approach
are
identical
to
those
established
by
OSHA
using
more
traditional
methods.
For
2­
EE,
Table
VI­
L
shows
that
for
all
but
one
outcome
in
rats,
total
abnormal
ribs,
Crump's
NOSTAOTs
are
the
same
as
OSHA's
NOELs,
but
for
rabbits,
Crump's
NOELs
are
lower.
This
difference
is
due
to
the
fact
that
Crump
used
fetus
data
for
its
analysis
of
2­
EE
whereas
OSHA
used
litter
data
in
its
analysis
to
establish
the
NOEL
Table
VI­
K
NOSTASOT
and
Benchmark
Doses
Calculated
for
2­
ME
Data
Sets
(
a)

DEVELOPMENTAL
EFFECTS
NOSTASOT
(
b)
Benchmark
(
c)

Species
Adverse
Effect
Exposure
(
ppm)
Dose(
ppm)

Rats
(
d)
Delayed
ossification
of
Centra
10
12
Rib
spurs
10
8.5
Major
malformations
10
53
Rabbits(
d)
Resorptions
10
2
Major
malformations
10
10
Mice
(
e)
Resorptions
10
9.3
Extra
lumbar
ribs
10
2.5
REPRODUCTIVE
EFFECTS
NOSTASOT
Benchmark
Species
Adverse
Effect
Exposure
(
ppm)
Dose
(
ppm)

Rats
(
f)
Testicular
degeneration
100
N/
C
(
g)

Rabbits(
f)
Testicular
degeneration
30
N/
C
[
page
15569]
Reduced
testes
size
30
N/
C
a
­
From
the
Crump
Report,
Ex.
5­
136
b
­
NOSTASOT
=
No
statistical
significance
of
trend
(
i.
e.
the
NOSTASOT
exposure
is
the
highest
dose
for
which
dta
did
not
show
a
statistically
significant
dose­
related
trend).
See
text
for
details
c
­
Benchmark
exposure
is
the
95%
lower
limit
on
doses
corresponding
to
an
extra
risk
of
1%.
See
text
for
details
d
­
Data
from
Hanley
et
al,
Ex.
4­
042a
e
­
Data
from
Hanley
et
al,
Ex.
4­
106
f
­
Data
from
Miller
et
al,
Ex.
4­
045
g
­
N/
C
=
not
calculated
Table
VI­
L
NOSTASOT
and
Benchmark
Doses
Calculated
for
2­
EE
Data
Sets
(
a)

DEVELOPMENTAL
EFFECTS
NOSTASOT(
b)
Benchmark(
c)

Species
Adverse
Effect
Exposure
(
ppm)
Dose
(
ppm)

Rats
(
d)
Minor
skeletal
defects
50
15
Minor
visceral
defects
50
46
Total
abnormal
ribs
10
1.8
Late
intra­
uterine
deaths
50
18
Rabbits(
e)
Minor
skeletal
defects
N/
D
(
f)
3.5
Skeletal
variants
10
2.2
REPRODUCTIVE
EFFECTS
NOSTASOT
Benchmark
Species
Adverse
Effect
Exposure
(
ppm)
Dose
(
ppm)

Rabbits(
g)
Focal
tubule
degeneration
100
N/
C
(
h)

Weights
of
testes/
epididymis
100
N/
C
a
­
From
the
Crump
Report,
Ex.
5­
136
b
­
NOSTASOT
=
No
statistical
significance
of
trend
(
i.
e.
the
NOSTASOT
exposure
is
the
highest
dose
for
which
dta
did
not
show
a
statistically
significant
dose­
related
trend).
See
text
for
details
c
­
Benchmark
exposure
is
the
95%
lower
limit
on
doses
corresponding
to
an
extra
risk
of
1%.
See
text
for
details
d
­
Data
from
Tinston
et
al,
Ex.
4­
038
e
­
Data
from
Tinston
et
al,
Ex.
4­
039
f
­
Not
defined.
A
significant
effect
was
seen
at
the
lowest
dose
g
­
Data
from
Terrill
et
al,
Ex.
4­
108
h
­
N/
C
=
not
calculated
For
almost
every
adverse
outcome
considered,
Tables
VI­
K
and
VI­
L
show
that
the
benchmark
dose
is
lower
than
the
NOEL
estimated
using
the
NOSTASOT
approach.
Here
again,
this
could
be
due
to
the
fact
that
benchmark
doses
were
estimates
from
models
which
use
fetal
data
rather
than
litter
data.
Were
benchmark
doses
to
be
used
to
calculate
the
ADIs,
the
result
would
be
a
more
conservative
estimate
of
the
exposure
below
which
an
adverse
outcome
is
unlikely
than
the
estimates
derived
by
OSHA
Tables
VI­
M
and
VI­
N
show
that
despite
the
differences
among
the
models
used
by
Crump,
for
the
majority
of
data
sets
the
models
predict
surprisingly
consistent
risks.
The
largest
difference
in
predicted
risks
are
found
at
low
doses
between
the
threshold
and
non­
threshold
models.
Much
less
difference
can
be
attributed
to
whether
the
models
use
fetal
or
litter
data.
Crump
suggests
one
reason
that
the
shape
of
the
dose­
response
curve
is
more
important
in
determining
a
risk
estimate
than
the
type
of
data
used
may
be
the
low
intra­
litter
correlation
estimated
for
the
2­
ME
data
sets.
Crump
explains
that
"[
f]
or
the
rat
data,
intra­
litter
correlations,
as
estimated
by
the
Kodell­
QLR
or
Kodell­
Weibull
models,
did
not
exceed
0.05
.
Somewhat
larger
correlations
were
observed
in
some
of
the
rabbit
and
mouse
data
sets
(
ranging
up
to
about
0.27).
Apparently,
intra­
litter
correlations
of
this
magnitude
are
not
sufficient
to
cause
maximum­
likelihood
estimates
derived
ignoring
the
litter
effect
to
be
seriously
in
error."

Table
VI­
M
Estimates
of
Number
of
Extra
Cases
of
Various
Developmental
Effects
per
1000
Fetus
from
Exposure
to
2­
ME
a
Rats:
Delayed
Ossification
of
the
Centra
b
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
33
31
30
27
33
31
25
(
50)
(
51)
(
47)
(
47)
(
46)
(
270)
­­

5
4
4.1
3.6
3.1
4.1
4.1
3.1
(
10)
(
10)
(
9.3)
(
9.4)
(
8.2)
(
62)
­­

1
0
0.54
0
0.36
0
0.54
0.57
(
2)
(
2.1)
(
1.9)
(
1.9)
(
0.48)
(
13)
­­

0.5
0
0.23
0
0.14
0
0.23
0.28
(
1)
(
1)
(
0.93)
(
0.94)
(
0)
(
6.4)
­­

0.1
0
0.03
0
0.016
0
0.03
0.056
(
0.2)
(
0.21)
(
0.19)
(
0.19)
(
0)
(
1.3)
­­

0.03
0
0.0066
0
0.0033
0
0.0065
0.017
(
0.061)
(
0.062)
(
0.056)
(
0.057)
(
0)
(
0.38)
­­

Rats:
Rib
Spurs
b
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
89
75
89
86
97
82.4
89
[
page
15570]
(
120)
(
120)
(
150)
(
150)
(
130)
(
132)
­­

5
3.8
5.8
0
7.3
6.7
7.2
16
(
24)
(
24)
(
30)
(
30)
(
27)
(
28)
­­

1
0
0.43
0
0.62
0
0.61
3
(
4.8)
(
4.9)
(
6.1)
(
6)
(
5.6)
(
5.6)
­­

0.5
0
0.14
0
0.22
0
0.21
1.5
(
2.4)
(
2.5)
(
3)
(
3)
(
2.8)
(
2.8)
­­

0.1
0
0.011
0
0.018
0
0.018
0.3
(
0.48)
(
0.49)
(
0.61)
(
0.6)
(
0.56)
(
0.57)
­­

0.03
0
0.0015
0
0.0029
0
0.0028
0.091
(
0.15)
(
0.15)
(
0.18)
(
0.18)
(
0.17)
(
0.17)
­­

Rats:
Total
Major
Malformations
b
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
6.2
6.2
6.5
6.5
5.3
5.4
6.2
(
15)
(
15)
(
10)
(
12)
(
13)
(
N/
P)
­­

5
1.3
1.3
1.3
1.3
0.64
0.97
1.3
(
3.1)
(
3.1)
(
2)
(
2.4)
(
2.6)
(
N/
P)
­­

1
0.25
0.25
0.26
0.26
0
0.18
0.25
(
0.62)
(
0.62)
(
0.41)
(
0.47)
(
0.53)
(
N/
P)
­­

0.5
0.13
0.13
0.13
0.13
0
0.084
0.13
(
0.31)
(
0.31)
(
0.2)
(
0.24)
(
0.27)
(
N/
P)
­­

0.1
0.025
0.025
0.026
0.026
0
0.015
0.025
(
0.062)
(
0.062)
(
0.041)
(
0.047)
(
0.053)
(
N/
P)
­­

0.03
0.0075
0.0075
0.0078
0.0078
0
0.0042
0.0075
(
0.019)
(
0.019)
(
0.012)
(
0.014)
(
0.016)
(
N/
P)
­­

Rabbits:
Resorptions
b
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
140
140
150
150
150
150
180
(
190)
(
190)
(
210)
(
210)
(
240)
(
240)
­­

5
31
31
29
29
33
33
49
(
41)
(
41)
(
43)
(
43)
(
53)
(
53)
­­

1
6.2
6.2
5.8
5.8
6.7
6.7
10
(
8.3)
(
8.3)
(
8.6)
(
8.6)
(
11)
(
11)
­­

0.5
3.1
3.1
2.9
2.9
3.3
3.3
5.2
(
4.2)
(
4.2)
(
4.3)
(
4.3)
(
5.5)
(
5.5)
­­

0.1
0.62
0.62
0.58
0.58
0.67
0.67
1.1
(
0.84)
(
0.84)
(
0.86)
(
0.86)
(
1.1)
(
1.1)
­­

0.03
0.19
0.19
0.18
0.18
0.2
0.2
0.32
(
0.25)
(
0.25)
(
0.26)
(
0.26)
(
0.33)
(
0.33)
­­

25
430
2.2
360
1.4
420
36
230
(
490)
(
290)
(
430)
(
220)
(
520)
(
280)
­­

5
0
0
0
0
0
0.0001
19
(
0)
(
5.4)
(
0)
(
3.5)
(
0)
(
6.3)
­­

1
0
0
0
0
0
0
3.3
(
0)
(
0.088)
(
0)
(
0.056)
(
0)
(
0.12)
­­

0.5
0
0
0
0
0
0
1.6
(
0)
(
0.015)
(
0)
(
0.0094)
(
0)
(
0.022)
­­

0.1
0
0
0
0
0
0
0.31
(
0)
(
0.00024)
(
0)
(
0.00015)
(
0)
(
0.00042)
­­

0.03
0
0
0
0
0
0
0.094
(
0)
(
0.00001)
(
0)
(
0)
(
0)
(
0.00002)
­­

Mice:
Resorptions
d
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
35
35
45
45
44
44
51
(
65)
(
65)
(
80)
(
80)
(
78)
(
78)
­­

5
7.1
7.1
8.9
8.9
8.9
8.9
19
(
13)
(
13)
(
16)
(
16)
(
16)
(
16)
­­

1
1.4
1.4
1.8
1.8
1.8
1.8
4.2
(
2.7)
(
2.7)
(
3.2)
(
3.2)
(
3.3)
(
3.3)
­­

0.5
0.72
0.72
0.89
0.89
0.89
0.89
2.1
(
1.3)
(
1.3)
(
1.6)
(
1.6)
(
1.6)
(
1.6)
­­

0.1
0.14
0.14
0.18
0.18
0.18
0.18
0.43
(
0.27)
(
0.27)
(
0.32)
(
0.32)
(
0.033)
(
0.033)
­­

0.03
0.043
0.043
0.054
0.054
0.053
0.053
0.13
(
0.08)
(
0.08)
(
0.096)
(
0.096)
(
0.098)
(
0.098)
­­

Mice:
Extra
Lumbar
Ribs
d
Kodell­
Kodell­
Rin
and
Dose(
c)
QLR
Weibull
QCR
CP
QLR
Weibull
Van
Ryzin
25
140
140
160
160
140
140
140
(
190)
(
190)
(
240)
(
240)
(
240)
(
240)
­­

5
29
29
31
31
30
30
34
(
41)
(
41)
(
48)
(
48)
(
52)
(
52)
­­

[
page
15571]
1
4.2
5.7
6.2
6.2
6.2
6.2
7.2
(
8.4)
(
8.4)
(
9.6)
(
9.5)
(
11)
(
11)
­­

0.5
1.1
2.8
3.1
3.1
3.1
3.1
3.6
(
4.2)
(
4.2)
(
4.8)
(
4.8)
(
5.4)
(
5.4)
­­

0.1
0
0.54
0.62
0.62
0.62
0.62
0.73
(
0.84)
(
0.84)
(
0.96)
(
0.95)
(
1.1)
(
1.1)
­­

0.03
0
0.16
0.19
0.19
0.19
0.19
0.22
(
0.25)
(
0.25)
(
0.29)
(
0.29)
(
0.32)
(
0.32)
­­

a
­
From
the
Crump
Report,
Ex.
5­
136.
The
models
considered
are
the
quantal
linear
regression
(
QLR)
model,
the
Weibull
model,
the
continuous
linear
regression
(
QCR)
model,
the
continuous
power
(
CP)
model,
two
cases
of
the
Kodell
model
­
the
Kodel­
QLR
model
and
the
Kodel­
Weibull
model,
and
the
Rai
and
Van
Ryzin
model.
The
number
in
parentheses
are
the
95%
upper
confidence
limit
on
risk.
No
95%
upper
confidence
limit
was
calculated
for
the
Rai
and
Van
Ryzin
model.
See
text
for
details
b
­
Dose
is
adjusted
by
a
factor
of
8/
6.
See
the
Crump
report
for
details
c
­
Data
from
Hanley
et
al,
Ex.
4­
042a
d
­
Data
from
Hanley
et
al,
Ex.
4­
106
Table
VI­
N
Estimates
of
Number
of
Extra
Cases
of
Various
Developmental
Effects
per
1000
Fetus
from
Exposure
to
2­
EE
a
Rats:
Minor
Skeletal
Defects
b
Dose
c
QLR
Weibull
5
0
1.8
(
0)
(
15)

1
0
0.065
(
0)
(
1.4)

0.5
0
0.015
(
0)
(
0.51)

0.25
0
0.0037
(
0)
(
0.19)

0.1
0
0.00056
(
0)
(
0.049)

Rats:
Minor
Visceral
Defects
b
Dose
c
QLR
Weibull
5
1.4
1.4
(
2.8)
(
2.8)

1
0.29
0.29
(
0.56)
(
0.56)

0.5
0.14
0.14
(
0.28)
(
0.28)

0.25
0.072
0.072
(
0.14)
(
0.14)

0.1
0.029
0.029
(
0.056)
(
0.056)

Rats:
Total
Abnormal
Ribs
b
Dose
c
QLR
Weibull
5
37
23
(
45)
(
44)

1
7.5
3.7
(
9.1)
(
8.9)

0.5
3.8
1.7
(
4.6)
(
4.5)

0.25
1.9
0.76
(
2.3)
(
2.2)

0.1
0.75
0.27
(
0.91)
(
0.9)

Rabbits:
Minor
Skeletal
Defects
d
Dose
c
QLR
Weibull
5
19
0
(
27)
(
21)

1
3.9
0
(
5.5)
(
4.3)

0.5
1.9
0
(
2.7)
(
2.2)

0.25
0.97
0
(
1.4)
(
1.1)

0.1
0.39
0
(
0.55)
(
0.43)
Rabbits:
Skeletal
Variants
d
Dose
c
QLR
Weibull
5
29
29
(
41)
(
41)

1
6
6
(
8.4)
(
8.4)

0.5
3
3
(
4.2)
(
4.2)

0.25
1.5
1.5
(
2.1)
(
2.1)

0.1
0.6
0.6
(
0.84)
(
0.84)

Rabbits:
Late
Intra­
uterine
Death
d
Dose
c
QLR
Weibull
5
0
0.0035
(
15)
(
15)

1
0
0.000022
(
3)
(
3)

0.5
0
0.000002
(
1.5)
(
1.5)

0.25
0
0
(
0.74)
(
0.74)

0.1
0
0
(
0.3)
(
0.3)

a
­
From
the
Crump
Report,
Ex.
5­
136.
The
models
considered
are
the
quantal
linear
regression
(
QLR)
model,
the
Weibull
model,
the
continuous
linear
regression
(
QCR)
model,
the
continuous
power
(
CP)
model,
two
cases
of
the
Kodell
model
­
the
Kodel­
QLR
model
and
the
Kodel­
Weibull
model,
and
the
Rai
and
Van
Ryzin
model.
The
number
in
parentheses
are
the
95%
upper
confidence
limit
on
risk.
No
95%
upper
confidence
limit
was
calculated
for
the
Rai
and
Van
Ryzin
model.
See
text
for
details
b
­
Dose
is
adjusted
by
a
factor
of
8/
6.
See
the
Crump
report
for
details
c
­
Data
from
Tinston
et
al,
Ex.
4­
038
d
­
Data
from
Tinston
et
al,
Ex.
4­
039
Crump
notes
that
although
the
maximum
likelihood
estimates
(
MLEs)
of
risk
are
similar
regardless
of
whether
one
accounts
for
the
litter
effect,
the
95%
upper
confidence
level
(
UCL)
can
be
noticeably
affected.
Crump
states
that
for
"
several
data
sets
for
which
the
maximum
likelihood
estimates
are
similar
when
estimated
by
the
QLR
(
or
Weibull)
model
and
the
Kodell­
QLR
(
or
Kodell­
Weibull)
model
(
e.
g.
extra
lumbar
ribs
in
mice,
for
which
the
intra­
litter
correlation
estimates
are
highest),
the
upper
limits
are
smaller
when
the
litter
effect
is
ignored."

For
2­
ME,
the
models
and
data
sets
predict
a
range
of
risks
of
developmental
effects
from
2.2
to
430
per
1000
fetuses
at
the
current
OSHA
PEL
of
25
ppm.
The
lowest
risk
comes
from
the
Weibull
model
applied
to
data
on
total
major
malformations
in
rabbits.
The
highest
risk
comes
from
the
QLR
model
applied
to
these
same
data.
Crump
attributes
this
large
spread
within
the
same
data
set
to
the
non­
linearity
of
the
dose­
response
relationship
and
"
the
lack
of
experimental
evidence
regarding
the
dose­
response
curve
between
10
and
50
ppm."
Crump
concludes
that
if
"
there
had
been
an
additional
experimental
exposure
between
10
ppm
and
50
ppm,
the
difference
among
the
models
would
likely
have
been
sharply
reduced."

For
2­
EE,
Crump
did
not
estimate
risks
at
the
current
OSHA
PEL
of
200
ppm.
The
highest
dose
level
which
Crump
considered
for
its
analysis
of
2­
EE
was
5
ppm.
At
this
exposure
level,
the
models
and
data
sets
predict
a
range
of
risk
of
developmental
effects
from
0
to
37
per
1000
fetuses.
The
lowest
risk
comes
from
the
QLR
model
applied
to
data
on
minor
skeletal
defects
in
rats.
The
highest
risk
comes
from
the
same
[
page
15572]

model
applied
to
data
on
total
abnormal
ribs
in
rats.

At
0.1
ppm,
Table
VI­
M
shows
that
the
predicted
risks
of
developmental
effects
range
from
0
to
.67
per
1000
fetuses
when
derived
from
models
which
incorporate
thresholds
and
from
approximately
zero
to
1.1
per
1000
fetuses
when
derived
from
models
which
do
not
incorporate
thresholds.
At
0.5
ppm,
Table
VI­
N
shows
that
the
predicted
risks
of
developmental
effects
range
from
0
to
3
per
1000
fetuses
when
derived
from
the
model
which
incorporates
a
threshold
and
from
approximately
zero
to
3
per
1000
fetuses
when
derived
from
the
model
which
does
not
incorporate
a
threshold
Although
Crump's
approach
provides
methods
for
quantifying
reproductive
and
developmental
risks,
none
of
the
methods
proposed
in
the
report
has
been
generally
accepted
within
the
risk
assessment
community.
The
NOEL/
uncertainty
factor
approach,
on
the
other
hand,
has
broad
acceptance
for
the
assessment
of
reproductive
and
developmental
risks.
Furthermore,
Crump's
risk
assessment
provides
no
criteria
for
selecting
one
model
or
method
over
another.
Since
none
of
the
models
has
a
biological
basis,
it
is
impossible
to
determine
which
is
the
most
appropriate
model
to
use.
Given
the
broad
range
of
risks
predicted
from
each
of
the
models,
some
criteria
must
be
developed
for
choosing
one
or
another
before
Crump's
approach
can
be
used
for
quantitative
risk
assessment.
For
these
reasons,
OSHA
has
not
relied
upon
the
Crump
report
as
the
basis
of
its
quantitative
risk
assessment
for
glycol
ethers
Crump 
s
risk
assessment
raises
a
number
of
issues
including
whether
developmental
and
reproductive
risks
can
be
quantified
and
these
issues
deserve
serious
discussion.
In
addition
to
proposing
dose­
response
models
for
quantifying
the
risk
of
developmental
effects,
Crump
has
proposed
two
alternatives,
the
NOSTASOT
dose
and
the
benchmark
dose,
to
the
traditional
NOEL
used
by
OSHA
in
its
risk
assessment.
OSHA
seeks
comment
on
the
issues
raised
in
this
report
as
well
as
on
the
specific
methodology
employed
by
Crump
to
quantify
the
risk
of
adverse
reproductive
and
developmental
effects
2.
The
Hattis
Risk
Assessment
In
an
attempt
to
quantify
the
reproductive
and
developmental
risks
associated
with
glycol
ethers
exposure,
Dale
Hattis
et
al
developed
three
quantitative
approaches:
one
for
estimating
the
risks
of
adverse
effects
on
male
fertility
(
Ex.
5­
109);
one
for
estimating
the
risks
of
adverse
developmental
outcomes
(
Ex.
5­
121);
and
one
for
estimating
the
risks
of
infant
mortality
(
Ex.
5­
121).
To
estimate
risks
on
male
fertility,
sperm
counts
and
pharmacokinetically­
derived
exposures
from
workers
exposed
to
2­
ME
and
2­
EE
were
used
as
a
basis
for
estimating
percentage
reductions
in
fertility.
Animal
studies
in
which
2­
ME
and
2­
EE
induced
fetal
death
and
fetal
malformations
were
used
as
a
basis
for
estimating
the
risk
of
adverse
developmental
outcomes
in
human
fetuses.
Animal
studies
in
which
2­
ME
and
2­
EE
induced
fetal
weight
reduction
were
used
as
a
basis
for
estimating
the
risk
of
infant
mortality
in
humans.
The
following
discussion
briefly
summarizes
these
approaches.
For
a
more
complete
description
of
these
analyses
and
the
underlying
assumptions,
the
original
studies
should
be
consulted
a.
Risk
Analysis
on
Male
Fertility
Effects
(
Ex.
5­
109)

The
goal
of
this
analysis
was
to
quantify
the
effects
on
male
fertility
that
could
be
expected
from
reductions
of
sperm
counts
induced
by
2­
EE
and
2­
ME.
Thus
sperm
count
was
the
basic
measure
used
to
calculate
a
risk
of
infertility.
The
authors
acknowledged
that
sperm
counts
are
not
ideal
for
this
purpose
because
sperm
counts
are
only
one
of
several
parameters
(
e.
g.
%
normal
sperm,
%
motile
sperm,
and
age
of
patient)
that
are
known
to
have
an
effect
on
male
reproductive
potential.
In
addition
the
authors
stated
that
a
direct
relationship
between
sperm
count
and
male
fertility
performance
may
be
an
over
simplification.
However
the
authors
chose
sperm
counts
because
no
other
type
of
sperm
quality
parameters
were
available
in
the
underlying
data
used
for
this
quantitative
analysis
The
sources
of
experimental
data
used
in
this
analysis
included
(
1)
a
pharmacokinetic
model
developed
by
Hattis
et
al
for
2­
EE
(
Ex.
5­
095),
(
2)
worker
exposure
studies
on
shipyard
painters
(
Exs.
5­
101,
5­
102
and
5­
103)
and
foundry
workers
(
Ex.
5­
003)
and
(
3)
a
quantitative
model
developed
by
Meistrich
(
Ex.
4­
161)
for
estimating
sperm
reduction
factors
and
increases
in
excess
infertility
In
their
pharmacokinetic
analysis
(
Ex.
5­
095),
Hattis
et
al
developed
four
different
pharmacokinetic
models
using
clinical
data
from
studies
in
which
human
volunteers
were
exposed
to
2­
EE.
These
models
described
the
uptake
and
metabolism
of
2­
EE
to
its
primary
metabolite
ethoxyacetic
acid
(
EAA).
The
models
also
described
the
urinary
excretion
of
EAA.
Mathematical
formulas
derived
from
these
models
were
presented
as
a
means
for
calculating
2­
EE
equivalent
air
exposure
levels
from
urinary
EAA
excretion
data
As
a
first
step
in
the
risk
analysis,
urinary
EAA
excretion
data
from
the
foundry
workers
and
the
shipyard
painters
were
converted
to
2­
EE
equivalent
air
exposures
(
ppm)
using
the
formulas
derived
from
the
Hattis
et
al
pharmacokinetic
model.
The
authors
noted
that
the
shipyard
painters
also
had
"
appreciable"
exposures
to
2­
ME.
Thus
2­
EE
equivalents
for
these
workers
were
adjusted
to
account
for
2­
ME.
This
was
accomplished
by
assuming
that
2­
ME
was
4.3
times
more
potent
than
2­
EE
(
based
on
animal
studies
)
and
that
workers
were
exposed
to
0.8
ppm
2­
ME
for
every
2.6
ppm
2­
EE
In
the
second
step
of
this
analysis,
sperm
counts
were
analyzed
and
found
to
decline
among
both
sets
of
workers
although
neither
of
the
observations
from
these
groups
was
statistically
significant.
The
percent
reduction
in
sperm
count
for
these
groups
of
workers
was
then
compared
to
the
calculated
2­
EE
equivalents
air
levels:

2­
EE
equivalent
Overall
%

(
ppm­
8
Hr/
day)
Sperm
Count
Reduction
Shipyard
Painters
Arithmetic
Mean
6.1
27.5
Geometric
Mean
4.9
Foundry
workers
Arithmetic
Mean
13.9
14
Geometric
Mean
12.8
The
authors
noted
that
results
from
both
of
these
studies
reinforced
one
another
showing
suggestive
declines
in
sperm
counts
with
2­
EE
exposure.
However
these
results
indicate
that
there
is
a
stronger
sperm
reduction
effect
with
lower
dose
among
the
shipyard
painters.
Possible
explanations
offered
by
the
authors
included
(
1)
chance
statistical
fluctuations
in
the
data
and
(
2)
potential
peak
exposures
prior
to
sampling
the
population.
Nevertheless,
the
shipyard
painter
data
was
selected
for
the
authors
"
best
estimate"
risk
projections
as
this
study
had
more
complete
exposure
data
and
a
larger
number
of
workers,
making
this
study
"
more
likely
representative
of
reality"
In
the
final
step
in
this
analysis,
work
by
Meistrich
(
Ex.
4­
161)
was
applied
to
sperm
count
reductions
calculated
in
[
page
15573]

the
previous
steps
to
estimate
an
"
excess
infertility
risk".
Meistrich
developed
a
method,
using
testicular
toxicity
data
in
rats
and
analyses
of
sperm
count
distributions
in
"
fertile"
and
"
infertile"
couples,
to
calculate
the
"
risk
of
infertility"
as
a
function
of
sperm
count.
In
his
model
Meistrich
defined
infertility
as
the
degree
of
subfertility
required
to
bring
about
a
need
to
consult
a
physician.
Meistrich
assumed
that
a
1%
increase
in
infertility
(
i.
e.
1
in
100
couples)
was
an
"
acceptable
risk".
He
also
assumed
that
the
background
risk
of
infertility
in
the
general
population
was
15%.
Using
these
assumptions
and
definitions,
Meistrich
estimated
that
a
1%
increase
in
excess
infertility
corresponds
to
a
sperm
reduction
factor
of
1.24.
Using
this
basic
relationship,
Hattis
et
al.
calculated
sperm
reduction
factors
and
corresponding
increases
in
excess
infertility
for
the
sperm
count
reductions
observed
among
the
shipyard
painters
at
various
2­
EE
equivalent
air
exposures:

Geometric
Mean
%
sperm
count
reduction
excess
dose
(
ppm)
reduction
factor
infer­

8
Hr­
TWA
tility
0.89
5.70
1.06
0.25%

1.72
10.80
1.12
0.50%

3.28
19.40
1.24
1.00%

4.9
27.5
1.38
1.58%

5.97
32.40
1.48
2.00%

Based
on
the
results
of
this
analysis
Hattis
concluded
that
in
order
to
achieve
a
goal
of
having
no
more
than
1
in
100
couples
(
i.
e.
1%)
suffering
"
infertility",
exposures
to
2­
EE
must
be
kept
below
a
geometric
mean
of
3.3
ppm.
Achieving
a
goal
of
no
more
than
1
in
400
couples
suffering
infertility
would
require
exposures
1/
4
of
that
level
(
i.
e.
0.82
ppm).
Furthermore
assuming
that
2­
ME
is
4.3
times
more
potent
than
2­
EE,
Hattis
estimates
that
a
corresponding
dose
for
2­
ME
of
0.46
ppm
would
be
required
to
assure
that
no
more
than
1
in
100
couples
will
suffer
from
infertility
These
quantitative
estimates
must
be
viewed
in
light
of
the
uncertainties
and
assumptions
used
to
calculate
them.
First,
both
the
shipyard
painter
and
foundry
worker
studies
had
a
small
number
of
exposed
workers
with
sperm
count
reductions
bordering
on
statistical
significance.
Furthermore,
as
noted
by
Hattis
et
al,
as
well
as
the
original
authors
of
the
shipyard
painter
studies,
the
EAA
excretion
levels
calculated
from
these
may
be
a
poor
proxy
for
exposures
associated
with
sperm
count
reduction.
The
EAA
excretion
levels
represented
exposure
to
2­
EE
in
the
last
few
days
whereas
the
sperm
counts
which
were
measured
at
approximately
the
same
time.
would
have
been
effected
by
exposures
weeks
earlier.
Because
the
shipyard
painters
changed
tasks
at
the
shipyard
frequently,
EAA
excretion
levels
representing
these
workers'
exposure
within
the
last
few
days
may
not
adequately
represent
exposure
levels
weeks
earlier
which
would
have
been
responsible
for
the
sperm
counts
collected
Second,
the
Meistrich
approach
for
calculating
sperm
reduction
factors
assumes
a
"
onehit
killing
function
for
sperm
which
may
or
may
not
be
biologically
correct.
Furthermore
Meistrich
uses
a
very
subjective
definition
of
infertility
(
i.
e.
degree
of
subfertility
required
to
bring
about
the
need
to
consult
a
physician)

These
sources
of
uncertainty
are
compounded
by
the
uncertainty
of
the
2­
EE
air
equivalents
which
were
calculated
using
the
Hattis
pharmacokinetic
model.
This
pharmacokinetic
model
carries
with
it
its
own
set
of
assumptions
and
uncertainties.
Thus
considerable
uncertainty
is
associated
with
the
quantitative
estimates
derived
from
this
risk
analysis
on
male
fertility
b.
Risk
Analysis
on
Developmental
Effects
(
Ex.
5­
121)

The
goal
of
this
analysis
was
to
quantify
the
risk
of
adverse
developmental
effects
associated
with
in
utero
exposure
to
glycol
ethers.
Two
separate
approaches
were
employed.
In
the
first
approach,
quantal
effects
data
from
animal
studies
(
e.
g.
fetal
death
and
malformations)
were
used
to
estimate
the
risk
of
similar
adverse
effects
in
humans.
In
the
second
approach,
continuous
effects
data
from
animal
studies
(
e.
g.
changes
in
fetal
weight)
were
used
to
project
changes
in
birth
weight
and
potential
changes
in
infant
mortality
in
humans.
Quantal
Effects
Analysis
Hattis
et
al
selected
six
different
animal
studies
examining
the
developmental
toxicity
of
various
glycol
ethers.
[
Andrew
and
Hardin
(
Ex.
5­
069),
Doe
(
Ex.
5­
0710,
Hardin
and
Eisenmann
(
Ex.
5­
097),
Weir
(
Ex.
5­
120),
Greene
(
Ex.
5­
096),
and
Hanley
et
al
(
Ex.
4­
120)].
These
studies
reported
statistically
significant
increases
in
the
incidence
of
adverse
developmental
effects
including
fetal
death,
skeletal
defects,
external
malformations
and
digit
or
limb
malformations.
Dose
response
data
from
the
animal
studies
were
used
to
calculate
an
ED50
for
those
effects
which
were
statistically
significantly
different
from
the
controls.
An
ED50
is
the
dose
at
which
50%
of
an
otherwise
unaffected
proportion
of
the
population
suffers
an
effect.
The
ED50
was
derived
using
a
log­
probit
analysis.
This
probit
analysis
assumes
that
effects
occur
in
individual
animals
when
specific
thresholds
of
dose
are
exceeded
and
that
there
is
a
lognormal
distribution
of
thresholds
in
the
exposed
group
of
animals
or
humans.
ED50s
from
the
animal
studies
were
then
converted
to
8
hour
human
ED50s
(
ppm).
This
ED50
represents
a
dose
at
which
50%
of
an
population
will
be
affected
by
the
chemical
after
an
8
hour
exposure.
Overall
ED50
estimates
were
derived
by
taking
geometric
means
of
ED50s
calculated
for
2­
ME
and
2­
EE
for
individual
effects.
Six
"
best
estimates"
were
derived
in
this
manner.
These
"
best
estimates"
were
then
used
to
calculate
the
doses
of
2­
ME
or
2­
EE
corresponding
to
risks
of
one
in
a
hundred
(
10­
2),
one
in
ten
thousand
(
10­
4)
and
one
in
a
million
(
10­
6)
for
a
particular
developmental
effect
(
Table
VI­
O)

TABLE
VI­
O
Doses
(
ppm)
at
"
Best
Estimate"
Risks
of
One
in
a
Hundred,

One
in
Ten
Thousand,
and
One
in
a
Million
ED50
Dose
Dose
Dose
Response
humans
(
ppm)
(
ppm)
(
ppm)

8
hr(
ppm)
at
10­
2
at
10­
4
at
10­
6
risk
risk
risk
post
implantation
loss
2­
EE
127
8.7
1.8
0.53
2­
ME
16
1.1
0.22
0.067
minor
skeletal
defects
2­
EE
5.3
0.36
0.073
0.022
malformations
2­
EE
"
external"
255
17
3.5
1.1
2­
ME
"
total"
9.9
0.68
0.14
0.042
[
page
15574]
"
forepaw"
35
2.4
0.48
0.147
Extracted
from
Table
3­
7,
Hattis
et
al,
(
Ex.
5­
121)

Assuming
that
a
ppm
exposure
in
humans
would
present
the
same
risk
as
those
observed
in
animals,
Hattis
et
al
concluded
that
these
projections
suggest
that
doses
as
low
as
0.36
ppm
2­
EE
would
produce
a
risk
of
one
in
a
hundred
for
skeletal
defects
and
doses
as
low
as
0.68
ppm
2­
ME
would
produce
a
risk
of
one
in
a
hundred
for
total
malformations.
It
is
interesting
to
note
that
from
these
two
estimates
2­
ME
appears
to
be
less
potent
than
2­
EE
which
is
contrary
to
most
of
the
experimental
data
Continuous
Effects
Analysis
In
this
analysis
animal
data
showing
fetal
weight
reduction
after
exposure
to
2­
ME
and
2­
EE
were
used
to
calculate
percentage
reductions
in
fetal
weight
as
a
function
of
dose
of
2­
ME
or
2­
EE.
For
purposes
of
this
analysis
it
was
assumed
that
animals
and
humans
would
exhibit
equal
growth
retardation
for
a
given
rate
of
glycol
ether
exposures
expressed
in
ppm­
hours
per
day.
It
was
further
assumed
that
percentage
changes
in
fetal
weight
prior
to
birth
would
reflect
similar
percentage
changes
in
birth
weight.
Percentage
reductions
in
birth
weight
could
then
be
used
to
project
likely
effects
on
infant
mortality
As
a
first
step,
Hattis
et
al
analyzed
birth
weight
distributions
and
infant
mortality
rates
from
both
black
and
white
infants
in
the
United
States
.
These
distributions
were
used
to
derive
a
relationship
between
infant
mortality
and
birth
weight
changes
As
a
second
step,
the
relationship
between
fetal
weight
reduction
(
i.
e.
birth
weight
reduction)
and
the
dose
of
2­
ME
or
2­
EE
from
the
animal
studies
were
combined
with
the
relationship
between
birth
weight
changes
and
infant
mortality
from
human
infants.
These
two
sets
of
relationships
were
used
together
to
estimate
expected
changes
in
infant
mortality
for
a
given
8
hour
exposure
to
2­
EE
or
2­
ME.
Table
VI­
P
presents
the
projected
changes
in
infant
mortality
due
to
possible
changes
in
infant
birth
weight
associated
with
2­
EE
and
2­
ME
exposures
TABLE
VI­
P
Projected
Changes
in
Infant
Mortality
Due
to
possible
Changes
in
Infant
Birth
Weights
Associated
with
2­
ME
and
2­
EE
Exposures
PPM
Exposure
Projected
%
Total
Excess
Level
Birthwt
Reduction
Infant
Mortality
2­
EE:

0.01
.0003
1.45
x
10­
7
0.1
.003
1.45
x
10­
6
1
.03
1.45
x
10­
5
5
.15
7.3
x
10­
5
25
.75
3.7
x
10­
4
2­
ME:

0.01
.00243
1.18
x
10­
6
0.1
.0243
1.18
x
10­
5
1
.243
1.18
x
10­
4
5
1.215
6.1
x
10­
4
25
6.075
3.6
x
10­
3
Extracted
from
Table
4­
6,
Hattis
et
al
(
Ex.
5­
121)
As
was
the
case
for
the
male
fertility
analysis,
the
quantitative
estimates
derived
from
both
the
quantal
and
continuous
effects
data
incorporate
a
number
of
large
assumptions.
The
largest
of
these
may
be
the
assumption
that
a
particular
defect
observed
in
an
animal
will
translate
into
a
similar
defect
in
humans.
As
discussed
earlier
in
the
Health
Effects
section
of
this
preamble,
although
adverse
developmental
effects
in
animals
provide
clear
evidence
of
a
chemical's
potential
ability
to
perturb
development
in
humans,
the
effects
observed
in
animals
may
not
necessarily
be
identical
to
those
which
could
potentially
occur
in
humans.
Even
the
authors
themselves
acknowledge
that
the
risk
calculations
are
based
on
a
series
of
assumptions
which
carry
considerable
uncertainty.
OSHA
acknowledges
that
assumptions
are
often
necessary
for
quantitative
risk
analyses.
However
given
the
lack
of
knowledge
about
the
biological
processes
involved
in
reproductive
and
developmental
toxicity,
OSHA
believes
that
the
assumptions
of
these
quantitative
analyses
may
carry
much
more
uncertainty
than
for
other
types
of
health
outcomes
such
as
cancer
where
the
biological
mechanisms
are
better
understood
In
summary,
the
quantitative
approaches
of
Hattis
et
al
are
very
innovative.
These
approaches
however,
require
that
a
number
of
large
assumptions
be
made.
These
assumptions
create
considerable
uncertainty
in
the
quantitative
risk
estimates
which
are
derived.
In
addition,
the
underlying
data
upon
which
these
approaches
are
constructed
have
weaknesses
of
their
own
which
further
compound
the
uncertainties
in
the
risk
estimates.
Nevertheless,
these
approaches
do
provide
a
starting
point
for
a
discussion
of
the
quantitative
risk
assessment
for
reproductive
and
developmental
toxins.
Therefore
OSHA
welcomes
all
comments
and
analyses
on
these
approaches
for
deriving
quantitative
risk
estimates
for
adverse
reproductive
and
developmental
effects
3.
The
Environ
Risk
Assessment
Under
contract
to
the
Chemical
Manufacturer's
Association
(
CMA),
Environ
Corporation
prepared
a
report
entitled
"
Scientific
Basis
for
Safety
Factors
Needed
to
Protect
Workers
from
Reproductive
Toxicities
of
Glycol
Ethers"
(
Ex.
4­
016f).
This
report
contains
a
brief
review
of
the
data
available
for
a
qualitative
analysis
of
the
health
effects
associated
with
glycol
ethers
and
their
acetates,
but
the
primary
focus
of
the
report
is
the
choice
of
uncertainty
factor
for
determining
an
acceptable
daily
intake
(
ADI)
for
each
of
the
substances
Environ's
approach
for
choosing
an
uncertainty
factor,
(
which
Environ
refers
to
as
a
safety
factor),
was
to
compare
the
lowest
effective
dose
(
i.
e.
the
LOEL)
in
humans
measured
in
milligrams
per
kilogram
per
day
for
ten
substances
known
to
cause
developmental
effects
with
the
lowest
effective
dose
measured
in
milligrams
per
kilogram
per
day
in
the
most
sensitive
species
of
animal
in
which
the
substance
has
been
tested
and
in
which
the
observed
effects
were
similar
to
those
in
humans.
These
data
come
from
two
sources:
a
1981
report
from
the
Council
on
Environmental
Quality
(
CEQ)
entitled
"
Chemical
Hazards
to
Human
Reproduction"
and
a
1984
report
from
the
National
Center
for
Toxicological
Research
(
NCTR)
entitled
"
Reliability
of
Experimental
Studies
for
Prediction
of
Hazards
to
Human
Development."
By
examining
these
data
on
other
developmental
toxicants,
[
page
15575]

Environ
sought
to
obtain
information
which
could
be
"
useful
for
judging
the
magnitude
of
the
uncertainty
factor
needed
to
protect
humans
from
the
developmental
effects
of
[
glycol
ethers]."

Environ
drew
two
conclusions
from
its
analysis:

1.
Application
of
a
safety
factor
of
10
to
NOELs
from
the
most
sensitive
animal
species
would
have
been
adequate
to
protect
humans
from
the
effects
of
most
developmental
toxicants
for
which
quantitative
doseresponse
data
are
available;
and
2.
A
safety
factor
of
50,
similarly
applied,
would
have
been
adequate
to
protect
humans
from
the
effects
of
all
developmental
toxicants
for
which
quantitative
human
dose­
response
data
are
available,
although
this
factor
may
not
have
been
adequate
for
one
substance,
thalidomide,
assuming
the
rabbit
(
rather
than
the
most
sensitive
species)
had
been
chosen
as
the
basis
for
establishing
acceptable
human
exposures.
If
the
most
sensitive
species
had
been
chosen
for
thalidomide,
a
safety
factor
of
10­
20
would
have
been
adequate
Environ
supplemented
this
approach
with
an
examination
of
historical
precedents
for
the
selection
of
uncertainty
factors
used
to
protect
worker
populations
from
the
types
of
toxicity
associated
with
glycol
ethers
or
from
other
serious
forms
of
toxicity.
Environ
stated
that
such
information,
"
while
not
strictly
scientific
in
nature,
can
further
assist
decision­
making
because
it
reveals
the
range
of
safety
margins
which
other
responsible
decision­
makers
have
accepted,
and
presumably
reveals
the
safety
margins
that
have
proved
adequate
to
protect
worker
populations.
Information
on
the
expected
relative
susceptibilities
of
the
worker
and
the
general
populations
and
on
how
this
has
influenced
the
selection
of
safety
factors
will
also
be
useful."

Environ
looked
at
the
guidelines
or
standards
for
protecting
workers
from
reproductive
hazards
developed
by
OSHA,
NIOSH,
ACGIH,
and
the
American
Industrial
Hygiene
Association
(
AIHA)
"
in
order
to
provide
an
estimation
of
the
margin
of
safety
associated
with
[
their]
standards
and
guidelines."
Environ
noted
that
"[
u]
nlike
the
case
of
standards
developed
for
general
population
exposure
to
chemicals,
[
for
worker
populations]
there
has
been
no
generic
approach
we
can
identify
for
the
application
of
safety
factors
to
the
NOEL
identified
in
experimental
animals.
This
is
true
for
both
reproductive
and
other
non­
carcinogenic
effects."

Environ
found
that
as
of
1985,
the
date
of
the
Environ
report,
OSHA
had
regulated
five
substance
principally
on
the
basis
of
reproductive
toxicity.
These
substances
and
their
respective
margins
of
safety
were
carbaryl,
5
times
lower
than
the
NOEL
identified
in
animals;
carbon
disulfide,
1.3
times
higher
than
the
LOEL
identified
in
animals;
DBCP,
38
times
lower
than
the
NOEL
identified
in
animals;
chloroprene,
5
to
25
times
higher
than
the
LOEL
identified
in
humans;
and
PCBs,
6
times
lower
than
the
LOEL
identified
in
humans.
(
OSHA
notes
that
the
Environ
report
was
written
prior
to
promulgation
of
OSHA's
Final
Rule
for
Air
Contaminants,
29
CFR
Part
1910,
published
January
19,
1989.
In
that
rulemaking,
OSHA
reduced
the
permissible
exposure
limits
for
both
carbon
disulfide
and
chloroprene.)
In
comparison,
Environ
found
that
NIOSH
used
uncertainty
factors
in
its
recommended
standards
for
the
same
five
substances
ranging
from
1
for
a
15
minute
exposure
ceiling
for
chloroprene
to
6000
for
PCBs.
The
ACGIH
had
issued
TLVs
for
all
these
substances
except
DBCP,
and
these
TLVs
ranged
from
2
to
10
times
higher
than
the
LOEL
identified
in
humans
for
chloroprene
to
6
times
lower
than
the
LOEL
identified
in
animals
for
PCBs.
According
to
Environ,
the
AIHA
had
established
a
workplace
environmental
exposure
level
only
for
the
reproductive
toxicant
piperidine,
and
in
making
its
recommendation,
the
AIHA
provided
no
margin
of
safety
below
the
NOEL
for
embryotoxicity
in
the
rat
On
the
basis
of
its
analysis
of
the
CEQ
data,
the
NCTR
data,
and
historical
precedent,
Environ
concludes
that
"
the
100­
fold
[
safety]
factor
has
not
been
used
for
worker
protection"
and
"
there
is
support
for
a
safety
factor
of
10
as
adequate
to
protect
workers
against
the
developmental
toxicities
of
the
[
glycol
ethers
and
their
acetates]."
Environ
goes
on
to
note
that
a
safety
factor
of
10
"
appears
to
be
adequate
to
cover
most
cases
and
it
also
accords
with
most
past
occupational
risk
management
practices.
If
one
seeks
a
margin
that
has
limited
historical
precedent
but
which
appears
more
certain
to
cover
all
likely
cases,
then
a
factor
of
50
is
recommended."

Noting
that
the
factors
10
and
50
are
not
alternatives
and
that
"
it
may
be
reasonable
to
settle
on
a
factor
between
these
two
values",
Environ
applied
these
two
uncertainty
factors
to
the
NOELs
identified
for
the
glycol
ethers
and
their
acetates.
In
its
review
of
the
literature,
Environ,
like
OSHA,
found
the
NOELs
to
be
10
ppm
for
2­
ME,
10
ppm
for
2­
MEA,
50
ppm
for
2­
EE,
and
50
ppm
for
2­
EEA.
(
Environ
found
no
data
on
the
reproductive
effects
of
2­
MEA,
and
like
OSHA,
used
the
NOEL
identified
for
2­
ME
to
estimate
the
ADI
for
2­
MEA.)
In
its
estimation
of
the
ADI's,
however,
Environ
took
a
different
approach.
First,
that
species
most
sensitive
to
the
effects
of
the
glycol
ethers
or
their
acetates
was
identified.
In
each
case,
this
was
found
to
be
the
rabbit.
Next,
the
NOEL
was
converted
from
units
of
ppm
to
units
of
milligrams
per
kilogram
per
day.
Then,
the
safety
factors
of
10
or
50
were
applied
to
the
converted
NOEL
to
arrive
at
two
estimates
of
the
ADI.
These
estimates,
in
turn,
were
converted
back
to
units
of
ppm
assuming
human
parameters.
Results
of
these
calculations
are
presented
in
Table
VI­
Q
Table
VI­
Q
Estimates
of
Acceptable
Human
Daily
Intakes
(
ADIs)

Of
Four
Glycol
Ethers
Based
on
Animal
Data
and
Safety
Factors
of
10
and
50
a
Glycol
NOEL
b
ADI/
10
c
ADI/
50
d
ADI/
10
e
ADI/
50
f
Ether
mg/
kg/
d
Species
mg/
kg/
d
mg/
kg/
d
ppm
ppm
2­
ME
4.3
Rabbit
0.43
0.086
0.9
0.18
2­
EE
25.5
Rabbit
2.6
0.52
4.6
0.92
2­
MEA
6.7
g
0.67
0.13
0.9
0.18
2­
EEA
18.8
Rabbit
2.6
0.52
4.6
0.92
a
­
From
the
Environ
Report
(
Ex.
4­
016f)
b
­
The
NOEL
identified
in
the
most
sensitive
species
converted
from
units
of
ppm
to
units
of
milligram
per
kilogram
per
day
c
­
ADI
based
on
a
safety
factor
of
10
and
measured
in
units
of
milligrams
per
kilograms
per
day
d
­
ADI
based
on
a
safety
factor
of
50
and
measured
in
units
of
milligrams
per
kilograms
per
day
e
­
ADI
based
on
a
safety
factor
of
10
and
measured
in
units
of
ppm
as
an
8
hour
time
weighted
average
f
­
ADI
based
on
a
safety
factor
of
50
and
measured
in
units
of
ppm
as
an
8
hour
time
weighted
average
g
­
No
data
available.
Assumes
2­
MEA
is
equipotent
with
2­
ME
on
a
mole
basis.

[
page
15576]

The
interesting
result
in
Table
VI­
Q
is
that
the
ADIs
estimated
by
Environ
using
a
uncertainty
factor
of
50
are
not
very
different
than
the
ADIs
estimated
by
OSHA
using
an
uncertainty
factor
of
100
without
conversion
of
the
NOEL
to
milligrams
per
kilogram
per
day.
For
2­
ME
and
2­
MEA,
Environ
found
the
ADI
to
be
0.18
ppm
whereas
OSHA
found
the
ADI
to
be
0.1
ppm.
For
2­
EE
and
2­
EEA,
Environ
found
the
ADI
to
be
0.92
ppm
whereas
OSHA
found
the
ADI
to
be
0.5
ppm.
Obviously,
the
results
are
not
so
similar
when
an
uncertainty
factor
of
10
is
used
Despite
the
similarity
in
results,
OSHA
has
a
number
of
concerns
about
the
approach
used
by
Environ
to
estimate
the
ADI
for
the
glycol
ethers
and
their
acetates.
First
of
all,
OSHA
questions
the
appropriateness
of
using
the
CEQ
data
and
the
NCTR
data
to
establish
the
magnitude
of
safety
factors
needed
to
protect
humans
from
the
developmental
effects
of
glycol
ethers.
Environ
acknowledges
a
number
of
the
data's
limitations
including
the
varying
quality
and
extensiveness
of
the
data
bases
from
which
these
data
were
drawn,
the
subjective
determination
regarding
the
meaning
of
the
term
"
lowest
effective
dose",
the
relatively
small
number
of
compounds
examined,
and
the
difficulty
of
obtaining
accurate
estimates
of
the
human
doses
responsible
for
producing
developmental
toxicity
OSHA
believes
that
these
limitations
alone
make
these
data
unsuitable
for
the
use
to
which
Environ
has
put
them.
OSHA,
however,
sees
additional
limitations.
Environ
is
comparing
experimental
LOELs
in
the
most
sensitive
species
to
LOELs
observed
in
humans
to
determine
adequate
safety
factors.
Implicit
in
this
approach
is
the
assumption
that
experimental
LOELs
are
the
"
true"
LOELs
and
that
any
exposure
below
that
LOEL
for
either
humans
or
animals
will
not
result
in
adverse
effects.
As
noted
in
a
previous
section
of
this
risk
assessment,
there
is
in
fact
little
reason
to
believe
that
the
LOEL
(
or
NOEL)
identified
in
any
study
is
indeed
the
"
true"
LOEL.
Environ's
approach
makes
no
allowance
for
such
a
possibility
Another
limitation
which
Environ
acknowledges
is
that
it
is
not
known
whether
the
empirical
relationships
observed
in
the
data
reflect
only
interspecies
differences
or
whether
they
reflect
both
interspecies
differences
and
intraspecies
differences.
Environ
concludes
that
it
"
seems
likely
although
it
is
not
certain,
that
the
empirical
relations
discussed
above
would
be
protective
of
the
most
sensitive
members
of
the
human
population",
but
OSHA
notes
that
the
opposite
conclusion
could
just
as
easily
be
drawn.
If
the
human
data
represent
responses
for
the
mid­
range
of
the
distribution
of
human
responses,
then,
as
Environ
states,
"
the
empirical
relations
reflect
only
interspecies
differences,
and
an
additional
safety
factor
would
seem
necessary
to
compensate
for
intraspecies
variability."

OSHA
is
also
concerned
about
Environ's
use
of
historical
precedent
to
determine
the
margin
of
safety
acceptable
for
protecting
worker
populations.
Of
the
five
substances
reported
by
Environ
to
have
been
regulated
by
OSHA
on
the
basis
of
reproductive
toxicity,
all
but
one,
DBCP,
were
adopted
as
consensus
standards
by
the
Agency
in
1971
under
Section
6(
a)
of
the
Occupational
Safety
and
Health
Act
of
1970.
Under
that
Section
of
the
Act,
Congress
directed
the
Agency
to
"
promulgate
as
an
occupational
safety
and
health
standard
any
national
consensus
standard,
and
any
established
Federal
standard,
unless
[
the
Secretary
of
Labor]
determines
that
the
promulgation
of
such
a
standard
would
not
result
in
improved
safety
or
health
for
specifically
designated
employees"
(
29
U.
S.
C.
651
et
seq).
In
the
case
of
DBCP,
the
only
one
of
the
five
substances
to
be
considered
individually
in
a
6(
b)
rulemaking,
the
standard
set
by
OSHA,
as
Environ
acknowledges,
was
constrained
by
technological
feasibility
and
not
by
acceptable
margin
of
safety.
In
as
much
as
standards
for
four
of
these
substances
were
adopted
without
consideration
of
the
individual
substance
and
the
standard
for
the
fifth
was
constrained
by
technological
feasibility,
it
is
disingenuous
of
Environ
to
conclude
that
OSHA
finds
any
particular
margin
of
safety
as
acceptable
for
working
populations
Finally,
OSHA
questions
the
appropriateness
of
Environ's
conversion
of
NOELs
from
units
of
ppm
to
units
of
milligrams
per
kilograms
per
day
to
estimate
an
ADI.
On
the
one
hand,
Environ
states
that
with
regard
to
interspecies
differences,
"
the
available
data
on
the
ethers
show
a
remarkably
consistent
pattern
among
the
species
tested.
This
suggests
that
the
10­
fold
factor
conventionally
used
for
interspecies
extrapolation
is
not
indicated."
On
the
other
hand,
when
the
NOEL
is
converted
into
units
of
milligrams
per
kilogram
per
day,
this
"
remarkable"
consistency
vanishes.
For
example,
for
2­
ME,
Environ
found
that
a
NOEL
of
10
ppm
in
rabbits
corresponds
to
4.3
mg/
kg/
day.
For
mice,
however,
the
NOEL
of
10
ppm
found
by
Hanley
et
al
(
Ex.
4­
106)
corresponds
to
approximately
9.2
mg/
kg/
day,
(
using
the
mean
weight
for
the
10
ppm
exposure
group
on
day
12,
half­
way
through
exposure,
and
assuming,
like
Environ,
100%
absorption),
more
than
two
times
greater
than
the
NOEL
for
rabbits
measured
in
the
same
units.
For
rats,
the
NOEL
of
10
ppm
found
by
Hanley
et
al
(
Ex.
4­
042a)
corresponds
to
approximately
5.93
mg/
kg/
day
(
also
using
the
mean
weight
for
the
10
ppm
group
on
day
12,
half­
way
through
exposure,
and
assuming
100%
absorption.)
Thus,
if
Environ
is
going
to
convert
the
NOEL
into
units
of
milligrams
per
kilogram
per
day,
an
adjustment
for
interspecies
variation
must
be
considered
OSHA
seeks
comment
on
whether
the
NOEL
should
be
expressed
in
units
of
ppm
or
units
of
milligrams
per
kilogram
per
day.
A
number
of
commentors
support
the
latter
measure
including
CMA
(
Ex.
7­
17)
and
NIOSH
(
Ex.
7­
22),
but
the
Agency
notes
that
those
commentors
who
calculated
their
own
ADIs
did
no
such
conversion
of
units
(
see,
for
example,
Ex.
7­
23).
Furthermore,
the
Agency
is
uncertain
as
to
how
one
would
convert
a
NOEL
from
units
of
ppm
to
units
of
milligram
per
kilogram
per
day
from
a
study
of
developmental
effects.
Animals
exposed
during
gestation
are
gaining
weight
rapidly.
Thus,
as
a
study
progresses,
the
dose
an
animal
receives
decreases
in
terms
of
milligrams
per
kilogram
per
day.
Clearly
weight
gain
will
be
a
function
not
only
of
the
genetics
of
an
individual
animal
but
also
of
the
number
of
fetuses
a
pregnant
female
is
carrying.
OSHA
seeks
comment
on
whether
these
factors
should
be
accounted
for
in
measuring
dose,
and
if
so,
how
this
should
be
done
VII.
Significance
Of
Risk
OSHA
believes
that
the
type
of
significant
risk
analysis
the
Agency
has
undertaken
in
this
rulemaking
is
consistent
with
the
studies
generally
available
and,
for
the
reasons
set
forth
below
and
in
the
section
on
risk
assessment,
is
a
valid,
accepted
and
customary
scientific
approach
Section
6(
b)(
5)
of
the
OSH
Act
vests
authority
in
the
Secretary
of
Labor
to
issue
health
standards.
This
section
provides,
in
part,
that
:

The
Secretary,
in
promulgating
standards
dealing
with
toxic
materials
or
harmful
physical
agents
under
this
subsection,
shall
set
the
standard
which
most
adequately
assures,
to
the
extent
feasible,
on
the
basis
of
the
best
available
evidence,
that
no
employee
will
suffer
material
impairment
of
health
or
functional
capacity
even
if
such
employee
has
regular
exposure
to
the
hazard
dealt
[
page
15577]

with
by
such
standard
for
the
period
of
his
working
life.

OSHA
is
required
to
make
two
threshold
findings
before
it
can
issue
a
health
standard
under
section
6
(
b)(
5)
of
the
Act.
In
accordance
with
the
Supreme
Court's
decision
in
the
benzene
case,
Industrial
Union
Department,
AFL\
CIO
v.
American
Petroleum
Institute,
448
U.
S.
601,
642
(
1980),
OSHA
may
promulgate
a
standard
only
if
it
finds
that
it
is
at
least
more
likely
than
not
that
the
risk
OSHA
seeks
to
regulate
is
"
significant"
and
that
the
change
in
practices
contemplated
in
the
issuance
of
a
standard
would
reduce
or
eliminate
that
risk
OSHA's
analytical
approach
to
making
a
determination
that
a
significant
risk
of
material
impairment
exists
from
exposure
to
hazardous
materials
or
harmful
physical
agents
in
the
workplace
takes
into
consideration
a
number
of
factors
that
are
consistent
with
recent
court
interpretations
of
the
Act
and
with
rational,
objective
policy
formulation.
As
prescribed
by
section
6(
b)(
5)
of
the
Act,
OSHA
examines
the
body
of
the
"
best
available
evidence"
on
the
adverse
effects
of
the
toxic
materials
or
harmful
physical
agents
to
determine
the
nature
and
extent
of
possible
health
consequences
resulting
from
exposure
to
the
hazard
in
question.
Where
possible,
quantitative
assessments
are
conducted
and
the
results
are
considered
along
with
other
relevant
information,
such
as
the
nature
and
severity
of
the
health
consequences,
as
well
as
other
qualitative
evidence
and
expert
opinion,
to
determine
whether
a
hazard
poses
a
significant
risk
to
workers
The
Court
gave
some
general
guidance
to
the
Agency
for
determining
significant
risk:

Some
risks
are
plainly
acceptable
and
others
are
plainly
unacceptable.
If,
for
example,
the
odds
are
one
in
a
billion
that
a
person
will
die
from
cancer
by
taking
a
drink
of
chlorinated
water,
the
risk
clearly
could
not
be
considered
significant.
On
the
other
hand,
if
the
odds
are
one
in
a
thousand
that
regular
inhalation
of
gasoline
vapors
that
are
2
percent
benzene
will
be
fatal,
a
reasonable
person
might
well
consider
the
risk
significant
and
take
the
appropriate
steps
to
decrease
or
eliminate
it.
(
I.
U.
D.
v.
A.
P.
I.,
448
U.
S.,
607,
655)

The
Court
indicated,
that
where
possible,
the
determination
of
significant
risk
should
be
based
upon
quantitative
risk
assessment.
However,
recognizing
the
uncertainties
involved,
the
Court
qualified
its
predilection
for
quantitative
assessment,
saying:

[
T]
he
requirement
that
a
"
significant"
risk
be
identified
is
"
not
a
mathematical
straitjacket.
It
is
OSHA's
responsibility
to
determine,
in
the
first
instance,
what
it
considers
to
be
a
"
significant"
risk.
Id.
The
Court
also
pointed
out
that:
OSHA
is
not
required
to
support
its
findings
that
a
significant
risk
exists
with
anything
approaching
scientific
certainty.
.
.
.[
Section]
6
(
b)(
5)
[
of
the
Act]
specifically
allows
the
Secretary
to
regulate
on
the
basis
of
the
"
best
available
evidence."
.
.
.
Thus,
so
long
as
they
are
supported
by
a
body
of
reputable
scientific
thought,
the
Agency
is
free
to
use
conservative
assumptions
.
.
.
risking
error
on
the
side
of
overprotection
rather
than
under
protection.
Id.,
at
656.

The
Court
noted
that
the
ultimate
determination
that
a
particular
level
of
risk
is
significant
"
will
be
based
largely
on
policy
considerations."
Id.,
at
655­
56,
n.
62
Quantification
of
risk,
the
Court
understood,
cannot
be
achieved
for
every
hazard.
The
four­
judge
plurality,
speaking
for
the
Court
in
the
benzene
decision,
did
not
intend
to
require
OSHA
to
do
what
cannot
be
done.
The
concurring
opinion
of
Mr.
Justice
Powell
and
the
dissenting
opinion
of
Mr.
Justice
Marshall,
speaking
for
four
other
members
of
the
Court,
confirm
this.
Mr.
Justice
Powell
stated:

The
statutory
preferences
for
the
"
best
available
evidence"
.
.
.
implies
that
OSHA
must
use
the
best
known
techniques
for
the
accurate
estimation
of
risks
and
benefits
when
such
techniques
are
available.
But
neither
the
statute
nor
the
legislative
history
suggests
that
OSHA's
hands
are
tied
when
reasonable
quantification
cannot
be
accomplished
by
any
known
methods.
.
.
.
In
this
litigation,
OSHA
found
that
"
it
is
impossible
to
precisely
quantify
the
anticipated
benefits.
.
.
"
If
this
finding
is
supported
by
substantial
evidence,
the
statute
does
not
prevent
the
Secretary
from
finding
a
significant
health
hazard
on
the
basis
of
the
weight
of
expert
testimony
and
opinion.
I
do
not
understand
the
plurality
to
hold
otherwise.
Id.,
at
666­
7.

Similarly,
Mr.
Justice
Marshall,
in
dissent,
stated
"[
i]
t
is
fortunate
indeed
that
at
least
a
majority
of
the
Justices
reject
the
view
that
the
Secretary
is
prevented
from
taking
regulatory
action
when
the
magnitude
of
a
health
risk
cannot
be
quantified
on
the
basis
of
current
techniques"
and
concluded
that
"
the
Court
appears
willing
not
to
require
quantification
when
it
is
not
fairly
possible."
Id.,
690,
716­
17
As
a
part
of
the
overall
significant
risk
determination,
OSHA
considers
a
number
of
factors.
These
include
the
type
of
risk
presented,
the
quality
of
the
underlying
data,
the
reasonableness
of
the
risk
assessments,
the
statistical
significance
of
the
findings
and
the
significance
of
risk
(
48
FR
1864;
January
14,
1983)

The
types
of
risk
posed
by
exposure
to
glycol
ethers
are
of
the
most
serious
kind.
Developing
fetuses
exposed
to
glycol
ethers
may
suffer
the
effects
of
such
exposure
for
a
lifetime,
leading
to
a
life
of
dependency
instead
of
a
life
as
a
productive
member
of
society.
As
noted
by
the
Office
of
Technology
Assessment
in
its
report
on
Reproductive
Hazards
in
the
Workplace,
"
risk
to
a
fetus
may
also
be
a
risk
to
the
woman
herself.
It
may
be
direct,
as
in
the
risk
of
her
own
reproductive
health;
less
direct,
as
in
the
risk
to
her
health
posed
by
spontaneous
abortion;
or
indirect,
in
that
she
may
suffer
psychological
damage
and
diminished
life
prospects
with
the
occurrence
of
a
miscarriage
or
on
the
birth
of
a
dead
or
damaged
baby."
(
Ex.
5­
135,
p.
330).
It
is
also
important
to
note
that
the
father
may
also
share
the
harm
caused
by
the
birth
of
a
dead
or
damaged
child
The
reproductive
effects
from
exposure
to
glycol
ethers
are
not
solely
loss
of
fertility,
a
serious
effect
in
and
of
itself,
but
also
include
major
dysfunction
of
the
reproductive
organs.
Obviously
material
impairment
of
health
includes
not
only
death,
but
also
impairments
in
basic
biological
processes,
such
as
normal
reproductive
function,
which
can
be
of
extraordinary
personal
importance.
In
its
report
on
Reproductive
Hazards
in
the
Workplace,
OTA
states,
and
OSHA
agrees,
that
"[
c]
oncern
about
reproductive
processes
is
not
limited
to
the
brief
periods
in
an
individual's
life
during
which
reproduction
may
actually
occur.
Reproductive
function
is
an
integral
part
of
everyday
human
health
and
well
being.
Before,
during,
and
after
the
child
bearing
years,
reproductive
hormones
may
act,
for
example,
on
such
variables
as
resistance
to
heart
disease
and
cancer,
immune
function,
complexion,
bone
mineral
content,
and
feeling
and
mood.
Threats
to
reproductive
function
can
take
place
at
nearly
any
point
during
an
individual's
life
span."
(
Ex.
5­
135,
p.
43)

The
hematological
effects
associated
with
exposure
to
glycol
ethers
may
be
reversible
but
are
nonetheless
debilitating
and
may
reduce
a
worker's
normal
functional
capacity.
In
addition,
reduction
in
the
white
blood
cell
count
may
compromise
an
individual's
capacity
to
fend
off
diseases,
and
for
these
reasons
the
hematological
effects
from
exposure
to
glycol
ethers
must
be
considered
to
represent
additional
material
impairment
of
health
The
data
which
support
the
finding
of
adverse
health
effects
from
exposure
to
glycol
ethers
are
of
the
highest
quality.
As
described
in
the
Health
Effects
Section
of
this
preamble,
studies
in
[
page
15578]

several
animal
species,
by
various
routes
of
exposure,
have
consistently
shown
that
exposure
to
2­
ME,
2­
EE
and
their
acetates
cause
adverse
reproductive,
developmental
and
hematological
effects.
For
example,
male
test
animals
exposed
to
2­
ME,
2­
EE
and
their
acetates
have
exhibited
interferences
in
spermatogenesis
resulting
in
reduced
sperm
count
and
decreased
fertility.
Exposed
males
have
also
exhibited
degeneration
of
the
seminiferous
tubules
resulting
in
testicular
atrophy.
Pregnant
females
exposed
to
these
glycol
ethers
exhibited
signs
of
maternal
toxicity
such
as
decreases
in
maternal
weight,
decreased
organ
weights
and
increases
in
the
lengths
of
gestation.
Developmental
effects
among
litters
from
exposed
females
include
increased
rates
of
resorptions
(
early
embryonic
death),
decreased
litter
sizes,
decreased
fetal
weights,
visceral
malformations,
skeletal
malformations,
heart
defects,
neurochemical
alterations
and
behavioral
abnormalities.
Experimental
studies
have
also
demonstrated
exposure
related
decreases
in
several
blood
parameters
including
white
blood
cell
counts,
red
blood
cell
counts
and
hemoglobin
concentrations.
Studies
of
humans
exposed
to
these
agents
have
reported
findings
of
testicular
atrophy,
reduced
sperm
count
and
blood
abnormalities
In
this
preamble,
OSHA
has
assessed
the
risk
of
adverse
health
effects
from
exposure
to
2­
ME,
2­
EE,
and
their
acetates
and
has
determined
that
exposure
to
these
glycol
ethers
poses
developmental,
reproductive,
and
hematological
risks.
While
the
Agency
has
assessed
these
risks,
the
present
risk
assessment
differs
from
most
previous
OSHA
risk
assessments
in
that
the
Agency
has
not
quantified
the
risks
in
the
manner
as
it
usually
does.
Instead,
OSHA
has
performed
a
risk
assessment
using
an
uncertainty
factor
approach
to
determine
its
proposed
permissible
exposure
limits
(
PELs)

The
uncertainty
factor
approach
entails
identifying
the
most
appropriate
studies
for
each
glycol
ether
(
i.
e.,
high
quality
studies
using
the
most
sensitive
species)
and
determining
the
no
observed
effect
level
(
NOEL)
for
each
study.
The
NOELs
are
then
divided
by
an
uncertainty
factor
to
arrive
at
estimates
of
the
acceptable
daily
intakes
(
ADIs).
These
ADIs
have
been
put
forth
as
OSHA's
proposed
PELs
For
2­
ME,
the
same
NOEL
was
identified
for
reproductive
effects
in
three
species:
rats,
rabbits,
and
mice.
The
replication
of
the
NOEL
in
each
of
these
bioassays
lends
confidence
that
the
finding
of
any
individual
bioassay
is
not
a
statistical
artifact.
Likewise
the
replication
of
the
NOELs
for
reproductive
effects
in
two
species
exposed
to
2­
EE,
rats
and
rabbits,
also
lends
confidence
in
these
studies'
results.
A
NOEL
for
reproductive
effects
was
identified
in
only
one
species
for
2­
EEA
and
in
no
species
for
2­
MEA,
(
this
last
substance
has
not
been
tested),
but
knowledge
of
the
metabolism
and
pharmacokinetics
of
2­
ME
and
2­
EE
supports
using
the
results
of
studies
of
these
substances
to
assess
the
risk
from
exposure
to
their
acetates
OSHA's
approach
to
the
assessment
of
reproductive
and
developmental
risks
is
consistent
with
the
approach
to
non­
carcinogenic
risk
assessment
adopted
by
a
number
of
governmental
agencies
and
international
organizations
including
the
U.
S.
Environmental
Protection
Agency
(
EPA),
the
U.
S.
Food
and
Drug
Administration
(
FDA),
the
Joint
Food
and
Agricultural
Organization
of
the
World
Health
Organization
(
FAO/
WHO),
and
the
National
Academy
of
Sciences
(
NAS).
This
approach
is
favored
because
it
requires
no
assumptions
akin
to
those
underlying
carcinogenic
risk
assessment
(
i.
e.,
that
cancer
is
a
multi­
stage
process).
Little
is
known
about
the
processes
that
lead
to
developmental
and
reproductive
effects
from
exposure
to
toxic
substances,
and
there
are
no
generally
accepted,
biologically­
based
models
for
assessing
these
risks
In
addition,
uncertainty
factors
and
qualitative
risk
assessment
have
been
utilized
in
other
health
standards
when
there
have
not
been
quantitative
models
available
like
those
used
to
assess
carcinogenic
risk.
(
e.
g.,
Hazard
Communication,
48
FR
53280;
Ethylene
Oxide,
49
FR
25734;
Field
Sanitation,
52
FR
16050;
Formaldehyde,
52
FR
46196)
1.
In
an
analogous
context,
the
Court
of
Appeals
for
the
District
of
Columbia
Circuit
has
upheld
EPA's
use
of
"
margins
of
safety"
in
setting
ambient
air
standards
to
address
uncertainties
associated
with
inconclusive
scientific
and
technical
information.
American
Petroleum
Institute
v.
Costle,
665
F.
2d
1176,
1186­
87
(
1981),
cert.
denied,
449
U.
S.
1042
(
1980)

1
In
the
update
of
the
air
contaminants
standard,
54
FR
2332,
uncertainty
factors
were
also
used
in
the
significant
risk
analysis
for
non­
carcinogens.
On
July
7,
1992,
the
Court
of
Appeals
for
the
Eleventh
Circuit
determined
that
OSHA's
use
of
uncertainty
factors
was
unsupported.
OSHA
has
addressed
the
concerns
raised
by
the
Eleventh
Circuit
in
this
preamble.
In
this
and
the
preceding
section,
OSHA
has
provided
a
detailed
analysis
of
the
data
and
evidence
that
supports
use
of
the
NOEL­
Uncertainty
Factor
approach
as
well
as
the
appropriateness
of
an
uncertainty
factor
of
100.
In
addition,
OSHA
has
requested
public
comment
on
the
appropriateness
of
the
NOEL­
Uncertainty
Factor
approach
for
making
risk
assessment
regarding
reproductive/
developmental
health
effects
and
the
use
of
an
uncertainty
factor
of
100.
Moreover,
OSHA
has
requested
interested
parties
to
discuss
alternative
safety
factors
and
methodologies
for
assessing
risk
of
reproductive/
developmental
health
effects
OSHA's
choice
of
an
uncertainty
factor
for
estimating
a
human
ADI
from
animal
studies
is
also
consistent
with
the
recommendations
of
many
of
these
organizations.
For
example,
the
FDA
recommends
using
an
uncertainty
factor
of
100
when
NOELs
are
identified
in
chronic
studies
(
such
as
those
used
by
OSHA)
in
animals.
Likewise,
the
NAS
recommends
an
uncertainty
factor
of
100
when
calculating
an
ADI
from
a
NOEL
found
in
animals.
Although
the
choice
of
uncertainty
factor
may
appear
to
be
arbitrary,
Dourson
and
Stara
have
provided
a
review
of
experimental
evidence
supporting
this
choice
(
Ex.
4­
113)

The
100­
fold
uncertainty
factor
used
by
OSHA
in
this
risk
assessment
is
comprised
of
two
factors:
a
ten­
fold
factor
to
account
for
inter­
species
variability
(
i.
e.,
varying
sensitivity
across
species)
and
a
ten­
fold
factor
to
account
for
intra­
species
variability
(
i.
e.,
varying
sensitivity
among
members
of
a
population).
By
making
these
adjustments,
we
increase
the
certainty
that
the
ADI
represents
an
exposure
level
below
which
adverse
effects
are
unlikely
By
choosing
a
100­
fold
uncertainty
factor,
however,
OSHA
is
not
regulating
below
the
level
of
significant
risk.
A
ten­
fold
factor
for
inter­
species
variability
and
a
ten­
fold
factor
for
intra­
species
variability
are
necessary
to
assure
that
exposure
at
or
below
the
OSHA
proposed
PELs
will
be
unlikely
to
cause
adverse
health
effects
The
ten­
fold
factor
for
inter­
species
variability
is
necessary
to
account
for
the
potential
differences
between
species'
sensitivity
to
toxic
agents.
Differences
in
sensitivity
may
result
from
differences
in
metabolism
or
differences
in
reproductive
function.
For
example,
as
noted
by
EPA
in
their
guidelines
for
assessing
male
reproductive
toxicity
(
Ex.
5­
123),
males
of
most
test
species
produce
sperm
in
numbers
that
greatly
exceed
the
minimum
requirements
for
fertility.
However,
human
males,
in
general,
produce
fewer
sperm
relative
to
the
number
required
for
fertility.
Thus,
human
males
may
be
more
sensitive
to
a
reduction
in
sperm,
as
they
may
function
nearer
to
the
threshold
for
the
number
of
sperm
needed
to
ensure
reproductive
competence.
Also
differences
in
sensitivity
may
result
from
differences
in
metabolism.
In
the
case
of
glycol
ethers,
both
animals
and
humans
appear
to
utilize
the
same
metabolic
pathway
to
produce
the
same
[
page
15579]

primary
metabolite.
This
primary
metabolite
is
generally
considered
to
be
the
active
agent
in
the
induction
of
adverse
reproductive
and
developmental
effects.
However,
the
evidence
also
indicates
that
the
biological
half
life
of
the
metabolites
in
humans
is
greater
than
in
animals.
Thus
the
accumulation
rates
between
animals
and
humans
are
not
directly
comparable.
The
above
reasons
reinforce
the
general
support
for
the
use
of
a
ten
fold
uncertainty
factor
for
inter
species
variability
Furthermore,
while
it
may
appear
that
there
is
no
inter­
species
variation
in
the
NOELs
for
2­
ME
and
2­
EE,
as
discussed
in
the
Risk
Assessment
Section
of
this
preamble,
this
is
a
function
of
the
study
designs
used
by
Hanley
et
al
and
Tinston
et
al
and
does
not
prove
there
is
no
inter­
species
variation
in
developmental
risk
from
these
glycol
ethers.
Lastly,
although
the
bounds
of
normal
reproductive
function
can
be
very
broad,
the
complexity
in
the
reproductive
processes
and
the
difficulty
in
conducting
studies
on
the
broad
range
of
possible
outcomes
have
resulted
in
experimental
studies
concentrating
for
the
most
part
on
only
a
few
distinct
periods
in
normal
reproductive
functioning.
OSHA
has
relied
upon
these
studies
to
determine
the
reproductive
and
developmental
risks
associated
with
glycol
ethers,
but
the
limitations
of
these
studies
provide
additional
support
for
a
ten­
fold
factor
for
inter­
species
variability
The
ten­
fold
factor
for
intra­
species
variability
is
also
necessary,
and
use
of
this
factor
does
not
result
in
reducing
insignificant
risk.
Worker
populations
exposed
to
glycol
ethers
are
not
as
homogeneous
as
the
animal
populations
used
in
experimental
studies.
Furthermore,
even
if
workers
are
healthier
than
the
general
population,
it
does
not
necessarily
follow
that
this
"
healthy
worker
effect"
will
be
conferred
upon
a
developing
fetus.
In
addition,
both
parents
of
the
fetus
need
not
necessarily
be
"
healthy
workers",
and
the
fetus
may
inherit
the
genetic
traits
of
either
parent
In
utilizing
the
uncertainty
factors
in
setting
the
proper
PELs
for
the
glycol
ethers
under
consideration
in
this
rulemaking,
it
has
not
been
the
Agency's
objective
to
apply
an
uncertainty
factor
to
eliminate
all
risk.
If
that
had
been
the
Agency's
objective
or
mandate
under
the
Act,
a
much
higher
uncertainty
factor
would
have
to
have
been
applied
to
ensure
elimination
of
all
risks.
Rather,
the
Agency
has
used
uncertainty
factors
to
take
into
account
only
the
highest
uncertainties,
such
as
inter­
species
and
intra­
species
variability.
The
Agency
believes
that
it
has
used
the
uncertainty
factors
in
a
reasonable
manner
and
in
utilizing
the
uncertainty
factors
the
Agency
has
had
as
its
goal
reducing
risks
that
are
significant
After
considering
the
severity
of
the
types
of
risk
as
shown
by
the
qualitative
analysis
of
the
data,
OSHA
preliminarily
concludes
that
exposure
to
2­
ME,
2­
EE
and
their
acetates
presents
a
significant
risk
to
employees
exposed
to
these
substances
at
the
current
PELs.
The
current
PELs
for
2­
ME
and
2­
MEA
are
25
ppm,
two
and
one­
half
times
larger
than
the
NOEL
for
2­
ME
in
three
species
(
i.
e.,
10
ppm).
The
current
PELs
for
2­
EE
and
2­
EEA
are
200
ppm
and
100
ppm
respectively.
For
2­
EE,
this
PEL
is
four
times
greater
than
the
NOEL
identified
in
two
species
(
i.
e.,
50
ppm),
and
for
2­
EEA,
this
PEL
is
two
times
greater
than
the
NOEL
identified
in
one
species
(
i.
e.,
50
ppm).
If
the
NOEL
is
an
estimate
of
the
threshold
of
exposure
resulting
in
adverse
effects
in
animals,
and
if
humans
have
the
same
degree
of
sensitivity
as
animals,
exposure
at
the
current
PELs
poses
risk
of
material
impairment
of
health.
If
humans
are
more
sensitive
than
animals
and
respond
to
exposure
in
a
less
homogeneous
manner,
then
the
risk
is
greater
still
that
workers
exposed
at
the
current
PELs
will
suffer
adverse
effects
from
such
exposure
OSHA
also
preliminarily
concludes
that
the
new
glycol
ethers
standard
will
result
in
a
reduction
of
significant
risk.
However
as
discussed
earlier
in
the
section
on
Risk
Assessment
there
are
uncertainties
to
the
NOEL/
Uncertainty
Factor
approach.
It
is
assumed
that
at
exposure
levels
derived
by
dividing
an
experimental
NOEL
by
an
uncertainty
factor
of
100,
humans
are
unlikely
to
exhibit
effects
observed
in
experimental
animals.
However
the
ADI
does
not
represent
a
level
of
exposure
above
which
there
is
significant
risk
and
below
which
there
is
no
significant
risk.
For
some
individuals
there
may
be
some
remaining
risk
below
the
ADI.
For
these
reasons
OSHA
believes
that
the
ancillary
provisions
of
the
standard
such
as
exposure
monitoring
and
medical
surveillance
will
provide
greater
assurance
that
workers
will
not
be
at
significant
risk.
Thus
OSHA
believes
that
these
provisions
are
reasonably
necessary
VIII.
Summary
Of
The
Regulatory
Impact
And
Regulatory
Flexibility
Analysis
Introduction
Executive
Order
12291
(
46
FR
13197,
Feb.
19,
1981)
requires
that
a
regulatory
analysis
be
conducted
for
any
rule
having
major
economic
consequences
on
the
national
economy,
individual
industries,
geographical
regions,
or
levels
of
government.
The
Regulatory
Flexibility
Act
(
5
U.
S.
C.
601
et.
seq.)
similarly
requires
the
Occupational
Safety
and
Health
Administration
(
OSHA)
to
consider
the
impact
of
the
proposed
regulation
on
small
entities
Consistent
with
these
requirements,
OSHA
has
prepared
a
Preliminary
Regulatory
Impact
and
Regulatory
Flexibility
Analysis
(
PRIA)
for
the
proposed
glycol
ethers
standard
with
8­
hour
time­
weighted
average
(
TWA)
permissible
exposure
limits
(
PELs)
of
0.1
parts
per
million
(
ppm)
for
2­
methoxyethanol
(
2­
ME)
and
2­
methoxyethanol
acetate
(
2­
MEA),
and
0.5
ppm
for
2­
ethoxyethanol
(
2­
EE)
and
2­
ethoxyethanol
acetate
(
2­
EEA)
(
Ex.
5­
165).
This
analysis
describes
the
industries
affected
by
the
standard,
the
regulatory
alternatives
considered,
some
of
the
potential
benefits
that
will
accrue
to
employees
exposed
to
glycol
ethers
at
their
places
of
work,
the
costs
of
the
proposed
standard,
and
the
technological
and
economic
feasibility
of
the
proposed
provisions.
The
following
is
a
summary
of
this
analysis
Background
The
chemicals
2­
ME,
2­
EE,
2­
MEA,
and
2­
EEA
are
members
of
the
family
of
ethylene
glycol
ethers.
Referred
to
collectively
in
this
analysis
as
"
glycol
ethers",
these
four
chemicals
have
versatile
solvent
properties
that
make
them
useful
in
a
wide
variety
of
industries.
The
principal
uses
of
glycol
ethers
are
in
chemical
intermediates,
paints
and
coatings,
inks,
and
electronics
The
current
OSHA
PELs
for
8­
hour
TWAs
are
25
ppm
for
2­
ME
and
2­
MEA,
200
ppm
for
2­
EE,
and
100
ppm
for
2­
EEA.
They
were
established
in
1971
based
on
the
1968
Threshold
Limit
Values
(
TLVs)
recommended
by
the
American
Conference
of
Governmental
Industrial
Hygienists
(
ACGIH).
These
TLVs
were
based
on
hematotoxic
and
neurotoxic
effects
and
on
exposure
concentrations
reported
in
the
early
case
reports
on
human
health
effects.
More
recent
information
from
animal
studies,
however,
indicates
that
adverse
reproductive
effects
may
occur
at
much
lower
concentrations.
The
ACGIH
now
recommends
for
all
four
glycol
ethers
an
8­
hour
TLV
of
5
ppm,
plus
a
"
skin"
notation
to
draw
attention
to
the
need
to
prevent
cutaneous
absorption
In
1984,
the
U.
S.
Environmental
Protection
Agency
(
EPA)
published
an
Advance
Notice
of
Proposed
Rulemaking
(
ANPR)
regarding
2­
ME,
2­

[
page
15580]

EE,
2­
MEA,
and
2­
EEA.
In
1986,
the
EPA
referred
the
issue
of
rulemaking
for
these
chemicals
to
OSHA.
Subsequently,
OSHA
made
a
preliminary
determination
that
the
occupational
risks
identified
by
EPA
could
be
eliminated
or
reduced
by
a
revised
OSHA
standard.
In
1987,
OSHA
published
an
ANPR
announcing
its
intention
to
initiate
rulemaking
action
for
four
glycol
ethers
(
OSHA
Docket,
Ex.
6.)

The
objective
of
this
analysis
is
to
measure
the
regulatory
impact
of
the
proposed
TWAs
and
associated
requirements,
including
Excursion
Limits
(
ELs)
equivalent
to
five
times
each
TWA
and
action
levels
(
ALs)
equivalent
to
one­
half
of
each
TWA
The
principal
source
of
information
for
this
analysis
is
a
study
conducted
for
OSHA
by
PEI
Associates,
Inc.,
Technological
Feasibility
and
Economic
Impact
Assessment
of
a
Proposed
Revision
to
the
Glycol
Ethers
Standards,
1990,
OSHA
Docket,
Ex.
5­
164.
A
major
source
for
PEI's
report
was
an
earlier
study
conducted
for
OSHA
by
Meridian
Research,
Inc.,
Industry
Profile
and
Analysis
of
Processes,
Occupational
Exposures,
and
Substitutes
for
Glycol
Ethers,
1987,
OSHA
Docket,
Ex.
5­
108
PEI
conducted
three
major
data
collection
activities:

1)
All
available
monitoring
data
from
work
establishments
were
collected,
categorized,
and
tabulated.
These
historical
data
were
obtained
primarily
from
OSHA,
the
National
Institute
for
Occupational
Safety
and
Health
(
NIOSH),
and
a
study
that
PEI
had
conducted
previously
for
EPA.
Only
post­
1984
data
were
used
because
of
a
change
in
the
limit
of
detection
in
the
glycol
ether
sampling
and
analytical
method
in
1984
2)
A
joint
PEI/
NIOSH
team
visited
nine
facilities
selected
to
be
representative
of
the
industries
currently
manufacturing,
processing,
and/
or
using
at
least
one
of
the
glycol
ethers
under
consideration.
Information
was
obtained
at
each
site
regarding
processes,
use
of
engineering
and
work
practice
controls
and
personal
protective
equipment
(
PPE),
characteristics
of
the
exposed
work
force,
medical
and
industrial
hygiene
programs,
and
experience
with
substitute
chemicals.
To
characterize
full­
shift
and
peak
exposures
in
each
job
category
with
potential
for
exposure
to
glycol
ethers,
NIOSH
also
sampled
at
least
one
shift
at
each
site
3
)
PEI
mailed
a
survey
questionnaire
to
approximately
2500
randomly
selected
potential
users
of
glycol
ethers
in
order
to
characterize
the
following:

­
Extent
of
usage
of
glycol
ethers
in
different
industry
segments
­
Process
operations
­
Demographics
of
potentially
exposed
workers
­
Engineering
and
work
practice
controls
currently
in
place
and
those
necessary
to
achieve
specified
exposure
levels
­
PPE
currently
in
place
and
PPE
necessary
to
achieve
specified
exposure
levels
­
Financial
characteristics
of
the
industries
­
Experience
with
potential
substitutes
for
glycol
ethers
Usable
responses
were
obtained
from
1,424
facilities
through
the
mail
questionnaire
and
subsequent
telephone
followup.
Of
the
establishments
submitting
usable
responses,
70
percent
had
never
handled
any
of
the
four
glycol
ethers
which
are
the
subjects
of
this
rulemaking,
13
percent
had
discontinued
handling
them,
and
17
percent
currently
handled
at
least
one
of
them
Based
primarily
on
data
from
the
survey
questionnaire
and
site
visits,
PEI
developed
model
plants
to
represent
average
establishments
in
each
industry
category.
The
model
plants
were
used
to
develop
an
exposure
profile
and
estimate
compliance
costs.
The
number
of
model
plants
developed
for
each
industry
category
depended
on
market
structure
and
work
force
characteristics,
including
exposures.
PEI
also
developed
model
plants
for
small
businesses
Industry
Profile
The
estimated
1987
domestic
net
sales
(
i.
e.,
production
less
inventory
changes)
of
the
four
glycol
ethers
amounted
to
286
million
pounds.
The
most
widely
distributed
chemical
was
2­
EE
(
149
million
pounds
in
1987),
followed
by
2­
EEA
(
85
million
pounds),
2­
ME
(
51
million
pounds),
and
2­
MEA
(
1
million
pounds).
The
largest
consumption
category
for
these
chemicals
was
export
(
45
percent
of
sales),
followed
by
use
as
chemical
intermediates
(
24
percent
of
sales).
The
remaining
31
percent
of
sales
of
the
glycol
ethers
was
primarily
for
solvent
use
Table
VIII­
1
presents
estimates
of
the
number
of
glycol
ether­
using
establishments
covered
by
the
proposed
regulation,
percent
of
small
establishments,
total
employment,
and
number
of
exposed
workers.
Although
jet
fuel
additives
consume
much
2­
ME,
they
are
excluded
from
this
analysis
because
they
are
used
almost
exclusively
in
military
applications.
All
other
miscellaneous
uses
not
addressed
in
this
analysis
are
estimated
to
account
for
less
than
1
percent
of
total
usage
of
the
glycol
ethers
Sales
of
the
four
glycol
ethers
have
declined
steadily
over
the
past
decade,
probably
as
a
result
of
increased
concern
over
environmental
and
health
issues
Manufacture
of
Glycol
Ethers
Four
establishments
operated
by
three
companies
(
Union
Carbide,
Eastman
Chemical,
and
Oxy
Petrochemical)
currently
produce
at
least
one
of
the
four
glycol
ethers.
(
In
1990,
Union
Carbide,
the
sole
producer
of
2­
MEA,
discontinued
its
manufacture
and
sale.
A
submission
by
the
Chemical
Manufacturers
Association
(
CMA)
to
OSHA
reported
that
"
only
a
very
few
users"
were
working
off
inventories
of
2­
MEA,
OSHA
Docket,
Ex.
3­
002.)
Because
of
similarities
in
the
production
processes,
plant
capacity
can
be
shifted
from
one
of
the
four
TABLE
VIII­
1
GLYCOL
ETHERS
INDUSTRY
PROFILE
Estima­

ted
number
Estimated
Exopsed
Workers
of
Percent
Estimated
__________________________

Estab­
small
total
lish­
estab­
employ­
Females
ments
lish­
ment
Total
Males
under
using
ments
age
Industry
glyco
(*)
45
Category
ethers
Manufacture
of
Glycol
4
0
5,120
344
320
24
Ethers
Manufacture
Of
5
0
44,500
80
60
20
Chemical
inter­

Mediates
Formulation
Of
183
57
13,176
2,745
2,562
183
paints
and
Coatings
Aircraft
54
NA
244,782
1,998
1,998
0
manufacturing/

Repainting
Motor
vehicle
Body
16
57
69,920
736
736
0
manufacturing
Other
metal
366
55
37,698
1,464
1,464
0
applications
Automobile
8,777
75
43,885
26,331
26,331
0
refinishing
Wood
Furniture
370
67
27,750
8,140
3,330
2,590
manufacturing
Formulation
of
inks
86
67
5,848
946
860
86
Inks
Application
of
inks
86
89
11,180
946
516
430
Inks
Semiconductor
142
54
47,428
1,704
710
852
manufacturing
[
page
15581]
Printed
Circuit
44
61
7,392
352
220
132
Board
manufacturing
Total
10,133
.
558,679
45,786
39,107
4,317
(*)
Establishments
with
fewer
than
20
employees
NA
=
Not
Available
Source:
PEI
chemicals
to
another,
as
well
as
to
other
ethylene
oxide
derivatives
Manufacture
of
Chemical
Intermediates
In
addition
to
the
plants
that
produce
2­
EEA
and
2­
MEA,
four
major
producers
of
chemicals
use
2­
EE
or
2­
MEA
as
an
intermediate
in
five
other
plants:
Eastman
Chemical,
Reichold
Chemical,
CPS
Chemical,
and
Sartomer
Company.
The
major
use
of
2­
EE
(
86
percent
of
domestic
consumption)
is
as
a
chemical
intermediate.
Its
principal
product
is
2­
EEA;
2­
EE
is
also
used
as
a
chemical
intermediate
in
the
manufacture
of
ethoxyethyl
methacrylate,
ethoxyethyl
ricinoleate,
ethoxyethyl
acrylate,
and
di(
ethoxyethyl)
phthalate
The
use
of
2­
ME
as
an
intermediate
to
produce
other
chemicals,
including
2­
MEA,
accounts
for
24
percent
of
its
domestic
consumption.
These
chemicals
also
include
di(
2­
methoxyethyl)
phthalate
(
DEMP),
which
is
used
as
a
plasticizer
in
the
manufacture
of
35­
mm
film,
vinyl­
tris­
B­
methoxyethoxysilane,
methoxyethylacrylate,
2­
methoxyethyl
silicate,
methoxyethyl
oleate,
methoxyethyl
acetyl
ricinoleate,
methoxyethyl
ricinoleate,
and
methoxyethyl
stearate
Formulation
of
Paints
and
Coatings
Glycol
ethers
are
used
in
polymerization,
as
a
medium
for
pigment
dispersion,
and
as
a
"
let
down"
solvent
to
achieve
desired
coating
application
properties.
They
are
used
primarily
in
the
formulation
of
Original
Equipment
Manufacture
(
OEM)
paints
for
automobiles,
metal
furniture,
and
appliances
and
also
as
special­
purpose
coatings.
The
formulation
of
paints
and
coatings
involves
mixing
glycol
ethers
and
other
solvents
with
resins,
pigments,
or
base
materials
Aircraft
Manufacturing/
Repainting
Glycol
ethers
are
contained
in
aircraft
top
coat
paint
and
sometimes
in
paint
additives.
Aircraft
are
generally
repainted
every
4
to
5
years.
Painting
takes
place
in
open
bays
in
aircraft
hangars,
where
the
paints
are
applied
by
brush,
roller,
airless
spray,
or
electrostatic
spray.
Smaller
parts
and
support
equipment
are
usually
spray
painted
in
a
separate
paint
shop
Motor
Vehicle
Body
Manufacturing
Glycol
ethers
can
be
contained
in
electrocoat
primers
that
are
initially
applied
for
corrosion
protection,
as
well
as
in
other
primer
and
exterior
color
coatings.
Electrocoats
are
applied
to
vehicle
bodies
by
using
conveyors
to
dip
them
into
tanks
containing
the
primer.
Other
primers
and
paints
are
generally
applied
by
electrostatic
guns
in
spray
booths
equipped
with
downdraft
flow­
through
ventilation.
Automatic
spray
guns
are
used
to
apply
the
primer
coats
on
passenger
car
bodies
Other
Metal
Applications
This
industry
category
includes
miscellaneous
other
establishments
at
which
paints
and
coatings
are
spray
painted
onto
metal:

SIC
2514
(
Metal
Household
Furniture)
SIC
2522
(
Metal
Office
Furniture)

SIC
3411
(
Metal
Cans)
SIC
3412
(
Metal
Shipping
Barrels,
Drums,
Kegs,
and
Pails)
SIC
34421
(
Metal
Doors,
Sash
and
Frames
Except
Storm
Doors)
SIC
34699
(
Other
Stamped
and
Pressed
Metal
Products)
SIC
3523
(
Farm
Machinery
and
Equipment)
SIC
3563
(
Air
and
Gas
Compressors)
SIC
3631
(
Household
Cooking
Equipment)
SIC
3632
(
Household
Refrigerators
and
Home
and
Farm
Freezers)
SIC
3714
(
Motor
Vehicle
Parts
and
Accessories)

Automobile
Refinishing
Some
paints
and
coatings
used
in
automobile
refinishing
contain
small
quantities
of
glycol
ethers.
Some
spray
painting
operations
take
place
in
a
spray
booth,
while
other
painting
operations
occur
in
the
general
shop
environment.
Wood
Furniture
Manufacturing
Glycol
ethers
are
used
in
some
wood
stains
or
lacquers
because
of
their
solvent
properties.
In
general,
the
stains
or
lacquers
are
applied
by
spraying
in
booths,
followed
by
additional
hand­
padding
operations.
The
stains
or
lacquers
may
also
be
blended
prior
to
the
finishing
operations.
Formulation
of
Inks
Glycol
ethers
are
used
as
a
solvent
in
inks,
primarily
in
gravure,
flexographic,
and
screen
inks.
They
serve
as
co­
solvents
for
ink
resins
and
dyes
in
water­
based
inks.
They
are
also
used
as
solvents
for
textile
printing
and
as
active
solvents
to
dissolve
organic
dyes.
Glycol
ethers
are
used
in
inks
that
are
typically
manufactured
in
small
batches,
to
achieve
the
desired
viscosity
Application
of
Inks
Glycol
ethers
are
used
as
ink
solvents
and
thinners
in
silk
screen,
flexographic,
and
gravure
printing.
In
silk
screening,
solvent­
based
inks
are
spread
over
and
squeezed
through
the
pores
of
a
screen
to
print
an
image.
After
printing,
the
screen
is
washed
by
hand
with
a
lacquer
thinner.
In
flexographic
printing,
the
plate
with
the
image
area
is
fastened
to
a
cylinder,
which
is
then
immersed
into
the
ink­
filled
reservoir
of
a
letterpress.
The
image
is
transferred
from
the
raised
surface
of
the
plate
to
a
[
page
15582]

flexible
substrate.
In
gravure
printing,
an
image
is
etched
into
the
surface
of
a
cylinder,
which
is
then
immersed
in
the
reservoir
of
a
web
rotogravure
or
sheet­
fed
press.
In
a
high­
speed
process,
ink
is
transferred
from
the
cylinder
to
the
substrate
by
a
capil­
lary
action.
Printing
operators
may
be
exposed
to
glycol
ethers
during
blending
of
inks
and
cleaning
of
printing
press
rollers
Semiconductor
Manufacturing
Glycol
ethers
are
used
primarily
as
photoresists
in
the
photolithographic
portion
of
the
wafer
manufacturing
process.
The
photoresist
may
be
applied
to
the
silicon
wafer
either
manually
by
syringe
or
in
an
automated
system
that
pumps
the
solution
directly
from
storage
to
a
spin
coater.
Glycol
ethers
may
also
be
used
as
components
of
the
inks
used
for
marking
the
completed
devices
with
a
part
number.
The
cleaning
compounds
used
to
dissolve
the
epoxy
resin
that
mounts
wafers
to
polishing
fixtures
also
may
contain
glycol
ethers
Printed
Circuit
Board
Manufacturing
Glycol
ethers
are
used
as
a
solvent
in
epoxy
resin
that
is
laminated
onto
fiberglass
reinforcement.
It
is
normally
applied
in
enclosed
spray
chambers.
Glycol
ethers
also
may
be
present
in
formulations
used
for
marking,
bonding,
and
labeling
the
printed
circuit
boards
Worker
Exposures
Workers
may
be
exposed
to
glycol
ethers
in
many
of
the
activities
in
the
12
industry
categories
evaluated
in
this
study.
Table
VIII­
2
lists
the
principal
job
categories
in
each
industry
category
and
the
current
weighted
plant
geometric
mean
(
GM)
exposures
and
weighted
plant
arithmetic
mean
(
AM)
exposures
for
each
glycol
ether
Geometric
means
are
usually
the
preferred
measure
of
expressing
central
tendency
for
observations
which
are
log­
normally
distributed.
By
design,
the
formula
for
geometric
means
suppresses
the
value
of
outlying
data
observations.
When
used
in
combination
with
prescriptions
for
engineering
controls
to
reduce
employee
exposure
levels,
for
example,
it
makes
the
case
for
technological
feasibility
clearer
by
using
geometric
means
(
compared
with
a
single
arithmetic
mean
calculation,
in
which
the
values
of
outlyers
are
not
suppressed)

TABLE
VIII­
2
EXPOSURE
CHARACTERIZATION
BY
INDUSTRY
AND
JOB
CATEGORY
|
|
|

Industry
|
Esti­
|
Weighted
plant
|
Weighted
plant
catagory
|
mated
|
geometric
mean
|
arithmetic
mean
and
|
number
|
baseline
|
baseline
job
|
of
|
exposure,
PPM
|
exposure,
PPM
category
|
expos­
|
|

|
ed
|
_________________________
|
__________________________

|
work­
|
|
|
|
|
|
|
|

|
ers
|
2­
ME*
|
2­
MEA*
|
2­
EE*
|
2­
EEA
|
2­
ME*
|
2­
MEA*
|
2­
EE*
|
2­
EEA
_________
|
______
|
_____
|
______
|
_____
|
______
|
_____
|
_______
|
______
|
_____

|

Manufacture
of
Glycol
Ethers:
|

All
|

workers
344
|

Loading
|

Tech
96
0.046
N/
A
0.022
0.027
|
0.151
(
a)
0.047
0.043
Process
|

Tech
72
0.032
N/
A
0.092
0.049
|
0.044
(
a)
0.177
0.077
Lab
Tech
68
0.023
N/
A
0.015
0.023
|
0.027
(
a)
0.017
0.031
Maint.
|

Tech
92
(
b)
N/
A
0.057
0.058
|
(
b)
(
c)
0.079
0.116
Super­
|

visor
16
0.017
N/
A
0.026
0.017
|
0.017
(
a)
0.047
0.017
|

Manufacture
of
Chemical
Intermediates**:
|

All
|

workers
80
|

Tech
50
0.046
N/
A
0.022
N/
A
|
0.151
N/
A
0.047
N/
A
Process
|

Tech
10
0.032
N/
A
0.092
N/
A
|
0.044
N/
A
0.177
N/
A
Lab
Tech
10
0.023
N/
A
0.015
N/
A
|
0.027
N/
A
0.017
N/
A
Maint.
|

Tech
10
(
b)
N/
A
0.057
N/
A
|
(
b)
N/
A
0.079
N/
A
|

Formulation
of
Paints
and
Coatings:
|

All
|

workers
2,745
|

Packer
732
(
b)
(
c)
1.249
1.370
|
(
b)
(
c)
1.980
3.643
Batch­
|

maker
1,464
0.354
(
a)
0.673
0.870
|
0.906
(
a)
0.714
1.072
Lab
Tech
549
0.215
(
a)
(
d)
0.107
|
0.215
(
a)
(
d)
0.118
|

Aircraft
Manufacturing/
Repainting:
|

Spray
|

paint
1,998
N/
A
N/
A
(
d)
3.781
|
N/
A
N/
A
(
d)
7.916
|

Motor
Vehicle
Body
Manufacturing:
|

All
|

workers
736
|

Spray
|

painter
576
N/
A
N/
A
(
d)
0.005
|
N/
A
N/
A
(
d)
0.035
Dip
|

painter
64
N/
A
N/
A
(
d)
0.012
|
N/
A
N/
A
(
d)
0.013
Paint
|
mixer
96
N/
A
N/
A
(
d)
0.010
|
N/
A
N/
A
(
d)
0.227
|

Other
Metal
Applications:
|

Painter
1,464
0.218
0.104
0.052
0.072
|
0.275
0.364
0.111
0.397
|

Automobile
Refinishing***:
|

Spray
|

paint­
|

er
26,331
0.218
0.104
0.052
0.071
|
0.275
0.364
0.111
0.395
|

Wood
Furniture
Manufacturing:
|

Finisher
8,140
(
e)
N/
A
(
d)
0.656
|
(
e)
N/
A
(
d)
0.830
|

Formulation
of
Inks****:
|

All
|

workers
946
|

Packer
86
(
b)
(
c)
1.249
1.370
|
(
b)
(
c)
1.980
3.643
Batchmaker
602
0.354
(
a)
0.673
0.870
|
0.906
(
a)
0.714
1.072
Lab
Tech
258
0.215
(
a)
(
d)
0.107
|
0.215
(
a)
(
d)
0.118
|

Application
of
Inks:
|

Printing
946
0.035
(
a)
0.056
0.038
|
0.043
(
a)
2.441
2.071
operator
|

Semiconductor
Manufacturing:
|

Techni­
|

cian
,704
0.020
(
a)
(
d)
0.011
|
0.022
(
a)
(
d)
0.048
|

Printed
Circuit
Board
Manufacturing:
|

All
|

workers
352
|

Coater
176
0.078
(
a)
0.017
0.012
|
0.378
(
a)
0.031
0.030
Lab
Tech
132
(
e)
(
c)
(
d)
0.134
|
(
e)
(
c)
(
d)
0.217
Mfg
Spec.
44
N/
A
N/
A
N/
A
N/
A
|
N/
A
N/
A
N/
A
N/
A
[
page
15583]

Total
45,786
|

|

__________________________________________
|
__________________________
*
If
no
monitoring
data
were
available
for
a
substance,
PEI
assumed
that
exposures
were
equal
to
those
for
similar
glycol
ether
in
the
same
industry
and
job
category:

(
a)
indicates
2­
MEA
exposures
were
assumed
to
equal
2­
ME
exposures
(
b)
indicates
2­
ME
exposures
were
assumed
to
equal
2­
EE
exposures
(
c)
indicates
2­
MEA
exposures
were
assumed
to
equal
2­
EEA
exposures
(
d)
indicates
2­
EE
exposures
were
assumed
to
equal
2­
EEA
exposures
(
e)
indicates
2­
ME
exposures
were
assumed
to
equal
2­
EEA
exposures
**
Baseline
exposures
were
assumed
to
equal
those
for
Manufacture
of
Glycol
Ethers
***
Baseline
exposures
were
assumed
to
equal
those
for
Other
Metal
Applications
****
Baseline
exposures
were
assumed
to
equal
those
for
Formulation
of
Paints
and
Coatings
N/
A
=
Not
Applicable
Source:
PEI
But
there
is
a
problem
for
health
analysis
when
the
traditional
geometric
mean
representation
is
used
to
categorize
employee
exposures
to
hazardous
substances.
Epidemiological
and
animal
studies
often
document
or
suggest
the
greater
vulnerability
of
the
human
organism
to
short
term
high
dose
exposures
to
hazardous
substances,
as
opposed
to
continual,
routine
exposure
at
lower
doses.
In
statistical
terms,
the
intermittent,
infrequent,
high
dose
exposures
represent
outlyers
in
the
data.
The
values
which
are
potentially
most
threatening
or
harmful
to
humans
are
deliberately
suppressed
when
a
geometric
mean
is
used
to
categorize
the
data
In
policy
terms,
because
the
underlying
distribution
is
normally
distributed
(
lognormal)
and
susceptible
to
a
geometric
mean
representation,
does
not
require
that
this
measure
of
central
tendency
be
used
for
health
benefits
calculations.
In
fact,
to
the
extent
that
it
camouflages
or
distracts
attention
from
potentially
dangerous
short
term
exposure
conditions,
it
probably
should
not
be
used
for
such
calculations
or
used
only
in
combination
with
information
on
the
distribution
of
the
outlying
data.
In
this
analysis,
geometric
mean
analysis
is
supplemented
with
arithmetic
mean
data
which
better
reflect
the
influence
of
the
outlying
observations.
In
most
industry/
job
categories,
average
exposures
are
already
below
the
proposed
TWAs
(
although
it
is
possible
that
individual
exposures
may
exceed
the
proposed
levels).
The
lowest
average
exposures
occur
during
the
manufacture
of
glycol
ethers
and
in
the
manufacture
of
semiconductors
and
printed
circuit
boards
There
are
a
total
of
45,786
exposed
workers
in
10,133
establishments
in
the
12
industry
categories.
The
largest
number
of
exposed
workers
occurs
in
the
automobile
refinishing
category,
which
also
has
the
lowest
number
of
exposed
workers
per
establishment
Benefits
Analysis
The
benefits
of
reducing
employee
exposure
to
glycol
ethers
are
estimated
using
incidence
data
from
animal
studies
and
worker
exposure
data.
The
levels
above
which
adverse
health
effects
are
likely
to
occur
in
humans
are
developed
from
the
animal
studies
using
an
uncertainty
factor
of
100;
that
is,
each
"
no
observed
effect
level"
(
NOEL)
observed
in
the
animal
studies
is
reduced
by
a
factor
of
100
to
yield
the
corresponding
human
exposure
level
OSHA's
analysis
of
the
benefits
that
are
likely
to
occur
as
a
result
of
limiting
exposures
to
glycol
ethers
does
not
consider
decreases
in
adverse
hematological
effects
and
in
behavioral
abnormalities
in
the
offspring
of
exposed
adults.
Also,
OSHA's
analysis
relies
on
animal
studies
that
use
inhalation
as
the
route
of
exposure;
the
dosages
of
glycol
ethers
administered
in
inhalation
studies
are
more
readily
quantifiable
than
those
in
absorption
or
ingestion
studies
and
the
majority
of
job
categories
considered
at
risk
involve
the
inhalation
of
glycol
ether
vapors.
However,
dermal
workplace
exposures
do
occur,
but
these
were
not
quantified.
Thus,
the
benefits
in
this
analysis
are
underestimated.
The
health
effects
estimated
in
this
analysis
and
shown
in
Table
VIII­
3
are
the
estimated
incidence
of
developmental
effects
of
glycol
ether
exposure
on
the
pregnancies
of
females
under
age
45
and
the
estimated
incidence
of
adverse
reproductive
effects
in
male
employees.
The
benefits
were
calculated
assuming
a
45
year
working
lifetime
for
both
sexes.
No
effort
is
directed
at
delineating
the
types
of
fetal
defects
avoided.
Since
both
2­
ME
and
2­
MEA
are
metabolized
in
humans
to
methoxyacetic
acid,
the
benefits
of
limiting
exposure
to
these
compounds
are
displayed
together.
Similarly,
the
benefits
associated
with
reductions
in
2­
EE
and
2­
EEA
exposures
are
displayed
together
TABLE
VIII­
3
PROJECTED
BENEFITS
OF
PROPOSED
STANDARD
Number
of
Annual
Workers
Number
of
Exposed
Adverse
above
Effects
Proposed
or
Cases
Effects
PEL
Avoided
Developmental
Effects/

Female
Workers
Aged
18
to
45
From
Exposure
to
2­
ME/
2­
MEA
157
0.4
to
4.5
From
Exposure
to
2­
EE/
2­
EEA
573
1.7
to
8.0
Total
Developmental
Effects
730
2.0
to
12.4
Reproductive
Cases/
Male
Workers
From
Exposure
to
2­
ME/
2­
MEA
2,604
200
to
490
[
page
15584]
From
Exposure
to
2­
EE/
2­
EEA
4,294
63
to
611
Total
Reproductive
Cases
6,898
262
to
1,101
Note:
Other
benefits
have
not
been
quantified:
reductions
in
hematological
effects,
behavioral
abnormalities
in
offspring,
and
effects
of
dermal
exposure
Sources:
PEI,
Office
of
Regulatory
Analysis
An
estimated
total
of
2.0
to
12.4
adverse
effects
on
fetal
development
per
year
would
be
avoided
under
the
proposed
standard
(
TWAs
of
0.1
ppm
for
2­
ME
and
2­
MEA;
0.5
ppm
for
2­
EE
and
2­
EEA).
These
adverse
developmental
effects
would
be
avoided
principally
in
ink
application,
electronics,
formulation
of
paints
and
coatings,
and
wood
furniture
manufacturing
For
male
workers,
an
estimated
262
to
1,101
adverse
reproductive
conditions
(
reduced
testes
size,
reduced
sperm
count
and/
or
other
impairment
of
reproductive
functioning)
would
be
avoided
per
year
under
the
proposed
standard.
The
impairments
will
persist
in
exposed
workers
for
as
long
as
they
are
exposed.
New
cases
will
develop
among
new
workers
as,
over
time,
work
forces
turn
over
and
new
individuals
become
exposed.
These
benefits
would
occur
principally
in
automobile
refinishing,
aircraft
manufacturing
and
repainting,
and
formulation
of
paints
and
coatings
Technological
Feasibility
OSHA
has
preliminarily
determined
that
the
proposed
standard
is
technologically
feasible.
OSHA
determines
that
the
proposed
TWAs
are
capable
of
being
achieved
in
most
of
the
operations
most
of
the
time
by
means
of
engineering
and
work
practice
controls.
In
certain
situations
for
a
very
limited
number
of
employees
(
i.
e.,
under
2%
of
all
full­
time
equivalent
(
FTE)
workers
exposed
to
glycol
ethers
in
the
industries
involved)
supplementary
respiratory
protection
may
be
necessary.
In
most
instances,
when
the
8­
hour
TWA
has
been
met
through
engineering
controls,
no
use
of
respirators
would
be
necessary
to
meet
the
15­
minute
EL
For
example,
in
auto
refinishing,
which
employs
an
estimated
26,331
exposed
workers,
who
constitute
58%
of
all
workers
exposed
to
glycol
ethers,
OSHA
estimates
that
the
exposure
levels
for
98%
of
these
workers
can
be
reduced
to
or
below
the
proposed
TWAs
and
ELs
by
means
of
substitution,
engineering,
and
work
practice
controls.
OSHA
estimates
that,
on
an
FTE
basis,
fewer
than
1%
of
all
currently
exposed
auto
refinishing
workers
would
require
respiratory
protection.
In
addition,
OSHA
preliminarily
determines
that
exposure
levels,
as
measured
by
geometric
means,
can
be
controlled
to
or
below
the
proposed
8­
hour
TWAs
solely
by
means
of
engineering
and
work
practice
controls
in
a
vast
majority
of
operations
across
the
affected
industries.
Specifically,
geometric
mean
exposure
levels
can
be
controlled
to
or
below
the
TWAs
in
16
of
22
2­
ME
operations,
in
8
of
12
2­
MEA
operations,
in
25
of
26
2­
EE
operations,
and
in
17
of
18
2­
EEA
operations
The
best
evidence
of
technological
feasibility
is
that
the
proposed
levels
are
already
being
achieved
in
the
affected
industries
with
current
controls.
Across
industries
using
glycol
ethers,
geometric
mean
exposures
are
already
at
or
below
the
proposed
TWAs
in
a
majority
of
operations.
These
exposure
data
suggest
that
relatively
few
additional
controls
would
be
necessary
to
consistently
reduce
8­
hour
exposures
and
peak
exposures
to
or
below
the
proposed
standard
In
order
to
assess
technological
feasibility,
PEI
considered
substitution
of
other
solvents
for
glycol
ethers,
other
engineering
controls,
personal
protective
equipment
(
PPE),
and
administrative
measures,
such
as
inspections
to
detect
leaks
in
areas
where
glycol
ethers
are
handled.
PEI
applied
specific
engineering
or
other
controls
until
the
predicted
exposure
level
for
each
industry/
job
category
was
reduced
to
no
more
than
one­
half
of
each
of
the
proposed
alternative
TWAs
for
each
glycol
ether.
The
exposure
level
for
determining
when
additional
controls
would
be
necessary
was
based
on
weighted
plant
geometric
mean
exposures
or
weighted
plant
arithmetic
mean
exposures.
The
purpose
of
conducting
the
technological
feasibility
analysis
using
each
of
the
two
types
of
means
was
to
determine
if
the
costs
and
exposure
levels
differ
significantly
with
the
varying
degrees
of
engineering
controls
and
respirators
necessitated
by
the
two
different
approaches.
In
most
cases,
there
is
little
difference
The
technological
feasibility
of
meeting
ELs
that
were
equivalent
to
five
times
each
TWA
was
assessed
separately.
During
its
site
visits,
PEI
was
able
to
collect
both
short­
term
and
full­
shift
monitoring
data
on
some
individuals
whose
jobs
involved
the
potential
for
peak
exposures.
PEI
assumed
that
job
categories
with
TWA
levels
that
are
currently
below
one­
half
the
proposed
TWA
would
not
experience
excursions
above
the
EL
during
normal
operations.
In
establishments
that
required
only
engineering
controls
to
meet
a
proposed
TWA,
the
use
of
ASRs
would
be
required
for
about
one
quarter
of
the
workers
in
job
categories
that
had
a
potential
for
peak
exposures.
With
both
respirators
and
engineering
controls,
no
additional
requirements
were
assumed
to
be
necessary
to
meet
the
EL
Engineering
Controls
The
systems
which
PEI
specified
were
based
on
American
Conference
of
Governmental
Industrial
Hygienists
(
ACGIH)
recommendations
for
good
engineering
practice.
They
are
conventional,
readily
available,
and
in
use
today.
The
primary
engineering
control
recommended
for
most
categories
was
local
exhaust
ventilation
(
LEV).
Process
enclosures,
which
provide
greater
exposure
control
than
hoods,
were
recommended
for
some
operations
The
following
incremental
engineering
controls
are
considered
technically
feasible
for
the
industry
categories
in
this
study:

Manufacture
of
Glycol
Ethers:
­
Closed­
loop
transfer
for
loading
operations
­
Enclosed
sampling
systems
with
sample
coolers
­
Laboratory
hood
in
quality
control
(
QC)
laboratory
Manufacture
of
Chemical
Intermediates:
­
Automated
drum
filling
station
with
LEV
­
Enclosed
sampling
systems
with
sample
coolers
­
Laboratory
hood
in
QC
laboratory
Formulation
of
Paints
and
Coatings:

[
page
15585]
­
Closed­
loop
transfer
system
­
LEV
on
packaging
line
­
LEV
on
mixing
tank
­
Drum
hoist/
scale
(
small
formulator
plants)
­
Laboratory
hood
in
QC
and
R&
D
laboratories
Aircraft
Manufacturing/
Repainting:
­
Paint
spray
booth
for
small
parts
­
Airless
spray
guns
with
"
cup
collars"

Motor
Vehicle
Body
Manufacturing:
­
LEV
on
paint
mixing
tank
­
Paint
spray
booth
Other
Metal
Applications:
­
Paint
spray
booth
Automobile
Refinishing:
­
Paint
spray
booth
Wood
Furniture
Manufacturing:
­
Paint
spray
booth
Formulation
of
Inks:
­
Closed­
loop
transfer
system
­
LEV
on
packaging
line
­
LEV
on
mixing
tank
­
Drum
hoist/
scale
(
small
formulator
plants)
­
Laboratory
hood
in
QC
and
R&
D
laboratories
Application
of
Inks:
­
LEV
at
press
rollers
and
inkwell
­
Process
enclosure
of
press
Semiconductor
Manufacturing:
­
LEV
at
the
application
of
photoresist
­
Process
enclosure
at
the
application
of
photoresist
Printed
Circuit
Board
Manufacturing:
­
LEV
on
blending/
mixing
operations
­
LEV
on
masking
operation
­
LEV
on
coating
operation
­
Process
enclosure
of
coating
operation
Personal
Protective
Equipment
When
the
implementation
of
engineering
controls
did
not
reduce
the
predicted
exposures
for
a
job
category
to
below
the
target
level,
ASRs
were
prescribed.
Cartridge
respirators
are
considered
inadequate
because
the
odor
thresholds
of
the
four
glycol
ethers
do
not
allow
workers
to
adequately
detect
breakthrough
at
concentrations
as
low
as
the
proposed
regulatory
alternatives
Dermal
exposure
can
be
reduced
through
gloves,
protective
clothing,
and
eye
protection.
Evidence
indicates
that
butyl
rubber
gloves
may
be
appropriate
for
operations
that
involve
heavy
handling
and
high
potential
for
direct
contact.
Neoprene
gloves
may
be
appropriate
for
some
production­
related
activities,
such
as
loading
rail
cars
and
taking
quality
control
samples.
Latex
gloves
may
be
appropriate
for
operations
that
involve
light
handling
and
only
occasional
contact
Substitution
Substitution
of
other
chemicals
is
an
option
for
eliminating
exposure
to
2­
ME,
2­
MEA,
2­
EE,
and
2­
EEA,
although
no
single
"
drop
in"
substitute
exists
for
all
applications.
The
most
common
substitutes,
according
to
PEI's
survey,
are
propylene
glycol
monomethyl
ether
(
PGME),
ethylene
glycol
monobutyl
ether
(
2­
BE),
ethylene
glycol
monopropyl
ether
(
2­
PE),
and
their
acetates.
Together,
these
six
chemicals
account
for
almost
90
percent
of
reported
substitutions.
Evidence
suggests
that
they
would
pose
a
lower
hazard
in
the
workplace
than
the
four
glycol
ethers
being
considered
in
this
standard
A
substitution
rate
was
assumed
for
each
industry
category
based
on
the
availability,
suitability,
and
cost
of
substitutes;
the
capital
and
operating
and
maintenance
(
O&
M)
costs
of
compliance
techniques;
and
the
industry
category's
position
in
the
chain
of
distribution
(
i.
e.,
its
flexibility
in
forcing
or
responding
to
substitution).
The
rate
of
substitution
is
assumed
to
be
the
same
for
the
geometric
mean
and
arithmetic
mean
exposure
approaches.
The
following
substitution
rates
were
developed:
Manufacture
of
Glycol
Ethers
and
Intermediates:
No
substitution;
export
and
chemical
intermediate
uses
represent
large
proportions
of
total
production
of
all
four
glycol
ethers
Formulation
of
Paints
and
Coatings:
90%;
most
formulators
already
have
or
are
developing
substitutes
Aircraft
Manufacturing/
Repainting:
70%

Motor
Vehicle
Body
Manufacturing:
70%

Other
Metal
Applications:
70%

Automobile
Refinishing:
90%

Wood
Furniture
Manufacturing:
90%;
use
of
glycol
ethers
is
already
dropping
rapidly
Formulation
and
Application
of
Inks:
90%;
much
substitution
has
already
taken
place
Semiconductors:
10%;
acceptable
substitutes
are
not
generally
available
Printed
Circuit
Boards:
50%;
acceptable
substitutes
are
generally
available
Exposure
Reduction
Tables
VIII­
4
through
VIII­
7
show
exposure
reductions
for
each
glycol
ether
after
applying
engineering
controls.
In
many
industry/
job
categories,
no
engineering
controls
would
be
needed
to
meet
the
proposed
TWAs,
although
respirators
might
be
needed
to
meet
the
proposed
ELs.

Of
the
workers
who
are
currently
exposed
to
glycol
ethers,
only
five
percent
(
under
either
the
geometric
mean
approach
or
the
arithmetic
mean
approach)
would
require
air­
supplied
respirators.
The
highest
percentages
of
workers
who
would
require
ASRs
are
found
in
aircraft
manufacturing/
repainting
and
"
other"
metal
applications.
On
a
full­
time
equivalent
basis,
only
two
percent
(
under
either
approach)
would
require
ASRs.
(
See
Tables
VIII­
8
and
VIII­
9.)

TABLE
VIII­
4
EXPOSURE
REDUCTIONS
FOR
2­
ME
AFTER
APPLYING
ENGINEERING
CONTROLS
|
|
|

|
|
Geometric
mean
|
Arithmetic
mean
Industry
|
Current
|
approach
|
approach
category
|
utili­
|
_______________________
|
_______________________
and
job
|
zation
|
|
|
|

category
|
of
eng­
|
Baseline
|
Average
|
Baseline
|
Average
|
ineering
|
weighted
|
exposures
|
weighted
|
exposures
|
controls
|
plant
|
after
|
plant
|
after
|
(
percent)
|
geometric
|
applying
|
arthmatic
|
applying
|
|
mean
|
engineering
|
mean
|
engineering
|
|
exposure
|
controls
|
exposure
|
controls
|
|
(
ppm)
|
(
ppm)
|
(
ppm)
|
(
ppm)

__________
|
__________
|
__________
|
__________
|
__________
|
__________

Manufacture
of
Glycol
Ethers:

Loading
Tech
50
0.046
NC
0.151
0.008
Process
Tech
90
0.032
NC
0.044
NC
Laboratory
Tech
90
0.023
NC
0.027
NC
Maintenance
Tech
0
0.057*
NC
0.079*
NC
Supervisor
0
0.017
NC
0.017
NC
Manufacture
of
Chemical
Intermediates:

Loading
Tech
90
0.046
NC
0.151
0.027
Process
Tech
90
0.032
NC
0.044
NC
[
page
15586]
Laboratory
Tech
90
0.023
NC
0.027
NC
Maintenance
Tech
0
0.057*
NC
0.079*
NC
Formulation
of
Paints
and
Coatings:

Packer
10
1.249*
0.250
1.980*
0.396
Batchmaker
70
0.354
0.223
0.906
0.289
Laboratory
Tech
70
0.215
0.019
0.215
0.025
Other
Metal
Applications:

Painter
90
0.218
0.212
0.275
0.242
Auto
Refinishing:

Spray
Painter
67
0.218
0.060
0.275
0.110
Wood
Furniture
Mfg:

Finisher
90
0.656**
0.485
0.830**
0.490
Formulation
of
Inks:

Packer
20
1.249*
0.431
1.980*
0.532
Batchmaker
80
0.354
0.223
0.906
0.289
Laboratory
Tech
70
0.215
0.019
0.215
0.025
Application
of
Inks:

Printing
Operator
63
0.035
NC
0.043
NC
Semiconductor
Mfg:

Technician
82
0.020
NC
0.022
NC
Printed
Circuit
Board
Manufacturing:

Manufacturing
Specialist
63
0.078
0.021
0.378
0.054
Coater
63
0.134**
0.027
0.217**
0.043
NC
=
No
change
from
baseline;
no
use
of
engineering
controls
(
although
respirators
may
be
required
to
meet
EL)

*
No
data
on
baseline
8­
hour
TWA
exposure
to
2­
ME
available
for
this
job
category.
Data
for
2­
EE
were
used
**
No
data
on
baseline
8­
hour
TWA
exposure
to
2­
ME
available
for
this
job
category.
Data
for
2­
EEA
were
used
Source:
PEI
TABLE
VIII­
5
EXPOSURE
REDUCTIONS
FOR
2­
MEA
AFTER
APPLYING
ENGINEERING
CONTROLS
|
|
|

|
|
Geometric
mean
|
Arithmatic
mean
Industry
|
Current
|
approach
|
approach
category
|
utili­
|
_______________________
|
_______________________

and
job
|
zation
|
|
|
|
category
|
of
eng­
|
Baseline
|
Average
|
Baseline
|
Average
|
ineering
|
weighted
|
exposures
|
weighted
|
exposures
|
controls
|
plant
|
after
|
plant
|
after
|
(
percent)
|
geometric
|
applying
|
arthmatic
|
applying
|
|
mean
|
engineering
|
mean
|
engineering
|
|
exposure
|
controls
|
exposure
|
controls
|
|
(
ppm)
|
(
ppm)
|
(
ppm)
|
(
ppm)

__________
|
__________
|
__________
|
__________
|
__________
|
__________

Formulation
of
paints
and
coatings:

Packer
10
1.370**
0.274
3.643**
0.729
Batchmaker
70
0.354*
0.223
0.906*
0.289
Laboratory
Technicion
70
0.215*
0.019
0.215*
0.025
Other
metal
applications:

Painter
90
0.104
0.043
0.364
0.233
Auto
refinishing:

Spray
painter
67
0.104
0.043
0.364
0.233
Formulation
of
inks:

Packer
20
1.370**
0.330
3.643**
0.757
Batchmaker
80
0.354*
0.223
0.906*
0.532
Laboratory
technician
70
0.215*
0.019
0.215*
0.025
Application
of
inks:

Printing
operator
63
0.035*
NC
0.043*
NC
Semiconductor
manufacturing:

Technician
82
0.020*
NC
0.022*
NC
Printed
circuit
board
manufacturing:

Manufacturing
specialist
63
0.078*
0.021
0.378*
0.054
Coater
63
0.134**
0.027
0.217**
0.043
NC
=
No
change
from
baseline;
no
use
of
engineering
controls
(
although
respirators
may
be
required
to
meet
EL)

*
No
monitoring
data
on
baseline
8­
hour
TWA
exposure
to
2­
MEA
were
available.
Data
for
2­
ME
were
used
**
No
monitoring
data
on
baseline
8­
hour
TWA
exposure
to
2­
MEA
were
available.
Data
for
2­
EEA
were
used
Source:
PEI
[
page
15587]

TABLE
VIII­
6
EXPOSURE
REDUCTIONS
FOR
2­
EE
AFTER
APPLYING
ENGINEERING
CONTROLS
|
|
|

|
|
Geometric
mean
|
Arithmatic
mean
Industry
|
Current
|
approach
|
approach
category
|
utili­
|
_______________________
|
_______________________

And
job
|
zation
|
|
|
|

category
|
of
eng­
|
Baseline
|
Average
|
Baseline
|
Average
|
ineering
|
weighted
|
exposures
|
weighted
|
exposures
|
controls
|
plant
|
after
|
plant
|
after
|
(
percent)
|
geometric
|
applying
|
arthmatic
|
applying
|
|
mean
|
engineering
|
mean
|
engineering
|
|
exposure
|
controls
|
exposure
|
controls
|
|
(
ppm)
|
(
ppm)
|
(
ppm)
|
(
ppm)

__________
|
__________
|
__________
|
__________
|
__________
|
__________

Manufacture
of
Glycol
Ethers:

Loading
Technician
50
0.022
NC
0.047
NC
Process
Technician
90
0.092
0.049
0.177
0.119
Laboratory
Technician
90
0.015
NC
0.017
NC
Maintenance
Technician
0
0.057
NC
0.079
NC
Supervisor
0
0.026
NC
0.047
NC
Manufacture
of
Chemical
Intermediates:

Loading
Technician
90
0.022
NC
0.047
NC
Process
Technician
90
0.092
0.049
0.177
0.119
Laboratory
Technician
90
0.015
NC
0.017
NC
Maintenance
Technician
0
0.057
NC
0.079
NC
Formulation
of
Paints
and
Coatings:

Packer
10
1.249
0.250
1.980
0.396
Batchmaker
70
0.673
0.324
0.714
0.361
Laboratory
Technician
70
0.107*
0.041
0.118*
0.056
Aircraft
Mfg/
Repainting:
Spray
painter
67
3.781*
1.569
7.916*
2.160
Motor
Vehicle
Body
Manufacturing:

Spray
painter
90
0.005*
NC
0.035*
NC
Dip
painter
90
0.012*
NC
0.013*
NC
Paint
mixer
50
0.010*
NC
0.227*
0.050
Other
Metal
Applications:

Painter
90
0.052
0.051
0.111
0.098
Auto
Refinishing:

Spray
Painter
67
0.052
0.048
0.111
0.080
Wood
Furniture
Mfg:

Finisher
90
0.656*
0.485
0.830*
0.490
Formulation
of
Inks:

Packer
20
1.249
0.431
1.980
0.532
Batchmaker
80
0.673
0.324
0.714
0.361
Laboratory
70
0.107*
0.041
0.118*
0.056
Technician
Application
of
Inks:

Printing
Operator
63
0.056
0.046
2.441
NC
Semiconductor
Mfg:

Technician
82
0.011*
NC
0.048*
NC
Printed
Circuit
Board
Manufacturing:

Manufact­

uring
Spec
63
0.017
NC
0.031
NC
Coater
63
0.134*
0.027
0.217*
0.043
NC
=
No
change
from
baseline;
no
use
of
engineering
controls
(
although
respirators
may
be
required
to
meet
EL)

*
No
data
on
baseline
8­
hour
TWA
exposure
to
2­
EE
available
for
this
job
category.
Data
for
2­
EEA
were
used
Source:
PEI
TABLE
VIII­
7
EXPOSURE
REDUCTIONS
FOR
2­
EEA
AFTER
APPLYING
ENGINEERING
CONTROLS
|
|
|

|
|
Geometric
mean
|
Arithmatic
mean
Industry
|
Current
|
approach
|
approach
category
|
utili­
|
_______________________
|
_______________________

And
job
|
zation
|
|
|
|

category
|
of
eng­
|
Baseline
|
Average
|
Baseline
|
Average
|
ineering
|
weighted
|
exposures
|
weighted
|
exposures
|
controls
|
plant
|
after
|
plant
|
after
|
(
percent)
|
geometric
|
applying
|
arthmatic
|
applying
|
|
mean
|
engineering
|
mean
|
engineering
|
|
exposure
|
controls
|
exposure
|
controls
|
|
(
ppm)
|
(
ppm)
|
(
ppm)
|
(
ppm)

__________
|
__________
|
__________
|
__________
|
__________
|
__________

Manufacture
of
Glycol
Ethers:

Loading
Technician
50
0.027
NC
0.043
NC
Process
Technician
90
0.049
NC
0.077
0.062
Laboratory
Technician
90
0.023
NC
0.031
NC
Maintenance
Technician
0
0.058
NC
0.116
NC
Supervisor
0
0.017
NC
0.017
NC
Formulation
of
Paints
and
Coatings:

Packer
10
1.370
0.274
3.643
0.729
Batchmaker
70
0.870
0.450
1.072
0.581
Laboratory
Technician
70
0.107
0.041
0.118
0.056
Aircraft
Mfg/
Repainting:

Spray
painter
67
3.781
1.569
7.916
2.160
Other
Metal
Applications:

Painter
90
0.072
0.063
0.397
0.210
[
page
15588]

Wood
Furniture
Mfg:

90
0.656
0.485
0.830
0.490
Finisher
Formulation
of
Inks:

Packer
20
1.370
0.330
3.643
0.757
Batchmaker
80
0.870
0.450
1.072
0.581
Laboratory
Technician
70
0.107
0.041
0.118
0.056
Application
of
Inks:

Printing
Operator
63
0.038
NC
2.071
0.111
Semiconductor
Manufacturing:

Technician
82
0.011
NC
0.048
NC
Printed
Circuit
Board
Manufacturing:

Manufacturing
Specialist
63
0.012
NC
0.030
NC
Coater
63
0.134
0.027
0.217
0.043
NC
=
No
change
from
baseline;
no
use
of
engineering
controls
(
although
respirators
may
be
required
to
meet
EL)

Source:
PEI
TABLE
VIII­
8
METHODS
OF
CONTROLLING
EMPLOYEE
EXPOSURES
(
GEOMETRIC
MEAN
APPROACH)

|
|
|
|
|
|

|
|
Estimated
|
|
|
|
|
|
number
of
|
|
|
|
FTE
|
Estimated
|
workers
|
Estimated
|
Percent
|
Estimated
|
workers
|
total
|
with
|
number
of
|
of
|
number
of
|
in
Industry
|
exposed
|
exposures
|
workers
|
total
|
full­
time
|
ASRs
category
|
workers
|
reduced
|
in
air­
|
exposed
|
equiva­
|
due
|
|
to
TWA
by
|
supplied
|
workers
|
lent
|
to
|
|
substi­
|
respir­
|
in
ASRs
|
workers
|
standard
|
|
tution
or
|
ators
|
due
|
in
ASRs
|
as
|
|
engineer­
|
due
to
|
to
|
due
to
|
percent
|
|
ing
|
standard
|
stand­
|
standard
|
of
total
|
|
controls
|
|
ard
|
|
workers
___________
|
_________
|
_________
|
_________
|
_______
|
_________
|
__________

Manufacture
of
Glycol
Ethers
344
330
14
4%
7
2%

Manufacture
of
Chemical
Intermedi­

ates
80
80
0
0%
0
0%

Formulation
of
Paints
and
Coatings
2,745
2,637
108
4%
26
1%

Aircraft
Manufact­

uring/
Re­

painting
1,998
1,488
510
26%
255
13%

Motor
Vehicle
Body
Manufact­

uring
736
736
0
0%
0
0%

Other
Metal
Applica­

tions
1,464
1,243
221
15%
221
15%

Automobile
Refinish­

ing
26,331
25,893
438
2%
54
0%*

Wood
Furniture
Manufact­

uring
8,140
7,384
756
9%
152
2%

Formulation
of
Inks
946
894
52
5%
20
2%

Application
of
Inks
946
946
0
0%
0
0%

Semi­

conductor
Manufact­

uring
1,704
1,704
0
0%
0
0%

Printed
Circuit
Board
Manufact­

uring
352
306
46
13%
12
4%
Total
45,786
43,641
2,145
5%
795
2%

*
More
than
zero,
but
less
than
0.5%

Source:
PEI
[
page
15589]

TABLE
VIII­
9
METHODS
OF
CONTROLLING
EMPLOYEE
EXPOSURES
(
ARITHMETIC
MEAN
APPROACH)

|
|
|
|
|
|

|
|
Estimated
|
|
|
|

|
|
number
of
|
|
|
|
FTE
|
Estimated
|
workers
|
Estimated
|
Percent
|
Estimated
|
workers
|
total
|
with
|
number
of
|
of
|
number
of
|
in
Industry
|
exposed
|
exposures
|
workers
|
total
|
full­
time
|
ASRs
category
|
workers
|
reduced
|
in
air­
|
exposed
|
equiva­
|
due
|
|
to
TWA
by
|
supplied
|
workers
|
lent
|
to
|
|
substi­
|
respir­
|
in
ASRs
|
workers
|
standard
|
|
tution
or
|
ators
|
due
|
in
ASRs
|
as
|
|
engineer­
|
due
to
|
to
|
due
to
|
percent
|
|
ing
|
standard
|
stand­
|
standard
|
of
total
|
|
controls
|
|
ard
|
|
workers
___________
|
_________
|
_________
|
_________
|
_______
|
_________
|
__________

Manufacture
of
Glycol
Ethers
344
315
29
8%
10
3%

Manufacture
Of
Chemical
Interme­

Diates
80
68
12
15%
3
4%

Formulation
of
Paints
And
Coatings
2,745
2,637
108
4%
26
1%

Aircraft
Manufact­

uring/
Re­

Painting
1,998
1,488
510
26%
255
13%

Motor
Vehicle
Body
Manufact­

Uring
736
736
0
0%
0
0%

Other
Metal
Applica­

Tions
1,464
1,216
248
17%
248
17%

Automobile
Refinishing
26,331
25,600
731
3%
91
0%*

Wood
Furniture
Manufact­

Uring
8,140
7,384
756
9%
152
2%

Formulation
of
Inks
946
894
52
5%
20
2%

Application
of
Inks
946
930
16
2%
5
1%
Semiconductor
Manufact­

Uring
1,704
1,704
0
0%
0
0%

Printed
Circuit
Board
Manufact­

Uring
352
306
46
13%
12
4%

Total
45,786
43,278
2,508
5%
822
2%

*
More
than
zero,
but
less
than
0.5%

Source:
PEI
Costs
Of
The
Proposed
Regulation
OSHA
has
preliminarily
determined
that
the
proposed
standard
is
economically
feasible.
It
is
performance­
oriented.
Employers
may
choose
any
combination
of
engineering
and
work
practice
controls,
or
substitution
of
other
chemicals
for
glycol
ethers,
to
reduce
exposures
to
or
below
the
proposed
TWAs
and
ELs
Table
VIII­
10
shows
estimated
first
year
costs
by
industry
category.
All
substitution
costs
are
expected
to
be
incurred
in
the
first
year
only.
By
substituting,
establishments
would
avoid
all
other
costs
in
the
first
year,
as
well
as
all
costs
in
future
years
Total
first­
year
regulatory
costs
(
substitution
and
compliance)
would
be
$
30.7
million
under
the
geometric
mean
approach
or
$
30.9
million
under
the
arithmetic
mean
approach
Total
substitution
costs
exceed
total
compliance
costs,
primarily
because
of
the
large
amount
of
substitution
that
would
occur
in
formulation
of
paints
and
coatings.
The
highest
first­
year
cost
is
estimated
for
the
paints
and
coatings
formulation
category.
Substitution
occurs
in
all
industry
categories
except
the
manufacturing
of
glycol
ethers
and
chemical
intermediates;
however,
substitution
costs
occur
in
only
four
categories:
formulation
of
paints
and
coatings,
formulation
of
inks,
semiconductor
manufacturing,
and
printed
circuit
board
manufacturing
TABLE
VIII­
10
FIRST
YEAR
COSTS
OF
PROPOSED
STANDARD,
BY
INDUSTRY
CATEGORY
|
|

|
Geometric
mean
approach
|
Arthmatic
mean
approach
|
__________________________
|
____________________________

Industry
|
|
|
|
|
|

Category
|
Cost
of
|
Cost
of
|
Cost
of
|
Cost
of
|
Cost
of
|
Cost
of
|
comp­
|
substi­
|
regula­
|
comp­
|
substi­
|
regulation
|
liance*
|
tution**
|
tion
|
liance*
|
tution**
|
($
000)

|
($
000)
|
($
000)
|
($
000)
|
($
000)
|
($
000)
|

___________
|
________
|
________
|
________
|
________
|
________
|
__________

Manufacture
of
Glycol
Ethers
67
0
67
85
0
85
Manufacture
Of
Chemical
Inter­

mediates
40
0
40
47
0
47
Formulation
Of
Paints
and
Coatings
556
15,400
15,956
559
15,400
15,959
Aircraft
Manufact­

uring/
Re­

painting
695
0
695
695
0
695
Motor
Vehicle
Body
Manufact­

uring
57
0
57
66
0
66
Other
Metal
Applica­

tions
903
0
903
997
0
997
Automobile
Refinish­

ing
5,866
0
5,866
5,866
0
5,866
Wood
Furniture
Manufact­

uring
997
0
997
997
0
997
Formulation
of
Inks
136
3,900
4,036
139
3,900
4,039
Application
of
Inks
67
0
67
103
0
103
Semiconductor
Manufact­

uring
525
650
1,175
525
650
1,175
Printed
Circuit
Board
Manufact­

uring
217
600
817
249
600
849
Total
10,124
20,550
30,674
10,328
20,550
30,878
*
The
first
year
costs
of
engineering
controls
are
annualized;
costs
of
workplace
monitoring,
medical
surveillance
and
recordkeeping
are
estimated
to
be
higher
during
the
first
year
than
they
will
be
in
subsequent
years
**
Although
substitution
costs
are
incurred
in
only
four
industry
categories,
substitution
takes
place
in
all
industry
categories
except
manufacture
of
glycol
ethers
and
manufacture
of
chemical
Intermediates
Source:
PEI
Table
VIII­
11
shows
estimated
annual
costs
by
industry
category.
These
total
$
7.2
million
(
geometric
mean
approach)
or
$
7.4
million
(
arithmetic
mean
approach).
The
highest
annual
cost
is
estimated
to
be
for
the
automobile
refinishing
category.
This
is
due
to
the
large
number
of
establishments;
other
industry
categories
have
higher
per­
establishment
recurring
costs
Tables
VIII­
12
shows
estimated
first
year
and
annual
costs
by
requirement.
Substitution
is
the
most
significant
component
of
the
first
year
costs.
Engineering
controls
(
annualized)
and
exposure
monitoring
are
the
most
significant
components
of
annual
costs.

TABLE
VIII­
11
ANNUAL
COSTS
OF
PROPOSED
STANDARD,
BY
INDUSTRY
CATEGORY
|
|

|
Geometric
|
Arithmetic
|
Mean
Approach
|
Mean
Approach
Industry
Category
|
_________________
|
_________________

|
|

|
Total
Cost
|
Total
Cost
|
($
000)
|
($
000)

__________________________
|
_________________
|
_________________

Manufacture
of
Glycol
Ethers
15
20
Manufacture
of
Chemical
Intermediates
18
23
Formulation
of
Paints
and
Coatings
418
421
Aircraft
Manufacturing/
Repainting
525
525
Motor
Vehicle
Body
Manufacturing
21
21
Other
Metal
Applications
683
757
Automobile
Refinishing
4,254
4,254
Wood
Furniture
Manufacturing
762
762
Formulation
of
Inks
106
109
Application
of
Inks
34
59
Semiconductor
Manufacturing
244
244
Printed
Circuit
Board
Manufacturing
125
157
Total
7,205
7,353
Source:
PEI
TABLE
VIII­
12
FIRST
YEAR
AND
ANNUAL
COSTS
OF
PROPOSED
STANDARD,
BY
REQUIREMENT
|
|

|
Geometric
mean
approach
|
Arithmetic
mean
approach
|
__________________________
|
__________________________

Regulatory
|
|
|
|

requirement
|
First
year
|
Annual
|
First
year
|
Annual
|
($
000)
|
($
000)
|
($
000)
|
($
000)

_____________
|
____________
|
_____________
|
____________
|
_____________

Engineering
Controls
2,611
2,611
2,642
2,642
Protective
Clothing
707
707
707
707
Exposure
Monitoring
3,309
1,815
3,377
1,882
Medical
Surveillance
1,445
618
1,524
641
Respirator
Protection
763
763
784
784
Respirator
Fit
Testing
20
20
20
20
Regulated
Areas,
Signs,

Labels
22
22
23
23
Hygiene
Facilities
160
160
160
160
Information
and
Training
194
194
194
194
Housekeeping
37
37
37
37
Recordkeeping
857
259
860
262
Total
Compliance
Costs
10,124
7,205
10,328
7,353
Substitution
Costs
20,550
0
20,550
0
GRAND
TOTAL
30,674
7,205
30,878
7,353
Source:
PEI
Economic
Feasibility
Analysis
OSHA
preliminarily
determines
that
companies
in
the
industries
involved
in
this
rulemaking
should
be
able
to
absorb
the
costs
of
compliance
with
the
proposed
standard
without
experiencing
undue
burden.
In
addition,
OSHA
also
preliminarily
determines
that
the
compliance
costs
of
this
rulemaking
will
not
threaten
massive
dislocation
in
any
of
the
affected
industries,
will
not
threaten
the
competitive
stability
of
any
of
the
affected
industries,
and
will
not
lead
to
undue
concentration
in
any
of
the
industries.
see
American
Iron
and
Steel
Institute
v.
OSHA,
939
F.
2d
975,
980
(
D.
C.
Cir.
1991;
United
Steelworkers
of
America
v.
Marshall,
647
F.
2d
1189,
1265­
66
(
D.
C.
Cir.
1980),
cert.
denied,
453
U.
S.
913
(
1981).
Therefore,
OSHA
preliminarily
concludes
that
it
is
economically
feasible
to
achieve
the
proposed
standard
by
means
of
engineering
and
work
practice
controls
and
substitution
PEI
compared
regulatory
costs
to
financial
and
economic
parameters
to
determine
the
impacts
of
a
revised
standard
for
glycol
ethers
on
affected
industries.
They
examined
the
extent
to
which
establishments
can
pass
costs
of
regulation
on
to
their
customers,
absorb
costs
that
cannot
be
passed
on,
and
finance
capital
and
up­
front
regulatory
costs.
They
also
analyzed
the
impacts
of
regulatory
requirements
on
competition
and
the
differential
impacts
on
small
businesses.
Information
for
these
analyses
was
obtained
from
Dun
&
Bradstreet
industry
financial
profiles
and
various
reports
issued
by
the
Commerce
Department.
Industry­
wide
impacts
of
first
year
and
recurring
costs
of
the
proposed
standard
are
shown
in
Tables
VIII­
13
and
VIII­
14.
[
page
15591]

TABLE
VIII­
13
INDUSTRY­
WIDE
IMPACTS
OF
FIRST
YEAR*
COSTS
OF
PROPOSED
STANDARD
|
|

|
Geometric
mean
approach
|
Arthmatic
mean
approach
|
____________________________
|
___________________________

Industry
|
|

Category
|
First
year
regulatory
costs
|
First
year
regulatory
costs
|
____________________________
|
___________________________

|
|
|
|
|
|

|
|
As
|
As
|
|
As
|
As
|
Thousands
|
percent
|
percent
|
Thousands
|
percent
|
percent
|
|
Of
|
of
|
|
of
|
of
|
|
revenue
|
profit
|
|
revenue
|
profit
____________
|
_________
|
_________
|
________
|
_________
|
________
|
________

Manufacture
of
Glycol
Ethers
67
0.04%
1.71%
85
0.05%
2.17%

Manufacture
of
Chemical
Interme­

diates
40
0.21%
8.25%
47
0.24%
9.76%

Formulation
of
Paints
And
Coatings
15,956
1.05%
16.41%
15,959
1.05%
16.42%

Aircraft
Manufact­

uring/
Re
painting
695
0.01%
0.43%
695
0.01%
0.43%
Motor
Vehicle
Body
Manufact­

uring
57
0.001%
0.02%
66
0.001%
0.02%

Other
Metal
Applica­

tions
903
0.06%
1.07%
997
0.07%
1.18%

Automobile
Refinish­

ing
5,866
0.02%
0.25%
5,866
0.02%
0.25%

Wood
Furniture
Manufact­

uring
997
0.09%
0.96%
997
0.09%
0.96%

Formulation
of
Inks
4,036
1.15%
27.25%
4,039
1.15%
27.28%

Application
of
Inks
67
0.02%
0.25%
103
0.03%
0.38%

Semiconductor
Manufact­

uring
1,175
0.04%
0.55%
1,175
0.04%
0.55%

Printed
Circuit
Board
Manufact­

uring
817
0.27%
2.77%
849
0.28%
2.88%

Total
30,674
0.05%
0.90%
30,878
0.05%
0.91%

*
First
year
costs
of
engineering
controls
are
annualized;
costs
of
workplace
monitoring,
medical
surveillance,
and
recordkeeping
are
estimated
to
be
higher
during
the
first
year
than
they
will
be
in
subsequent
years
Source:
PEI
TABLE
VIII­
14
INDUSTRY­
WIDE
IMPACTS
OF
ANNUAL
COSTS
OF
PROPOSED
STANDARD
|
|

|
Geometric
mean
approach
|
Arithmetic
mean
approach
|
____________________________
|
___________________________

Industry
|
|

category
|
Annual
regulatory
costs
|
Annual
regulatory
costs
|
____________________________
|
___________________________

|
|
|
|
|
|

|
|
As
|
As
|
|
As
|
As
|
(
Thous­
|
percent
|
percent
|
(
Thous­
|
percent
|
percent
|
ands)
|
of
|
of
|
ands)
|
of
|
of
|
|
revenue
|
profit
|
|
revenue
|
profit
____________
|
_________
|
_________
|
________
|
_________
|
________
|
________

Manufacture
of
Glycol
Ethers
15
0.01%
0.38%
20
0.01%
0.51%

Manufacture
of
Chemical
Interme­

diates
18
0.09%
3.68%
23
0.12%
4.79%

Formulation
of
Paints
And
Coatings
418
0.03%
0.43%
421
0.03%
0.43%

Aircraft
Manufact­

uring/
Re
painting
525
0.01%
0.32%
525
0.01%
0.32%

Motor
Vehicle
Body
Manufact­

uring
21
0.0004%
0.01%
21
0.0004%
0.01%

Other
Metal
Applications
683
0.04%
0.81%
757
0.05%
0.90%

Automobile
Refinishing
4,254
0.01%
0.18%
4,254
0.01%
0.18%

Wood
Furniture
Manufact­

uring
762
0.07%
0.73%
762
0.07%
0.73%

Formulation
of
Inks
106
0.03%
0.72%
109
0.03%
0.74%

Application
of
Inks
34
0.01%
0.13%
59
0.02%
0.22%

Semiconductor
Manufact­

uring
244
0.01%
0.11%
244
0.01%
0.11%

Printed
Circuit
Board
Manufact­

uring
125
0.04%
0.42%
157
0.05%
0.53%

Total
7,205
0.01%
0.21%
7,353
0.01%
0.22%

Source:
PEI
Substitution
is
not
believed
to
place
a
significant
burden
on
those
firms
which
would
be
able
to
use
that
method
of
responding
to
the
proposed
regulation.
Substituting
firms
would
fund
substitution
costs
in
the
first
year
of
the
proposed
regulation;
there
would
be
no
recurring
substitution
costs
For
those
firms
which
do
not
choose
to
substitute,
compliance
costs
should
not
pose
a
significant
problem.
In
most
cases,
costs
can
be
recovered
through
a
price
increase.
Possible
exceptions
are
automobile
refinishing
and
wood
furniture
manufacturing.
If
complying
wood
office
furniture
makers
cannot
increase
prices,
their
compliance
costs
would
cause
their
net
income
to
decline
by
as
much
as
11
percent
under
the
proposed
standard.
If
complying
automobile
repair
shops
and
paint
shops
cannot
increase
prices,
their
net
income
could
decline
by
as
much
as
13
percent
under
the
proposed
standard.
In
general,
automobile
refinishers
should
be
able
to
accommodate
these
impacts.
However,
they
would
likely
present
a
financial
hardship
for
some
operations
with
marginal
profits
Regulatory
Flexibility
Analysis
The
revised
standards
would
have
a
greater
impact
on
small
than
average­
sized
businesses
because
compliance
costs
would
not
necessarily
be
proportional
to
establishment
size.
Thus,
small
establishments
would
have
a
greater
incentive
to
substitute
than
would
larger
establishments.
Because
of
their
comparatively
small
size
(
revenue
of
$
400,000
or
less),
small
printed
circuit
board
manufacturers
within
the
electronics
industry
could
encounter
difficulty
financing
the
up­
front
costs
of
substitution.
However,
small
semiconductor
operations
(
also
within
the
electronics
sector)
should
have
no
trouble
complying;
at
most,
a
price
increase
of
only
0.2
percent
would
be
needed
to
recover
compliance
costs.
In
the
absence
of
a
price
increase,
net
income
would
decline
by
2.4
percent
for
this
industry
category
If
small
printed
circuit
board
manufacturers
cannot
achieve
price
increases
of
from
0.5
to
0.8
percent
to
recover
costs
of
the
proposed
standard,
their
earnings
would
decline
by
5
to
8
percent.

[
page
15592]

IX.
Environmental
Impact
Introduction
OSHA
has
preliminarily
determined
that
no
significant
environmental
impact
will
result
from
the
lower
PELs
and
ancillary
provisions
being
considered
for
the
four
glycol
ethers
­­
2­
methoxyethanol
(
2­
ME),
2­
methoxyethanol
acetate
(
2­
MEA),
2­
ethoxyethanol
(
2­
EE),
and
2­
ethoxyethanol
acetate
(
2­
EEA).
The
principal
source
for
this
analysis
is
a
study
conducted
for
OSHA
by
PEI
Associates,
Inc.,
Technological
Feasibility
and
Economic
Impact
Assessment
of
A
Proposed
Revision
to
the
Glycol
Ethers
Standards,
110,
OSHA
Docket,
Ex.
5­
164
PEI
determined
on
the
basis
of
survey
results
and
site
visits
that
the
following
six
substances
(
all
of
them
also
glycol
ethers)
are
the
most
frequently
used
substitutes
for
2­
ME,
2­
MEA,
2­
EE
and
2­
EEA:
ethylene
glycol
monopropyl
ether
and
its
acetate,
ethylene
glycol
monobutyl
ether
and
its
acetate,
and
propylene
glycol
monomethyl
ether
and
its
acetate.
The
potential
for
environmental
impact
resulting
from
these
six
substitutes
is
examined
Air
Emissions
The
major
Federal
air
pollution
regulation
that
affects
glycol
ether
users
or
manufacturers
is
40
CFR
60,
New
Source
Performance
Standards
(
NSPS),
which
covers
volatile
organic
compounds
(
VOCs).
Users
or
manufacturers
of
glycol
ethers
regulated
under
this
standard
are
Automobile
and
Light
Truck
Surface
Coating,
Graphic
Arts
and
Rotogravure
Printing,
Synthetic
Organic
Chemicals
Manufacturing
and
Surface
Coating
of
Large
Appliances
Mono­,
di­
and
tri­
ethers
of
ethylene
glycol
and
their
acetates
are
listed
as
toxic
chemicals
under
Section
313
of
the
Emergency
Planning
and
Community
Right­
to­
Know
Act
(
Title
III
of
the
Superfund
Amendments
and
Reauthorization
Act
of
1986),
which
requires
recordkeeping
and
reporting
of
emissions
for
all
chemicals
listed
for
facilities
meeting
the
threshold
requirements
of
the
Act.
Thus,
the
major
substitutes
for
the
glycol
ethers
would
be
covered
by
Section
313
in
the
same
manner
as
are
the
glycol
ethers
For
industries
that
use
or
manufacture
glycol
ethers
and
their
substitutes,
Federal
regulations
will
prevent
increases
in
emissions
beyond
those
now
permitted.
Also,
the
glycol
ethers
and
their
major
substitutes
have
low
vapor
pressures,
which
results
in
low
concentrations
in
air
exhaust
streams.
Thus,
no
incremental
air
environmental
impact
is
likely
to
occur
as
a
result
of
reductions
in
the
workplace
exposure
limit
Glycol
ether­
using
industries
that
are
not
subject
to
NSPS
Federal
regulations
(
such
as
the
electronics
industry)
use
some
engineering
controls
to
control
workplace
air
concentrations,
but
do
not
appear
to
use
emission
controls.
That
portion
of
the
glycol
ethers
used
that
does
nor
remain
with
the
product
eventually
evaporates
and
may
enter
the
environment
OSHA
action
to
reduce
workplace
levels
is
projected
to
increase
the
trend
to
substitute
other
substances
for
glycol
ethers.
This
substitution
should
reduce
the
quantity
of
glycol
ethers
entering
the
environment.
The
substitutes
are
generally
less
toxic
than
the
four
glycol
ethers
under
study
and
are
expected
to
have
little
environmental
impact.
Water
Emissions
Because
of
the
way
glycol
ethers
are
sued,
a
water
pollution
problem
does
not
appear
likely.
Neither
the
glycol
ethers
nor
their
substitutes
are
subject
to
pretreatment
standards
that
regulate
discharges
of
industrial
waste
or
municipal
sewage
to
publicly
owned
treatment
works.
State
and
local
standards
regarding
biological
oxygen
demand
and
chemical
oxygen
demand
should
be
sufficient
to
prevent
nay
increase
in
releases
to
water
that
might
occur
as
a
result
of
more
stringent
occupational
exposure
limits.
Thus,
no
negative
impact
on
the
environment
is
projected
X.
Summary
And
Explanation
Of
The
Proposed
Standard
OSHA
believes
that
the
proposed
requirements
set
forth
in
this
notice
are
necessary
and
appropriate
to
provide
adequate
protection
to
employees
exposed
to
ethylene
glycol
ethers
based
on
currently
available
information.
Numerous
reference
works,
journal
articles,
and
other
data
obtained
by
OSHA
have
been
taken
into
consideration
in
the
development
of
this
proposed
standard
Scope
and
Application:
Paragraph
(
a)

The
proposed
standard
would
apply
to
all
occupational
exposures
to
the
ethylene
glycol
ethers
2­
Methoxyethanol
(
2­
ME),
2­
Ethoxyethanol
(
2­
EE),
and
their
respective
acetates
2­
Methoxyethanol
Acetate
(
2­
MEA),
and
2­
Ethoxyethanol
Acetate
(
2­
EEA)
except
where
the
exposure
occurs
from
1)
liquid
mixtures
which
contain
less
than
1%,
by
volume,
of
the
above
compounds
unless
the
employer
has
reason
to
believe
that
such
mixtures
could
release
vapors
in
quantities
sufficient
to
result
in
an
airborne
concentration
which
meets
or
exceeds
the
ALs
or
ELs
of
the
compounds
or
could
present
a
hazard
through
dermal
contact;
and
2)
solids
made
from
or
containing
2­
ME,
2­
MEA,
2­
EE,
or
2­
EEA
that
are
incapable
of
releasing
these
compounds
into
the
workplace
air
at
or
above
the
ALs
or
above
the
ELs
The
exemption
for
liquids
with
less
than
1%
glycol
ethers
is
consistent
with
the
Hazard
Communication
Standard
(
HCS),
29
CFR
1910.1200,
paragraph
(
g)(
2)(
C)(
1),
which
does
not
require
inclusion
of
a
non­
carcinogenic
chemical
on
a
Material
Safety
Data
Sheet
(
MSDS)
if
it
comprises
less
than
1%
of
the
composition
of
the
mixture.
However
while
OSHA
believes,
in
general,
that
liquid
mixtures
containing
less
than
1%
glycol
ethers
may
present
little
hazard,
there
may
be
situations
where
the
mixture,
despite
its
low
concentration
of
glycol
ethers,
might
release
vapors
at
or
above
the
action
levels
or
above
the
excursion
levels
or
present
a
hazard
through
dermal
contact.
For
example
a
large
volume
of
a
mixture
containing
less
than
1%
of
glycol
ethers
may
be
released
(
e.
g.
spill
or
tank
rupture)
and
give
rise
to
high
airborne
levels
of
the
glycol
ethers
by
virtue
of
the
large
volume
of
mixture
that
is
released.
Also
a
work
practice
involving
a
prolonged
or
repeated
dermal
contact
to
a
mixture
containing
less
than
1%
glycol
ethers
could
provide
enough
exposure
to
the
glycol
ethers
in
the
mixture
to
result
in
a
significant
dermal
exposure.
Thus
it
is
proposed
that
if
an
employer
has
reason
to
believe
that
liquid
mixtures
with
less
than
1%
glycol
ethers
could
release
glycol
ethers
vapors
in
concentrations
at
or
above
the
action
levels
or
above
the
excursion
levels
or
could
present
a
hazard
through
dermal
contact,
then
that
employer
must
comply
with
all
provisions
of
the
standard
for
glycol
ethers.
An
employer's
belief
of
the
potential
for
such
occurrences
may
be
based
on
such
things
as
information
from
a
manufacturer
or
trade
association
or
the
employer's
knowledge
about
chemical
processes
or
work
practices
in
his
workplace
OSHA
also
proposes
that
solids
made
from
or
containing
glycol
ethers
that
are
capable
of
releasing
those
glycol
ethers
into
the
workplace
air
at
or
above
the
action
levels
or
above
the
excursion
levels
are
also
exempt
from
the
scope
of
this
standard.
In
general
glycol
ethers
are
used
as
solvents
in
compounds
which
are
used
in
the
workplace.
During
the
use
of
these
compounds,
the
glycol
ethers
evaporate.
Thus
upon
drying
there
is
no
glycol
ether
left
in
the
[
page
15593]

dried
compound
which
could
off
gas
vapors
to
the
workplace
air.
Since
these
solids
would
present
little
hazard,
it
is
proposed
that
they
be
exempted
from
the
scope
of
the
standard.
However
if
there
are
situations
where
solids
containing
glycol
ethers
could
release
vapors
at
or
above
the
action
levels
or
above
the
excursion
levels,
then
these
solids
would
be
covered
under
the
scope
of
the
standard.
OSHA
is
unaware
of
any
such
situations
and
requests
information
on
the
existence
of
such
occurrences
in
the
workplace
This
proposed
standard
covers
only
the
four
ethylene
glycol
ethers
(
2­
ME,
2­
MEA,
2­
EE,
and
2­
EEA)
referred
to
OSHA
by
EPA
under
section
9(
a)
of
the
TSCA.
In
the
ANPR
for
these
substances
OSHA
discussed
the
possibility
of
expanding
the
scope
of
the
rulemaking
to
cover
other
glycol
ethers.
In
that
notice,
OSHA
stated
that,
based
on
their
similarities
in
structure
and
routes
of
metabolism,
the
adverse
effects
of
at
least
some
of
the
other
glycol
ethers
may
be
similar
to
2­
ME,
2­
EE
and
their
acetates.
For
these
reasons
OSHA
stated
that
it
might
be
appropriate
to
include
other
glycol
ethers
within
the
scope
of
a
proposed
standard
for
glycol
ethers
Several
commentors
to
the
ANPR
(
Exs.
7­
11,
7­
12,
7­
13,
7­
14,
7­
16,
7­
17,
7­
18,
7­
20,
7­
21,
7­
23,
7­
24
and
7­
28)
did
not
support
expanding
the
scope
of
the
rulemaking.
In
general
these
commentors
stated
that
because
of
the
differences
in
the
toxicities
between
the
four
subject
glycol
ethers
and
longer
chain
glycol
ethers,
they
did
not
believe
that
it
was
appropriate
to
promulgate
a
generic
standard
for
all
glycol
ethers.
In
particular,
ARCO
(
Ex.
7­
19)
stressed
the
differences
between
ethylene
glycol
ethers
and
propylene
glycol
ethers.
ARCO
presented
statements
and
evidence
that
propylene
glycol
ethers
are
metabolized
by
different
pathways
than
the
ethylene
glycol
ethers
resulting
in
different
primary
metabolites
of
lesser
toxicity.
Furthermore
ARCO
added
that
the
propylene
glycol
ethers
have
not
been
shown
to
induce
adverse
reproductive
and/
or
developmental
effects
similar
to
2­
ME,
2­
EE
and
their
acetates.
NIOSH
(
Ex.
7­
22)
stated
that
in
general
they
would
support
a
generic
approach
to
rulemaking.
However,
in
the
case
of
other
glycol
ethers
they
stated
that
the
data
were
limited
and
therefore
they
recommended
one
standard
with
two
PELs,
one
for
2­
ME/
2­
MEA
and
one
for
2­
EE/
2­
EEA.
Two
commentors
to
the
ANPR,
TVA
and
Public
Citizen
(
Exs.
7­
15
and
7­
25),
did
support
a
generic
glycol
ethers
standard,
stating
that
the
effects
may
potentially
be
similar
for
other
glycol
ethers
As
discussed
in
Section
V
­
Health
Effects,
OSHA
believes
that
the
data
are
limited
on
the
toxicity
for
glycol
ethers
other
than
2­
ME,
2­
EE
and
their
acetates.
The
data
which
are
available,
indicate
that
toxicities,
as
well
as
the
uses
of
other
glycol
ethers,
may
vary
to
such
an
extent
that
a
generic
standard
for
all
glycol
ethers
may
be
inappropriate.
For
this
reason
the
scope
of
this
proposal
is
limited
to
occupational
exposure
to
2­
ME,
2­
EE
and
their
acetates.
OSHA
requests
comments
on
this
approach.
In
particular,
the
Agency
is
interested
in
health
effects
data
on
other
glycol
ethers
OSHA
is
also
proposing
that
construction
be
included
under
the
scope
of
the
standard,
by
amending
section
1910.19
to
add
a
new
paragraph
(
n)
for
glycol
ethers.
OSHA's
reasoning
is
as
follows.
Firstly,
based
on
current
evidence,
OSHA
believes
that
the
proposed
standard
would
have
little
impact
on
construction.
However
a
significant
source
of
exposure
may
occur
in
maintenance
operations
at
facilities
that
manufacture,
formulate
or
use
glycol
ethers
or
liquids
containing
glycol
ethers.
Exposure
during
these
operations
may
be
relatively
high
and
it
is
necessary,
therefore,
that
employees
wear
respirators,
receive
medical
examinations
and
be
protected
by
the
other
provisions
of
the
proposed
glycol
ethers
standard.
Sometimes
such
facilities
hire
outside
contractors
to
perform
maintenance
operations.
The
contention
is
sometimes
made
that
the
maintenance
operations
should
be
considered
to
be
construction
activities
and
not
subject
to
general
industry
standards.
Employees
of
such
contractors
are
subject
to
the
same
levels
of
glycol
ethers
and
need
the
same
protection
as
other
exposed
employees.
OSHA
proposes
to
cover
these
employees
under
the
glycol
ethers
standard
Thus,
although
the
impact
of
the
standard
will
be
limited,
OSHA
believes
that
construction
should
not
be
exempted
from
the
standard.
OSHA
believes
that
a
loophole
would
be
opened
in
the
enforcement
of
the
standard
if
construction
were
exempted.
The
distinction
between
maintenance
and
construction
activities
is
often
an
ambiguous
one.
The
independent
contractors
who
perform
maintenance
clearly
need
to
be
covered.
If
construction
were
excluded,
these
maintenance
contractors
might
argue
that
their
work
is
"
construction"
and
that
they
are
not
covered
by
the
standard.
By
covering
construction,
this
ambiguity
does
not
arise.
This
approach
is
consistent
with
other
standards
(
e.
g.,
Ethylene
Oxide,
29
CFR
1910.1047
and
Benzene,
29
CFR
1910.1028).
OSHA
requests
comments
on
this
approach
for
glycol
ethers.
OSHA
also
welcomes
data
on
the
exposure
and
use
of
glycol
ethers
in
the
construction
industry
which
may
be
different
from
those
in
general
industry
Definitions:
Paragraph
(
b)

Action
level
is
defined
as
an
airborne
concentration
of
0.05
ppm
for
2­
ME
and
2­
MEA
and
an
airborne
concentration
of
0.25
ppm
for
2­
EE
and
2­
EEA,
calculated
as
an
8­
hour
time
weighted
average
(
TWA).
For
workers
exposed
at
or
above
the
action
level,
without
regard
to
the
use
of
respiratory
protection,
medical
surveillance
and
air
monitoring
are
required.
Generally,
where
exposures
are
determined
to
be
below
the
action
levels
of
0.05
ppm
(
2­
ME,
2­
MEA)
and
0.25
ppm
(
2­
EE,
2­
EEA),
no
further
action
is
required
of
the
employer
except
provision
of
training
as
required
by
paragraph
(
m)
of
this
section
and
provision
of
appropriate
personal
protective
equipment
as
required
by
paragraph
(
h)
of
this
section
Measurements
of
employee
exposure
can
vary
considerably
for
a
number
of
reasons
including
process
variations,
sampling
and
analytical
methods
limitations,
and
seasonal
changes.
Therefore,
even
if
all
the
measurements
taken
on
a
given
day
fall
below
the
8­
hour
time
weighted
average
(
TWA)
permissible
exposure
limit,
the
possibility
exists
that
on
unmeasured
days
an
employee's
actual
exposure
may
exceed
the
TWA.
More
explicitly,
when
measured
exposure
levels
are
over
one­
half
of
the
TWA,
the
employer
cannot
have
a
high
degree
of
confidence
that
employees
are
not
overexposed
to
glycol
ethers
during
unmeasured
periods
of
the
work
week.
Conversely,
when
the
measured
concentrations
are
below
the
action
level,
the
employer
can
have
a
reasonable
degree
of
confidence
that
the
TWA
is
not
being
exceeded
on
days
when
exposure
measurements
are
not
being
performed
Based
on
the
above
concept,
the
action
level
provides
a
means
of
triggering
various
provisions
of
the
proposed
regulation
relative
to
the
exposure
levels
of
employees.
This
approach
increases
cost­
effectiveness
and
performance
orientation
of
the
standard
while
enhancing
employee
protection.
For
example,
it
is
proposed
that
employers
who
maintain
employee
exposure
below
the
action
level
be
relieved
of
the
obligations
of
further
monitoring
and
medical
surveillance
of
those
employees.
Employers
are
thereby
encouraged
to
develop
cost­
effective,

[
page
15594]

innovative
approaches
for
reducing
employee
exposures
below
the
action
level
in
order
to
eliminate
the
expense
of
implementing
certain
provisions
of
the
standard
Employees
will
benefit
by
improved
protection
since
their
exposures
will
be
less
than
one­
half
of
the
TWA
permissible
exposure
limit.
In
addition,
employers
can
focus
their
attention
on
employees
whose
exposure
levels
may
be
significant.
Those
employees
exposed
at
or
above
the
action
level
will
have
the
added
protection
of
medical
surveillance,
monitoring,
and
other
provisions
of
the
proposed
standard
The
use
of
action
levels
to
trigger
provisions
of
the
proposed
standard
and
the
setting
of
the
action
level
at
one­
half
of
the
TWA
is
consistent
with
other
OSHA
health
standards,
such
as
Asbestos
(
51
FR
22612,
June
20,
1986;
29
CFR
1910.1001),
Benzene
(
52
FR
34460,
September
11,
1987;
29
CFR
1910.1028),
and
Formaldehyde
(
52
FR
46168,
December
4,
1987;
29
CFR
1910.1048).
This
uniformity
provides
administrative
consistency
and
continuity
in
developing
and
implementing
compliance
strategies
for
this
and
other
applicable
OSHA
health
standards
at
individual
worksites
Authorized
Person
means
any
person
specifically
authorized
by
the
employer,
whose
duties
require
the
person
to
enter
a
regulated
area,
or
any
person
entering
such
an
area
as
a
designated
representative
of
employees
for
the
purpose
of
exercising
the
right
to
observe
monitoring
and
measuring
procedures
under
paragraph
(
d)
of
this
section,
or
any
other
person
authorized
by
the
Act
or
regulations
issued
under
the
Act.
Examples
of
such
people
would
include,
but
are
not
limited
to,
employees
who
normally
work
in
the
regulated
area,
union
representatives,
and
OSHA
compliance
officers
Emergency
is
defined
to
mean
any
occurrence
such
as,
but
not
limited
to,
equipment
failure,
rupture
of
containers,
or
failure
of
control
equipment
which
may
or
does
result
in
an
unexpected
release
of
a
significant
amount
of
glycol
ethers.
Every
spill
or
leak
does
not
automatically
constitute
an
emergency
situation.
The
exposure
to
employees
must
be
high
as
well
as
unexpected.
This
is
a
performance­
oriented
definition
relying
upon
judgment
Employee
exposure
is
defined
as
that
exposure
to
airborne
or
liquid
glycol
ethers
which
would
occur
if
the
employee
were
not
using
respiratory
protective
equipment
or
other
personal
protective
equipment.
This
definition
is
consistent
with
OSHA's
previous
use
of
the
term
in
other
standards
Ethylene
Glycol
Ethers
for
the
purposes
of
this
section,
means
2­
Methoxyethanol
(
2­
ME)
(
CAS
No.
109­
86­
4),
2­
Methoxyethanol
acetate
(
2­
MEA)
(
CAS
No.
110­
49­
6),
2­
Ethoxyethanol
(
2­
EE)
(
CAS
No.
110­
80­
5),
and
2­
Ethoxyethanol
acetate
(
2­
EEA)
(
CAS
No.
111­
15­
9).
The
family
of
ethylene
glycol
ethers
is
comprised
of
a
large
number
of
compounds.
At
the
present
time,
however,
this
proposed
standard
will
deal
with
only
those
four
compounds
noted
above.
These
four
chemicals
are
also
known
by
a
variety
of
chemical
and
trade
names.
Therefore,
to
eliminate
confusion
as
to
which
compounds
are
being
considered
for
regulation,
they
have
also
been
identified
by
their
CAS
number.
This
number
is
assigned
by
the
Chemical
Abstract
Service
and,
without
regard
to
system
of
chemical
nomenclature
or
trade
name,
is
unique
to
a
specific
chemical.
A
detailed
discussion
of
the
chemical
properties
of
these
compounds
can
be
found
in
Section
IV,
"
Chemical
Identification,
Production
and
Use
of
Ethylene
Glycol
Ethers"
of
this
document.
Glycol
Ethers
is
defined
the
same
as
"
Ethylene
glycol
ethers"

above
and
for
the
purpose
of
the
document
is
used
interchangeably
with
the
above
term
Objective
Data
means
information
demonstrating
that
a
particular
product
or
material
containing
glycol
ethers
or
a
specific
process,
operation,
or
activity
involving
glycol
ethers
cannot
release
glycol
ethers
in
airborne
concentrations
at
or
above
the
action
level
or
above
the
excursion
limit
or
result
in
dermal
exposure,
even
under
worst­
case
release
conditions
of
foreseeable
use.
A
more
detailed
discussion
of
"
objective
data"
can
be
found
in
paragraph
(
d),
Exposure
Monitoring,
of
this
section
Regulated
Area
means
any
area
where
airborne
concentrations
of
glycol
ethers
exceed
or
can
reasonably
be
expected
to
exceed
the
permissible
exposure
limits,
either
the
8­
hour
time­
weighted
average
(
TWA)
permissible
exposure
limits
of
0.1
ppm
(
2­
ME,
2­
MEA)
and
0.5
ppm
(
2­
EE,
2­
EEA)
or
the
15­
minute
excursion
limits
(
EL)
of
0.5
ppm
(
2­
ME,
2­
MEA)
and
2.5
ppm
(
2­
EE,
2­
EEA).
Regulated
areas
must
be
established
anytime
the
airborne
concentration
of
glycol
ethers
exceeds
or
can
be
expected
to
exceed
the
TWAs
and/
or
ELs.
Their
existence
may
be
of
extended
duration,
such
as
when
currently
feasible
engineering
and
work
practice
controls
are
inadequate
to
lower
airborne
glycol
ether
concentrations
below
the
PELs,
or
they
may
exist
for
only
a
short
period
of
time
as
could
be
expected
during
a
maintenance
operation.
Requirements
specifically
pertaining
to
regulated
areas
are
found
in
paragraph
(
e)
of
this
section
Permissible
Exposure
Limits:
Paragraph
(
c)

OSHA
proposes,
in
paragraph
(
c)(
1),
to
establish
new
permissible
exposure
limits
for
ethylene
glycol
ethers
by
amending
the
current
standards
found
in
29
CFR
1910.1000,
Table
Z­
1­
A,
which
are
8­
hour
time
weighted
averages
(
TWAs)
of
200
ppm
for
2­
EE,
100
ppm
for
2­
EEA,
and
25
ppm
for
both
2­
ME
and
2­
MEA.
OSHA
is
proposing
new
permissible
exposure
limits
of
0.1
ppm
for
2­
ME
and
2­
MEA
and
0.5
ppm
for
2­
EE
and
2­
EEA
calculated
as
an
8­
hour
TWA.
In
addition,
the
Agency
is
proposing,
in
paragraph
(
c)(
2),
15­
minute
excursion
limits
(
ELs)
of
0.5
ppm
(
2­
ME,
2­
MEA)
and
2.5
ppm
(
2­
EE,
2­
EEA).
These
limits
are
the
airborne
concentration,
averaged
over
a
15­
minute
sampling
period,
resulting
from
monitoring
conducted
during
an
employee's
anticipated
highest
level
of
exposure
OSHA
has
proposed
to
amend
the
current
TWAs
based
upon
evidence
that
occupational
exposure
to
ethylene
glycol
ethers
at
the
current
standards
presents
a
significant
risk
of
adverse
hematologic,
reproductive
and
developmental
effects
while
the
proposed
TWAs
would
achieve
a
significant
reduction
in
that
risk.
The
basis
for
this
action
is
discussed
in
the
significance
of
risk,
health
effects,
and
feasibility
sections
preceding
this
section.
Overall,
however,
OSHA
has
made
the
preliminary
determination
that
the
proposed
TWAs
reduce
significant
risk
and
are
feasible
In
conjunction
with
the
8­
hour
TWAs,
OSHA
is
proposing
15­
minute
excursion
limits
for
these
ethylene
glycol
ethers
in
paragraph
(
c)(
2).
The
Agency
feels
that
establishing
ELs
will
further
reduce
significant
risk.
As
discussed
in
the
preliminary
risk
assessment
section,
the
proposed
TWAs
of
0.1
ppm
for
2­
ME
and
2­
MEA
and
0.5
ppm
for
2­
EE
and
2­
EEA
were
derived
by
dividing
the
NOELs
from
experimental
studies
by
uncertainty
factors
of
100.
OSHA
believes
that
using
an
uncertainty
factor
of
100
results
in
a
level
at
which
workers
will
be
less
likely
to
experience
adverse
reproductive
or
developmental
effects
such
as
those
observed
in
animal
studies.
However,
it
should
be
kept
in
mind
that
these
levels
(
0.1
and
0.5
ppm)
represent
eight­
hour
time
weighted
averages.
Thus,
it
is
possible
that
the
levels
for
2­
ME/
2­
MEA
and
2­
EE/
2­
EEA
could
reach
as
high
as
3.2
ppm
or
16.0
ppm,
respectively,
for
any
15­
minute
period
and
still
meet
the
8­
hour
[
page
15595]

TWAs
of
0.1
and
0.5
ppm,
provided
that
there
are
no
other
exposures
in
the
8­
hour
period.
Under
this
exposure
scenario,
the
uncertainty
factor
is
lowered
from
100
to
approximately
3.
This
reduction
in
the
margin
of
safety
may
be
important
in
the
case
of
reproductive
and
developmental
effects
where
peak
doses
rather
than
cumulative
doses
may
play
an
important
role
in
the
biological
effects.
For
example,
peak
doses
occurring
at
critical
periods
of
fetal
or
spermatogenic
development
may
induce
adverse
effects
due
to
the
sensitivity
of
that
particular
period
of
development.
Thus,
OSHA
believes
that
it
is
important
to
reduce
peak
exposures
to
the
extent
possible.
Implementing
excursion
limits
five
times
the
TWAs
(
i.
e.,
0.5
for
2­
ME/
2­
MEA
and
2.5
ppm
for
2­
EE/
2­
EEA)
will
decrease
the
reduction
in
the
uncertainty
factors
and
thus
provide
a
greater
likelihood
that
workers
will
not
suffer
an
adverse
reproductive
or
developmental
effect
from
exposure
While
OSHA
is
proposing
15­
minute
excursion
limits
of
5
times
the
respective
TWAs,
it
should
be
noted
that
paragraph
(
c)(
2)(
A)
prohibits
an
employee's
exposure
from
exceeding
the
TWAs
through
such
15­
minute
exposures.
Therefore,
even
though
an
employee
receives
his/
her
exposure
in
short
bursts,
the
overall
exposure
level
cannot
exceed
the
TWAs
when
the
excursion
limit
exposures
are
calculated
as
an
8­
hour
time
weighted
average.
In
addition,
when
an
employee's
15­
minute
excursion
exposures,
calculated
as
an
8­
hour
time
weighted
average,
are
at
or
above
the
action
level,
then
all
provisions
of
this
section
which
are
triggered
at
the
action
level
must
be
implemented
for
that
employee
In
addition
to
exposure
by
inhalation,
glycol
ethers
are
readily
absorbed
through
the
skin.
As
a
result,
both
the
OSHA
PELs
and
the
American
Conference
of
Governmental
Industrial
Hygienists
(
ACGIH)
TLVs
carry
a
"
skin"
notation
for
the
four
glycol
ethers
under
consideration.
Studies
have
shown
that
dermal
absorption
of
these
compounds,
either
alone
or
in
conjunction
with
inhalation
exposure,
is
capable
of
inducing
adverse
effects
in
animals
and/
or
humans
(
Exs.
4­
121,
4­
139,
5­
049,
5­
073).
The
Agency,
therefore,
has
proposed
in
paragraph
(
c)(
3)
that
the
employer
assure
that
no
employee
is
exposed
to
glycol
ethers
through
dermal
contact
Exposure
Monitoring:
Paragraph
(
d)

Paragraphs
(
d)(
1)
through
(
d)(
7)
of
the
proposed
standard
would
impose
monitoring
requirements
pursuant
to
Section
6(
b)(
7)
of
the
OSH
Act
(
29
U.
S.
C.
§
655)
which
mandates
that
any
standard
promulgated
under
section
6(
b)
shall,
where
appropriate,
"
provide
for
monitoring
or
measuring
of
employee
exposure
at
such
locations
and
intervals,
and
in
such
manner
as
may
be
necessary
for
the
protection
of
employees."
The
Agency
believes
that
the
employer's
knowledge
of
exposures
existing
among
employees
is
fundamental
to
the
provision
of
a
healthful
workplace.
The
purposes
served
by
requiring
initial
and
periodic
air
sampling
for
employee
exposures
to
glycol
ethers
include:
prevention
of
employee
overexposure;
determination
of
the
extent
of
exposure
at
the
worksite;
identification
of
the
sources
of
exposure
to
glycol
ethers;
collection
of
exposure
data
so
that
the
employer
can
select
the
proper
control
methods
to
be
used;
and
evaluation
of
the
effectiveness
of
the
selected
methods.
Monitoring
enables
employers
to
meet
the
legal
obligation
of
the
standard
to
ensure
that
their
employees
are
not
exposed
to
ethylene
glycol
ethers
in
excess
of
the
prescribed
levels
and
to
notify
employees
of
their
exposure
levels,
as
required
by
section
8(
c)(
3)
of
the
Act.
In
addition,
collection
of
exposure
monitoring
data
enables
the
examining
physician
to
be
informed
of
the
existence
and
extent
of
potential
sources
of
occupational
diseases
Exposure
monitoring
is
critical
to
determining
the
specific
levels
of
glycol
ethers
to
which
employees
are
exposed.
A
number
of
obligations
are
delineated
by
specific
exposure
levels
above
which
certain
provisions
have
to
be
implemented
to
protect
the
employees
and
achieve
compliance
with
the
standard.
Medical
surveillance
and
exposure
monitoring
provisions
of
the
standard
are
triggered,
for
example,
for
employees
exposed
at
or
above
the
AL
or
above
the
EL.
The
remaining
provisions
of
the
standard
are
triggered
by
employee
exposure
above
the
TWA
The
exposure
monitoring
provision
of
paragraph
(
d)(
1)(
i)
would
require
each
employer
who
has
a
workplace
or
work
operation
covered
by
this
section
to
accurately
determine
employee
exposure
to
ethylene
glycol
ethers.
While
initial
evaluation
of
employee
exposure
would
require
either
actual
monitoring
of
each
employee
or
the
use
of
objective
data,
subsequent
determinations
may
be
carried
out
through
representative
sampling
and
would
not
necessarily
entail
sampling
of
all
exposed
employees
Paragraph
(
d)(
1)(
ii)
would
require
that
these
determinations
be
made
from
samples
that
are
taken
within
the
employee's
breathing
zone
(
personal
samples)
and
which
accurately
reflect
the
employee's
exposure,
without
regard
to
the
use
of
respirators,
to
airborne
concentrations
of
glycol
ethers
over
an
eight­
hour
period.
This
permits
the
employer
to
ascertain
compliance
with
the
ALs
and
the
TWAs.
In
addition,
the
employer
must
monitor
employees
over
a
fifteen
minute
period
to
determine
whether
they
are
in
compliance
with
the
excursion
limits
(
ELs)
at
operations
where
there
is
reason
to
believe
that
exposures
may
be
above
the
ELs.
Examples
of
situations
which
may
present
the
potential
for
elevated
short
term
exposures
include,
but
are
not
limited
to,
where
tanks
are
opened,
filled,
unloaded,
or
gauged;
where
containers
or
process
equipment
are
opened;
where
glycol
ethers
are
transferred
between
containers
or
added
to
mixtures
in
open
systems;
and
where
glycol
ethers
are
used
for
cleaning
or
as
a
solvent
in
an
uncontrollable
situation
as
may
be
found,
for
example,
in
the
cleaning
of
machinery
where
neither
permanent
nor
temporary
engineering
or
work
practice
controls
are
adequate
to
reduce
the
levels
of
glycol
ethers
to
or
below
the
ELs
Paragraph
(
d)(
1)(
iii)
would
require
the
employer
to
determine
TWA
and
EL
employee
exposures
for
each
employee
in
each
job
classification,
in
each
work
area,
and
for
each
shift
whenever
exposure
to
glycol
ethers
exists.
Except
for
the
initial
monitoring
that
would
be
required
by
this
section,
paragraph
(
d)(
1)(
iv)
states
that
a
representative
sampling
strategy
may
be
developed
which
will
measure
sufficient
exposure
levels
within
each
job
classification
or
for
each
job
task
(
if
there
is
task
variation
within
a
job
classification
which
could
result
in
different
exposure
levels
within
that
job
classification)
for
each
workshift,
in
each
work
area
to
correctly
characterize
and
not
underestimate
the
exposure
of
any
employee
within
each
exposure
group.
However,
exposure
levels
shall
be
determined
for
each
employee
in
each
job
classification
in
each
work
area
for
each
shift
unless
the
employer
can
document
that
exposure
levels
for
a
given
job
classification
are
equivalent
for
different
work
shifts
Representative
exposure
sampling
is
permitted
when
there
are
a
number
of
employees
performing
the
same
job
function
in
the
same
job
classification
under
the
same
conditions.
For
such
employees,
it
may
be
sufficient
to
monitor
some
fraction
of
such
employees
in
order
to
obtain
data
that
are
"
representative"
of
the
remaining
employees.
Representative
personal
sampling
of
these
employees
must
include
that
member(
s)
of
the
exposed
group
reasonably
expected
to
have
the
[
page
15596]

highest
exposure.
This
result
can
then
be
applied
to
the
remaining
employees
of
the
group.
In
developing
a
representative
sampling
strategy,
the
employer
must
systematically
examine
process
and
workplace
variables
to
identify
which
employees
are
to
be
monitored.
Strategy
development
should
include:
1)
investigation
of
worksites
where
the
nature
of
the
operation
or
process
indicates
possible
release
of
glycol
ethers
into
the
work
environment
to
identify
the
sources
of
these
emissions;
2)
investigation
of
worksites
where
there
have
been
employee
complaints
or
symptoms
indicative
of
possible
exposure
to
glycol
ethers;
3)
analysis
of
exposure
patterns
within
the
worksite,
including
each
employee's
distance
from
the
source
of
glycol
ethers,
variations
in
tasks
among
employees
in
the
same
job
classification,
employee
mobility,
air
movement
patterns,
and
differences
in
work
habits
As
stated
in
paragraph
(
d)(
1)(
v),
objective
data
[
as
defined
in
paragraph
(
b)]
may
also
be
used
by
the
employer
to
document
that
the
presence
of
glycol
ethers
in
the
workplace
or
products
containing
glycol
ethers
cannot
result
in
the
release
of
airborne
concentrations
of
glycol
ethers
that
would
cause
any
employee
to
be
exposed
at
or
above
the
action
level
or
above
the
EL
under
worst­
case
release
conditions
of
foreseeable
use.
If
the
employer
can
adequately
demonstrate
with
objective
data
that
the
preceding
conditions
exist,
then
the
employer
is
relieved
of
measuring
employee
exposure
to
glycol
ethers
A
detailed
discussion
of
"
objective
data"
can
be
found
in
the
final
standard
for
Formaldehyde
(
52
FR
46255).
Pertinent
portions
of
that
discussion
are
reproduced
here
for
the
sake
of
convenience
and
clarification
.
Employers
can
use
data
on
physical
properties,
combined
with
information
as
to
room
dimensions,
air
exchange
rates,
and
other
pertinent
data,
including,
for
example,
information
on
work
practices,
to
estimate
the
maximum
exposures
that
could
be
anticipated
in
the
workplace.
Relying
on
such
an
approach
to
estimate
worker
exposures
from
objective
data
requires
the
use
of
safety
factors
to
account
for
uneven
distribution
of
formaldehyde
vapor
in
the
air
and
the
proximity
of
workers
to
emissions
sources
(
Ex.
73­
176).
Objective
data
could
also
include
historical
data
on
employee
exposures,
area
monitoring
conducted
to
determine
ambient
formaldehyde
levels
and
emissions
from
sources
of
formaldehyde
releases,
or
carefully
evaluated
monitoring
conducted
for
other
than
a
full
shift
or
15­
minute
period.
.
OSHA
recognizes
that
many
workplace
factors
must
be
taken
into
account
by
employers
relying
on
objective
data
(
see
50
FR
50473).

In
retaining
the
objective
data
requirement,
OSHA
does
not
intend
that
employers
engage
in
complex
modeling
exercises
as
a
substitute
for
employee
exposure
monitoring,
and
the
Agency
recognizes
that,
in
workplaces
where
many
complex
factors
must
be
considered
to
use
objective
data,
a
high
degree
of
uncertainty
will
be
associated
with
trying
to
assess
employee
exposures
from
objective
data.
In
these
instances,
employers
should
conduct
exposure
monitoring
instead
of
relying
on
objective
data
so
that
they
can
have
confidence
that
they
are
in
compliance
with
the
standard's
provisions
Moreover,
in
workplaces
where
many
complex
factors
combine
to
influence
employee
exposures
to
formaldehyde,
employers
may
find
it
easier,
more
useful,
and
less
costly
to
monitor
rather
than
to
try
to
evaluate
employee
exposures
through
generation
and
evaluation
of
objective
data
Briefly
summarizing
the
above
discussion,
a
number
of
workplace
factors
must
be
taken
into
account
when
relying
on
objective
data
(
e.
g.
temperature,
humidity,
ventilation
rate,
employee
proximity
to
contaminant
source),
however,
it
is
not
the
Agency's
intent
that
employers
engage
in
complex
modeling
exercises
in
place
of
employee
exposure
monitoring.
In
workplaces
where
a
number
of
complex
factors
must
be
considered,
the
employer
should
conduct
exposure
monitoring,
rather
than
relying
upon
objective
data,
to
increase
confidence
that
they
are
in
compliance
with
the
standard's
provisions.
Initial
monitoring
of
workplace
exposures
would
be
required
of
all
employers
who
have
a
place
of
employment
covered
under
the
scope
of
this
standard.
Paragraph
(
d)(
2)(
i)
would
require
the
employer
to
identify
all
employees
who,
without
regard
to
respirator
use,
are
exposed
or
may
reasonably
be
anticipated
to
be
exposed,
at
or
above
the
action
level
or
above
the
EL
and
to
perform
initial
monitoring
to
accurately
determine
the
exposure
of
employees
so
identified.
The
initial
monitoring
must
be
conducted
within
60
days
of
the
effective
date
of
the
final
standard
as
set
forth
in
paragraph
(
o)(
2)(
i).
However,
to
relieve
some
of
the
monitoring
burden
and
associated
cost,
paragraph
(
d)(
2)(
ii)
of
the
proposal
would
permit
an
employer
who
has
comparable
and
adequate
workplace
monitoring
data
gathered
within
180
days
prior
to
the
effective
date
of
the
standard
to
rely
on
those
data
to
satisfy
the
requirements
of
the
initial
monitoring.
To
meet
the
"
comparable
and
adequate"
intent
of
this
provision,
such
monitoring
data
must
have
been
gathered
under
conditions
closely
resembling
those
currently
prevailing
in
the
workplace,
each
employee
must
have
been
monitored,
and
the
monitoring
must
satisfy
all
other
requirements
of
this
section
including
accuracy
of
the
analytical
method
at
the
proposed
action
levels
It
should
be
noted
that
this
provision
would
require
initial
monitoring
to
be
performed
for
all
employees
who
are
potentially
exposed
to
glycol
ethers
at
or
above
the
ALs
or
above
the
ELs.
For
the
purpose
of
this
section,
representative
sampling
will
not
be
an
accepted
method
of
initial
monitoring.
The
reasoning
behind
this
is
that
the
permissible
exposure
limits
for
the
8­
hour
TWAs
are
being
reduced
to
such
an
extent
(
e.
g.,
from
25
ppm
to
0.1
ppm
for
2­
ME)
that
the
Agency
does
not
believe
that
the
initial
assessment
of
employee
exposure
can
be
accurately
determined
through
representative
sampling.
This
approach
is
further
supported
when
one
considers
that
the
action
levels
of
these
compounds
are
even
lower,
0.05
ppm
(
2­
ME,
2­
MEA)
and
0.25
ppm
(
2­
EE,
2­
EEA).
At
these
levels,
minor
variations
in
employee
work
practices
or
job
tasks,
workplace
ventilation,
compound
concentration,
and
so
forth
can
affect
the
level
of
employee
exposure
and
thereby
implementation
of
various
provisions
of
this
proposal.
It
is
OSHA's
belief,
therefore,
that
employee
exposure
levels
relative
to
the
TWAs,
ELs,
and
ALs
can
be
accurately
determined
only
by
conducting
initial
monitoring
for
each
employee.
The
only
exception
to
performing
initial
monitoring
is
the
use
of
objective
data
as
discussed
in
paragraph
(
d)(
1)(
v).
In
assembling
objective
data,
however,
it
should
be
noted
that
the
Agency
would
question
historical
data
used
to
substantiate
claims
of
exposure
levels
below
the
proposed
action
levels,
since
the
proposed
action
levels
are
near
the
level
of
reliable
quantitation
of
the
1985
OSHA
analytical
method
for
these
substances
(
the
proposed
action
level
for
2­
ME
is
actually
below
the
level
of
quantitation
or
LOQ
of
the
1985
methodology).
The
level
of
quantitation
(
LOQ)/
level
of
detection
(
LOD)
discussion
in
the
1985
analytical
method
states:
(
Ex.
5­
005)

The
reliable
quantitation
limits
and
detection
limits
reported
in
the
method
are
based
upon
optimization
of
the
instrument
for
the
smallest
possible
amounts
of
analytes.
When
target
concentration
of
an
analyte
is
exceptionally
higher
than
these
limits,
they
may
not
be
attainable
at
the
routine
operating
parameters.

Since
the
previous
permissible
exposure
limits
range
from
25
ppm
(
2­
ME/
2­
MEA)
to
200
ppm
(
2­
EE),
it
is
doubtful
that
normal
analytical
procedures
and
apparatus
would
be
optimized
to
achieve
a
target
concentration
at
the
[
page
15597]

method's
LOD/
LOQ.
Therefore,
the
Agency
would
seriously
question
the
accuracy
and
reliability
of
historical
monitoring
results
at
such
levels
The
outcome
of
the
monitoring
determines
what
subsequent
action
must
be
taken
by
the
employer.
If
initial
or
periodic
monitoring
results
show
employee
exposure
to
be
below
the
action
level,
the
employer
may
discontinue
monitoring
for
that
employee
unless
there
is
a
change
in
production,
equipment,
process,
personnel,
control
measures,
or
any
other
such
factor
which
may
result
in
new
or
additional
exposure
to
glycol
ethers.
However,
paragraph
(
d)(
3)(
i)
stipulates
that
if
initial
monitoring
reveals
employee
exposure
to
be
at
or
above
the
AL
or
above
the
EL,
then
periodic
monitoring
must
be
initiated
as
discussed
below
and
in
paragraphs
(
d)(
3)(
ii)
through
(
d)(
3)(
iv)
of
the
proposed
standard
Periodic
measurements
are
one
of
the
most
informative
ways
of
detecting
hazardous
shifts
in
exposure
concentrations,
an
indicator
that
engineering
controls
are
not
working
properly
or
that
good
work
practices
are
not
being
followed.
The
results
of
monitoring
determine
the
monitoring
frequency
which
must
be
adopted
by
the
employer.
Paragraph
(
d)(
3)(
ii)
states
that
if
the
initial
or
periodic
monitoring
results
show
employee
exposures
at
or
above
the
AL,
but
at
or
below
the
TWA
then
the
employer
must
repeat
monitoring
for
these
individuals
at
least
every
six
months.
As
discussed
previously,
when
monitoring
results
are
above
the
action
level,
the
employer
can
no
longer
be
confident
that
employees
are
not
being
exposed
over
the
TWA.
Therefore,
OSHA
feels
that
periodic
monitoring
of
employees
exposed
at
or
above
the
action
level
is
necessary
to
assure
employers
that
their
employees
are
not
overexposed
If
initial
or
periodic
exposures
are
above
the
TWA
then
the
employer
must
monitor
every
three
months
as
would
be
required
by
paragraph
(
d)(
3)(
iii)
of
this
section.
Once
employee
exposures
exceeding
the
TWA
have
been
identified,
the
employer
is
obligated
to
implement
measures
directed
at
eliminating
or
minimizing
those
exposures.
More
frequent
monitoring
is
warranted
to
determine
the
effectiveness
of
the
measures
in
protecting
workers
Monitoring
for
the
EL
is
generally
to
be
carried
out
simultaneously
with,
and
according
to,
the
required
monitoring
frequencies
discussed
above.
However,
as
stated
in
paragraph
(
d)(
3)(
iv),
if
an
employee
is
exposed
in
excess
of
the
EL,
that
employee
shall
be
monitored
at
least
every
three
months
under
conditions
of
highest
exposure.
As
related
previously
in
the
discussion
on
excursion
limits,
exposure
to
short
bursts
of
elevated
levels
of
glycol
ethers
may
play
an
important
role
in
biological
effects
of
these
compounds.
Therefore,
protection
against
this
type
of
exposure
could
be
of
equal
concern
compared
to
exposures
exceeding
the
TWA.
As
a
result,
the
same
periodic
monitoring
frequency
has
been
proposed
for
exposures
in
excess
of
either
the
TWAs
or
ELs
OSHA
believes
these
frequencies,
which
are
similar
to
those
required
by
other
OSHA
standards,
such
as
Arsenic
(
43
FR
19854
May
5,
1978;
29
CFR
1910.1018)
and
Ethylene
Oxide
(
49
FR
25734
June
22,
1984
and
53
FR
11414
April
6,
1988;
29
CFR
1910.1047),
are
necessary
and
sufficient
for
providing
useful
information
to
evaluate
employees'
exposures.
Periodic
re­
monitoring
provides
the
employer
with
assurance
that
employees
are
not
experiencing
higher
exposures
that
may
require
the
use
of
additional
controls.
In
addition,
these
measurements
remind
employees
and
employers
of
the
continued
need
to
protect
against
the
hazards
which
could
result
from
exposure
to
glycol
ethers
Employees
are
further
protected
because
additional
monitoring
would
be
required
by
paragraph
(
d)(
4)
when
there
has
been
a
change
in
production,
equipment,
raw
materials,
process,
personnel,
or
work
practices
which
may
result
in
new
or
additional
exposures
to
glycol
ethers
at
or
above
the
ALs
or
above
the
ELs,
or
whenever
the
employer
has
any
other
reason
to
suspect
that
a
change
may
result
in
new
or
additional
exposures
at
or
above
the
ALs
or
above
the
ELs
OSHA
recognizes
that
monitoring
can
be
a
time­
consuming,
expensive
endeavor.
Therefore,
this
proposal
offers
employers
the
incentive
to
minimize
employees'
exposures
by
allowing
employers
to
discontinue
monitoring
for
employees
under
certain
conditions.
It
is
hoped
that
such
a
provision
will
encourage
employers
to
maintain
their
employees'
exposures
to
glycol
ethers
below
the
Al
and
the
EL,
thus
maximizing
the
protection
of
employees'
health
Paragraph
(
d)(
5)(
i)
through
(
d)(
5)(
iii)
would
permit
the
employer
to
discontinue
monitoring
for
an
employee,
except
as
noted
otherwise
in
paragraph
(
d)(
4)
of
this
section,
if
the
initial
monitoring
results
show
the
employee's
exposure
to
be
below
the
AL
and
at
or
below
the
ELs.
If
periodic
monitoring
results
indicate,
by
at
least
two
consecutive
measurements
taken
at
least
seven
days
apart,
that
employee
exposures
have
fallen
below
the
ALs,
and
are
at
or
below
the
ELs,
the
employer
may
discontinue
monitoring
for
those
employees
whose
exposures
are
represented
by
such
monitoring.
However,
the
results
must
be
statistically
representative
and
consistent
with
the
employer's
knowledge
of
the
job
and
work
operation.
Also,
paragraph
(
d)(
5)(
iii)
states
that
if
the
initial
or
periodic
monitoring
reveals
the
employee
to
be
at
or
above
the
AL
but,
on
two
consecutive
measurements
taken
at
least
seven
days
apart,
the
employee
is
not
exposed
above
the
EL,
no
further
monitoring
for
the
EL
is
necessary
except
as
required
by
paragraph
(
d)(
4)
of
this
section
When
considering
termination
of
monitoring
an
employee's
exposure
level,
the
employer
should
have
reasonable
confidence
that
the
employee's
exposure
has
truly
been
reduced
below
the
AL
and/
or
EL.
Variations
in
job
task,
daily
production,
ventilation
patterns,
and
so
forth
could
result
in
a
non­
characteristically
low
exposure
measurement
and,
if
only
one
sample
is
considered,
lead
the
employer
to
incorrectly
deduce
that
the
employee
is
no
longer
overexposed.
To
minimize
the
possibility
of
the
occurrence
of
such
an
incorrect
supposition,
increase
the
employer's
confidence
in
terminating
monitoring,
and
to
further
protect
employees
against
overexposure,
the
Agency
would
require
that,
at
a
minimum,
the
employer
monitor
the
employee's
exposure
level
a
second
time,
at
least
seven
days
later,
to
confirm
the
reduced
exposure
level
before
termination
of
monitoring.
This
requirement
is
consistent
with
other
recent
OSHA
standards
Paragraph
(
d)(
6)
would
require
the
employer
to
use
monitoring
and
analytical
methods
which
have
an
accuracy
(
at
a
confidence
level
of
95%)
within
plus
or
minus
25%
for
airborne
concentrations
of
glycol
ethers
at
or
above
the
level
being
investigated.
This
is
necessary
to
assure
that
95
percent
of
the
measurements
are
accurate
to
within
plus
or
minus
25
percent
of
the
"
true"
exposure
level.
OSHA
has
included
this
accuracy
requirement
in
other
toxic
substance
standards
(
Formaldehyde,
29
CFR
1910.1048).
A
method
of
measurement
is
presently
available
to
detect
ethylene
glycol
ethers
to
this
degree
of
accuracy
and
is
described
in
Appendix
(
E).
The
proposed
standard,
in
paragraph
(
d)(
7),
would
require
that
employers
notify
each
of
their
employees
individually
of
the
results
of
personal
monitoring
samples.
This
notification
is
to
be
given
within
15
days
of
receipt
of
exposure
monitoring
results
and
is
to
be
given
in
writing
and
[
page
15598]

by
posting
a
notice
in
an
appropriate
location
accessible
to
affected
employees.
A
written
notice
ensures
that
each
employee
is
notified
while
posting
the
results
ensures
that
employers
and
supervisors
are
aware
of
the
results.
Posting
results
also
permits
employees
to
compare
their
monitoring
results
with
those
of
co­
workers
and
results
obtained
from
other
shifts
If
the
results
of
the
monitoring
show
employee
exposure
to
be
in
excess
of
the
TWA
and/
or
EL
permissible
exposure
limits,
the
written
notice
to
the
employees
shall
include
a
statement
that
the
TWA
and/
or
EL
has
been
exceeded
and
a
description
of
the
corrective
action
which
is
being
taken
by
the
employer
to
decrease
the
exposure
to
within
the
permissible
exposure
limits.
This
requirement
to
inform
employees
is
in
accordance
with
section
8(
c)(
3)
of
the
OSH
Act
and
is
necessary
to
assure
employees
that
the
employer
is
making
efforts
to
furnish
them
with
a
safe
and
healthful
work
environment
As
required
by
Section
8(
c)(
3)
of
the
Act
[
29
U.
S.
C.
657(
c)(
3)],
this
proposal
contains
provisions
for
employee
observation
of
exposure
monitoring.
Paragraph
(
d)(
8)(
i)
would
require
employers
to
provide
affected
employees
or
their
designated
representative
with
the
opportunity
to
observe
any
monitoring
of
employee
exposures
to
glycol
ethers
as
required
by
this
section.
In
paragraph
(
d)(
8)(
ii),
observation
procedures
are
set
forth
which
would
require
the
employer
to
provide
the
observer
with
the
personal
protective
clothing
and
equipment
(
e.
g.
coveralls,
gloves,
respiratory
protection,
protective
eyewear)
that
is
required
to
be
worn
by
the
employees
who
are
working
in
the
area.
In
addition,
the
employer
must
ensure
that
the
observer
uses
such
clothing
and
equipment
and
complies
with
all
other
applicable
safety
and
health
procedures.
This
requirement
ensures
that
the
observer
receives
adequate
protection
from
exposure
to
glycol
ethers
Regulated
Areas:
Paragraph
(
e):

In
paragraph
(
e)(
1),
the
proposed
standard
would
require
the
employer
to
establish
regulated
areas
wherever
exposures
to
glycol
ethers
exceed
or
can
be
expected
to
exceed
the
TWA
and/
or
EL
permissible
exposure
limits.
Such
areas
must
be
established
even
though
no
employee
is
routinely
assigned
to
the
area;
the
potential
for
overexposure
is
the
determining
factor
The
Agency
feels
that
it
is
the
existence
of
a
hazard
which
is
the
basis
for
determining
the
need
for
protective
measures
rather
than
the
type
of
operation
being
performed.
Therefore,
establishment
of
a
regulated
area
is
to
be
carried
out
not
only
for
situations
where
the
concentration
of
airborne
glycol
ethers
must
unavoidably
exceed
the
permissible
exposure
limits
for
extended
periods
but
also
for
areas
where
exposures
are
temporarily
over
either
the
TWA
or
EL
for
short
periods,
such
as
might
be
expected
while
maintenance
is
being
performed.
The
establishment
of
regulated
areas
is
consistent
with
good
industrial
hygiene
practice
as
it
provides
an
effective
means
of
limiting
excess
exposure
to
as
few
employees
as
possible.
In
addition,
the
regulated
area
provision
of
this
standard
conforms
with
similar
provisions
in
other
OSHA
health
standards.
It
should
also
be
noted
that
this
requirement
has
additional
benefits
to
employers
in
that
by
limiting
access
to
these
areas
to
only
authorized
persons,
the
employer's
obligation
to
implement
the
provisions
of
this
standard
triggered
by
exposure
above
the
TWAs
or
ELs
is
limited
to
a
minimum
number
of
employees
The
purpose
of
designating
regulated
areas
is
to
ensure
that
employers
make
employees
aware
of
the
presence
of
glycol
ethers
in
the
workplace
at
levels
above
the
permissible
exposure
limits,
thereby
helping
to
minimize
the
number
of
employees
exposed
and
ensuring
that
employees
who
must
enter
the
area
are
provided
with
training
and
appropriate
personal
protective
equipment.
Paragraph
(
e)(
1)(
i)
would
require
that
regulated
areas
be
demarcated
from
the
rest
of
the
workplace
in
any
manner
that
adequately
establishes
and
alerts
employees
to
the
boundary
of
the
regulated
area
while
paragraph
(
e)(
1)(
ii)
stipulates
that
these
areas
be
posted
at
all
entrances
and
accessways
with
signs
meeting
the
requirements
specified
in
paragraph
(
m)(
1)(
i)
of
this
standard.
To
increase
the
performance
orientation
of
the
standard,
no
detailed
requirements
are
specified
on
how
regulated
areas
should
be
demarcated.
However,
it
must
be
assured
that
the
manner
of
demarcation
chosen
adequately
alerts
employees
to
the
boundaries
of
the
area.
In
addition,
readily
observable
signs
at
all
entrances
and
accessways
serve
to
alert
the
employee
not
only
to
the
existence
of
the
regulated
area
but
reminds
them
to
use
proper
personal
protective
equipment
and
respiratory
protection
and
to
observe
good
personal
hygiene
practices,
such
as
refraining
from
smoking
or
eating
in
regulated
areas
and
washing
hands
and
face
after
leaving
the
area
The
proposed
standard
also
states,
in
paragraph
(
e)(
2),
that
the
employer
shall
limit
access
to
regulated
areas
to
only
authorized
persons.
By
limiting
access
to
authorized
persons
only,
the
employer
minimizes
the
number
of
persons
exposed
to
glycol
ethers.
In
addition,
this
requirement
assures
that
only
those
persons
who
have
been
properly
trained
and
utilize
proper
protective
equipment
are
permitted
into
the
area
In
paragraph
(
e)(
3)
of
the
proposal,
it
is
stipulated
that
whenever
an
employer
at
a
multiemployer
worksite
establishes
a
regulated
area,
that
employer
shall
communicate
the
location
and
restrictions
of
access
to
the
regulated
area
to
other
employers
with
work
operations
at
that
worksite.
This
requirement
would
lessen
the
possibility
that
unauthorized,
unprotected
people
would
enter
the
area
and
be
inadvertently
exposed.
OSHA
is
concerned
that
employees
at
nearby
sites
be
aware
of
the
existence
of
the
hazard
and
remain
outside
of
the
regulated
area.
Even
though
the
signs
posted
by
the
first
employer
serve
to
warn
employees
of
a
second
employer
to
stay
out
of
the
area,
there
is
no
assigned
accountability
for
these
employees.
Therefore,
if
the
second
employer
is
aware
of
the
hazards,
then
it
is
the
responsibility
of
the
second
employer
to
assure
that
his
employees
do
not
enter
the
regulated
area
of
the
first
employer
without
permission
and
proper
protective
equipment
It
would
be
required,
under
paragraph
(
e)(
4)
of
the
proposal,
that
each
person
entering
a
regulated
area
be
provided
with
and
required
to
use
appropriate
personal
protective
equipment,
including
respiratory
protection
selected
in
accordance
with
paragraph
(
g)(
3).
This
provision
is
also
consistent
with
other
OSHA
standards
(
e.
g.,
Asbestos,
29
CFR
1910.1001).
This
provision
applies
not
only
to
employees
working
"
full
time"
in
the
regulated
area
but
to
any
person
entering
the
area.
This
approach
provides
a
number
of
benefits:
1)
"
walk
through"
by
employees
will
be
discouraged
since
use
of
appropriate
personal
protective
equipment
will
be
required
of
all
persons
entering
the
area;
2)
employees
whose
duties
require
them
to
be
in
the
area
for
a
longer
period
of
time
than
originally
anticipated
will
be
adequately
protected
since
it
eliminates
the
need
for
employees
to
estimate
length
of
time
in
the
regulated
area
and
make
individual
decisions
regarding
personal
protective
equipment;
and
3)
enforcement
will
be
simplified
for
the
employer
since
the
use
of
personal
protective
equipment
will
be
uniformly
required
of
all
persons
in
the
regulated
area,
regardless
of
the
length
of
time
they
will
be
present
in
the
area.

[
page
15599]

Methods
of
Compliance:
Paragraph
(
f)

Paragraph
(
f)(
1)
of
the
proposed
standard
would
require
employers
to
institute
engineering
and
work
practice
controls,
to
the
extent
feasible,
as
the
primary
means
to
reduce
and
maintain
employee
exposures
to
glycol
ethers
to
levels
at
or
below
the
TWAs
or
the
ELs
and
to
eliminate
dermal
exposure
.
Paragraph
(
f)(
2)
also
requires
employers,
whenever
they
establish
that
feasible
engineering
and
work
practice
controls
are
not
sufficient
to
lower
exposures
to
or
below
the
TWAs
or
the
ELs
or
to
eliminate
foreseeable
dermal
exposure,
to
nonetheless
implement
such
controls
to
reduce
employee
exposures
to
the
lowest
levels
achievable
and
then
to
provide
supplemental
personal
protective
equipment
to
eliminate
dermal
exposure
and/
or
achieve
the
TWAs
or
ELs
through
the
use
of
respirators
that
comply
with
the
requirements
of
paragraph
(
g)
of
this
proposed
standard
Engineering
controls
serve
to
reduce
employee
exposure
in
the
workplace
by
either
removing
or
containing
the
hazard
or
isolating
the
worker
from
exposure.
These
controls
include,
but
are
not
limited
to,
process
or
equipment
redesign
(
including
substitution
of
glycol
ethers
with
a
less
toxic
chemical),
installation
of
ventilation
equipment
(
localized
and/
or
general),
process
or
equipment
enclosure,
and
employee
isolation.
In
general,
engineering
controls
act
on
the
source
of
the
hazard
and
eliminate
or
reduce
employee
exposure
without
reliance
on
the
employee
taking
self­
protective
action
or
intervention.
Once
implemented,
engineering
controls
protect
the
employee,
subject
only,
to
periodic
replacement
or
preventative
maintenance.
Engineering
controls
are:
reliable;
provide
consistent
levels
of
protection
to
a
large
number
of
workers;
are
not
dependent
upon
individual
human
performance;
can
be
monitored
continually/
inexpensively;
allow
for
predictable
performance
levels;
remove
hazards
from
the
workplace.
Once
removed,
the
health
hazard
no
longer
poses
a
threat
to
the
employee.
Engineering
controls
are
preferred
by
OSHA
since
they
remove
hazards
from
the
workplace
Engineering
controls
can
be
grouped
into
3
categories:
(
1)
substitution,
(
2)
isolation,
and
(
3)
ventilation,
both
general
and
localized.
Quite
often
a
combination
of
these
controls
can
be
applied
to
an
industrial
hygiene
control
problem
to
achieve
satisfactory
air
quality.
It
may
not
be,
and
usually
is
not,
necessary
or
appropriate
to
apply
all
these
measures
to
any
specific
potential
hazard
Substitution
should
not
be
overlooked
as
an
appropriate
solution
to
an
industrial
hygiene
problem.
One
of
the
best
ways
to
keep
people
from
being
exposed
to
a
toxic
substance
is
to
stop
using
it
entirely.
This
is
not
always
possible,
but
at
least
the
following
question
should
be
asked:
"
Can
a
less
toxic
material
be
substituted
in
the
process?"
Other
examples
of
substitution
which
may
provide
effective
control
of
an
air
contaminant
are
changing
from
one
type
of
process
equipment
to
another,
or
even
in
some
cases
changing
the
process
itself
In
general,
a
change
in
any
process
from
a
batch
to
a
continuous
type
of
operation
carries
with
it
an
inherent
reduction
in
potential
hazard.
This
is
true
primarily
because
the
frequency
and
duration
of
worker's
potential
contact
with
the
process
materials
is
reduced
when
the
overall
process
approach
becomes
one
of
continuous
operation.
The
substitution
of
processes
can
be
applied
on
a
fundamental
basis.
For
example,
substitution
of
airless
spray
for
conventional
spray
equipment
can
reduce
the
exposure
of
a
painter
to
toxic
substances.
Substitution
of
a
paint
dipping
operation
for
the
paint
spray
operation
can
reduce
the
potential
hazard
even
further.
In
any
of
these
cases
the
automation
of
the
process
can
further
reduce
the
potential
hazard
In
addition
to
substitution,
the
principle
of
isolation
should
be
considered.
Although
"
isolation"
is
frequently
envisioned
as
consisting
of
installation
of
a
physical
barrier
between
a
hazardous
operation
and
the
workers,
isolation
can
be
provided
without
a
physical
barrier
by
appropriately
placing
the
employee
at
greater
distance
from
the
source
of
the
glycol
ethers
exposure
and
by
controlling
employees'
exposures
by
scheduling
work
assignments
when
the
fewest
employees
are
present.
Examples
of
this
latter
method
would
be
operating
a
contaminant­
producing
operation
at
night
in
the
absence
of
most
of
the
employees.
Clean­
up
operations
in
which
toxic
substances
are
involved
sometimes
can
be
performed
at
night
in
the
absence
of
the
usual
production
staff.
Such
methods
of
controlling
worker
exposures
to
contaminants
by
work
assignment
away
from
the
contaminant
are
known
as
administrative
controls
Frequently
the
application
of
the
principle
of
isolation
maximizes
the
benefits
of
additional
engineering
concepts
such
as
local
exhaust
ventilation.
For
example,
the
charging
of
mixers
is
the
most
significant
operation
in
many
processes
that
use
formulated
ingredients.
When
one
of
the
ingredients
in
the
formulation
is
of
relatively
high
toxicity,
it
is
worthwhile
to
isolate
the
mixing
operation,
that
is,
install
a
mixing
room,
thereby
confining
the
airborne
contaminants
potentially
generated
by
the
operation
to
a
small
area
rather
than
having
them
influence
a
larger
area
of
the
plant.
By
ensuring
containment,
the
application
of
ventilation
principles
to
control
the
contaminant
at
the
source
(
i.
e.,
the
mixer)
is
much
more
effective
Ventilation,
applied
as
either
a
general
or
local
control,
is
by
far
the
most
important
engineering
control
principle
available
to
the
industrial
hygienist.
Its
principal
application
is
to
maintain
airborne
concentrations
of
contaminants
at
acceptable
levels
in
the
workplace
A
local
exhaust
system
is
used
to
carry
off
an
air
contaminant
by
capturing
it
at
or
near
its
source,
before
it
spreads
throughout
the
workplace.
Some
examples
of
local
ventilation
systems
include
a
canopy
hood
over
a
hot
process,
slot
ventilation
around
the
periphery
of
a
vat,
and
a
laboratory
hood
enclosure.
General
ventilation,
on
the
other
hand,
lets
the
contaminant
spread
throughout
the
workroom
but
dilutes
it
by
circulating
large
quantities
of
air
into
and
out
of
the
workroom.
A
local
exhaust
system
is
generally
preferred
to
ventilation­
by­
dilution
(
general
ventilation
only)
because
it
provides
a
cleaner
and
healthier
work
environment
By
comparison,
work
practice
controls
reduce
the
likelihood
of
exposure
through
alteration
of
the
manner
in
which
a
task
is
performed
such
as
how
an
employee
positions
himself/
herself
relative
to
the
source
and/
or
engineering
control.
While
work
practice
controls
also
act
on
the
source
of
the
hazard,
the
protection
they
provide
is
based
upon
employer
and
employee
behavior
rather
than
installation
of
a
physical
device
such
as
a
ventilation
system.
Examples
of
some
basic
work
practices
include,
but
are
not
limited
to,
(
1)
limiting
access
to
regulated
work
areas
to
authorized
and
specially­
trained
personnel
with
proper
personal
protective
equipment,
(
2)
drawing
tank
car
samples
from
an
upwind
position,
and
(
3)
performing
glycol
ether
analyses,
such
as
quality
checks,
within
a
chemical
fume
hood
In
many
instances,
the
two
control
methodologies
discussed
above
work
in
tandem
as
it
is
often
necessary
to
employ
work
practices
to
insure
effective
operation
of
engineering
controls.
For
example,
if
an
employee
inappropriately
performs
an
operation
[
page
15600]

outside
of
an
exhaust
hood
then
the
protection
afforded
by
the
engineering
control
(
i.
e.,
the
exhaust
hood)
will
be
of
little
or
no
use.
As
can
be
seen,
therefore,
in
many
situations
it
is
important
not
only
that
an
engineering
control
be
functioning
properly
but
also
that
employees
are
aware
of
the
work
practices
that
are
necessary
to
assure
effectiveness
of
the
control
Primary
reliance
on
engineering
controls
and
work
practices
is
consistent
with
good
industrial
hygiene
practice
and
with
the
Agency's
traditional
adherence
to
a
particular
hierarchy
of
preferred
controls.
This
hierarchy
specifies
that
engineering
controls
and
work
practices
are
to
be
used
in
preference
to
respirators.
OSHA
has
traditionally
relied
less
on
respirators
in
the
hierarchy
of
controls
because
there
are
so
many
problems
associated
with
their
use.
Often
work
is
strenuous
and
the
increased
breathing
resistance
of
the
respirator
reduces
its
acceptability
to
employees.
Safety
problems
are
presented
by
respirators
since
they
limit
vision.
In
some
difficult
and
dangerous
jobs,
effective
communication
facilitates
a
safe,
efficient
operation.
Voice
transmission
through
a
respirator
can
be
difficult,
annoying,
and
fatiguing.
Movement
of
the
jaw
in
speaking
causes
leakage
thereby
reducing
the
efficiency
of
the
respirator
and
decreasing
the
employee's
protection
against
glycol
ethers
exposures.
Also,
skin
irritation
can
result
from
wearing
a
respirator
in
hot,
humid
conditions.
Such
irritation
can
cause
considerable
distress
and
disrupt
work
schedules.
To
be
used
effectively,
respirators
must
be
individually
selected
and
fitted,
conscientiously
and
properly
worn,
regularly
maintained,
and
replaced
as
necessary.
In
many
workplaces,
these
conditions
are
difficult,
if
not
impossible,
to
satisfy.
For
these
reasons
and
others,
OSHA
has
concluded
that
reliance
on
respirators
should
be
minimized
Paragraph
(
f)(
3)
of
the
proposal
would
require
that
engineering
controls
be
inspected
and
maintained
or
replaced
on
a
regular
schedule
to
ensure
their
effectiveness.
Regularlyscheduled
inspections
are
required
to
confirm
that
engineering
controls
such
as
protective
shields
have
not
been
broken
or
removed;
that
ventilation
systems
are
operating
properly;
that
filters
are
being
replaced
on
a
sufficiently
frequent
interval;
and
that
any
other
physical,
mechanical,
or
replacement­
dependent
controls
are
functioning
as
intended
In
consideration
of
glycol
ethers'
ability
to
be
absorbed
through
the
skin
and
thereby
contribute
to
overall
exposure,
paragraph
(
f)(
4)
would
require
the
employer
to
permit
employees
to
leave
the
work
area
immediately
or
as
soon
as
feasible
to
wash
skin
areas
which
have
had
contact
with
glycol
ethers
Whenever
the
TWAs
and/
or
ELs
are
exceeded
or
dermal
exposure
exists,
paragraph
(
f)(
5)(
i)
would
require
employers
to
establish
and
implement
a
written
compliance
program
to
reduce
employee
exposure
to
or
below
the
TWAs
and/
or
ELs
and
eliminate
dermal
exposure.
The
plan
should
provide
for
this
reduction
to
be
accomplished,
where
feasible,
through
the
use
of
engineering
and
work
practice
controls.
If
engineering
and
work
practice
controls
cannot
reduce
exposures
to
or
below
the
TWA
and
EL
permissible
exposure
limits
and
eliminate
dermal
exposures
then
the
plan
shall
include
the
use
of
whatever
respiratory
protection
equipment
is
necessary
to
achieve
compliance
and
all
appropriate
personal
protective
equipment
necessary
to
eliminate
contact
with
glycol
ethers.
In
addition,
the
Agency
believes
that
the
emergency
plan
prescribed
in
paragraph
(
k)
is
inherently
a
part
of
the
overall
compliance
program
since
it
addresses
prevention
of
employee
exposure
in
emergency
situations.
Therefore,
paragraph
(
f)
(
5)
(
i)
(
B)
would
require
that
the
the
written
emergency
plan
be
included
in
the
compliance
plan
The
written
program
requirement
commits
the
employer
to
evaluating
employee
exposure
and
setting
down
an
organized
and
complete
plan
of
reducing
employee
exposures
to
permissible
limits.
Inclusion
of
personal
protective
equipment,
including
respiratory
protection,
in
the
plan
assures
that
the
appropriate
protective
equipment
is
selected,
based
on
level
and
mode
of
exposure,
and
written
into
the
plan
for
reference
Paragraph
(
f)(
5)(
ii)
would
require
that
the
written
compliance
program
be
reviewed
and
updated
at
least
annually,
or
more
often
if
necessary,
to
reflect
significant
changes
in
the
employer's
compliance
status.
By
requiring,
at
a
minimum,
annual
review
of
the
compliance
program,
the
Agency
assures
that
the
employer
will
update
the
program
to
reflect
the
current
compliance
status
of
the
workplace.
This
review
would
require
the
employer
to
evaluate
all
new
or
altered
tasks,
procedures,
processes,
and
so
forth
to
determine
whether
they
would
result
in
occupational
exposure
and,
if
so,
what
exposure
reduction
methods
must
be
implemented
Paragraph
(
f)(
5)(
iii)
states
that
the
employer's
written
compliance
program
shall
be
submitted
upon
request
for
examination
and
copying
to
the
Assistant
Secretary,
the
Director,
affected
employees,
and
authorized
employee
representatives.
Employee
and
employee
representative
access
allows
workers
to
gain
an
awareness
of
where
the
permissible
exposure
limits
are
exceeded,
what
steps
the
employer
is
taking
to
reduce
or
eliminate
exposure,
and
the
appropriate
respiratory
protection
and
personal
protective
equipment
to
use
in
these
areas.
Access
to
the
plan
by
the
Assistant
Secretary
is
important
for
compliance
enforcement.
Access
by
the
Director
is
required
for
that
agency
to
carry
out
the
various
investigations
and
research
it
deems
necessary.
For
example,
performing
health
hazard
evaluations
of
a
plant,
determining
the
current
exposure
patterns
and
control
methodologies
in
industry
use,
and
conducting
epidemiological
studies
Respiratory
Protection:
Paragraph
(
g)

Respirators
serve
as
supplemental
protection
to
reduce
employee
exposures
when
engineering
and
work
practice
controls
are
not
sufficient
to
achieve
the
necessary
reduction
to
or
below
the
TWAs
and
ELs.
The
proposed
standard,
in
paragraph
(
g)(
1),
states
that
where
respiratory
protection
is
required
the
employer
shall
provide,
at
no
cost
to
the
employee,
and
shall
assure
the
proper
use
of
respirators
which
comply
with
the
requirements
of
this
section
to
reduce
employee
exposures
to
or
below
the
TWA
and
EL
permissible
exposure
limits
In
paragraph
(
g)(
1)(
i)
through
(
g)(
1)(
iv),
the
proposed
standard
would
require
that
respiratory
protection
be
worn
(
1)
during
the
interval
necessary
to
install
or
implement
feasible
engineering
and
work
practice
controls;
(
2)
in
work
operations,
such
as
maintenance
and
repair
activities
and
during
brief
or
intermittent
operations,
for
which
the
employer
has
established
that
engineering
and
work
practice
controls
are
not
yet
feasible;
(
3)
in
work
situations
where
the
employer
has
implemented
all
feasible
engineering
and
work
practice
controls
and
such
controls
are
not
sufficient
to
reduce
exposure
to
or
below
the
TWA
and/
or
EL
permissible
exposure
limits;
and
(
4)
in
emergencies.

In
some
circumstances
(
e.
g.,
certain
maintenance
and
repair
operations,
emergencies,
or
during
periods
when
engineering
and
work
practice
controls
are
being
installed
and
implemented)
OSHA
recognizes
that
respirators
may
be
essential
to
guarantee
worker
health
and
safety.
Therefore,
provision
is
made
in
paragraph
(
g)(
1)
for
their
use
as
[
page
15601]

primary
controls
in
these
instances
where
engineering
and
work
practice
controls
cannot
be
used
to
achieve
the
TWAs
or
ELs.
In
other
circumstances
where
engineering
and
work
practice
controls
alone
cannot
reduce
exposure
levels
to
the
TWAs
or
ELs,
respirators
may
also
be
used
for
supplemental
protection
However,
it
must
be
kept
in
mind
that
the
burden
of
proof
of
infeasibility
rests
with
the
employer
in
those
circumstances
where
respiratory
protection
is
used
in
lieu
of
engineering
and
work
practice
controls
It
would
be
required
that
all
employees
who
wear
respiratory
protection
be
medically
screened
to
determine
whether
any
health
conditions
exist
which
could
affect
the
employee's
ability
to
wear
a
respirator.
Considering
the
health
problems
which
may
be
exacerbated
with
respirator
use
and
their
associated
detrimental
effects
on
an
employee,
the
proposal
states
in
paragraph
(
g)(
2)
that
no
employee
shall
be
assigned
tasks
requiring
the
use
of
respiratory
protection
if,
based
upon
his
or
her
most
recent
medical
examination,
an
examining
physician
determines
that
the
employee
will
be
unable
to
function
normally
while
wearing
a
respirator.
Common
health
problems
which
could
present
difficulty
with
respirator
use
include
claustrophobia
(
an
intolerance
of
feeling
enclosed
and
a
subjective
feeling
of
breathing
difficulty),
chronic
rhinitis,
nasal
allergies
(
necessitating
frequent
removal
of
the
respirator
to
deal
with
nasal
discharges),
and
chronic
sinusitis.
In
addition,
difficulties
with
use
of
respirators
may
arise
in
employees
with
respiratory
or
cardiac
diseases.
Respiratory
diseases
include
chronic
obstructive
pulmonary
disease,
emphysema,
asthma,
and
moderate
to
severe
pneumoconiosis.
Cardiac
or
cardiorespiratory
diseases
that
may
affect
respirator
wear
include
coronary
thrombosis,
any
type
of
congestive
heart
disease,
other
ischemic
heart
diseases,
and
hypertension
This
paragraph
would
also
require
that
such
employees
be
given
the
opportunity
to
transfer
to
a
position
where
no
respirator
use
is
required.
That
position
shall
be
with
the
same
employer,
in
the
same
geographical
area,
and
with
the
same
seniority
and
rate
of
pay
the
employee
had
just
prior
to
such
a
transfer,
if
such
a
position
is
available.
The
Agency
believes
that
this
provision
will
minimize
the
reluctance
of
all
employees,
including
those
experiencing
difficulty
with
respirator
use,
to
participate
in
the
Medical
Surveillance
Program
for
fear
of
losing
his
or
her
job
due
to
the
possible
inability
to
wear
a
respirator
Paragraph
(
g)(
3)
specifies
the
type
of
respirators
that
may
be
used
to
provide
protection
from
exposure
to
glycol
ethers.
This
proposal
would
permit
only
supplied­
air
respirators
and
would
prohibit
the
use
of
air­
purifying
respirators
equipped
with
organic
vapor
cartridges
or
canisters.
The
rationale
behind
this
decision
relates,
in
part,
to
the
odor
threshold
of
the
glycol
ethers.
Generally,
an
employee
using
an
air
purifying
respirator
can
detect
a
poor
facepiece
seal
or
sorbent
cartridge
breakthrough
by
the
odor
of
a
chemical
as
it
finds
its
way
into
the
respirator,
provided
the
chemical
possesses
good
warning
properties.
If
the
odor
threshold
of
a
compound
exceeds
the
permissible
exposure
limit,
however,
the
employee
is
deprived
of
such
an
inherent
odor
warning
and
is
not
aware
of
a
respirator
inadequacy
until
he/
she
is
overexposed
to
the
compound.
Consequently,
an
important
factor
in
the
selection
of
appropriate
respiratory
protection
is
the
odor
threshold
of
the
chemical
of
concern
When
considering
the
odor
threshold
of
a
substance,
one
finds
that
reported
values
are
widely
divergent.
Two
major
factors
which
influence
odor
detection
are
differences
between
individuals
in
the
ability
to
perceive
a
particular
odor
and
the
methodology
employed
in
conducting
the
odor
threshold
determination.
In
their
"
Guide
to
Industrial
Respiratory
Protection
­
Appendix
C"
(
Ex.
5­
142),
NIOSH
states:

Amoore
and
Hautala
(
33)
found
that
on
average,
95%
of
a
population
will
have
a
personal
odor
threshold
that
lies
within
the
range
from
about
one­
sixteenth
to
sixteen
times
the
reported
mean
"
odor
threshold"
for
a
substance.

In
further
explanation,
Amoore
and
Hautala
state:
(
Ex.
5­
141)

The
ability
of
members
of
the
population
to
detect
a
given
odor
is
strongly
influenced
by
the
innate
variability
of
different
persons'
olfactory
powers,
their
prior
experience
with
that
odor,
and
by
the
degree
of
attention
they
accord
the
matter.

This
statement
addresses
not
only
personal
factors
which
influence
odor
detection
but
also
raises
the
issue
of
differences
in
testing
methodology.
Examples
of
methodology
differences
include:
awareness
or
lack
of
awareness
of
the
test
subject
to
the
purpose
of
the
test
(
i.
e.,
to
detect
an
odor)
thereby
increasing
his/
her
attentiveness
to
odor
detection;
presentation
mode
of
the
odor
samples
to
the
test
subject;
purity
of
the
test
compound;
vapor
modality
(
liquid
or
gaseous);
and
number
of
trials.
As
can
be
seen,
lack
of
standard
testing
methodology
in
conjunction
with
individual
differences
in
odor
perception
can
lead
to
the
wide
variation
of
odor
thresholds
found
in
the
literature
OSHA
is
aware
of
two
documents
that
have
attempted
to
account
for
the
variabilities
of
reported
odor
thresholds
­
Amoore
and
Hautala's
"
Odor
as
an
Aid
to
Chemical
Safety:
Odor
Thresholds
Compared
with
Threshold
Limit
Values
and
Volatilities
for
214
Industrial
Chemicals
in
Air
and
Water
Dilution"
(
Ex.
5­
141)
and
the
American
Industrial
Hygiene
Association's
(
AIHA)
"
Odor
Thresholds
for
Chemicals
with
Established
Occupational
Health
Standards"
(
Ex.
5­
143)

Both
documents
calculated
and
utilized
the
geometric
means
of
the
odor
thresholds
reported
in
their
respective
data
collections
to
deal
with
the
broad
range
of
values.
In
the
absence
of
conducting
new,
standardized
testing,
the
Agency
believes
that
this
is
a
sound
approach
to
obtaining
a
single
odor
threshold
value
which
can
be
used
in
evaluating
warning
properties
of
compounds
Amoore
and
Hautala
also
present
a
method
for
comparing
the
exposure
limit
of
a
substance
and
its
odor
threshold
through
calculation
of
an
"
odor
safety
factor"
(
i.
e.,
exposure
limit
divided
by
odor
threshold).
The
odor
safety
factor
can
then
be
used
to
classify
a
compound,
using
the
scale
shown
in
Table
A,
and
thereby
determine
what
percentage
of
attentive
persons
can
detect
the
compound
at
the
exposure
limit
and
what
percentage
of
distracted
persons
will
detect
a
warning
of
the
compound
at
the
exposure
limit
Table
A
Class
Odor
Safety
Factor
Interpretation
A
>
550
>
90%
of
distracted
persons
perceive
warning
of
TLV
concentration
in
air
B
26
­
550
50
 
90%
of
distracted
persons
perceive
warning
of
TLV
concentration
in
air
C
1
­
26
<
50%
of
distracted
persons
perceive
warning
of
TLV
concentration
in
air
D
0.18
­
1
10
 
50%
of
attentive
persons
can
detect
TLV
concentration
in
air
E
<
0.18
<
10%
of
attentive
persons
can
detect
TLV
concentration
in
air
Utilizing
this
methodology
and
the
odor
thresholds
calculated
by
Amoore
and
Hautala,
the
four
glycol
ethers
[
page
15602]

under
consideration,
at
the
proposed
TWA
permissible
exposure
limits,
yield
the
following
classifications:

Table
B
Proposed
Odor
Odor
Compound
TWA
(
ppm)
Threshold
(
ppm)
Safety
Factor
Class
2­
ME
0.1
2.3
0.04
E
2­
MEA
0.1
N/
A
N/
A
N/
A
2­
EE
0.5
2.7
0.2
D
2­
EEA
0.5
0.056
8.9
C
Both
2­
ME
and
2­
EE
have
very
low
odor
safety
factors
with
resultant
classifications
of
Class
E
and
Class
D,
respectively,
which
means
that
most
employees
would
not
be
able
to
detect
breakthrough
of
these
compounds
at
the
proposed
TWA
permissible
exposure
limits.
The
highest
classification,
Class
C,
is
achieved
in
the
case
of
2­
EEA,
in
which
less
than
50%
of
distracted
persons
perceive
a
warning
of
2­
EEA
at
the
proposed
TWA
concentration.
The
Agency
does
not
find
this
to
be
adequate
warning
capability
to
permit
use
of
air­
purifying
respirators
Table
C
presents
the
results
obtained
when
the
odor
thresholds
given
in
the
AIHA
document
are
utilized
in
the
above
methodology.
One
should
note
that
the
AIHA
lists
two
odor
thresholds
for
the
four
glycol
ethers:
1)
the
detection
threshold
(
d)
which
is
the
lowest
concentration
at
which
a
specific
percentage
of
the
test
subjects,
usually
50%,
can
detect
the
stimulus
as
different
from
odor­
free
blanks
and
2)
the
recognition
threshold
(
r)
which
is
the
lowest
concentration
at
which
a
specific
percentage
of
the
test
subjects,
usually
50%,
can
ascribe
a
definite
character
to
the
odor
(
Ex.
5­
143).
The
AIHA
detection
threshold
values
are
very
similar
to
the
odor
threshold
values
presented
in
Amoore
and
Hautala's
paper
and
give
the
same
classification
results,
therefore,
only
odor
safety
factors
and
classifications
associated
with
recognition
threshold
values
appear
in
Table
C
Table
C
Proposed
Odor
Odor
Compound
TWA
(
ppm)
Threshold
(
ppm)
Safety
Factor
Class
2­
ME
0.1
2.4
(
d)

4.4
(
r)
0.011
E
2­
MEA
0.1
0.33
(
d)

0.64
(
r)
0.17
E
2­
EE
0.5
2.7
(
d)

6.5
(
r)
0.08
E
2­
EEA
0.5
0.06
(
d)

0.13
(
r)
3.8
C
Performing
the
calculations
using
the
recognition
thresholds
again
results
in
2­
EE
and
2­
MEA
having
very
low
odor
safety
factors.
The
AIHA
data
also
yields
a
low
odor
safety
factor
for
2­
MEA
(
Amoore
and
Hautala
present
no
odor
threshold
for
this
substance).
2­
EEA
once
more
achieves
the
highest
odor
safety
factor
and
classification,
Class
C,
which,
as
stated
previously,
can
be
interpreted
to
mean
that
less
than
50%
of
distracted
persons
will
perceive
a
warning
of
the
compound
at
the
proposed
TWA
concentration
Amoore
and
Hautala
state
that
their
thresholds
represent
the
most
favorable
conditions
for
odor
testing,
that
is,
the
subjects
were
aware
of
the
test,
were
attentive,
and
were
trying
to
detect
an
odor
The
studies
utilized
by
the
AIHA
for
determining
the
odor
thresholds
of
the
four
glycol
ethers
also
appear
to
have
utilized
test
subjects
who
were
aware
of
their
objective
and
therefore
would
be
concentrating
on
detecting
and/
or
recognizing
an
odor.
OSHA
does
not
believe
that
such
idealized
circumstances
for
odor
detection
normally
occur
in
the
workplace.
An
employee
would
be
distracted
by
performing
other
tasks
(
e.
g.,
operating
machinery,
reviewing
charts,
observing
production
processes)
and
would
not
normally
be
focusing
his/
her
attention
on
detecting
a
minimal
odor
level.
Even
the
higher
recognition
threshold
values
are
likely
not
to
be
indicative
of
odor
perception
of
a
distracted
employee
in
the
workplace
with
actual
odor
recognition
occurring
at
even
higher
concentrations
Considering
the
preceding
information,
the
Agency
does
not
feel
that
any
of
the
four
glycol
ethers
display
adequate
warning
properties
at
the
proposed
TWA
permissible
exposure
limits
to
permit
use
of
air­
purifying
respirators.
Therefore,
only
supplied­
air
respiratory
protection
is
deemed
appropriate
for
use
with
these
compounds
The
use
of
supplied­
air
respiratory
protection
is
supported
by
the
following
NIOSH
comments
to
the
ANPR:
(
Ex.
7­
22)

In
NIOSH
CIB
#
39:
The
Glycol
Ethers,
with
particular
reference
to
2­
methoxyethanol
and
2­
ethoxyethanol,
NIOSH
recommended
that
exposure
to
the
glycol
ethers
be
reduced
to
the
lowest
extent
feasible.
Only
the
most
protective
respirators
are
consistent
with
that
recommendation:
self­
contained
breathing
apparatus
with
full
facepiece
operated
in
the
pressure
demand
mode,
or
a
combination
respirator
which
includes
a
Type
C
supplied­
air
respirator
with
a
full
facepiece
operated
in
the
pressure­
demand
mode
and
an
auxiliary
self­
contained
breathing
apparatus
operated
in
the
pressuredemand
mode.

NIOSH
goes
on
to
state
that
if
the
proposed
permissible
exposure
limits
are
below
the
odor
threshold
and
OSHA
decides
not
to
follow
their
recommendation
to
permit
only
supplied­
air
respiratory
protection,
then
[
page
15603]

only
cartridge
or
canister
respirators
with
effective
end­
of­
service­
life
indicators
should
be
allowed.
The
Agency
is
not
aware
of
any
NIOSH/
MSHA
approved
cartridges
or
canisters
with
end­
of­
service­
life
indicators
for
glycol
ethers
Following
a
conservative
approach
and
allowing
only
supplied­
air
respirators
eliminates
the
question
of
whether
employees
could
be
unknowingly
exposed
as
a
result
of
the
compound's
actual
odor
threshold
being
above
the
permissible
exposure
limits
since
the
employee
is
no
longer
inhaling
ambient
air
through
a
sorbent
cartridge.
While
the
employer
must
select
the
appropriate
respirator
from
the
table
based
upon
the
airborne
concentration
of
glycol
ethers,
the
employer
may
always
select
a
respirator
providing
greater
protection
(
i.
e.,
one
prescribed
for
higher
concentrations
of
glycol
ethers
than
are
present
in
the
workplace)

The
respirator
selection
table
in
the
proposed
standard
lists
the
type
of
respiratory
protection
which,
at
a
minimum,
must
be
provided
and
used
at
each
airborne
concentration
of
glycol
ethers
in
the
workplace.
In
no
circumstance
shall
a
respirator
be
used
in
atmospheric
concentrations
which
exceed
that
respirator's
assigned
protection
factor.
The
respirators
selected
by
the
employer
must
be
approved
by
the
Mine
Safety
and
Health
Administration
(
MSHA)
and
by
the
National
Institute
for
Occupational
Safety
and
Health
(
NIOSH)
under
the
provisions
of
30
CFR
Part
11
or
any
future
revisions.
It
should
be
noted
that
NIOSH
is
currently
in
the
process
of
revising
the
30
CFR
Part
11
respirator
testing
and
certification
standards.
When
published,
this
revision
will
be
listed
as
42
CFR
Part
84.
OSHA
will
expect
employers
to
base
respirator
selection
on
the
most
recent
published
standards
of
the
aforementioned
agencies
In
those
situations
in
which
respirator
use
is
required,
the
employer
shall
institute
a
respiratory
protection
program
in
accordance
with
29
CFR
1910.134
(
b),
(
d),
(
e),
and
(
f)
as
would
be
required
by
paragraph
(
g)(
4)
of
this
proposed
standard.
This
general
industry
standard
(
29
CFR
1910.134)
includes
provisions
for
the
selection,
fit,
use,
cleaning,
and
maintenance
of
respirators.
In
addition,
it
contains
requirements
for
a
written
respiratory
protection
program
and
minimum
air
quality
standards
for
supplied­
air
respiratory
protection
systems
A
drawback
to
respirator
use
is
the
skin
irritation
that
can
develop
with
some
employees,
particularly
in
hot,
humid,
and/
or
dirty
environments.
The
Agency
recognizes
that
this
irritation
adds
to
the
discomfort
and
inconvenience
already
experienced
by
employees
wearing
respirators
and
has
included
paragraph
(
g)(
5)
with
the
intent
of
minimizing
skin
irritation
and
assuring
adequate
employee
protection
This
provision
states
that
employers
must
permit
employees
to
leave
the
work
area
to
wash
their
faces
and
respirator
facepieces
as
needed
to
prevent
skin
irritation
from
respirator
use
Paragraph
(
g)(
6)
deals
with
the
fit
testing
of
respirators.
The
employer
would
be
required,
by
paragraph
(
g)(
6)(
i),
to
assure
that
the
respirator
issued
to
the
employee
exhibits
the
least
possible
facepiece
leakage
and
that
the
respirator
is
fitted
properly
and
will
not
permit
the
employee
to
inhale
glycol
ethers
in
excess
of
either
the
TWAs
or
ELs.
Good
face
fit
is
critical
in
assuring
proper
performance
of
respiratory
protection.
When
an
employee
inhales
through
a
respirator
which
fits
poorly,
contaminated
workplace
air
can
enter
the
respirator
through
gaps
and
leaks
in
the
seal
between
the
face
and
the
facepiece.
Obtaining
a
proper
respirator
fit
may
require
the
fit
testing
of
a
variety
of
different
mask
sizes
from
several
manufacturers
to
select
the
facepiece
with
the
best
fit
(
least
leakage
around
the
faceseal)
for
each
employee.
This
methodology
will
reduce
inhalation
leakage
to
a
minimum
Quantitative
fit
testing
is
a
procedure
whereby
the
level
of
penetration
of
a
test
agent
of
a
known
concentration
is
measured
inside
the
facepiece
of
the
respirator.
It
provides
a
quantitative
assessment
of
the
fit
(
the
fit
factor).
It
allows
the
employer
to
continue
testing
different
facepieces
until
the
optimum
or
best
fitting
respirator
is
identified
and
selected
for
the
employee.
Quantitative
fit
testing
requires
the
use
of
moderately
sophisticated
testing
equipment
and
is
more
expensive
to
perform
than
qualitative
fit
testing,
which
may
reduce
its
availability
in
some
worksites.
Also
testing
services
may
not
be
available
in
all
parts
of
the
country
to
provide
quantitative
fit
testing
services
for
small
employers
Qualitative
fit
testing
does
not
provide
a
numerical
measure
of
the
quality
of
the
fit
but
simply
determines
whether
a
respirator
fits
or
not.
Qualitative
fit
testing
is
a
technique
whereby
a
person
wearing
a
respirator
is
tested
to
see
whether
a
test
agent
with
a
detectable
odor
or
taste
threshold
can
be
detected
inside
the
respirator.
If
the
test
agent
is
not
detected
by
the
employee
wearing
the
respirator,
the
respirator
is
said
to
fit.
Qualitative
fit
testing
is
more
subjective
than
quantitative
testing
because
it
depends
on
the
individual's
ability
to
detect
the
test
agent
OSHA
believes
that
while
quantitative
fit
testing
may
have
some
advantages,
qualitative
testing
conducted
in
accordance
with
the
protocols
described
in
Appendix
F
can
adequately
accomplish
the
intent
of
the
standard
of
ensuring
that
each
employee
is
assigned
and
wears
the
respirator
that
provides
a
proper
fit
with
the
least
possible
leakage.
Comments
are
requested
on
all
aspects
of
fit
testing
Paragraph
(
g)(
6)(
ii)
states
that
for
each
employee
wearing
a
tight­
fitting
supplied­
air
respirator,
the
employer
shall
perform
either
a
qualitative
or
quantitative
fit
test.
Fit
testing
may
be
accomplished
by
testing
the
particular
facepiece
to
be
used
(
make,
model,
and
size),
without
any
air
supplying
equipment
or
attachments
Testing
is
conducted
by
equipping
the
facepiece
with
appropriate
air
purifying
elements.
Upon
obtaining
adequate
fit
with
a
particular
facepiece,
then
that
facepiece
is
to
be
used
with
the
supplied­
air
system
(
i.
e.,
air­
supplying
equipment
or
attachments).
When
quantitative
fit
testing
is
performed,
half
mask
facepieces
must
exhibit
a
fit
factor
of
100
and
full
facepieces
a
fit
factor
of
500,
at
a
minimum.
Regardless
of
the
fit
testing
protocol
utilized,
qualitative
or
quantitative,
respirator
protection
factors
are
to
be
assigned
according
to
the
respirator
selection
table
in
the
proposed
standard
Paragraph
(
g)(
6)(
iii)
would
require
the
employer
to
perform
and
certify
the
results
of
the
appropriate
fit
tests
at
the
time
of
an
employee's
initial
fitting,
at
least
annually
thereafter,
when
a
different
size
or
make
of
respirator
is
used,
and
when
a
change
in
facial
structure
occurs.
This
frequency
of
fit
testing
is
necessary
to
assure
that
factors
which
may
affect
the
proper
fit
of
a
respirator
are
detected
and
necessary
adjustments
are
performed
to
assure
the
integrity
of
the
faceseal.
For
example,
the
fit
of
respirators
is
not
standardized
between
manufacturers.
Fit
testing
would
be
required,
therefore,
whenever
a
different
size
or
make
of
respirator
is
used.
In
addition,
a
change
in
an
employee's
facial
structure
can
compromise
a
respirator's
faceseal.
Examples
of
such
changes
include
loss
of
weight,
cosmetic
surgery,
facial
scarring,
and
the
installation
of
dentures.
Therefore,
fit
testing
is
required
at
least
annually
and
when
any
facial
changes,
such
as
those
mentioned
above,
occur.

[
page
15604]

In
order
to
assure
that
employees
willingly
participate
in
fit
testing
and
that
such
procedures
are
standardized,
paragraph
(
g)(
6)(
iv)
would
require
that
all
tests
be
performed
at
a
reasonable
time
and
place
and
at
no
cost
to
the
employee
and
must
be
conducted
in
accordance
with
Appendix
F
of
this
proposal
Personal
Protective
Equipment:
Paragraph
(
h)

The
underlying
premise
of
personal
protective
equipment
is
that
its
use
will
protect
against
exposure
during
performance
of
a
task.
Paragraph
(
h)
of
the
proposal
contains
a
number
of
provisions
concerned
with
the
use
of
personal
protective
equipment.
In
this
paragraph,
employers
would
be
required
to
select
and
provide
appropriate
personal
protective
equipment
in
accordance
with
29
CFR
1910.132
(
General
Requirements)
and
29
CFR
1910.133
(
Eye
and
Face
Protection)
of
the
General
Industry
Standards
as
often
as
necessary
throughout
the
work
shift
to
prevent
employee
exposure
to
glycol
ethers.
Based
on
good
industrial
hygiene
practice,
paragraph
(
h)(
1)(
i)
of
the
proposed
standard
would
require
that
selection
of
personal
protective
equipment
must
be
based
upon
the
type
of
exposure
anticipated
(
e.
g.,
hand
contact,
splashing,
spraying,
inhalation),
conditions
of
use
(
i.
e.
suitability
of
the
equipment
to
maintain
its
protective
capabilities
under
the
conditions
in
which
it
will
be
used),
and
the
hazard
to
be
prevented
(
e.
g.,
splashes
to
the
face,
eye
irritation,
dermal
exposure,
aerosol
inhalation).
This
approach
is
performance
oriented
as
it
requires
that
the
employer
evaluate
each
process
or
task
which
could
present
a
possibility
of
exposure
and
then
implement
the
most
efficient
means
for
protecting
against
the
exposure
The
employer
would
also
be
required
by
paragraph
(
h)(
1)(
ii)
of
the
proposal
to
provide
the
appropriate
personal
protective
equipment
at
no
cost
to
the
employee
and
assure
that
employees
use
this
equipment
Provision
of
personal
protective
equipment
at
no
cost
to
the
employee
helps
assure
employees'
acceptance
of
its
use
in
exposure
situations.
Since
it
is
the
employer's
obligation
to
prevent
employee
exposure
to
glycol
ethers
in
the
workplace,
the
responsibility
to
provide
personal
protective
equipment
and
assure
its
use
rightfully
rests
with
the
employer
In
order
to
prevent
employees
from
being
unwittingly
exposed
and
to
achieve
adequate
protection,
paragraph
(
h)(
1)(
iii)
states
that
personal
protective
equipment
such
as,
but
not
limited
to,
coveralls,
gloves,
faceshields,
and
rubber
boots,
must
be
made
of
materials
sufficiently
impervious
to
glycol
ethers
to
prevent
employee
exposure
to
these
compounds.
For
example,
information
submitted
in
response
to
the
ANPR
included
breakthrough
and
permeation
studies
of
various
glove
materials
relative
to
glycol
ethers
(
Exs.
4­
017c,
7­
22
attachment
17).
Both
the
study
by
Union
Carbide
and
that
of
Dow
Chemical
indicate
that
butyl
rubber
gloves
provide
good
protection
against
exposure
to
these
compounds.
The
proposed
regulation
is
performance
oriented,
however,
and
does
not
stipulate
that
protective
gloves
or
other
protective
equipment
be
made
of
a
specific
material
but
simply
that
any
equipment
selected
be
adequate
to
prevent
employee
contact
with
glycol
ethers.
In
this
way,
the
proposed
standard
will
not
interfere
with
any
developing
technology
or
innovative
techniques
that
may
efficiently
protect
employees
from
contact
with
glycol
ethers
Paragraph
(
h)(
1)(
iv)
is
closely
related
to
the
preceding
provision
in
that
it
would
require
employers
to
provide
uncontaminated
personal
protective
equipment
as
often
as
necessary
throughout
the
work
shift
to
prevent
employee
exposure
to
glycol
ethers
Removal
and
storage
of
personal
protective
equipment
is
covered
under
paragraph
(
h)(
2)
of
the
proposal.
Employers
would
be
required
to
assure
that
employees
remove
all
personal
protective
equipment
contaminated
with
glycol
ethers
prior
to
leaving
the
work
area
or
as
soon
as
feasible
if
the
potential
for
soak­
through/
breakthrough
exists.
This
paragraph
would
also
require
that
removal
of
contaminated
personal
protective
equipment
be
done
in
an
area
which
would
minimize
exposure
of
other
employees
to
glycol
ethers
Paragraph
(
h)(
2)(
ii)
states
that
the
employer
must
assure
that
no
employee
takes
home
glycol
ethers
contaminated
personal
protective
equipment.
In
addition,
paragraph
(
h)(
2)(
iii)
would
require
the
employer
to
assure
that
no
employee
takes
glycol
ether
contaminated
equipment
out
of
the
workplace
unless
authorized
to
do
so
for
the
purposes
of
laundering,
cleaning,
maintenance,
or
disposal
As
stated
previously,
the
intent
of
personal
protective
equipment
is
to
protect
the
employee
against
exposure.
Therefore,
if
a
situation
arises
in
which
glycol
ethers
may
soak
through
the
equipment
provided
then
the
employer
must
assure
that
the
employee
removes
the
equipment
as
soon
as
possible
to
prevent
dermal
absorption.
In
addition,
contaminated
equipment
is
to
be
removed
prior
to
leaving
the
work
area
and
in
an
area
which
would
minimize
exposure
of
other
employees
in
order
to
minimize
migration
of
the
contaminant
away
from
the
worksite
and
prevent
possible
exposure
of
additional
individuals
such
as
fellow
employees
and
family
members
through
airborne
or
dermal
routes.
Only
authorized
employees
are
to
be
permitted
to
take
contaminated
protective
equipment
out
of
the
workplace
and
only
for
the
purposes
of
laundering,
cleaning,
maintenance,
or
disposal.
It
should
be
noted
that
the
Agency
does
not
intend
for
employees
to
be
authorized
to
launder
and
clean
contaminated
items
at
home
or
at
a
public
laundromat.
Therefore,
these
activities
have
been
specifically
prohibited.
Instead,
only
those
employees
who
are
trained
and
informed
as
required
in
paragraphs
(
h)(
3)(
ii)
and
(
h)(
3)(
iii)
are
to
be
authorized
to
remove
contaminated
personal
protective
equipment
from
the
workplace
Contaminated
personal
protective
equipment
must
be
stored
in
such
a
manner
so
as
to
minimize
employee
exposure
and
shall
not
be
worn
again
until
cleaned
or
laundered.
Thus,
the
area
where
protective
equipment
dampened
with
glycol
ethers
or
glycol
ethercontaining
compounds
are
stored
must
be
sufficiently
apart
from
areas
where
employees
work
or
congregate
to
prevent
additional
exposure
to
employees.
Re­
wearing
of
contaminated
equipment
is
prohibited
to
prevent
additional
employee
exposure
and
an
enhanced
potential
for
dermal
absorption.
Storage
areas
or
containers
with
glycol
ethers
contaminated
personal
protective
equipment
must
have
either
a
sign
or
a
label,
respectively,
as
specified
in
paragraph
(
m)(
1)(
ii)

Paragraph
(
h)(
3)(
i)
would
require
that
each
employer
must
clean,
launder,
repair,
or
replace,
at
no
cost
to
the
employee,
all
required
personal
protective
equipment
for
each
affected
employee
as
necessary
to
assure
its
effectiveness
and
stipulates
that
the
employer
is
responsible
for
disposal
of
these
items.
The
requirement
to
repair
or
replace
the
protective
equipment
is
necessary
to
insure
the
proper
functioning
of
these
items
and,
thereby,
proper
employee
protection.
Requiring
that
the
employer
be
responsible
for
cleaning,
laundering,
repair,
and
disposal
insures
that
contaminated
equipment
will
be
handled
only
by
personnel
who
have
been
trained
in
the
proper
work
practices
for
handling
this
equipment
as
specified
in
paragraph
(
h)(
3)(
ii)
and
(
h)(
3)(
iii).
Overall,
this
[
page
15605]

paragraph
assures
that
contaminated
equipment
remains
under
the
control
of
the
employer.
This
approach
permits
standardized,
consistent
cleaning,
laundering,
repair,
and
replacement
of
these
items
thereby
maximizing
their
effectiveness
and
helping
to
assure
that
they
are
properly
disposed
of
at
the
end
of
their
service
life
The
employer
would
also
be
required
by
paragraph
(
h)(
3)(
ii)
to
assure
that
only
trained
persons
remove
contaminated
personal
protective
equipment
from
storage
for
the
purpose
of
laundering,
cleaning,
repair
or
disposal.
In
this
way,
only
those
employees
who
are
aware
of
the
hazards
of
glycol
ethers
and
use
proper
handling
work
practices
will
contact
the
equipment.
Whether
the
employer
has
an
on­
site
laundry/
cleaning/
repair
facility
or
sends
the
equipment
off­
site
for
laundering,
cleaning,
or
repair,
the
employer
shall
inform
any
person
who
may
have
contact
with
such
equipment
of
glycol
ethers'
potentially
harmful
effects
and
of
procedures
to
safely
handle
the
personal
protective
equipment
as
would
be
required
by
paragraph
(
h)(
3)(
iii)

Paragraph
(
h)(
3)(
iv)
states
that
the
employer
shall
assure
that
laundering,
cleaning,
maintenance,
and
disposal
are
performed
only
at
facilities
which
are
appropriate
to
handle
glycol
ethers
contaminated
personal
protective
equipment.
Therefore,
as
stated
previously,
activities
such
as
laundering
contaminated
personal
protective
equipment
at
a
public
laundromat
or
in
an
employee's
home
would
be
prohibited.
This
is
to
assure
that
these
operations
are
properly
performed
and
to
prevent
inadvertent
exposure
of
unknowing
individuals
Paragraph
(
h)(
3)(
v)
stipulates
that
when
contaminated
personal
protective
equipment
is
destined
for
disposal,
it
shall
be
placed
in
a
sealed
container
which
is
labeled
in
accordance
with
paragraph
(
m)(
1)(
ii)
of
this
section.
This
provision
will
assure
that
those
individuals
who
may
come
in
contact
with
the
container
will
be
protected
against
exposure
and
will
be
warned
of
the
container's
contents
Hygiene
Protection:
Paragraph
(
i)

A
characteristic
of
a
number
of
solvents,
including
glycol
ethers,
is
that
they
can
be
readily
absorbed
through
the
skin.
Therefore,
if
employees
may
become
splashed
with
liquids
containing
glycol
ethers,
paragraph
(
i)(
1)
would
require
the
employer
to
provide
conveniently
located
quick
drench
showers
and
assure
that
affected
employees
use
these
facilities
immediately.
Quick
drench
showers
must
be
able
to
rapidly
drench
the
employee
with
a
forceful
flow
of
water
in
order
to
effectively
remove
the
glycol
ether,
thereby
minimizing
dermal
absorption.
These
showers
must
also
be
located
in
the
immediate
work
area
of
an
employee
who
could
be
splashed
so
that
they
may
be
reached
quickly
should
an
accidental
splash
occur,
once
again
reducing
the
length
of
time
glycol
ethers
remain
in
contact
with
the
skin
and
consequently
the
absorption
of
these
compounds
into
the
body.
It
is
particularly
important
to
locate
showers
in
areas
where
employees
do
not
normally
wear
full
body
protective
clothing
yet
could
potentially
be
accidently
splashed
or
in
areas
where
large
volume
splashes
could
occur.
Criteria
for
assessing
quick­
drench
showers
and
eyewashes
can
be
found
in
consensus
standards
such
as
ANSI
Z358.1­
1981
and
NSA
Data
Sheet
1­
686­
80.
References
such
as
these
can
be
used
to
evaluate
characteristics
such
as
flowrate,
accessibility,
construction,
testing
schedules,
and
so
forth
Paragraph
(
i)(
2)
would
require
the
employer
to
provide
eye­
wash
fountains
within
the
immediate
work
area
of
employees
whose
eyes
could
possibly
be
splashed
with
liquids
containing
glycol
ethers
since
these
compounds
are
eye
irritants.
For
the
same
reasons
as
above,
an
employee
must
be
able
to
reach
the
fountains
quickly
so
that
the
flushing
can
be
initiated
as
soon
as
possible
after
an
accidental
eye
splash.
In
addition,
eye­
wash
fountains
should
be
capable
of
maintaining
an
appropriate
water
pressure
for
an
appropriate
length
of
time
to
remove
glycol
ethers
from
the
eyes
OSHA
has
not
proposed
that
separate
change
rooms
and
shower
facilities
be
provided.
In
addition,
showering
at
the
end
of
the
work
shift
would
not
be
required.
Based
upon
its
understanding
of
glycol
ethers
usage
patterns,
the
Agency
envisions
the
use
of
personal
protective
equipment
as
a
temporary
measure
utilized
intermittently
during
performance
of
an
employee's
duties
and
worn
over
the
employee's
regular
work
clothes.
It
is
felt
that
prohibiting
removal
of
this
equipment
in
common
areas
will
provide
adequate
protection
from
exposure
for
other
employees.
Due
to
the
dermal
absorption
properties
of
glycol
ethers,
the
Agency
feels
that
requiring
showering
at
the
end
of
the
work
shift
would
not
provide
added
protection
since
absorption
would
have
already
occurred.
Minor
splashes
can
be
washed
off
in
normal
lavatory
facilities
while
quick­
drench
showers
are
available
for
major
exposures.
In
both
cases,
other
provisions
of
this
standard
require
employers
to
assure
removal
of
glycol
ethers
from
the
skin
immediately
or
as
soon
as
feasible
and
replacement
of
contaminated
equipment
Paragraph
(
i)(
3)
would
prohibit
eating,
drinking,
smoking,
and
application
of
cosmetics
in
areas
of
glycol
ethers
exposure.
The
purpose
of
this
provision
is
to
prevent
inadvertent
ingestion,
inhalation,
or
dermal
application
of
glycol
ethers.
In
addition,
paragraph
(
i)(
4)
would
prohibit
wearing
of
personal
protective
equipment
in
lunch
areas
to
prevent
migration
of
glycol
ethers
to
an
area
where
other
employees
may
be
unknowingly
exposed
Housekeeping:
Paragraph
(
j)

Paragraph
(
j)(
1)
would
require
that
all
surfaces
(
e.
g.
floors,
working
surfaces,
exterior
surfaces
of
equipment)
be
kept
free
of
glycol
ethers
to
the
extent
feasible.
Not
only
is
this
consistent
with
the
intent
of
General
Industry
Standards
29
CFR
1910.141
(
a)(
3),
Housekeeping,
but
this
provision
minimizes
both
the
unnecessary
spread
of
glycol
ethers
in
the
workplace
and
an
increased
potential
for
employee
exposure
Paragraph
(
j)(
2)
would
require
employers
to
conduct
a
program
to
detect
leaks
and
spills,
including
visual
inspections
of
operations
involving
liquids
containing
glycol
ethers.
The
intent
of
this
provision
is
to
minimize
the
number
of
employees
who
could
be
inadvertently
exposed
through
either
dermal
contact
with
liquid
glycol
ethers
or
elevated
airborne
concentrations
evolving
from
evaporation
of
such
liquids
In
addition
to
the
above
program,
paragraph
(
j)(
3)
would
require
preventative
maintenance
of
equipment
that
handle
glycol
ethers,
including
surveys
for
leaks
at
intervals
appropriate
to
assure
proper
functioning
of
equipment.
This
provision
should
assist
in
reducing
exposure
resulting
from
leakage
caused
by
items
such
as
cracked
joints,
corroded
tanks,
broken
gaskets,
worn
valve
packings,
malfunctioning
equipment,
and
so
forth
Periodic
inspection
and
maintenance
of
process
equipment
and
control
equipment
such
as
ventilation
systems
is
an
important
work
practice
control.
In
plants
where
total
containment
is
used
as
an
engineering
control,
the
failure
of
process
equipment
or
the
ventilation
system
can
seriously
increase
the
probable
occurrence
of
exposures.
Frequently,
equipment
which
is
near
failure
or
in
disrepair
will
not
perform
normally.
Regular
inspections
can
detect
abnormal
conditions
so
that
maintenance
can
then
be
performed.
If
equipment
is
routinely
inspected,
replaced,
or
repaired
before
failure
is
[
page
15606]

likely,
the
risk
of
exposure
occurring
will
be
reduced.

The
Agency
has
intentionally
kept
inspection
and
maintenance
requirements
in
performance­
oriented
terms
rather
than
dictating
specific
time
intervals
for
these
activities.
OSHA
is
aware
that
different
industry
sectors
and
even
different
manufacturing
processes
within
the
same
facility
may
vary
in
the
frequency
of
occurrence
of
leaks/
spills
or
the
need
for
preventative
maintenance
of
equipment.
The
employer,
therefore,
is
afforded
the
flexibility
to
determine
the
frequency
of
inspection/
maintenance
and,
as
a
result,
gain
any
cost
savings
accrued
through
elimination
of
an
arbitrarily
assigned
frequency
schedule
In
areas
where
spillage
may
occur,
paragraph
(
j)(
4)
stipulates
that
the
employer
must
make
provisions
to
contain
the
spill,
to
decontaminate
the
work
area,
and
to
dispose
of
the
waste
generated
by
the
clean­
up.
Should
a
spill
occur,
having
such
provisions
in
place
will
assist
in
quickly
limiting
the
area
affected
by
the
spill,
facilitate
its
clean­
up,
and
will
permit
more
rapid
and
efficient
decontamination
of
the
spill
area
and
proper
disposal
of
clean­
up
waste.
The
intent
of
this
proposed
requirement
is
to
increase
preparedness
for
the
eventuality
of
a
spill,
thereby
minimizing
employee
exposure
by
reducing
the
time
necessary
to
control
and
clean
up
a
spill
and
properly
dispose
of
waste.
Since
glycol
ethers
exist
in
a
variety
of
work
environments,
it
is
left
to
employers
to
assess
what
methods
are
appropriate
to
their
workplace
and
conditions
of
use
and
are
protective
of
their
employees
Paragraph
(
j)(
5)
would
require
that
upon
discovery
of
a
leak
or
spill
the
employer
assure
that
repair
of
the
leak
and/
or
clean
up
of
the
spill
is
initiated
promptly
in
order
to
limit
the
area
affected
and
eliminate
the
source
of
leakage.
The
employees
performing
this
repair
and
clean
up
must
be
adequately
protected
by
suitable
personal
protective
equipment,
which
may
include
respiratory
protection,
to
prevent
exposure
during
these
operations.
These
employees
must
also
be
trained
in
proper
methods
for
clean­
up
and
decontamination
so
that
such
operations
can
be
accomplished
safely,
efficiently,
and
without
exacerbating
the
hazard
The
final
provision
of
the
housekeeping
section,
paragraph
(
j)(
6),
would
require
that
waste
and
debris
contaminated
with
glycol
ethers
be
placed
in
sealed
containers
bearing
a
warning
label
as
specified
in
paragraph
(
m)(
1)(
ii).
The
containers
will
minimize
airborne
concentrations
resulting
from
evaporation
of
glycol
ethers
from
the
wastes
and
prevent
possible
accidental
employee
contact
or
re­
spillage
of
the
material.
The
warning
label
is
necessary
to
warn
employees
who
may
handle
the
containers
of
the
hazard
they
contain.
The
Agency
recognizes
that
wastes
destined
for
disposal
may
need
to
meet
packaging
and
labeling
requirements
of
other
local,
State
or
Federal
regulatory
bodies.
It
is
not
OSHA's
intent
to
issue
duplicative
or
conflicting
regulations.
This
provision
is
directed
at
protecting
and
warning
employees
at
the
worksite.
However,
OSHA
notes
that
the
containers
should
leave
the
worksite
for
final
disposal
in
a
form
that
meets
the
requirements
of
the
appropriate
regulatory
bodies
Emergencies:
Paragraph
(
k)

This
paragraph
addresses
the
handling
of
emergency
situations
involving
glycol
ethers.
The
proposal
requires
that
for
each
workplace
or
work
operation
where
there
is
a
possibility
of
an
emergency
involving
glycol
ethers,
the
employer
must
develop
a
written
emergency
plan
including,
at
a
minimum,
those
elements
prescribed
in
29
CFR
1910.38
(
a).
For
example,
29
CFR
1910.38
(
a)
includes
provisions
concerning
emergency
escape
procedures
and
escape
route
assignments;
procedures
to
be
followed
by
employees
remaining
to
operate
critical
plant
operations
before
they
evacuate;
alarm
systems;
evacuation
plans;
employee
training;
fire
protection;
and
so
forth.
It
should
be
noted
that
development
of
this
plan
is
not
dependent
upon
the
existence
of
employee
exposure
but
is
based
on
the
possibility
of
an
emergency
situation
arising.
That
is,
an
employee
may
be
exposed
to
glycol
ethers
and
yet
the
potential
for
an
emergency
may
not
exist
in
the
employee's
work
area.
Conversely,
there
may
be
no
employees
in
an
area
where
there
is
a
large
quantity
of
glycol
ethers,
such
as
a
storage
tank,
but
the
potential
for
an
emergency
exists
(
e.
g.,
rupture
of
the
tank).
An
emergency
could
be
a
massive
release
affecting
a
large
area
or
may
be
a
spill
or
leak
which
creates
an
emergency
situation
only
in
the
immediate
area.
Emergency
situations,
therefore,
may
not
be
likely
to
occur
in
every
workplace.
Consequently,
the
Agency
has
adopted
a
performance
oriented
approach
which
allows
the
employer
to
evaluate
and
tailor
the
emergency
plan
to
fit
the
workplace
so
long
as
it
meets
the
requirements
of
29
CFR
1910.38
(
a)
and
the
specific
provisions
of
this
section
In
addition
to
requiring
that
the
emergency
plan
comply
with
the
requirements
of
29
CFR
1910.38
(
a),
paragraph
(
k)(
1)
also
states
the
provisions
of
paragraph
(
q)
of
the
Hazardous
Waste
Operations
and
Emergency
Response
standard,
29
CFR
1910.120,
remain
in
effect
as
applicable.
Also,
an
emergency
response
plan
meeting
requirements
of
29
CFR
1910.120
(
q)
would
be
deemed
to
meet
the
requirements
for
an
emergency
response
plan
under
paragraph
(
k)

Paragraph
(
q)
of
the
Hazardous
Waste
Operations
and
Emergency
Response
standard,
29
CFR
1910.120,
deals
with
emergency
responses
by
employees
outside
the
immediate
worksite
to
releases
of
hazardous
substances
that
occur
at
locations
other
than
uncontrolled
hazardous
waste
sites
and
hazardous
treatment,
storage
and
disposal
operations
conducted
under
the
Resource,
Conservation
and
Recovery
Act
of
1976
as
amended
[
42
U.
S.
C.
6901
et.
seq.].
The
typical
site
covered
by
paragraph
(
q)
would
include
hazardous
substance
releases
at
chemical
manufacturing
facilities.
Paragraph
(
k)(
1)
makes
clear
that
this
paragraph
does
not
override
the
provisions
of
29
CFR
1910.120
(
q)
and
that
paragraph
(
q)
remains
applicable
pursuant
to
its
terms.
In
addition,
paragraph
(
k)(
1)
specifies
that
an
emergency
response
plan
meeting
the
requirements
of
paragraph
(
q)
shall
also
be
deemed
to
meet
the
requirements
of
paragraph
(
k)
for
all
employees
responding
to
an
emergency
Paragraph
(
k)(
2)
would
require
that
all
employees
be
trained
in
their
responsibilities
in
the
event
of
an
emergency
to
minimize
employee
exposure,
injury,
and
loss
of
life
while
increasing
efficiency
in
dealing
with
the
situation
Generally,
emergencies
entail
large
quantities
of
free
glycol
ethers
resulting
in
elevated
airborne
concentrations,
increased
chance
of
dermal
contact,
and,
in
some
circumstances,
the
possibility
of
fire.
In
view
of
this,
paragraph
(
k)(
3)
would
require
the
employer
to
assure
that
only
designated
personnel
furnished
with
appropriate
personal
protective
equipment,
including
respiratory
protection,
and
trained
in
re­
entry
procedures
are
permitted
to
correct
the
emergency
conditions.
The
employer
would
also
be
responsible
for
assuring
that
the
appropriate
personal
protective
equipment,
housekeeping,
and
other
emergency
equipment
and
supplies
for
handling
the
emergency
are
located
in
each
area
where
an
emergency
could
occur
so
that
the
situation
can
be
dealt
with
quickly
and
safely.
As
stipulated
in
paragraph
(
k)(
5),
all
employees,
except
those
designated
to
correct
the
situation,
must
be
evacuated
from
and
normal
[
page
15607]

operations
halted
in
the
area
where
the
emergency
has
occurred
until
the
emergency
conditions
have
been
abated.
This
will
minimize
the
number
of
employees
exposed
and
eliminate
the
presence
of
untrained
personnel
in
the
area.
In
addition,
this
provision
minimizes
the
potential
for
exacerbation
of
the
hazard
as
a
result
of
attempting
to
maintain
operations
during
an
emergency
situation
Paragraph
(
k)(
6)
of
this
section
would
require
the
employer
to
make
provisions
for
immediate
evacuation,
transportation,
and
medical
assistance
at
a
designated
medical
facility
for
affected
employees.
This
provision
will
help
assure
that
acutely
exposed
employees
will
receive
appropriate
medical
attention
as
quickly
as
possible
after
exposure.
By
having
such
arrangements
made
beforehand,
confusion
or
delay
in
obtaining
prompt
medical
attention
for
the
employee
will
be
minimized
Medical
Surveillance:
Paragraph
(
l)

Paragraph
(
l)(
1)(
i)
of
the
proposal
requires
each
employer
to
institute
a
medical
surveillance
program
for
all
employees
who
are
or
will
be
exposed
at
or
above
the
action
level
or
above
the
EL.
Providing
medical
surveillance
for
employees
exposed
at
or
above
the
action
level
or
above
the
EL
is
consistent
with
other
health
standards
that
incorporate
an
action
level
or
an
EL
and
is
considered
by
OSHA
to
be
necessary
and
appropriate
for
monitoring
the
adequacy
of
the
exposure
limit
to
protect
individual
employees
The
proposal
requires
that
the
medical
surveillance
program
provide
each
covered
employee
with
an
opportunity
for
a
medical
examination.
Paragraph
(
l)(
1)(
ii)
provides
that
all
examinations
and
procedures
be
performed
by
or
under
the
supervision
of
a
qualified
physician
and
be
provided
without
cost
to
the
employee.
Clearly,
a
qualified
physician
is
the
appropriate
person
to
be
supervising
and
evaluating
a
medical
examination.
However,
certain
parts
of
the
required
examination
do
not
necessarily
require
the
physician's
expertise
and
may
be
conducted
by
another
person
under
the
supervision
of
the
physician
OSHA
is
proposing
to
require
that
persons
who
administer
the
pulmonary
function
tests
required
by
this
proposal,
must
complete
a
training
course
in
spirometry
sponsored
by
an
appropriate
governmental,
academic,
or
professional
institution.
This
provision
is
consistent
with
other
OSHA
standards,
Benzene
(
29
CFR
1910.28)
and
Cotton
Dust
(
29
CFR
1910.1043),
and
it
will
assure
that
employees
who
must
wear
respiratory
protection
will
receive
adequate
assessment
of
their
lung
capacity,
a
vital
test
in
determining
if
they
are
capable
of
wearing
a
respirator
This
standard
provides
that
all
examinations
and
procedures
shall
be
performed
at
a
reasonable
time
and
place.
It
is
necessary
that
exams
be
convenient
and
be
provided
during
the
workday
without
loss
of
pay
to
the
employee
to
assure
that
they
are
taken.
The
employer
is
required
to
establish
and
maintain
an
accurate
record
for
each
employee
subject
to
medical
surveillance
Paragraph
(
l)(
2)
would
require
that
the
employer
provide
an
initial
medical
examination
to
each
employee.
The
purpose
of
the
initial
medical
examination
is
to:
(
1)
establish
the
current
health
status
of
the
employee
and
to
determine
whether
employment
in
areas
with
glycol
ethers
exposure
is
appropriate;
(
2)
establish
essential
baseline
data
against
which
to
measure
any
change
which
might
be
attributable
to
glycol
ethers
exposure;
and
(
3)
determine
whether
the
individual
can
safely
wear
a
respirator.
OSHA
believes
that
the
preplacement
examination
assessing
each
worker's
state
of
health
prior
to
the
beginning
of
exposure
to
glycol
ethers
is
essential
to
determine
whether
an
employee's
health
changes
over
the
period
of
employment
and
to
determine
pre­
existing
conditions
that
could
influence
initial
job
placement
The
medical
examination
proposed
is
to
include:
(
1)
medical
and
work
histories
with
emphasis
on
the
pulmonary
and
mucous
membranes
and
hematologic
system,
(
2)
a
reproductive
history,
(
3)
a
physical
examination,
(
4)
a
blood
analysis
including
at
least
a
red
blood
cell
count,
white
cell
count,
hemoglobin
and
hematocrit,
(
5)
a
pulmonary
function
test
for
respirator
wearers
and
(
6)
any
additional
tests
deemed
appropriate
by
the
examining
physician
This
information,
in
conjunction
with
a
complete
physical
examination,
will
assist
the
physician
in
the
determination
of
the
employee's
health
status,
possible
past
exposures
to
glycol
ethers
or
other
substances
that
may
have
damaged
organs
or
systems
susceptible
to
glycol
ethers
toxicity,
and
suitability
for
employment
in
an
area
where
exposure
to
glycol
ethers
will
occur.
Special
emphasis
is
placed
on
the
portions
of
the
history
and
physical
examination
which
evaluate
organ
systems
known
to
be
particularly
susceptible
to
glycol
ethers
toxicity.
Emphasis
is
placed
on
examination
of
the
skin
as
evidence
indicates
that
glycol
ethers
are
rapidly
absorbed
through
the
skin.
Therefore,
the
skin
should
be
examined
for
conditions
such
as
dermatitis
which
might
facilitate
absorption.
Emphasis
is
also
placed
on
the
hematologic
system
because
of
the
human
and
animal
evidence
which
has
shown
adverse
effects
on
various
constituents
of
the
blood
as
a
result
of
glycol
ethers
exposure.
The
physical
examination
should
also
include
attention
to
the
mucous
membranes
and
respiratory
systems
as
these
two
systems
can
be
nonspecifically
irritated
by
glycol
ethers.
The
pulmonary
system
takes
on
added
importance
with
respirator
use
Also
included
in
the
initial
or
preplacement
examination
are
any
additional
tests
deemed
appropriate
by
the
examining
physician.
This
provision
authorizes
the
physician
to
include
further
tests
which
could
assist
the
physician
in
determining
the
employee's
suitability
for
work
in
an
area
in
which
glycol
ethers
exposure
will
occur
or
in
determining
whether
a
worker
can
safely
wear
a
respirator
In
the
proposed
medical
examination,
OSHA
has
not
prescribed
any
specific
tests
for
the
surveillance
of
adverse
reproductive
or
developmental
effects.
Information
presently
available
to
OSHA
is
insufficient
for
the
Agency
to
justify
specification
of
the
precise
tests
to
be
administered.
Few
tests
are
available
which
can
reliably
be
used
to
detect
the
early
onset
of
reproductive/
developmental
effects.
For
example,
serum
hormones
such
as
follicle
stimulating
hormone(
FSH),
luteinizing
hormone
(
LH),
prolactin,
and
testosterone,
may
provide
information
on
alterations
in
endocrine
function
which
might
be
early
indicators
of
adverse
reproductive
functioning.
However,
due
to
the
cyclical
nature
of
these
hormones,
multiple
and
sequential
blood
samples
rather
than
single
time
point
samples
would
be
required
to
detect
exposure
related
fluctuations
in
hormone
levels.
Furthermore,
OSHA
is
not
aware
of
any
data
specifically
correlating
alterations
in
endocrine
function
and
glycol
ethers
exposure.
Other
tests
such
as
sperm
count
or
measurement
of
testes
size
are
very
invasive
and
the
results
of
these
types
of
tests
are
highly
variable
and
thus
difficult
to
standardize.
For
these
reasons,
employees
may
be
unwilling
to
submit
to
testing.
Due
to
the
variability,
results
from
individual
workers
may
be
difficult
to
interpret
and
may
not
provide
meaningful
diagnostic
information.
Because
these
types
of
tests
are
invasive
and
unlikely
to
give
meaningful
information
on
an
individual
basis,
they
have
not
been
included
in
provisions
for
a
medical
[
page
15608]

examination.
OSHA
is
seeking
comment
on
the
availability
of
tests
which
can
be
used
to
detect
the
early
onset
of
adverse
reproductive/
developmental
effects
OSHA
has
proposed
that
the
employer
provide
his/
her
employees
with
the
opportunity
for
medical
advice
or
counseling
with
respect
to
their
ability
to
produce
a
healthy
child.
Glycol
Ethers
have
been
shown
to
produce
adverse
reproductive
and
developmental
effects
in
several
animal
species
and
thus
may
potentially
effect
exposed
workers
ability
to
produce
healthy
children.
Therefore,
workers
who
have
past
or
current
exposure
to
glycol
ethers
and
are
experiencing
difficulties
in
conceiving
a
child
should
be
afforded
the
opportunity
for
medical
advice,
counseling,
and
reproductive
testing
where
it
is
deemed
appropriate
by
the
examining
physician.
This
approach
is
consistent
with
other
health
standards
for
substances
shown
to
induce
adverse
reproductive
and
developmental
effects
(
e.
g.,
Lead,
29
CFR
1910.1025
and
Ethylene
Oxide,
29
CFR
1910.1047)

OSHA
proposes
periodic
medical
examinations
to
be
administered
annually.
The
purposes
of
the
annual
examination
are:
(
1)
the
early
detection
of
biological
effects
of
glycol
ethers;
(
2)
the
detection
of
non­
occupationally­
related
diseases
that
might
require
reduction
of
glycol
ethers
exposure;
(
3)
the
assessment
of
fitness
for
respirator
usage;
and
(
4)
the
monitoring
of
general
health
status
and
recent
illnesses.
The
requirement
that
medical
examinations
be
provided
annually,
as
a
minimum,
is
consistent
with
other
OSHA
health
standards
(
e.
g.,
Formaldehyde,
1910.1048
and
Benzene,
1910.1028).
In
addition,
the
adverse
effects
of
overexposure
to
glycol
ethers
are
subchronic
in
nature
(
i.
e.,
the
effects
may
occur
within
a
year).
Periodic
examinations
performed
at
one
year
intervals
will
allow
for
the
detection
of
these
effects.
More
frequent
reviews
of
specific
biological
tests
may
be
performed,
if
evidence
indicates
such
tests
are
necessary
OSHA
also
proposes
a
periodic
medical
re­
evaluation
of
workers
required
to
wear
respirators.
The
re­
evaluation
is
necessary
because
an
illness,
a
new
medication
or
a
change
in
facial
structure
may
affect
and
impact
on
an
employee's
continuing
ability
to
wear
a
respirator.
The
re­
evaluation
will
enable
the
physician
to
determine
whether
the
individual
can
safely
continue
to
wear
the
same
type
of
respirator,
should
be
re­
fitted
with
another
type,
or
should
be
removed
from
any
area
where
respirator
use
is
required
In
addition
to
routine
medical
surveillance,
the
proposal
also
requires
that
employers
make
medical
examinations
available
as
soon
as
possible
to
all
employees
who
may
have
been
acutely
exposed
to
glycol
ethers
in
an
emergency.
The
emergency
surveillance
provisions
reflect
OSHA's
concern
for
those
employees
who,
because
of
equipment
breakdown,
container
rupture
or
other
causes,
may
be
exposed
to
higher
doses
of
glycol
ethers.
Medical
evaluations
should
be
made
available
in
the
event
that
such
emergencies
occur.
No
specific
examination
elements
have
been
stipulated
in
this
provision
in
order
to
provide
the
physician
with
sufficient
flexibility
to
deal
with
the
nature
and
degree
of
exposure
sustained
OSHA
has
not
included
a
medical
examination
at
the
termination
of
employment.
Because
of
the
relatively
short
biological
half
life
of
glycol
ethers
(
i.
e.,
24­
48
hours)
and
the
subchronic
nature
of
the
reproductive/
developmental
effects
associated
with
glycol
ethers,
a
examination
at
the
termination
of
employment
may
not
be
necessary.
However,
medical
records
at
termination
of
employment
may
be
useful
to
physicians
to
determine
the
status
of
an
employee's
health
and
to
identify
any
potential
future
health
effects.
Thus,
OSHA
requests
comments
on
whether
provisions
for
medical
examinations
at
termination
of
employment
should
be
included
in
a
final
standard
for
glycol
ethers
The
employer
is
required,
in
paragraph
(
l)(
5),
to
provide
the
physician
with
the
following
information:
A
copy
of
this
standard
and
its
appendices;
a
description
of
the
affected
employee's
former
and
current
duties
as
they
relate
to
the
employee's
glycol
ethers
exposure
level;
the
employee's
former
and
current
exposure
level
or
anticipated
exposure
level;
a
description
of
any
personal
protective
and
respiratory
equipment
used
or
to
be
used;
and
information
or
medical
records
from
the
employee's
previous
medical
examinations
that
were
provided
or
made
available
by
the
employer
to
the
affected
employee.
Making
this
information
available
to
the
physician
will
aid
in
the
evaluation
of
the
employee's
health
in
relation
to
assigned
duties
and
fitness
to
wear
personal
protective
equipment,
when
required
In
paragraph
(
l)(
6),
the
employer
is
required
to
obtain
a
written
opinion
from
the
examining
physician
containing
the
results
of
the
medical
examination
as
they
relate
to
occupational
exposures;
the
physician's
opinion
as
to
whether
the
employee
has
any
detected
medical
conditions
which
would
place
the
employee
at
increased
risk
of
material
health
impairment
from
exposure
to
glycol
ethers;
the
physician's
opinion
as
to
whether
the
employee
is
exhibiting
any
symptoms/
signs
from
overexposure
to
glycol
ethers;
any
recommended
restrictions
upon
the
employee's
exposure
to
glycol
ethers
or
upon
the
use
of
protective
clothing
or
equipment
such
as
respirators;
and
a
statement
that
the
employee
has
been
informed
by
the
physician
of
the
results
of
the
medical
examination
and
of
any
medical
conditions
which
require
further
evaluation
or
treatment.
This
written
opinion
must
not
reveal
specific
findings
or
diagnoses
unrelated
to
occupational
exposures.
The
employer
must
provide
a
copy
of
the
opinion
to
the
affected
employee
The
purpose
in
requiring
the
employer
to
obtain
a
written
opinion
from
the
examining
physician
is
to
provide
the
employer
with
a
medical
basis
to
aid
in
the
determination
of
initial
placement
of
employees
and
to
assess
the
employee's
ability
to
use
protective
clothing
and
equipment.
The
physician's
opinion
will
also
provide
information
to
the
employer
as
to
whether
the
employee
may
be
suffering
from
overexposure
to
glycol
ethers.
The
employer
can
then
reassess
the
employee's
exposure
and
work
practices
and
take
steps
to
reduce
that
employee's
exposure.
The
requirement
that
a
physician's
opinion
be
in
written
form
will
ensure
that
employers
have
had
the
benefit
of
this
information.
The
employer
shall
provide
a
copy
of
the
physician's
written
opinion
to
the
affected
employee
within
15
days
of
its
receipt.
The
requirement
that
an
employee
be
provided
with
a
copy
of
the
physicians's
written
opinion
will
ensure
that
the
employee
is
informed
of
the
results
of
the
medical
examination.
The
requirement
that
the
physician
sign
the
opinion
is
to
ensure
that
the
information
that
is
given
to
the
employer
has
been
seen
and
read
by
the
physician
The
purpose
in
requiring
that
specific
findings
or
diagnoses
unrelated
to
occupational
exposures
not
be
included
in
the
written
opinion
is
to
encourage
employees
to
participate
in
the
medical
surveillance
program
by
removing
any
concern
that
the
employer
will
obtain
adverse
information
about
the
employee's
physical
condition
that
is
unrelated
to
occupational
exposures
In
the
proposed
standard,
in
Appendix
D,
OSHA
has
included
a
non­
mandatory,
reproductive
history
questionnaire.
The
questionnaire
which
was
excerpted
and
modified
comes
from
[
page
15609]

the
Office
of
Technology
Assessment's
(
OTA)
report,
Reproductive
Health
Hazards
in
the
Workplace
(
Ex.
5­
135,
pp.
382­
388)
and
is
included
in
the
standard
to
give
guidance
on
conducting
reproductive
histories
for
workers
exposed
to
glycol
ethers.
As
stated
in
the
OTA
report,
this
questionnaire
is
a
composite
derived
from
several
research
facilities,
it
is
not
a
validated
questionnaire.
Nevertheless
it
has
value
in
providing
guidance
and
information
on
pertinent
factors
which
may
be
important
in
understanding
a
worker's
medical
background
Communication
of
Glycol
Ethers
Hazards
to
Employees:

Paragraph
(
m)

Paragraph
(
m)
of
this
proposal
entitled:
"
Communication
of
Glycol
Ethers
Hazards
to
Employees"
addresses
the
issue
of
transmitting
information
to
employees
about
the
hazards
of
ethylene
glycol
ethers
through
the
use
of:
(
1)
signs
and
labels,
(
2)
material
safety
data
sheets,
and
(
3)
information
and
training.
While
previous
OSHA
health
standards
generally
included
separate
paragraphs
on
employee
information
and
training
and
signs
and
labels,
both
of
these
areas
have
been
incorporated
into
this
single
paragraph,
along
with
material
safety
data
sheet
provisions,
to
provide
consistency
with
the
Hazard
Communication
Standard
(
HCS)
which
addresses
these
areas
The
Hazard
Communication
Standard
(
HCS),
29
CFR
1910.1200,
requires
all
chemical
manufacturers
and
importers
to
assess
the
hazards
of
the
chemicals
they
produce
or
import,
and
all
employers
to
provide
information
concerning
the
hazards
of
such
chemicals
to
their
employees.
The
transmittal
of
hazard
information
to
employees
is
to
be
accomplished
by
means
of
comprehensive
hazard
communication
programs,
which
are
to
include
container
labeling
and
other
forms
of
warning,
material
safety
data
sheets
and
employee
training.
The
HCS
also
addresses
the
responsibility
of
producers
of
chemicals
to
provide
information
to
downstream
employers
In
paragraph
(
m)
of
this
proposal,
it
is
the
intent
of
the
Agency
to
avoid
repetition
of
those
requirements
comprehensively
laid
out
in
§
1910.1200,
while
specifying
additional
requirements
that
are
directed
at
protecting
employees
against
the
particular
hazards
associated
with
exposure
to
glycol
ethers
The
proposed
standard,
paragraph
(
m)(
1)(
i),
would
require
that
all
entry
and
accessways
to
regulated
areas
be
posted
with
appropriate
warning
signs
which
bear,
at
a
minimum,
the
legend:
"
Danger,
Glycol
Ethers
[
specific
chemical
name(
s)],
Blood
and
Reproductive
Hazard,
Eye
and
Respiratory
System
Irritant,
Avoid
Inhalation
and
Skin/
Eye
Contact,
Authorized
Personnel
Only,
Respiratory
Protection
Required"

In
addition,
these
signs
should
include
any
other
appropriate
warnings
such
as
"
Flammable
­
No
Smoking,
Sparks,
or
Open
Flames"
whenever
such
hazards
may
exist.
It
is
intended
that
these
signs
will
serve
to
warn
employees,
who
may
otherwise
not
know,
that
they
are
entering
a
regulated
area.
These
warning
signs
are
required
to
be
posted
whenever
a
regulated
area
exists,
that
is,
whenever
airborne
concentrations
exceed
or
can
reasonably
be
expected
to
exceed
the
permissible
exposure
limits
It
could
be
possible
that
at
some
work
sites
or
operations
the
airborne
concentrations
of
glycol
ethers
cannot
be
reduced
below
the
permissible
exposure
limits
through
the
use
of
engineering
controls.
In
such
instances,
a
regulated
area
may
exist
for
an
extended
period
of
time.
Signs
would
be
needed
in
these
circumstances
to
warn
employees
that
entry
is
permitted
only
if
the
employee
is
authorized,
is
wearing
respiratory
protection,
and
there
is
a
specific
need
to
enter
the
area
Regulated
areas
may
also
exist
on
a
temporary
basis,
as
would
occur
during
maintenance
and/
or
emergency
situations.
In
these
types
of
situations,
the
use
of
warning
signs
is
also
important
since
a
maintenance
or
emergency
situation
is
by
nature
a
new
or
unexpected
source
of
exposure
to
employees
who
are
regularly
scheduled
to
work
at
these
sites.
It
is
expected
and
required
by
other
provisions
of
this
standard
that
employees
will
also
be
provided
with
any
other
personal
protective
equipment
and
training
that
is
necessary
to
assure
their
health
and
safety
while
in
these
areas
These
signs
will
also
supplement
the
training
which
employees
are
to
receive
under
the
other
provisions
of
this
paragraph,
since
even
trained
employees
need
to
be
reminded
of
the
locations
of
regulated
areas
(
or
made
aware
of
new
ones)
and
of
the
precautions
necessary
to
be
taken
before
entering
these
areas
The
wording
of
the
warning
signs
for
regulated
areas
has
been
specified
in
the
proposal
in
order
to
ensure
that
an
adequate
warning
is
given
to
employees.
OSHA
believes
that
the
use
of
the
word
"
Danger"
is
appropriate,
based
on
the
evidence
of
the
toxicity
of
glycol
ethers.
"
Danger"
is
used
to
attract
the
attention
of
workers,
to
alert
them
to
the
fact
that
they
are
in
an
area
where
the
permissible
exposure
limits
are
exceeded,
and
to
emphasize
the
importance
of
the
message
that
follows.
The
use
of
the
word
"
Danger"
is
consistent
with
other
recent
OSHA
health
standards
such
as
Formaldehyde
(
29
CFR
1910.1048).
Inclusion
of
the
statements
"
Blood
and
Reproductive
Hazard"
and
"
Eye
and
Respiratory
System
Irritant"
is
consistent
with
the
effects
that
have
been
demonstrated
to
be
associated
with
these
substances
(
see
Section
V,
Health
Effects,
of
this
document).
The
signs
are
also
required
to
bear
the
legend,
"
Respiratory
Protection
Required".
While
OSHA
recognizes
that
some
employees
entering
the
regulated
areas
may
not
be
exposed
above
either
the
8­
hour
TWAs
of
0.5
ppm
(
2­
EE,
2­
EEA)
and
0.1
ppm
(
2­
ME,
2­
MEA)
or
the
Els
of
2.5
ppm
(
2­
EE,
2­
EEA)
and
0.5
ppm
(
2­
ME,
2­
MEA)
as
averaged
over
a
15­
minute
period,
it
is
still
possible
that
some
employees
who
are
assigned
to
work
in
these
areas
without
the
use
of
respiratory
protection
may
remain
in
these
locations
for
long
enough
periods
of
time
so
that
they
would
be
needlessly
overexposed
to
glycol
ethers.
To
ensure
that
these
employees
are
adequately
protected,
it
is
necessary
to
post
the
sign
in
order
to
alert
them
to
the
need
to
wear
respirators.
The
employer
should
note
that
in
addition
to
respiratory
protection,
paragraph
(
e)(
4)
requires
that
all
persons
entering
a
regulated
area
be
provided
with
and
required
to
use
appropriate
personal
protective
equipment
while
paragraph
(
m)(
4)
would
require
training
of
these
persons
Inclusion
of
the
phrase
"
Authorized
Personnel
Only"
on
these
signs
serves
to
notify
employees
that
only
those
persons
specifically
authorized
by
the
employer
are
permitted
in
the
regulated
area
Paragraph
(
m)(
2)
would
require
that
warning
labels
or
other
appropriate
forms
of
warning
complying
with
the
requirements
of
29
CFR
1910.1200
(
f)
of
the
General
Industry
Standards
be
affixed
to
all
shipping
and
storage
containers
containing
glycol
ethers
or
glycol
ethers­
contaminated
materials.
These
labels
must
state:
"
Caution,
Contains
Glycol
Ethers
[
specific
chemical
name(
s)],
Blood
and
Reproductive
Hazard,
Eye
and
Respiratory
System
Irritant,
Avoid
Inhalation
and
Skin/
Eye
Contact".
In
addition,
the
label
shall
include
any
other
hazard
warnings
(
e.
g.,
"
Flammable
­
Keep
away
from
heat,
sparks,
and
flame")
which
are
appropriate
to
the
contents
of
the
container
along
with
any
other
information
required
by
the
Hazard
Communication
Standard,
29
CFR
1910.1200.
It
is
proposed
that
required
labels
would
remain
affixed
not
only
to
[
page
15610]

containers
being
used
at
the
work
site/
operation
but
also
those
leaving
the
workplace
The
purpose
of
this
requirement
is
to
assure
that
downstream
employers
and
employees
are
informed
of
the
presence
of
glycol
ethers,
their
associated
hazards,
and
that
special
practices
may
need
to
be
implemented
to
insure
against
exposure.
An
employer's
obligation,
under
section
6(
b)(
7)
of
the
Act,
to
inform
employees
of
hazardous
conditions
is
not
limited
to
the
employer's
own
employees.
When
an
employer
manufactures,
formulates,
or
sells
a
product,
it
may
unavoidably
expose
the
employees
of
downstream
employers
to
the
hazards
of
glycol
ethers.
This
is
especially
important
when
the
manufacturer,
formulator,
or
seller
is
the
only
employer
able,
through
his
knowledge
of
the
product,
to
provide
the
information
necessary
to
protect
employees.
Furthermore,
hazard
labels
alert
other
employers
who,
in
the
absence
of
such
labels
,
might
not
know
that
glycol
ethers
are
present
in
their
workplace
and
that
they
have
incurred
the
obligation
of
complying
with
the
standard
In
addition
to
being
consistent
with
the
requirements
of
the
HCS,
these
requirements
are
consistent
with
the
mandate
of
section
6(
b)(
7)
of
the
Act,
which
requires
OSHA
health
standards
to
prescribe
the
use
of
labels
or
other
appropriate
forms
of
warning
to
apprise
employees
of
the
hazards
to
which
they
are
exposed
OSHA
also
proposes
in
paragraph
(
m)(
3)
of
this
standard
to
require
the
employer
to
obtain
or
develop
and
to
distribute
and
provide
access
to
material
safety
data
sheets
for
ethylene
glycol
ethers
in
accordance
with
the
requirements
of
29
CFR
1910.1200
(
g).
OSHA
feels
that
a
properly
completed
material
safety
data
sheet
(
MSDS),
if
readily
available
to
employees,
can
serve
as
an
excellent,
concise
source
of
information
regarding
the
hazards
associated
with
glycol
ethers.
OSHA's
primary
intent
in
this
section
of
the
proposed
standard,
as
stated
in
the
Hazard
Communication
Standard
(
HCS),
is
to
ensure
that
employees
will
receive
as
much
information
as
is
needed
concerning
the
hazards
posed
by
chemicals
in
their
workplaces
The
material
safety
data
sheet
ensures
that
this
information
will
be
available
to
them
in
a
usable,
readily
accessible
and
concise
form.
The
material
safety
data
sheet
also
serves
as
the
central
source
of
information
to
employees
and
downstream
employers
who
must
be
provided
with
an
MSDS
if
glycol
ethers
or
a
product
containing
glycol
ethers
is
produced
and
shipped
out
of
the
plant.
In
addition,
the
MSDS
serves
as
the
basic
source
of
information
on
the
hazards
of
ethylene
glycol
ethers
essential
to
the
training
provisions
of
this
and
other
applicable
health
standards
Producers
and
importers
have
the
primary
responsibility,
under
the
HCS
to
develop,
update,
and
distribute
the
material
safety
data
sheet.
The
manufacturer
or
importer
is
most
likely
to
have
the
best
access
to
information
about
the
product,
and
is
therefore
responsible
for
disseminating
this
information
to
downstream
users
of
the
material.
The
requirements
for
the
information
that
is
to
be
contained
on
the
material
safety
data
sheet
are
explained
in
detail
at
29
CFR
1910.1200
(
g)
All
employers
with
employees
potentially
exposed
to
glycol
ethers
must
maintain
material
safety
data
sheets
and
provide
their
employees
with
access
to
them
in
accordance
with
29
CFR
1910.1200
(
g).
For
employers
whose
employees'
exposure
to
glycol
ethers
is
from
products
received
from
outside
sources,
the
information
necessary
for
a
complete
MSDS
or
the
MSDS
itself
is
to
be
obtained
from
the
manufacturer
and
made
available
to
affected
employees
Paragraphs
(
m)(
4)(
i)
through
(
m)(
4)(
iii)
of
this
proposed
standard
would
require
employers
who
have
a
workplace
or
work
operation
covered
by
this
section
to
provide
information
and
training
to
all
employees
who
are
potentially
exposed
to
these
chemicals.
The
training
program
is
to
be
in
accordance
with
the
requirements
of
the
HCS
paragraph
(
h),
including
specific
information
required
to
be
provided
by
that
section
and
those
items
stipulated
in
paragraph
(
m)(
4)(
iv)
of
this
standard.
In
addition,
paragraph
(
m)(
4)(
ii)
would
require
the
employer
to
institute
a
training
program
for
all
employees
who
are
potentially
exposed
to
glycol
ethers,
to
assure
each
employee's
participation
in
the
program
and
maintain
a
record
of
this
participation,
and
to
maintain
a
record
of
the
contents
of
such
programs.
This
will
assist
the
employer
in
determining
which
employees
have
received
training,
the
information
provided
to
the
employees,
and
those
employees
who
are
still
in
need
of
such
training.
Training
is
to
be
provided,
at
no
cost
to
the
employee,
prior
to
or
at
the
time
of
initial
assignment
to
a
job
involving
potential
exposure
to
glycol
ethers,
at
least
annually
thereafter,
and
whenever
a
new
hazard
from
glycol
ethers
is
introduced
into
their
work
area.
Examples
of
a
new
glycol
ethers
hazard
would
include,
but
are
not
limited
to,
use
of
glycol
ethers
or
glycol
ethers­
containing
mixtures
where
none
were
previously
utilized
and
installation
of
a
process
which
could
result
in
employee
exposure
to
glycol
ethers
or
increase
existing
exposure
levels.
These
types
of
situations
would
warrant
additional
training
to
ensure
that
employees
remain
apprised
of
any
new
or
increased
glycol
ethers
exposure
hazards
and
the
precautions
necessary
to
protect
themselves
from
exposure
Paragraph
(
m)(
4)(
iv)
would
require
that
the
training
program
be
conducted
in
a
manner
that
the
employee
is
able
to
understand
and
shall
include
at
least
the
following:
A)
the
health
hazards
associated
with
glycol
ether
exposure
with
special
attention
to
the
information
in
Appendix
A
of
this
section;
B)
the
quantity,
location,
manner
of
use,
release,
and
storage
of
glycol
ethers
at
the
worksite
and
the
specific
nature
of
operations
that
could
result
in
exposure
to
glycol
ethers,
especially
above
the
TWAs
or
ELs;
C)
an
explanation
of
the
importance
of
engineering
and
work
practice
controls
for
employee
protection
and
necessary
instruction
in
the
use
of
these
controls;
D)
the
measures
employees
can
take
to
protect
themselves
from
exposure
to
glycol
ethers,
such
as
diligent
personal
hygiene,
proper
use
of
protective
equipment,
and
specific
procedures
the
employer
has
implemented
to
protect
employees
against
exposure,
including
appropriate
work
practices,
emergency
procedures,
and
personal
protective
equipment;
E)
the
details
of
the
hazard
communication
program
developed
by
the
employer,
including
an
explanation
of
the
signs,
labeling
system,
and
material
safety
data
sheets
and
how
employees
can
obtain
and
use
the
appropriate
hazard
information;
F)
the
purpose,
proper
selection,
fitting,
proper
use,
and
limitations
of
respiratory
protection
and
personal
protective
clothing
and
eye
protection;
G)
the
purpose
and
a
description
of
the
medical
surveillance
program
required
under
paragraph
(
l)
of
this
proposed
section
including
the
right
of
any
employee
exposed
to
glycol
ethers
at
or
above
the
AL
or
above
the
EL
to
obtain
1)
medical
examinations
as
required
by
paragraph
(
l)
of
this
section
at
no
cost
to
the
employee,
2)
the
employee's
medical
records
required
to
be
maintained
by
paragraph
(
n)(
2)
of
this
section,
and
3)
all
air
monitoring
results
representing
the
employee's
exposure
to
glycol
ethers
and
required
to
be
kept
by
paragraph
(
n)(
1)
of
this
section;
H)
a
copy
of
the
final
glycol
ethers
standard
and
its
appendices
and
a
discussion
of
its
contents
with
an
explanation
of
the
contents
of
the
MSDSs
for
glycol
ethers;
I)
instructions
for
the
handling
of
spills
and
clean­
up
[
page
15611]

procedures;
and
J)
a
review
of
emergency
procedures
including
specific
duties
or
assignments
of
each
employee
in
the
event
of
an
emergency
Paragraph
(
m)(
4)(
iv)(
A)
is
of
primary
importance
in
communicating
hazards
and
training
employees.
Until
employees
understand
the
health
hazards
of
a
compound
to
which
they
are
potentially
exposed,
the
work
practices,
engineering
controls,
use
of
personal
protective
equipment,
and
any
other
precautions
which
should
be
taken
have
little
meaning.
The
Agency
feels,
therefore,
that
effectively
communicating
a
compound's
health
hazards
to
employees
is
the
initial
step
in
their
understanding
of
other
steps
necessary
to
protect
them
against
exposure.
OSHA
feels
strongly
that
it
is
important
for
each
worker
to
be
able
to
recognize
how
and
where
he
or
she
might
be
occupationally
exposed
to
glycol
ethers
and
what
steps
should
be
taken
to
limit
exposure.
Therefore,
the
Agency
has
required,
in
paragraphs
(
m)(
4)(
iv)(
B),
(
C),
(
D),
(
E),
(
F),
and
(
I),
that
workers
be
provided
information
and
trained
in
practices
pertinent
to
location,
use,
and
so
forth
of
glycol
ethers
in
the
workplace;
work
practices
and
engineering
controls;
spills
and
cleanup
self
protective
measures;
the
employer's
hazard
communication
program;
and
personal
protective
equipment
as
they
apply
to
glycol
ethers
and
reduction
of
exposure.
Providing
a
description
of
the
medical
surveillance
program
and
its
purpose,
as
stipulated
in
paragraph
(
m)(
4)(
iv)(
G),
will
allow
employees
to
understand
what
medical
follow­
up
has
been
initiated
and
is
available
to
evaluate
occupational
exposure.
This
section
would
also
require
that
employees
be
informed
that
the
medical
examinations
required
under
paragraph
(
l)
are
to
be
provided
at
no
cost
to
the
employee.
The
Agency
anticipates
that
this
fact,
along
with
an
understanding
of
the
medical
surveillance
program,
will
encourage
employees
to
participate.
In
addition,
employees
must
be
informed
of
their
right
to
access
of
their
personal
medical
records
and
all
air
monitoring
results
representing
their
exposure
to
glycol
ethers
since
these
records
are
concerned
directly
with
the
employee's
health
as
it
relates
to
exposure
to
glycol
ethers.
The
purpose
of
paragraph
(
m)(
4)(
iv)(
H)
is
to
assure
that
employees
are
aware
of
the
existence
of
the
standard
and
material
safety
data
sheet(
s)
and
are
familiarized
with
the
information
contained
in
these
documents.
In
order
to
assist
in
successfully
achieving
the
goals
outlined
in
the
emergency
plan,
paragraph
(
m)(
4)(
iv)(
J)
states
that
employees
must
be
trained
in
emergency
procedures
including
their
specific
responsibilities
should
an
emergency
occur
Finally,
this
section
would
require
that
employees
be
informed
that
the
medical
examinations
required
under
paragraph
(
l)
are
to
be
provided
at
no
cost
to
the
employee.
The
Agency
anticipates
that
this
fact,
along
with
an
understanding
of
the
medical
surveillance
program,
will
encourage
employees
to
participate.
In
addition,
employees
must
be
informed
of
their
right
to
access
of
their
personal
medical
records
and
all
air
monitoring
results
representing
their
exposure
to
glycol
ethers
since
these
records
are
concerned
directly
with
the
employee's
health
as
it
relates
to
exposure
to
glycol
ethers
OSHA
has
determined
during
other
rulemakings
that
an
information
and
training
program,
as
incorporated
in
this
proposed
standard
in
an
overall
"
Communication
of
Hazards
to
Employees"
paragraph,
is
essential
to
inform
employees
of
the
hazards
to
which
they
are
exposed
and
to
provide
employees
with
the
necessary
understanding
of
the
degree
to
which
they
themselves
can
minimize
the
health
hazard
potential.
Training
is
essential
to
an
effective
overall
hazard
communication
program
and
serves
to
explain
and
reinforce
the
information
presented
to
employees
on
signs,
labels,
and
material
safety
data
sheets.
These
written
forms
of
information
and
warning
will
be
relevant
and
meaningful
only
when
employees
understand
the
information
presented
and
are
aware
of
the
actions
to
be
taken
to
avoid
or
minimize
exposures.
Active
employee
participation
in
training
sessions
can
result
in
the
effective
communication
of
hazard
information
to
employees
which
can
further
result
in
workers
taking
conscientious
protective
actions
at
their
job
duties,
thereby
decreasing
the
possibility
of
occupationally­
induced
illnesses
and
injuries
OSHA
proposes
the
training
provisions
of
this
standard
to
be
in
performance­
oriented,
rather
than
specified
and
detailed
language.
The
proposed
standard,
in
requiring
training
to
be
in
accordance
with
the
requirements
of
29
CFR
1910.1200,
lists
the
categories
of
information
to
be
transmitted
to
employees
and
not
the
specific
ways
that
this
is
to
be
accomplished.
The
Agency
believes
that
the
employer
is
in
the
best
position
to
determine
how
the
training
he
or
she
is
providing
is
being
received
and
absorbed
by
the
employees.
OSHA
has
therefore
laid
out
the
objectives
to
be
met
and
the
intent
of
its
training
to
ensure
employees
are
made
aware
of
the
hazards
in
their
workplace
and
how
they
can
help
to
protect
themselves.
The
specifics
of
how
this
is
to
be
accomplished
are
left
up
to
the
employer.
The
Agency
anticipates
that
the
use
of
such
performance­
oriented
requirements
will
encourage
employers
to
tailor
their
training
needs
to
their
specific
workplaces,
consequently
resulting
in
the
most
effective
training
program
suitable
for
each
specific
workplace
Recordkeeping:
Paragraph
(
n)

Section
8(
c)
of
the
Occupational
Safety
and
Health
Act
obligates
employers
to
keep
and
make
available
such
records
as
the
Secretary
may
prescribe
as
necessary
or
appropriate
for
the
enforcement
of
the
Act,
or
for
developing
information
regarding
occupational
injuries
and
illnesses.
Accordingly,
paragraph
(
n)
of
this
proposal
requires
employers
to
keep
several
types
of
records
to
achieve
the
intent
of
this
section
of
the
Act.
These
include
records
of
1)
exposure
measurements
and
all
objective
data
relied
on
as
a
basis
for
exemption
from
the
monitoring
requirements,
2)
medical
surveillance,
and
3)
training
Paragraph
(
n)(
1)
of
the
proposal
mandates
that
the
employer
establish
and
maintain
exposure
records
consistent
with
29
CFR
1910.20,
to
accurately
reflect
the
extent
and
duration
of
employee
exposure
to
glycol
ethers.
Specifically,
records
must
include
the
following
information:
(
a)
the
name,
social
security
number,
and
job
classification
of
the
employee(
s)
monitored
and
of
all
other
employees
whose
exposure
the
monitoring
is
intended
to
represent;
(
b)
the
dates
of
monitoring,
sample
identification
number,
sampling
duration,
time
of
day,
and
exposure
monitoring
results
of
each
of
the
samples
taken
including
a
description
of
the
procedure
used
to
determine
representative
employee
exposures;
(
c)
the
operation(
s)
covered
by
the
monitoring;
(
d)
the
sampling
and
analytical
methods
used
and
evidence
of
their
accuracy;
(
e)
the
type
of
respiratory
protective
devices,
if
any,
worn
by
the
employee;
and
(
f)
any
other
conditions
that
might
have
affected
the
employee
monitoring
results.
Unusual
conditions
which
may
affect
monitoring
results
generally
stem
from,
but
are
not
limited
to,
situations
which
could
cause
an
abnormal
increase/
decrease
in
the
airborne
concentration
of
glycol
ethers.
Examples
of
such
situations
are
a
temporary
increase/
decrease
in
production;
failure
of
an
engineering
control
to
operate
properly;
release
of
glycol
ethers
in
the
employee's
vicinity
[
page
15612]

as
may
occur
during
an
emergency
or
maintenance
operation;
seasonal
variations
caused
by
increased/
decreased
air
movement
resulting
from
opening
or
closing
of
doors
and
windows
or
use
of
fans;
or
a
change
in
an
employee's
mobility
or
proximity
to
a
source
of
glycol
ethers.
The
proposal
would
require
that
employee
exposure
measurement
records
be
maintained
for
each
measurement
taken.
The
record
may
represent
several
employee
exposure
measurements
if
representative
sampling,
as
described
in
paragraph
(
d),
is
conducted.
The
exposure
monitoring
results
that
would
be
required
under
paragraph
(
n)(
1)(
ii)(
B)
above
must
be
expressed,
at
a
minimum,
as
either
an
8­
hour
time
weighted
average
(
TWA)
or
a
15­
minute
excursion
limit
(
EL),
whichever
is
applicable.
OSHA
believes
that
this
is
necessary
to
allow
employees,
their
designated
representatives,
and
others
accessing
these
records
to
be
able
to
determine
employee
exposure
levels
without
performing
numerous
and
sometimes
unfamiliar
calculations
This
proposal
has
included
a
provision
for
the
use
of
objective
data
in
place
of
initial
monitoring
to
minimize
the
costs
of
initial
monitoring
in
circumstances
where
the
employer
can
demonstrate
that
insignificant
amounts
of
glycol
ethers
are
present
in
the
workplace
and
the
potential
for
exposure
to
glycol
ethers
above
the
ALs
or
ELs
does
not
exist.
OSHA
feels
that
requiring
an
employer
to
document
objective
data
determinations
and
retain
them,
as
stipulated
in
paragraph
(
n)(
1)(
iii),
should
discourage
abuse
of
this
provision
since
employees
and
their
representatives
are
permitted
access
to
this
information.
Access
would
enable
employees
and
their
representatives
to
ensure
that
the
exemption
determination
is
a
reasonable
one,
thereby
encouraging
use
of
objective
determinations
only
in
cases
where
the
data
warrant
such
use.
Maintaining
a
record
of
the
data
employed
for
objective
determinations
will
also
permit
OSHA
to
ascertain
whether
compliance
with
the
standard
has
been
achieved
For
the
purpose
of
acquiring
the
capability
of
correlating
employee
exposure
level
data
with
an
individual's
medical
surveillance
results,
OSHA
is
proposing
in
paragraph
(
n)(
1)(
iv)
that
exposure
monitoring
records
be
maintained
for
at
least
duration
of
employment
plus
30
years
In
addition
to
records
on
employee
exposure
measurements,
paragraph
(
n)(
2)(
i)
would
require
the
employer
to
establish
and
maintain
an
accurate
individual
record
for
each
employee
subject
to
medical
surveillance
as
stipulated
by
paragraph
(
l)
of
the
proposed
standard,
in
accordance
with
29
CFR
1910.20.
OSHA
believes
that
medical
records,
like
exposure
monitoring
records,
are
necessary
and
appropriate
both
to
the
enforcement
of
the
standard,
and
to
the
development
of
information
regarding
the
causes
and
prevention
of
occupational
illnesses.
Furthermore,
medical
records
are
necessary
for
the
proper
evaluation
of
the
employee's
health
Paragraph
(
n)(
2)(
ii)
would
require
that
this
record
include
at
least
the
following:
1)
the
name
and
social
security
number
of
the
employee;
2)
the
physician's
written
opinion
on
the
initial,
periodic,
and
additional
examinations;
3)
any
employee
medical
complaints
related
to
exposure
to
ethylene
glycol
ethers;
4)
a
copy
of
the
information
provided
by
the
employer
to
the
physician
as
required
by
paragraph
(
l)(
6)
of
this
section;
and
5)
a
copy
of
the
medical
and
reproductive
histories,
medical
questionnaire
responses,
and
results
of
any
medical
tests
required
by
the
standard
or
mandated
by
the
examining
physician
Paragraph
(
n)(
2)(
iii)
would
require
the
employer
to
retain
these
medical
records
for
at
least
the
duration
of
employment
plus
30
years.
The
extended
record
retention
period
is
needed
because
diagnosis
of
disease
in
employees
is
assisted
by,
and
in
some
cases
can
only
be
made
by,
having
present
and
past
exposure
data
as
well
as
the
results
of
present
and
past
medical
examinations.
In
revising
29
CFR
1910.20
"
Access
to
Employee
Exposure
and
Medical
Records"
OSHA
initially
proposed
to
reduce
the
retention
period
for
medical
records.
However,
in
the
final
rule
the
Agency
states:

"
Based
on
the
evidence
submitted,
OSHA
has
determined
that
the
proposed
reduction
in
the
retention
period
for
medical
records
is
not
justified.
The
long­
term
retention
of
records
is
necessary
to
provide
a
data
base
for
the
detection
of
occupational
diseases
that
may
not
manifest
themselves
for
many
years
after
onset
of
exposure."
(
53
FR
38154
September
29,
1988)

The
Agency
therefore
believes
that
maintenance
of
records
for
duration
of
employment
plus
thirty
years
is
prudent
and
warranted
for
developing
information
regarding
the
causes
and
prevention
of
occupationally­
induced
illness
With
regard
to
training
records,
paragraph
(
n)(
3)
would
require
the
employer
to
retain
all
employee
training
records
for
1
year
beyond
the
last
date
of
employment
for
that
employee
Paragraph
(
n)(
4)(
i)
mandates
that
the
employer
assure
that
all
records
required
to
be
maintained
by
this
section
are
made
available
upon
request
to
the
Assistant
Secretary
and
the
Director
for
examination
and
copying.
In
addition
to
being
given
records
access
specifically
by
this
section,
the
Assistant
Secretary
and
the
Director
are
empowered
to
examine
and
copy
records
by
Section
8(
c)(
1)
of
the
OSH
Act.
This
portion
of
the
Act
states:

Each
employer
shall
make,
keep
and
preserve,
and
make
available
to
the
Secretary
or
the
Secretary
of
Health,
Education,
and
Welfare
[
now
Health
and
Human
Services
(
HHS)],
such
records
regarding
his
activities
relating
to
this
Act
as
the
Secretary,
in
cooperation
with
the
Secretary
of
Health,
Education
and
Welfare
[
HHS],
may
prescribe
by
regulation
as
necessary
or
appropriate
for
the
enforcement
of
this
Act
or
for
developing
information
regarding
the
causes
and
prevention
of
occupational
accidents
and
illness.

While
the
Assistant
Secretary
is
empowered
to
examine
and
copy
records,
access
to
personally
identifiable
records
is
subject
to
Agency
rules
of
practice
and
procedure
which
have
been
published
at
29
CFR
1913.10
(
45
FR
35384)

Paragraph
(
n)(
4)(
ii)
would
require
the
employer
to
provide
upon
request
for
examination
and
copying,
all
employee
exposure
monitoring
records
required
to
be
maintained
by
paragraph
(
n)(
1)
of
this
section
to
affected
employees,
former
employees,
and
designated
representatives
in
accordance
with
29
CFR
1910.20
(
a)
through
(
e)
and
(
g)
through
(
i).
In
addition,
paragraph
(
n)(
4)(
iii)
would
require
employers
to
provide
upon
request
for
examination
and
copying,
all
employee
medical
records
required
to
be
maintained
by
paragraph
(
n)(
2)
of
this
section
to
the
subject
employee
and
to
anyone
having
the
specific
written
consent
of
the
subject
employee
in
accordance
with
29
CFR
1910.20
Section
8(
c)
of
the
Act
explicitly
provides
employees
and
their
representatives
with
the
right
to
have
access
to
monitoring
records.
Several
other
provisions
of
the
Act
contemplate
that
employees
and
their
representatives
are
entitled
to
have
an
active
role
in
the
enforcement
of
the
Act
.
Employees
and
their
representatives
need
the
pertinent
information
concerning
exposures
to
toxic
substances
and
the
consequences
to
the
health
and
safety
of
the
employees
if
they
are
to
benefit
properly
from
these
statutorily­
created
rights
In
29
CFR
1910.20,
are
spelled
out
the
procedures
for
access
to
records
by
[
page
15613]

OSHA,
employees,
and
employees'
designated
representatives.
This
General
Industry
Standard
was
promulgated
as
the
generic
rule
for
access
to
employee
exposure
and
medical
records
It
is
discussed
here
to
make
the
employer
aware
that
it
applies
not
only
to
records
created
pursuant
to
specific
standards
but
also
to
records
which
are
voluntarily
created
by
employers.
A
more
detailed
discussion
of
the
rationale
and
provisions
for
29
CFR
1910.20
can
be
found
at
45
FR
35312
(
May
23,
1980)
The
transfer
of
employee
exposure
monitoring
and
medical
records
is
to
be
in
accordance
with
the
provisions
of
paragraph
(
h)
of
29
CFR
1910.20.
If
an
employer
ceases
to
do
business
and
there
is
no
successor
employer
to
receive
and
retain
the
records
for
the
prescribed
period,
the
employer
is
to
notify
the
Director
at
least
90
days
prior
to
disposal
and
transmit
the
records
to
the
Director
for
retention,
if
requested
by
the
Director
within
that
period
Requirements
for
recordkeeping
under
the
Paperwork
Reduction
Act
are
discussed
under
Section
XI
­
Clearance
of
Information
Collection
Requirements
Dates:
Paragraph
(
o)

It
is
proposed
that
the
final
standard
become
effective
60
days
after
its
publication
in
the
Federal
Register
(
the
Effective
Date).
This
will
permit
time
for
public
distribution
of
the
standard
and
provides
a
sufficient
period
for
employers
to
familiarize
themselves
with
the
regulatory
provisions.
All
obligations
under
the
final
standard
will
commence
on
the
Effective
Date
except
those
discussed
in
the
following
paragraphs,
which
will
be
phasedin
during
the
indicated
periods
of
time
The
initial
exposure
monitoring
required
by
paragraph
(
d)
and
the
training
required
by
paragraph
(
m)(
4)
of
this
section
are
proposed
to
be
completed
as
soon
as
possible
but
not
later
than
90
days
after
the
effective
date
of
the
final
standard.
The
Agency
believes
that
this
is
adequate
time
to
conduct
monitoring
and
train
employees,
even
in
those
workplaces
which
operate
on
a
multi­
shift
work
schedule
Upon
receipt
and
evaluation
of
the
monitoring
results,
regulated
areas
can
be
established;
respiratory
protection
can
be
selected
and
provided;
and
medical
surveillance
can
be
implemented.
Therefore,
those
requirements
found
in
paragraphs
(
e),(
g),
and
(
l)
respectively,
are
to
be
complied
with
as
soon
as
possible
but
not
later
than
120
days
after
the
effective
date
of
the
final
standard
Since
development
of
the
emergency
plan
necessitates,
among
other
things,
purchase
of
and
distribution/
placement
of
appropriate
equipment
and
supplies,
evaluation
of
potential
emergency
sites
in
the
facility
and
appropriate
evacuation
routes,
and
additional
training
of
employees,
it
is
proposed
that
the
emergency
plan
required
by
paragraph
(
k)
be
completed
as
soon
as
possible
but
not
later
than
180
days
after
the
effective
date
Development
of
the
written
compliance
plan
stipulated
in
paragraph
(
f)(
6)
of
this
section
requires
that
the
employer
determine
effective
and
appropriate
engineering
controls
and
work
practices
to
reduce
employee
exposure
levels.
Since
the
provisions
in
this
paragraph
may
require
an
in­
depth
analysis
of
the
workplace
and
could
necessitate
obtaining
outside
expertise,
a
longer
period
of
time
has
been
allotted
for
compliance.
However,
the
written
compliance
plan
is
to
be
completed
no
later
than
1
year
after
the
effective
date
In
addition,
the
installation
of
emergency
showers
and
eyewashes
required
in
paragraph
(
i)
may
also
demand
extra
time
for
the
completion
of
necessary
plumbing
and
construction.
Therefore,
the
Agency
is
proposing
that
eyewashes
and
showers
be
installed
and
usable
as
soon
as
possible
but
in
any
event
not
later
than
1
year
after
the
effective
date
The
Agency
believes
that
the
implementation
of
engineering
controls
will
be
the
most
time­
consuming
aspect
of
the
final
standard.
While
the
initial
evaluation
and
planning
of
these
controls
will
have
been
completed
as
a
result
of
the
development
of
the
compliance
plan,
OSHA
realizes
that
additional
time
could
be
required
for
ordering
and
installing
the
necessary
equipment.
Therefore,
engineering
controls
are
to
be
implemented
as
soon
as
possible
but
no
later
than
2
years
after
the
effective
date
Overall,
work
practices
are
to
be
implemented
as
soon
as
possible.
Those
work
practices
directly
related
to
engineering
controls
being
installed
in
accordance
with
the
compliance
plan
are
to
be
implemented
as
soon
as
possible
after
these
engineering
controls
are
functional.
OSHA
solicits
comments
on
the
appropriateness
of
these
proposed
start­
up
dates
Appendices:
Paragraph
(
p)

The
proposed
standard
contains
5
appendices
which
are
designed
to
assist
employers
and
employees
in
implementing
the
provisions
of
this
standard.
Appendices
A,
B,
C,
D
and
E
are
nonmandatory
and
are
included
primarily
to
provide
information
and
guidance.
In
addition
these
appendices
are
not
intended
to
detract
from
any
obligation
that
the
proposed
standard
imposes
In
particular
Appendix
D,
is
a
sample
Reproductive
History
Questionnaire.
This
questionnaire
was
derived
from
Appendix
B
of
the
Office
of
Technology
and
Assessment's
(
OTA)
report
Reproductive
Hazards
in
the
Workplace
(
Ex.
5­
135).
As
noted
by
the
OTA,
elements
of
the
questionnaire
were
derived
from
various
research
facilities
to
develop
a
composite
questionnaire.
They
also
note
that
it
is
not
a
validated
questionnaire.
Nevertheless,
OSHA
believes
that
this
sample
questionnaire
provides
useful
information
which
may
provide
guidance
and
information
on
pertinent
factors
in
conducting
a
reproductive
history.
OSHA
seeks
comment
on
the
usefulness
of
this
questionnaire.
OSHA
also
welcomes
other
information
on
other
reproductive
history
questionnaires
which
may
be
more
useful
or
appropriate
The
appendices
which
are
included
in
the
standard
are:
Appendix
A­
Substance
Safety
Data
Sheet
for
Glycol
Ethers;
Appendix
B­
Substance
Technical
Guidelines
for
Glycol
Ethers;
Appendix
C­
Medical
Surveillance
Guidelines
for
Glycol
Ethers;
Appendix
DReproductive
History
Questionnaire;
Appendix
E­
Sampling
and
Analytical
Method
for
Glycol
Ethers;
Appendix
F­
Qualitative
and
Quantitative
Fit
Test
Procedures
XI.
Clearance
Of
Information
Collection
Requirements
On
March
31,
1983,
the
Office
of
Management
and
Budget
(
OMB)
published
a
new
5
CFR
Part
1320,
implementing
the
information
collection
provisions
of
the
Paperwork
Reduction
Act
of
1980,
44
U.
S.
C.
3501
et
seq.
(
48
FR
13666).
Part
1320,
which
became
effective
on
April
30,
1983,
sets
forth
procedures
for
agencies
to
follow
in
obtaining
OMB
clearance
for
collection
of
information
requirements
contained
in
proposed
rules
to
OMB
not
later
than
the
date
of
publication
of
the
proposal
in
the
Federal
Register.
It
also
requires
agencies
to
include
a
statement
in
the
notice
of
proposed
rulemaking,
indicating
that
such
information
requirements
have
been
submitted
to
OMB
for
review
under
Section
3504
(
h)
of
the
Paperwork
Reduction
Act
In
accordance
with
the
Paperwork
Reduction
Act
of
1980
(
44
U.
S.
C.
3501
et.
seq.),
and
the
regulation
issued
pursuant
thereto
(
5
CFR
Part
1320),
OSHA
certifies
that
is
has
submitted
the
information
collection
requirements
contained
in
this
proposed
standard
to
the
Office
of
Management
and
Budget
(
OMB)
for
review
under
Section
3504
(
h)
of
the
Act.
Paragraph
(
n)
is
the
provision
[
page
15614]

that
makes
the
major
contribution
to
the
information
collection
requirements
in
the
proposed
standard.
Comments
on
these
information
collection
requirements
may
be
submitted
by
interested
parties
to
the
Office
of
Information
and
Regulatory
Affairs
of
OMB,
Attention:
Desk
Officer
for
the
Occupational
Safety
and
Health
Administration,
New
Executive
Office
Building,
Washington,
D.
C.
20503.
OSHA
requests
that
copies
of
such
comments
also
be
submitted
to
the
OSHA
rulemaking
docket,
at
the
following
address:
Docket
Officer,
Docket
No.
H­
044,
Room
N2625,
U.
S.
Department
of
Labor,
200
Constitution
Avenue.,
N.
W.,
Washington,
D.
C.
20210
Public
Reporting
Burden
Public
reporting
burden
for
this
collection
of
information
is
estimated
to
be
approximately
24
hours
initially
and
approximately
24
recurring
hours
with
and
average
.08
hours
per
response.
Send
comments
regarding
this
burden
estimate
or
any
other
aspect
of
this
collection
of
information,
including
suggestions
for
reducing
this
burden,
to
the
OSHA
rulemaking
docket,
at
the
address
previously
set
forth;
and
to
the
Office
of
Information
and
Regulatory
Affairs
of
OMB
XII.
Public
Participation
­
Notice
Of
Hearing
Interested
persons
are
invited
to
submit
written
data,
views,
and
arguments
with
respect
to
this
proposed
standard.
These
comments
must
be
postmarked
on
or
before
June
7,
1993,
and
submitted
in
quadruplicate
to
the
Docket
Officer,
Docket
No.
H­
044,
Room
N2625,
U.
S.
Department
of
Labor,
200
Constitution
Avenue
NW,
Washington,
DC
20210.
Comments
limited
to
10
pages
or
less
also
may
be
transmitted
by
facsimile
to
(
202)
219­
5046,
provided
the
original
and
three
copies
are
sent
to
the
Docket
Officer
thereafter
Written
submissions
must
clearly
identify
the
provisions
of
the
proposal
which
are
being
addressed
and
the
position
taken
with
respect
to
each
issue.
The
data,
views,
and
arguments
that
are
submitted
will
be
available
for
public
inspection
and
copying
at
the
above
address.
All
timely
written
submissions
will
be
made
a
part
of
the
record
of
the
proceeding
Pursuant
to
section
6(
b)(
3)
of
the
Act,
an
opportunity
to
submit
oral
testimony
concerning
the
issues
raised
by
the
proposed
standard
will
be
provided
at
an
informal
public
hearing
scheduled
to
begin
at
10:
00
A.
M.
on
July
20,
1993,
in
Washington,
DC
in
the
auditorium
of
the
Frances
Perkins
Building,
U.
S.
Department
of
Labor,
200
Constitution
Avenue,
NW,
Washington,
DC,
20210
Notice
of
Intention
to
Appear
All
persons
desiring
to
participate
at
the
hearings
must
file
in
quadruplicate
a
Notice
of
Intention
to
Appear,
postmarked
on
or
before
June
7,
1993,
addressed
to
Mr.
Tom
Hall,
OSHA
Division
of
Consumer
Affairs,
Docket
No.
H­
044,
Room
N­
3649,
U.
S.
Department
of
Labor,
200
Constitution
Avenue
N.
W.,
Washington,
D.
C.
20210;
telephone
(
202)
219­
8615.
The
Notice
of
Intention
to
Appear
also
may
be
transmitted
by
facsimile
to
(
202)
219­
5046,
provided
the
original
and
3
copies
of
the
Notice
are
sent
to
the
above
address
thereafter
The
Notices
of
Intention
to
Appear,
which
will
be
available
for
inspection
and
copying
at
the
OSHA
Docket
Office
(
Room
N­
2625),
telephone
(
202)
219­
7894,
must
contain
the
following
information:

(
1)
The
name,
address,
and
telephone
number
of
each
person
to
appear;
(
2)
The
capacity
in
which
the
person
will
appear;

(
3)
The
approximate
amount
of
time
requested
for
the
presentation;
(
4)
The
specific
issues
that
will
be
addressed;

(
5)
A
detailed
statement
of
the
position
that
will
be
taken
with
respect
to
each
issue
addressed;
and
(
6)
Whether
the
party
intends
to
submit
documentary
evidence,
and
if
so,
a
brief
summary
of
that
evidence
Filing
of
Testimony
and
Evidence
Before
Hearings
Any
party
requesting
more
than
10
minutes
for
a
presentation
at
the
hearing,
or
who
will
submit
documentary
evidence,
must
provide
in
quadruplicate
the
complete
text
of
the
testimony,
including
any
documentary
evidence
to
be
presented
at
the
hearing
to
the
OSHA
Division
of
Consumer
Affairs.
This
material
must
be
postmarked
by
June
28,
1993,
and
will
be
available
for
inspection
and
copying
at
the
OSHA
Docket
Office.
Each
such
submission
will
be
reviewed
in
light
of
the
amount
of
time
requested
in
the
Notice
of
Intention
to
Appear.
In
those
instances
where
the
information
contained
in
the
submission
does
not
justify
the
amount
of
time
requested,
a
more
appropriate
amount
of
time
will
be
allocated
and
the
participant
will
be
notified
of
that
fact
Any
party
who
has
not
substantially
complied
with
this
requirement
may
be
limited
to
a
10­
minute
presentation.
Any
party
who
has
not
filed
a
Notice
of
Intention
to
Appear
may
be
allowed
to
testify,
as
time
permits,
at
the
discretion
of
the
Administrative
Law
Judge
OSHA
emphasizes
that
the
hearing
is
open
to
the
public,
and
that
interested
persons
are
welcome
to
attend.
However,
only
persons
who
have
filed
proper
notices
of
intention
to
appear
will
be
entitled
to
ask
questions
and
otherwise
participate
fully
in
the
proceeding
Conduct
and
Nature
of
Hearings
The
hearings
will
commence
at
10:
00
a.
m.
on
July
20,
1993.
At
that
time
any
procedural
matters
relating
to
the
proceeding
will
be
resolved
The
nature
of
an
informal
hearing
is
established
in
the
legislative
history
of
section
6
of
the
Act
and
is
reflected
by
the
OSHA
hearing
regulations
(
see
29
CFR
1911.15
(
a)).
Although
the
presiding
officer
is
an
Administrative
Law
Judge
and
questioning
by
interested
persons
is
allowed
on
crucial
issues,
the
proceeding
shall
remain
informal
and
legislative
in
type.
The
essential
intent
is
to
provide
an
opportunity
for
effective
oral
presentations
which
can
proceed
expeditiously,
in
the
absence
of
rigid
procedures
which
impede
or
protract
the
rulemaking
process
Additionally,
since
the
hearing
is
primarily
for
information
gathering
and
clarification,
it
is
an
informal
administrative
proceeding,
rather
than
an
adjudicative
one.
The
technical
rules
of
evidence,
for
example,
do
not
apply.
The
regulations
that
govern
hearings
and
the
pre­
hearing
guidelines
to
be
issued
for
this
hearing
will
ensure
fairness
and
due
process
and
also
facilitate
the
development
of
a
clear,
accurate
and
complete
record.
Those
rules
and
guidelines
will
be
interpreted
in
a
manner
that
furthers
that
development.
Thus,
questions
of
relevance,
procedure
and
participation
generally
will
be
decided
so
as
to
favor
development
of
the
record
The
hearing
will
be
conducted
in
accordance
with
29
CFR
Part
1911.
The
hearing
will
be
presided
over
by
an
Administrative
Law
Judge
who
makes
no
recommendation
on
the
merits
of
OSHA's
proposal.
The
responsibility
of
the
Administrative
Law
Judge
is
to
ensure
that
the
hearing
proceeds
at
a
reasonable
pace
and
in
an
orderly
manner.
The
Administrative
Law
Judge,
therefore,
will
have
all
the
powers
necessary
and
appropriate
to
conduct
a
full
and
fair
informal
hearing
as
provided
in
29
CFR
Part
1911
and
the
prehearing
guidelines,
including
the
powers:

1.
To
regulate
the
course
of
the
proceedings;

2.
To
dispose
of
procedural
requests,
objections,
and
comparable
matters;
[
page
15615]

3.
To
confine
the
presentation
to
the
matters
pertinent
to
the
issues
raised;

4.
To
regulate
the
conduct
of
those
present
at
the
hearing
by
appropriate
means;

5.
At
the
Judge's
discretion,
to
question
and
permit
the
questioning
of
any
witness
and
to
limit
the
time
for
questioning;
and
6.
At
the
Judges's
discretion,
to
keep
the
record
open
for
a
reasonable,
stated
time
to
written
information
and
additional
data,
views
and
arguments
from
any
person
who
has
participated
in
the
oral
proceeding
Certification
of
Record
and
Final
Determination
After
Hearing
Following
the
close
of
the
posthearing
comment
period,
the
presiding
Administrative
Law
Judge
will
certify
the
record
to
the
Assistant
Secretary
of
Labor
for
Occupational
Safety
and
Health.
The
Administrative
Law
Judge
does
not
make
or
recommend
any
decisions
as
to
the
content
of
the
final
standard
The
proposed
standard
will
be
reviewed
in
light
of
all
testimony
and
written
submissions
received
as
part
of
the
record,
and
a
standard
will
be
issued
based
on
the
entire
record
of
the
proceeding,
including
the
written
comments
and
data
received
from
the
public
List
of
Subjects
in
29
CFR
Pat
1910
Chemicals,
2­
Ethoxyethanol,
2­
Ethoxyethanol
Acetate,
Glycol
Ethers,
2­
Methoxyethanol,
2­
Methoxyethanol
Acetate,
Occupational
Safety
and
Health,
Reproductive
and
Developmental
Toxicity
XIII.
Authority
and
Signature
This
document
was
prepared
under
the
direction
of
David
C.
Zeigler,
Acting
Assistant
Secretary
of
Labor,
200
Constitution
Avenue,
N.
W.,
Washington,
D.
C.,
20210
It
is
issued
under
sections
4,
6,
and
8
of
the
Occupational
Safety
and
Health
Act
of
1970
(
29
U.
S.
C.
653,
655,
657),
Secretary
of
Labor's
Order
1­
90
(
55
FR
9033)
and
29
CFR
Part
1911
Signed
at
Washington,
D.
C.,
this
9th
day
of
March,
1993
David
C.
Zeigler
Acting
Assistant
Secretary
of
Labor
XIV.
The
Proposed
Standard
Part
1910
­
[
AMENDED]
Part
1910
of
title
29
of
the
Code
of
Federal
Regulation
is
hereby
proposed
to
be
amended
as
follows:
Subpart
B
­
[
AMENDED]

1.
The
authority
citation
for
subpart
B
of
29
CFR
part
1910
continues
to
read
as
follows:

Authority:
Secs.
4,
6,
and
8
of
the
Occupational
Safety
and
Health
Act,
29
U.
S.
C.
653,
655,
657;
Walsh­
Healy
Act,
41
U.
S.
C.
35
et
seq;
Service
Contract
Act
of
1965,
41
U.
S.
C.
351
et
seq;
sec.
107,
Contract
Work
Hours
and
Safety
Standards
Acts
(
Construction
Safety
Act),
40
U.
S.
C.
333;
sec
41,
Longshoremen's
and
Harbor
Worker's
Compensation
Act,
33
U.
S.
C.
941;
National
Foundation
of
Arts
and
Humanities
Act,
20
U.
S.
C.
951
et
seq.,
Secretary
of
Labor's
Order
No.,
12­
71
(
36
FR
8754);
8­
76
(
41
FR
25059),
or
9­
83
(
48
FR
35736),
as
applicable;
and
29
CFR
Part
1911
Sections
1910.16
and
1910.19
also
issued
under
29
CFR
Part
1911
2.
A
new
paragraph
(
n)
is
proposed
to
be
added
to
1910.19
to
read
as
follows:

1910.19
special
provisions
for
air
contaminants.
(
n)
Glycol
ethers.
Section
1910.1031
shall
apply
to
the
exposure
of
every
employee
to
glycol
ethers,
as
defined
in
section
1910.1031,
in
every
employment
and
place
of
employment
covered
by
1910.12,
1910.13,
1910.14,
1910.15,
1910.16,
1926
and
1928
in
lieu
of
any
different
standard
on
exposures
to
glycol
ethers
which
would
otherwise
be
applicable
by
virtue
of
those
sections
Subpart
Z
­
[
AMENDED]

3.
The
authority
citation
for
Subpart
Z
of
Part
1910
continues
to
read
as
follows:

Authority:
Secs.
6,
8
Occupational
Safety
and
Health
Act,
29
U.
S.
C.
655,
657:
Secretary
of
Labor's
Order
12­
71
(
36
FR
8754),
9­
76
(
41
FR
25059),
9­
83
(
48
FR
35736)
or
1­
90
(
55
FR
9033),
as
applicable;
and
29
CFR
Part
1911
All
of
subpart
Z
issued
under
section
6(
b)
of
the
Occupational
Safety
and
Health
Act,
listed
in
the
Final
Rule
Limits
columns
of
Table
Z­
1­
A,
which
have
identical
limits
listed
in
the
Transitional
Limits
columns
of
Table
Z­
1­
A,
Z­
2
or
Table
Z­
3.
The
latter
were
issued
under
section
6(
a)
(
29
U.
S.
C.
655
(
a))

Section
1910.1000,
the
Transitional
Limits
columns
of
Table
Z­
1­
A,
Table
Z­
2
and
TableZ­
3
not
issued
under
5
U.
S.
C.
553
1910.1000,
the
Transitional
limits
columns
of
Table
Z­
1­
A.
Table
Z­
2
and
Table
Z­
3
not
issued
under
29
CFR
part
1911
except
for
the
arsenic,
benzene,
cotton
dust,
and
formaldehyde
listings
Section
1910.1001
also
issued
under
sec.
107
of
Contract
Work
Hours
and
Safety
Standards
Act,
40
U.
S.
C.
333
Section
1910.1002
not
issued
under
29
U.
S.
C.
655
or
29
CFR
part
1911;
also
issued
under
5
U.
S.
C.
553
Sections
1910.1003
through
1910.1018
also
issued
under
29
CFR
U.
S.
C.
653
Section
1910.1025
also
issued
under
29
U.
S.
C.
653
and
5
U.
S.
C.
553.
Section
1910.1028
also
issued
under
29
U.
S.
C.
653.
Section
1910.1043
also
issued
under
5
U.
S.
C.
551
et
seq.
Sections
1910.1045
and
1910.1047
also
issued
under
29
U.
S.
C.
653.
Section
1910.1048
also
issued
under
29
U.
S.
C.
653
Sections
1910.1200,
1910.1499
and
1910.1500
also
issued
under
5
U.
S.
C.
553
Section
1910.1450
is
also
issued
under
sec.
6(
b),
8(
c)
and
8(
g)(
2),
Pub.
L.
91­
596,
84
Stat.
1593,
1599,
1600;
29
U.
S.
C.
655,
657.
1910.1000
[
AMENDED]

4.
The
entries
"
2­
Ethoxyethanol
*
*
*
110­
80­
5)
*
*
*
200
ppm
*
*
*
740
mg/
m3,
"
2­
Ethoxyethyl
acetate
(
Cellosolve
Acetate)
*
*
*
111­
15­
9
*
*
*
100
ppm
*
*
*
540
mg/
m3,
"
2­
Methoxyethanol;
see
Methyl
Cellosolve",
"
Methyl
Cellosolve
(
2­
Methoxyethanol)
*
*
*
109­
86­
4
*
*
*
25
ppm
*
*
*
80
mg/
m3"
and
"
Methyl
Cellosolve
Acetate
(
2­
Methoxyethyl
Aceate)
*
*
*
110­
49­
6
25
ppm
*
*
*
120
mg/
m3
"
are
proposed
to
be
deleted
from
Table
Z­
1­
A
of
1910.1000
5.
A
new
1910.1031
and
Appendices
A,
B,
C,
D,
E
and
F
to
the
section
are
proposed
to
be
added
to
subpart
Z
to
read
as
follows:

1910.1031
­
Glycol
ethers
(
a)
Scope
and
application
­
(
1)
This
section
applies
to
all
occupational
exposures
to
2­
Methoxyethanol
(
2­
ME),
2­
Methoxyethanol
Acetate
(
2­
MEA),
2­
Ethoxyethanol
(
2­
EE)
and
2­
Ethoxyethanol
Acetate
(
2­
EEA)
Chemical
Abstracts
Service
Registry
Nos.
109­
86­
4,
110­
49­
6,
110­
80­
5
and
111­
15­
9,
respectively,
except
as
provided
for
in
paragraph
(
a)(
2)
of
this
section.
(
2)
This
section
does
not
apply
to:

(
i)
Work
operations
where
the
only
exposure
to
2­
ME,
2­
MEA,
2­
EE,
or
2­
EEA
is
from
liquid
mixtures
containing
less
than
1%
2­
ME,
2­
MEA,
2­
EE
or
2­
EEA,
respectively,
by
volume,
unless
the
employer
has
reason
to
believe
that
such
mixtures
could
release
vapors
in
quantities
sufficient
to
result
in
an
airborne
concentration
which
meets
or
exceeds
the
action
levels
or
exceeds
the
excursion
limits
for
these
compounds
or
could
present
a
hazard
through
dermal
contact
(
ii)
Work
operations
using
solid
materials
made
from
or
containing
2­
ME,
2­
MEA,
2­
EE
or
2­
EEA
that
are
incapable
of
releasing
2­
ME,
2­
MEA,
2­
EE
or
2­
EEA
to
the
workplace
air
in
concentrations
at
or
above
the
AL
or
above
the
EL
(
b)
Definitions.
For
purposes
of
this
standard,
the
following
definitions
shall
apply:
Action
Level
(
AL)
means
airborne
concentrations
of
0.05
ppm
(
2­
ME
or
2­
MEA)
and
0.25
ppm
(
2­
EE
or
2­
EEA)
calculated
as
an
8­
hour
time­
weighted
average
(
TWA)

Assistant
Secretary
means
the
Assistant
Secretary
of
Labor
for
[
page
15616]

Occupational
Safety
and
Health,
U.
S.
Department
of
Labor,
or
designee
Authorized
person
means
any
person
specifically
authorized
by
the
employer
whose
duties
require
the
person
to
enter
a
regulated
area,
or
any
person
entering
such
an
area
as
a
designated
representative
of
employees
for
the
purpose
of
exercising
the
right
to
observe
monitoring
and
measuring
procedures
under
paragraph
(
d)
of
this
section,
or
any
other
person
authorized
by
the
Act
or
regulations
issued
under
the
Act
Director
means
the
Director
of
the
National
Institute
for
Occupational
Safety
and
Health,
U.
S.
Department
of
Health
and
Human
Services,
or
designee
Emergency
means
any
occurrence
such
as,
but
not
limited
to,
equipment
failure,
rupture
of
containers,
or
failure
of
control
equipment
which
may
or
does
result
in
an
unexpected
significant
release
of
glycol
ethers
Employee
exposure
means
the
exposure
to
airborne
or
liquid
glycol
ethers
which
would
occur
if
the
employee
were
not
using
respiratory
protective
equipment
or
other
personal
protective
equipment
Ethylene
glycol
ethers,
for
the
purposes
of
this
section,
means
2­
Methoxyethanol
(
2­
ME)(
CAS
No.
109­
86­
4),
2­
Methoxyethanol
acetate
(
2­
MEA)(
CAS
No.
110­
49­
6),
2­
Ethoxyethanol
(
2­
EE)(
CAS
No.
110­
80­
5)
and
2­
Ethoxyethanol
acetate
(
2­
EEA)(
CAS
No.
111­
15­
9).
Glycol
ethers
is
defined
the
same
as
"
Ethylene
glycol
ethers"

above
Objective
Data
means
information
which
can
be
used
to
reliably
calculate
the
anticipated
airborne
concentration
of
a
compound
in
a
work
area.
Such
information
may
include,
but
is
not
limited
to,
physical
properties
of
the
compound,
room
dimensions,
air
exchange
rates,
information
on
work
practices,
historical
data
on
employee
exposures,
and
employee
proximity
to
emissions
sources
Regulated
area
means
any
area
where
airborne
concentrations
of
glycol
ethers
exceed
or
can
reasonably
be
expected
to
exceed
the
permissible
exposure
limits
(
PELs),
either
the
8­
hour
time
weighted
average
(
TWA)
limits
of
0.1
ppm
(
2­
ME,
2­
MEA)
and
0.5
ppm
(
2­
EE,
2­
EEA)
or
as
the
15­
minute
excursion
limits
(
ELs)
of
0.5
ppm
(
2­
ME,
2­
MEA)
and
2.5
ppm
(
2­
EE,
2­
EEA)
(
c)
Permissible
exposure
limits
(
PELs)
­
(
1)
Eight­
Hour
Time
Weighted
Average
(
TWA)
The
employer
shall
assure
that
no
employee
is
exposed
to
an
airborne
concentration
of
glycol
ethers
which
exceeds
0.1
ppm
for
2­
ME
and
2­
MEA
or
0.5
ppm
for
2­
EE
and
2­
EEA,
calculated
as
an
8­
hour
time­
weighted
average
(
TWA)

(
2)
Excursion
Limit
(
EL)
The
employer
shall
assure
that
no
employee
is
exposed
to
an
airborne
concentration
of
glycol
ethers
in
excess
of
0.5
ppm
for
2­
ME
and
2­
MEA
or
2.5
ppm
for
2­
EE
and
2­
EEA,
averaged
over
a
sampling
period
of
15
minutes.
Monitoring
for
EL
is
to
be
conducted
during
the
period
in
which
the
employee
would
be
expected
to
receive
his/
her
highest
level
of
exposure
(
3)
Dermal
Exposure
The
employer
shall
assure
that
no
employee
is
exposed
to
glycol
ethers
through
dermal
contact
(
d)
Exposure
monitoring
­
(
1)
General
­
(
i)
Except
as
provided
by
paragraph
(
d)(
1)(
v)
of
this
section,
each
employer
who
has
a
workplace
or
work
operation
covered
by
this
section
shall
accurately
determine
the
level
of
employee
exposure
to
glycol
ethers
(
ii)
Determinations
of
employee
exposure
shall
be
made
from
personal
breathing
zone
air
samples
that
accurately
reflect
each
employee's
average
exposures
to
airborne
glycol
ethers
over
an
8­
hour
period
(
AL
and
TWA)
and
over
a
15­
minute
period
at
operations
where
there
is
reason
to
believe
that
exposures
may
be
above
the
excursion
limit
(
EL)

(
iii)
The
employer
shall
determine
8­
hour
TWA
employee
exposures
for
each
employee
in
each
job
classification
in
each
work
area
during
each
shift.
At
operations
where
there
is
reason
to
believe
that
exposures
may
be
above
the
excursion
limit
(
EL),
the
employer
shall
determine
the
EL
employee
exposures
for
each
job
classification
in
each
work
area
during
each
shift
(
iv)
Except
for
initial
monitoring
required
in
paragraphs
(
d)(
2)(
i)
and
(
d)(
2)(
ii)
of
this
section,
the
employer
may
develop
a
representative
sampling
strategy
that
sufficiently
monitors
exposure
levels
within
each
job
classification
or
for
each
job
task,
for
each
workshift,
in
each
work
area
to
correctly
characterize
and
not
underestimate
the
exposure
of
any
employee
within
each
exposure
group.
In
representative
sampling,
the
employer
shall
sample
those
employees
expected
to
have
the
highest
exposures.
Exposure
levels
shall
be
determined
for
each
employee
in
each
job
classification
in
each
work
area
for
each
shift
unless
the
employer
can
document
that
exposure
levels
for
a
given
job
classification
are
equivalent
for
different
work
shifts
(
v)
Where
the
employer
has
objective
data,
as
defined
in
paragraph
(
b)
of
this
section,
showing
the
presence
of
glycol
ethers
in
the
workplace
or
products
containing
glycol
ethers
cannot
result
in
the
release
of
airborne
concentrations
of
glycol
ethers
that
would
cause
any
employee
to
be
exposed
at
or
above
the
AL
or
above
the
EL,
under
worst­
case
release
conditions
of
foreseeable
use,
the
employer
may
rely
upon
such
data
and
is
not
required
to
monitor
employee
exposure
levels
to
glycol
ethers
(
2)
Initial
Monitoring.
(
i)
Except
as
provided
in
paragraphs
(
d)(
1)(
v)
or
(
d)(
2)(
ii)
of
this
section,
each
employer
shall
identify
all
employees
who,
without
regard
to
respirator
use,
are
exposed
or
may
reasonably
be
anticipated
to
be
exposed,
at
or
above
the
AL
or
above
the
EL
and
shall
perform
initial
monitoring
to
accurately
determine
the
exposure
of
all
employees
so
identified
(
ii)
Where
the
employer
has
monitored
an
employee
who
is
at
or
above
the
AL
and/
or
above
the
EL
after
[
180
days
prior
to
Effective
Date]
and
the
monitoring
occurred
under
conditions
closely
resembling
those
currently
prevailing
and
that
monitoring
satisfies
all
other
requirements
of
this
section,
the
employer
may
rely
on
such
monitoring
results
to
satisfy
the
requirements
of
paragraph
(
d)(
2)(
i)
of
this
section
with
respect
to
the
employee
monitored
(
3)
Periodic
monitoring.
(
i)
The
employer
shall
periodically
measure
and
accurately
determine
exposure
to
glycol
ethers
for
employees
shown
by
the
initial
or
other
monitoring
to
be
exposed
at
or
above
the
action
level
(
AL)
or
above
the
EL
(
ii)
If
the
initial
or
periodic
monitoring
results
reveal
employee
exposure
to
be
at
or
above
the
AL
but
at
or
below
the
TWA,
the
employer
shall
monitor
these
employees
at
least
every
6
months
(
iii)
If
the
initial
or
periodic
monitoring
results
reveal
employee
exposure
above
the
TWA,
the
employer
shall
monitor
these
employees
at
least
every
3
months
(
iv)
If
the
initial
or
periodic
monitoring
results
reveal
employee
exposure
above
the
EL,
the
employer
shall
monitor
these
employees
at
least
every
3
months
under
conditions
of
highest
exposure
(
4)
Additional
monitoring.
The
employer
shall
also
institute
the
exposure
monitoring
required
under
paragraphs
(
d)(
2)(
i)
and
(
d)(
3)
of
this
section
each
time
there
is
a
change
in
production,
equipment,
raw
materials,
process,
personnel,
or
work
practices
that
may
result
in
new
or
additional
exposure
to
glycol
ethers
at
or
above
the
ALs
or
above
the
ELs,
or
whenever
the
employer
has
any
other
reason
to
[
page
15617]

suspect
that
a
change
may
result
in
new
or
additional
exposures
at
or
above
the
ALs
or
above
the
ELs
(
5)
Termination
of
Monitoring.
(
i)
If
the
initial
monitoring
reveals
employee
exposure
to
be
below
the
ALs
and
at
or
below
the
ELs,
the
employer
may
discontinue
monitoring
for
that
employee,
except
as
noted
otherwise
in
paragraph
(
d)(
4)
of
this
section
(
ii)
If
the
periodic
monitoring
indicates
that
employee
exposures
are
below
the
ALs
and
at
or
below
the
ELs
and
that
result
is
confirmed
by
the
results
of
another
monitoring
taken
at
least
7
days
later,
the
employer
may
discontinue
the
monitoring
for
those
employees
whose
exposures
are
represented
by
such
monitoring.
The
results
must
be
statistically
representative
and
consistent
with
the
employer's
knowledge
of
the
job
and
work
operation
(
iii)
If
initial
or
periodic
monitoring
reveals
employee
exposure
at
or
above
the
AL,
but
on
two
consecutive
measurements
taken
at
least
seven
days
apart,
the
employee
exposure
is
not
above
the
EL,
no
further
monitoring
for
the
EL
is
necessary
except
as
required
by
paragraph
(
d)(
4)
of
this
section
(
6)
Accuracy
of
measurement.
The
employer
shall
use
a
method
of
monitoring
and
analysis
that
shall
be
accurate,
(
to
a
95
percent
confidence
level),
to
within
plus
or
minus
25
percent
for
airborne
concentrations
of
glycol
ethers
at
or
above
the
level
being
investigated
(
7)
Employee
notification
of
monitoring
results.
(
i)
Within
15
working
days
of
receiving
the
results
of
exposure
monitoring
conducted
under
this
section,
the
employer
shall
notify
each
affected
employee,
individually,
of
these
results
in
writing.
In
addition,
within
the
same
period,
the
employer
shall
post
the
results
in
an
appropriate
location
that
is
accessible
to
affected
employees
(
ii)
Whenever
monitoring
results
indicate
that
employee
exposure
is
over
the
TWA
and/
or
EL
permissible
exposure
limits,
the
employer
shall
include
in
the
written
notice
a
statement
that
the
TWA
and/
or
EL
has
been
exceeded
and
a
description
of
the
corrective
action
being
taken
by
the
employer
to
decrease
the
exposure
to
within
the
permissible
exposure
limits
(
8)
Observation
of
monitoring.
(
i)
The
employer
shall
provide
affected
employees
or
their
designated
representative
an
opportunity
to
observe
any
monitoring
of
employee
exposure
to
glycol
ethers
required
by
this
section
(
ii)
When
observation
of
the
monitoring
of
employee
exposure
to
glycol
ethers
requires
entry
into
an
area
where
the
use
of
protective
clothing
or
equipment
is
required,
the
employer
shall
provide
and
require
the
observer
to
use
such
clothing
and
equipment
and
shall
assure
that
the
observer
complies
with
all
other
applicable
safety
and
health
procedures
(
e)
Regulated
areas.
(
1)
The
employer
shall
establish
regulated
areas
wherever
exposures
to
glycol
ethers
exceed
or
can
be
expected
to
exceed
either
the
TWA
or
EL
permissible
exposure
limits
prescribed
in
paragraph
(
c)
of
this
section
(
i)
These
areas
shall
be
demarcated
from
the
rest
of
the
workplace
in
any
manner
that
adequately
establishes
and
alerts
employees
to
the
boundary
of
the
regulated
area
(
ii)
Regulated
areas
shall
be
posted
at
all
entrances
and
accessways
with
signs
as
specified
in
paragraph
(
m)(
1)(
i)
of
this
section
(
2)
The
employer
shall
limit
access
to
regulated
areas
to
authorized
persons
(
3)
Whenever
an
employer
at
a
multi­
employer
worksite
establishes
a
regulated
area,
that
employer
shall
communicate
the
location
and
restrictions
of
access
to
the
regulated
area
to
other
employers
with
work
operations
at
that
worksite
(
4)
The
employer
shall
assure
that
each
person
entering
a
regulated
area
is
provided
with
and
required
to
use
appropriate
personal
protective
equipment,
including
respiratory
protection
selected
in
accordance
with
paragraph
(
g)(
3)
of
this
section
(
f)
Methods
of
compliance
­
(
1)
Engineering
controls
and
work
practices.
Whenever
any
employee
is
exposed
to
glycol
ethers
above
either
the
TWA
or
EL
permissible
exposure
limits
prescribed
in
paragraph
(
c)
of
this
section
or
may
forseeably
experience
dermal
exposure
to
glycol
ethers,
the
employer
shall
institute
engineering
and
work
practice
controls
to
reduce
and
maintain
employee
exposures
to
glycol
ethers
at
or
below
the
TWAs
and
the
ELs
and
to
eliminate
dermal
exposure
to
glycol
ethers,
except
to
the
extent
that
the
employer
can
establish
that
these
controls
are
not
feasible
or
where
the
provisions
of
paragraph
(
g)
of
this
section
apply
(
2)
Whenever
feasible
engineering
and
work
practice
controls
which
can
be
instituted
are
not
sufficient
to
reduce
employee
exposure
to
or
below
the
TWA
and/
or
EL
permissible
exposure
limits
or
eliminate
foreseeable
dermal
exposure
,
the
employer
shall
implement
them
to
reduce
employee
exposures
to
the
lowest
levels
achievable
and
shall
supplement
such
controls
with
personal
protective
equipment
and/
or
respiratory
protection
that
complies
with
the
requirements
of
paragraph
(
g)
of
this
section
(
3)
Engineering
controls
shall
be
inspected
and
maintained
or
replaced
to
ensure
their
effectiveness
(
4)
The
employer
shall
permit
employees
to
leave
the
work
area
immediately
or
as
soon
as
feasible
to
wash
skin
areas
which
have
had
contact
with
glycol
ethers
(
5)
Compliance
program
.
(
i)
Where
the
TWAs
and/
or
ELs
are
exceeded
or
dermal
exposure
exists,
the
employer
shall
establish
and
implement
a
written
compliance
program
to
reduce
employee
exposure
to
or
below
the
TWA
and/
or
EL
permissible
exposure
limits
and
eliminate
dermal
exposure
by
means
of
engineering
and
work
practice
controls,
as
required
by
paragraph
(
f)
of
this
section.
To
the
extent
that
engineering
and
work
practice
controls
cannot
reduce
exposures
to
or
below
the
TWAs
and/
or
ELs
and/
or
eliminate
dermal
exposure,
the
employer
shall
include
in
the
written
compliance
program
the
use
of
appropriate
respiratory
protection
and/
or
personal
protective
equipment
to
achieve
compliance.
The
compliance
program
shall
include
the
written
plan
for
emergency
situations
prescribed
in
paragraph
(
k)
of
this
section
(
ii)
The
written
compliance
programs
shall
be
reviewed
and
updated
at
least
annually,
or
more
often
if
necessary,
to
reflect
significant
changes
in
the
employer's
compliance
status
(
iii)
Written
compliance
programs
shall
be
submitted
upon
request
for
examination
and
copying
to
affected
employees,
authorized
employee
representatives,
the
Assistant
Secretary,
and
the
Director
(
g)
Respiratory
protection
­
(
1)
General.
Where
respiratory
protection
is
required
by
this
section,
the
employer
shall
provide
it
at
no
cost
to
the
employee
and
shall
assure
its
proper
use,
in
compliance
with
the
requirements
of
this
paragraph,
to
reduce
employee
exposures
to
or
below
the
TWA
and/
or
EL
permissible
exposure
limits.
Respiratory
protection
shall
be
used
in
the
following
circumstances:

(
i)
During
the
interval
necessary
to
install
or
implement
feasible
engineering
and
work
practice
controls;

(
ii)
In
work
operations,
such
as
maintenance
and
repair
activities
and
during
brief
or
intermittent
operations,
for
which
the
employer
establishes
that
engineering
and
work
practice
controls
are
not
feasible;

(
iii)
In
work
situations
where
the
employer
has
implemented
all
feasible
engineering
and
work
practice
controls
and
such
controls
are
not
sufficient
to
[
page
15618]

reduce
exposure
to
or
below
the
TWA
and/
or
EL
permissible
exposure
limits,
and;

(
iv)
In
emergencies.

(
2)
Assignment
of
respiratory
protection.
No
employee
shall
be
assigned
tasks
requiring
the
use
of
respiratory
protection
if,
based
upon
his
or
her
most
recent
medical
examination,
an
examining
physician
determines
that
the
employee
will
be
unable
to
function
normally
while
wearing
a
respirator.
Such
employee
shall
be
given
the
opportunity
to
transfer
to
a
position
where
no
respirator
use
is
required.
That
position
shall
be
with
the
same
employer,
in
the
same
geographical
area,
and
with
the
same
seniority
status
and
rate
of
pay
the
employee
had
just
prior
to
such
transfer,
if
such
a
position
is
available
(
3)
Respirator
selection.
Where
respiratory
protection
is
required
under
this
standard,
the
employer
shall
select
and
provide
the
appropriate
respirator
as
specified
in
Table
1.
The
employer
shall
select
respirators
from
among
those
approved
by
the
Mine
Safety
and
Health
Administration
(
MSHA)
and
by
the
National
Institute
for
Occupational
Safety
and
Health
(
NIOSH)
under
the
provisions
of
30
CFR
Part
11
or
any
future
revisions
Table
1­
1.
MINIMUM
REQUIREMENTS
FOR
RESPIRATORY
PROTECTION
AGAINST
2­
EE,
2­
EEA,
2­
ME,
and
2­
MEA.
2
Condition
of
use
Minimum
required
or
glycol
ether
concentration
respirator
(
ppm
2­
EE/
2­
EEA)

(
ppm
2­
ME/
2­
MEA)

Up
to
10X
the
PEL
Supplied
air
half­
mask
respirator
(
1
ppm)
in
negative
pressure
(
demand)

(
5
ppm)
mode1
Up
to
25X
the
PEL
Supplied
air
respirator
with
hood
(
2.5
ppm)
or
helmet
in
continuous
flow
mode
(
12.5
ppm)

Up
to
50X
the
PEL
Supplied
air
half­
mask
in
(
2
ppm)
continuous
flow
mode1
(
25
ppm)

Supplied
air
full
facepiece
in
negative
pressure
(
demand)
mode
SCBA
full
facepiece
in
negative
pressure
(
demand)
mode
Up
to
250X
the
PEL
Supplied
air
full
facepiece
in
(
25
ppm)
continuous
flow
mode
(
125
ppm)

Up
to
1000X
the
PEL
Supplied
air
half­
mask
or
full
(
100
ppm)
facepiece
in
pressure
demand
mode1
(
500
ppm)

Greater
then
1000X
SCBA
in
pressure
demand
mode
the
PEL
(>
100
ppm)
Supplied
air
full
facepiece
in
(>
500
ppm)
pressure
demand
mode
in
combination
with
auxiliary
self­
contained
air
supply
Firefighting
SCBA
in
pressure
demand
mode
1
Full
face
piece
is
required
when
eye
irritation
is
experienced
2
Respirators
assigned
for
high
environmental
concentrations
may
be
used
for
lower
environmental
concentrations
(
4)
Respirator
program.
Where
respirator
use
is
required
by
this
standard,
the
employer
shall
institute
a
respiratory
protection
program
in
accordance
with
29
CFR
1910.134
(
b),
(
d),
(
e),
and
(
f)

(
5)
Respirator
use.
Employers
shall
permit
employees
to
leave
the
work
area
to
wash
their
faces
and
respirator
facepieces
as
needed
to
prevent
skin
irritation
from
respirator
use
(
6)
Respirator
fit
testing.
(
i)
The
employer
shall
assure
that
the
respirator
issued
to
the
employee
exhibits
the
least
possible
facepiece
leakage
and
that
the
respirator
is
fitted
properly
and
will
not
permit
the
employee
to
inhale
glycol
ethers
in
excess
of
either
the
TWAs
or
ELs
(
ii)
For
each
employee
wearing
a
tight­
fitting
supplied­
air
respirator,
employers
shall
perform
either
a
quantitative
or
qualitative
face
fit
test
of
the
facepiece
while
it
is
equipped
with
appropriate
air
purifying
elements.
When
quantitative
fit
testing
is
performed,
half
mask
facepieces
must
exhibit
a
fit
factor
of
100
and
full
facepieces
a
fit
factor
of
500,
at
a
minimum
(
iii)
The
employer
shall
perform
and
certify
the
results
of
the
appropriate
fit
tests
at
the
time
of
initial
fitting,
at
least
annually
thereafter,
when
a
different
make
or
size
respirator
is
used,
and
when
a
change
in
facial
structure
occurs
(
iv)
Fit
testing
shall
be
performed
at
a
reasonable
time
and
place
and
at
no
cost
to
the
employee
and
shall
be
conducted
in
accordance
with
Appendix
F
of
this
section
(
h)
Personal
protective
equipment
­
(
1)
Provision
and
use.
The
employer
shall
select
and
provide
appropriate
personal
protective
equipment,
including
clothing
and
eye
protection,
in
accordance
with
29
CFR
1910.132
and
29
CFR
1910.133
(
i)
The
employer
shall
select
the
appropriate
personal
protective
equipment
based
upon
the
type
of
exposure
anticipated,
conditions
of
use,
and
the
hazard
to
be
prevented
(
ii)
The
employer
shall
provide
the
appropriate
personal
protective
equipment
at
no
cost
to
the
employee
and
assure
that
employees
use
this
equipment
(
iii)
Personal
protective
equipment,
such
as,
but
not
limited
to,
coveralls,
gloves,
faceshields,
and
rubber
boots,
shall
be
made
of
materials
sufficiently
impervious
to
glycol
ethers
to
prevent
employee
exposure
to
these
compounds
(
iv)
The
employer
shall
provide
uncontaminated
personal
protective
equipment
as
often
as
necessary
and
at
least
weekly
to
prevent
employee
exposure
to
glycol
ethers
(
2)
Removal
and
storage.
(
i)
The
employer
shall
assure
that
employees
remove
all
personal
protective
equipment
contaminated
with
glycol
ethers
prior
to
leaving
the
work
area
or
as
soon
as
feasible
if
the
potential
for
soakthrough/
breakthrough
exists.
This
shall
be
done
in
an
area
which
minimizes
exposure
of
other
employees
(
ii)
The
employer
shall
assure
that
no
employee
takes
home
personal
protective
equipment
contaminated
with
glycol
ethers
(
iii)
The
employer
shall
assure
that
no
employee
takes
personal
protective
equipment
contaminated
with
glycol
ethers
out
of
the
workplace
unless
authorized
to
do
so
for
the
purposes
of
laundering,
cleaning,
maintenance,
or
disposal
(
iv)
The
employer
shall
assure
that
personal
protective
equipment
contaminated
with
glycol
ethers
shall
be
stored
in
a
manner
so
as
to
minimize
employee
exposure
and
not
be
worn
again
until
cleaned
or
laundered
(
v)
The
employer
shall
assure
that
storage
areas
and
containers
with
glycol
etherscontaminated
personal
protective
equipment
shall
have
a
sign
or
label,
respectively,
as
specified
in
paragraph
(
m)(
1)(
ii)
of
this
section
(
3)
Cleaning,
replacement,
and
disposal.
(
i)
The
employer
shall
clean,
launder,
repair,
and
replace,
at
no
cost
to
the
employee,
all
required
personal
protective
equipment
for
each
affected
employee
as
necessary
to
assure
its
effectiveness
and
shall
be
responsible
for
the
disposal
of
these
items
(
ii)
The
employer
shall
assure
that
only
trained
persons
remove
contaminated
personal
protective
[
page
15619]

equipment
from
storage
for
the
purpose
of
laundering,
cleaning,
repair,
or
disposal
(
iii)
The
employer
shall
inform
any
person
who
launders,
cleans,
or
repairs
personal
protective
equipment
contaminated
by
glycol
ethers
of
the
potentially
harmful
effects
of
exposure
to
glycol
ethers
and
of
procedures
to
safely
handle
the
clothing
and
equipment
(
iv)
The
employer
shall
assure
that
laundering,
cleaning,
maintenance,
and
disposal
are
performed
only
at
facilities
which
are
appropriate
to
handle
glycol
ethers
contaminated
personal
protective
equipment
(
v)
All
contaminated
personal
protective
equipment
destined
for
disposal
shall
be
placed
in
a
sealed
container
which
is
labeled
in
accordance
with
paragraph
(
m)(
1)(
ii)
of
this
standard
(
i)
Hygiene
protection
­
(
1)
If
employee's
skin
may
become
splashed
with
liquids
containing
glycol
ethers,
except
as
provided
by
paragraph
(
a)(
2)(
i)
of
this
section,
the
employer
shall
provide
conveniently
located
quick
drench
showers
and
assure
that
affected
employees
use
these
facilities
immediately
(
2)
If
there
is
any
possibility
that
an
employee's
eyes
may
be
splashed
with
liquids
containing
glycol
ethers,
except
as
provided
by
paragraph
(
a)(
2)(
i)
of
this
section,
the
employer
shall
provide
eye­
wash
fountains
within
the
immediate
work
area
for
emergency
use
(
3)
Eating,
drinking,
smoking,
and
application
of
cosmetics
is
prohibited
in
areas
of
glycol
ethers
exposure
(
4)
Personal
protective
equipment
shall
not
be
worn
in
lunch
areas
(
j)
Housekeeping
­
(
1)
All
surfaces
(
e.
g.
floors,
working
surfaces,
exterior
surfaces
of
equipment)
shall
be
kept
free
of
glycol
ethers
to
the
extent
feasible
(
2)
The
employer
shall
conduct
a
program
to
detect
leaks
and
spills,
including
visual
inspections
of
operations
involving
liquids
containing
glycol
ethers
(
3)
Preventative
maintenance
of
equipment,
including
surveys
for
leaks,
shall
be
undertaken
at
intervals
appropriate
to
assure
proper
functioning
of
the
equipment
(
4)
In
work
areas
where
spillage
may
occur,
the
employer
shall
make
provisions
to
contain
the
spill,
to
decontaminate
the
work
area,
and
to
dispose
of
waste
(
5)
The
employer
shall
assure
that
all
leaks
are
repaired
and
spills
are
cleaned
up
as
soon
as
possible
by
employees
wearing
suitable
protective
equipment,
which
may
include
respiratory
protection,
and
who
are
trained
in
proper
methods
of
cleanup
and
decontamination
(
6)
Waste
and
debris
contaminated
with
glycol
ethers
shall
be
placed
for
disposal
in
sealed
containers
bearing
a
label
as
specified
in
paragraph
(
m)(
1)(
ii)
of
this
section
(
k)
Emergencies
­
(
1)
The
employer
shall
develop
a
written
emergency
plan
for
each
workplace
or
work
operation
covered
by
this
section
in
accordance
with
the
requirements
of
29
CFR
1910.38
(
a).
The
provisions
of
29
CFR
1910.120
(
q)
remain
in
effect
as
applicable
and
an
emergency
response
plan
meeting
the
requirements
of
29
CFR
1910.120
(
q)
shall
be
deemed
to
meet
the
requirements
for
an
emergency
response
plan
in
this
paragraph
(
2)
All
employees
shall
be
thoroughly
trained
in
their
responsibilities
in
the
event
of
an
emergency
(
3)
The
employer
shall
assure
that
only
designated
personnel,
furnished
with
appropriate
personal
protective
equipment
which
shall
include
respiratory
protection,
and
who
are
trained
in
re­
entry
procedures
shall
correct
the
emergency
conditions
(
4)
The
employer
shall
assure
that
appropriate
personal
protective,
housekeeping,
and
other
emergency
equipment
and
supplies
shall
be
located
in
each
area
where
an
emergency
could
occur
(
5)
All
employees,
except
those
designated
to
correct
the
situation,
shall
be
evacuated
from
and
normal
operations
shall
be
halted
in
the
area
where
the
emergency
occurred
until
the
emergency
has
been
abated
(
6)
The
employer
shall
make
provisions
for
immediate
evacuation,
transportation,
and
medical
assistance
at
a
designated
medical
facility
for
affected
employees
(
l)
Medical
surveillance
­
(
1)
General.
(
i)
Employees
covered.
The
employer
shall
institute
medical
surveillance
programs
for
all
employees
who
are
or
will
be
exposed
to
airborne
concentrations
of
glycol
ethers
at
or
above
the
action
level
or
above
the
excursion
level
(
ii)
Examination
by
a
physician.
The
employer
shall
assure
that
all
medical
examinations
and
procedures
are
performed
by
or
under
the
supervision
of
a
licensed
physician
and
are
provided
without
cost
to
the
employee,
without
loss
of
pay,
and
at
a
reasonable
time
and
place.
Persons
who
administer
pulmonary
function
tests
required
by
this
standard
shall
complete
a
training
course
in
spirometry
sponsored
by
an
appropriate
governmental,
academic
or
professional
institution
(
2)
Initial
examinations
(
i)
Within
90
days
of
the
effective
date
of
this
standard
or
before
the
time
of
assignment,
which
ever
comes
later,
the
employer
shall
provide
each
employee
covered
by
paragraph
(
l)(
1)(
i)
of
this
section
with
a
medical
examination
including
at
a
minimum
the
following
elements:

(
A)
A
medical
and
work
history,
including
a
reproductive
history,
with
emphasis
on
the
hematologic
system,
skin,
eyes
and
symptoms
related
to
pulmonary
and
mucous
membrane
irritation
(
B)
A
physical
examination
with
emphasis
given
to
hematologic
and
pulmonary
system,
mucous
membranes,
skin
and
eyes
(
C)
A
complete
blood
count
to
include
at
a
minimum
a
red
cell
count,
a
white
cell
count,
hemoglobin,
and
hematocrit
(
D)
Pulmonary
function
testing
for
employees
who
are
or
will
be
wearing
respiratory
protection.
As
a
minimum,
these
tests
shall
consist
of
forced
vital
capacity
(
FVC),
forced
expiratory
volume
in
one
second
(
FEV1),
and
forced
expiratory
flow
(
FEF)

(
E)
Any
other
test
which
the
examining
physician
deems
necessary
(
ii)
No
initial
medical
examination
is
required
to
satisfy
the
requirements
of
paragraph
(
l)(
2)(
i)
of
this
section
if
adequate
records
show
that
the
employee
has
been
examined
in
accordance
with
the
procedures
of
paragraph
(
l)(
2)(
i)
of
this
section
within
twelve
months
prior
to
the
effective
date
of
this
standard.
Results
of
tests
meeting
such
requirements
shall
be
provided
to
the
physician
to
complete
the
written
opinion
(
3)
Periodic
examinations.
(
i)
Periodic
medical
examinations
shall
be
made
available
at
least
annually
(
ii)
The
scope
of
the
medical
examination
shall
be
made
in
conformance
with
the
protocol
established
in
paragraph
(
l)(
2)(
i)
of
this
section
(
iii)
Where
the
results
of
the
examination
of
the
respiratory
system
indicate
abnormalities,
or
the
employee
experiences
difficulty
breathing
during
the
use
of
or
fit
testing
for
respirators,
the
physician
will
further
evaluate
the
employee's
ability
to
wear
a
respirator
(
iv)
Anytime
the
employee
develops
signs
and
symptoms
commonly
associated
with
toxic
exposure
to
glycol
ethers,
or
the
employee
desires
medical
advice
or
tests
concerning
the
effects
of
current
or
past
exposure
to
glycol
ethers
on
the
employee's
ability
to
produce
a
healthy
child,
the
employer
shall
provide
the
employee
with
an
additional
medical
examination
and/
or
a
consultation
which
shall
include
those
[
page
15620]

elements
considered
appropriate
by
the
examining
physician
(
4)
Emergency
Situations.
In
addition
to
medical
surveillance
required
in
paragraphs
(
l)(
1)­(
l)(
3)
of
this
section,
the
employer
shall
make
medical
examinations
available
as
soon
as
possible
to
all
employees
who
may
have
been
acutely
exposed
to
glycol
ethers
in
an
emergency
(
5)
Information
provided
to
the
physician.
The
employer
shall
provide
the
following
information
to
the
examining
physician:
(
i)
A
copy
of
this
standard
and
appendices;
(
ii)
A
description
of
the
affected
employee's
former,
current
and
anticipated
future
duties
as
they
relate
to
the
employee's
glycol
ethers
exposure.
(
iii)
The
employee's
former
or
current
occupational
representative
exposure
level
or
anticipated
exposure
level;

(
iv)
A
description
of
any
personal
protective
equipment
and
respiratory
protection
used
or
to
be
used
by
the
employee;
and
(
v)
Information
from
previous
medical
examinations
of
the
affected
employee
within
the
control
of
the
employer
(
6)
Physician's
written
opinion.
(
i)
The
employer
shall
obtain
a
written
signed
opinion
from
the
examining
physician.
This
written
opinion
shall
contain
the
results
of
the
medical
examination
except
that
it
shall
not
reveal
specific
findings
or
diagnoses
unrelated
to
occupational
exposure
to
glycol
ethers.
The
written
opinion
shall
include:

(
A)
The
physician's
opinion
as
to
whether
the
employee
has
any
medical
condition
that
would
place
the
employee
at
an
increased
risk
of
material
impairment
of
health
from
exposure
to
glycol
ethers
or
from
use
of
a
respirator
(
B)
The
results
of
any
testing
or
related
evaluation
concerning
glycol
ethers
exposure
carried
out
as
part
of
the
examination
(
C)
The
physician's
opinion
as
to
whether
the
employee
is
exhibiting
symptoms
and/
or
signs
from
overexposure
to
glycol
ethers
(
D)
The
physician's
opinion
as
to
whether
there
is
a
need
to
reevaluate
the
effectiveness
of
the
respirator
used
by
the
employee
(
E)
Any
recommended
limitations
on
the
employee's
exposure
to
glycol
ethers
or
upon
the
use
of
personal
protective
equipment,
including
respirators
(
F)
A
statement
that
the
employee
has
been
informed
by
the
physician
of
any
medical
conditions
which
would
be
aggravated
by
exposure
to
glycol
ethers,
whether
these
conditions
may
have
resulted
from
past
glycol
ethers
exposure,
and
whether
there
is
a
need
for
further
evaluation
or
treatment
(
ii)
The
employer
shall
provide
a
copy
of
the
physician's
written
opinion
to
the
affected
employee
within
15
days
of
its
receipt
(
m)
Communication
of
glycol
ethers
hazards
to
employees
­
(
1)
Signs.
The
employer
shall
post
signs
at
all
entry
and
accessways
to
regulated
areas
that
appropriately
warn
of
existing
hazards
and
which
bear,
at
a
minimum,
the
following
legend:

DANGER
GLYCOL
ETHERS
[
Specific
chemical
name(
s)]

BLOOD
AND
REPRODUCTIVE
HAZARD
EYE
AND
RESPIRATORY
SYSTEM
IRRITANT
AVOID
INHALATION
AND
SKIN/
EYE
CONTACT
AUTHORIZED
PERSONNEL
ONLY
RESPIRATORY
PROTECTION
REQUIRED
[
Any
other
appropriate
warnings
­­
e.
g.,
"
Flammable
­
No
Smoking,
Sparks,
or
Open
Flame"]

(
2)
Labels.
The
employer
shall
assure
that
shipping
and
storage
containers
containing
glycol
ethers
or
glycol
ethers­
contaminated
materials
bear
an
appropriate
warning
label,
which
complies
with
the
requirements
of
the
Hazard
Communication
Standard,
29
CFR
1910.1200
(
f)
of
the
General
Industry
Standards.
At
a
minimum,
these
labels
shall
include
the
following
legend:

DANGER
CONTAINS
GLYCOL
ETHERS
[
Specific
chemical
name(
s)]

BLOOD
AND
REPRODUCTIVE
HAZARD
EYE
AND
RESPIRATORY
SYSTEM
IRRITANT
AVOID
INHALATION
AND
SKIN/
EYE
CONTACT
[
Any
other
appropriate
warnings
­­
e.
g.
"
Flammable
­
Keep
away
from
heat,
sparks,
and
open
flame
"]

(
3)
Material
safety
data
sheets.
Employers
who
are
manufacturers
or
importers
of
glycol
ethers
or
glycol
ethers­
containing
compounds
shall
comply
with
the
requirements
regarding
development,
updating,
and
distribution
of
material
safety
data
sheets
specified
in
29
CFR
1910.1200(
g)
of
OSHA's
Hazard
Communication
Standard.
All
employers
with
employees
potentially
exposed
to
glycol
ethers
shall
maintain
material
safety
data
sheets
and
provide
their
employees
with
access
to
them,
in
accordance
with
the
requirements
of
29
CFR
1910.1200(
g)

(
4)
Employee
information
and
training.
(
i)
Employers
who
have
a
workplace
or
work
operation
covered
by
this
section
shall
provide
employees
who
are
potentially
exposed
to
glycol
ethers
with
information
and
training
in
accordance
with
the
requirements
of
the
Hazard
Communication
Standard,
29
CFR
1910.1200(
h)
of
the
General
Industry
Standards
(
ii)
The
employer
shall
institute
a
training
program
for
all
employees
who
are
potentially
exposed
to
glycol
ethers,
assure
each
employee's
participation
in
the
program,
maintain
a
record
of
this
participation,
and
maintain
a
record
of
the
contents
of
such
program
(
iii)
Training
shall
be
provided,
at
no
cost
to
the
employee,
prior
to
or
at
the
time
of
initial
assignment
to
a
job
involving
potential
exposure
to
glycol
ethers,
at
least
annually
thereafter,
and
whenever
a
new
hazard
from
glycol
ethers
is
introduced
into
their
work
area
(
iv)
The
employer
shall
conduct
the
training
program
in
a
manner
that
the
employee
is
able
to
understand.
The
employer
shall
assure
that
each
employee
is
informed
of
at
least
the
following:

(
A)
The
health
hazards
associated
with
glycol
ethers
exposure
with
special
attention
to
the
information
in
Appendix
A
of
this
section;

(
B)
The
quantity,
location,
manner
of
use,
release,
and
storage
of
glycol
ethers
at
the
worksite
and
the
specific
nature
of
operations
that
could
result
in
exposure
to
glycol
ethers,
especially
exposures
above
the
TWAs
or
ELs;

(
C)
An
explanation
of
the
importance
of
engineering
and
work
practice
controls
for
employee
protection
and
necessary
instruction
in
the
use
of
these
controls;

(
D)
The
measures
employees
can
take
to
protect
themselves
from
exposure
to
glycol
ethers,
such
as
diligent
personal
hygiene
and
proper
use
of
personal
protective
equipment,
and
specific
procedures
the
employer
has
implemented
to
protect
employees
against
exposure,
including
appropriate
work
practices,
emergency
procedures,
and
personal
protective
equipment
(
E)
The
details
of
the
hazard
communication
program
developed
by
the
employer,
including
an
explanation
of
the
signs,
labeling
system,
and
material
safety
data
sheets
and
how
employees
can
obtain
and
use
the
appropriate
hazard
information;

(
F)
The
purpose,
proper
selection,
fitting,
proper
use,
and
limitations
of
respiratory
protection
and
personal
protective
clothing
and
eyewear;

(
G)
The
purpose
and
description
of
the
medical
surveillance
program
[
page
15621]

required
by
paragraph
(
l)
of
this
section
including
the
right
of
any
employee
exposed
to
glycol
ethers
at
or
above
the
AL
or
above
the
EL
to
obtain:
(
1)
Medical
examinations
as
required
by
paragraph
(
l)
of
this
section
at
no
cost
to
the
employee;

(
2)
The
employee's
medical
records
required
to
be
maintained
by
paragraph
(
n)(
2)
of
this
section;

(
3)
All
air
monitoring
results
representing
the
employee's
exposure
to
glycol
ethers
and
required
to
be
kept
by
paragraph
(
n)(
1)
of
this
section
(
H)
A
copy
of
this
standard
and
its
appendices
with
a
discussion
of
its
contents;

(
I)
Instructions
for
the
handling
of
spills
and
cleanup
procedures;

(
J)
A
review
of
emergency
procedures
including
the
specific
duties
or
assignments
of
each
employee
in
the
event
of
an
emergency;

(
n)
Recordkeeping
­
(
1)
Exposure
measurements.
(
i)
The
employer
shall
establish
and
maintain
an
accurate
record
of
all
measurements
required
by
paragraph
(
d)
of
this
section,
in
accordance
with
29
CFR
1910.20.
(
ii)
This
record
shall
include
at
least
the
following:

(
A)
The
name,
social
security
number,
and
job
classification
of
the
employee(
s)
monitored
and
all
other
employees
whose
exposure
the
measurement
is
intended
to
represent;

(
B)
The
dates
of
monitoring,
sample
identification
number,
sampling
duration,
time
of
day,
and
exposure
monitoring
results
of
each
of
the
samples
taken,
including
a
description
of
the
procedure
used
to
determine
representative
employee
exposures.
Exposure
monitoring
results
shall
be
expressed,
at
a
minimum,
as
either
an
8­
hour
timeweighted
average
(
TWA)
or
a
15­
minute
excursion
limit
(
EL),
whichever
is
applicable;
(
C)
The
operation(
s)
covered
by
the
monitoring;

(
D)
The
sampling
and
analytical
methods
used
and
evidence
of
their
accuracy;
(
E)
The
type
of
respiratory
protective
devices
worn,
if
any;

and
(
F)
Any
other
conditions
that
might
have
affected
the
employee
monitoring
results
(
iii)
The
employer
shall
maintain
a
record
of
the
objective
data
relied
upon
to
support
the
determination
that
no
employee
is
exposed
to
glycol
ethers
at
or
above
the
action
level
or
EL
whenever
the
employer
has
used
objective
data
to
determine
that
no
monitoring
is
required
under
this
section
(
iv)
The
employer
shall
maintain
this
record
for
at
least
the
duration
of
employment
plus
30
years
in
accordance
with
29
CFR
1910.20
(
2)
Medical
surveillance.
(
i)
The
employer
shall
establish
and
maintain
an
accurate
record
for
each
employee
subject
to
medical
surveillance
required
by
paragraph
(
l)
of
this
section,
in
accordance
with
29
CFR
1910.20
(
ii)
This
record
shall
include
at
least
the
following
information:
(
A)
The
name
and
social
security
number
of
the
employee;

(
B)
The
physician's
written
opinions
from
the
initial,
periodic
and
additional
examinations;

(
C)
Any
employee
medical
complaints
related
to
exposure
to
glycol
ethers
(
D)
A
copy
of
the
information
provided
by
the
employer
to
the
physician
as
required
by
paragraph
(
l)(
5)(
ii)­(
l)(
5)(
v)
of
this
section;

(
E)
A
copy
of
the
medical
and
reproductive
histories,
medical
questionnaire
responses,
and
the
results
of
any
medical
tests
required
by
the
standard
or
mandated
by
the
examining
physician
(
iii)
The
employer
shall
assure
that
this
record
is
maintained
for
at
least
the
duration
of
employment
plus
30
years,
in
accordance
with
29
CFR
1910.20
(
3)
Training.
The
employer
shall
maintain
all
employee
training
records
for
one(
1)
year
beyond
the
last
date
of
employment
of
that
employee
(
4)
Availability.
(
i)
The
employer
shall
assure
that
all
records
required
to
be
maintained
by
this
section
shall
be
made
available
upon
request
to
the
Assistant
Secretary
and
the
Director
for
examination
and
copying
(
ii)
The
employer
shall
provide
upon
request
for
examination
and
copying,
all
employee
exposure
monitoring
records
required
to
be
maintained
by
paragraph
(
n)(
1)
of
this
section
to
affected
employees,
former
employees,
and
designated
representatives
in
accordance
with
29
CFR
1910.20
(
a)­(
e)
and
(
g)­(
i)

(
iii)
The
employer
shall
provide
upon
request
for
examination
and
copying,
all
employee
medical
records
required
to
be
maintained
by
paragraph
(
n)(
2)
of
this
section
to
the
subject
employee
and
to
anyone
having
the
specific
written
consent
of
the
subject
employee
in
accordance
with
29
CFR
1910.20
(
5)
Transfer
of
records.
If
the
employer
ceases
to
do
business,
the
employer
shall
comply
with
the
requirements
involving
transfer
of
records
set
forth
in
29
CFR
1910.20
(
h)

(
o)
Dates
­
(
1)
Effective
date.
This
section
shall
become
effective
[
60
days
after
publication
of
the
final
rule].
All
obligations
under
this
section
commence
on
the
Effective
Date
(
ED),
except
as
follows:
(
2)
Start­
up­
dates
(
i)
Exposure
monitoring.
Initial
monitoring
required
by
paragraph
(
d)
of
this
section
shall
be
completed
as
soon
as
possible
and
in
any
event
not
later
than
[
90
days
after
the
Effective
Date
of
this
section]

(
ii)
Training.
Training
required
by
paragraph
(
m)(
4)
of
this
section
shall
be
completed
as
soon
as
possible
and
in
any
event
not
later
than
[
90
days
after
the
Effective
Date
of
this
section]

(
iii)
Regulated
areas.
Regulated
areas
required
to
be
established
by
paragraph
(
e)
of
this
section
shall
be
set
up
as
soon
as
possible
after
the
results
of
exposure
monitoring
are
known
and
in
any
event
not
later
than
[
120
days
after
the
Effective
Date
of
this
section]

(
iv)
Respiratory
protection.
Respiratory
protection
required
by
paragraph
(
g)
of
this
section
shall
be
provided
as
soon
as
possible
and
in
any
event
not
later
than
[
120
days
after
the
Effective
Date
of
this
section]

(
v)
Medical
surveillance.
Medical
surveillance
required
by
paragraph
(
l)
of
this
section
shall
be
completed
as
soon
as
possible
or
in
any
event
not
later
than
[
120
days
after
the
Effective
Date
of
this
section]

(
vi)
Emergency
Plan.
The
emergency
plan
required
by
paragraph
(
k)
of
this
section
shall
be
completed
as
soon
as
possible
and
in
any
event
not
later
than
[
180
days
after
the
Effective
Date
of
this
section]

(
vii)
Compliance
program.
The
written
compliance
program
required
by
paragraph
(
f)(
5)
of
this
section
shall
be
completed
and
available
for
inspection
and
copying
as
soon
as
possible
and
in
any
event
not
later
than
[
1
year
after
the
Effective
Date
of
this
section]

(
viii)
Showers
and
eyewashes.
Showers
and
eyewashes
required
by
paragraph
(
i)
of
this
section
shall
be
installed
and
usable
as
soon
as
possible
and
in
any
event
not
later
than
[
1
year
after
the
Effective
Date
of
this
section]

(
iv)
Methods
of
Compliance.
Engineering
controls
required
by
this
standard
shall
be
implemented
as
soon
as
possible,
but
no
later
than
[
2
years
after
the
Effective
Date
of
this
section].
Work
practices
shall
be
implemented
as
soon
as
possible.
Work
practice
controls
that
are
directly
related
to
engineering
controls
being
installed
in
accordance
with
the
compliance
plan
shall
be
implemented
as
soon
as
these
engineering
controls
are
functional
(
p)
Appendices.
The
information
contained
in
Appendices
A,
B,
C,
D
and
[
page
15622]

E
is
not
intended,
by
itself,
to
create
any
additional
obligations
not
otherwise
imposed
or
to
detract
from
existing
regulations.
The
protocols
on
respiratory
fit
testing
in
Appendix
F
are
incorporated
as
part
of
this
section
and
are
mandatory
APPENDIX
A
­
Substance
Safety
Data
Sheet
for
Glycol
Ethers
I.
Substance
Identification
A.
Substance:
Glycol
Ethers
(
2­
Methoxyethanol,

2­
Methoxyethanol
acetate,
2­
Ethoxyethanol
and
2­
Ethoxyethanol
acetate).

B.
Permissible
Exposure:

1.
Airborne:

A.
8­
Hour
Time
Weighted
Average
(
TWA­
PEL):

2­
ME:
0.1
ppm
2­
MEA:
0.1
ppm
2­
EE:
0.5
ppm
2­
EEA:
0.5
ppm
B.
Excursion
Limit
(
EL)
15
Minute:

2­
ME:
0.5
ppm
2­
MEA:
O.
5
ppm
2­
EE:
2.5
ppm
2­
EEA:
2.5
ppm
2.
Dermal:
Contact
wiyh
eyes
or
skin
should
be
eliminated
II.
Health
Hazard
Data
A.
Glycol
ethers
can
affect
your
body
if
you
inhale
the
vapor
(
breathing),
if
it
comes
into
contact
with
your
eyes
or
skin,
or
if
you
swallow
it
B.
Effects
of
over
exposure:

1.
Short
term
exposure:
Glycol
ethers
can
cause
eye
and
upper
respiratory
tract
irritation.
In
addition
they
can
be
mildly
irritating
to
skin.
Ingestion
of
large
doses
of
glycol
ethers
may
cause
vomiting
or
lead
to
death.
Systemic
effects
from
short­
term
high
exposures
may
include
lung,
kidney
and
brain
damage
2.
Long
term
exposure:
Repeated
or
prolonged
exposure
to
glycol
ethers
may
cause
kidney,
liver
and
lung
damage
as
well
as
central
nervous
system
depression
and
anemia.
Glycol
ethers
have
also
been
shown
to
cause
testicular
degeneration,
reduced
sperm
counts,
fetal
with
and
malformations,
and
adverse
hematologic
effects
in
several
animal
species
3.
Reporting
Signs
and
Symptoms:
You
should
inform
your
employer
if
you
develop
any
signs
or
symptoms
and
suspect
they
are
caused
by
glycol
ethers
III.
Emergency
First
Aid
Procedures
A.
Eye
exposure:
If
glycol
ethers
get
into
your
eyes,
wash
immediately
with
large
amounts
of
water,
lifting
the
lower
and
upper
lids
occasionally.
If
irritation
is
present
after
washing,
get
medical
attention.
Contact
lenses
should
not
be
worn
when
working
with
glycol
ethers
B.
Skin
exposure:
If
glycol
ethers
get
on
the
skin,
promptly
wash
the
contaminated
skin
with
water.
If
glycol
ethers
soak
through
your
clothing,
remove
the
clothing
and
wash
the
skin
with
water.
If
irritation
persists
after
washing,
get
medical
attention.
Wash
the
clothing
thoroughly
before
reusing
C.
Inhalation:
If
a
person
breaths
in
large
amounts
of
glycol
ethers,
move
the
exposed
person
to
fresh
air
at
once.
If
breathing
has
stopped
perform
artificial
respiration.
Keep
the
affected
person
warm
and
at
rest.
Get
medical
attention
as
soon
as
possible
D.
Swallowing:
When
glycol
ethers
have
been
swallowed,
get
medical
attention
immediately.
If
medical
attention
is
not
immediately
available,
get
the
afflicted
person
to
vomit
by
having
him
touch
the
back
of
his
throat
with
his
finger
or
by
giving
him
syrup
of
ipecac
as
directed
on
the
package.
This
non­
prescription
drug
is
available
at
most
drug
stores
and
drug
counters
and
should
be
kept
with
emergency
medical
supplies
in
the
workplace.
Do
not
make
an
unconscious
person
vomit
E.
Rescue:
Move
the
effected
person
from
the
hazardous
exposure.
If
the
exposed
person
has
been
overcome,
notify
someone
else
and
put
into
effect
the
established
emergency
rescue
procedures.
Do
not
become
a
casualty.
Understand
the
facility's
emergency
rescue
procedures
and
know
the
locations
of
rescue
equipment
before
the
need
arises
IV.
Protective
Clothing
and
Equipment
A.
Respirators:
Respirators
are
required
for
those
operations
in
which
engineering
controls
or
work
practice
controls
are
not
feasible
to
reduce
exposure
to
the
permissible
level.
If
respirators
are
worn,
they
must
have
joint
Mine
Safety
and
Health
Administration
and
the
National
Institute
for
Occupational
Safety
and
Health
(
NIOSH)
seal
of
approval.
For
effective
protection,
respirators
must
fit
the
face
and
head
snugly.
Respirators
should
not
be
loosened
or
removed
in
work
situations
where
their
use
is
required.
Glycol
ethers
do
not
have
detectable
odors
except
at
levels
above
permissible
levels.
Do
not
depend
on
odor
to
warn
you
when
a
respirator
is
malfunctioning
If
you
experience
difficulty
breathing
while
wearing
a
respirator,
tell
your
employer.
You
must
be
thoroughly
trained
to
use
the
assigned
respirator,
and
the
training
will
be
provided,
at
no
cost
to
you,
by
your
employer
B.
Protective
Clothing:
You
must
wear
impervious
clothing,
gloves,
face
shield,
or
other
appropriate
protective
clothing
to
prevent
skin
contact
with
liquid
glycol
ethers.
Wherever
protective
clothing
is
required,
your
employer
is
required
to
provide,
at
no
cost,
clean
garments
to
you
as
necessary
to
assure
that
the
clothing
protects
you
from
dermal
exposure
to
glycol
ethers
C.
Eye
Protection:
You
must
wear
splashproof
goggles
in
areas
where
liquid
glycol
ethers
may
contact
your
eyes.
In
addition,
contact
lenses
should
not
be
worn
in
areas
where
eye
contact
with
glycol
ethers
can
occur
V.
Medical
Requirements:

If
you
are
will
be
exposed
to
glycol
ethers
at
or
above
the
action
level,
[
0.05
ppm(
2­
ME/
2­
MEA)
or
0.25
ppm
(
2­
EE/
2­
EEA)
as
an
8­
hour
time
weighted
average],
or
above
0.5
ppm(
2­
ME/
2­
MEA)
or
2.5
ppm(
2­
EE/
2­
EEA)
as
a
15­
minute
excursion
limit,
your
employer
is
required
to
provide
a
medical
examination
and
history
and
laboratory
tests
within
90
days
of
the
effective
date
of
this
standard
or
before
the
time
of
assignment
to
an
area
at
or
above
the
action
level
or
above
the
excursion
limit,
which
ever
comes
later
and
annually
thereafter.
These
tests
shall
be
provided
without
cost
to
you.
In
addition,
if
you
are
accidentally
exposed
to
glycol
ethers
(
either
by
ingestion,
inhalation,
or
skin/
eye
contact)
under
conditions
known
or
suspected
to
constitute
toxic
exposure
to
glycol
ethers,
your
employer
is
required
to
make
a
medical
examination
available
to
you
VI.
Observation
of
Monitoring
Your
employer
is
required
to
make
measurements
that
are
representative
of
your
exposure
to
glycol
ethers
and
you
or
your
designated
representative
are
entitled
to
observe
the
steps
taken
in
the
measurements
procedure,
and
to
record
the
results
obtained.
When
the
monitoring
procedure
is
in
an
area
where
respirators
or
personal
protective
clothing
must
be
worn
you
or
your
representative
must
also
be
provided
with,
and
must
wear
the
protective
clothing
and
equipment
VII.
Access
to
Records
You
or
your
representative
are
entitled
to
see
the
records
of
measurements
of
your
exposure
to
glycol
ethers
upon
written
request
to
your
employer.
Your
medical
examination
records
can
be
furnished
to
your
physician
or
designated
representative
upon
request
by
you
to
your
employer
VIII.
Precautions
for
Safe
Use,
Handling
and
Storage
Glycol
ether
liquids
are
flammable.
They
should
be
stored
in
closed
containers
in
cool,
well
ventilated
areas.
Non
sparking
tools
must
be
used
to
open
and
close
containers.
Glycol
ethers
vapors
may
form
explosive
mixtures
in
air.
All
sources
of
ignition
must
be
controlled.
Fire
extinguisher,
where
provided,
must
be
readily
available.
Know
where
they
are
located
and
how
to
operate
them.
Ask
your
supervisor
where
glycol
ethers
are
used
in
your
work
area
and
for
additional
plant
safety
rules
APPENDIX
B
­
Substance
Technical
Guidelines
for
Glycol
Ethers
I.
2­
Methoxyethanol
A.
Physical
and
Chemical
Data
1.
Substance
Identification
Chemical
name:
2­
Methoxyethanol
Formula:
CH3OCH2CH2OH
Molecular
Weight:
76
Chemical
Abstracts
Service
(
CAS)
NO.:
109­
86­
4
Synonyms:
Methyl
Cellosolve;
Ethylene
glycol
monomethyl
ether;
methyl
oxitol;
Ektasolve;
Jeffersol
EM
2.
Physical
data
Boiling
point
(
760
mm
Hg):
124.*
c
Freezing
point:
­
85.1*
c
Specific
Gravity
(
H20=
1
@
20*
c):
0.9663
Vapor
Pressure
(
20*
c):
6
mm
Hg
Vapor
Density
(
air
=
1
@
20*
c):
2.6
Solubility
in
H20
(%
by
wt
@
20*
c):
miscible
in
all
proportions.

[
page
15623]

Appearance
and
Odor:
colorless
liquid
with
a
mild,
pleasant
odor
B.
Fire,
Explosion
and
Reactivity
Data
1.
Fire
Flammable
limits
in
air
(%
by
volume):
Lower:
2.3
Upper:
24.5
Flash
point:
39*
C
(
closed
cup)
Extinguishing
media:
Dry
chemical,
alcohol
foam,
carbon
dioxide
Fire
and
Explosion
Hazards:
Moderate
fire
hazard
when
exposed
to
heat
or
flame.
Forms
explosive
peroxides
in
air.
Vapors
are
heavier
than
air
and
may
travel
a
considerable
distance
to
source
of
ignition
and
flash
back
2.
Reactivity
Conditions
contributing
to
instability:
Heat
Incompatibilities:
Strong
oxidizing
agents,
strong
caustics
Hazardous
decomposition
products:
Thermal
decomposition
products
may
include
toxic
oxides
of
carbon
C.
Spill,
Leak
and
Disposal
Procedures
1.
Steps
to
be
taken
if
the
material
is
released
or
spilled.
Remove
all
ignition
sources
and
ventilate
the
area
of
spill
or
leak.
Stop
leak
if
you
can
do
it
without
risk.
Use
water
to
reduce
vapors.
For
small
quantities,
absorb
on
paper
towels
and
evaporate
in
a
safe
place
(
such
as
a
fume
hood).
Burn
the
paper
in
a
suitable
location
away
from
combustible
materials.
Large
quantities
may
be
collected
and
atomized
in
a
suitable
combustion
chamber.

2.
Disposal.
2­
ME
may
be
disposed
of
by
atomizing
in
a
suitable
combustion
chamber
II.
2­
Methoxyethanol
acetate
A.
Physical
and
Chemical
Data
1.
Substance
Identification
Chemical
name:
2­
Methoxyethanol
acetate
Formula:
CH3C00CH2CH2OCH3
Molecular
Weight:
118.13
CAS
No.
110­
49­
6
Synonyms:
Methyl
Cellosolve
acetate,
ethylene
glycol
monomethyl
ether
acetate,

2.
Physical
data
Boiling
point::
144*
c
Freezing
point:
­
70*
c
Specific
Gravity
(
H20
=
1
@
20*
c):
1.01
Vapor
Pressure
(
20*
c):
2
mm
Hg
Vapor
Density
(
air
=
1
@
20*
c):
4.1
Solubility
in
H20
(%
by
wt
@
20*
c):
completely
miscible
Appearance
and
Odor:
Colorless
liquid
with
mild,
ether­
like
odor
B.
Fire,
Explosion
and
Reactivity
Data
1.
Fire
Flammable
limits
in
air
(%
by
volume):
Lower:
1.7
Upper:
8.2
Flash
point:
44*
c
(
closed
cup)
Extinguishing
media:
Dry
chemical,
alcohol
foam,
carbon
dioxide
Fire
and
Explosion
Hazards:
Moderate
fire
hazard
when
exposed
to
heat
or
flame.

Forms
explosive
peroxides
in
air.
Vapors
are
heavier
than
air
and
may
travel
a
considerable
distance
to
source
of
ignition
and
flash
back
2.
Reactivity
Conditions
contributing
to
instability:
Heat
Incompatibilities:
Strong
acids,
strong
alkalies,
strong
oxidizers
Hazardous
decomposition
products:
Toxic
vapors
and
gases
(
such
as
carbon
monoxide).
Thermal
decomposition
may
release
acrid
smoke
or
irritating
fumes
C.
Spill
Leak
and
Disposal
Procedures
1.
Steps
to
be
taken
if
the
material
is
released
or
spilled.
Remove
all
ignition
sources
and
ventilate
the
area
of
spill
or
leak.
Stop
leak
if
you
can
do
so
without
risk.
Use
water
to
reduce
vapors.
For
small
quantities,
absorb
on
paper
towels
and
evaporate
in
a
safe
place
(
such
as
a
fume
hood).
Burn
the
paper
in
a
suitable
location
away
from
combustible
materials.
Large
quantities
may
be
collected
and
atomized
in
a
suitable
combustion
chamber
2.
Disposal.
2­
MEA
may
be
disposed
of
by
absorbing
it
in
vermiculite,
dry
sand,
earth
or
a
similar
material
and
disposing
it
in
a
secured
landfill
or
by
atomizing
in
a
suitable
combustion
chamber
III.
2­
Ethoxyethanol
A.
Physical
and
Chemical
Data
1.
Substance
Identification
Chemical
name:
2­
Ethoxyethanol
Formula:
C2H20CH2CH2OH
Molecular
weight:
90.12
CAS
N0.
110­
80­
5
Synonyms:
Cellosolve,
Ethylene
glycol
monoethyl
ether
2.
Physical
data
Boiling
point:
135.6*
c
Freezing
point:
­
70*
c
Specific
Gravity
(
H20=
1@
20*
c):
.93
Vapor
Pressure
(
20*
c):
4mm
Hg
Vapor
Density
(
air
=
1
@
20*
c):
3.0
Solubility
in
H2O
(%
by
wt
@
20*
c):
Miscible
in
all
proportions
Appearance
and
Odor:
Colorless
liquid
with
sweetish
odor
B.
Fire,
Explosion
and
Reactivity
Data
1.
Fire
Flammable
limits
in
air
(%
by
volume):
Lower:
1.7
Upper:
15.6
Flash
point:
43*
c
(
closed
cup)
Extinguishing
media:
Dry
chemical,
alcohol
foam,
carbon
dioxide
Fire
and
Explosion
Hazards:
Moderate
fire
hazard
when
exposed
to
heat
or
flame.
Vapor
air
mixtures
are
explosive
above
flash
point.
Forms
explosive
peroxides
in
air.
Vapors
are
heavier
than
air
and
may
travel
a
considerable
distance
to
source
of
ignition
and
flash
back
2.
Reactivity
Conditions
contributing
to
instability:
Elevated
temperatures
Incompatibilities:
Strong
oxidizers,
acid
and
alkalies
Hazardous
decomposition
products:
Toxic
vapors
and
gases
(
such
as
carbon
monoxide)

C.
Spill
Leak
and
Disposal
Procedures
1.
Steps
to
be
taken
if
the
material
is
released
or
spilled.
Remove
all
ignition
sources
and
ventilate
the
area
of
spill
or
leak.
Stop
leak
if
you
can
do
so
without
risk.
Use
water
to
reduce
vapors.
For
small
quantities,
absorb
on
paper
towels
and
evaporate
in
a
safe
place
(
such
as
a
fume
hood).
Burn
the
paper
in
a
suitable
location
away
from
combustible
materials.
Large
quantities
may
be
collected
and
atomized
in
a
suitable
combustion
chamber
2.
Disposal.
2­
EE
may
be
disposed
of
by
absorbing
it
in
vermiculite,
dry
sand,

earth
or
a
similar
material
and
disposing
it
in
a
secured
landfill
or
by
atomizing
in
a
suitable
combustion
chamber
IV.
2­
Ethoxyethanol
acetate
A.
Physical
and
Chemical
Data
1.
Substance
Identification
Chemical
name:
2­
Ethoxyethanol
acetate
Formula:
C2H5OCH2CH2OCOCH3
Molecular
weight:
132.16
CAS
No.:
111­
15­
9
Synonyms:
Cellosolve
acetate,
ethylene
glycol
monoethyl
ether
acetate
2.
Physical
data
Boiling
point:
156.4*
c
Freezing
point:
­
62*
c
Specific
Gravity
(
H20
=
1
@
20*
c):
.98
Vapor
Pressure
(
20*
c):
2
mm
Hg
Vapor
Density
(
air
=
1
@
20*
c):
4.6
Solubility
in
H20
(%
by
wt
@
20*
c):
23
Appearance
and
Odor:
Colorless
viscous
liquid
with
a
mild,
non­
residual
odor
B.
Fire,
Explosion
and
Reactivity
Data
1.
Fire
Flammable
limits
in
air
(%
by
volume):
Lower:
1.7
Upper:
13
Flash
point:
47*
c
(
closed
cup)

Extinguishing
media:
Dry
chemical,
alcohol
foam,
carbon
dioxide
Fire
and
Explosion
Hazards:
Moderate
fire
hazard
when
exposed
to
heat
or
flame.
Vapor
air
mixtures
are
explosive
above
flash
point.
Forms
explosive
peroxides
in
air.
Vapors
are
heavier
than
air
and
may
travel
a
considerable
distance
to
source
of
ignition
and
flash
back
2.
Reactivity
Conditions
contributing
to
instability:
Heat
Incompatibilities:
Nitrates,
strong
oxidizers,
strong
alkalies,
strong
acids
Hazardous
decomposition
products:
Toxic
vapors
and
gases
(
such
as
carbon
dioxide).
Thermal
decomposition
produces
acrid
smoke
and/
or
irritating
toxic
fumes
C.
Spill
Leak
and
Disposal
Procedures
1.
Steps
to
be
taken
if
the
material
is
released
or
spilled.
Remove
all
ignition
sources
and
ventilate
the
area
of
spill
or
leak.
Stop
leak
if
you
can
do
it
without
risk.
Use
water
to
reduce
vapors.
For
small
quantities,
absorb
on
paper
towels
and
evaporate
in
a
safe
place
(
such
as
a
fume
hood).
Burn
the
paper
in
a
suitable
location
away
from
combustible
materials.
Large
quantities
may
be
collected
and
atomized
in
a
suitable
combustion
chamber.

[
page
15624]

2.
Disposal.
2­
EEA
may
be
disposed
of
by
absorbing
it
in
vermiculite,
dry
sand,
earth
or
a
similar
material
and
disposing
it
in
a
secured
landfill
or
by
atomizing
in
a
suitable
combustion
chamber
APPENDIX
C
­
Medical
Surveillance
Guidelines
for
Glycol
Ethers
I.
Toxicology
Studies
of
inhalation
exposures
to
glycol
ethers
have
shown
that
these
exposures
produce
adverse
reproductive
and
developmental
effects
in
several
animal
species.
The
effects
observed
include
testicular
damage,
reduced
fertility,
maternal
toxicity
and
developmental
abnormalities
of
the
fetus.
Data
from
experimental
animals
have
also
demonstrated
that
exposure
to
glycol
ethers
may
result
in
a
variety
of
hematologic
effects
including
hemolysis,
bone
marrow
depression
and
reduced
red
and
white
blood
cell
counts.
Adverse
hematologic
and
testicular
effects
have
also
been
observed
in
humans
exposed
to
glycol
ethers.
Among
these
effects
are
testicular
degeneration,
reduced
sperm
count,
anemia,
lowered
white
blood
cell
counts
and
bone
marrow
depression.
In
addition
to
inhalation
exposure,
glycol
ethers
are
also
readily
absorbed
dermally
and
can
also
be
swallowed.
Exposure
to
glycol
ethers
in
liquid
form
or
high
air
concentrations
may
cause
irritation
of
the
eyes,
nose
and
throat
Ingestion
or
large
does
may
be
fatal.
Acute
effects
from
overexposure
also
include
drowsiness,
weakness
and
shaking
II.
Signs
and
Symptoms
of
Acute
Overexposure
Glycol
ethers
are
only
mildly
irritating
to
the
skin.
Vapor
may
cause
conjunctivitis
and
upper
respiratory
tract
irritation.
Temporary
corneal
clouding
may
also
result
and
may
last
several
hours.
Acetate
derivatives
cause
greater
irritation
than
the
parent
compounds.
Acute
exposure
may
also
result
in
narcosis,
pulmonary
edema
and
severe
kidney
and
liver
damage.
Symptoms
from
repeated
overexposure
to
vapors
are
fatigue
and
lethargy,
headache,
nausea,
anorexia,
and
tremor.
Anemia
and
encephalopathy
have
been
reported
with
2­
ME.
Acute
poisoning
by
ingestion
resembles
glycol
ether
toxicity,
with
death
from
renal
failure
III.
Surveillance
and
Preventative
Considerations
As
noted
above
glycol
ethers
have
been
connected
with
adverse
reproductive,
developmental
and
hematologic
effects.
The
physician
should
be
aware
of
the
findings
of
these
studies
in
evaluating
the
health
of
employers
exposed
to
glycol
ethers
It
is
also
important
for
the
physician
to
become
familiar
with
the
operating
conditions
in
which
exposure
to
glycol
ethers
may
occur.
Employees
with
skin
diseases
may
not
be
able
to
tolerate
the
wearing
of
whatever
protective
clothing
may
be
necessary
to
protect
them
from
exposure.
In
addition,
employees
with
chronic
respiratory
disease
may
not
be
able
to
tolerate
the
wearing
of
respirators.
The
employer
is
required
to
institute
a
medical
surveillance
program
for
all
employees
who
are
or
will
be
exposed
above
the
action
level
or
above
the
excursion
limit
without
regard
to
the
use
of
respirators.
The
medical
surveillance
program
must
provide
each
covered
employee
with
an
opportunity
for
medical
examination.
All
examinations
and
procedures
must
be
performed
by
or
under
the
supervision
of
a
licensed
physician
and
be
provided
at
a
reasonable
place
and
time
at
no
cost
to
the
employee.
The
examining
physician
is
given
broad
latitude
in
prescribing
specific
tests
to
be
included
in
the
medical
surveillance
program.
However,
certain
elements
of
an
examination
are
suggested
as
being
appropriate
by
the
health
data
regarding
the
reproductive
and
hematologic
effects.
These
elements
include:
(
i)
Comprehensive
medical,
work
and
reproductive
histories
with
special
emphasis
directed
to
the
hematologic
system
and
symptoms
related
to
pulmonary
and
mucous
membrane
irritation
(
ii)
A
comprehensive
physical
examination
with
emphasis
given
to
hematologic
and
pulmonary
systems,
mucous
membranes,
skin
and
eyes
(
iii)
A
complete
blood
count
to
include
at
least
a
red
cell
count,
a
white
cell
count,
hemoglobin
and
hematocrit
In
addition,
the
physician
must
determine
the
worker's
suitability
for
respirator
use.
Workers
or
job
applicants
who
have
medical
conditions
that
would
be
aggravated
by
the
use
of
a
respirator
need
to
receive
counseling
on
the
increased
risk
of
impairment
of
their
health.
In
certain
cases,
to
provide
sound
medical
advice
to
the
employer
and
the
employee,
the
physician
must
evaluate
situations
not
directly
related
to
glycol
ethers.
For
example,
employees
with
skin
diseases,
whether
or
not
they
are
glycol
ethers
related,
may
be
unable
to
tolerate
wearing
protective
clothing.
In
addition,
those
with
chronic
respiratory
diseases
may
not
tolerate
the
wearing
of
respirators.
Additional
tests
and
procedures
that
will
help
the
physician
determine
which
employees
are
medically
unable
to
wear
respirators
must
include
a
pulmonary
function
test
with
measurement
of
the
employee's
forced
vital
capacity
(
FVC),
and
forced
expiratory
volume
at
one
second
(
FEV1).
Ratios
of
FEV1
to
FVC
as
well
as
measured
FVC
and
measured
FEV1
to
their
expected
values
corrected
for
variations
due
to
age,
sex,
race,
and
height
must
be
calculated.
Whether
a
chest
X­
ray
will
provide
useful
information
should
be
considered
The
employer
is
required
to
provide
physical
examinations
to
any
employee
exposed
to
emergency
conditions.
While
little
is
known
about
the
effects
of
high
short­
term
exposures,
it
appears
prudent
to
monitor
such
affected
employers
closely
in
light
of
existing
health
data
The
employer
is
required
to
provide
the
physician
with
the
following
information:
a
copy
of
this
standard
and
appendices;
a
description
of
the
affected
employee's
duties
as
they
relate
to
the
employee's
exposure
concentration;
the
exposure
concentration
from
representative
monitoring
along
with
the
employee's
duration
of
exposure
(
e.
g.,
15
hr/
wk,
three
8­
hour
shifts
a
week,
full­
time);
a
description
of
any
personal
protective
equipment,
including
respirators,
used
by
the
employee;
and
the
results
of
any
previous
medical
determinations
related
to
glycol
ethers
exposure
for
the
affected
employee
that
are
within
the
employer's
control
The
employer
is
required
to
obtain
the
results
of
the
medical
examinations
and
a
written
statement
from
the
physician.
This
statement
must
contain
the
physician's
opinion
as
to
whether
the
employee
has
any
medical
condition
which
would
place
the
employee
at
increased
risk
of
impaired
health
from
exposure
to
glycol
ethers
or
use
of
respirators.
The
physician
must
also
state
his
opinion
regarding
any
restrictions
that
should
be
placed
on
the
employee's
exposure
to
glycol
ethers
or
upon
the
use
of
protective
clothing
or
equipment
such
as
respirators.
The
physician's
opinion
must
also
contain
a
statement
regarding
the
suitability
of
the
employee
to
wear
the
type
of
respirator
assigned
and
a
recommendation
as
to
whether
or
not
respirator
fit
testing
should
be
conducted
Finally,
the
physician
must
inform
the
employer
that
the
employee
has
been
informed
by
the
physician
of
the
results
of
the
medical
examination
and
of
any
medical
conditions
which
require
further
explanation
or
treatment.
This
written
opinion
is
not
to
contain
any
information
on
specific
findings
or
diagnoses
unrelated
to
occupational
exposure
to
glycol
ethers.
After
the
employer
has
received
the
physician's
statement,
the
employer
is
required
to
make
this
information
available
to
the
affected
employee
The
purpose
in
requiring
the
examining
physician
to
supply
the
employer
with
a
written
opinion
is
to
provide
the
employer
with
a
medical
basis
to
assist
the
employer
in
placing
employees
initially,
in
determining
that
their
health
is,
or
is
not,
being
impaired
by
glycol
ethers,
and
to
assess
the
employee's
ability
to
use
protective
clothing
and
equipment
APPENDIX
D
(
Nonmandatory)
­
Reproductive
History
Questionnaire
(
Adapted
From
Appendix
B,
Office
of
Technology
Assessment
Report,
Reproductive
Health
Hazards
in
the
Workplace,
Ex.
5­
135)

REPRODUCTIVE
HISTORY
1
HAVE
THERE
BEEN
ANY
PREGNANCIES
WITH
YOUR
PRESENT
MATE?
YES
NO
If
so,
when
did
they
occur?__________

2
HAVE
THERE
BEEN
ANY
MISCARRIAGES,
ECTOPIC
PREGNANCIES
OR
STILLBIRTHS
WITH
YOUR
PRESENT
MATE?
YES
NO
If
so,
when
did
they
occur?_____________

3
HAVE
YOU
EVER
HAD
OR
FATHERED
A
CHILD
THAT
RESULTED
IN
ANY
OF
THE
FOLLOWING?

If
so,
please
specify
whether
it
was
with
your
present
or
a
previous
mate:

___
Low
birth
weight
baby
(
less
than
5
1/
2
lbs.)

___
Baby
born
more
than
2
weeks
early?

___
Twins,
triplets,
etc
___
Baby
with
a
birth
defect:

___
Cleft
palate
___
Harelip
___
Limb
deformity
___
Disease
or
deformity
of
the
heart,
lungs,

kidney,
genitals,
urinary
tract,

gastrointestinal
tract,
nervous
system
[
page
15625]
___
Malformations
of
the
skull,
spine
___
Musculoskeletal
disorders
(
e.
g.,
muscular
dystrophy)

4
HAVE
YOU
GIVEN
BIRTH
TO
OR
FATHERED
CHILDREN
WHO
HAVE
ANY
OF
THE
FOLLOWING
CONDITIONS?

Please
specify
whether
these
children
were
born
to
you
with
your
present
or
a
previous
Mate
___
Allergy
___
Mental
retardation
___
Asthma
or
learning
problem
___
Epilepsy
___
Leukemia
___
Downs
syndrome
___
Tumor
or
Cancer
___
Cystic
fibrosis
___
Tay­
sachs
___
Hemophilia
___
Other
(
specify)

___
Cerebral
palsy
5
HAVE
YOU
AND
YOUR
PRESENT
OR
ANY
PREVIOUS
MATE
HAD
DIFFICULTY
CONCEIVING?
YES
NO
(
unprotected
intercourse
for
a
year
or
more
with
no
pregnancy)

6
HOW
LONG
HAVE
YOU
BEEN
TRYING
FOR
A
PREGNANCY
WITH
YOUR
PRESENT
MATE?

______________________________

7
HAVE
YOU
OR
YOUR
MATE
EVER
ATTENDED
AN
INFERTILITY
CLINIC
OR
HAD
PREVIOUS
TREATMENT
FOR
INFERTILITY?
YES
NO
If
so,
please
give
name
of
the
doctor
and
the
facility:
_________________________

8
IS
THERE
ANY
HISTORY
OF
FERTILITY
PROBLEMS
IN
YOUR
FAMILY?
YES
NO
(
Difficulty
conceiving,
miscarriage,
still
birth,
deformed
offspring)

Parents?____________________________

Brothers/
Sisters?___________________

Uncles/
Aunts?______________________

9
HOW
MANY
TIMES
PER
WEEK
DO
YOU
HAVE
SEXUAL
INTERCOURSE
WITH
YOUR
PRESENT
MATE?_______________________

10
DO
YOU
AND
YOUR
MATE
USE
OR
HAVE
YOU
USED
ANY
OF
THE
FOLLOWING
TYPES
OF
CONTRACEPTION?

Oral
contraceptive
pill__

Permanent
sterilization___

Diaphragm______
Tubal
ligation______

Condom______
Vasectomy___

Spermicidal
foam
or
gel__

IUD_____
Coitus
interruptus____

Other______________

11
WHAT
FORM
OF
CONTRACEPTION,
IF
ANY,
ARE
YOU
CURRENTLY
USING?

12
DO
YOU
TRY
TO
HAVE
INTERCOURSE
DURING
THE
FERTILE
TIME
OF
THE
MONTH?
YES
NO
If
so,
how
do
you
decide
the
best
time?_____

_______________________________________

13
DO
YOU
HAVE
ANY
PHYSICAL
DIFFICULTIES
WITH
SEX
THAT
WOULD
PREVENT
A
CONCEPTION?
YES
NO
(
e.
g.,
pain
during
intercourse
sufficient
to
Prevent
penetration)?

14
DO
YOU
USE
LUBRICANTS
DURING
SEXUAL
INTERCOURSE?
YES
NO
15
HAVE
YOU
AND
YOUR
PRESENT
MATE
EVER
HAD
A
POST
COITAL
TEST
(
examination
of
the
cervix
for
sperm
after
intercourse)?
YES
NO
If
so,
was
any
incompatibility
noted?____

REPRODUCTIVE
HEALTH
A
MALE
1
HAVE
YOU
EVER
HAD
ANY
INJURY
OR
OPERATION
TO
THE
PENIS
OR
TESTICLES?

Circumcision
YES
NO
Other
operations
on
penis
YES
NO
Explain_________________________

Varicocele
operation
(
varicose
veins
near
testicles)
YES
NO
Vasectomy
YES
NO
Biopsy
of
the
testicle
YES
NO
Other
operations
of
injuries
to
the
testicles
YES
NO
2
HAVE
YOU
EVER
HAD
AN
INFECTION
OF
THE
Bladder
YES
NO
Urethra
YES
NO
Epididymis
YES
NO
Kidney
YES
NO
If
so,
please
give
details:

3
HAS
THERE
BEEN
ANY
RECENT
CHANGE
IN
THE
SIZE
OF
YOUR
TESTICLES?
YES
NO
If
so,
please
give
details:

4
HAVE
YOU
EVER
HAD
A
HERNIA
OPERATION
(
Evens
as
a
baby)?
YES
NO
If
so,
please
give
details:

5
ARE
YOU
IN
THE
HABIT
OF
TAKING
VERY
HOT
BATHS?
YES
NO
6
ARE
YOU
IN
THE
HABIT
OF
TAKING
SAUNAS?

YES
NO
7
WHAT
SORT
OF
UNDERWEAR
DO
YOU
NORMALLY
WEAR?

___
Boxer
trunks
___
Jockey
shorts
___
Other
8
HAVE
YOU
EVER
BEEN
TOLD
BY
A
DOCTOR
HAT
YOU
HAD
A
PROSTATE
PROBLEM?
YES
NO
9
HAVE
YOU
EVER
GONE
THROUGH
A
PERIOD
OF
SEVERAL
MONTHS
WHEN
YOU
HAD
TROUBLE
GETTING
OR
KEEPING
AN
ERECTION?
YES
NO
10
DO
YOU
GET
SATISFACTORY
EJACULATION
OF
SPERM
DURING
INTERCOURSE?
YES
NO
HAVE
YOU
EVER
GONE
THROUGH
A
PERIOD
OF
11
SEVERAL
MONTHS
WHEN
YOU
HAD
LITTLE
INTEREST
IN
SEX?
YES
NO
If
so,
please
give
details:

12
DO
YOU
HAVE
ANY
PROBLEMS
URINATING?
YES
NO
13
HAVE
YOU
EVER
BEEN
EXAMINED
BY
A
UROLOGIST?
YES
NO
If
so
when?_______
For
what
reason?_________

Were
any
problems
identified?
______________

14
HAVE
YOU
HAD
GENITAL
HERPES?
YES
NO
15
HAVE
YOU
HAD
SEXUALLY
TRANSMITTED
DISEASE?
YES
NO
16
HAS
YOUR
SEMEN
BEEN
EVALUATED
BEFORE?

YES
NO
How
many
times?_______________

When
most
recently?__________

What
were
the
results?_____________________

Have
any
other
tests
(
e.
g.
antibody,
mucous
penetration)
been
done
with
your
semen?

YES
NO
If
so,
when?_______________________________

What
were
the
results?_____________________

17
HAVE
ANY
ENDOCRINE
(
HORMONE)
STUDIES
BEEN
DONE
WITH
YOUR
BLOOD?
YES
NO
If
so,
when?_________________________

What
were
the
results?_______________

HAVE
YOU
EVER
HAD
A
FERTILITY
INVESTIGATION?
18
YES
NO
If
so,
what
was
the
diagnosis?

________
Anatomical
defect
________
Hormonal/
Glandular
disorder
________
Other
________
No
abnormality
found
19
HAVE
YOU
EVER
HAD
SURGERY
FOR
INFERTILITY?

YES
NO
If
so,
give
details:

B
FEMALE
MENSTRUAL
HISTORY
1
HOW
OLD
WERE
YOU
WHEN
YOU
BEGAN
TO
MENSTRUATE?_______

2
ARE
YOUR
PERIODS
REGULAR?

Yes___
No___

3
WHAT
IS
THE
AVERAGE
LENGTH
OF
YOUR
CYCLE?___________________________

4
GIVE
THE
DATE
OF
THE
1st
DAY
OF
YOUR
LAST
PERIOD:______________________

5
GIVE
THE
DATE
OF
THE
1st
DAY
OF
THE
PERIOD
BEFORE
LAST:____________________________

6
FOR
HOW
MANY
DAYS
DO
YOU
BLEED?_________________

IF
YOU
EXPERIENCE
ANY
OF
THESE
SYMPTOMS,
7
NOTE
HOW
MANY
DAYS
BEFORE
ONSET
OF
BLEEDING
THE
SYMPTOM
BEGINS:

Premenstrual:

Abdominal
Bloating____
Urinary
Tract
Symptoms___

Swelling
of
face,
hands
Headache_________________

or
feet______________

Irritability_________
Breast
Tenderness_____

Weight
Gain______________

Bowel
Changes_________

Other____________________

During
Period:

Cramps_______
Hot
Flashes_______________

Nausea_______
Fever_____________________

Diarrhea_____
Sweats____________________

Chills_______
Constipation______________

Headaches____
Rectal
Pain_______________

Fainting______
Other_____________________

Dizziness___

8
DO
YOU
HAVE
ANY
BLEEDING
OR
BLOODY
DISCHARGE:

Between
Periods
YES
NO
After
Intercourse
YES
NO
After
Douching
YES
NO
GYNECOLOGIC
HISTORY:

1
DO
YOU
HAVE
ANY
PAIN
OR
DISCOMFORT
ASSOCIATED
WITH
INTERCOURSE?
YES
NO
2
DO
YOU
HAVE
ANY
PROBLEMS
OR
DIFFICULTY
RELATED
TO
SEXUAL
ACTIVITY
YES
NO
3
HAVE
YOU
EVER
GONE
THROUGH
A
PERIOD
OF
SEVERAL
MONTHS
WHEN
YOU
HAD
LITTLE
INTEREST
IN
SEX?
YES
NO
If
so,
give
details:

4
HAVE
YOU
HAD
GENITAL
HERPES?
YES
NO
5
HAVE
YOU
HAD
SEXUALLY
TRANSMITTED
DISEASE?
YES
NO
6
HAVE
YOU
EVER
HAD
AN
ABNORMAL
PAP
SMEAR?

YES
NO
7
HAVE
YOU
HAD
OR
DO
YOU
RECURRENT
VAGINAL
INFECTION?
YES
NO
[
page
15626]

8
HAVE
YOU
HAD
OR
DO
YOU
HAVE
PROBLEMS
WITH
VAGINAL
DISCHARGE?
YES
NO
9
DID
YOUR
MOTHER
TAKE
Diethylstilbestrol(
DES)

WHILE
PREGNANT
WITH
YOU?
YES
NO
DISEASE,
ABNORMALITY
OR
SURGERY
OF
THE
10
HAVE
YOU
HAD
ANY
TYPE
OF
PELVIC
INFECTION,

Vulva___
Vagina___
Cervix___

Uterus__
Tubes____
Ovaries__

Urinary
Tract___
Anus___
Rectum___

11
HAVE
YOU
EVER
HAD
ENDOMETRIOSIS?
YES
NO
If
so,
when?_______
How
was
it
Treated?________

12
DO
YOU
KNOW
WHETHER
OR
NOT
YOUR
FALLOPIAN
TUBES
ARE
OPEN?
YES
NO
13
HAS
EITHER
TUBE
BEEN
REMOVED?
YES
NO
14
HAVE
YOU
EVER
HAD
A
HYSTEROSALPINGOGRAM
(
Tubal
dye
study)?
YES
NO
If
so,
when?_____
What
were
the
results?______

15
HAVE
YOU
EVER
HAD
A
LAPAROSCOPY?
YES
NO
If
so,
when____
What
were
the
results?________

16
HAVE
ANY
ENDOCRINE
(
HORMONE)
STUDIES
BEEN
DONE
WITH
YOUR
BLOOD?
YES
NO
If
so,
when?___________________

What
were
the
results?______________________

17
HAVE
YOU
EVER
HAD
A
FERTILITY
INVESTIGATION?

YES
NO
If
so,
what
was
the
diagnosis?

_____
Anatomical
defect
_____
Hormonal/
Glandular
disorder
_____
Other
_____
No
abnormality
found
18
HAVE
YOU
EVER
HAD
SURGERY
FOR
INFERTILITY?

YES
NO
If
so,
give
details:
APPENDIX
E­
Sampling
and
Analytical
Methods
for
2­
Methoxyethanol,
2­
Ethoxyethanol,
and
their
Acetates
This
appendix
describes
the
method
presently
used
at
the
OSHA
Analytical
Laboratory
in
Salt
Lake
City
for
measurement
of
2­
Methoxyethanol,
2­
Ethoxyethanol
and
their
acetates.
The
method
is
the
most
sensitive
method
presently
available
for
measurement
of
employee
exposure.
Inclusion
of
this
method
in
the
appendix
does
not
imply
that
it
is
the
only
one
which
will
be
satisfactory.
Other
methods
may
also
be
acceptable
provided
they
can
determine
these
glycol
ethers
at
the
permissible
exposure
limit
within
+
25%
of
the
"
true"
value
at
the
95%
confidence
level.
Where
applicable,
the
method
must
also
be
able
to
measure
glycol
ethers
at
the
action
level
to
+
35%
of
the
"
true"
value
with
95%
confidence
The
following
is
extracted
from
the
OSHA
Analytical
Laboratory
Method
No.
79.
For
a
more
complete
copy
of
the
method
see
Exhibit
5­
139
Method
number:
79
Matrix:
Air
Procedure:
Samples
are
collected
by
drawing
air
through
standard
size
cocunut
shell
charcoal
tubes.
Samples
are
desorbed
with
95/
5
(
v/)
methylene
choride/
methonal
and
analyzed
by
gas
chromatography
using
a
flame
inonization
detector
Recommended
air48
L
at
0.1
L/
min
for
TWA
samples
volume
and
sampling
15
L
at
1.0
L/
min
for
STEL
samples
rate:

____________________________________________

2ME
2MEA
2EE
2EEA
Target
conc.:

ppm
(
mg/
m3)
0.1
0.1
0.5
0.5
(
0.3)
(
0.5)
(
1.8)
(
2.7)

Reliable
quanti­
6.7
1.7
2.1
1.2
tation
limit:
(
21)
(
8.4)
(
7.8)
6.5)

ppb(
ug/
m3)

Standard
error
of
estimate
at
the
6.0%
5.7%
6.2%
5.7%

target
concentra­

tion:

(
Section
4.7)
Special
requirements:
As
indicated
in
OSHA
Method
53
(
Ref.
5.1.),
samples
for
2MEA
and
2EEA
should
be
refrigerated
upon
receipt
by
the
laboratory
to
minimize
hydrolysis
Status
of
method:
Evaluated
method.
This
method
has
been
subjected
to
the
established
evaluation
procedures
of
the
Organic
Methods
Evaluation
Branch
1.
General
Discussion
1.1.
Background
1.1.1.
History
An
air
sampling
and
analytical
procedure
for
2ME,
2MEA,
2EE,
and
2EEA
(
OSHA
Method
53)
was
previously
evaluated
by
the
Organic
Methods
Evaluation
Branch
of
the
OSHA
Analytical
Laboratory.
(
Ref.
5.1.)
The
target
concentration
for
all
four
analytes
in
that
method
was
5
ppm.
OSHA
is
now
in
the
process
of
6(
b)
rulemaking
to
consider
reducing
occupational
exposure
to
these
glycol
ethers.
Because
the
proposed
exposure
limits
may
be
significantly
lower
than
the
target
concentrations
in
Method
53,
the
methodology
was
re­
evaluated
at
lower
levels
A
number
of
changes
were
made
to
Method
53
to
accommodate
the
lower
target
concentrations
(
1)
The
recommended
air
volume
for
TWA
samples
was
increased
from
10
L
to
48
L.
This
allows
for
lower
detection
limits
and
increases
the
TWA
sampling
time
to
a
more
convenient
480
min
(
8
h)
when
sampling
at
0.1
L/
min
(
2)
A
capillary
GC
column
was
substituted
for
a
packed
column
to
attain
higher
resolution.
This
was
especially
helpful
in
achieving
better
separation
of
2ME
and
methylene
chloride,
a
major
component
of
the
desorption
solvent
(
3)
It
was
found
that
the
desorption
efficiency
from
wet
charcoal
was
significantly
lower
for
2ME,
and
to
a
lesser
extent
for
2EE,
at
these
lower
concentrations.
This
problem
was
overcome
by
adding
about
125
mg
of
anhydrous
magnesium
sulfate
to
each
desorption
vial
to
remove
the
desorbed
water.
Because
charcoal
will
always
collect
some
water
from
sampled
air,
all
2ME
and
2EE
air
samples
must
be
treated
in
this
manner
Utilizing
these
three
major
modifications
of
Method
53,
a
successful
evaluation
was
performed
for
these
glycol
ethers
at
the
lower
target
concentrations.
Also,
a
minor
modification
was
made
in
the
determination
of
desorption
efficiencies.
Aqueous
instead
of
methanolic
stock
solutions
were
used
to
determine
the
desorption
efficiencies
for
2MEA
and
2EEA.
It
was
found
that
at
these
lower
levels,
when
stock
methanolic
solutions
are
spiked
on
dry
Lot
120
charcoal,
part
of
the
2MEA
and
2EEA
react
with
the
methanol
to
form
methyl
acetate
and
2ME
and
2EE
respectively.
The
reaction,
which
is
analogous
to
hydrolysis,
is
called
transesterification
(
alcoholysis)
and
is
catalyzed
by
acid
or
base.
The
surface
of
dry
Lot
120
charcoal
is
basic
and
the
reaction
was
verified
to
occur
by
quantitatively
determining
methyl
acetate
and
the
corresponding
alcohol
(
2ME
for
2MEA
samples,
2EE
for
2EEA
samples)
from
spiked
samples.
Transesterification
was
not
observed
when
methanolic
stock
solutions
were
spiked
onto
wet
charcoal.
Therefore,
transesterification
is
not
expected
to
occur
for
samples
collected
from
workplace
air
containing
methanol
as
well
as
2MEA
or
2EEA
because
workplace
atmospheres
are
seldom
completely
dry
Because
of
the
number
of
modifications
and
the
extensive
amount
of
data
generated
in
this
evaluation,
the
findings
are
presented
as
a
separate
method
instead
of
a
revision
of
Method
53.
This
method
supersedes
Method
53,
although
Method
53
is
still
valid
at
the
higher
analyte
concentrations.
Although
hydrolysis
of
2MEA
and
2EEA
does
not
appear
to
be
a
problem
at
lower
concentrations,
as
a
precautionary
measure,
the
special
requirement
that
2MEA
and
2EEA
samples
should
be
refrigerated
upon
receipt
by
the
laboratory
was
retained
from
Method
53
1.1.2.
Toxic
effects
(
This
section
is
for
information
only
and
should
not
be
taken
as
the
basis
of
OSHA
policy.)

As
reported
in
the
Documentation
of
Threshold
Limit
Values
(
Refs.
5.2.­
5.5.),
all
four
analytes
were
investigated
by
Nagano
et
al.
(
Ref.
5.6.)
in
terms
of
potency
for
testicular
effects.
They
concluded
that
on
an
equimolar
basis,
the
respective
acetate
esters
were
about
as
potent
as
2ME
and
2EE
in
producing
testicular
atrophy
and
leukopenia
(
an
abnormally
low
number
of
white
blood
cells)
in
mice.
Based
on
this
study
and
because
2MEA
and
2EEA
hydrolyze
to
2ME
and
2EE
respectively
in
the
body,
ACGIH
suggests
lowering
the
time­
weighted
TLVs
for
all
four
analytes
to
5
ppm
The
following
is
quoted
from
NIOSH
Current
Intelligence
Bulletin
39.
(
Ref.
5.7.)

The
National
Institute
for
Occupational
Safety
and
Health
(
NIOSH)
recommends
that
2­
methoxyethanol
(
2ME)
and
2­
ethoxyethanol
(
2EE)
be
regarded
in
the
workplace
as
having
the
potential
to
cause
adverse
reproductive
effects
in
male
and
female
workers.
These
recommendations
are
based
on
the
results
of
several
recent
studies
that
have
demonstrated
dose­
related
[
page
15627]

embryotoxicity
and
other
reproductive
effects
in
several
species
of
animals
exposed
by
different
routes
of
administration.
Of
particular
concern
are
those
studies
in
which
exposure
of
pregnant
animals
to
concentrations
of
2ME
or
2EE
at
or
below
their
respective
Occupational
Safety
and
Health
Administration
(
OSHA)
Permissible
Exposure
Limits
(
PELs)
led
to
increased
incidences
of
embryonic
death,
teratogenesis,
or
growth
retardation.
Exposure
of
male
animals
resulted
in
testicular
atrophy
and
sterility.
In
each
case
the
animals
had
been
exposed
to
2ME
or
2EE
at
concentrations
at
or
below
their
respective
OSHA
PELs.
Therefore,
appropriate
controls
should
be
instituted
to
minimize
worker
exposure
to
both
compounds.

On
May
20,
1986,
EPA
referred
these
four
analytes
to
OSHA
in
accordance
with
the
Toxic
Substances
Control
Act
(
TSCA).
On
April
2,
1987,
OSHA
issued
an
Advanced
Notice
of
Proposed
Rulemaking
(
ANPR)
which
summarized
the
information
currently
available
to
OSHA
concerning
the
uses,
health
effects,
estimates
of
employee
exposure
and
risk
determinations
for
these
glycol
ethers.
OSHA
invited
comments
from
interested
parties
and
based
on
the
gathered
information
will
decide
on
appropriate
action.
(
Ref.
5.8.)
1.1.3.
Workplace
exposure
2ME­
It
is
used
as
a
solvent
for
many
purposes:
cellulose
esters,
dyes,
resins,
lacquers,
varnishes,
and
stains;
and
as
a
perfume
fixative
and
jet
fuel
deicing
additive.
(
Ref.
5.2.)

2MEA­
It
is
used
in
photographic
films,
lacquers,
textile
printing,
and
as
a
solvent
for
waxes,
oils,
various
gums
and
resins,
cellulose
acetate,
and
nitrocellulose.
(
Ref.
5.3.)

2EE­
It
is
used
as
a
solvent
for
nitrocellulose,
natural
and
synthetic
resins,
and
as
a
mutual
solvent
for
the
formulation
of
soluble
oils.
It
is
also
used
in
lacquers,
in
the
dyeing
and
printing
of
textiles,
in
varnish
removers,
cleaning
solutions,
in
products
for
the
treatment
of
leather,
and
as
an
anti­
icing
additive
for
aviation
fuels.
(
Ref.
5.4.)

2EEA­
It
is
used
as
a
blush
retardant
in
lacquers;
as
a
solvent
for
nitrocellulose,
oils
and
resins;
in
wood
stains,
varnish
removers,
and
in
products
for
the
treatment
of
textiles
and
leathers.
(
Ref.
5.5.)

1.1.4.
Physical
properties
(
Refs.
5.2.­
5.5.)

chemical
formulae:

2ME­
CH3OCH2CH2OH
2MEA­
CH3OCH2CH2OOCCH3
2EE­
CH3CH2OCH2CH2OH
2EEA­
CH3CH2OCH2CH2OOCCH3
synonyms:
(
Ref.
5.9.)

2ME­
methyl
Cellosolve;
glycol
monomethyl
ether;
ethylene
glycol
monomethyl
ether;
methyl
oxitol;
Ektasolve;
Jeffersol
EM;

2MEA­
methyl
Cellosolve
acetate;
glycol
monomethyl
ether
acetate;
ethylene
glycol
monomethyl
ether
acetate
2EE­
Cellosolve
solvent;
ethylene
glycol
monoethyl
ether
2EEA­
Cellosolve
acetate;
glycol
monoethyl
ether
acetate;
ethylene
glycol
monoethyl
ether
acetate
________________________________________________________

2ME
2MEA
2EE
2EEA
________________________________________________________
CAS
number:
109­
86­
4
110­
49­
6
110­
80­
5
11­
15­
9
Molecular
Wt.:
76.09
118.13
90.11
132.16
Boiling
Point:
124.5oC
145oC
135.6oC
156.4oC
Color:
colorless
colorless
colorless
colorless
Specific
Gravity:
0.9663f
1.005
0.931
0.975
Vapor
Press­

ure
at
20oC:
0.8
kPa
0.3
kPa
0.49
kPa
0.3
kPa
Flash
Point,

closed
cup:
43oC
49oC
40oC
49oC
Odor:
mild,
mild,
sweetish
mild
(
Ref.
5.9)
nonresid­
ether­
nonresid­

ual
like
ual
Explosive
Limits:

(
ref.
5.9)

Lower:
2.5%
1.1%
1.8%
1.7%

Upper:
19.8%
8.2%
14%
?

The
analyte
air
concentrations
throughout
this
method
are
based
on
the
recommended
TWA­
sampling
and
analytical
parameters.
Air
concentrations
listed
in
ppm
and
ppb
are
referenced
to
25
C
and
101.3
kPa
(
760
mm
Hg.)
1.2.
Limit
defining
parameters
1.2.1.
Detection
limit
of
the
analytical
procedure
The
detection
limits
of
the
analytical
procedure
are
0.10,
0.04,
0.04,
and
0.03
ng
per
injection
(
1.0­
L
injection
with
a
10:
1
split)
for
2ME,
2MEA,
2EE,
and
2EEA
respectively.
These
are
the
amounts
of
each
analyte
that
will
give
peaks
with
heights
approximately
5
times
the
height
of
baseline
noise.
(
Section
4.1.)
1.2.2.
Detection
limit
of
the
overall
procedure.
The
detection
limits
of
the
overall
procedure
are
1.0,
0.40,
0.37,
and
0.31
g
per
sample
for
2ME,
2MEA,
2EE,
and
2EEA
respectively.
These
are
the
amounts
of
each
analyte
spiked
on
the
sampling
device
that
allow
recovery
of
amounts
of
each
analyte
equivalent
to
the
detection
limits
of
the
analytical
procedure.
These
detection
limits
correspond
to
air
concentrations
of
6.7
ppb
(
21
g/
m),
1.7
ppb
(
8.4
g/
m),
2.1
ppb
(
7.8
g/
m),
and
1.2
ppb
(
6.5
g/
m)
for
2ME,
2MEA,
2EE,
and
2EEA
respectively.
(
Section
4.2.)
1.2.3.
Reliable
quantitation
limit
The
reliable
quantitation
limits
are
the
same
as
the
detection
limits
of
the
overall
procedure
because
the
desorption
efficiencies
are
essentially
100%
at
these
levels.
These
are
the
smallest
amounts
of
each
analyte
that
can
be
quantitated
within
the
requirements
of
recoveries
of
at
least
75%
and
precisions
(+/­
1.96
SD)
of
+/­
25%
or
better.
(
Section
4.3.)
The
reliable
quantitation
limits
and
detection
limits
reported
in
the
method
are
based
upon
optimization
of
the
GC
for
the
smallest
possible
amounts
of
each
analyte.
When
the
target
concentration
of
an
analyte
is
exceptionally
higher
than
these
limits,
they
may
not
be
attainable
at
the
routine
operating
parameters.
1.2.4.
Instrument
response
to
the
analyte
The
instrument
response
over
the
concentration
ranges
of
0.5
to
2
times
the
target
concentrations
is
linear
for
all
four
analytes.
(
Section
4.4.)
1.2.5.
Recovery
The
recovery
of
2ME,
2MEA,
2EE,
and
2EEA
from
samples
used
in
a
15­
day
storage
test
remained
above
84,
87,
84,
and
85%
respectively
when
the
samples
were
stored
at
ambient
temperatures.
The
recovery
of
analyte
from
the
collection
medium
after
storage
must
be
75%
or
greater.
(
Section
4.5.,
from
regression
lines
shown
in
Figures
4.5.1.2.,
4.5.2.2.,
4.5.3.2.
and
4.5.4.2.)
1.2.6.
Precision
(
analytical
procedure)

The
pooled
coefficients
of
variation
obtained
from
replicate
determinations
of
analytical
standards
at
0.5,
1,
and
2
times
the
target
concentrations
are
0.022,
0.004,
0.002,
and
0.002
for
2ME,
2MEA,
2EE,
and
2EEA
respectively.
(
Section
4.6.)
1.2.7.
Precision
(
overall
procedure)

The
precisions
at
the
95%
confidence
level
for
the
ambient
temperature
15­
day
storage
tests
are
+/­
11.7,
+/­
11.1,
+/­
12.3,
and
+/­
11.2%
for
2ME,
2MEA,
2EE,
and
2EEA
respectively.
These
include
an
additional
+/­
5%
for
sampling
error.
The
overall
procedure
must
provide
results
at
the
target
concentration
that
are
+/­
25%
or
better
at
the
95%
confidence
level.
(
Section
4.7.)
1.2.8.
Reproducibility
Six
samples
for
each
analyte
collected
from
controlled
test
atmospheres
and
a
draft
copy
of
this
procedure
were
given
to
a
chemist
unassociated
with
this
evaluation.
The
samples
were
analyzed
after
12
days
of
refrigerated
storage.
No
individual
sample
result
deviated
from
its
theoretical
value
by
more
than
the
precision
reported
in
Section
1.2.7.
(
Section
4.8.)

1.3.
Advantages
1.3.1.
Charcoal
tubes
provide
a
convenient
method
for
sampling
1.3.2.
The
analysis
is
rapid,
sensitive,
and
precise
1.4.
Disadvantage
It
may
not
be
possible
to
analyze
co­
collected
solvents
using
this
method.
Most
of
the
other
common
solvents
which
are
collected
on
charcoal
are
analyzed
after
desorption
with
carbon
disulfide
2.
Sampling
Procedure
[
page
15628]

2.1.
Apparatus
2.1.1.
Samples
are
collected
using
a
personal
sampling
pump
calibrated
to
within
+/­
5%
of
the
recommended
flow
rate
with
a
sampling
tube
in
line
2.1.2.
Samples
are
collected
with
solid
sorbent
sampling
tubes
containing
coconut
shell
charcoal.
Each
tube
consists
of
two
sections
of
charcoal
separated
by
a
urethane
foam
plug.
The
front
section
contains
100
mg
of
charcoal
and
the
back
section,
50
mg.
The
sections
are
held
in
place
with
glass
wool
plugs
in
a
glass
tube
4­
mm
i.
d.
x
70­
mm
length.
For
this
evaluation,
SKC
Inc.
charcoal
tubes
(
catalog
number
226­
01,
Lot
120)
were
used.
2.2.
Reagents
None
required
2.3.
Technique
2.3.1.
Immediately
before
sampling,
break
off
the
ends
of
the
charcoal
tube.
All
tubes
should
be
from
the
same
lot
2.3.2.
Connect
the
sampling
tube
to
the
sampling
pump
with
flexible
tubing.
Position
the
tube
so
that
sampled
air
first
passes
through
the
100­
mg
section
2.3.3.
Air
being
sampled
should
not
pass
through
any
hose
or
tubing
before
entering
the
sampling
tube
2.3.4.
Place
the
sampling
tube
vertically
(
to
avoid
channeling)
in
the
employee's
breathing
zone
2.3.5.
After
sampling,
seal
the
tubes
immediately
with
plastic
caps
and
wrap
lengthwise
with
OSHA
Form
21
2.3.6.
Submit
at
least
one
blank
sampling
tube
with
each
sample
set.
Blanks
should
be
handled
in
the
same
manner
as
samples,
except
no
air
is
drawn
through
them
2.3.7.
Record
sample
volumes
(
in
liters
of
air)
for
each
sample,
along
with
any
potential
interferences
2.3.8.
Ship
any
bulk
sample(
s)
in
a
container
separate
from
the
air
samples.
2.4.
Sampler
capacity
2.4.1.
Sampler
capacity
is
determined
by
measuring
how
much
air
can
be
sampled
before
breakthrough
of
analyte
occurs,
i.
e.,
the
sampler
capacity
is
exceeded.
Individual
breakthrough
studies
were
performed
on
each
of
the
four
analytes
by
monitoring
the
effluent
from
sampling
tubes
containing
only
the
100­
mg
section
of
charcoal
while
sampling
at
0.2
L/
min
from
atmospheres
containing
10
ppm
analyte.
The
atmospheres
were
at
approximately
80%
relative
humidity
and
20­
25
C.
No
breakthrough
was
detected
in
any
of
the
studies
after
sampling
for
at
least
6
h
(>
70
L).
(
This
data
was
collected
in
the
evaluation
of
OSHA
Method
53,
Ref.
5.1.)
2.4.2.
A
similar
study
as
in
2.4.1.
was
done
while
sampling
an
atmosphere
containing
10
ppm
of
all
four
analytes.
The
atmosphere
was
sampled
for
more
than
5
h
(>
60
L)
with
no
breakthrough
detected.
(
This
data
was
collected
in
the
evaluation
of
OSHA
Method
53,
Ref.
5.1.)
2.5.
Desorption
efficiency
2.5.1.
The
average
desorption
efficiencies
of
2ME,
2MEA,
2EE,
and
2EEA
from
Lot
120
charcoal
are
95.8,
97.9,
96.5,
and
98.3%
respectively
over
the
range
of
0.5
to
2
times
the
target
concentrations.
Desorption
samples
for
2MEA
and
2EEA
must
not
be
determined
by
using
methanolic
stock
solutions
since
a
transesterification
reaction
can
occur.
(
Section
4.9.)

2.5.2.
Desorbed
samples
remain
stable
for
at
least
24
h.
(
Section
4.10.)
2.6.
Recommended
air
volume
and
sampling
rate
2.6.1.
For
TWA
samples,
the
recommended
air
volume
is
48
L
collected
at
0.1
L/
min
(
8­
h
samples)

2.6.2.
For
short­
term
samples,
the
recommended
air
volume
is
15
L
collected
at
1.0
L/
min
(
15­
min
samples)

2.6.3.
When
short­
term
samples
are
required,
the
reliable
quantitation
limits
become
larger.
For
example,
the
reliable
quantitation
limit
is
21
ppb
(
67
ug/
m3)
for
2ME
when
15
L
is
sampled.
2.7.
Interferences
(
sampling)

2.7.1.
It
is
not
known
if
any
compound(
s)
will
severely
interfere
with
the
collection
of
any
of
the
four
analytes
on
charcoal.
In
general,
the
presence
of
other
contaminant
vapors
in
the
air
will
reduce
the
capacity
of
charcoal
to
collect
the
analytes
2.7.2.
Suspected
interferences
should
be
reported
to
the
laboratory
with
submitted
samples.
2.8.
Safety
precautions
(
sampling)

2.8.1.
Attach
the
sampling
equipment
to
the
employee
so
that
it
will
not
interfere
with
work
performance
or
safety
2.8.2.
Wear
eye
protection
when
breaking
the
ends
of
the
charcoal
tubes
2.8.3.
Follow
all
safety
procedures
that
apply
to
the
work
area
being
sampled
3.
Analytical
Procedure
3.1.
Apparatus
3.1.1.
A
GC
equipped
with
a
flame
ionization
detector.
For
this
evaluation,
a
Hewlett­
Packard
5890
Series
II
Gas
Chromatograph
equipped
with
a
7673A
Automatic
Sampler
was
used
3.1.2.
A
GC
column
capable
of
separating
the
analyte
of
interest
from
the
desorption
solvent,
internal
standard
and
any
interferences.
A
thick
film,
60­
m
X
0.32­
mm
i.
d.,
fused
silica
RTx­
Volatiles
column
(
Cat.
no.
10904,
Restek
Corp.,
Bellefonte,
PA)
was
used
in
this
evaluation
3.1.3.
An
electronic
integrator
or
some
other
suitable
means
of
measuring
peak
areas
or
heights.
A
Hewlett­
Packard
18652A
A/
D
converter
interfaced
to
a
Hewlett­
Packard
3357
Lab
Automation
Data
System
was
used
in
this
evaluation.
3.1.4.
Two­
milliliter
vials
with
Teflon­
lined
caps
3.1.5.
A
dispenser
capable
of
delivering
1.0
mL
to
prepare
standards
and
samples.
If
a
dispenser
is
not
available,
a
1.0­
mL
volumetric
pipet
may
be
used
3.1.6.
Syringes
of
various
sizes
for
preparation
of
standards
3.1.7.
Volumetric
flasks
and
pipets
to
dilute
the
pure
analytes
in
preparation
of
standards.
3.2.
Reagents
3.2.1.
2­
Methoxyethanol,
2­
methoxyethyl
acetate,
2­
ethoxyethanol,
and
2­
ethoxyethyl
acetate,
reagent
grade.
Aldrich
Lot
HB062777
2ME,
Eastman
Lot
701­
2
2MEA,
Aldrich
Lot
DB040177
2EE,
and
Aldrich
Lot
04916HP
2EEA
were
used
in
this
evaluation
3.2.2.
Anhydrous
magnesium
sulfate,
reagent
grade.
Chempure
Lot
M172
KDHM
was
used
in
this
evaluation
3.2.3.
Methylene
chloride,
chromatographic
grade.
American
Burdick
and
Jackson
Lot
AQ098
was
used
in
this
evaluation
3.2.4.
Methanol,
chromatographic
grade.
American
Burdick
and
Jackson
Lot
AT015
was
used
in
this
evaluation
3.2.5.
A
suitable
internal
standard,
reagent
grade.
"
Quant
Grade"
3­
methyl­
3­
pentanol
from
Polyscience
Corporation
was
used
in
this
evaluation
3.2.6.
The
desorption
solvent
consists
of
methylene
chloride/
methanol,
95/
5
(
v/
v)
containing
an
internal
standard
at
a
concentration
of
20
uL/
L.
3.2.7
GC
grade
nitrogen,
air,
and
hydrogen.
3.3.
Standard
preparation
3.3.1.
Prepare
concentrated
stock
standards
by
diluting
the
pure
analytes
with
methanol.
Prepare
working
standards
by
injecting
microliter
amounts
of
concentrated
stock
standards
into
vials
containing
1.0
mL
of
desorption
solvent
delivered
from
the
same
dispenser
used
to
desorb
samples.
For
example,
to
prepare
a
stock
standard
of
2ME,
dilute
195
uL
of
pure
2ME
(
sp
gr
=
0.9663)
to
50.0
mL
with
methanol.
This
stock
solution
would
contain
3.769
ug/
uL.
A
working
standard
of
15.08
ug/
sample
is
prepared
by
injecting
4.0
uL
of
this
stock
into
a
vial
containing
1.0
mL
of
desorption
solvent
3.3.2.
Bracket
sample
concentrations
with
working
standard
concentrations.
If
samples
fall
outside
of
the
concentration
range
of
prepared
standards,
prepare
and
analyze
additional
standards
to
ascertain
the
linearity
of
response.
3.4.
Sample
preparation
3.4.1.
Transfer
each
section
of
the
samples
to
separate
vials.
Discard
the
glass
tubes
and
plugs
3.4.2.
For
2ME
and
2EE
samples,
add
about
125
mg
of
magnesium
sulfate
to
each
vial
3.4.3.
Add
1.0
mL
of
desorption
solvent
to
each
vial
using
the
same
dispenser
as
used
for
preparation
of
standards
3.4.4.
Immediately
cap
the
vials
and
shake
them
periodically
for
about
30
min
3.5.
Analysis
3.5.1
GC
conditions
zone
temperatures:
column­
80
C
for
4
min
10
C/
min
to
125
C
125
C
for
4
min
injector­
150
C
detector­
200
C
gas
flows:
hydrogen
(
carrier)­
2.5
mL/
min
(
80
kPa
head
pressure)

nitrogen
(
makeup)­
20
mL/
min
hydrogen
(
flame)­
65
mL/
min
air­
400
mL/
min
injection
volume:
1.0
uL
(
with
a
10:
1
split)

column:
60­
m
X
0.32­
mm
i.
d.
fused
silica,

RTx­
Volatiles,
thick
film
retention
times:
2ME­
5.0
min
2MEA­
10.0
min
2EE­
6.7
min
2EEA­
11.9
min
(
3­
methyl­
3­
pentanol­
7.5
min)

3.5.2.
Peak
areas
(
or
heights)
are
measured
by
an
integrator
or
other
suitable
means
3.5.3.
An
internal
standard
(
ISTD)
calibration
method
is
used.
Calibration
[
page
15629]

curves
are
prepared
by
plotting
micrograms
of
analyte
per
sample
versus
ISTD­
corrected
response
of
standard
injections.
Sample
concentrations
must
be
bracketed
by
standards.
3.6.
Interferences
(
analytical)

3.6.1.
Any
compound
that
responds
on
a
flame
ionization
detector
and
has
the
same
general
retention
time
of
the
analyte
or
internal
standard
is
a
potential
interference.
Possible
interferences
should
be
reported
to
the
laboratory
with
submitted
samples
by
the
industrial
hygienist.
These
interferences
should
be
considered
before
samples
are
desorbed
3.6.2.
GC
parameters
(
i.
e.
column
and
column
temperature)
may
be
changed
to
possibly
circumvent
interferences
3.6.3.
Retention
time
on
a
single
column
is
not
considered
proof
of
chemical
identity.
Analyte
identity
should
be
confirmed
by
GC/
mass
spectrometer
if
possible.
3.7.
Calculations
The
analyte
concentration
for
samples
is
obtained
from
the
appropriate
calibration
curve
in
terms
of
micrograms
of
analyte
per
sample,
uncorrected
for
desorption
efficiency.
The
air
concentration
is
calculated
using
the
following
formulae.
The
back
(
50­
mg)
section
is
analyzed
primarily
to
determine
if
there
was
any
breakthrough
from
the
front
(
100­
mg)
section
during
sampling.
If
a
significant
amount
of
analyte
is
found
on
the
back
section
(
e.
g.,
greater
than
25%
of
the
amount
found
on
the
front
section),
this
fact
should
be
reported
with
sample
results.
If
any
analyte
is
found
on
the
back
section,
it
is
added
to
the
amount
found
on
the
front
section.
This
total
amount
is
then
corrected
by
subtracting
the
total
amount
(
if
any)
found
on
the
blank
(
ug
of
analyte
per
sample)

mg/
m3
=
(
L
of
air
sampled)(
desorption
efficiency)

where
desorption
efficiency=
0.958
for
2ME
0.979
for
2MEA
0.965
for
2EE
0.983
for
2EEA
ppm
=
(
mg/
m3)(
24.46)/(
molecular
weight
of
analyte)
where
24.46
is
the
molar
volume
at
25
C
and
101.3
kPa
(
760
mmHg)

and
molecular
weights
=
76.09
for
2ME,
118.13
for
2MEA
90.11
for
2EE,
132.16
for
2EEA
3.8
Safety
precautions
(
analytical)

3.8.1.
Avoid
skin
contact
and
inhalation
of
all
chemicals
3.8.2.
Restrict
the
use
of
all
chemicals
to
a
fume
hood
when
possible
3.8.3.
Wear
safety
glasses
and
a
lab
coat
at
all
times
while
in
the
lab
area
4.
Backup
Data
(
For
backup
data
see
Section
4
of
OSHA
Analytical
Method
Number
79,
Exhibit
5­
139)

5.
References
5.1
"
OSHA
Analytical
Methods
Manual"
U.
S.
Department
of
Labor,
Occupational
Safety
and
Health
Administration;
OSHA
Analytical
Laboratory:
Salt
Lake
City,
UT,
1985;
Method
53;
American
Conference
of
Governmental
Industrial
Hygienists
(
ACGIH):
Cincinnati,
OH,
ISBN:
0­
936712­
66­
X
5.2
"
American
Conference
of
Governmental
Industrial
Hygienists:
Documentation
of
the
Threshold
Limit
Values,
Supplemental
Documentation
for
1982",

pp.
259­
260,
Cincinnati,
OH
(
1982)

5.3
"
American
Conference
of
Governmental
Industrial
Hygienists:
Documentation
of
the
Threshold
Limit
Values,
Supplemental
Documentation
for
1982",
p
260,
Cincinnati,
OH
(
1982)

5.4
"
American
Conference
of
Governmental
Industrial
Hygienists:
Documentation
of
the
Threshold
Limit
Values,
Supplemental
Documentation
for
1982",
p
171,
Cincinnati,
OH
(
1982)

5.5
"
American
Conference
of
Governmental
Industrial
Hygienists:
Documentation
of
the
Threshold
Limit
Values,
Supplemental
Documentation
for
1982",
p
172,
Cincinnati,
OH
(
1982)

5.6
Nagano,
K.;
Nakayama,
E.;
Koyano,
M.;
Oobayaski,

H.;
Adachi,
H.;
Yamada,
T.
Jap.
J.
Ind.
Health
1979,
21,
29­
35
5.7
"
Current
Intelligence
Bulletin
39,
Glycol
Ethers";
May
2,
1983,
U.
S.
Department
of
Health
and
Human
Services,
Public
Health
Service,

Center
for
Disease
Control,
NIOSH
5.8
Fed.
Regist.
1987,
52
(
No.
63,
Thursday,
April
2),
10586­
10593
5.9
"
Pocket
Guide
to
Chemical
Hazards",
NIOSH/
OSHA,

Sept.
1978,
DHEW
(
NIOSH)
Publ.
No.
78­
210
APPENDIX
F
­
Qualitative
and
Quantitative
Fit
Testing
Procedures­
Mandatory
I.
Fit
Test
Protocols
A.
The
employer
shall
include
the
following
provisions
in
the
fit
test
procedures.
These
provisions
apply
to
both
qualitative
fit
testing
(
QLFT)
and
quantitative
fit
testing
(
QNFT)

1.
The
test
subject
shall
be
allowed
to
pick
the
most
comfortable
respirator
from
a
selection
including
respirators
of
various
sizes
from
different
manufacturers.
The
selection
shall
include
at
least
three
sizes
of
elastomeric
facepieces
of
the
type
of
respirator
that
is
to
be
tested,
i.
e.,
three
sizes
of
half
mask;
or
three
sizes
of
full
facepiece;
and
units
from
at
least
two
manufacturers
2.
Prior
to
the
selection
process,
the
test
subject
shall
be
shown
how
to
put
on
a
respirator,
how
it
should
be
positioned
on
the
face,
how
to
set
strap
tension
and
how
to
determine
a
comfortable
fit.
A
mirror
shall
be
available
to
assist
the
subject
in
evaluating
the
fit
and
positioning
the
respirator.
This
instruction
may
not
constitute
the
subject's
formal
training
on
respirator
use,
as
it
is
only
a
review
3.
The
test
subject
shall
be
informed
that
he/
she
is
being
asked
to
select
the
respirator
which
provides
the
most
comfortable
fit.
Each
respirator
represents
a
different
size
and
shape,
and
if
fitted
and
used
properly,
will
provide
adequate
protection
4.
The
test
subject
shall
be
instructed
to
hold
each
facepiece
up
to
the
face
and
eliminate
those
which
obviously
do
not
give
a
comfortable
fit
5.
The
more
comfortable
facepieces
are
noted;
the
most
comfortable
mask
is
donned
and
worn
at
least
five
minutes
to
assess
comfort.
Assistance
in
assessing
comfort
can
be
given
by
discussing
the
points
in
item
6
below.
If
the
test
subject
is
not
familiar
with
using
a
particular
respirator,
the
test
subject
shall
be
directed
to
don
the
mask
several
times
and
to
adjust
the
straps
each
time
to
become
adept
at
setting
proper
tension
on
the
straps
6.
Assessment
of
comfort
shall
include
reviewing
the
following
points
with
the
test
subject
and
allowing
the
test
subject
adequate
time
to
determine
the
comfort
of
the
respirator:
(
a)
position
of
the
mask
on
the
nose
(
b)
room
for
eye
protection
(
c)
room
to
talk
(
d)
position
of
mask
on
face
and
cheeks
7.
The
following
criteria
shall
be
used
to
help
determine
the
adequacy
of
the
respirator
fit:
(
a)
chin
properly
placed;
(
b)
adequate
strap
tension,
not
overly
tightened;
(
c)
fit
across
nose
bridge;

(
d)
respirator
of
proper
size
to
span
distance
from
nose
to
chin;
(
e)
tendency
of
respirator
to
slip;

(
f)
self­
observation
in
mirror
to
evaluate
fit
and
respirator
position
8.
The
test
subject
shall
conduct
the
negative
and
positive
pressure
fit
checks
as
described
below
or
ANSI
Z88.2­
1980.
Before
conducting
the
negative
or
positive
pressure
test,
the
subject
shall
be
told
to
seat
the
mask
on
the
face
by
moving
the
head
from
side­
to­
side
and
up
and
down
slowly
while
taking
in
a
few
slow
deep
breaths.
Another
facepiece
shall
be
selected
and
retested
if
the
test
subject
fails
the
fit
check
tests
(
a).
Positive
pressure
test.
Close
off
the
exhalation
valve
and
exhale
gently
onto
the
facepiece.
The
face
fit
is
considered
satisfactory
if
a
slight
positive
pressure
can
be
built
up
inside
the
facepiece
without
any
evidence
of
outward
leakage
of
air
at
the
seal
For
most
respirators
this
method
of
leak
testing
requires
the
wearer
to
first
remove
the
exhalation
valve
cover
before
closing
off
the
exhalation
valve
and
then
carefully
replacing
it
after
the
test
(
b).
Negative
pressure
test.
Close
off
the
inlet
opening
of
the
canister
or
cartridge(
s)
by
covering
with
the
palm
of
the
hand(
s)
or
by
replacing
the
filter
seal(
s),
inhale
gently
so
that
the
facepiece
collapses
slightly,
and
hold
the
breath
for
ten
seconds.
If
the
facepiece
remains
in
its
slightly
collapsed
condition
and
no
inward
leakage
of
air
is
detected,
the
tightness
of
the
respirator
is
considered
satisfactory
9.
The
test
shall
not
be
conducted
if
there
is
any
hair
growth
between
the
skin
and
the
facepiece
sealing
surface,
such
as
stubble
beard
growth,
beard,
or
long
sideburns
which
cross
the
respirator
sealing
surface.
Any
type
of
apparel
which
interferes
with
a
satisfactory
fit
shall
be
altered
or
removed
10.
If
a
test
subject
exhibits
difficulty
in
breathing
during
the
tests,
she
or
he
shall
be
referred
to
a
physician
trained
in
respiratory
disease
or
pulmonary
medicine
to
determine
whether
the
test
subject
can
wear
a
respirator
while
performing
her
or
his
duties
11.
The
test
subject
shall
be
given
the
opportunity
to
wear
the
successfully
fitted
[
page
15630]

respirator
for
a
period
of
two
weeks.
If
at
any
time
during
this
period
the
respirator
becomes
uncomfortable,
the
test
subject
shall
be
given
the
opportunity
to
select
a
different
facepiece
and
to
be
retested
12.
The
employer
shall
certify
that
a
successful
fit
test
has
been
administered
to
the
employee.
The
certification
shall
include
the
following
information:
(
a)
Name
of
employee;
(
b)
Type,
brand
and
size
of
respirator;
and
(
c)
Date
of
test;

(
e)
Where
QNFT
is
used,
the
fit
factor,
strip
chart,
or
other
recording
of
the
results
of
the
test,
shall
be
retained
with
the
certification.
The
certification
shall
be
maintained
until
the
next
fit
test
is
administered
13.
Exercise
regimen.
Prior
to
the
commencement
of
the
fit
test,
the
test
subject
shall
be
given
a
description
of
the
fit
test
and
the
test
subject's
responsibilities
during
the
test
procedure.
The
description
of
the
process
shall
include
a
description
of
the
test
exercises
that
the
subject
will
be
performing.
The
respirator
to
be
tested
shall
be
worn
for
at
least
5
minutes
before
the
start
of
the
fit
test
14.
Test
Exercises.
The
test
subject
shall
perform
exercises,
in
the
test
environment,
in
the
manner
described
below:

(
a)
Normal
breathing.
In
a
normal
standing
position,
without
talking,
the
subject
shall
breathe
normally
(
b)
Deep
breathing.
In
a
normal
standing
position,
the
subject
shall
breathe
slowly
and
deeply,
taking
caution
so
as
to
not
hyperventilate
(
c)
Turning
head
side
to
side.
Standing
in
place,
the
subject
shall
slowly
turn
his/
her
head
from
side
to
side
between
the
extreme
positions
on
each
side.
The
head
shall
be
held
at
each
extreme
momentarily
so
the
subject
can
inhale
at
each
side
(
d)
Moving
head
up
and
down.
Standing
in
place,
the
subject
shall
slowly
move
his/
her
head
up
and
down.
The
subject
shall
be
instructed
to
inhale
in
the
up
position
(
i.
e.,
when
looking
toward
the
ceiling)

(
e)
Talking.
The
subject
shall
talk
out
loud
slowly
and
loud
enough
so
as
to
be
heard
clearly
by
the
test
conductor.
The
subject
can
read
from
a
prepared
text
such
as
the
Rainbow
Passage,
count
backward
from
100,
or
recite
a
memorized
poem
or
song
(
f)
Grimace.
The
test
subject
shall
grimace
by
smiling
or
frowning
(
g)
Bending
over.
The
test
subject
shall
bend
at
the
waist
as
if
he/
she
were
to
touch
his/
her
toes.
Jogging
in
place
shall
be
substituted
for
this
exercise
in
those
test
environments
such
as
shroud
type
QNFT
units
which
prohibit
bending
at
the
waist
(
h)
Normal
breathing.
Same
as
exercise
1.
Each
test
exercise
shall
be
performed
for
one
minute
except
for
the
grimace
exercise
which
shall
be
performed
for
15
seconds
The
test
subject
shall
be
questioned
by
the
test
conductor
regarding
the
comfort
of
the
respirator
upon
completion
of
the
protocol.
If
it
has
become
uncomfortable,
another
model
of
respirator
shall
be
tried
B.
Qualitative
Fit
Test
(
QLFT)
Protocols
1.
General
(
a)
The
employer
shall
assign
specific
individuals
who
shall
assume
full
responsibility
for
implementing
the
respirator
qualitative
fit
test
program
(
b)
The
employer
shall
ensure
that
persons
administering
QLFT
are
able
to
prepare
test
solutions,
calibrate
equipment
and
perform
tests
properly,
recognize
invalid
tests,
and
assure
that
test
equipment
is
in
proper
working
order
(
c)
The
employer
shall
assure
that
QLFT
equipment
is
kept
clean
and
well
maintained
so
as
to
operate
at
the
parameters
for
which
it
was
designed
2.
Isoamyl
Acetate
Protocol
(
a)
Odor
threshold
screening.
The
odor
threshold
screening
test,
performed
without
wearing
a
respirator,
is
intended
to
determine
if
the
individual
tested
can
detect
the
odor
of
isoamyl
acetate.
(
1)
Three
1­
liter
glass
jars
with
metal
lids
are
required
(
2)
Odor
free
water
(
e.
g.
distilled
or
spring
water)
at
approximately
25
degrees
C
shall
be
used
for
the
solutions
(
3)
The
isoamyl
acetate
(
IAA)
(
also
known
at
isopentyl
acetate)
stock
solution
is
prepared
by
adding
1
cc
of
pure
IAA
to
800
cc
of
odor
free
water
in
a
1
liter
jar
and
shaking
for
30seconds.
A
new
solution
shall
be
prepared
at
least
weekly
(
4)
The
screening
test
shall
be
conducted
in
a
room
separate
from
the
room
used
for
actual
fit
testing.
The
two
rooms
shall
be
well
ventilated
but
shall
not
be
connected
to
the
same
recirculating
ventilation
system
(
5)
The
odor
test
solution
is
prepared
in
a
second
jar
by
placing
0.4
cc
of
the
stock
solution
into
500
cc
of
odor
free
water
using
a
clean
dropper
or
pipette.
The
solution
shall
be
shaken
for
30
seconds
and
allowed
to
stand
for
two
to
three
minutes
so
that
the
IAA
concentration
above
the
liquid
may
reach
equilibrium.
This
solution
shall
be
used
for
only
one
day
(
6)
A
test
blank
shall
be
prepared
in
a
third
jar
by
adding
500
cc
of
odor
free
water
(
7)
The
odor
test
and
test
blank
jars
shall
be
labeled
1
and
2
for
jar
identification.
Labels
shall
be
placed
on
the
lids
so
they
can
be
periodically
peeled,
dried
off
and
switched
to
maintain
the
integrity
of
the
test
(
8)
The
following
instruction
shall
be
typed
on
a
card
and
placed
on
the
table
in
front
of
the
two
test
jars
(
i.
e.,
1
and
2):
"
The
purpose
of
this
test
is
to
determine
if
you
can
smell
banana
oil
at
a
low
concentration.
The
two
bottles
in
front
of
you
contain
water.
One
of
these
bottles
also
contains
a
small
amount
of
banana
oil.
Be
sure
the
covers
are
on
tight,
then
shake
each
bottle
for
two
seconds.
Unscrew
the
lid
of
each
bottle,
one
at
a
time,
and
sniff
at
the
mouth
of
the
bottle.
Indicate
to
the
test
conductor
which
bottle
contains
banana
oil."

(
9)
The
mixtures
used
in
the
IAA
odor
detection
test
shall
be
prepared
in
an
area
separate
from
where
the
test
is
performed,
in
order
to
prevent
olfactory
fatigue
in
the
subject
(
10)
If
the
test
subject
is
unable
to
correctly
identify
the
jar
containing
the
odor
test
solution,
the
IAA
qualitative
fit
test
shall
not
be
performed
(
11)
If
the
test
subject
correctly
identifies
the
jar
containing
the
odor
test
solution,
the
test
subject
may
proceed
to
respirator
selection
and
fit
testing.
(
b)
Isoamyl
acetate
fit
test
(
1)
The
fit
test
chamber
shall
be
similar
to
a
clear
55­
gallon
drum
liner
suspended
inverted
over
a
2­
foot
diameter
frame
so
that
the
top
of
the
chamber
is
about
6
inches
above
the
test
subject's
head.
The
inside
top
center
of
the
chamber
shall
have
a
small
hook
attached
(
2)
Each
respirator
used
for
the
fitting
and
fit
testing
shall
be
equipped
with
organic
vapor
cartridges
or
offer
protection
against
organic
vapors.
The
cartridges
or
masks
shall
be
changed
at
least
weekly
(
3)
After
selecting,
donning,
and
properly
adjusting
a
respirator,
the
test
subject
shall
wear
it
to
the
fit
testing
room.
This
room
shall
be
separate
from
the
room
used
for
odor
threshold
screening
and
respirator
selection,
and
shall
be
well
ventilated,
as
by
an
exhaust
fan
or
lab
hood,
to
prevent
general
room
contamination
(
4)
A
copy
of
the
test
exercises
and
any
prepared
text
from
which
the
subject
is
to
read
shall
be
taped
to
the
inside
of
the
test
chamber
(
5)
Upon
entering
the
test
chamber,
the
test
subject
shall
be
given
a
6­
inch
by
5­
inch
piece
of
paper
towel,
or
other
porous,
absorbent,
single­
ply
material,
folded
in
half
and
wetted
with
0.75
cc
of
pure
IAA.
The
test
subject
shall
hang
the
wet
towel
on
the
hook
at
the
top
of
the
chamber
(
6)
Allow
two
minutes
for
the
IAA
test
concentration
to
stabilize
before
starting
the
fit
test
exercises.
This
would
be
an
appropriate
time
time
to
talk
with
the
test
subject;
to
explain
the
fit
test,
the
importance
of
his/
her
cooperation,
and
the
purpose
for
the
head
exercises;
or
to
demonstrate
some
of
the
exercises
(
7)
If
at
any
time
during
the
test,
the
subject
detects
the
banana
like
odor
of
IAA,
the
test
has
failed.
The
subject
shall
quickly
exit
from
the
test
chamber
and
leave
the
test
area
to
avoid
olfactory
fatigue
(
8)
If
the
test
has
failed,
the
subject
shall
return
to
the
selection
room
and
remove
the
respirator,
repeat
the
odor
sensitivity
test,
select
and
put
on
another
respirator,
return
to
the
test
chamber
and
again
begin
the
procedure
described
in
(
1)
through
(
7)
above.
The
process
continues
until
a
respirator
that
fits
well
has
been
found.
Should
the
odor
sensitivity
test
be
failed,
the
subject
shall
wait
about
5
minutes
before
retesting.
Odor
sensitivity
will
usually
have
returned
by
this
time
(
9)
When
a
respirator
is
found
that
passes
the
test,
its
efficiency
shall
be
demonstrated
for
the
subject
by
having
the
subject
break
the
face
seal
and
take
a
breath
before
exiting
the
chamber
(
10)
When
the
test
subject
leaves
the
chamber,
the
subject
shall
remove
the
saturated
towel
and
return
it
to
the
person
conducting
the
test.
To
keep
the
test
area
from
becoming
contaminated,
the
used
towels
shall
be
kept
in
a
self
sealing
bag
so
there
is
no
significant
IAA
concentration
build­
up
in
the
test
chamber
during
subsequent
tests
3.
Saccharin
Solution
Aerosol
Protocol
The
saccharin
solution
aerosol
QLFT
protocol
is
the
only
currently
available,
validated
test
protocol
for
use
with
[
page
15631]

particulate
disposable
dust
respirators
not
equipped
with
high­
efficiency
filters.
The
entire
screening
and
testing
procedure
shall
be
explained
to
the
test
subject
prior
to
the
conduct
of
the
screening
test
(
a)
Taste
threshold
screening.
The
saccharin
taste
threshold
screening,
performed
without
wearing
a
respirator,
is
intended
to
determine
whether
the
individual
being
tested
can
detect
the
taste
of
saccharin
(
1)
Threshold
screening
as
well
as
fit
testing
subjects
shall
wear
an
enclosure
about
the
head
and
shoulders
that
isapproximately
12
inches
in
diameter
by
14
inches
tall
with
at
least
the
front
portion
clear
and
that
allows
free
movements
of
the
head
when
a
respirator
is
worn.
An
enclosure
substantially
similar
to
the
3M
hood
assembly,
parts
#
FT
14
and
#
FT
15
combined,
is
adequate
(
2)
The
test
enclosure
shall
have
a
3/
4­
inch
hole
in
front
of
the
test
subject's
nose
and
mouth
area
to
accommodate
the
nebulizer
nozzle
(
3)
The
test
subject
shall
don
the
test
enclosure.
Throughout
the
threshold
screening
test,
the
test
subject
shall
breathe
through
his/
her
wide
open
mouth
with
tongue
extended
(
4)
Using
a
DeVilbiss
Model
40
Inhalation
Medication
Nebulizer
the
test
conductor
shall
spray
the
threshold
check
solution
into
the
enclosure.
This
nebulizer
shall
be
clearly
marked
to
distinguish
it
from
the
fit
test
solution
nebulizer
(
5)
The
threshold
check
solution
consists
of
0.83
grams
of
sodium
saccharin
USP
in
1
cc
of
warm
water.
It
can
be
prepared
by
putting
1
cc
of
the
fit
test
solution
(
see
(
b)(
5)
below)
in
100
cc
of
distilled
water
(
6)
To
produce
the
aerosol,
the
nebulizer
bulb
is
firmly
squeezed
so
that
it
collapses
completely,
then
released
and
allowed
to
fully
expand
(
7)
Ten
squeezes
are
repeated
rapidly
and
then
the
test
subject
is
asked
whether
the
saccharin
can
be
tasted
(
8)
If
the
first
response
is
negative,
ten
more
squeezes
are
repeated
rapidly
and
the
test
subject
is
again
asked
whether
the
saccharin
is
tasted
(
9)
If
the
second
response
is
negative,
ten
more
squeezes
are
repeated
rapidly
and
the
test
subject
is
again
asked
whether
the
saccharin
is
tasted
(
10)
The
test
conductor
will
take
note
of
the
number
of
squeezes
required
to
solicit
a
taste
response
(
11)
If
the
saccharin
is
not
tasted
after
30
squeezes
(
step
10),
the
test
subject
may
not
perform
the
saccharin
fit
test
(
12)
If
a
taste
response
is
elicited,
the
test
subject
shall
be
asked
to
take
note
of
the
taste
for
reference
in
the
fit
test
(
13)
Correct
use
of
the
nebulizer
means
that
approximately
1
cc
of
liquid
is
used
at
a
time
in
the
nebulizer
body
(
14)
The
nebulizer
shall
be
thoroughly
rinsed
in
water,
shaken
dry,
and
refilled
at
least
each
morning
and
afternoon
or
at
least
every
four
hours.
(
b)
Saccharin
solution
aerosol
fit
test
procedure
(
1)
The
test
subject
may
not
eat,
drink
(
except
plain
water),
or
chew
gum
for
15
minutes
before
the
test
(
2)
The
fit
test
uses
the
same
enclosure
described
in
(
a)
above
(
3)
The
test
subject
shall
don
the
enclosure
while
wearing
the
respirator
selected
in
section
(
a)
above.
The
respirator
shall
be
properly
adjusted
and
equipped
with
a
particulate
filter(
s)

(
4)
A
second
DeVilbiss
Model
40
Inhalation
Medication
Nebulizer
is
used
to
spray
the
fit
test
solution
into
the
enclosure.
This
nebulizer
shall
be
clearly
marked
to
distinguish
it
from
the
screening
test
solution
nebulizer
(
5)
The
fit
test
solution
is
prepared
by
adding
83
grams
of
sodium
saccharin
to
100
cc
of
warm
water
(
6)
As
before,
the
test
subject
shall
breathe
through
the
open
mouth
with
tongue
extended
(
7)
The
nebulizer
is
inserted
into
the
hole
in
the
front
of
the
enclosure
and
the
fit
test
solution
is
sprayed
into
the
enclosure
using
the
same
number
of
squeezes
required
to
elicit
a
taste
response
in
the
screening
test
(
8)
After
generating
the
aerosol
the
test
subject
shall
be
instructed
to
perform
the
exercises
in
section
I.
A.
14
above
(
9)
Every
30
seconds
the
aerosol
concentration
shall
be
replenished
using
one
half
the
number
of
squeezes
as
initially
(
10)
The
test
subject
shall
indicate
to
the
test
conductor
if
at
any
time
during
the
fit
test
the
taste
of
saccharin
is
detected
(
11)
If
the
taste
of
saccharin
is
detected,
the
fit
is
deemed
unsatisfactory
and
a
different
respirator
shall
be
tried
4.
Irritant
Fume
Protocol
(
a)
The
respirator
to
be
tested
shall
be
equipped
with
high­
efficiency
particulate
air
(
HEPA)
filters
(
b)
The
test
subject
shall
be
allowed
to
smell
a
weak
concentration
of
the
irritant
smoke
before
the
respirator
is
donned
to
become
familiar
with
its
characteristic
odor
(
c)
Break
both
ends
of
a
ventilation
smoke
tube
containing
stannic
oxychloride,
such
as
the
MSA
part
No.
5645,
or
equivalent.
Attach
one
end
of
the
smoke
tube
to
a
low
flow
air
pump
set
to
deliver
200
milliliters
per
minute
(
d)
Advise
the
test
subject
that
the
smoke
can
be
irritating
to
the
eyes
and
instruct
the
subject
to
keep
his/
her
eyes
closed
while
the
test
is
performed
(
e)
The
test
conductor
shall
direct
the
stream
of
irritant
smoke
from
the
smoke
tube
towards
the
face
seal
area
of
the
test
subject.
He/
She
shall
begin
at
least
12
inches
from
the
facepiece
and
gradually
move
to
within
one
inch,
moving
around
the
whole
perimeter
of
the
mask
(
f)
The
exercises
identified
in
section
I.
A.
14
above
shall
be
performed
by
the
test
subject
while
the
respirator
seal
is
being
challenged
by
the
smoke
(
g)
Each
test
subject
passing
the
smoke
test
without
evidence
of
a
response
shall
be
given
a
sensitivity
check
of
the
smoke
from
the
same
tube
once
the
respirator
has
been
removed
todetermine
whether
he/
she
reacts
to
the
smoke.
Failure
to
evoke
a
response
shall
void
the
fit
test
(
h)
The
fit
test
shall
be
performed
in
a
location
with
exhaust
ventilation
sufficient
to
prevent
general
contamination
of
the
testing
area
by
the
test
agent
C.
Quantitative
Fit
Test
(
QNFT)
Protocol
1.
General
(
a)
The
employer
shall
assign
specific
individuals
who
shall
assume
full
responsibility
for
implementing
the
respirator
quantitative
fit
test
program
(
b)
The
employer
shall
ensure
that
persons
administering
QNFT
are
able
to
calibrate
equipment
and
perform
tests
properly,
recognize
invalid
tests,
calculate
fit
factors
properly
and
assure
that
test
equipment
is
in
proper
working
order
(
c)
The
employer
shall
assure
that
QNFT
equipment
is
kept
clean
and
well
maintained
so
as
to
operate
at
the
parameters
for
which
it
was
designed
2.
Definitions
(
a)
Quantitative
fit
test.
The
test
is
performed
in
a
test
chamber.
The
normal
air­
purifying
element
of
the
respirator
is
replaced
by
a
high­
efficiency
particulate
air
(
HEPA)
filter
in
the
case
of
particulate
QNFT
aerosols
or
a
sorbent
offering
contaminant
penetration
protection
equivalent
to
high­
efficiency
filters
where
the
QNFT
test
agent
is
a
gas
or
vapor
(
b)
Challenge
agent
means
the
aerosol,
gas
or
vapor
introduced
into
a
test
chamber
so
that
its
concentration
inside
and
outside
the
respirator
may
be
measured
(
c)
Test
subject
means
the
person
wearing
the
respirator
for
quantitative
fit
testing
(
d)
Normal
standing
position
means
standing
erect
and
straight
with
arms
down
along
the
sides
and
looking
straight
ahead
(
e)
Maximum
peak
penetration
method
means
the
method
of
determining
test
agent
penetration
in
the
respirator
as
determined
by
strip
chart
recordings
of
the
test.
The
highest
peak
penetration
for
a
given
exercise
is
taken
to
be
representative
of
average
penetration
into
the
respirator
for
that
exercise
(
f)
Average
peak
penetration
method
means
the
method
of
determining
test
agent
penetration
into
the
respirator
utilizing
a
strip
chart
recorder,
integrator,
or
computer.
The
agent
penetration
is
determined
by
an
average
of
the
peak
heights
on
the
graph
or
by
computer
integration,
for
each
exercise
except
the
grimace
exercise.
Integrators
or
computers
which
calculate
the
actual
test
agent
penetration
into
the
respirator
for
each
exercise
will
also
be
considered
to
meet
the
requirements
of
the
average
peak
penetration
method
(
g)
"
Fit
Factor"
means
the
ration
of
challenge
agent
concentration
outside
with
respect
to
the
inside
of
a
respirator
inlet
covering
(
facepiece
or
enclosure)

3.
Apparatus
(
a)
Instrumentation.
Aerosol
generation,
dilution,
and
measurement
systems
using
corn
oil
or
sodium
chloride
as
test
aerosols
shall
be
used
for
quantitative
fit
testing
(
b)
Test
chamber.
The
test
chamber
shall
be
large
enough
to
permit
all
test
subjects
to
perform
freely
all
required
exercises
without
disturbing
the
challenge
agent
concentration
or
the
measurement
apparatus.
The
test
chamber
shall
be
equipped
and
constructed
so
that
the
challenge
agent
is
effectively
isolated
from
the
ambient
air,
yet
uniform
in
concentration
throughout
the
chamber.
[
page
15632]

(
c)
When
testing
air­
purifying
respirators,
the
normal
filter
or
cartridge
element
shall
be
replaced
with
a
high­
efficiency
particulate
filter
supplied
by
the
same
manufacturer
(
d)
The
sampling
instrument
shall
be
selected
so
that
a
strip
chart
record
may
be
made
of
the
test
showing
the
rise
and
fall
of
the
challenge
agent
concentration
with
each
inspiration
and
expiration
at
fit
factors
of
at
least
2,000.
Integrators
or
computers
which
integrate
the
amount
of
test
agent
penetration
leakage
into
the
respirator
for
each
exercise
may
be
used
provided
a
record
of
the
readings
is
made
(
e)
The
combination
of
substitute
air­
purifying
elements,
challenge
agent
and
challenge
agent
concentration
in
the
test
chamber
shall
be
such
that
the
test
subject
is
not
exposed
in
excess
of
an
established
exposure
limit
for
the
challenge
agent
at
any
time
during
the
testing
process
(
f)
The
sampling
port
on
the
test
specimen
respirator
shall
be
placed
and
constructed
so
that
no
leakage
occurs
around
the
port
(
e.
g.
where
the
respirator
is
probed),
a
free
air
flow
is
allowed
into
the
sampling
line
at
all
times
and
so
that
there
is
no
interference
with
the
fit
or
performance
of
the
respirator
(
g)
The
test
chamber
and
test
set
up
shall
permit
the
person
administering
the
test
to
observe
the
test
subject
inside
the
chamber
during
the
test
(
h)
The
equipment
generating
the
challenge
atmosphere
shall
maintain
the
concentration
of
challenge
agent
inside
the
test
chamber
constant
to
within
a
10
percent
variation
for
the
duration
of
the
test
(
i)
The
time
lag
(
interval
between
an
event
and
the
recording
of
the
event
on
the
strip
chart
or
computer
or
integrator)
shall
be
kept
to
a
minimum.
There
shall
be
a
clear
association
between
the
occurrence
of
an
event
inside
the
test
chamber
and
its
being
recorded
(
j)
The
sampling
line
tubing
for
the
test
chamber
atmosphere
and
for
the
respirator
sampling
port
shall
be
of
equal
diameter
and
of
the
same
material.
The
length
of
the
two
lines
shall
be
equal
(
k)
The
exhaust
flow
from
the
test
chamber
shall
pass
through
a
high­
efficiency
filter
before
release
(
l)
When
sodium
chloride
aerosol
is
used,
the
relative
humidity
inside
the
test
chamber
shall
not
exceed
50
percent
(
m)
The
limitations
of
instrument
detection
shall
be
taken
into
account
when
determining
the
fit
factor
(
n)
Test
respirators
shall
be
maintained
in
proper
working
order
and
inspected
for
deficiencies
such
as
cracks,
missing
valves
and
gaskets,
etc
4.
Procedural
Requirements
(
a)
When
performing
the
initial
positive
or
negative
pressure
test
the
sampling
line
shall
be
crimped
closed
in
order
to
avoid
air
pressure
leakage
during
either
of
these
tests
(
b)
An
abbreviated
screening
isoamyl
acetate
test
or
irritant
fume
test
may
be
utilized
in
order
to
quickly
identify
poor
fitting
respirators
which
passed
the
positive
and/
or
negative
pressure
test
and
thus
reduce
the
amount
of
QNFT
time.
When
performing
a
screening
isoamyl
acetate
test,
combination
high­
efficiency
organic
vapor
cartridges/
canisters
shall
be
used
(
c)
A
reasonably
stable
challenge
agent
concentration
shall
be
measured
in
the
test
chamber
prior
to
testing.
For
canopy
or
shower
curtain
type
of
test
units
the
determination
of
the
challenge
agent
stability
may
be
established
after
the
test
subject
has
entered
the
test
environment
(
d)
Immediately
after
the
subject
enters
the
test
chamber,
the
challenge
agent
concentration
inside
the
respirator
shall
be
measured
to
ensure
that
the
peak
penetration
does
not
exceed
5
percent
for
a
half
mask
or
1
percent
for
a
full
facepiece
respirator
(
e)
A
stable
challenge
concentration
shall
be
obtained
prior
to
the
actual
start
of
testing
(
f)
Respirator
restraining
straps
shall
not
be
overtightened
for
testing.
The
straps
shall
be
adjusted
by
the
wearer
without
assistance
from
other
persons
to
give
a
reasonable
comfortable
fit
typical
of
normal
use
(
g)
The
test
shall
be
terminated
whenever
any
single
peak
penetration
exceeds
5
percent
for
half
masks
and
1
percent
for
full
facepiece
respirators.
The
test
subject
shall
be
refitted
and
retested.
If
two
of
the
three
required
tests
are
terminated,
the
fit
shall
be
deemed
inadequate
(
h)
In
order
to
successfully
complete
a
QNFT,
three
successful
fit
tests
are
required.
The
results
of
each
of
the
three
independent
fit
tests
must
exceed
the
minimum
fit
factor
needed
for
the
class
of
respirator
(
e.
g.
half
mask
respirator,
full
facepiece
respirator).
(
i)
Calculation
of
fit
factors
(
1)
The
fit
factor
shall
be
determined
for
the
quantitative
fit
test
by
taking
the
ratio
of
the
average
chamber
concentration
to
the
concentration
inside
the
respirator
(
2)
The
average
test
chamber
concentration
is
the
arithmetic
average
of
the
test
chamber
concentration
at
the
beginning
and
of
the
end
of
the
test
(
3)
The
concentration
of
the
challenge
agent
inside
the
respirator
shall
be
determined
by
one
of
the
following
methods:

(
i)
average
peak
concentration
(
ii)
Maximum
peak
concentration
(
iii)
Integration
by
calculation
of
the
area
under
the
individual
peak
for
each
exercise.
This
includes
computerized
integration
(
j)
Interpretation
of
test
results.
The
fit
factor
established
by
the
quantitative
fit
testing
shall
be
the
lowest
of
the
three
fit
factor
values
calculated
from
the
three
required
fit
tests
(
k)
The
test
subject
shall
not
be
permitted
to
wear
a
half
mask,
or
full
facepiece
respirator
unless
a
minimum
fit
factor
equivalent
to
at
least
10
times
the
hazardous
exposure
level
is
obtained
(
l)
Filters
used
for
quantitative
fit
testing
shall
be
replaced
at
least
weekly,
or
whenever
increased
breathing
resistance
is
encountered,
or
when
the
test
agent
has
altered
the
integrity
of
the
filter
media.
Organic
vapor
cartridges/
canisters
shall
be
replaced
daily
(
when
used)
or
sooner
if
there
is
any
indication
of
breakthrough
by
a
test
agent
[
FR
Doc.
93­
1277
Filed
1­
26­
93;
8:
45
Billing
Code
4510­
26­
M