Document ID: EPA-HQ-OPP-2005-0060-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-04-08T04:00Z

Page
1
of
21
March
25,
2005
MEMORANDUM
SUBJECT:
Document
to
Support
the
FIFRA
Scientific
Advisory
Panel
Meeting
on
TSCA
Inventory
Nomenclature
for
Enzymes
and
Proteins
FROM:
Neil
Patel,
Associate
Director
Economics,
Exposure
and
Technology
Division
Office
of
Pollution
Prevention
and
Toxics
TO:
Clifford
Gabriel,
Director
Office
of
Science
Coordination
and
Policy
Attached
is
the
supporting
document
for
the
FIFRA
Scientific
Advisory
Panel
Meeting
on
TSCA
Inventory
Nomenclature
for
Enzymes
and
Proteins
scheduled
for
May
3­
4,
2005
at
the
Holiday
Inn
Rosslyn
at
Key
Bridge.
The
attached
document
is:
Treatment
of
Enzymes
on
the
TSCA
Chemical
Inventory.
U.
S.
Environmental
Protection
Agency
(
2005).
If
you
have
any
questions,
please
contact
Dr.
Henry
Lau
at
564­
8572
or
myself
at
564­
8804.

Attachment
Page
2
of
21
Treatment
of
Enzymes
on
the
TSCA
Chemical
Inventory
I.
ISSUE
EPA's
Office
of
Pollution
Prevention
and
Toxics
(
OPPT)
is
responsible
for
implementing
the
Toxic
Substances
Control
Act
(
TSCA).
It
requires
EPA
to
ensure
that
chemicals
sold
and
used
in
the
United
States
pose
no
unreasonable
risks
to
human
health
or
the
environment.
TSCA
also
requires
EPA
to
maintain
a
list
of
all
chemicals
existing
in
U.
S.
commerce
as
a
way
to
identify
new
substances
that
should
be
reviewed
for
potential
risks.

In
1977,
EPA
promulgated
the
Inventory
Reporting
Regulations
that
provided
the
basis
for
the
first
compilation
of
the
TSCA
Chemical
Substance
Inventory
("
the
TSCA
Inventory"
or
"
the
Inventory").
It
listed
more
than
62,000
substances,
including
about
150
enzymes.
The
1977
regulations
did
not
specifically
address
how
enzymes
should
be
identified
when
reported
to
EPA.
Consequently,
most
enzymes
were
only
broadly
defined,
with
some
individual
listings
actually
describing
a
whole
category
of
commercial
enzymes.
EPA
is
therefore
unable
to
identify
when
an
enzyme
is
"
new"
and
should
be
subject
to
Premanufacture
Notification
(
PMN)
reporting
requirements
that
enable
the
Agency
to
review
new
chemicals
before
introduction
into
U.
S.
commerce.
Specific
reporting
guidance
for
enzymes
is
needed
so
that
enzymes
will
be
accurately,
uniquely,
and
unambiguously
identified
on
the
TSCA
Inventory.

EPA
is
currently
working
to
develop
an
improved
and
standardized
method
of
identifying
proteinaceous
enzymes
(
hereafter
"
enzymes")
on
the
TSCA
Inventory
so
that
each
Inventory
listing
will
cover
only
one
enzyme.
EPA
issued
an
Advanced
Notice
of
Proposed
Rulemaking
(
ANPR)
in
November
2004
that
outlined
its
proposed
approach
to
enzyme
identification,
and
solicited
comment
on
all
aspects
of
the
proposal.
In
the
ANPR,
EPA
proposed
that
enzymes
be
identified
using
information
on
function,
source,
processing,
and
sequence.
EPA
is
convening
a
group
of
technical
experts
under
the
aegis
of
the
Scientific
Advisory
Panel
to
evaluate
several
scientific
and
technical
issues
associated
with
this
proposal.

II.
THE
TSCA
INVENTORY
Congress
recognized
during
its
development
of
TSCA
that
very
little
was
known
about
chemicals
in
commercial
use.
When
TSCA
was
enacted
in
1976,
it
was
not
even
known
how
many
chemicals
there
were,
in
what
quantities
or
where
they
were
produced,
what
their
byproducts
or
impurities
were,
or
who
was
exposed
to
them
under
what
conditions.
Therefore,
Congress
gave
EPA
the
authority
to
compile
an
Inventory
of
existing
chemical
substances
and
to
develop
additional
information
on
these
basic
questions.

The
first
inventory
was
published
in
1979,
based
on
information
reported
to
EPA
by
chemical
manufacturers,
importers,
and
processors.
The
Inventory
­
to
which
new
chemicals
are
added
when
they
go
into
production
­
shows
now
that
over
82,000
commercial
chemical
substances
are,
or
have
been,
manufactured
or
imported
into
the
United
States
since
January
1,
1975.
(
Most
of
Page
3
of
21
the
more
than
twenty­
two
million
known
chemical
substances
in
existence
are
excluded
from
TSCA
reporting,
such
as
those
substances
used
only
for
research
and
development1.)

It
is
important
to
note
that
the
Inventory
is
not
a
list
of
toxic
or
hazardous
chemicals.
Rather,
it
lists
existing
chemicals,
generally
by
their
specific
chemical
name,
giving
an
overall
picture
of
the
chemicals
used
for
commercial
purposes
in
the
United
States.
Chemicals
not
on
the
Inventory
and
not
specifically
excluded
from
TSCA's
regulatory
authorities
or
exempt
from
PMN
reporting
must
be
reviewed
by
EPA
under
the
PMN
program
before
they
are
allowed
into
U.
S.
commerce.

Premanufacture
notices
submitted
for
new
chemicals
or
significant
new
uses
of
existing
chemicals
are
to
include:
the
specific
chemical
identity
(
the
chemical
name)
of
the
substance;
its
molecular
structure
and
molecular
formula;
proposed
categories
of
use;
an
estimate
of
the
amount
to
be
manufactured,
imported,
or
processed;
its
impurities;
the
byproducts
resulting
from
the
manufacture,
processing,
use,
and
disposal
of
the
chemical;
estimates
of
the
exposure;
and
any
available
test
data
related
to
the
health
and
environmental
effects
of
the
chemical.
Inventory
names
are
developed
from
this
information
according
to
a
rigorous,
comprehensive
set
of
nomenclature
rules
to
ensure
that
a
single,
unique,
and
unambiguous
name
can
be
constructed
for
each
chemical
substance.
In
most
cases,
the
preferred
Chemical
Abstracts
(
CA)
Index
Name
for
a
substance
contains
sufficient
information
to
reflect
a
specific,
corresponding
chemical
structure.

Some
substances
listed
on
the
Inventory
are
tagged
to
indicate
that
their
preferred
CA
Index
Names
are
not
sufficient
or
complete
enough
to
permit
unambiguous
identification
of
the
substance.
For
such
substances,
the
Inventory
lists
a
supplemental
definition.
Definitions
may
include
a
genus/
species
or
identity
of
other
types
of
source
material,
the
nature
of
the
process
by
which
the
substance
was
manufactured
or
processed
,
the
predominant
components,
and
characterizing
physical
data
such
as
approximate
boiling
point
range.
The
information
EPA
is
proposing
to
require
for
identification
of
enzymes
on
the
TSCA
Inventory
is
thus
similar
to
information
that
is
already
provided
for
other
substances
when
it
is
needed
to
create
a
unique,
unambiguous
description.
More
detailed
information
about
current
Inventory
practices
and
examples
of
current
Inventory
listings
are
available
in
Appendix
I.

III.
CURRENT
TSCA
INVENTORY
LISTING
CONVENTIONS
FOR
ENZYMES
Enzymes
currently
on
the
TSCA
Inventory
are
identified
by
a
Chemical
Abstracts
Service
(
CAS)
Registry
Number2
and
Chemical
Abstracts
(
CA)
Index
Name3
with
supplemental
definitions
of
1
Eight
product
categories
are
exempt
from
TSCA's
regulatory
authorities:
pesticides,
tobacco
and
tobacco
products,
certain
nuclear
materials,
firearms
and
ammunition,
food,
food
additives,
drugs,
and
cosmetics.
Many
of
these
product
categories
are
regulated
under
other
Federal
laws.
Chemicals
produced
in
small
quantities
solely
for
research
and
development
purposes
are
also
exempt.
In
addition,
any
person
may
apply
for
an
exemption
from
PMN
reporting
for
chemicals
used
solely
for
test
marketing
purposes
or
for
those
determined
by
EPA
not
to
present
an
unreasonable
risk
of
injury
to
human
health
or
the
environment.

2
A
CAS
Registry
Number
is
included
for
each
nonconfidential
substance
on
the
Inventory.
CAS
Registry
Numbers
are
assigned
in
sequential
order
as
new
substances
are
entered
into
the
CAS
Registry
File.
Each
Registry
Number
in
the
TSCA
inventory
designates
only
one
chemical
substance
in
terms
of
numbers
and
types
of
atoms,
the
bonding
between
atoms,
and
stereochemistry,
insofar
as
that
substance
has
been
Page
4
of
21
varying
detail.
These
listings
are
based
on
information
that
submitters
provided
to
EPA
without
having
any
agency
guidance
as
to
the
type
or
specificity
of
information
that
should
be
included
in
enzyme
descriptions.

In
general,
the
type
of
information
included
in
current
enzyme
listings
consists
solely
of
the
category
of
the
enzyme's
catalytic
activity
(
although
in
a
few
cases
supplemental
definitions
include
additional
information
such
as
source,
identity
of
co­
factors,
or
processing
techniques
used
in
the
enzyme's
production).
Enzyme
catalytic
activity
has
historically
been
the
basis
for
CAS
and
other
enzyme
nomenclature
systems.
Often
a
new
catalytic
activity
is
discovered
before
anything
is
known
about
the
structure
of
the
catalyst.
In
addition,
a
satisfactory,
systematic
nomenclature
for
protein
structures
that
is
useful
for
EPA's
regulatory
purposes
does
not
yet
exist.

Using
function
to
identify
enzymes
on
the
TSCA
Inventory
is
an
approach
that
differs
substantially
from
that
used
for
other
listed
chemicals.
CA
Index
Names
generally
allow
derivation
of
the
chemical
structure
(
or
as
much
of
the
chemical
structure
as
is
known).
Structure
provides
a
way
to
unambiguously
identify
chemicals
so
that
they
can
be
differentiated
and
thus
new
chemicals
can
be
recognized.
Function
allows
no
such
differentiation
because
often
several
structurally­
diverse
enzymes
have
the
same
function.
Thus,
even
under
ideal
circumstances,
a
function­
based
enzyme
nomenclature
system
would
inappropriately
subsume
multiple
enzymes
under
a
single
listing
on
the
TSCA
Inventory.
This
problem
is
compounded
on
the
current
TSCA
Inventory
because
many
descriptions
of
enzyme
function
that
were
submitted
to
EPA
defined
only
the
most
general
catalytic
activity
of
the
enzyme
(
e.
g.,
proteinase).
Both
the
type
and
specificity
of
information
included
in
current
enzyme
names
on
the
Inventory
therefore
create
listings
that
often
encompass
several
enzymes
that
have
structural
differences
and
are
recognized
to
be
distinct
products.
In
fact,
most
new
commercial
enzymes
that
are
created,
regardless
of
similarity
or
lack
thereof,
could
be
subsumed
under
one
of
the
current
listings.

IV.
REASONS
TO
UPDATE
CURRENT
TSCA
INVENTORY
LISTING
CONVENTIONS
FOR
ENZYMES
EPA
believes
that
current
reporting
conventions
do
not
allow
the
Agency
to
fulfill
its
obligation
to
identify
and
review
new
enzymes
before
they
are
manufactured
or
used
in
the
United
States.
Enzyme
listings
must
allow
the
Agency
to
determine
that
an
enzyme
is
new
and
is
therefore
subject
to
reporting
requirements
under
TSCA
so
that
the
Agency
could
review
the
chemical
for
potential
risks
to
human
health
or
the
environment.
Enzymes
are
used
in
a
wide
variety
of
products
and
industries
including
detergents;
cleansing
and
degreasing
agents;
leather,
textiles,

elucidated
or
defined.
The
fact
that
a
substance
has
been
assigned
a
CAS
Registry
Number
does
not
define
the
substance
as
being
on
the
TSCA
Inventory.
The
non­
confidential
portion
of
the
TSCA
Inventory
includes
only
approximately
80,000
substances
in
the
CAS
Registry
File,
which
represents
less
than
one
percent
of
the
total
number
of
CAS
Registry
Numbers.

3
Preferred
CA
Index
Names
are
derived
according
to
a
rigorous,
comprehensive
set
of
nomenclature
rules
to
ensure
that
a
single,
preferred
name
can
be
constructed
for
each
chemical
substance.
For
substances
that
have
definite
chemical
structures,
the
preferred
CA
Index
Name
contains
sufficient
information
to
permit
derivation
of
those
structures.
Page
5
of
21
and
paper
manufacturing
industries;
waste
degradation;
oil
recovery;
and
biosensing.
Many
of
these
uses
expose
large
populations
to
products
containing
enzymes,
and
the
potential
exposure
is
constantly
increasing
as
new
enzymes
and
uses
are
discovered.
Nevertheless,
the
risk
implications
of
many
enzymes
produced
since
the
initial
Inventory
compilation
have
not
been
evaluated
by
EPA
because
the
current
enzyme
listings
do
not
allow
the
Agency
to
differentiate
among
many
widely
disparate
enzymes
currently
in
commerce.
Broad
Inventory
listings
that
may
encompass
hundreds
or
even
thousands
of
distinct
substances
prevent
the
Agency
from
fulfilling
the
mandate
of
TSCA
by
undermining
EPA
review
of
all
new
chemicals.

Broad
Inventory
listings
also
lead
to
uncertainty
for
EPA
and
the
regulated
community.
The
lack
of
clarity
surrounding
enzyme
listings
has
led
to
an
increasing
number
of
inquiries
from
chemical
manufacturers
who
need
assistance
in
determining
whether
an
enzyme
they
plan
to
manufacture
is
already
listed
on
the
Inventory
or
whether
they
will
have
to
submit
a
PMN
notification
to
the
Agency.
Resolving
this
uncertainty
creates
an
unnecessary
burden
for
both
EPA
and
the
regulated
community,
as
the
Agency
must
make
a
case­
by­
case
determination
for
each
enzyme,
many
of
which
are
ultimately
found
to
be
subsumed
under
a
current
Inventory
listing.

V.
CHALLENGES
ASSOCIATED
WITH
LISTING
ENZYMES
ON
THE
TSCA
INVENTORY
The
current
function­
based
approach
for
listing
enzymes
on
the
Inventory
has
become
increasingly
inadequate
for
TSCA
Inventory
listings
as
the
number
and
diversity
of
enzymes
has
grown.
A
disparate
set
of
enzymes
may
share
a
single
enzymatic
function,
even
one
that
is
narrowly
defined.
However,
there
is
no
other
standard,
scientifically­
recognized
nomenclature
system
for
enzymes
with
which
to
replace
the
current
function­
based
system.
For
non­
enzymatic
chemicals,
EPA
relies
heavily
on
a
structural
approach
to
identification.
However,
adopting
a
strictly
structure­
based
approach
for
enzymes
on
the
Inventory
would
be
impractical.

Proteinaceous
enzymes
consist
of
polypeptide
chains.
The
amino
acid
sequence
ultimately
determines
how
the
chains
fold
to
form
three­
dimensional
(
3­
D)
structures
with
active
sites
for
binding
to
particular
substrates.
In
some
enzymes,
proteins
are
the
only
structural
components.
However,
most
enzymes
also
contain
covalently­
bonded,
non­
protein
moieties
such
as
carbohydrates
that
can
have
a
significant
effect
on
an
enzyme's
3­
D
structure
and
function.
Other
important
factors
include
metal
ions
(
called
cofactors)
and
low
molecular
weight
organic
molecules
(
called
coenzymes).

A
complete
structural
description
of
an
enzyme
would
need
to
describe,
at
a
minimum,
the
complete
amino
acid
sequence
and
the
location
and
identity
of
all
non­
protein
moieties.
Determination
of
such
a
precise
description
would
be
technically
difficult.
However,
even
if
this
information
were
readily
available,
such
a
detailed
description
would
so
finely
differentiate
enzymes,
that
even
enzyme
preparations
that
are
considered
the
same
for
all
practical
purposes
would
have
unique
identities.
As
is
the
case
for
most
biological
substances,
a
certain
degree
of
genetic
variation
can
be
accommodated
without
altering
the
function
or
three­
dimensional
structure
of
an
enzyme.
Page
6
of
21
Genetic
variation
in
what
is
consistently
considered
to
be
a
single
enzyme
can
arise
at
least
three
different
ways:
1)
an
enzyme
sample
may
contain
differences
due
to
inherent
genetic
variability
within
the
population
of
an
organism
serving
as
production
source
at
any
point
in
time,
2)
an
enzyme
sample
may
change
over
time
as
the
genetics
of
the
predominant
organism
serving
as
production
source
change,
and
3)
fluctuations
in
environmental
conditions
during
enzyme
production
may
produce
variation.

V.
A.
Inherent
genetic
variability
of
the
source
organism
Most
commercial
enzymes
are
produced
by
microbial
fermentation
of
bacteria
or
fungi.
A
large
population
of
microorganisms
must
be
cultured
to
enable
production
of
a
sufficient
quantity
of
enzyme
product.
A
bacterial
population
may
have
a
spontaneous
mutation
frequency
of
10­
6
or
10­
7
mutations
per
gene
per
generation.
With
a
production
volume
of
up
to
100,000
liters
at
a
density
of
1012
colony­
forming
units
per
milliliter,
the
fermenting
population
is
likely
to
contain
genetic
variation
at
any
point
in
time,
even
when
accounting
for
DNA
repair
mechanisms.
This
variation
may
result
in
some
members
of
the
population
producing
slightly
different
enzyme
structures
from
the
same
genetic
locus.
The
result
is
an
enzyme
preparation
generally
dominated
by
one
structure
but
containing
inherent
variability.

Enzymes
may
also
be
produced
by
extraction
and
isolation
from
plant
or
animal
sources,
for
example,
from
swine
pancreatic
tissue
or
from
papaya.
Natural
genetic
variation
will
exist
within
a
populations
of
plants
and
animals
that
may
lead
to
inherent
variation
in
these
types
of
enzyme
preparations
as
well.

V.
B.
Variability
of
the
source
organism
over
time
Even
when
initial
variation
within
a
cell
culture
is
minimized,
continued
growth
of
the
microorganism
population
throughout
enzyme
production
provides
opportunity
for
the
introduction
of
genetic
variation
through
mutation.
Just
as
with
any
population,
genetic
drift
(
changes
in
allele
frequency
due
to
chance
alone)
and
selection
(
changes
in
allele
frequency
due
to
differential
survival
of
organisms
that
are
better
able
to
use
environmental
resources)
may
cause
the
precise
genetic
makeup
of
the
population
to
change
over
an
extended
production
period.
Changes
in
the
composition
of
the
source
population
over
time
may
yield
slightly
different
enzyme
structures
throughout
the
production
period
unless
regular
quality
control
adjustments
are
made.
The
significance
of
the
specific
genomic
location
of
these
genetic
changes
will
vary.
Some
point
mutations
will
produce
no
change
in
the
amino
acid
sequence
of
the
enzyme,
while
others
may
produce
a
conformational
change.
The
latter
may
not
necessarily
affect
specific
enzymatic
activity
and
could
thus
evade
detection
if
only
enzymatic
function
were
evaluated.

V.
C.
Variability
produced
by
differences
in
production
conditions
Page
7
of
21
Enzyme
structure
may
also
be
affected
by
environmental
conditions
during
enzyme
production.
The
goal
of
a
given
production
facility
will
generally
be
to
maintain
constant
conditions
to
the
extent
possible.
However,
variation
in
enzyme
product
may
be
caused
by
changes
in
pressure,
density
of
the
population,
substrate
availability,
osmotic
pressure,
aeration,
and
oxygen
availability
among
other
factors.
Quality
control
may
involve
ensuring
that
the
final
enzyme
product
has
the
desired
functionality
but
is
unlikely
to
involve
verification
of
the
enzyme
structure
in
spite
of
probable
non­
sequence
structural
variations.

V.
D.
Apparent
variability
In
addition
to
the
actual
variation
in
an
enzyme
sample,
variation
will
appear
to
occur
due
to
limitations
in
our
ability
to
accurately
determine
and
describe
an
enzyme's
structure,
limitations
that
are
exacerbated
by
the
relative
impurity
of
many
enzyme
preparations.
Product
impurity
and
other
sample
preparation
problems
can
lead
to
incomplete
or
reduced
quality
sequence
information.

Some
enzyme
products
may
be
highly­
purified
materials
for
analytical
or
medical
use.
Other
applications
may
require
only
very
crude
preparations
such
as
ground
and/
or
extracted
plant
material
or
animal
organs.
Such
crude
products
are
likely
to
contain
only
small
amounts
of
the
active
enzyme
with
a
large
proportion
of
by­
products.
Purification
is
only
attempted
if
a
more
concentrated
or
purer
product
is
desired
because
each
purification
step
reduces
the
total
yield.
To
retain
the
activity
in
commercial
preparations,
stabilizing
agents
and/
or
preservatives
are
typically
added
to
ensure
the
maintenance
of
the
native
conformation
by
preventing
unfolding
of
the
protein
and/
or
its
degradation
by
other
enzymes.
Some
commercial
enzyme
preparations
may
consist
of
enzyme
mixtures,
either
by
intent
or
through
a
lack
of
purification.
Impurities
and
byproducts
in
enzyme
preparations
may
impede
the
accurate
description
of
the
enzyme
structure.

VI.
EPA'S
PROPOSED
APPROACH
FOR
ENZYME
IDENTIFICATION
ON
THE
TSCA
INVENTORY
EPA
wants
to
establish
TSCA
nomenclature
guidance
for
enzymes
that
enables
the
Agency
to
unambiguously
differentiate
among
enzymes
while
taking
into
account
the
challenges
associated
with
fitting
enzymes
into
a
structure­
based
system.
EPA
has
developed
an
approach
it
believes
balances
these
concerns.
EPA
intends
to
use
a
combination
of
four
elements
to
create
an
enzyme's
name
for
listing
on
the
TSCA
Inventory:
function,
sequence,
source,
and
processing
(
described
below).
A
supplemental
description
would
be
part
of
an
enzyme's
identity
on
the
Inventory
that
would
incorporate
information
about
each
of
these
characteristics
at
a
level
of
detail
that
must
still
be
determined.

None
of
the
four
identification
elements
alone
would
be
adequate
to
unambiguously
describe
an
enzyme.
Historically,
function
has
been
used
but
has
proved
to
be
inadequate
for
EPA
to
be
able
to
determine
clearly
and
unambiguously
whether
a
potential
new
enzyme
is
already
listed
on
the
Inventory.
Adoption
of
a
strictly
structure­
based
approach
for
enzyme
identification
would
complicate
the
differentiation
among
enzymes
by
often
requiring
Page
8
of
21
unnecessary
detail.
EPA's
approach
for
enzyme
identification
would
retain
function
as
part
of
enzyme
identity
to
avoid
confusion
that
could
result
from
complete
departure
from
conventional
enzyme
nomenclature
and
because
function
provides
useful
information.
In
addition,
using
one
aspect
of
enzyme
structure
(
amino
acid
sequence)
along
with
certain
source
and
processing
information
would
provide
an
appropriate
amount
of
both
direct
and
indirect
information
about
enzyme
structure
to
differentiate
enzymes
and
allow
review
of
unique
products.

In
convening
this
expert
panel,
EPA
is
soliciting
scientific
input
on
how
and
to
what
degree
changes
in
each
of
these
elements
affects
the
chemical
identity
of
enzymes.
This
information
is
critical
to
the
Agency

s
efforts
to
develop
a
nomenclature
system
that
will
enable
EPA
to
discriminate
among
distinct
chemical
substances.

VI.
A.
Function
The
FUNCTION
of
an
enzyme
refers
to
its
catalytic
activity.
Internationally­
accepted
nomenclature
conventions
of
the
Nomenclature
Committee
of
the
International
Union
of
Biochemistry
and
Molecular
Biology
(
NC­
IUBMB)
describe
and
differentiate
enzymes
based
on
this
catalytic
activity4.
The
NC­
IUBMB
assigns
enzymes
a
code
number
designated
by
the
prefix
EC.
The
code
number
is
based
on
the
reaction
catalyzed
by
the
enzyme,
the
nature
of
the
bond
involved,
and
the
substrate
acted
upon.
Enzymes
with
different
amino
acid
sequences
may
be
assigned
the
same
EC
code.
EPA
intends
to
incorporate
function
into
enzyme
identity
on
the
TSCA
Inventory
by
using
these
EC
codes
and
the
associated
function
descriptor(
s).

Using
function
follows
historically
important
enzyme
nomenclature
conventions
of
the
NCIUBMB
that
are
scientifically
accepted,
readily
interpretable,
and
widely
used
for
enzyme
identification.
Although
EPA
has
determined
that
function
alone
is
not
sufficient
for
describing
an
enzyme's
identity
for
regulatory
purposes,
the
Agency
believes
it
would
be
a
necessary
component
of
enzyme
identity.
Information
about
the
type
of
reaction
catalyzed
by
an
enzyme
indicates
potential
and
likely
uses
for
the
enzyme.
A
description
of
function
is
the
only
way
that
multiple
catalytic
activities
in
a
single
enzyme
may
be
identified.
Finally,
information
about
function
is
readily
available
and
would
require
little
additional
effort
to
provide
it
to
EPA.
The
Agency
is
seeking
guidance
as
to
how
specifically
function
should
be
described
to
uniquely
identify
enzymes
if
function
were
to
be
a
part
of
the
enzyme
definition.

VI.
B.
Amino
Acid
Sequence
The
AMINO
ACID
SEQUENCE
of
an
enzyme
polypeptide
chain
is
known
as
its
primary
structure.
It
is
a
systematic
representation
of
the
linear
sequence
of
amino
acids
that
are
connected
via
amide
bonds
to
form
a
polypeptide.
Sequence
information
is
a
precise
way
to
characterize
the
primary
structure
of
an
enzyme,
and
it
provides
information
that
is
analogous
to
the
structural
4
For
more
information
about
classification
and
nomenclature
of
enzyme­
catalyzed
reactions
by
the
IUBMB,
see
http://
www.
chem.
qmul.
ac.
uk/
iubmb/
enzyme/
rules.
html
Page
9
of
21
information
that
EPA
uses
to
differentiate
among
most
standard
chemicals.
In
addition,
changes
in
sequence
may
lead
to
changes
in
important
chemical
properties
that
should
be
reviewed
by
the
Agency.
The
Agency
is
seeking
guidance
as
to
how
much
variation
in
amino
acid
sequence
would
be
appropriate
to
uniquely
identify
enzymes
if
amino
acid
sequence
were
to
be
a
part
of
the
enzyme
definition.

VI.
C.
Source
The
SOURCE
of
an
enzyme
would
refer
to
(
1)
the
organism
from
which
the
gene
encoding
the
enzyme
was
derived,
i.
e.,
the
original
source
and
(
2)
the
organism
or
manufacturing
platform
(
e.
g.,
tissue
culture)
in
which
the
enzyme
is
produced,
i.
e.,
the
production
source.
Given
that
post­
translational
processes
(
including
but
not
limited
to
methylation
and
glycosylation)
may
vary
with
the
source
and
can
affect
the
chemical
properties
of
an
enzyme,
EPA
anticipates
that
information
about
an
enzyme

s
source
will
be
useful
in
precisely
and
unambiguously
identifying
and
distinguishing
between
enzymes.

Using
production
source
information
for
identification
of
enzymes
is
consistent
with
current
practices
of
the
scientific
community,
enzyme
manufacturers,
and
protein
database
repositories.
Source
may
provide
information
about
differences
in
chemical
structure
or
chemical
properties,
including
post­
translational
changes
associated
with
different
production
sources
that
would
not
be
reflected
in
the
amino
acid
sequence.
Source
information
may
also
allow
identification
of
potential
impurities
or
byproducts
associated
with
particular
organisms
or
manufacturing
platforms.
Such
indirect
information
about
chemical
structure
or
properties
would
be
particularly
important
when
product
purity
or
technical
difficulties
make
obtaining
accurate
sequence
information
difficult
or
even
impossible.
Finally,
as
with
function,
source
information
is
readily
available
to
submitters.
The
Agency
is
seeking
guidance
as
to
how
specifically
original
and
production
source
should
be
described
to
uniquely
identify
enzymes,
if
original
and/
or
production
source
were
to
be
a
part
of
the
enzyme
definition.

VI.
D.
Processing
The
PROCESSING
of
an
enzyme
refers
to
procedures
used
to
isolate
the
enzyme
from
the
production
organism
or
manufacturing
platform,
procedures
used
to
purify
the
enzyme,
and/
or
any
chemical
reactions
to
which
the
enzyme
is
subjected
to
produce
the
final
enzyme
product.
Certain
processing
information
would
enable
EPA
to
identify
chemical
differences
among
enzymes
that
resulted
from
the
way
in
which
they
were
isolated
and
purified.
Certain
processes
may
change
chemical
properties
such
as
structure,
product
stability,
efficacy,
and
use.
The
use
of
certain
processing
information
would
allow
identification
and
review
of
modified
enzymes
and
corresponding
reaction
byproducts
that
result
from
the
chemical
treatment
and
would
enable
EPA
to
review
new
techniques
for
isolating
and
modifying
enzymes.
The
Agency
is
seeking
guidance
as
to
what
processing
techniques
would
be
appropriate
to
include
and
at
what
level
of
detail
they
should
be
described
to
uniquely
identify
enzymes
if
processing
were
to
be
included
as
part
of
the
enzyme
definition.
Page
10
of
21
Page
11
of
21
Questions
for
the
SAP
Panel
EPA
is
proposing
the
use
of
four
data
elements
(
function,
sequence,
source,
and
processing)
for
comprehensively
listing
and
distinguishing
among
enzymes
on
the
TSCA
Inventory.
The
following
questions
are
intended
to
help
the
Agency
make
a
final
decision
on
how
enzymes
will
be
listed
on
the
Inventory
in
the
future.

Function
The
FUNCTION
of
an
enzyme
refers
to
its
catalytic
activity.
Internationally­
accepted
nomenclature
conventions
of
the
Nomenclature
Committee
of
the
International
Union
of
Biochemistry
and
Molecular
Biology
(
NC­
IUBMB)
describe
and
categorize
enzymes
based
on
their
function.
The
NC­
IUBMB
assigns
enzymes
an
Enzyme
Committee
(
EC)
code
number
based
on
the
specific
reaction(
s)
catalyzed
by
the
enzyme,
the
nature
of
the
bond
involved,
and
the
substrate
acted
upon.
EPA
intends
to
incorporate
function
into
TSCA
Inventory
enzyme
listings
by
using
these
EC
codes
and
the
systematic
name
for
the
specific
catalytic
activity.
In
the
questions
below,
please
identify
the
scientific
merit
for
using
function
information
to
differentiate
among
enzymes
and
identify
what
level
of
detail
regarding
function
would
be
scientifically
appropriate
for
this
purpose.

1.
While
the
Agency
recognizes
the
practical,
historical
advantages
of
using
function
to
describe
enzymes,
in
the
context
of
the
Agency's
need
for
unique
and
unambiguous
naming,
what
is
the
scientific
rationale
for
identifying
an
enzyme
based
on
the
chemical
reaction(
s)
it
catalyzes?

2.
How
precise
is
the
IUBMB
EC
categorizing
system
for
describing
enzyme
function?
For
example,
in
addition
to
the
EC
function
category
to
which
an
enzyme
belongs,
what
additional
information
about
enzyme
structure
and/
or
chemical
properties,
if
any,
would
be
gained
by
a
more
detailed
functional
description
that
included
a.
enzyme
reaction
conditions
(
e.
g.,
pH
range,
reaction
temperature
range)?

b.
non­
catalytic
enzyme
functions
that
are
not
represented
by
EC
codes
(
e.
g.,
binding
properties)?

c.
other
additional
information
about
function
that
could
be
used
to
differentiate
enzymes
(
please
specify
what
would
be
of
value)?

3.
The
Agency
is
trying
to
gauge
the
probable
comprehensiveness
of
enzyme
catalytic
function
descriptions
for
subsequent
enzyme
reporting.

a.
How
common
are
multifunctional
enzymes?

b.
How
frequently
are
new
catalytic
functions
for
existing
enzymes
discovered?

c.
How
good
are
existing
models
to
assess
the
likelihood
that
an
enzyme
may
have
several
catalytic
functions?

d.
What
information
is
required
to
utilize
such
models?
Page
12
of
21
Sequence
The
AMINO
ACID
SEQUENCE
of
an
enzyme
is
known
as
its
primary
structure.
It
is
a
systematic
representation
of
the
linear
sequence
of
amino
acids
that
are
connected
via
amide
bonds
to
form
a
polypeptide.
In
the
questions
below,
please
consider
what
scientific
support
there
is
for
using
sequence
information
to
differentiate
among
enzymes
and
what
level
of
detail
would
be
scientifically
appropriate
for
this
purpose.

4.
What
information
about
an
enzyme
could
be
gained
by
identifying
it
based
on
its
amino
acid
sequence?

5.
The
Agency
is
trying
to
assess
the
expected
amount
of
variation
in
an
enzyme
amino
acid
sequence
due
to
various
causes
in
spite
of
current
quality
control
standards.

a.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
produced
in
multiple
batches
that
will
arise
due
to
unintended
differences
in
production
conditions?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

b.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
within
a
given
sample
of
a
single
production
batch
due
to
individual­
level
variation
in
an
enzyme­
producing
population?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

c.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
across
multiple
samples
collected
over
time
(
e.
g.,
in
microbial
cultures
stored
for
extended
periods)
due
to
changes
in
an
enzyme­
producing
population?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

i.
Over
what
time
scale
will
such
variation
arise?
That
is,
is
there
a
predictable
relationship
between
the
amount
of
variation
and
the
length
of
time
in
culture?

ii.
What
kinds
of
changes
might
occur
to
an
enzyme
preparation
if
naturally
occurring
variants
become
the
dominant
component
(
e.
g.,
changes
in
rates
of
activity,
reactions
catalyzed,
substrate
range,
response
to
environmental
conditions)?

iii.
Have
any
enzymes
in
commerce
or
research
been
known
to
change
in
amino
acid
sequence
over
time?
Have
any
been
known
to
remain
unchanged
in
amino
acid
sequence
for
a
year/
decade
or
longer?

6.
EPA
is
trying
to
judge
whether
a
scientifically
appropriate
level
of
maximum
permissible
overall
amino
acid
sequence
variation
could
be
determined
when
identifying
a
specific
enzyme.

a.
What
types
of
differences
may
exist
among
enzyme
variants
that
differ
by
a
single
amino
acid
change?
that
differ
in
amino
acid
composition
by
0.5%?
1%?
10%?
etc.?
Page
13
of
21
b.
How
much
does
the
region
of
the
enzyme
in
which
the
variation
occurs
matter?
For
example,
how
important
are
changes
in
the
amino
acid
sequence
of
the
active
site
versus
the
rest
of
the
molecule?
Are
there
other
regions
of
the
enzyme
that
are
considered
important,
i.
e.,
where
sequence
is
generally
conserved?

c.
How
important
are
deletions
and/
or
excisions
in
determining
differences
between
enzymes?

d.
How
easy
would
it
be
for
a
typical
enzyme
manufacturer
to
determine
the
location
of
the
active
site
or
other
specific
regions
mentioned
in
6b?

7.
EPA
wants
to
assess
the
efficacy
of
existing
sequencing
technologies.

a.
How
accurate
and
reproducible
are
readily
available
amino
acid
sequencing
techniques
and
instrumentation?

b.
How
accurate
and
reproducible
are
readily
available
nucleotide
sequencing
techniques
and
instrumentation?

c.
Does
the
accuracy
of
the
result
depend
on
the
choice
of
method?

d.
How
rapidly
are
sequencing
techniques
improving
or
new
techniques
being
developed?

e.
How
reliably
can
one
predict
the
amino
acid
sequence
of
the
final
gene
product
based
on
the
nucleotide
sequence?

8.
What
additional
information
would
be
gained,
if
any,
by
a
more
detailed
structural
description
that
included
in
addition
to
amino
acid
sequence:

a.
glycosylation
sites
(
and
the
composition
of
these
carbohydrate
moieties),

b.
coenzymes
(
prosthetic
groups),

c.
cofactors,
and/
or
d.
other
post­
translational
modifications
to
residues
of
the
amino
acid
chain?

Source
The
SOURCE
of
an
enzyme
refers
to
(
1)
the
organism
from
which
the
gene
encoding
the
enzyme
was
derived,
i.
e.,
the
original
source
and
(
2)
the
organism
or
manufacturing
platform
(
e.
g.,
tissue
culture)
in
which
the
enzyme
is
produced,
i.
e.,
the
production
source.
In
the
questions
below,
please
consider
what
scientific
support
there
is
for
using
source
information
to
differentiate
among
enzymes
and
what
level
of
detail
would
be
scientifically
appropriate
for
this
purpose.

9.
What
information
about
an
enzyme's
structure
could
be
gained
by
knowing
a.
the
original
source
of
the
enzyme?

b.
the
production
source
of
the
enzyme?

10.
If
original
source
information
were
used
as
an
identification
element
to
discriminate
among
enzymes,
what
level
of
taxonomic
specificity
(
e.
g.,
family,
genus,
species,
subspecies,
population,
biovar,
culture
line)
would
be
most
scientifically
appropriate
to
use
for
each
of
the
following
categories?
What
if
production
source
information
were
used?
(
Note:
EPA
recognizes
that
taxonomic
revisions
may
change
the
names
of
particular
organisms
and
can
Page
14
of
21
utilize
mechanisms
for
normalizing
organism
nomenclature,
but
that
consideration
does
not
need
to
be
addressed
by
the
panel.)

a.
plants
b.
animals
c.
fungi
d.
bacteria
e.
other
micro­
organisms
11.
How
could
source
be
described
if
taxonomic
names
were
inappropriate
because
either
the
original
or
production
source
were
artificial?
Examples
of
such
new
technologies
could
include
enzymes
produced/
developed
through
gene
splicing
or
ex
vivo
chemical
synthesis.

12.
What
information
about
an
enzyme's
structure
could
be
gained
by
additional
details
about
source
including:

a.
the
particular
tissue
or
organ
of
a
given
source
organism
from
which
they
were
derived
(
e.
g.,
swine
pancreatic
tissue
vs.
swine
salivary
glands)?

b.
the
chemical,
geographic,
and/
or
environmental
conditions
from
which
source
organisms
were
isolated
(
e.
g.,
soil,
water,
feces,
etc.)?

c.
manipulations
of
the
enzyme

s
original
source
prior
to
gene
transfer
(
e.
g.,
through
rDNA
technology,
radiation
treatment,
altered
rearing
conditions,
etc.)?

d.
manipulations
of
an
enzyme

s
production
source
prior
to
and/
or
following
gene
transfer?

e.
other
relevant
aspects
of
source
that
are
not
mentioned
(
please
specify
what
would
be
of
value).

Processing
The
PROCESSING
of
an
enzyme
refers
to
procedures
used
to
isolate
the
enzyme
from
the
production
organism
or
manufacturing
platform,
procedures
used
to
purify
the
enzyme,
and/
or
any
chemical
reactions
to
which
the
enzyme
is
subjected
to
produce
the
final
enzyme
product.
In
the
questions
below,
please
consider
what
scientific
support
there
is
for
using
certain
processing
information
to
differentiate
among
enzymes
and
identify
the
level
of
detail
that
would
be
scientifically
appropriate
for
this
purpose.

13.
What
information
about
an
enzyme's
structure
could
be
gained
by
knowing
which
of
certain
processing
techniques
were
used
in
its
production?

14.
EPA
anticipates
that
certain
processing
techniques
may
be
so
routine
and/
or
chemically
inconsequential
that
their
reporting
would
be
unnecessary,
while
other
processing
techniques
would
have
significant
effects
on
the
chemical
structure
and/
or
properties
of
an
enzyme.
The
Agency
is
trying
to
assess
how
practical
it
would
be
to
create
a
list
of
processing
techniques
that
need
not
be
included
as
part
of
enzyme
identity.

a.
What
processing
techniques
are
used
in
the
isolation
and
purification
of
enzymes?
Page
15
of
21
b.
Which
processing
techniques
could
change
the
chemical
structure
of
the
enzyme?
Which
could
change
chemical
properties
that
would
indicate
an
underlying
structural
change?

c.
Describe
the
chemical
or
structural
changes
expected
to
occur
from
the
use
of
the
processing
techniques
identified
in
14(
b).

d.
Which
processing
techniques
would
not
be
expected
to
cause
any
structural
changes
to
the
enzyme?
Which
would
not
be
expected
to
cause
any
chemical
property
changes?

15.
EPA
is
trying
to
anticipate
whether
inclusion
of
processing
in
enzyme
identity
will
increase
in
importance
as
a
result
of
future
advances
in
enzyme
production.

a.
What
new
processing
techniques
are
being
developed?

b.
How
might
these
techniques
change
an
enzyme's
chemical
structure
or
properties?

c.
How
frequently
are
new
processing
techniques
for
enzymes
adopted?

Other/
General
Questions:

16.
Aside
from
function,
sequence,
source,
and
processing,
are
any
other
data
elements
crucial
for
enzyme
identification?

17.
Are
there
any
special
considerations
that
should
be
taken
into
account
when
identifying
enzymes
with
multiple,
non­
identical
subunits?
For
example,
a.
when
only
one
subunit
is
modified?
b.
when
a
modified
enzyme
is
a
component
of
an
enzyme
complex?
c.
when
a
multi­
functional,
multi­
component
enzyme
performs
a
sequence
of
reactions?
d.
when
an
enzyme
has
another
non­
catalytic
function,
e.
g.,
a
binding
site?
e.
under
any
other
circumstances?

18.
Although
EPA
believes
that
all
four
identification
elements
are
critical
for
enzyme
identification
for
TSCA
purposes,
the
Agency
is
trying
to
judge
their
relative
importance.
a.
Do
any
data
elements
warrant
greater
emphasis
than
others
because
differences
in
those
data
element(
s)
reflect
more
significant
differences
in
an
enzyme's
physical
and/
or
chemical
properties
than
the
others
do?

b.
If
data
for
sequence,
source,
and
processing
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
function?

c.
If
data
for
function,
sequence,
and
processing
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
original
source?
production
source?

d.
If
data
for
function,
sequence,
and
source
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
processing?
Page
16
of
21
Page
17
of
21
Appendix
I:
Definitions
and
Examples
of
Substances
on
the
TSCA
Inventory
I.
CLASS
1,
CLASS
2,
AND
UVCB
SUBSTANCES
The
TSCA
Inventory
lists
chemical
substances
with
diverse
characteristics,
and
Inventory
nomenclature
conventions
vary
accordingly.
In
terms
of
composition,
some
chemical
substances
are
single
compounds
composed
of
molecules
with
particular
atoms
arranged
in
a
definite,
known
structure.
EPA
designates
such
substances
as
Class
1
substances.
Examples
of
Class
1
substances
include:
acetone,
iron,
benzene,
and
dimethylmercury.

Some
commercial
chemical
substances
have
unknown
or
variable
structures
or
compositions,
or
they
are
composed
of
a
complex
combination
of
different
molecules.
EPA
designates
these
as
Class
2
substances.
Many
Class
2
substances
(
including
enzymes)
are
called
UVCB
substances,
for
"
chemical
substances
of
unknown
or
variable
composition,
complex
reaction
products
and
biological
materials."
Each
name
for
a
UVCB
substance
represents
more
than
one
molecular
entity;
as
such,
each
UVCB
can
be
considered
to
be
a
narrowly­
defined
category
of
molecules,
often
closely
related.
Examples
of
Class
2
UVCB
substances
are
listed
below.

II.
INVENTORY
DEFINITIONS
FOR
UVCB
CHEMICAL
SUBSTANCES
Entries
on
the
Inventory
identify
the
commercial
chemical
substance
as
precisely
as
possible
using
the
information
reported
by
the
submitter.
Listings
depend
on
the
degree
of
knowledge
that
the
submitters
possess
and
report
about
such
substances
as
well
as
on
how
submitters
intend
to
represent
the
chemical
identities
to
the
Agency
and
to
customers.
Therefore,
sometimes
substances
that
are
chemically
indistinguishable
or
even
identical
have
different
listings
on
the
Inventory.
On
the
other
hand,
sometimes
a
lack
of
detail
in
submitted
information
results
in
UVCB
substances
with
Chemical
Abstracts
(
CA)
Names
that
are
not
specific
or
complete
enough
to
permit
unambiguous
identification
of
the
substance.
The
CA
names
for
such
substances
may
contain:

°
Process
terms
that
are
not
chemically
descriptive
(
e.
g.,
distillation
residues,
distillation
overheads,
by­
products,
low­
boiling,
catalytic
reformed);
°
Trade
jargon
(
e.
g.,
slack
wax,
spelter,
winterized,
deodorized
distillates,
steep
liquor,
foots
oil);
°
Unqualified
or
very
broadly
qualified
substance
class
terms
(
e.
g.,
pyridine
bases,
petroleum
resins,
phenols
(
petroleum));
or
°
Physical
rather
than
chemical
terms
(
e.
g.,
microcrystalline,
pulp,
agglomerates,
sinter,
viscous).

The
substances
with
inadequate
CA
Names
are
further
described
with
supplemental
"
definitions"
that
are
considered
an
integral
part
of
the
name
for
TSCA
purposes.
In
general,
the
definitions
serve
to
narrow
the
scope
of
the
CA
Names.
Thus,
any
substance
that
matches
a
CA
Name
on
the
TSCA
Inventory
but
does
not
match
the
Inventory
substance
definition
is
not
considered
to
be
covered
by
that
Inventory
name.
Page
18
of
21
UVCB
chemical
substance
definitions
typically
begin
by
stating
that
the
substance
is
a
combination
of
substances
of
a
certain
class
and
indicating
the
nature
or
the
process
by
which
it
was
derived.
The
next
sentence(
s)
usually
identify
the
predominant
components.
UVCB
chemical
substance
definitions
also
may
include
information
such
as
the
typical
or
allowed
carbon
number,
physical
properties
ranges,
the
types
of
atoms
or
substances
that
may
be
included,
and/
or
the
raw
material
sources
or
processes
of
manufacture.

III.
EXAMPLES
OF
UVCB
NOMENCLATURE
The
following
examples
of
Inventory
names
are
provided
to
illustrate
the
variability
of
Inventory
listings.
These
examples
are
not
an
exhaustive
representation
of
all
possible
terms
used
in
TSCA
Inventory
names.
They
are
presented
only
to
demonstrate
that
Inventory
UVCB
names
vary
according
to
the
type
of
chemical
substance
being
described.

III.
A.
Substances
of
Unknown
Composition
A
wide
variety
of
substances
of
unknown
composition
are
listed
on
the
TSCA
Inventory.
Examples
include
distillation
residues,
spent
cooking
or
neutralizing
liquors,
and
residual
oils.
Each
Inventory
substance,
however,
has
a
commercial
purpose
under
TSCA;
if
it
were
an
impurity,
a
byproduct,
or
a
waste
with
no
commercial
use,
it
would
not
be
eligible
for
TSCA
Inventory
listing.

Example
1.
Dust,
iron­
ore,
sinter
(
CASRN5
69012­
53­
9)

The
UVCB
definition
for
this
substance
is:
"
Dust
generated
during
the
making,
breaking
and
handling
of
sinter
which
is
recovered
through
the
use
of
pollution
abatement
equipment."

5
CAS
Registry
Number.
Page
19
of
21
Example
2.
Fuel
oil,
no.
2
(
CASRN
68476­
30­
2)

The
UVCB
definition
for
this
substance
is:
"
A
distillate
oil
having
a
minimum
viscosity
of
32.6
SUS
at
100

F
to
a
maximum
of
37.9
SUS
at
100

F"

III.
B.
Substances
of
Variable
Composition
Many
substances
with
variable
composition
are
listed
on
the
Inventory.
The
examples
below
demonstrate
how
source
terms
may
be
used
in
Inventory
names
when
the
submitter
reports
the
use
of
a
single
source.
Process
terms
are
used
if
they
are
provided
by
the
submitter,
are
wellknown
and
are
well­
described.

Example
3.
Fatty
acids,
soya
(
CASRN
68308­
53­
2)

This
substance
has
no
UVCB
definition.
It
is
a
UVCB
substance
because
it
includes
variable
carbon
chain
lengths:
soya
fatty
acids
are
a
mixture
of
saturated
and
unsaturated
C14­
C18
fatty
acids.

Example
4.
Fatty
acids,
castor­
oil
(
CASRN
61789­
44­
4)

This
substance
has
no
UVCB
definition.
It
is
a
UVCB
substance
because
this
substance
includes
variable
carbon
chain
lengths:
castor­
oil
fatty
acids
are
a
mixture
of
saturated
and
unsaturated
C14­
C18
fatty
acids.
This
substance
is
listed
separately
in
the
Inventory
from
Example
3
because
the
fatty
acids
are
derived
from
a
different
source.

Example
5.
Fatty
acids,
castor­
oil,
hydrogenated
(
CASRN
61790­
39­
4)

This
substance
has
no
UVCB
definition.
It
is
a
UVCB
substance
because
this
substance
includes
variable
carbon
chain
lengths.
This
substance
is
listed
separately
in
the
Inventory
from
Example
4
because
additional
chemical
processing
was
carried
out
on
the
fatty
acids.

Example
6.
Natural
gas
(
petroleum),
raw
liq.
mix
(
CASRN
64741­
48­
6)

The
UVCB
definition
for
this
substance
is:
"
A
complex
combination
of
hydrocarbons
separated
as
a
liquid
from
natural
gas
in
a
gas
recycling
plant
by
processes
such
as
refrigeration
or
absorption.
It
consists
mainly
of
saturated
aliphatic
hydrocarbons
having
carbon
numbers
in
the
range
of
C2
through
C8."
Thus,
this
substance
includes
variable
carbon
chain
lengths.

III.
C.
Substances
that
are
Biological
Materials
or
are
Made
from
Biological
Materials
Some
chemicals
derived
from
biological
materials
are
completely
defined
in
terms
of
chemical
structure
and
thus
are
listed
as
Class
1
substances,
e.
g.,
sucrose.
However,
numerous
biological
materials
and
chemicals
derived
from
biological
materials
are
listed
as
UVCB
substances
on
the
TSCA
Inventory,
either
by
themselves
or
as
components
of
further
reaction
products;
including
enzymes,
organisms,
and
products
of
the
biotechnology
industry.
Names
of
these
more
complex
Page
20
of
21
structures
often
define
the
chemical
identity
with
certain
elements
that
characterize
the
chemical
in
terms
of
source,
composition,
and/
or
manufacturing
processes.

Example
7.
Beeswax
(
CASRN
8012­
89­
3)

The
UVCB
definition
for
this
substance
is:
"
The
wax
obtained
from
the
honeycomb
of
the
bee.
It
consists
primarily
of
myricyl
palmitate,
cerotic
acid
and
esters
and
some
high­
carbon
paraffins."

Example
8.
Soybean,
flour
(
CASRN
68513­
95­
1)

The
UVCB
definition
for
this
substance
is:
"
A
fine­
ground
powder
made
by
steaming
soybeans,
followed
by
removal
of
hulls
and
mechanical
grinding."
If
another
type
of
soybean
flour
were
made
without
steaming
the
soybeans
or
without
removal
of
the
hulls,
the
resultant
flour
would
not
fit
within
this
definition
and
would
require
a
different
listing
on
the
Inventory.

Example
9.
Collagens
(
CASRN
9007­
34­
5)

The
UVCB
definition
for
this
substance
is:
"
A
fibrous
protein
comprising
one
third
of
the
total
protein
in
mammalian
organisms.
It
is
a
polypeptide
containing
three
peptide
chains
and
rich
in
proline
and
hydroxyproline."
In
this
case
source
is
defined
to
indicate
that
the
collagen
must
be
from
a
mammalian
species,
although
no
tissue
or
organ
source
is
specified.
Structure
is
defined
in
that
all
single
chain
proteins
are
excluded,
and
proline
and
hydroxyproline
must
be
abundant.

Example
10.
Gelatins
(
CASRN
9000­
70­
8)

The
UVCB
definition
for
this
substance
is:
"
A
complex
combination
of
proteins
obtained
by
hydrolysis
of
collagen
by
boiling
skin,
tendons,
ligaments,
bones,
etc."
In
this
case
no
specific
animal
(
or
tissue/
organ)
source
is
given,
although
the
source
of
the
collagen
used
to
produce
gelatin
must
meet
the
specifications
given
in
the
definition
of
collagen
(
example
9).
Any
acid/
base
catalytic
reaction
conditions
may
be
used
in
the
hydrolysis,
although
other
processing
reactions
performed
on
collagen
would
not
fall
under
this
definition.

Example
11.
Gelatins,
hydrolyzates
(
CASRN
68410­
45­
7)

The
UVCB
definition
for
this
substance
is:
"
Enzymatic
digest
produced
by
hydrolysis
of
gelatin."
If
the
gelatin
were
hydrolyzed
chemically
rather
than
enzymatically,
the
resultant
product
would
not
fit
the
definition
and
would
require
a
different
Inventory
listing.

Example
12.
Oils,
lavender
(
CASRN
8000­
28­
0)

The
UVCB
definition
for
this
substance
is:
"
Extractives
and
their
physically
modified
derivatives.
Lavandula
officianalis,
Labiatae."
Note
that
use
of
another
source
even
if
the
same
composition
of
oil
were
obtained
would
require
a
separate
Inventory
listing
since
it
would
represent
a
different
substance.
Page
21
of
21
Example
13.
Glutens,
corn
(
CASRN
66071­
96­
3)

The
UVCB
definition
for
this
substance
is:
"
The
dried
residue
from
corn
after
the
removal
of
the
larger
part
of
the
starch
and
germ
and
the
separation
of
the
bran
in
the
wet­
milling
manufacture
of
corn
starch
or
syrup,
or
by
enzymatic
treatment
of
the
endosperm."