Page
1
of
4
HED
DOC.
NO.
014634
August
07,
2001
MEMORANDUM
SUBJECT:
ZINC
OMADINE
­
Report
of
the
FQPA
Safety
Factor
Committee.

FROM:
Brenda
Tarplee,
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(
7509C)

THROUGH:
Ed
Zager,
Chair
FQPA
Safety
Factor
Committee
Health
Effects
Division
(
7509C)

TO:
Timothy
McMahon,
Risk
Assessor
Risk
Assessment
and
Science
Support
Branch
Antimicrobials
Division
(
7510C)

PC
Code:
088002
The
Health
Effects
Division
(
HED)
FQPA
Safety
Factor
Committee
met
on
June
25,
2001
to
evaluate
the
hazard
and
exposure
data
for
zinc
omadine
and
recommended
that
the
FQPA
safety
factor
(
as
required
by
the
Food
Quality
Protection
Act
of
August
3,
1996)
be
retained
at
10x
in
assessing
the
risk
posed
by
this
chemical.
Page
2
of
4
I.
HAZARD
ASSESSMENT
(
Memorandum:
T.
McMahon
to
E.
Zager
dated
06/
07/
01)

1.
Adequacy
of
Toxicity
Database
The
toxicology
data
base
for
zinc
omadine
is
incomplete.
There
is
a
data
gap
for
the
twogeneration
reproduction
study
in
rats.
Also,
the
HIARC
required
a
developmental
neurotoxicity
study
be
conducted
with
zinc
omadine
(
see
I.
3.
below).

2.
Determination
of
Susceptibility
There
is
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
zinc
omadine
in
the
developmental
toxicity
studies
in
both
rats
and
rabbits.
In
rats,
fetal
effects
were
manifested
as
increased
incidence
of
fused
ribs
at
the
same
dose
that
caused
only
minimal
maternal
toxicity
(
salivation).
In
the
rabbit
study,
fetal
effects
were
manifested
as
increased
post­
implantation
loss
and
decreased
viable
fetuses
at
the
same
dose
that
caused
only
minimal
maternal
toxicity
(
resorptions).

Reproductive
susceptibility
could
not
be
assessed
following
pre­/
postnatal
exposure
to
zinc
omadine
since
there
is
a
data
gap
for
the
2­
generation
reproduction
study
in
rats.

3.
Requirement
of
a
Developmental
Neurotoxicity
Study
The
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
zinc
omadine
is
required
due
to
the
observance
of
neurotoxicity
and
the
presence
of
neuropathology
(
axonal
degeneration)
in
the
toxicology
data
base.

4.
Other
Findings
in
Open
Literature
Publications
in
the
open
literature
indicate
neurotoxicity
in
adult
animals
at
doses
of
approximately
3
mg/
kg/
day
and
higher
(
HED
Doc.
No.
013318).

II.
EXPOSURE
ASSESSMENT
AND
RISK
CHARACTERIZATION
(
Memorandum:
T.
McMahon
to
E.
Zager
dated
06/
07/
01)

1.
Dietary
(
Food)
Exposure
Considerations
Dietary
exposure
to
zinc
omadine
can
occur
indirectly
from
the
incorporation
of
zinc
omadine
into
sponges
as
well
as
in
dishwashing
detergent.
Zinc
omadine
is
also
incorporated
into
plastics
that
are
used
in
manufacture
of
food
storage
containers.
Residues
of
zinc
omadine
are
assumed
to
exist
on
dishware
and
food
contact
surfaces
from
these
uses.
Page
3
of
4
There
are
no
agricultural
uses
for
zinc
omadine
and
no
metabolites
of
zinc
omadine
that
currently
require
regulation.
FDA
Models
and
worst­
case
assumptions
were
employed
to
estimate
potential
dietary
exposure
(
Recommendations
for
Chemistry
Data
for
Indirect
Food
Additive
Petitions;
June
1995,
FDA).

2.
Dietary
(
Drinking
Water)
Exposure
Considerations
Drinking
water
exposures
to
zinc
omadine
were
estimated
using
EPA
methodologies.
There
were
no
monitoring
data
available
for
zinc
omadine
so
worst
case
assumptions
were
made
regarding
exposure
(
i.
e.
drinking
water
exposure
was
assumed
to
be
equal
to
the
residue
that
was
estimated
to
leach
from
sponges
or
that
was
contained
in
dishwashing
liquid).

3.
Residential
Exposure
Considerations
Zinc
omadine
is
registered
as
a
preservative
for
many
home
use
products.
Postapplication
exposure
to
infants
and
children
could
occur
as
a
result
of
this
use.
No
chemical­
specific
exposure
data
are
available
for
zinc
omadine.
The
Draft
Standard
Operating
Procedures
for
Residential
Exposure
Assessments
will
be
used
as
the
basis
for
all
post­
application
risk
assessment
scenarios.

III.
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
1.
FQPA
Safety
Factor
Recommendation
The
Committee
recommended
that
the
FQPA
safety
factor
for
protection
of
infants
and
children
(
as
required
by
FQPA)
should
be
retained
at
10x
for
zinc
omadine.

2.
Rationale
for
Retaining
the
FQPA
Safety
Factor
The
FQPA
SFC
concluded
that
the
FQPA
safety
factor
be
retained
at
10x
for
the
following
weight­
of­
evidence
considerations:


there
is
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
zinc
omadine
in
the
developmental
toxicity
studies
in
rats
and
rabbits;


there
is
a
data
gap
for
the
2­
generation
reproduction
study
in
rats;


susceptibility
can
not
be
assessed
following
pre­/
postnatal
exposure
to
zinc
omadine
since
there
is
a
data
gap
for
the
2­
generation
reproduction
study
in
rats;
and
Page
4
of
4

a
developmental
neurotoxicity
study
with
zinc
omadine
is
triggered
due
to
the
observance
of
neurotoxicity
and
the
presence
of
neuropathology
(
axonal
degeneration)
in
the
toxicology
data
base.

3.
Application
of
the
Safety
Factor
­
Population
Subgroups
/
Risk
Assessment
Scenarios
The
safety
factor
is
required
for
All
Population
Subgroups
when
assessing
Acute
and
Chronic
Dietary
Exposure
and
Residential
Exposures
of
All
Durations
due
to
the
weight
of
the
evidence
stated
above.
