PMD, a Registered Botanical Mosquito Repellent with Deet-Like Efficacy

Abstract

para-Menthane-3,8-diol(PMD) is a monoterpene spent product of the distillation of leaves of the Australian lemon-scented gum tree (updated nomenclature Corymbia citriodora ssp. citriodora). In April 2005, the U.S. Centers for Disease Control and Prevention (CDC) endorsed two non-deet mosquito repellents, including PMD. However, few mosquito professionals have in-depth familiarity with the history and efficacy of PMD. In this article, we describe the origin and development of PMD as a repellent and offer a comprehensive review of its performance against Aedes, Anopheles, Culex, and Ochlerotatus. In addition, we present original data from field and laboratory studies involving large numbers of subjects and comparisons with high-concentration deet and other repellents. We conclude that not only is the CDC endorsement warranted but also that it probably underestimates the value of PMD as a deet alternative for public health applications.

Full text

Journal
of
the
American
Mosquito
Control
Association,
22(3):507-514,
2006
Copyright
(C)
2006
by
The
American
Mosquito
Control
Association,
Inc.
PMD,
A
REGISTERED
BOTANICAL
MOSQUITO
REPELLENT
WITH
DEET-LIKE
EFFICACY
SCOTT
P.
CARROLL
AND
JENELLA
LOYE
Department
of
Entomology,
University
of
California-Davis,
and
Carroll-Loye
Biological
Research,
711
Oak
Avenue,
Davis,
CA
95616
ABSTRACT.
para-Menthane-3,8-diol(PMD)
is
a
monoterpene
spent
product
of
the
distillation
of
leaves
of
the
Australian
lemon-scented
gum
tree
(updated
nomenclature
Corymbia
citriodora
ssp.
citriodora).
In
April
2005,
the
U.S.
Centers
for
Disease
Control
and
Prevention
(CDC)
endorsed
two
non-deet
mosquito
repellents,
including
PMD.
However,
few
mosquito
professionals
have
in-depth
familiarity
with
the
history
and
efficacy
of
PMD.
In
this
article,
we
describe
the
origin
and
development
of
PMD
as
a
repellent
and
offer
a
comprehensive
review
of
its
performance
against
Aedes,
Anopheles,
Culex,
and
Ochlerotatus.
In
addition,
we
present
original
data
from
field
and
laboratory
studies
involving
large
numbers
of
subjects
and
comparisons
with
high-concentration
deer
and
other
repellents.
We
conclude
that
not
only
is
the
CDC
endorsement
warranted
but
also
that
it
probably
underestimates
the
value
of
PMD
as
a
deet
alternative
for
public
health
applications.
KEY
WORDS
Aedes,
Anopheles,
Culex,
Ochlerotatus,
Corymbia
citriodora,
deet,
lemon
eucalyptus,
malaria,
p-menthane-3,8-diol,
PMD,
repellent
INTRODUCTION
Mosquito-transmitted
disease
continues
to
be
a
major
source
of
illness
and
death.
Most
parasitic
diseases
are
tropical,
and
intensifying
globalization
and
climatic
change
are
increasing
the
risk
of
cntracting
arthropod-borne
illnesses
(Brower
and
Chalk
2003,
Guenier
et
al.
2004).
One
ongoing
example
is
West
Nile
virus;
current
federal
statistics
indicate
that
it
will
be
responsi-
ble
for
thousands
of
cases
of
neuroinvasive
disease
in
North
America
over
the
next
several
years
(CDC
2005a).
Vector
control
and
other
public
health
initiatives
may
reduce
danger
of
contracting
disease,
but
persistent
risk
indicates
that
prevention
of
mosquito
bites
is
a
prudent
strategy
for
immediate
disease
avoidance.
Com-
mercial
insect
repellents
containing
the
active
H,N-diethyl-m-methylbenzamide
(deer)
have been
used
for
decades
as
highly
effective
and
generally
safe
means
of
bite
control
(Osimitz
and
Grothaus
1995).
Despite
its
excellent
repellency,
many
consum-
ers
do
not
use
deer
because
of
concerns
about
safety,
comfort,
and
its
plasticizing
capacity.
They
may
instead
use
other
types
of
repellents,
particularly
botanicals,
despite
that
most
are
of
relatively
low
efficacy
(Fradin
and
Day
2002).
Hence,
it
is
notable
that
in
April
2005,
the
Centers
for
Disease
Control
and
Prevention
(CDC)
added
two
non-deer
products
to
their
list
of
repellents
of
public
health
value
(CDC
2005b).
One
of
the
newly
recommended
actives
is
the
terpene
para-menthane
3,8-diol
(PMD),
obtained
from
botanical
sources
or
synthesized,
and
the
other
is
picaradin
(KBR3023),
a
synthetic
mar-
keted
under
the
trade
name
Autan
for
several
years
in
Europe,
and
beginning
in
2005
as
Cutter
Advanced
in
the
USA.
Although
their
endorse-
ment
by
CDC
offers
promise
to
programs
and
individuals
needing
deet
alternatives,
neither
is
well-known
to
professionals
or
the
U.S.
public.
This
article
focuses
on
PMD,
its
history
of
development,
and
its
efficacy.
Our
treatment
is
divided
into
two
sections.
In
the
first
section,
we
review
all
literature
we
could
obtain
on
PMD
pertaining
to
its
utility
as
a
mosquito
repellent.
In
the
second
section,
we
augment
what
is
known
about
the
performance
of
PMD,
particularly
in
the
United
States,
with data
from
our
own
field
and
laboratory
trials
comparing
Repel
TM
Brand
PMD-based
repellent
against
other
commercial
repellents,
including
high-
and
low-concentration
deet
and
S.C.
Johnson
Offl
Botanicals
TM,
which
uses
synthetic
PMD
at
a
relatively
low
concen-
tration.
PMD:
DEVELOPMENT
HISTORY,
SOURCE,
AND
PERFORMANCE
REVIEW
A
variety
of
plant
essential
oils
repel
blood-
feeding
arthropods,
and
several
are
used
in
commercial
repellent
products
(Curtis
et
al.
1991,
Fradin
and
Day
2002).Volatile
monoterpe-
noids
are
the
active
molecules
in
most
such
oils,
and
although
their
vapor
pressure
probably
promotes
their
repellency,
it
also
results
in
rapid
dissipation
of
efficacy
(Barasa
et
al.
2002).
At
high
concentrations
needed
to
enhance
duration,
dermatitis
may
result
(Barnard
1999).
As
a
mono-
terpene
of
relatively
low
volatility,
PMD
may
be
especially
promising
as
a
deet
alternative
(Barasa
et
al.
2002).
PMD
was
isolated
from
so-called
"lemon
eucalyptus"
leaves
as
part
of
mass
screenings
of
507

508
JOURNAL
OF
THE
AMERICAN
MOSQUITO
CONTROL
ASSOCIATION
VOL.
22,
No.
plants
for
repellent
properties
undertaken
in
China
beginning
in
1960
(Curtis
et
al.
1991).
Called
quwenling
("effective
mosquito
repeller"),
it
is
the
principal
waste
material
resulting
from
the
hydrodistillation
of
the
essential
oil
from
the
leaves
(Curtis
et
al.
1990).
Thus,
the
repellent
is
not
"oil
of
lemon
eucalyptus"
but
is
instead
the
leftovers
of
that
oil's
distillation
process.
The
source
tree
is
native
to
eastern
Queensland,
Australia,
and
planted
pantropically
and
sub-
tropically.
In
Australia,
it
is
called
"lemon-
scented
gum,"
and
its
botanical
name
was
until
recently
Eucalyptus
maculata
subsp,
citriodora.
Systematic
reorganization
of
the
genus
Eucalyp-
tus
(Hill
and
Johnson
1995)
led
to
its
placement
in
the
genus
Corymbia
as
well
as
the
elevation
and
further
division
of
the
subspecies.
Lemon-scented
gum,
then,
is
Corymbia
citriodora
(Hook.)
Hill
&
Johns.
subsp,
citriodora
(Henderson
2002).
In
China,
the
repellent
properties
of
PMD
were
successfully
commercialized,
and
it
is
widely
used
there
in
an
ethanol
base
(Curtis
et
al.
1991).
Li
et
al.
(1974)
(summarized
in
Curtis
et
al.
1991)
reported
high,
long-lasting
efficacy
against
Aedes
spp.
in
the
laboratory
and
field.
In
addition,
Nishimura
(unpublished
data
cited
in
Watanabe
et
al.
1993)
observed
high
efficacy
of
both
cis-
and
trans-isomers
of
PMD.
In
contrast,
the
first
western
studies
showed
mediocre-to-good
perfor-
mance
of
10-30%
PMD,
but
at
a
level
normally
below,
and
never
exceeding,
that
of
10-20%
deet
in
laboratory
and
field
tests
against
Aedes
and
Anopheles
mosquitoes
(Schreck
and
Leonhardt
1991,
Collins
et
al.
1993).
Collins
et
al.
(1993)
obtained
their
PMD
in
the
form
of
a
Chinese
commercial
repellent,
and
it
seems
that
Schreck
and
Leonhardt
(1991)
did
so
as
well.
In
reformulations
by
MASTA
in
the
United
Kingdom
in
the
mid-1990s,
PMD
con-
centration
was
increased
to
50%,
and
ethanol
was
replaced
with
more
cosmetically
sophisticated
carriers
(Trigg
1996a).
The
result
was
enhanced
efficacy.
In
field
evaluations
against
An.
funestus
and
An.
gambiae,
MASTA
Mosi-guard
Natural
gel,
spray,
and
stick
formulations
gave
"complete
protection
from
biting"
for
6-7.75
h,
not
differ-
ent
from
a
50%
deet
spray,
with
similar
results
in
the
laboratory
(Trigg
and
Hill
1996).
These
were
the
first
studies
to
suggest
that
by
altering
formulation,
the
efficacy
of
PMD
might
be
enhanced
to
reach
that
of
a
deet
standard.
These
results
were
far
superior
to
those
obtainable
from
citronella,
the
best-known
botanical
active
then
(Trigg
and
Hill
1996)
and
now.
Subsequent
studies
in
the
laboratory
and
field
have
largely
confirmed
this
positive
assessment
(Table
1).
In
general,
PMD
and
deet
have
shown
similar
performance
against
mosquitoes
of
sever-
al
species
and
genera.
The
studies
listed
in
Table
found
90
or
95%
repellency
(relative
to
untreated
or
negative
controls)
for
4-8.5
h
(minimum
and
maximum
test
durations
were
independent
of
repellent
performance
in
some
studies).
In
laboratory
tests
against
species
in
three
genera,
Barnard
and
Xue
(2004)
ranked
PMD
first
of
12
commercial
repellents
in
a
test
that
included
potent
synthetics:
PMD
(20%)
>
KBR3023
(10%)
>
deet
(15%)
>
IR3535
(7.5%).
Similarly,
in
our
laboratory
study,
a
20%
PMD
product
outperformed
10%
deet
and
was
only
slight
less
repellent
than
30%
deet
over
8
h
(this
study).
In
the
field,
Moore
et
al.
(2002)
found
30%
PMD
superior
to
15%
deet
in
a
4-h
test
(97%
vs.
85%
repellency)
(Table
1).
In
the
study
of
Barnard
et
al.
(2002),
percentage
of
repellency
did
not
differ
statistically,
but
deet
seemed
to
be
consistently
slightly
superior.
In
our
field
study,
artificially
truncated
at
6
h,
20%
(lotion)
and
26%
(spray)
PMD
were
at
least
as
repellent
as
Deep
Woods
Off
lotion
(--20%
deet).
MATERIALS
AND
METHODS
We
measured
degree
and
duration
of
pro-
tection
with
arm-in-cage
tests
and
field
trials.
In
cage
testing,
effects
of
potentially
confounding
environmental
variables
were
reduced,
whereas
field
tests
provided
complementary
data
under
conditions
resembling
those
of
actual
use.
We
recruited
adult
volunteers
from
the
Life
Science
programs
at
the
University
of
California-Davis.
The
institutional
review
board
othe
University
of
California-San
Francisco
School
of
Medicine
and
the
Department
of
Pesticide
Regulation
of
the
California
Environmental
Protection
Agency
approved
the
study
protocol.
Wisconsin
Pharma-
cal
(also
known
as
WPC
Brands,
Inc.,
Jackson,
WI)
supplied
its
lemon
eucalyptus
repellents
by
courier,
and
the
other
repellents
were
purchased
over-the-counter
in
Davis,
California.
Materials
were
stored
in
the
containers
in
which
they
were
received,
indoors
in
closed
containers
at
room
temperature.
Application
methods
were
based
on
the
guidelines
in
ASTM
E
939-94
(ASTM
1994).
Laboratory
test
In
February
2002,
we
conducted
cage
testing
to
compare
four
repellents:
l)
WPC
Brands
Repel
Oil
of
Lemon
Eucalyptus
(hereinafter
'Repel
OLE')
in
lotion
formulation
(20%
PMD);
2)
SC
Johnson
Offl
Botanicals
TM
lotion
(10%
synthetic
PMD);
3)
Cutter
Outdoorsman
lotion
(30%
deet);
and
4)
Offl
Skintastic
SPF
30
lotion
(10%
deet).
Test
mosquitoes
were
the
yellowfever
mos-
quito,
Aedes
aegypti,
reared
in
captivity.
Approx-
imately
200
unfed
females
were
present
in
each
of
two
test
cages.
Cages
were
45-cm
cubic
screen
enclosures.
The
females
were
3-4
days
posteclo-
sion.
Conditions
during
the
test
followed
a
stan-

SEPTEMBER
2006
MOSQUITO
CONTROL
WITHOUT
PESTICIDES
509
Table
1.
Comparison
of
relative
protection
times
of
recent
formulations
of
PMD
versus
deet
in
tests
of
duration
against
mosquitoes.
References
are
listed
in
chronological
order.
%
AI
and
relative
repellency
Type
of
test
Mosquito
PMD
vs.
Deet
Dosing
Reference
Laboratory
Anopheles
gambiae
50
20
Field
An.
funestus
and
An.
50
50
gambiae
Laboratory
An.
gambiae
202
>
7
Field
An.
arabiensis
71
15
Field
Ochlerotatus
20
25
taeniorhynchus
Field
An.
darlingi
30
>
>
15
Laboratory
Aedes
albopictus
20
15
Culex
nigripalpus
20
Oc.
triseriatus
Laboratory
Aedes
aegypti
Field
Oc.
melanimon
and
Ae.
vexans
0.68
vs.
0.48
g/cm
Trigg
and
Hill
(1996)
"Adequate
coverage"
Trigg
(1996a)
"Small
measured"
PMD
25%
lower
"Normal
practice"
g/650
cm
Hill
(1998)
Govere
et
al.
(2000)
Barnard
et
al.
(2002)
3
ml/lower
leg
Moore
et
al.
(2002)
g/650
cm
Barnard
and
Xue
(2004)
15
g/650
cm
Barnard
and
Xue
(2004)
20
15
g/650
cm
Barnard
and
Xue
(2004)
20
-->
10
g/600
cm
This
study
20
--<
30
g/600
cm
This
study
20/26
20
and
1.5
g/600
Gm
This
study
AI,
active
ingredient;
concentrations
are
rounded
up
to
the
integer.
Presswell,
personal
communication.
Based
on
ED90.
Barnard
et
al.
(2002)
indicate
that
they
tested
Repel
OLE
lotion
with
PMD
at
40%,
but
Barnard
and
Xue
(2004)
alter
this
value
to
26%
for
both
studies.
However,
our
records
and
those
of
Wisconsin
Pharmacal
(Wundrock,
personal
communication)
indicate
that
Repel
Ot,E
lotion
was
only
produced
with
65%
PMD
within
a
30%
OLE
fraction,
for
an
absolute
concentration
of
19.5%
PMD
(here
rounded
to
20%).
Values
of
40%
would
refer
to
the
OLE
concentration
in
the
spray,
in
which
PMD
is
again
at
65%,
for
an
absolute
concentration
of
26%
PMD
in
the
spray.
dard
diel
cycle,
with
air
temperature
27
_+
0.2C,
47
_+
3%
RH,
and
light
intensity
of
290
45
lux.
Subjects
were
7
males
and
3
females.
Techni-
cians
wearing
latex
gloves
applied
repellents
at
1.0
g/600
cm
skin
surface
area,
spreading
them
evenly
on
arms
between
the
bend
of
the
elbow
and
the
bend
of
the
wrist.
Nine
subjects
tested
Repel
OLE,
and
8
subjects
tested
Of
0.
Botanicals.
One
experienced
male
subject
served
as
untreated
control,
male
tested
30%
deet,
and
female
tested
10%
deet.
Allocation
to
test
subjects
was
alphabetical
and
in
that
manner
indiscriminate.
Test
materials
were
given
anonymous
code
designations
to
blind
the
study
subjects
and
staff
during
application
and
testing.
Subjects
wore
latex
gloves
to
protect
the
hands
from
biting
and
exposed
limb
at
a
time
to
mosquitoes
for
1-min
periods
at
30-min
intervals
for
8
h.
All
exposures
began
5-10
min
after
application.
We
divided
subjects
into
2
groups,
each
of
which
included
those
testing
the
PMD
and
deet,
which
alternated
between
the
2
cages
in
successive
exposure
periods.
In
addition,
the
order
of
subject
and
limb
exposure
was
altered
within
each
group
from
one
exposure
period
to
the
next.
Upon
receiving
4
or
more
bites
in
a
single
exposure
period
(i.e.,
not
necessarily
after
the
first
confirmed
bite
[FCB];
defined
below),
a
subject
arm
was
retired.
A
foraging
mosquito
was
considered
to
have
bitten
as
soon
as
penetration
of
the
subject
epidermis
began.
Bites
were
counted
by
2
observers
per
arm
(1
observer
on
each
side,
and
not
the
subject
individual),
and
a
3rd
assistant
recorded
the
total
number
of
bites
after
each
exposure
period.
Counts
were
recorded
on
data
sheets.
The
first
exposure
was
designated
as
time
0.
Field
test
We
tested
at
the
Gray
Lodge
State
Wildlife
Area
in
Butte
County,
California,
in
October
1999.
This
is
an
area
of
mixed
woodland
and
marsh
that
does
not
use
environmental
mosquito
control.
Data
were
collected
between
1000
and
1630
h,
with
temperature,
humidity,
light
in-
tensity,
wind
speed,
and
general
weather
condi-
tions
recorded
at
approximately
60-min
intervals
throughout
the
test.
Repel
OLE
was
in
lotion
(20%
PMD)
and
pump
spray
(26%
PMD)
forms.
The
deet
comparison
was
Deep
Woods
Offl
lotion
(approx.
20%
deet)
(hereinafter