Allergenic potential of abietic acid, colophony and pine resin-HA. Clinical and experimental studies


Karlberg, A T.; Boman, A.; Wahlberg, J.E.

Contact Dermatitis 6(7): 481-487

1980


Resin acids are considered to be the main allergens in colophony (rosin). Tall oils also contain resin acids and may then be potential sensitizers. A resin acid concentrate (pine resin-HA) together with Chinese colophony were included in our standard series and applied on 563 patients with contact dermatitis. Fourteen showed an isolated sensitivity to colophony and two to pine resin-HA. Six patients reacted to both test compounds. Guinea pig maximization tests (Magnusson & Kligman 1969) showed that pine resin-HA (2 series) was a grade I allergen, abietic acid a grade III allergen and colophony a grade IV allergen. The risk that the resin acids in tall oils would induce contact sensitivity to workers exposed to tall oil-containing products like cutting fluids and cleansing agents is considered to be minimal.

Contact
Dermatitis
1980:
6:
481-487
Allergenic
potential
of
abietic
acid,
colophony
and
pine
resin
-HA
Clinical
and
experimental
studies
ANN-THEASE
KARLBERG,
ANDERS
BOMAN
AND
JAN
E.
WAHLBERG
Department
of
Occupational
Dermatology,
National
Board
of
Occupational
Safety
and
Health
and
Karolinska
sjukhuset,
Stockholm,
Sweden
Resin
acids
are
considered
to
be
the
main
allergens
in
colophony
(rosin).
Tall
oils
also
contain
resin
acids
and
may
then
be
potential
sensitizers.
A
resin
acid
concentrate
(pine
resin
-HA)
together
with
Chinese
colophony
were
included
in
our
standard
series
and
applied
on
563
patients
with
contact
dermatitis.
Fourteen
showed
an
isolated
sensitivity
to
colophony
and
two
to
pine
resin
-HA.
Six
patients
reacted
to
both
test
compounds.
Guinea
pig
maximization
tests
(Magnusson
&
Kligman
1969)
showed
that
pine
resin
-HA
(2
series)
was
a
grade
I
allergen,
abietic
acid
a
grade
III
allergen
and
colophony
a
grade
IV
allergen.
The
risk
that
the
resin
acids
in
tall
oils
would
induce
contact
sensitivity
to
workers
exposed
to
tall
oil
-containing
products
like
cutting
fl
uids
and
cleansing
agents
is
considered
to
be
minimal.
Key
words:
Abietic
acid
colophony
contact
allergy
cutting
fluids
guinea
pig
maximization
test
patch
testing
pine
resin
resin
acids
tall
oils.
Received
for
publication
April
25,
1980
Several
studies
deal
with
the
clinical
prob-
lems
caused
by
colophony-containing
plas-
ters
varnishes
and
tapes
(Hering
1965,
Raith
&
Rosenstock
1979,
Jelen
et
al.
1979,
Cha-
beau
et
al.
1979);
as
well
as
the
multiple
sensitivities,
including
colophony
in
patients
with
longstanding
dermatitis
(Angelini
et
al.
1975,
Walshe
1975,
Lachapelle
&
Tenn-
stedt
1979).
In
colophony
(rosin),
obtained
from
vari-
ous
species
of
Pinaceae,
there
is
a
differ-
ence
in
resin
acid
content
due
to
species,
growth
locality,
handling
and
storage.
Resin
acid
content
in
colophony
is
usually
85-90
%
and
the
rest,
the
unsaponifiable
fraction,
consists
of
different
esters,
alcohols,
alde-
hydes
and
sterols
(Sandermann
1960,
Ull-
manns
Encyklopadie
1976).
The
main
al-
lergens
in
colophony
are
considered
to
be
the
resin
acids
(Bonnevie
1939,
Wikstrom
1969,
Foussereau
et
al.
1971).
Tall
oils,
by-products
of
the
wood
pulp
industry,
are
used
as
ingredients
of
cutting
fluids,
cleansing
agents,
adhesives,
paints
and
fungicides
(Merck
Index
1979).
Their
main
components
are
fatty
acids,
resin
acids
and
unsaponifiable
constituents.
Since
some
resin
acids
are
known
as
allergens,
a
dis-
cussion
arose
in
Sweden
(Wahlberg
1978a,
Fregert
1978,
1979)
about
the
future
use
of
tall
oils
in
cutting
fluids
and
cleansing
agents.
Pine
resin
-HA
is
a
resin
acid
concen-
trate
(>
99
%)
obtained
at
tall
oil
distilla-
0105-1873/80/070481-07502.50/0
©
1980
Munksgaard,
Copenhagen
482
KARLBERG,
BOMAN
AND
WAHLBERG
Table
I.
Gas
chromatographic
analysis
of
resin
acids
in
Chinese
and
Portuguese
colophony
and
pine
resin
-HA.
Distribution
of
detectable
resin
acids
in
the
resin
acid
fraction
Chinese
colophony
Portoguese
colophony
pine
resin
HA
Pimaric
18.1
9.8
4.3
Sandaracopimaric
3.1
3.4
Isopim
aric
9.0
8.3
10.8
Palustric
4.4
19.0
5.0
Abietic
11.9
34.0
20.5
Dehydroabietic
50.6
8.6
58.0
Neoabietic
0.2
16.0
Tetrahydroabietic
1.4
Dehydrodehydroabietic
2.7
tion.
It
can
then
be
used
as
a
screening
test
substance
in
patients
with
suspected
sensitivity
to
resin
acids.
The
aim
of
the
present
study
was
to
compare
the
frequency
of
test
reactions
to
this
resin
acid
concentrate
(HA)
with
that
of
Chinese
colophony,
used
in
the
standard
tray.
In
addition,
a
few
patients
with
contact
sensitivity
to
Chinese
colo-
phony
were
tested
with
Portuguese
colo-
phony,
pine
resin
-HA,
two
tall
oils
and
a
cleansing
agent
in
an
attempt
to
compare
the
reactivity
to
colophony
and
pine
resin
-
HA
with
that
of
commercial
products
con-
taining
various
amounts
of
resin
acids.
Finally,
the
allergenic
potential
of
abietic
acid,
Chinese
colophony,
and
pine
resin
-
HA
was
determined
according
to
the
gui-
nea
pig
maximization
test
method
of
Mag-
nusson
&
Kligman
(1969).
Material
and
Methods
Test
substances
Abietic
acid
of
commercial
quality
supplied
by
Carl
Roth,
Karlsruhe,
FRG.
Chinese
colophony
of
pharmaceutical
quality
supplied
by
Trolab,
Hellerup,
Den-
mark,
and
Apoteksbolaget
AB,
Solna,
Swe-
den.
Portuguese
colophony
of
commercial
quality,
pine
resin
-HA,
tall
oils
TO
10
and
TO
20
supplied
by
Bergviks
Hartsprodukter
AB,
Sandarne,
Sweden.
Colophony
and
pine
resin
-HA
were
ana-
lyzed
for
resin
acid
content
using
gas
li-
quid
chromatography.
Clinical
investigation
Patch
testing
with
Chinese
colophony
and
pine
resin
-HA
was
performed
on
563
con
-
Table
2.
Number
of
positive
reactions
to
Chinese
colophony
and
pine
resin
-HA
in
the
standard
series.
During
the
study
563
patients
(275
males
and
288
females)
with
suspected
contact
derma-
titis
were
tested
M
F
Total
Colophony
pos.
8
12
20
3.6
Pine
resin
-HA
pos.
3
5
8
1.4
Colophony
pos./pine
resin
-HA
pos.
2
4
6
1.1
Colophony
pos./pine
resin
-HA
neg.
6
8
14
2.5
Colophony
neg./pine
resin
-HA
pos.
1
1
2
0.4
ALLERGENICITY
OF
PINE
RESINS
483
Table
3.
Concomitant
test
reactions
in
22
patients
sensitive
to
Chinese
colophony
and/or
pine
resin
-HA
Allergen
Trolab
Colo
phony
pos.
No.
14
Pine
resin
-HA
pos.
No.
2
Colophony
and
resin
-HA
pos.
No.
6
Potassium
dichromate
0001
3
Cobalt
chloride
0002
3
1
1
Nickel
sulfate
0003
3
2
1
Formaldehyde
0004
3
1
Balsam
of
Peru
0008
4
3
Wood
tars
0019
5
3
Wool
alcohols
0020
4
1
Carba
mix
0026
6
3
Caine
mix
0404
4
TMTD
1011
1
2
Coal
tar
1203
4
1
Benzalkonium
chloride
(0.1
%
aq)
7
1
secutive
dermatitis
patients
at
our
depart-
ment
from
Feb.
1978
to
Sept.
1979.
Four
patients
with
previously
verified
sensitivity
to
colophony
were
retested
with
Portuguese
colophony,
tall
oils
TO
10
and
TO
20
and
a
cleansing
agent.
Sensitization
experiments
The
guinea
pig
maximization
test
method
(GPMT)
as
described
by
Magnuson
&
Kligman
(1969,
1970)
was
used,
under
the
same
conditions
reported
earlier
(Wahlberg
&
Boman
1978).
At
intradermal
induction
3
%
colophony,
4
%
abietic
acid
and
10
%
pine
resin
-HA
in
olive
oil
were
used.
At
epicutaneous
in-
duction
25
%
in
petrolatum
of
all
sub-
stances
were
used
with
previous
SLS
treat-
ment.
Challenge
testing
was
performed
with
10,
5
and
1
%
of
the
test
substances
in
pe-
trolatum.
Plasters
and
tapes
containing
colophony
were
avoided.
Results
The
distribution
of
detectable
resin
acids
of
Table
4.
Four
patients
who
had
reacted
to
Chinese
colophony
(Trolab
0017)
in
the
standard
series
were
tested
with
Portuguese
colophony,
pine
resin
-HA,
tall
oils
TO
20
and
TO
10
and
a
cleansing
agent.
Test
concentrations:
Portuguese
colophony
and
pine
resin
-HA
30,
20,
10,
and
1
%
in
petrolatum,
tall
oils
TO
20
and
TO
10,
30,
20,
10,
and
1
%
in
olive
oil,
the
cleansing
agent
6
%
in
distilled
water.
The
lowest
concentration
that
produced
a
reaction
is
given
in
the
table
Patients
Portuguese
colophony
cont.
85-90
%
resin
acids
Pine
resin
-HA
cont.
>99
%
resin
acids
neg.
TO
20
cont.
20
%
resin
acids
TO
10
cont.
10
%
resin
acids
Cleansing
agent
cont.
1
%
resin
acids
1
2
3
4
10
%
<1
%
5
%
<1%
30
%
10
%
<1
%
neg.
neg.
neg.
20
%
neg.
neg.
neg.
neg.
neg.
6
%
neg.
NT
484
KARLBERG,
BOMAN
AND
WAHLBERG
Table
5.
Sensitization
and
testing
of
guinea
pigs
according
to
GPMT.
The
number
of
animals
with
positive
test
reactions
at
the
different
challenge
concentrations
are
given.
Statistical
method:
x
2
analysis.
Induction:
Chinese
colophony.
Challenge:
Chinese
colophony
Challenge
conc.
(%
w/w)
10
5
1
Control
(pet.)
Controls
24
h
3
3
3 3
n
=
18
48h
3
1
1
3
Exposed
24
h
13
8
3
1
n
=
20
48h
13
8
2
2
P
24
h
<0.01
>0.05
>0.2
>0.2
48
h
<0.01
<0.05
>0.2 >0.2
Table
6.
Induction:
Abietic
acid.
Challenge:
Abietic
acid
Challenge
conc.
(%
w/w)
10
5
1
Control
(pet.)
Controls
24
h
0
0
0
1
n=
20
48
h
1
0
0
1
Exposed
24
h
11
8
1
0
n=
20
48
h
12
8
1
0
P
24
h
<0.001
<0.01
>0.2
>0.2
48
h
<0.001
<0.01
>0.2
>0.2
Table
7.
Induction:
Chinese
colophony
(see
Table
5).
Challenge:
Abietic
acid
Challenge
conc.
(%
w/w)
10
5
1
Control
(pet.)
Controls
24
h
0
0
2
0
n
=
17
48h
2
0
1
1
Exposed
24
h
7
5
3
0
n
=
20
48h
10
6
2
0
P
24
h
<0.05
>0.05
>0.2
-
48
h
<0.01
<0.05
>0.2 >0.2
Table
8.
Induction:
Abietic
acid
(see
Table
6).
Challenge:
Abietic
acid,
pine
resin
-HA,
colophony
(10
%
in
pet.)
Challenge
Control
substance
Abietic
acid
Pine
resin
Colophony
(pet.)
Controls
24
h
2 2
0
1
n
=
20
48h
5
3
0
1
Exposed
24
h
14
9
6
1
n
=
20
48
h
14
10
9
1
P
24
h
<0.001
<0.05
<0.01
>0.2
48
h
<0.01
<0.05
<0.001
>0.2
ALLERGENICITY
OF
PINE
RESINS
485
Table
9.
Induction:
Pine
resin
-HA,
series
I.
Challenge:
Pine
resin
-HA
Challenge
conc.
(%
w/w)
Controls
n
=
20
Exposed
n
=
20
P
24
h
48
h
24
h
48
h
24
h
48
h
10
5
1
Control
(pet.)
0
2
0
5
>0.2
0
1
0
0
0
0
0
>0.2
>0.2
0
2
0
0
>0.2
Chinese
and
Portuguese
colophony
and
pine
resin
-HA
is
given
in
Table
1.
At
the
standard
patch
test
procedure,
22
of
563
patients
reached
to
colophony
and/
or
pine
resin
-HA
(Table
2).
Concomitant
test
reactions
in
these
patients
are
given
in
Table
3.
No
case
of
isolated
contact
al-
lergy
to
colophony
was
found.
Four
pa-
tients
who
had
reacted
to
Chinese
colo-
phony
in
the
standard
series
showed
some
positive
reactions
when
tested
with
Portu-
guese
colophony,
tall
oil
TO
20,
pine
resin
-
HA,
and
a
cleansing
agent
(Table
4).
Experimental
sensitization
with
colo-
phony
and
abietic
acid
gave
clearly
positive
results
(Tables
5,
6).
Colophony
was
found
to
be
a
grade
IV
allergen
and
abietic
acid
a
grade
III
allergen.
In
both
series
testing
for
cross
reactivity
to
the
other
substance
was
carried
out
1
week
later.
The
group
sensitized
with
colo-
phony
reacted
when
challenged
with
abie-
tic
acid
and
vice
versa
(Tables
7,
8).
Ani-
mals
sensitized
with
abietic
acid
had
posi-
tive
reactions
when
challenged
with
pine
resin
-HA.
Experiments
with
pine
resin
-HA
were
carried
out
in
two
series,
but
no
defi-
nite
sensitization
was
observed
(Tables
9,
10).
Discussion
The
distribution
in
the
resin
acid
fraction
of
pine
resin
-HA,
Chinese
and
Portuguese
colophony
used
in
this
study
varied,
as
can
be
seen
in
Table
1.
However,
this
variation
does
not
seem
to
influence
the
reactivity
to
colophony
in
the
clinical
study
(Table
4)
as
the
patients
sensitive
to
Chinese
colo-
phony
also
reacted
to
Portuguese
colo-
phony.
In
a
study
by
Chabeau
et
al.
(1979)
on
patients
with
suspected
sensitivity
to
colophony,
cross
reactivity
between
rosins
from
different
countries
was
also
demon-
strated.
As
shown
in
Table
5,
Chinese
colophony,
commonly
used
in
standard
patch
testing,
was
found
to
be
a
grade
IV
allergen
ac
-
Table
10.
Induction:
Pine
resin
-HA,
series
II.
Challenge:
Pine
resin
-HA
Challenge
conc.
(%
w/w)
Controls
n
=
19
Exposed
11
=
20
P
24
h
48
h
24
h
48
h
24
h
48
h
10
5
1
0
1
1
3
>0.2
>0.2
0
0
1
3
>0.2
>0.05
0
2
0
1
>0.2
Control
(pet.)
0
0
0
0
486
KARLBERG,
BOMAN
AND
WAHLBERG
cording
to
the
classification
of
Magnusson
&
Kligman
(1969).
Abietic
acid,
considered
to
be
the
main
allergenic
component
of
colophony,
was
found
to
be
a
grade
III
allergen
(Table
6).
In
a
previous
study
(Wahlberg
1978b)
9
of
15
patients
sensitive
to
colophony
simul-
taneously
reacted
to
abietic
acid.
In
the
present
study
we
found
that
6
of
20
pa-
tients
sensitive
to
Chinese
colophony
simul-
taneously
reacted
to
pine
resin
-HA.
On
the
other
hand,
two
patients
were
positive
to
pine
resin
-HA
and
negative
to
colophony
(Table
2).
Our
results
imply
that
other
com-
ponents
beside
the
resin
acids
in
colophony
are
allergenic.
In
a
study
from
Belgium
(Dooms-Goossens
et
al.
1979)
20
of
39
pa-
tients
with
positive
reactions
to
colophony
reacted
to
abietic
acid.
The
unsaponifiable
fraction
of
colophony
contains
among
other
components
esters,
alcohols,
and
aldehydes
of
resin
acids.
Cases
of
contact
allergy
to
hydrated
resin
alcohols
have
been
reported
(Cronin
&
Cal-
nan
1978,
Dooms-Goossens
et
al.
1979)
and
their
allergenicity
is
verified
at
predictive
human
assays
(Kligman
1972,
Rapaport
1980).
It
is
desirable
that
additional
com-
ponents
of
colophony,
both
resin
acids
and
others,
are
defined
and
evaluated
accord-
ing
to
the
GPMT
method.
It
was
shown
that
pine
resin
-HA
was
less
likely
to
induce
contact
allergy
than
colo-
phony
(Tables
5,
7,
8)
and
therefore
the
risk
of
becoming
sensitized
to
the
resin
acids
in
tall
oils
is
less
than
to
colophony.
However,
patients
already
sensitized
to
colo-
phony
may
get
a
recurrence
after
contact
with
tall
oil
-containing
products.
This
can
be
seen
from
Table
4
where
a
patient
sen-
sitive
to
colophony
reacted
to
20
%
tall
oil
TO
20.
A
similar
case
was
reported
by
Fregert
(1979).
Like
colophony
the
unsaponifiable
frac-
tion
of
tall
oils
contains
esters,
alcohols,
and
aldehydes
of
resin
acids
(Holmbom
&
Avela
1971)
which
may
be
sensitizers
and
a
GPM
test
with
such
a
fraction
is
planned.
Acknowledgments
The
authors
are
greately
indebted
to
Miss
Gunnel
Hagelthorn
for
her
skillful
technical
assistance
and
to
Bergviks
Hartsprodukter
AB
who
supplied
pine
resins
and
tall
oils
and
carried
out
the
GLC
analyses.
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Address:
Dr.
Jan
E.
Wahlberg
Department
of
Occupational
Dermatology
Karolinska
sjukhuset
S-104
01
Stockholm
Sweden
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