Private and C onf idential R99oarch & Development
Entablishmentt
British-American Tobacco Co.Ltd.,
Southampton.
16 th July, 1958.
7 th 11ri-EMIATVIIIAL CAINGER CO!W.FSJ
P013DON. 6-12th JUL1. 195S.-
The Congroas was attended on two days only, 7th
July and
11 th July, when ptpers were presentod, concerned
particularly
with the problems of Smoking mnd Health.
11 onday. 7th JuXa.
Dr. Neukorm (Lausarrie) read a paper in which he
deocribed
his rnpil test using the ncwt. Hs in now in
contact with Bock
(Daffalo) and his studied the sqme hydrocarbons
used ki the latter
In his annonnmcnt of the value of tho seb-aceous
gland suppreorion tont
as a rapid inlicator of potentisl careinogenia
properties. With
three exceptions, the newt te3t and the Bebaceous
gland test yield
identical rosult3. The exceptions were
7,12-ftmethylbenarajanthracens
and 12-methylbenzEalruithracene which Dock found
to be stronsly
poe itive but which Houkomm found to be n -
gative. One hydrocarbon
gave a ponitive ncwt test but failed to suppress
sabsocoun gland
formation in Bock's test.
In the afternoon there was n group of papers
directly related
to Uie biological effect of cig-trotte amoke and
amoke fractions.
Lyons (Glasgow) de3cribed studies of the unstable
components (free
radicals) of eig--rette smoke. Uning electron
mtgnetLc resonance,
lie showed that whole amoke ter c-.)ntained 101'5
free electrons per
(Z.,:)
gram and that on fractionation these were
distributed net f ollownt-
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-2-
Whole tar 100%
Residue after water extrnetion SUA
Residue after extraction with dilute acid 43A
Reoidue after extraction with alkali 5",
Rosidue nft,r extraction with dilute acid
-..,,,--and Uien with dilute alkali 28%
Senaration br Chron;2Lorpla
ilhole tftr l'JU%
Ile,-ame f raction 0%
benzene fraction. - 3 5.".
Acetone fr-netiort 50,',
He aloo, doncribed the invu-stigation of
eigftratte amoke uaing
diphonylpicry1hydrazyl no a stable free ractical,
reagent. This showed
thmt tho water soluble reactive raterial
constituted 60% of the whole
reactive mmtcrisl. The discrepancy bet-.~een Via
two nethods was not
explained, however.
Kooak (N.I.U.) gave a rathrr pedentrimn account of
some of
his fractionation of cigarette amoke condensate
from American blended
cigarettes. lie has now isolated equalene and
lsS-p-menthadiens.
The latter compowid, aloo known no dipentQ;ie or
limonene, is a major
constituent of oil of lemont and has a
characteristic lemon amell.
it may be an importnnt Ilnvour component of amoks.
(Lts isolation
from smoko b7 Clono It-t-3 earlier beon
conmunicated privately by
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I.T. Co. Research Depirtment). Other compounds
Isolated by Kovsk
included dieth7l ketone, diacetyl, benzenp,
toluens, atkql soetats#
phenol and ethanol.
Royer pj &I (Faris) described their work on the
inhibition of-
benzpyrone formxtion by the use of a=onium
ffulplumte and of
a-tMqine re-~Csnto.
. Noulkomm Pad Donnet (Lnusanne) doncribed their
prodedurs, for the
--chemierd fr-ictionstion of smollco from thryland
cig-trottea without
producing arq rrally fresh evidence of
c-xcinoeenio fractions. They
hid founrl th,tt brown polymeric subatrtncov in
the acidic nnd alkalin
fractions proluT!ed tumours when nice wore treated
with them. The
incidence of ttunaurs wnn said to be gre-tter than
that of control
anina.13 (10'~ in 15 months no ngntn"t 10,~ in 22
months in the controls),
but serious doubt wns cast on the otntistierl
significance of this
in the discun3lon.
Kot1n (Los Angele3) gave an account of the vork
which he and
Falk had carried out on the effect or artificial
smog, produ".d by
ozondlysis of Cnooline vapour, on the c-,=alian
lung. fie also
describei the elution hypothesis and experiments
on the dissolution
of hydroenrbons, adsorbed on c-irbon particlos, in
plauma solution.
The affect of smog in pnralyaing cilia in the
bronchus and oesophagus
wis also mentionrd and the conoequont epithalial
denudation was
ilIustratod by photomicrograrlis.
Leuchtenberger (Clevelani) dencribed har work on
the caunation Q)
of bronchitic conditions in the lwiga of mice
expoced to cig-wette Qn
GN
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-4-
smoke. Those e-hanges in the lungs beemme
progressiV64 voree with
increase in e=om=e and resembled llemrcir-sl in
site an described
by Auerbach. When wcposure wns terminated.
however, the tissues In
time reverted to normal. Consequently, the state
of carcilmoma 4- 14tu,
as described histologically here, is not a true
premalignant stateg
although Leuchtenberger did not stress this,
Cowdray (St.Loula) dcacribed histological dianges
in the
bronchus leading, to squwaus cell, motapl2sitt in
humaa amokern., The
rcnaon for the lv~.alisation of these lesions in
the bronchus was
ascrib-d to mmoke settling out in those parts or
the br-,-Mal tree
Q,ere eddies are most likely to occur. The smaller
passages of the
alveoli are 1css IV~aly to be sites than are the
bronchial branches.
FrjAwr ~~rnjW. 11th Jul:r
This w-,c occupied by a r3incusrion of th-e
Petiology of Cancer
of the Lu!g.
Dr.'.'.C. ITueper (betheods) rmde a strong c-t3e
for the PrimarY
implication of atmo-irgicric pollution by metile
and asbestos mud
di.-,,c-j=tc!d the effect of cigarette amokirg,
especially In the onmdug
discus-iion.
Doll London) was coneprned to answer alternative
e=l=vitionn of the connection baLween rooking and
lung c-incer and
to claim that the statistical connection via one
of primary cause and
affect. Ile atill maintnined that there was no
difference between
those who inh-led nnd those who did not, nltbough
pipe and especially
C=
cigmr amakers chaw little stat'stictl essociation.
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-5-
11 yry3or Oloan-Kettaringv Now Tork) vho followed,
premented
,ything, pipe and cignr smoke was more earoiwgenic
evidence that, if an
to nice. fie accepted Li-Asny's figures that the
polycyclic hydrocarbon
content, especially of benzpyrone, was higher in
pipe and cigar smoke.
11 o -one pointed V) tho obvious discrepancy
between this and the
atatinticil fietmeo fcr ploo an!l eig-ir
unol-torp, which if inhalation
is not i fnctor. become incompatible. Wytyler
followed his unual
themo - thnre in n threshold for bioloCicnl
activity and n reduction
of 40-5U' in tho tnr intnke would rncluce the
dooege below threrlioldo
For thin purpose be ouf-,gosts tho uns of
clr!iretto filters and leas Ur.
Ho Plao mentinn-A the possible uns of catalysts
tuid perhaps the use
of metals nuch no r-luminium to reduce tho
combustion temperature below
tho critical 8Q04500. In tho latter cornoction,
lie said Viat it
coemod at; IS the 1--itter possibility was; a very
frall. arm. (rerhape
he has checked Vro. Linukence's cigrxettaa). In
the discussion
following, lie was ch&llonged by Doll as to the
mcaning he attached to
threshold done, Doll pointing out that there was a
finite risk even
for liaht amokcro. Wynder writ.,gled a little at
this and said lie
uzed threshold "in quotas". H's c%llod att-mtion
to a Rusoitn
cigarette lie had boon given, two thirds of which
uns filter, and said
this wts a atrp in tho right direction.
Waller (Lorrlon) cloarid tht- t3onsion with it
paper on thn possible
effect of nir pollution as an aetiological fnetor
Li limig wincer.
CO
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He interpreted tfibloo of mortality statistics for
a series of towns
in Engl--ind and Wales in terms of the population
coming into equilibrium
with a new fnetor ek. smoking. Contrai7 to Stocks
and to Fusper,
~-'aller fmols th-tt nir pollution due to
urbanication is a very minor
factor -knd put t1je. cause fairly and squarely
onto emoking.
Tho 1iic,!i!Aon afforded n nu-,iber of people the
opportunity to
call Atontion to their m;n work, in pirticular
fleukomm, an Italian
P~ofemaor nnd -!t Ciibftri giving fairly longttW
aecount3 viLich tended to
roitorsto tho u,3u--,l c!r.~rrrs.
Persons Gontnetnd.
(a) flowl-com.. rnd Bonnet. Mr. Anderson had
car3lor written to
Dr. ficukorm, inviting him and DrAonnet to 11.&
D.E., SoutMmpton.
NcWtomn, at firat, thauf:ht that we wiBhed to
consult him an a particular
matter, but was told it woo merely reciprocal
hospitality and an
opportunit7 to show him some of our work. There
were difficulties,
however, in that fleukor:m and Donnot wished to
attend all the Congress
and were then leaving at once for 11ruosels. In
the circumst4nees,
and in view of difficulties in violting I.T.Go.
Bristol, where
Dr. Bentley uns now in hospital, lieukori-m and
Bonnet asked to be
allowed to postpone their visit until the early
autwan (latter half
September, beginning of October) when thoy would
ag-Rin be vin. iting
the UA. Their su-guation was accepted and it wns
left that they
would contact us nearor the tim and arrange a
date.
(J-7
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-7-
(b) Dr. fiana Falk. Dr. Rotin introduced Dr. Falk,
who is
the Chemist worki!j with Kotin on the smog
production and an t1w
inhibition of cili-,try action by smog and
cigarette sooke. Rotin had
alrendy expl~-,inad something of this work without
going into detmil.
In the course of two fairly extonalve disousni*na
with Falk,
proc,-dure for the ev.,ilustion of the activity of
particular constituents
of cigarette sm6lce waa explained. Clemrly It in
not feasible to
....fraction-ate eig-rette amoke chemically Yind
still %pply it to isolated
Iroa oenophngus prep!%rations as sn saronol. The
technique adopted has
been to stirvey Vie known constituents of smoke
%nd to divide tile
apectrum into irbltrnry c1nanificntions depanding,
on the amounts found.
The m-ijor conponont or com-7onents of each class
are then npplied to the
prcp:~ration an in icronol of the pure conpound
wnd the inhibitory or
stitnulatory eL.iect n;-)Led. As yet. no effort
has been made to elucidate
.u,y synergim wilich mny occur t1irough two or
more ampounds acting
together m-nd, clearly, in no-no cases, chemical
interaotion ixty take
place betwoon two components. These effeet:s,
which will t'lke some
diaentanElin,r,, will be studied in the future.
Falk provided the following list of results to
date. In view
of Kotin' a roluctarice to any aqything to the 7-
M.3.C. Sub -Committee
about stimmIntion of ciliary activity, none
results are of c!;nsiderable
interest. Tile results are classified into
stimulatory effects
irdlibitory ofiects (-) and no effect ((;) and are
reported for
QD
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_a_
a) I minute exposure
b) 60 minutes exposure
c) chronic effect, showing a trend of activityo
Thc7 arO dO fOlIOUGS-
LpIngla 60 minutes Chronic Trend
OXMIlurle sy-nosure
stimulntiin of cilisi7 action
inhibition of ciliw7 action
U no offect
Acetyl peroxido 0.)
Peracetic acid
Pyridine 0
Formaldehyde
Acet.-adehyde
Acetone 0
_~_eoDutyraldehydo 0 11
a-Butyrnldek,de 4. 4.
Propionaldehyde 0 0
Metbyl bromide - 4. +
Mothyl chloride 0
Butadiene 4
G arbon ronoxido
Prop7lene o:ilde - +
Bron-oform - 0
Ilet4lamine - 0 0
Trims tb7lftmki a - 0 0
Profflone 0.) 0
ThioMnic acid + 0
Acetic ncid 0 0
Formic Ftaid 0
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2-methylbut-2-ene
2-metbylpontnna
2-methylpent-2-eno
Carb-)n totracliloride
MetSylene dichloride
Ofelohe.-Pene oxide
Am,.onium hydrorifl,
Mctlinna tbiol (-tcth,.l
mcrcaptan)
Acetonitrile (mehyl
cyl-nide)
Phonol
1 minute 60 minutes ChroM a Trend
eamosure exooeure
0 +
0 01 0
0 (4.) 0
- 0.)
0
W
0
0
0
0
Ao a ninbcr of these compounds are giseou-;, thr,7
are not
renoved by n cigiretto filter, even of the
Cnmbridge absolute filter
typo. Fall: st-itezzl Uhat the activity of wholn
cir,-t-stte amoko vae
dkdnishod by filtrition to some extent, but was
unable to give any
quantitative neasurn of this, nor of its relation
to filtration
officlency of tl~r.- filter.
Dr. Fal1c u-in i-mited to -':',aut1mmpt,)n, but
win unable to find a
suitable dny during the Conrrnnn. It wic learnei
lator th-nt he
visited I.T.Co. (Bristol) on Oednesday, 9th July.
Scientific F.,-Jilbition
Drs.Kotin and FA1k 11-id rin e.&Lbit mlong the
lines of the paper
re-d by Kotin nnd of the dincunsion nt the !.S.C.
nesting. BlackploCk
shourd p1hotorr-i-lis illu3trnting his toclirdque
of thoracotorv nnd
(J-7
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Inoculation of benzpyreno, met-hylaholnnthrene or
cigarette smoke
condensate. One c&rcinoni and one aarcomo fr(xi
eight rnts treated
with ciFmrette smoke condensate hsvo raoulted.
Kraybring (oula)
had illuntrntions of histologic-il prep-irntions
implicating cigarette
amoking, !-a % f.-!ctor in IuM enricor.
An c:djibit unrcInted to lum enncer but which wis
of some
inf02'(!Jt W-3 th,.b by tho Uppon!icincro raid
their collIburators
(Coluribin U. 0.1.) on carcinogencois tri Polynor
film3. implantation
of plqntic filmn of m-ny ki.-ids into rorlwitn,
Irive produced
c-1rcirom,tt-i. Th-it this in clue rolely to the
pl;ysic--a nature of"
the film follows from the lo,ier twicur
incirintico when perforated
or woven membran" or spongesof tbn poly-norn nro
unod, and from
the virtu,!l \bqcnica of tuniourn when tho aa-me
m-itari-In in powder
form are ct.-ibaddod. The pon.,sibility thit
c7trcinogrenesis is due to
rosidunl fr,-e rn,31eals in the polymcr structurn
neems to be thereby
clinprovc(l.
L)OFtIV46D
BATCo document for Province of British Columbia 2
November 1999