Private lind UoqfkLen go-I Roar-arch 04
Dovelopftnt Establishment,
rritimh-Americ?n Tobacco Co.Ltd.,
Southmpton.
16 th July, 1958.
7 th
1,901-1111. 6-1,2th JULL 1958
The Congrr;an wni mttenle-l on two dnys only, 7th
July and
11 th July, .,I--.cn Tirporn wcro rroaentaO,
eqncernH pnxtieulirly
'~M'thn prob1cmi of 3-noking nn4 llnptlth.
NonL
ne) rm-A a pnj-~r in -A&lh he do-icriLed
Dr :;ct!:o-.n (Laus-nm
hin rv-Ad tcat u-3im,, tho ti-A. Vo in no,.! in
c-rttait wit!j Pock
(Luffn1o) -Ind ft'?q Studied tho mrc hyrim?-mbonn
timail b. thn 1,~ttor
in h1a r:ine-rr-~.-nt tif Vin v-ilun of the
ncb-irooun 01nnd munprer!!-Vin Unt
as n rnnirl inlicator of potcntill c-=einogrria
prap-rticn. lith
thme exceptiom, thn -xvt tc:3t nnd Vie nobaccoun
el-knd tent yield
Vontiml rrmat3. 1ha ncepti=s u.-re
7,12-dinctlqlberr,[!!7nnthracens
and 12-metiVl'ceir-111-1p..,ithr-teens which VoT.-
fo-.LnA to be atrorgly
positive but uhich NoWtorm found to be n Cative.
One hye!rovarbon
eavo m positive n,-wt te-it but f-iiVd to au-presm
n-rbnceous
form-3tion in Vockla to-it.
In V!e qftrrnion- there w-t.-j n (.,-riup cf
pnpe-s rUrectly roInted
to Uie biologici-I offect of nig-roVe tymol-n nrA
en")ke fracV.-Mn.
Lyons: de-v-rV.-o-1 atudica of the urst-ible
component-3 (fr,-.o
r-idicals) of ri!~-vctte moke. Urdn-j eli~ctron
mqnietio renon-ance,
ho ahi,cel t!,.-,.t 0!,Ac r.:7ohe t:!r
cl-)-tt-~in-d 11) 15 free alectrnmi P-r
n-.1 thit m f r., ction-ttion the". urre
distributed is followss-
.,r7n ri, Q~)
41-
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whole tar 100%
Residue after water extrrtetion Sul.
Residu-a after extraction with dilute acid 4X1
Residue nftcr extraction With n1kall 5711,
Residue nft, r extraction vith dilute acid
and U= with dilute elkali 28A
Sanaration bv Chrom-torraphY
1!)0;g
.4 hole t!-r
Re3tana fr!7ction
Eanzene fraction
Acetone frnetion 5~~I.
e --lno doncribed the inv-stigntion of cigarette
moke Using
d1 pherqrlpicr7lh.ydrazyl as a stible free ridical
reagent. This ahowed
that t-ho wither voluble reactive rateritl
constituted 60% of the whole
rtactive natc-rinl. T,,,.* d1screpanc7 bott.*en
the two methods was not
explained, hcraever.
Kosqk (N.I.U.) gave a r*W-r pedestrian account of
some of
his fractionation of cigarette emoke condennate
from American blended
cigarettes. lie h-is nov isolated equalene and
lzS-p-menthadiene.
Tho latter comp~:und, aloo known as dipent4tne or
limoneno, is a major
constituent of oil of lemon, and k-%o a
characteristic lemon onell.
It mq be an imp,,)rtnnt flavour c-oponent of
smoke. (Its inolation
from smoke by, Cleno h-td earlier been
communicated privately by
Q:5
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-3-
I.T. Co. Research Depu-tmeat). Other compounds
Isolated b7 Konak
included diatIVI ketone; diacat~yl, benzene,
tolusno, *t1W1 acetatea
phenol and ethanol.
Royer It Al (Faris) described their work on the
Inhibition of
bonxjVrene forointion by Vie use of a=onium
sulphamte and of
oxidising reagenta.
NeWcc= and Bonnet (Lausanne) dencribed their
prododure for the
chimlc.-a frnetionition of smoke Irom 1hryland
cig-irotten without
producing tiny rc~.Iy fresh evidwice of
circlnogenio fractions. 1hey
had found Vint bro-m polymoria oubztances in the
acidic and Alkali=
fractions produced tumourn when mice were treated
with them. The
incidence of tumourn was said to be greater than
thst of control
anl=13 (lUf. in 15 months no ngninst 10% in 22
months in the controls),
but serious d-mbt via crtst an the atatistical
significance of tide
in the dincunsion.
Kotin (Los ArWles) gave an necount of the work
which he and
Falk had carried out on the effect of artificial
coog, Woduced by
ozonclysia of gnoolina vapour, on the ti=alian
lung. He also
described the elution hypothesis and experiments
on the dissolution
off lWdroenrbons, adsorbed an carbon particles, in
plasma solution.
Thu effect or amog in p:-.wQjsing alli-a In the
bronchus and oseophague
was also mentiont-d and the conoequont epithalial
denudation v,"
illustratod by photamicrographs.
Leuchtenberger (Clanlani) donariLed hor w(Yrk on
the anusation
of bronchitic c-,:nditiona in tho lungo of mice
exponni to cignretto
(J-1
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-4-
smoke. These olianges in the lungs becamp
progressively worse with
increaso in exposure and resembled "carcinoma in
sit~t* as described
t7 Auerbach. Uthen exposure wais terminated,
1wwavers the tissues In
time reverted to normml. Consequently, the stALe
of earainoma In w4tus
na described histologically here, is not a true pr
t stateo
althmgh Lauchtenberger did not strasa ULla.
7--- Cowdm..v M.Laula) described histological
diangsis in the
bro.nchus leadine. to squ-j-,nous cell inetaplasin
in h=au smokers. The
roacon for the localination of these lesions in
the bronchus uas
aacrib,~~d to inoke oettling out In thono p,!rts
or the bronchial tree
where eddies are most likely to occur. 1he smnller
passages of the
alveoli aro less Ukely to be sUos than are the
bronchial branchose
Er_idsy_1!~prn1nr. lj_Vi
. . _jWZ
This wns occuplod by s, dinatiaAon of the
Aetioloar of Cancer
of the Lune.
Dr.'I.C. Ruepor (IJetheada) mtde a strnng case for
the primnry
implication of atmo7plivric pollution by meteds wd
anbestas and
discounted the effect of eigmrstte making,
especially in the ensuing
discussion.
Doll W.R.C. London) was concern*d to answer
n1ternative
explamitioni of tho conmotion beLwarn smoking and
lung cancer and
to clsin thit the statistical conmotion win one of
primary amuse and
effect. I-1& ntill mnInttined that thero was no
diflarence between
those who Inh-ded nnd thone who did not, n1thm4i
pipe and supecinlly
oignr nmokera aliw littlo otatlatic-LI
aarjocintion.
QX7
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-5-
Wynder (Slonn-KettarLngs flow lork) who followed,
Wvnented
evidonco t1vito if arWthing, pipe and cig%r nooks,
was own carcinogenia
to mico. Ile accopted Lindamylo figures that the
po4eyoUo hyiLroaarbon
cantani, especially of banspyrenev urms higlier in
pipe and eig%r smokes
110--one pointed V) the obvious diecrepanay
between this and the
statist ic-il, figures for pipe and cigar mokers,
which if'Joh-MIRtion
is n6l ft fnctt)rp become incompatible. Wyndor
followed his unmil
theme - thero in n threshold for biological
activity wA a reduction
of in the tnr intaka would reduce the donsge belaw
throaholdo
For this purpnee he suegosta the una of cigarette
filters and leas tar.
Ile alco mentinnid the possible use of catalysts
and perhaps the use
of metala ouch an Uuminium to reduce the
combustion tunparature be1w
the critical WO-85U0. In tho latter connection, he
said that it
neemed an if the I.-Ater ponsibility was a vt-r7
frail arn. (Farbspe
lie hats chocked His. LvWencels cignretton). In
the discuscion
following, he was cliUlongod b.Y Doll as to the
scaning he att4chad to
threshold doso, Doll pointing out that tierv was a
Jinite risk even
for light amakera. Wynder wriggled a little at
this and said he
used throshold "in quoteo". 11.9 cnlled attrintion
to a Russiqin
eiga-ratto lie had been given, two Vhirda of whiah
wets filter, nnd said
t1 da vsa a atop in Uio right diraction.
Waller (Lomlon) closed the cossion with n papar on
the ;vosible
effect of Ur p3ilution as an aotitlofgic3l factor
In lung cancer.
Cb
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He interpretrd tnblca of mortmlity atntistion for
a series of townS
In EnCland and 1-Inles in terms of t1to
popul-ttlan co4M into equilibrim
with a now Vvotor c&. smal-ting. Contrw7 to
19tooks mA to Pueperp
WoMer feclq t1vtt air pollution clue to
urbay-ds!ttion in a very minor
factor !?nd put the, cau-io fairly Pnl equ-troly
onto smoking.
Tito -fticrr-ion nfforded n rnrr1?t-r of pooplo
the Opportunity to
call ettention tn ti,eir otin work, in
p-2rtletti-x floukomm, an Italian
profooa.,)r tind n Cvbnn riving fairly Jvnrt1W
ne-f-ounts Sdilch tended to
roiternto the u-iiv-l oh,~rcrs.
,rernons Uontnctnd.
(a) NeWrarm f-M Bonnet. 11r. -nlercan Ivid
a-trlirr writton to
"T. Neukomil, invitinj him and Dr.bonnnt to 11.)'t
D.E., Sout)rtmpt-311.
11 cultomm, at firat. thcueht that we iinhetl to
c-nstiit ILDi an a pnxticular
matter, but wa!! told it wis rarely reciproc-il
hospitality and an
ouporturLit7 to shotf him sorte of our work.
11tire, were Aiffiwl ties,
however, in that i:eulkom and Daiviet wigbed to
attend all the Congress
and wore then leavi:ng rLt once for 11ruasols. In
the cirmustrances,
and in view of diffivulties in visiting I.T.;o.
Bristol, whore
Dr. Beutlo.- unn now in hoopital, Nleukomm and
Pon.-Lot askod to be
allowed to pistpono their visit until th,.i
cirtrly %utWM (latter hslf
Zoptombor, begim-Unr of October) when tlv~y weiLld
agnin be visiti-iff
tha U.K. Their su7:rt.-,A1-)n was nerepter) -Inj
it wns left thmt they
would contiet us n-7irar the tir"- nnd erl"ITIC03
3 d-1tG.
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-7-
M Dr. F-~tna Falk. Dr- Kotin iz-Aroduced Dre Falk,
who is
the Chemist vorki?e uith Kotin on Via onog
production ond ou the
inhibition of cili-try rctl~?n by stiog and
aignrette =%cke. Utin. had
alrvidy axp1n.ir-A n~~othirjg of tlii--t work
without going into detail.
.'*:w In th,) courna of tuo Piir17 exton-viv*
disoxianiond with Falkv
tkam-proc-Aure for the eviluntion of Me !tativLty
of particular constituents
of--cigarette rmolce una explnined. Clearly it is
not feanible to
IvAction-Ato cig-rctte anoke cliemic:t!4 -ind
ntill !i;,7ply It to i3olatea
iroG oenoo.-Zus rre-virationa ms rin norovol. The
tochnIque adopted has
b"n t~p -3urvf:-y the knu,.,n c-)natitutt--to of
rr-loYe %ncl to divile, the
opectrum into -rbitrnry elmssillenti.:n-m
denrndIng on Vio vjn--.)unte found.
Tho L-Jor c:~~Donent or com-onarto of -%ch arn
then !!."r1i1-'1 to the
prpp-~ration no tn -cronol of Vv? ptLre c,-r-p~unl
ok-A the iddbitory or
oti:7(ul,ttory eflect notcd. An ~ct. no effort
Iris been mdo ti elucidate
-nry a~nerj-jnn w1d,!!h -my, occur Virnurh tv,) or
mire c-71pounds acting
together nn4. clenrly, in nome casen, rheniccl
intcrnoti,~n M--,'7 take
place betvaen tuo co-iponents. Thev, effect,,t,
Alch will Vti~e sorm
dinentqnelinj, wL'-! be studied in the future.
FrIk Provided V-o follovylnr~ It-it --~f results
to date. In view
of gotinle rcluct:xrce ti smy nrqthing tc) t1j,,
T. jj.0.!.'. Sub Tf7nm-ittee
about sUmul,!tion of ciller7 netivity, Rorn
revulto Pro of c ~nvlderable
intorent. The ronalts rre cln-3ilfiel Lnto
ot-Imul!,tory effects
inhibitory effectm (-) tind no eflec!t (U) n,rl
-!re reporteel fQr
BATCo document for Province of British Columbia 2
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-41-
a) 1 minute exposure
b) G-) minutes exposure
a) chronic effect, ahawing a trend of activity.
Tha7 are as follmrat-
1 viinuto 60 nLrmki Ctwonic Trend
Acatyl pero'-.Vla
P(mnotia ~-eid
ryridiro
Formaldchydo
Acct-,t1doIqde
Acetone
isaDutyr.-Lidehydo
a-Butyrradehqde
Fropioaaldel:7de
Ifethyl bromide
lfath7l cUoride
Butadiene
Crxbon monoxido
Prop7lone o.Ide
Dromoform
110tiqlamine,
Trimethylrualie
Propylono
Thiocy-mic acid
Acetic Icid
Fornic acid
exm~,,ura OxDonure
cWtuinti-in of cilim7 action
irMbition of eili=7 action
0 no Offect
- H
-
- 0
-
0
0
0 0
-
0
-
-
-
- 0
0 0
U 0
0
0 + a
- 0. 0
0
BATCo document for Province of British Columbia 2
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2-methylbut-2-ene
2-methylpentnne
2-metbylpent-2-eno
Ca rb,)n tatrneliloride
Mothyle-.* dichloride
-Afelohexene oxide
Ammonium Wrorilr.
14 nthano tbiol (Mcthyl
mcre-Aptan)
rthanol
Acetordtrile (re~hyl
cy'"MA40)
F-honol
-9-
1 Mimle 60 minutlog Phr-'a TrerA
0 =0011"O
0 N
0 .0; 0
0 H 0
- 0.)
0
0
0
0
An a r=bcr of these Compounds are gaseous, they
are not
removed by a cipretto filter, even of the
Cambridge absolute filter
tYPO. Falk atatez-l that the activity of whole
eignrette smoko vas
dimimished by filtrition to awe extent, but van
unnble to give arq
quantitative moatrare of this, nor of its rolation
to filtration
efficlenc7 of the filter.
Dr. Falk W-is irwited to 3outhampton, but wns
anable to find a
suitable d-ty during the Congrtva. It wqs learned
later thnt he
visited I.T.Co. (13ristol) on iledneedgy, 9tb
July.
Scientific Fxhlbition
Drs.K.otin and Falk hid dn exhibit nlong the linen
of the p-tper
re-A by Kotin -.ind of the discunsion at the
T.S.C. meeting. BL-ick4lotk
showed riiotoern-1hc illustrating his technique of
thoracatorq nn4
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-10-
inoculation of benapyrene, mothylabolanthrone or
cigarette woke
condensate. One carcinoma and one sarcoma from
*Uht rnts treated
e-
with ciLp-rette smake condensate hive resulted.
Xrovbb*g (Oslo)
had illustrntiong of histolegivnI prerratione
implicating cigarette
onoking to ~ f,,ctor in lung c-tneer.
An exbibit teirclqtnd to lung enneer but which was
of some
Internit w-n thit b7 the Oppenheiners and their
colleborators
(Colunbin U. H.T.) on caralnof,,eneois by Polymer
film*. Implantation
of pln3tic films of miyW kinds into rodento, h%ve
produced
c..rei,%o-,%,ttn. Th-t this is due solely to the
raWsic2l, n-Aure of
the film follmro fr= t1ho la.-tur tuncur Inoidenee
uhen perforated
or woven rtembrin-:~s or npongeoct the poly-ners
are used, -ind from
the virtu,~l ftbscnee of tumours when the a&-no
msterials in powder
form are embedde4. The poesib!IU7 th-A
earcinogenesis In due to
residual frio r!:-Jicals in the polymor structure
seems to be thereby
disproverl.
OGr/."D/46D
Uj
BATCo document for Province of British Columbia 2
November 1999