SCIENTIFIC RESEARCH GROUP
BERLIN JUNE 5 - 7 1991
P R Z's -2 1 T
Dr. P. Madsen
Dr. S. Massey
r. T.G. Mitchell
Dr. D. Pangritz
%:.r. T. Riehl
Dr. C.J.P. Siqueira
Dr. G. Smith
Dr. R.E. Thornton
External Speakers:
Pro". D. Adlkofer
Dr. D. Cooper
Dr. A. Daly
Dr. R. Kunze
Prof. Pawlik
Dr. F.J.C. Roe
Wednesdav 5th June (PM)
1. Reculatory Issues
ELrooe
Skandanavisk Tc-'-aks
ITL Canada
BATCo. (Additives)
BATCF
B & 1-7
Souza Cruz
BATCo. (Secret-mrv)
BATCo. (Chairman)
Berlin
London
Newcastle
Berlin
Hamburg
London
"embers of the European Tobacco Industry have
c~=-'-ined
:o form the Confederation of European Cigaretze
and
Cigar Manufacturers (CECCM) . The SRG was update-:
as to
its act4vities, in particular that of the
Additives Sub
Group. The potential importance of the new --.C.
'44rective on the use of additives on foo' was
--4iscusse-4.
com-"ined industry initiative would make any
'-idepen-4ent approach on additives
by the B.A.T Group
Jifficult to pursue, although there was no reas;:n
why
the indu-stry initiative should not incorporate
scme or
-all of p~,ints in the B.A.T approach.
CD
CD
-r~:*
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7 ea lan'
7 reat deal of activity in Ne-,,; Zealand relates
a-,S:'-'ss1cn between the industry and the
Government on
t'-1 a use of additives. Philip 11crris have
produce--2 a
cz.7zcsite list of tobacco additives, based on
combining
ex---z:ing lists from a number of ccuntries. The
merits
ox :.iis approach compared to a shorter
compilation
!:;as~--2 on one or two existina lists were
discussec.
A-`-~-':ives used on imported brands into France
may h1ave
tc -'-=- proviied.
Si.-.~=-=ore/?-'alavsia
Ac:::n by the New Zealand Gove--nment may well be
re=----azed in Singapore and Malaysia.
Switzerland
The --ndustry and the Swiss Department of Public
Heal-,,
are to meet on the subject oi Ad-4itives. A
composite
list was tabled by P.M.
AL:s:::--4a
Aus--r-'a are to produce their own tobacco
ordinance
base-~ on that in Germany.
It w--s proposed and accepted by the SRG that
B.A.T
s h c --, I dtable the B.A.T docunent on additives
at t, e
next meeting of CECCM to be held in Lausanne,
September
1991. The B.A.T list drawn up ty BATCo. and BAT-CF
co.-i'---::es both German and French Lecislation.
2. Product Assessment
The extensicn of the procedure used to evaluate
tobacco
additives -was endorsed by the SRG.
Reviews c--2 the properties of nine additives were
presented
includinc recomm enda t ions on their future use.
Members of
the SRG were asked to look at these evaluations
and repczt
back to Dr. Smit;i within 2 months.
4--
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3. Product Data Base
The SRG -,.as uo`a'e,4 on t~ 'e curzent status of
the od u c t
Data Base. The ocedure followed was accepted.
4. Aqrochemical Usaae
It was re-,orted that an increasing number of
countries are
publishing residue limits for agrochemicals on
tobaccc. In
addition, a possible E.C. initiative may result in
levels
quoted for 27 substances.
It was e::~Dhasisej that the Comoanv must be aware
cf the
issues invclve-f in tobacco residues and be in a
position to
monitor t"le-ir levels on tcbacco/products.
Thursday 6th June
S. An uodate of Existing Proiects
Professor Idle - Newcastle
.4 site visit in March 1991 by RET went a long way
to
diminish concerns expressed at the last meeting cf
the
SRG regarding progress of this project. Wc _- k i
s
currently aimed at cloning the gene controlling
the
enzyme respcrsible for debrisocuine metabolism.
Professor G. Grav - London
An u-:--,4ate on the work of Professor Cray w-'ll
be
avail-=ble following a site visit by RET.
Dr. 1'. Knott - Ottawa
initial technical problems have been resolved and
the monitoring of su!~Jects is to start mid-June
1991.
it was reoorted that the project was on schedule.
Professor Clausen
The extension of Professor Clausen's project to
include
the 7etabol-ism of caffeine was agreed. The
initial
intenzicn to evaluate debrisocuine metabolism was
not
possitle due to its unavailability, as the
manufa=turer's have apparently withdrawn
debrisocuine.
CZ:
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5. New PrODOsals
Prcfessor C--:-rie - London
In recocnit--on of the high standar--4 of work to
Jare on
p::-- research it was agreed to extend the
existing
fun_~inc by 12 months, with the possibility of a
further
12 7.cnzhs excension to 1993 to be considered in
1992.
Prcfassor S:=-ll - Liverpool
A _decision on the proposal from Professor Stall
to
investigate the expression of p53 in carcinoma cf
the
hea-4 and neck could not be made without a site
visit.
Sucr. a visit is to be arranged.
Scr--ncall & lee - London
A zrcDosal to investigate the use of segregation
arla-7SIS in evaluating genetics and lung cancer
was
accepted.
Prcfasscr Newson-Davis - Oxford
The =rcject designed to study Lambert-Eaton
myasthenic
syn":cme in cancer patients was not accepte,~.
The decisions of the SRG were based in part on the
views exp-ressed by the consultant, Dr. F.J.C.
Roe.
6. Budaet
RET_ presente-Z proposals for the 1992 budget
based on a
per Company contribution of E71,000 and making a
total
budze': of ~_284,000. For 1991, where the Company
con:ribLltion had been agreed at E74,000, (total
E299-MO) -z271,812 was allocated as at 14.6.91.
7. Presentations
Dr. --.J.C. Roe - London
a) .: recent paper on the toxicity of sidestream
smoke
=5 meas*;red by mouse skin painting was described.
7 ne conclusions reached were questioned due to
flaws in the procedures used and interpretation of
--ne cnances noted.
b) In overview on recent discussions on the
relative
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_i::ipor: _=:~ =a c 77~itocenesis, mutagenisis an~
tumor I ~~_nes Is was presented. Current t h _4
n,: in
consiz=_~_= the ability cf a material to induce
ce-'.;
-'ecrCELS and prol-i-era:ion an important
parameter
~ihen its toxicity.
c) Animal Tests
diet Icna term studies have s h o wn the
po:en-__-__- pitfalls in t- e
interpreting
carcinc7enlcitv daza from ad libitum fed animals.
Diet r=__=':rictio.-I re4-uced the incidence c f
soorltan=_CUS leslons', possibly due to t*-
-e.--;uct:.:.-. both in cell turnover and the
fornaticn
cf en-_~zzencus matefials
Dr. A. Dal,, - Newcastle
Dr. Dalv in:rocuced the ccicept of the metabolism
c f
xenobioticS and the variaticn between individuals.
Whilst mcre an--' more classes of enzyme are
identifie-4
each acting on specific substrates, the
informative
presentaticn concentrated on the enzyme
responsible for
metabolisin:: _`ebrisoquine.
BV measur`nc: the ratio o f debrisoquine and its
m~tabolii::e_=, Individuals mav be classified as
extensive
or poor me:-z'clisers. Extensive metabolisers are,
i r-
is argued, a: greater risk of lung cancer than the
poor
metaboliser-t.
Recent wc--'-, 'nas concentrated on the genotyping
of
indiviCuals -.;"-Icse metabolic =rofile is known.
The cook
correlation between the phenotype and the genctype
means tha: z3c:2 and poor metabolisers may, in
fuzure,
be de~-ermine_- by genetic analysis rather than
the less
convenient Zicchemiical approach.
Future -wcz*-: will include the cenotyping of 400
lunc
cancer and z~'n control oatients.
Professor Pawlik - Hamburq
By dividin= up the smoking process to include puff
duration, :,-.::er-puff duration and time b e c
-.-i e en
cigarettes, ': Pawlik has evaluated the
.rozessor
influence : f smoking on a range of variables.
Measuremen:-= 'were made on phlysiological,
behavioural
and subjec---ve paraneters.
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Experimental ci~:arett=-s containIng low and
medium
levels of an-4 two crourS of smokers used to
"low" and levels of nicctine, as defined by
their normal c:zare:te, were -se6 to note their
influence on the :ieasured variables.
Amongst an extenSive series of observations
Professor
Pawlik noted:
a) Heart rate inzreasad after puffinq a cigarette
b) Mi:2dle nicotine croup were mcre alert than the
low
nicotine grc,:-,
c) MUddle nicotine croup had faszer response time,
but
a slower reac----'cr. 6--ime in a vigilance test
Friday 7th June
Presentations
Dr. D. Cooper - T-ondon
Dr. Cooper discusse-- the new and elegant
techniques
used by molecu---ar geneticists. They include
restriction frac::enz lencth polymorpnism,
polymerase
chain reaction ana southern blott-ing.
A range of inherited- --'iseases were described,
mainly
associated with '--lee-4ing disor--~ers. In all
cases
changes in the -'NA could be identified that were
associated with t'e disorder.
The mutations were no-- considered to ta randomly
found,
there beina hot spc:s -where chances were more
likely to
occur. Such chances were due to endccenous
chemicals
rather than externai xenobiotic materials.
Dr. Cooper conclud=-,-~ his presentation by
considering
the project designe-d to map out the hurian
genome.
Dr. Kunze - Berlin
In vitro assavs '--=ve beer. develooed ov Dr.
Kunze to
investigate the cyrcr-cxicicy of ci~3are::te
smoke.
Endpoints includinc protein release, enzyme
release
(mitochondrial and cytoplasmic), loss of enzyme
activity and reduc=--- integrity of the cell wall
were
described.
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The test s--bs:ance introduzsJ Into the cell
culture by
either:
a) bubbling s~:-,oke through :ne cell suspension
so
ca-'Ie:! direct ::iethc--~; :r
b L:'-, ~- 1 in a smoke thrcug-. -~ buffered
medium and :nis
a--;--ed to t-e cell suspe:~-=:on the indirect
met---z.
7 n all cases presentec the --:rect method
producE---' the
zreater response.
initial exoerimenrs wi-n cz,==rettes illustrated
:.-. a t
product differences COLId found and the time
zz-:rse
of the resoonse sl-culd be n::=-=.
Professor Adlkofer - Berlin
review of the issu.es on ~.-.-.`ronmental tobacco
-=:- c", e
ncluding epi~4emiclogy, toxL=:logy and risk
asse-c-s--ent
procedures were described.
'The relevance of the repor:sf IRR of 1.28 was
ser--z.:-=-Iy
questioned due to the inf-1---ence of
misclassific-=::.=n,
other life-style factors an~- the wisdom of usinq
==-~:a
analysis.
7 oxicoloci-cal arguments use-- '--y IARC did not
take :.n~o
account differences in ---=::ake between side -=
nd
in addition =-:,:oosure to ETS di-4 t
increase urine miutacenic-~---: or adduct levels
;n
peripheral blood cells.
:'isk assessment procedures -here complicated by
:ne
azsence of any linear respc-Sa between biological
~-nd
zoints such as adduct fc:7ation, and DNA
zclymorphism. The relative :,.-:~ortance of
genotox-4- =.a
..cn-genctoxic inechanisms was -Also far from
clear.
The next meeting of the SRG is prc:ected for April
1992, zo
be held in Montreal, Canada.
Addendun Tentative Date: May 5-7::n 1992
Location Vikinc :nn
C)
~1-1
U-I
-rz:.
CC)
BATCo document for Province of BritiSh Columbia 28
October 1999