CHAIRMANS' ADVISORY CONFERENCE
MEXICO - MAY, 1980.
SMOKING AND HEALTH: RECENT SCIENTIFIC DEVELOPMENTS
AND
THE ROLE OF GROUP RESEARCH.
CONTENTS PAGE
Epidemiology and related factors 1
Critical values of daUy intake 4
Passive smoking 5
Nicotine 6
Other smoke components 8
Carbon monoxide 8
Nitrogen oxides 9
Nitrosamines 9
Irritants 10
Compensation 10
Other sensitive areas 11
The future 11
Relevant Group research 12
Summary 13
C=~
110
c0
BATCo document for Province of BritiSh Columbia 20
April 1999


I .
EPIDEMIOLOGY AND RELATED FACTORS
Retrospective epidemiology surveys depend on the
highly suspect accuracy
of memories about numbers of cigarettes smoked,
level of inhaling, type of
product etc. Also, by definition, they relate
largely to 'yesterday's
products'.
Prospective surveys are concerned with 'today's'
and Itomorrowls' products.
If well conducted, accurate habits are recorded
until death and there is the
ability to match age , sex , race , profession
etc. The problem , however , is
that large numbers are needed and hence the
surveys are very expensive.
Anti-smokers interpret a statistical association
between increased risk of
ill health or mortality as a clear "cause and
effect" relationship. The
extreme counter view (e.g. as propounded by Prof.
Burch of Leeds) is that
genetic make-up pre-disposes disease. A finding
that lends some support
to pre-disposition is the observation reported in
1978 by Dr. T.D. Sterling
that from a study of 39,00 households in the 1970
U.S. fiealth Interview
Survey, white smokers smoke about 20% more
cigarettes per day than
black smokers, yet they have significantly lower
rates of lung disease
(especially cancer).
Irrespective of the pros and cons of the various
assertions and hypotheses ,
there is growing evidence that changes in the
design of cigarettes since
around 1960 have brought about a significant
reduction in the risks
implied by the statistical associations (FIGURE 1)
.
It may be helpful to delegates to summartse some
of the very recent
publications and conference reports since they
approach this highly
complex subject from somewhat different angles.
110
co
_1 J
-J
L.pi
L_n
BATCo document for Province of BritiSh Columbia 20
April 1999


Auerbach, Hammond and Garfinkel.
The most valuable recent publication was by three
US medical scientists,
Auerbach, Hammond and Garfinkel, who are known
worldwide for their
anti-smoking researches. They reported greatly
reduced signs of pre-
cancerous bronchial lesions observed in autopsies
carried out in 1970 - 1977
compared with those in 1955 - 1960 (FIGURE 2) .
They ascribed this
significant finding to the reduced levels of tar
and nicotine in post-1960
cigarettes.
American Cancer Society.
Garfinkel (Vice Pres. American Cancer Society)
reported in World
Smoking and Health, Autumn 1979, on the American
Cancer Society
prospective study of I million men and women
(FIGURE 31 Over a 12
year pekiod a consistent decrease in mortality in
cigarette smokers has
been observed for smokers of 'low tar/nic' vs
'high tar/nic' cigarettes:
Male Female
Coronary heart 13% 19%
disease decrease
Lung cancer av. 26%
Garfinkel also reportes statistics comparing
reductions in mortality from
heart disease in the U.S. and U.K. from 1966 to
1976 which he ascribed
"partly because of these changes in smoking
patterns".
1979 New York Conference on Cancer
Hoffman, Tso and Gori, in a paper to the June
conference on the
"Primary Prevention of Cancer" compared "smoke
components from C:>
plaverage" U.S. cigarettes prior to 1960 with the
"average" low tar of .%D
co
1978/79 and said:
"These differences could be interpreted to report
a true
reduction of risk, if recent changes in smoke
flavour
BATCo document for Province of British Columbia 20
April 1999


components have no bearing on the biological
activities
of cigarette smoke"
The deliveries cited are given in FIGURE 4.
1979 Cold Sprinq Harbour Conference
The proceedings of the October 1979 conference on
"Towards a Less
Hazardous Cigarette" will shortly be published. In
the interim the
Conference Director summarised in a private
communication to our
consultant Peter Lee, his main impressions:
I . Epidemiological evidence strongly indicates
lower risk of death
from smoking -associated diseases with lower
rather than higher tar.
2. Auerbach's study left the audience 'fairly
convinced'
3. The U.S. market is shifting very rapidly to low
tar - with shifts
in sales ahead of advertising.
Generally, there was less emphasis on the alleged
harmful aspects of
smoking and more on the improvements that have
already been madc-
through reduction in tar, nicotine and CO. It was
significant that
Dr. Owen announced a reduction in funds for the
National Cancer
Institute "Less Hazardous Cigarette" programme
saying that, after all
the programme had achieved much of its original
goals.
There was growing realisation, even by the most
strong anti-smoking
advocates, that "safer" cigarettes were on the
market and are being
used. This is illustrated by the answers
formulated at the Conference C=3
to questions raised by Dr. Michael Russell (FIGURE
5). I'D
c0
--_j
BATCo document for Province of BritiSh Columbia 20
April 1999


4.
Dr. Richard Peto
In a very recent review of Samuel Epsteins' book "
The Politics of
Cancer" Dr. Peto, a virulent anti-smoking
crusader, argued for a more
dispassionate approach to the realistic assessment
both of the risk from
environmental carcinogens and of the preventative
regulations needed.
Without in any way retracting his well publicised
views on the risks
of smoking he openly acknowledge the trends in
statistical associations
(FIGURE 6).
In taking note of these hixjhly encouraging trends
and interpretations
we must note that the statistics do not relate to
the current low delivery products:
we shall need another 10/20 years before we can
expect to see unequivocal
evidence regarding their statistical link with
safety and health.
CRITICAL VALUES OF DAILY INTAKE
In October 1976 Dr. Gio Gort (then Chairman of NCI
Tobacco Working Group)
developed a thesis th# there exist maximum daily
intakes of various
"k-
s
mo e components below which the mortality risk of
smoking associated
diseases is minimal. Based on epidemiological
surveys carried out in
1950 - 60, Gori deduced that a person in those
days who smoked 2 cigarettes
a day had a risk of mortality eqTlal to that of a
non-smoker.
Using average delivery figures for pre-1960
cigarettes:
Tar
Nicotine
43 mg
3.0 mg
CD
%10
co
co
BATCo document for Province of l3ritiSh Columbia
20 April 1999


CO 23 mg
NOX 270 lAg
HCN 410 1.49
Acrolein 130 xtg
he computed ci-itical levels of daily intake for
the various componentsf,,k
.1 120
(FIGURE 7~. -FIGURE 9 an/dxam6le of the
implications of Gori Is
91 V~lv
I ~Although not popular among the medical world,
nor to date
appr ch.
I)A ShV'
widely adopted in the U.S., it is eossible that
the critical value approach
will have an influence on product development and
on thinking in the
area of smoking and health
PASSIVE SMOKING
Sidestream smoke is very different in composition
to mainstream
smoke. Several components, including the much
talked about
nitrosamines and carbon monoxide, are present in
much higher
concentrations in the actual I sidestream I
(FIGURE 9), but the
concentrations with respect to the passive smoker
are, of course,
very much lower because of massive dilution by the
ambient air.
Moreover, the smoke inhaled by the passive smoker
will be
qualitatively different from that inhaled by the
smoker. (The
s igniftcance of this, however t has yet to be
established).
Until very recently the attack on passive smoking
was largely social,
not medical and there are several recent
statements that clearly
separate these two aspects (FIGURE 10).
All this was shaken, however, by a paper this year
by White & Froeb of the
University of California in the New England
Journal of Medicine
co
reporting the impaired respiratory condition of
non-smokers working in a -4
-4
L.014
1 ~0
BATCo document for Province of BritiSh Columbia 20
April 1999


6.
smoke environment. Based on 27100 non-smokers,
some of whom were chronically
exposed at work for 20 years or more to other
peoples smoke, it was found that
non-smokers whose work places and homes were free
from cigarette smoke
exhaled up to 25% more air per second in tests on
forced expiration. Only
smokers who tnhaled more than 11 cigarettes a day
for 20 years were said
to have significantly lower forced expiratory
rates than the passive smokers!
The potentially serious political consequences of
the paper are countered by its
very dubious basis. Our consultants Dr. Francis
Roe and Peter Lee have so
strongly criticised the paper that it seems highly
likely that it will not survive
as credible evidence. But, we know only too well
that I mud sticks I in any
area of smoking issues.
Another aspect of passive smoke that has received
some attention is the
speculation that bronchitis and/or emphysema may
be an allergic response
to smoke. But the whole subject of allergy is
ill-defined and there is no
evidence to support the speculation. The U.S.
Surgeon General summarises:
"Tobacco smoke allergy in humans is unproven".
NICOTINE
Until recently, the allegation that nicotine in
tobacco smoke is the main
habit forming component has been balanced by the
lack of evidence as to its possible
risk to health. This was supported by the fact
that there has been no evidence that in
chemical form nicotine can act as a tumor
initiator.
There are now some signs that nicotine in tobacco
smoke may act as a
carcinogen in mice - or more likely as a
co-carcinogen.
C=)
When President Johnson set up the Cancer Task
Force, one sub-group %10
co
was concerned with smoking under the title
"Towards the Less Hazardous
BATCo document for Province of BritiSh Columbia 20
April 1999


Cigarette"., Within this Dr. Gori of the National
Cancer Institute
chaired the NCI Tobacco Working Group. Part of the
work programme
was concerned with four trials of 20 cigarettes in
which condensate was
assessed by mouse skin painting. A computer
correlation linked the
biological activity to the nicotine level - but we
regard the experimental design
as suspect: only two dose levels and one of these
clearly too high.
In another programme undertaken by Dr. Fred Bock
of the University
of Buffalo, different levels of chemical nicotine
were added to a mixture
of pure initiator (benzpyrene) + a co-carcinogen
formulated to be the
synthetic equivalent of tobacco condensate. Again
a dose related
response was found. Dr. Bock is now following up
this work by
incorporating tobacco sheet(both Virginia and U.S.
Burley) to which
nicotine has been added, into low delivery
cigarettes. The results can
be ?xpected in about two years time.
Finally, we have preliminary evidence from a
recent mouse skin
programme at GR&DC with condensate from cigarettes
doped with
different levels of nicotine salts. The tumor
incidence is dose related,
but the detailed. pathology examination is still
in hand.
Any link between these findings with mice and
possible health risk
with humans is extremely tenuous - though there is
a current U.S. theory
that nicotine could be associated with cancer of
the pancreas.
While our view is that the prime aim should be to
reduce tar, we may
-well be forced to consider our position on
nicotine vis a vis:
(1) Maintaining high levels in low/medium products
(A la Russell)
.
(2) Artifically raising levels In low delivery
products (cf. Kent III)
CXD
by using high nicotine tobaccos.
BATCO document for Province of BritiSh Columbia 20
April 1999


8.
Certainly the facts that nicotine is still widely
recognised as one
reason for people smoking (thought the danger that
it ever becomes
labelled as a drug of addiction is receding) , and
that a cloud has now
appeared on the horizon, underline our need to
understand as much as
possible about how nicotine exerts action on the
central nervous system
and how it links with motivation. This is
essential if full advantage is to
be taken in the future in marketing low delivery
cigarettes. Fortunately
GR&DC are in the forefront with I psychological I
studies. It will,
however, probably be another two or tJhree years
before we shall have
a more sound understanding of the subject.
OTHER SMOKE COMPONENTS
The whole area of smoking issues is so broad and
complex that it is in-
evitable that health issues are raised beyond the
key components of tar and
nicotine. A brief status review of the other main
contentious components
is given below.
Carbon Monoxide
Carbon monoxide has a high affinity to replace
oxygen carrying blood cells,
and hence is associated with the risk of
precipitating a heart attack.
But current thinking apropos carbon monoxide in
cigarette smoke is
perhaps best put in perspective by the 1980 Hunter
Committee Report:
"evidence to indicate that CO is the principal
factor
of
(in cardiovascular disease) is less than
convincing
Technically. ventilation of cigarettes is the only
solution to date - but
other routes are being actively pursued to reduce
this component.
co
BATCo document for Province of BritiSh Columbia 20
April 1999


9.
Nttroqen Oxides
Although most frequeritly referred to after tar,
nicotine and carbon
monoxide 9 and probably next in line for attack
against the cigarette
industry, the concern for nitrogen oxides is
mainly emotional; and no
doubt highly linked to Los Angeles smog!
There is no specific link with human disease other
than extrapolation
of some U.S. work (cf. Freeman) on emphysema in
animals.
NOx levels are very strongly depepdent on tobacco
types, typical
levels for non-ventilated cigarettes:
flue cured
air/sun cured
50 - 90 jug/cig.
200 - 260 #g/cig.
Some tobaccos. especially some Burleys with high
nitrate (perhaps
as a consequence of over fertilisation) can go
even higher to
C-300 )L&g/cig.
Nitrosamines
While a large number of nitrosamines are well
established as potent
carcinogens, their health status in real life.
(combustion products,
drinks, food stuffs, tobacco) is far from
resolved.
There are three "tobacco-specific" compounds, of
which nitroso-nornicotine
(NNN) is the major one. Though their role in
mainstream and sidestream
has yet to be established, it is clearly vital
that ways are found to reduce/
co
eliminate the compounds in smoke. Much
research/development is necessary
in the areas of sampling and analysis. In the
meanwhile the most likely
correlations with free nitrate and amino acids is
being actively pursued.
BATCo document for Province of BritiSh Columbia 20
April 1999


10.
Irritants
Acrolein, aldehydes and other similar chemicals
are frequently referred
to as irritants , but the real source of I
irritation I in smoke has yet to be
identified. And certainly they have not been
established as a significant
cause of W-health. On the contrary, irritants may
be advantageous by
discouraging the deep inhalation of smoke - a
possibUity raised by recent
GR&DC inhalation studies with rats.
COMPENSATION
There is increasing reference in the literature to
smokers compensating
for low delivery products, either by smoking more
cigarettes or by
smoking more intensely.
The experimental evidence, however, which is
highly confusing and
currently much debated, varies from almost total
to almost zero
compensation. Perhaps PJ50% is the best guess for
the current "average"
low/medium product. The doubt arises from two main
causes (0 hunians
tend to change their smoking habit when they know
they are under
observation, (H) widely different experimental
methods have and
are,being used.
As deliveries approach low single numbers. the
balance must almost
certainly swing in favour of low compensation and
greatly reduced health
risk with such products.
GR&DC has established a strong position in the
field of compensation
and recently was host to a gathering of leading
U.K. medical scientists
where the subject was debated. Much of the GR&DC
work has
been undertaken by external medical teams under
contract to B.A.T.
c0
BATCo document for Province of BritiSh Columbia 20
April 1999


OTHER SENSITIVE AREAS
The results of a number of surveys on the effects
of smoking during
pregnancy may be summarised as showing statistical
associations:
- Babies are born lighter (on average 200g) and
smaller
- The risk of peri-natal death is increased
- Post-natal development may be impaired.
Some of these findings are undoubtedly affected by
other, social factors.
But in the same way that as an industry we do not
encourage children
to smoke, we would support the view expressed in
the 1980 U.S. Surgeon
General's report that it is unwise for pregnant
women to smoke to any
significant degree.
A related, but very much more tenuous area of
sensitivity is the existence
of one or two papers that suggest that smoking by
males may be
incriminated as a cause of genetic mutation -
thereby affecting pregnancy.
The papers, which do not allege the cause,have not
attracted attention:
But if they were picked up by the press in
countries with strongly masculine
outlook, the PR effect could be bad.
THE FUTURE
1 . There will inevitably be a gradual (sometimes
fast) spread of anti-
smoking pressure from developed to developing
areas.
2. But equally, in the years to comethere should
be increasing
evidence from epidemiological studies of the
effect of low delivery
products on the statistical incidence of smoking
associated disease -
almost certainly indicating greatly reduced risk.
C=:)
110
3. There will probably be a shift away from the
self-inflicted alleged co
-4
risk of the smoker to that of the passive smoker.
BATCo document for Province of BritiSh Columbia 20
April 1999


12.
4. The concept of threshold levels of selected
components (as
pioneered by Gort) will probably be developed
further.
S. There could well be demands for simplification
of league
tables by combining component factors into a
simple number or
index. (This would have no scientific basis and
would be fraught
with legal implications.)
6. There could well be some significant changes in
tobacco growing and processing.
De-nicotinisation of tobacco
Close planting of tobacco
Homogenised leaf curing
Removal of protein
reduced alkaloids and other
components
reduction in smoke NOx, HCN,
nitrosamines, amines, quinolines,
and other tumorigenic aqents.
REIEVANT GROUP RESEARCH
As will be described in the later paper on "The
Direction and Future of
Group Research", the R&D programme is constructed
around 16 key technical
areas. Of these 5 are directly related to smoking
nnd health:
- biological/life sciences
- filters
- combustion
- sidestream
- human smoking and smoke retention.
and a further 5 are strongly related:
- cigarette design co
-j
- psychology and sensory testing -1)
- smoke taste and flavour improvement
0%
- ventilated cigarette technology
BATCo document for Province of BritiSh Columbia 20
April 1999


13.
- product development services
Even in the other 6 areas many of the component
activities have relevance
to smoking issues.
It is not possible to give a precise breakdown of
the effort and expenditure -
because it often depends on the definition chosen.
But a reasonable break-
down is about I: Sm out of the 1980 budget of V.6m
i.e. 65% of the total.
In view of the complexity of the subjectand of the
programme, no attempt
will be made even to summarise the individual
researches in this paper.
The main work will, however,be referred to in the
group discussion.
SUMMARY
At a time when pressures against the cigarette
industry seem to be
strengthening in all directions . the overall
balance is probably moving
towards soptal issues and away from direct health
issues - ironically at a time
whenjVvidence is mounting that actions taken by
the industry 10 - 20 years
ago are having thedetired effect of reducing
associated health risks.
The Centre is very much alive to both scientific
and public relations issues,
and is well equipped to provide a direct support
to operating companies.
L.C.F. BLACKMAN
April, 1980. CO
_j
NJ
BATCo document for Province of British Columbia 20
April 1999


cc
>
I
0
0
CL
0
0
0
0
=r
0
0
Cr
CO
FIGURE I
Reduction in Incidence of Diseases
Associated wit. h Smoki.ng
Bross and Gibson 1968-0.60 LC
Wynder, Mabuchi and Beattie 1970-0.60 LC
Hammond 1976-0.60 LC
Dean 1977 0.51-0.76 Diseases
:FT vs PL
:FT vs PL
:Reduced T N
:FT vs PL
Auerbach 1979 0.04-0.1 Changes :Autopsies
in Lung 1955-60
vs
Autopsies
1970-7


0
o
CL
0
0
C
0
0
Cr
V Kj 0 M, Z
CHANGSU PRI=-C C"-RO LIS BRONCHIAL LESION'S
% Sections with Advanced Changes
1 9155-60 1970-77
Non Smokers 0 0
1 - 19 Per Day 2.6 0.1
20 - 39 Per Day 13.2 0.8
40+ Per Day 22.5 2.2
20.424 Sections taken at autopsy f rom bronchial
tubes
of 445 Non-Lung-Cancer Deaths:
(a) 211 who died 1955 - 1960 - 154 Regular Smokers
(b) 234 who died 1970 - 1977 - 181 Regular Smokers
Auerback, Hammond Et Garfinkel - New England
Journal of Medicine 22.8.79.
6 UZL8601


W
>
i
0
0
a
0
CD
T
"I
0
CD
0
=r
0
0
V
FIGURE 3
PAPER TO WORLD SMOKING & HEALTH .19/9
LAWRENCE GARFINKEL
A Vice President in Ameri---a Can%,,.er So%ciety.
"Analysis made of the mortality in cigarette
smokers in
The American Cancer Society study showed that
there
was a small but consistent decrease in both men
and
women in those who smoked cigarettes with low Tar/
Nic compared to those smoking high Tar/Nic.
Over 12 Year Period, The Lung Cancer Rate Averaged
26% LOWER
Also reported from 1966 to 1976 statistics on
heart
disease for both US and UK:
% DECREASES MALE FEMALE
us UK us UK
Cardiovascular 22 6 28 11
Cerebrovascular 28 21 30 17
OMb


0
0
0.
0
0
CD
0
0
0
E,
(0
FIGURE 4
Changes in smoke composition of
U.S. cigarettes
Smoke Average delivery per cigaretie
Constituent Before 1960 1978/79
"All" (Low "Tar")
TPM 43 16 8
NICOTINE (mg) 3 1.1 0.6
CO (mg) 23 17 8.9
NO W)
x 270 280 100
HCN (pg) 410 200 130
ACROLEIN (pg) '130 80 50
PHENOL (pg) 100 60 20
6 ENZO(a)PYRENE(ng) 35 18 10


0
0
CL
0
r+
e
0
:r
0
0
M
(0
c0
(0
FIGURE 5
1 M COLD SPRING KARE~0'~.JR COMFERECNCE
"TOWARDS A LESS HAZARDOUS CIGARETTE"
Q. If so is it due to changes in cigarettes?
A. -Probably Yes.
Q. If so is it due to lowered tar and nicotine or
to a
lower carcinogenicity of tar?
A. BOTH
MLL~601
Conference Answers to DR.M.RUSSEL:
Q. Are risks to 4un.g cancer from cigarette
smoking
down?
A. YES.


W
>
f
0
0
CL
0
0
0
0
>
V
Lu
MIZ9601
Smokers of "Less Dangerou
s" cigarettes have already
been found in various epidemiological studies to
have
disease rates which are materially lower than
smokers
of other cigarettes.
At autopsy they have far fewer "Pre-Malignant"
histo-
logical changes in their bronchi and, perhaps due
to the
changes in cigarette composition 10 or 20 years
ago
male lung cancer death rates in early middle age
are
now decreasing in North America, in Britain and in
Finland.
Dr.Richard Peto, Reader in Cancer Studies, Oxford
University,
Nature - 27 March, 1980


0
0
CL
0
0
0
U)
:r
0
0
M
W
FIGURE 7
daRy Entake ol, selu e'cta%"
smoke components based on data associated with
"All causes for current smokers"
Critical Values
L LAv
Smoke Component Low Average High
Tar (mg) 65 86 151
Nicotine (mg) 4.5 6.0 10.5
COI-lb (increase in %) 2.6 3.2 4.8
NOx W) 405 540 945
HCN (pg) 492 820 1435
Acrolein W) 156 260 455


0
0
0
CD
M
I
0
0
0
E*
3
>
V
CO
W
FIGURE 8
Cflt-~cal leve0s of se0ected smoke
constituents (Gori, I S78)
Brand
No. of cigarettes
Carlton Menthol L & M Flavour
required
Lights (King)
Tar 72 12
Nicotine 43 8
Carbon monoxide 23 10
Nitrogen oxides 45 14
Hydrogen cyanide 68 13
Acrolein 26 9
Lowest column
23 8
entry
Highest column 72 14
entry
SML860i


0
0
CL
0
M
0
CD
0
0
0
Cr
FIGURE 9
Gas Phase itent Sidestream
firia5nstream Con
Mainstream
Carbon Dioxide 20-60 mg
Carbon Monoxide 10-20 mg
Arnmonia* 0.08 mg
Hydrogen Cyanide 0.40 mg
Pyridine 0.032 mg
Dimethyinitrosa mine 0.00001-0.000065 mg
Particulate Phase
"Tar
Nicotine
Behzpyrene
Nitrosonornicotine
1-40 mg.
1-2.5 mg
0.00002-0.00004 mg
0.00001-0.0005 mg
92 ULB 601
8.1
2.5
73
0.25
10
50
1.7
2.7
3.4
5


W
>
0
0
CL
0
0
C
3
CD
0
FRAME 10
P A,-!, SV S!"O 0 K I N G
1979 US SURGEON GENERAL-S REPORT
"Healthy non-smokers exposed to cigarette smoke
have little or no physiological response to the
smoke,
and what response does occur may be due to
psychological factors"
1979 CHAIRMAN OF THE AMERICAN HEART
ASSOCIATION TASK FORCE ON THE ENVIRONMENT
AND CARDIOVASCULAR DISEASE
"Studies indicate that non-smokers have negligible
levels of carboxyhemoglobin under good conditions
of ventilation, and with no ventilation have
accept-
ably low levels"
1980 HUGOD, HAWKINS and ASTRUIP
"It is pointed out that in spite of an often
consider-
able subjective discomfort, exposing non-smokers
to tobacco smoke under realistic conditions will
not
cause inhalation of such amounts of the components
of tobacco smoke traditionally considered harmful,
that a lasting, adverse health effect in otherwise
healthy, grown up individuals seems probable"