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DISCUSSION ON BrOLOGICAL RESEARCH:
MEETING HELD IN Re-DE, S0UT11X%1PTO:',,
23 RD SEPTEMBER, 1971
Present: Dr. S.J. Green
Sir Charles Ellis
Dr. H. Borowski
Dr. C.I. Ayres
Dr. S.R. Evelyn
Dr. D.G. Felton
Dr. F. Haslam
Dr. R.E. Thornton
In opening the meeting, it was suggested that
renewed
efforts should be made to capitalise on the work
already under-
taken at Frankfurt, and to produce new acceptable
cigarettes
with reduced activitv. For exampleg cigarette
condensate having
e 20% lower specific activity and a 40% lower
activity per
cigarette would be an initial target. CDE referred
to the
reduced activity resulting from ethanol extraction
and asked
what work was being undertaken to follow this up.
FH indicated
that P.J. Nicholl had undertaken a study of
extraction using low
polarity solvents. The ethanol extracted samples
will be
examined at Frankfurt using the promotion test.
SJG pointed out
that, on a large scale, the paper reconstitution
process involved
an initial extraction process (water) and that
variations on this
procedure could be examined.
It was mentioned, however, that ethanol extraction
generally
led to products with poor taste characteristics.
CDE also asked
what happened to nitrate in such extraction
processes. It was
probable that most of the nitrate would be
extracted but DGF
pointed out that the levels of nitrate in
flue-cured tobacco were
low.
SJG suggested that the need for long-term
mouse-skin
painting experiments would probably decline after
1974. It was
C)
expected that alternative tests would be
available.
Although the initial results of the promotion test
were
promising, DGF cautioned ar,",ainst over-optimism
until it was
certain that we had a reproducible meaninaful
test.
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In view of the emphasis on short-term tests9 the
various
techniques available were discussed briefly as
follo%*s:
1. Sebaceous Gland Test
The main feature of this test is the very good
correlation
currently found between the results and those of
long-term skin-
painting experiments. There is also a good
correlatioti with the
weight of the nitromethane fraction.
The mechanism of the test is not clear but it was
probable
that it was a measure of the toxicity of materials
which pene-
trated through the epidermis, Possibly via the
hair follicles.
DGF outlined the history of the test and mentioned
that (a) it
did not measure carcinogenicity, and (b) it
probably worked well
because it was applied to a group of materials
acting through
the same mechanism. The experimental conditions
were, of course,
similar to those in skin-painting experiments. CDE
asked whethor
the test should be set up at Frankfurt but it was
generally
considered that it would be better to concentrate
testing at one
centre for the time being. As with other tests,
the initial rush
of interest might well decline.
The position of the sebaceous gland test at
Huntingdon was
also discussed. SRE compared the results of a
recent test (on
tobaccos with various sucker control chemicals)
which 1,.ad been
carried out at Hamburg and Huntingdon using a
condensate prepared
at Bristol. From this it appeared that the test at
Huntingdon
had been improved considerably. A detailed
comparison of the two
sets of results had not been undertaken but there
were only m1nor
differences between the Hamburg and Huntingdon
results.
CDE suggested that the samples in the B9 long-term
experiment
should be submitted to the sebaceous gland test.
2. Hvperplasia Test
This test was currently "out of favour'19 but SRE
suggested
that this attitude was not entirely justified.
Although some sets
of results appeared misleading, some apparently
very good results
had been obtained; those for B9 and also for B8
were good examples-
The use of the test had declined but it could
still prove valuabl C)
in assessing process variants of reconstituted
tobaccos.
The basis of the test was ar
.jain questioned: SRE considered NJ
that, like the sebaceous L.;land test, the short
duration impliecl
that it was probably a response to promoters and
irritants.
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Emphasis on tests associated with promotion was
probably j125tifieti:
Lee's work on various models of the Harrogate
long-tfrm tesTs
indicated that the best fit wa5 found if it was
assumed that
about 80% of the activity of conclensate was due
to its promozin~-
activity.
3. Inhalation Tests and 'in housel Proaramm,--
It was suggested that the main emphasis should he
on short-
term tests. CDE considered that long-term
inhalation tests
would not be accepted for a long time. Inhalation
tests were
required, however, to compare coaunercial products
even if the
tests were empirical in nature.
CDE asked whether tests related to emphysema or
macrophage
activitv were being considered in the ?in house'
programme, and
SJG asked SRE to outline the proposals although
thase were
necessarily tentative at this stage.
SRE indicated that the most essential project was
concerned
with dosirnetry. This would involve retention
studies using
different types of cigarettes and substitute
materia3s, smoking
machines, smoke concentration and also respiratory
measuremenvs.
The objective was to determine appropriate methods
of comparing
different products similar to the specific
activity basis used for
condensates. A programme on the development of
various short-term
inhalation tests was also envisaged but the
entpha5iS within this
area would be decided most appropriately when the
staff had been
recruited. In general it was considered that it
would be pre-
ferable to recruit a respiratory physiologist and
possibly a
qualified histologist rather than an experimental
pathologist.
New Products of Reduced Biological Activitv.
It was considered that R&DE should provide the
guidance in
this area, based on the work that had been
undertaken at Frankfurt
and at Southampton. CDE suggested that it was
important to break
away from design exercises and small scale tests.
Cigarettes
should be produced which would have a markedly
reduced activily
and acceptable taste; the latter characteristic
could be judged
internally. Only at a later staGe was it essential
to modify suc
cigarettes for specific markets.
Various design details and criteria were
discussed. Carbon
monoxide and other gas- phase components were
likely to be _.;ncJu,J,xr11r_1
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in surveys in the future but in any case reduced
deliveries of
these materials were essential. The merits of PCL,
-4incel, NCF
and strand width were discussed with reference to
CO delAivery.
It was apparent that the conditions of combustion
must be con-
sidered as well as the material itself.
CIA stated that reductions in activity could be
achieved
more readily by reducing tar delivery than by
reducing the specific
activity of the condensate. As an example he
suggested the use
of NCF, a good particulate filter plus sufficient
vapour phase
filtration to provide a balanced smoke.
DGF questioned the use of NCF rather than 1-308 as
the
latter would reduce both TPM and CO delivery but
FH felt that it
was better to accept a moderate level of CO than
to use completel,
synthetic sheet material.
The difficulties of making an acceptable cigarette
were
emphasised and in particular it was necessary to
have a market
segment in mind so that "acceptable" could be
defined even if
only approximately. CDE did not agree with this
argument in the
first instance: it was sufficient to undertake
WOODROSE tests and
use a very restricted population for consumer
tests. SJG agreed
with this reasoning and considered that it was
necessary to break
away from the barriers which had been illustrated
by CIA.
In a first attempt to put forward a blend brief,
the
following was suggested:
(1) Cost comparable with high quality cigarette.
(2) TPM delivery, 10 mg.
(3) Carbon monoxide, lower than average.
(4) Reduced specific activity.
(5) The biological activity should compare
favourably with present
brands in any test.
It was impossible to incorporate all the factors
known to
lead to safer cigarettes into one type of
cigarette, this was
particularly true when acceptability is taken into
account. For
this reason it would be worthwhile considering the
manufacture of
or 3 different designs and CDE considered it most
important to C=)
examine the restrictions and compromises which
were inherent in
each cigarette. FH indicated that one R&DE
approach was to attemp%.n
to improve the smoke quality of blends containinG
50% PRT.
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CIA outlined three other prototype cioarettes
which had been,
or were beingy examined, These were:
(a) KSFT based on flue-cured tobacco. In this, 25%
CRS and 25%
PRT had been incorporated; a dual filter having an
efficiency
of about 50% was used.
(b) KSFT cigarette: in this design, based on
incorporation of
BATEX, the effect of carbon and chalk in BATEX had
been
examined.
(c) KSFT based on modified B&H blend with
incorporation of two
levels of NCF.
Following further discussion of the main points of
such a
brief, and the aspects normally covered in
Germany, SJG suggested
the followina:
(a) Length 84-85 mm.
(b) Draw resistance up to 14 cm.
(c) TPM delivery 10 mg.
(d) Nicotine delivery not greater than 1.2 mg.
(e) Impact comparable with current US cigarettes.
(f) Biological activity 40% lower (per cigarette)
than VICEROY
on every test.
(a) Carbon monoxide lower than typical US
cigarettes.
(h) Reduced delivery of other vapour phase
components, e.g.
acrolein, hydrogen cyanide.
It was suggested that the cigarette should be
based on a US
blend.
(=3
SRE/SEW/1.1.1.3 \0
29 th September, 1971
BATCo document for Province of BritiSh Columbia 2
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