Copy for: JANUS Fil-
DR. S. J. GREEN,
RESEARCH 4 DEVELOPMENT. D. G. FELTON
MILLBANK.
DGF/VC/460-2 28th January, 1966
I enclose a note summarising suFgestions for
the long term skin painting tests to be carried
out
under Project JANDS. These represent the
suggestions
from R.4 D.E. for discussion at the meeting to be
hold
in Millbank on Thursday. 3rd February.
r)
C.c. Sir Charles Ellis
Dr.w.n.rordyce
D.J.1food, Esq.
Janus File
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DGF/VC/46D-2
Project JANUS
1. Introduction
28 th January, 1966
The following suggestions are put forward by
R.& D.E. as the result of discussions between
C.I.A.,
D.J.W., I.W.H. and D.G.F. The aim has been to
propose
a scheme of interlocking experiments in which
there are
a small number of variables, which are susceptible
to
control over a limited range. These variables are:
(a) Temperature
(b) pH
(c) Aromatic polycyclic hydrocarbon concentration
in condensate
Other factors which are involved are:
(i) Tobacco change
(ii) Process changes, e.g., chemical or
microbiological
(iii) Cigarette parameters, e.g., porosity, cpi
and packing density
(iv) Puffing parameters (in practice, these are
restricted to puff volume change)
2. The mice which are to be used in JANUS do not
originate directly from I.C.I or Harrogate.
The assumption was made initially that their
mortality and tumour rates would be similar to
those of
the Harrogate mice, but this must be established
at the
earliest time. In view of the possibility that the
mice may be different from the Harrogate strain,
the
orders of difference in specific mouse skin
carcinogenicity,
which are demonstrable with the numbeis of mice
available,
may have to be larger if the same significance
levels
as are used at Harrogate are employed at
Frankfurt.
This point is under examination in R.& D.E.
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3. Standard Tobacco
For the purpose of examining the effect of the
interlocking variables on biological activity, it
is
necessary for a standard tobacco to be chosen.
Ideally,
this standard tobacco should be one permitting a
comparison with the results from Harrogate,
although the
possible difference in mouse strain may preclude
this
in practice. In what follows, it has been assumed
that
the standard tobacco is a flue-cured blend, for
the
following reasons.
(a) There is some evidence (Bock, Wynder) that a
U.K. type cigarette is more carcinogenic than a
U.S.
blended type.
(b) There is a considerable background of
experience
in R.& D.E. on the chemistry of flue-cured tobacco
smoke.
(c) Inherent in the schemes are chemical
treatments
which may only apply to flue-cured tobaccos.
4. Scheme 1 (see Fig.1)
This scheme would involve a total of 11 (or
possibly 13) samples and, moreover, does not
include a
repeat test on the standard cigarette, which is
thought
to be necessary.
The experiments outlined would serve to illustrate
the following changes in variables:
Change 1-2 Change in APH concentration but
probably not
temperature or pH.
1-3 May change temperature and APH, but not pH
3-4 As 1-2?
1-5 Change in APH, pH but probably not temperature
s-6 ?
to 1-7 Change in APH, pH but not temperature
7-8 ?
1-9 Change in APH, pH and temperature
9-10 ?
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The following additional points should be made.
(a) Change in puff parameter. This is important in
the context of human smoking where a lower puff
volume than 35 ml. should be investigated (10 ml.
is suggested). A reduction in puff volume
could be achieved by cigarette design.
(b) Change in cigarette parameters. By change in
paper porosity, cpi and packing density, it will
be hoped to achieve high puff temperatures.
Should the need arise, such changes could be
readily made by manufacturers.
(c) Chemical and microbiological treatments are
aimed
at producing a tobacco similar in characteristics
to an air-cured fermented type. A sample of a
commercially available tobacco of this type is
included for comparison.
5. Scheme 2 (see Fig.2)
This scheme only requires 10 samples and includes
a repeat on the standard tobacco. The interlocking
of
samples cannot be achieved here and the scheme
examines
a number of approaches.
only are:
The samples which are included in this scheme
(a) K2C03 treatment - Lowers APH, changes pH and
temperature.
(b) Low Bp. Burley - A filter tip cigarette with
low tar and low bp. with
normal nicotine.
(c) BONDEX filter - The viscosity of smoke
condensate
passing a BONDEX filter is
different from that of condensate
from plain or acetate or paper
filtered cigarettes.
(d) Added Bp.
C.c. Dr.S.J.Green
Sir Charles Ellis
Dr.W.B.Fordyce
D.J.Wood, Esq.
Dr.D.G.Felton
Janus File
- An attempt to determine whether
smoke is predominantly a
carcinogen or a co-carcinogen.
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November 1999