States that some possible modifications to reduce ignition potential of cigarettes "could be connected wtih a change in the biological activity of the smoke of these products."
States that the objective of the industry therefore is "to assure that these modifications do not lead to an increase (or arise) of an unwanted biological activity, which is harmful to the consumer." States means of measuring biological activity (chemical/physical analyses, in vitro or in vivo studies). States need to compare the levels of biological activity of fire-safe modified cigarettes with that of conventional cigarettes currently on the market.
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Short Proposal: Low Ignition-Potential Cigarettes
It is conceivable that at least some possible modifications to reduce the ignition po-
tential of cigarettes could be connected with a change in the biological activity of the
smoke of these products.
The objective of the industry therefore is to assure that these modifications do not
lead to an increase (or arise) of an unwanted biological activity, which is harmful to
An increase in the biological activity can be measured either indirectly by chemical/-
physical analyses or directly in biological systems. As epidemiological studies from
the practicable point of view are not capable to help in this respect, guidance can
only be expected from
in vitro and
in vivo studies.
It is obvious that, not only in view of the limited scientific resources, these assays
should only deal with these parameters which have shown that they are directly or at
least tightly associated with a possible negative impact on the consumer. That
means, these parameters have shown that they, in the context of the objective, are
In order to detect changes in the biological activity between the customary and the
new, low ignition-potential product the assays need to have proven their reproducibi-
lity, which means, for at least, they are
As a comparison between two products is required, a major prerequesite of each
assay is its ability to give not only qualitative data (yes/no answere) but also being
Furthermore the assays to be applied should have shown, that they are able to detect
differences between the biological activity of cigarettes which are extremely diffe-
rent with respect to their filler content. Although this is not necessarily a prerequesite
with respect to the objective, these assays would be judged as more sensitive than
others which have not shown that they are
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Conceptually there are two approaches to investigate the influence of a cigarette
modification on the biological activity of its smoke,
Following the so called performance-based approach, one would investigate the
biological activity of a cigarette prototype, which is identical to the cigarette intended
to put on the market place. The shortcomming of this approach is that the informa-
tion gained from the investigations would be only valid for that special prototype.
Each change in that cigarette, e.g. minor variations in the filler composition, would
therefore implicate the necessity of a reevaluation. Furthermore, and most impor-
tant, this approach would not give any insight into the biological importance of the
A scientificly more valid approach, which gives the information about the impact of
the modification itself, would be a
This means, investigated will be a series of cigarettes which differ in the ext~nd
of that modification, which is intended to reduce the ignition potentia of cigarettes. If
evidence is given, that effects or the absence of effects are not restricted to a given
cigarette type but is rather an intrinsic consequence of that modification, than that
information can be taken for the decision to give or to give not a general permission
for that modification.
The decision to accept a modification or not requires two elements: a comparison
and a decision rule.
As a first step, the results of the investigations have to be compared with some kind
of a reference. This reference could be #he biological activity of the cigarettes alrea-
dy on the market place or a defined segment of these. However, if a design-based
investigation has been choosen, this choice of reference results in the undesirable
situation, that the outcome of the comparison depends on the basic construction of
the cigarette type used to investigate the consequences of the modification. If this
basic construction leads to a rather low activity of the unmodified cigarette, than the
modification will probably not result in a biological activity which is higher than the
reference. The opposite is true, when using a high biological activity cigarette on top
of which a modification is placed.
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More appropriate seems the
comparison of the modified
with the unmodified cigarette, ~ 'k
which inherently underlies the design-based approach. Taking the unmodified ciga-
rette as a reference, the actual decrease or increase in the biological activity due to
the modification can be assessed quantitatively.
More problematic than the choice of the type of comparison seems the choice of the
decision rule, especially when more than one parameter are to be judged. In that
situation there are in principle only two alternatives:
1. Any increase in the biological activity of a single parameter due to the modification
leads to a rejection of that modification.
2. Increases in the biological activity of one parameter can be compensated by a
decrease of another parameter.
Decision rule 1 takes a more conservative approach and, at first sight, seems to
protect the consumer more than the alternative. But considering the situation when
only one parameter is minimally increased and all the other parametersinvestigated
are drastically decreased, then this decision rule is in fact detrimental to the consu-
increases in the biological activity
should be weighed against decreases.
There are obviously no conclusive criteria to perform such a balance. A reasonable
approach, however, seems to use the variation of the single parameters in those
cigarettes already on the market place as a guidance (the mathematical context for
this approach is given in the appendix).
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3 CHEMICAL/PHYSICAL ANALYSES
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4 IN VITRO STUDIES
4.1 Proposed Assays
One aspect which should be covered by in vitro investigations is the cytotoxicity of
the smoke. An assay which deals with this aspect and has proven to give reliable,
dose dependent responses for a lot of substances is the
neutral uptake assay.
This test is, to our experience, not only sensitive to cigarette smoke but also capable
to discriminate between different cigarette types. As the direct application of cigaret-
te smoke, as in other in vitro systems, poses major disadvantages, the particle
phase and the gas phase of the smoke should be assayed seperately. This can be
done by applying either condensate of the smoke or saline through which filtered
(particle free) smoke was bubbled.
An other aspect to be investigated is the genotoxicity of the smoke. An exceptional
reliable test system with this respect is the
Salmonella plate incorporation assay.
This assay, commonly called the Ames assay, has shown for cigarette smoke con-
densate to be able to discriminate between differrent cigarette types. For the gas
phase of the smoke we recommend the
Salmonella microsuspension assay,
which is an variation of the incorporation assay. Also here smoke bubbled saline
should be applied to the test system.
4.3 Further Considerations
additional assays with the same endpoints
additional assays with different endpoints