Where does a Pyrolysis method fit Where does a Pyrolysis method fit into answering the question of the into answering the question of the fate of an ingredient in Cigarette fate of an ingredient in Cigarette

combustion?combustion?

To Be or Not to be, That is the question.To Be or Not to be, That is the question.

EvaluatingEvaluating if ingredient(s) increase if ingredient(s) increase risk risk

Determine the fate of the ingredient(s).Determine the fate of the ingredient(s). Do they remain intact?Do they remain intact? Are they changed in the combustion process?Are they changed in the combustion process?

Are these changes due to new products not Are these changes due to new products not observed previously?observed previously?

Are they just adding to what is already Are they just adding to what is already present? present?

Determine if the products or transfer of Determine if the products or transfer of ingredients affect biological changes that increase ingredients affect biological changes that increase risk.risk. Exposure and kinetics of exposureExposure and kinetics of exposure Test for biological activity Test for biological activity Behavioral changesBehavioral changes

Ingredient(s): A simplified view.Ingredient(s): A simplified view.

Single component ingredients Single component ingredients Menthol Menthol

Complex mixtures Complex mixtures Cocoa Cocoa Honey Honey Apple juice Apple juice

Challenges of determining fate of Challenges of determining fate of ingredient(s)ingredient(s)

Burning process complexBurning process complex Some generalized Reaction pathways Some generalized Reaction pathways

taking place:taking place: TransferTransfer OxidationOxidation ReductionReduction Pyro synthesisPyro synthesis Particulate formationParticulate formation

Complex mixture of chemical products Complex mixture of chemical products (>4800)(>4800)

Major products COMajor products CO22, CO and H, CO and H22OO A signal-to-noise problemA signal-to-noise problem

Challenges of determining fate of Challenges of determining fate of ingredient(s) (continued)ingredient(s) (continued)

No single analytical method for everything.No single analytical method for everything. This means techniques mentioned here This means techniques mentioned here

would not be applicable to all problems. would not be applicable to all problems. New approaches may need to be New approaches may need to be

developed.developed.

Approaches to determining fateApproaches to determining fate

Comparison to referenceComparison to reference Stable isotope / radioisotopeStable isotope / radioisotope PyrolysisPyrolysis Direct measurementDirect measurement

Comparison to referenceComparison to reference

Reference without ingredient Reference without ingredient being tested.being tested.

Reference for evaluating inter- Reference for evaluating inter- and intra-laboratory methods.and intra-laboratory methods.

Considered necessary.Considered necessary.

Stable isotope / radioisotope - AdvantagesStable isotope / radioisotope - Advantages

Reduces chemical noiseReduces chemical noise Allows relative and absolute Allows relative and absolute

comparisonscomparisons Allows determination of products and Allows determination of products and

possible mechanismspossible mechanisms

Stable isotope / radioisotope - LimitationsStable isotope / radioisotope - Limitations

Labels may not be availableLabels may not be available Only certain position in the component may Only certain position in the component may

be labeled making it difficult to determine be labeled making it difficult to determine some of the productssome of the products

Complex mixtures would be difficult and Complex mixtures would be difficult and costly to form labels on each component of costly to form labels on each component of the mixturethe mixture This is an example of why flexibility of experimental This is an example of why flexibility of experimental

design is important.design is important.

PyrolysisPyrolysis

First, we do not consider pyrolysis to be First, we do not consider pyrolysis to be sufficient by itself.sufficient by itself. Performed under conditions of isolation. Performed under conditions of isolation.

Pyrolysis- AdvantagesPyrolysis- Advantages Used as a screen to indicate:Used as a screen to indicate:

Possible products of the pyro-synthesis process. (New Possible products of the pyro-synthesis process. (New products?)products?)

Help predict intact transfer. This could be most helpful in Help predict intact transfer. This could be most helpful in that if this predicted intact transfer, labeling would not be that if this predicted intact transfer, labeling would not be necessary. Analytical methods could be targeted for that necessary. Analytical methods could be targeted for that intact component (still need mass balance).intact component (still need mass balance).

Would be useful for complex mixtures.Would be useful for complex mixtures. Possible productsPossible products

Are they different from what is known to exist? Are they different from what is known to exist? Guidance for targeted analytical methods to determine Guidance for targeted analytical methods to determine if increases of these components have occurred. (If yes, if increases of these components have occurred. (If yes, what is the risk due to this increase?)what is the risk due to this increase?)

Are there components that would remain intact thus Are there components that would remain intact thus could isotopic methods or targeted analytical could isotopic methods or targeted analytical methods be used in comparison of the burning methods be used in comparison of the burning cigarette with and without the ingredient for those cigarette with and without the ingredient for those compounds?compounds?

ConclusionsConclusions Overall the determination of the fate of an Overall the determination of the fate of an

ingredient(s) under burning conditions is a signal-to-ingredient(s) under burning conditions is a signal-to-noise problem.noise problem.

Methods have been demonstrated as to how to Methods have been demonstrated as to how to undertake this problem but there is not a single undertake this problem but there is not a single approach that would cover all possibilities.approach that would cover all possibilities. Thus we have decided that flexibility in experimental Thus we have decided that flexibility in experimental

design is important.design is important. Pyrolysis is an important method for screening and Pyrolysis is an important method for screening and

giving guidance to the fate of ingredient(s) but giving guidance to the fate of ingredient(s) but pyrolysis is no substitute for comparison of matrix pyrolysis is no substitute for comparison of matrix with and without the ingredient.with and without the ingredient.

Isotopic labeling is an important approach to Isotopic labeling is an important approach to determining the fate of an ingredient but it may not determining the fate of an ingredient but it may not be practical for every ingredient especially for be practical for every ingredient especially for complex mixtures.complex mixtures.