Variation in Smoke Toxicant Yields from Selected Cigarettes

Transcription

1 Variation in Smoke Toxicant Yields from Selected igarettes lison Eldridge, Kevin Mcdam 67th TOO SIENE RESERH ONFERENE September 15-18, 2013 Williamsburg, Virginia US

2 ackground The FD have implemented the reporting of HPHs in cigarette mainstream smoke n understanding of variation is required in order to contextualise the HPH measurement data. Designed a study to provide data on variability in HPH emissions FD U.S. Food and Drug dministration HPH Harmful / Potentially Harmful onstituents

3 Study Design To understand how representative is a sample of commercial cigarettes taken at a single time-point 3 high volume commercial cigarettes from a single market - 2 x T products (10mg & 4mg ISO tar yield) - 1 product by another manufacturer (10mg ISO tar yield) - Sampled monthly for 10 consecutive months - ugust 2010 to May 2011 Laboratory control nalyses conducted at single T laboratory - Full Hoffmann suite at both HI and ISO regimes - igarette filler blend - igarette physical measurements Focus on 18 HPH defined by FD at HI & ISO smoking regimes

4 Data nalysis Real world approach - Did not control analysis schedule - Generally the 3 commercial products from a single month were analysed in the same analytical batch - 7 to 10 analysis batches per product per analysis - Each analysis batch included a sample - The reported mean, of 5 replicates, per sample was used in this analysis Results investigated using summary statistics - oefficient of Variation (V) - omparing within and between products - Standard Deviation (SD) - Empirical rule 2 x SD = ~95% of a normal distribution - n estimate of within laboratory tolerance around a single measured value

5 General Variation Mean V for the 3 commercial products Generally low variation Sources of variation - nalytical - instrument operator chemical standards - Product - blend composition product design manufacturing HPH ISO V (%)* HI V (%)* Nicotine mg/cig O mg/cig ,3-utadiene µg/cig Isoprene µg/cig crylonitrile µg/cig enzene µg/cig Toluene µg/cig minonaphthalene ng/cig minonaphthalene ng/cig minobiphenyl ng/cig NNN ng/cig NNK ng/cig mmonium µg/cig Formaldehyde µg/cig cetaldehdye µg/cig crolein µg/cig rotonaldehdye µg/cig enzo[a]pyrene ng/cig * Mean V for the 3 commercial products

6 nalytical Variation Sample Preparation Smoke sample preparation V (%) enzo[a]pyrene at HI igwt (mg/cig) Puff No TPM (mg/cig) [a]p (ng/cig) Practical lower limit of variation for a reasonably controlled analysis: typically 3 6% V for TPM

7 nalytical Variation nalytical Methods Grouped by analytical method Factors affecting variability of an analytical method - mount of HPH - omplexity of analysis TSN analysis was the most variable 1,3-utadiene and formaldehyde have noticeably greater variation at HI within analysis suite rotonaldehyde and formaldehyde at ISO within analysis suite HPH ISO V (%)* HI V (%)* Nicotine mg/cig O mg/cig ,3-utadiene µg/cig Isoprene µg/cig crylonitrile µg/cig enzene µg/cig Toluene µg/cig minonaphthalene ng/cig minonaphthalene ng/cig minobiphenyl ng/cig NNN ng/cig NNK ng/cig mmonium µg/cig Formaldehyde µg/cig cetaldehdye µg/cig crolein µg/cig rotonaldehdye µg/cig enzo[a]pyrene ng/cig * Mean V for the 3 commercial products

8 nalytical Variation: Volatiles nalysis at HI 1,3- utadiene (µg/cig) D E 1,3-utadiene F G H nalysis atch D oth HPH from the same analysis and at a similar level 1,3-butadiene clearly more variable (20.9% vs 6.1% V) Synchronous pattern across all 4 products indicative of analytical variability Potential for improvement in analytical method - Sample collection or detection? E F G H enzene (µg/cig) D E F enzene G H nalysis atch D E F G H

9 NNN Product Variation ug-10 Sep-10 Oct-10 Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 pr-11 May-11 ug-10 Sep-10 Oct-10 Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 pr-11 May NNN in lend NNN in Smoke HI NNN ug-10 Sep-10 Oct-10 Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 pr-11 May-11 ug-10 Sep-10 Oct-10 Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 pr-11 May-11 Month Month * NNN data normalised to mean per product from a single manufacturing batch Transfer of blend NNN to smoke NNN - Similar patterns of variation within a product. - Especially where product variation is greater than analytical variation

10 Product Variation: Effect of manufacturing batch omparing ommercial products - multiple manufacturing batches to - Single batch ratio >1 may indicate measureable manufacturing batch variability. Low ratio for 1,3- butadiene due to strong presence of analytical variability. HPH oefficients of Variation (%) ISO Smoking Regime ommercial Products ontrol HI Smoking Regime Ratio* ommercial Products ontrol Ratio* Nicotine O ,3-utadiene Isoprene crylonitrile enzene Toluene minonaphthalene minonaphthalene minobiphenyl NNN NNK mmonium Formaldehyde cetaldehdye crolein rotonaldehdye enzo[a]pyrene * ommercial Products /

11 Product Variation Differences between products variation in blend composition and design - ompare absolute levels of HPH Sources of variation within a product - blend composition (recipe constant but natural tobacco variability) - product design (constant) - manufacturing batch (variation between manufacturing runs) Effect of manufacturing batches within products by comparing variation in - (single manufactured batch) - commercial products (multiple manufacturing batches)

12 Product Variation: Uncertainty verage values for the 3 commercial products Empirically 2 x SD = ~95% of a normal distribution Suggests the range of values which might be reported for a single large volume commercial product over time in one lab This kind of variability has been recognised for TNO regulatory reporting under ISO where a tolerance of ± 15% applies for tar and nicotine +/- 20% for O with repeated sampling ISO Mean 2xSD HI Mean 2xSD 2xV (%) HPH Units 2xV (%) Nicotine mg/cig O mg/cig ,3-utadiene µg/cig Isoprene µg/cig crylonitrile µg/cig enzene µg/cig Toluene µg/cig minonaphthalene ng/cig minonaphthalene ng/cig minobiphenyl ng/cig NNN ng/cig NNK ng/cig mmonium µg/cig Formaldehyde µg/cig cetaldehdye µg/cig crolein µg/cig rotonaldehdye µg/cig enzo[a]pyrene ng/cig

13 onclusions We have investigated variability in HPH emissions of three high volume commercial cigarette products. Generally variability was low at <15% V (often < 10% V) nalytical variability - Several HPH showed relatively high levels of analytical variability, which may indicate a potential for analytical improvement - Formaldehyde and crotonaldehyde at ISO - 1,3-utadiene and formaldehyde at HI - TSN was the most variable analysis Product variability - Described the variability in products and the effect of different manufacturing batches. Together these demonstrate that measurement of HPHs from commercial cigarette products is associated with significant levels of variation. - This would naturally increase if measurement was conducted in more than one laboratory.