Quantitative Risk Assessment of Tobacco-Burning and Tobacco-Heating Cigarettes

Transcription

1 Quantitative Risk Assessment of Tobacco-Burning and Tobacco-Heating Cigarettes Kristin M. Marano, MS, MPH, CPH Ziad S. Naufal, PhD Michael F. Borgerding, PhD Ryan J. Potts, PhD 66 th TSRC Symposium September 10,

2 Objective Define risk assessment Example of how QRA has been applied for risk assessment of tobacco products 2

3 Risk Assessment Scientific evidence-based process Characterizes (quantifies) the nature and magnitude of a defined risk Important component of regulatory and related type of decision making Complements and makes use of biological data 3

4 Risk Assessment Risk depends on How much of a chemical is present How much contact (exposure) a person has The inherent toxicity of the chemical 4

5 Risk Assessment Four step process Hazard identification What adverse health effect is associated with the chemical of concern Exposure assessment What is the magnitude and route of exposure 5

6 Risk Assessment Dose-response assessment How much of the chemical does it take to cause the adverse biological response Risk characterization What is the risk (probability) of toxicity occurring in the exposed population Exposure X Toxicity = Risk 6

7 Tobacco: Risk Assessment Previous Publications Cigarette mainstream smoke/ prioritization of constituents Burns et al. 2008; Fowles and Dybing 2003; Cunningham et al. 2011; Xie et al Evaluation of combustible PREPs Pankow et al Smokeless tobacco constituents Ayo-Yusuf and Connolly

8 Tobacco: Risk Assessment Current Analyses Tobacco-burning versus tobacco-heating (Eclipse) cigarettes Calculated incremental lifetime cancer risk (ILCR) 8

9 Incremental Lifetime Cancer Risk (ILCR) Probability of an individual developing cancer over a lifetime of exposure ILCR = Lifetime Average Daily Intake X Cancer Potency Factor Calculated for each constituent with available chemistry data potency value Sum of individual constituent ILCRs to achieve overall ILCR 9

10 Cancer Potency Factors Upper bound estimate of the probability of a cancer response per unit of intake (of chemical over a lifetime) Inhalation unit risk (IUR), (µg/m 3 ) -1 Cancer slope factor (CSF), (mg/kg-d) -1 Derived from dose-response data Experimental animal studies Occupational/environmental human studies Publicly available (this analysis) 10

11 Lifetime Average Daily Intake (LADI) LADI (µg/m 3 ) = C x CpD x ED x EF BW x DIR x AT x CF where C = Constituent yield, µg/cigarette CpD = Cigarettes per day ED = Exposure duration, years EF = Exposure frequency, days/year BW = Body weight, kg DIR = Daily inhalation rate, L/kg-day AT = Averaging time, days (365 days/year x 70 years) CF = Conversion factor, 1E-3 m 3 /L 11

12 Lifetime Average Daily Intake (LADI) Probabilistic Methods Probability density functions for parameters Incorporates data range Accounts for uncertainty and variability Model Risk v (Boulder, Colorado) 12

13 LADI Input Parameters Parameter Description Units Source C Constituent yield µg/cigarette Machine-smoking, various regimens CpD Cigarettes per day cigarette/day NHANES EF Exposure frequency days/year NHANES ED Exposure duration years NHANES BW Body weight kg NHANES DIR Daily inhalation rate L/kg-d California EPA 13

14 Constituent Yield Distributions Approach I: Machine-Generated MSS 55/30/2, 100% vent blocking 11 constituents Eclipse versus 87 US cigarette brands 60/30/2, 0% vent blocking 24 constituents Eclipse versus 3 cigarette types 14

15 Results: Approach I 55/30/2, 100% vent blocking 11 Constituents, 87 US Cigarette Brands Product Mean ILCR Eclipse Percent Reduction Eclipse 2.10E mg tar 5.03E-03 58% 7-14 mg tar 4.62E-03 55% 1-6 mg tar 4.37E-03 52% Tar determined by the Cambridge Filter Method. Mean, compared with Eclipse. --, reference. 15

16 Results: Approach I 60/30/2, 0% vent blocking 24 Constituents, 3 Cigarette Types Product Mean ILCR Eclipse Percent Reduction Eclipse 2.72E UL 5.90E-03 54% K1R5F 4.66E-03 42% K2R4F 8.79E-03 69% Mean, compared with Eclipse. UL, Marlboro Ultra lights ; K1R5F and K2R4F, reference cigarettes. --, reference. 16

17 Constituent Yield Distributions Approach II: Biomarker Data Smokers who switched to Eclipse 5 constituents/ biomarkers Baseline exposure Machine-generated MSS constituent yields 12 and 24 week biomarker data Percent change in biomarkers used to adjust baseline values Exposure estimates at 12 and 24 weeks 17

18 Change in Urine Biomarkers after Switching* to Eclipse Constituent Biomarker Week Percent Change 2-Aminonaphthalene 2-Aminonaphthalene Aminobiphenyl 4-Aminobiphenyl ,3-Butadiene MHBMA Benzene SPMA NNK NNAL, total *Participants smoked usual brand tobacco-burning cigarettes at baseline and then switched to Eclipse. MHBMA, monohydroxybutenylmercapturic acid; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol; SPMA, S-phenylmercapturic acid. 18

19 Results: Approach II Switching to Eclipse Product Mean ILCR Percent Reduction Tobacco-burning 8.74E Eclipse (week 12) * 4.60E-04 47% Eclipse (week 24)^ 4.73E-04 46% Weighted based on usual brand of tobacco-burning cigarettes among study participants. Mean, compared with tobacco-burning cigarette (baseline). *Based on reductions in biomarkers of exposure at week 12. ^Based on reductions in biomarkers of exposure at week , reference. 19

20 Summary Eclipse cigarette smoking was observed to have ~50% reduction in calculated cancer risk relative to traditional tobaccoburning cigarettes using QRA methods 20

21 Limitations Complex Mixture Additive assumption Limited Dose-Response Data <25 constituents 21

22 Strengths Probabilistic Methods Constituent yields Duration, frequency Biomarker Data Best exposure estimate Actual smoking Puff volume, puffs per cigarette 22

23 Conclusion Notwithstanding the limitations, and in combination with other relevant data, QRA is an excellent tool for risk assessment of tobacco products 23

24 Acknowledgements Drs. Michael Borgerding, Ziad Naufal, Ryan Potts Drs. Steven Alderman, Paul Ayres, Geoff Curtin, Michael Ogden, Steven Sears 24

25 Quantitative Risk Assessment of Tobacco-Burning and Tobacco-Heating Cigarettes Kristin M. Marano, MS, MPH, CPH Ziad S. Naufal, PhD Michael F. Borgerding, PhD Ryan J. Potts, PhD 66 th TSRC Symposium September 10,