DEVELOPMENT OF A TECHNIQUE FOR THE DETERMINATION OF ph-values OF AEROSOLS GENERATED BY E-CIGARETTES

Transcription

1 DEVELOPMENT OF A TECHNIQUE FOR THE DETERMINATION OF ph-values OF AEROSOLS GENERATED BY E-CIGARETTES John H. Lauterbach, Ph.D., DABT Lauterbach & Associates, LLC Macon, GA USA

2 Outline for presentation Introduction Classical definition of ph and e-liquids Are e-liquid ph-values and e-cigarette aerosol ph-values important? Chemical importance? Toxicological importance? Differences between mainstream cigarette smoke (MSS) and e-cigarette aerosols Approaches to the determination of e-cigarette aerosol ph-values Results Conclusions 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 2

3 Introduction The nonissue of the ph-values of mainstream cigarette smoke (MSS) is a matter of history Thus, it was surprising to see some wishing to make ph values an issue for e-liquids Some examples Stepanov & Fujioka, Tob Control, Epub 2014 May 14 Used CDC method for smokeless tobacco Claimed ph menthol e-liquids > nonmenthol e-liquids Results could not be duplicated, menthol problematic (Lauterbach & Lauterbach, CORESTA 2014, ST48) Lisko et al., Nicotine Tob Res, Epub 2015 Jan 30 Using CDC method, claimed ph α nicotine concentration Henderson-Hasselbalch equation okay to use for percent unprotonated nicotine in e-liquids FDA E-cig draft guidance recommends reporting ph of e-liquids and resulting aerosol (Lines ) 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 3

4 Classical definition of ph and e-liquids Definition of ph is for dilute aqueous solution Many industrial uses of ph bend this definition Processed foods, fruits, vegetables, tobacco slurries Flat-surface electrodes used for atypical applications such as ph of bread dough, denim fabric Even with dilute aqueous solutions such as rain water and condensed fog there can be problems Contributions from other ambient anions and cations Direct ph determinations may not be enough (Johnson & Sigg, CHIMIA 1985,39:59-61) Thus, even with dilution of e-liquids with water, the ph-values obtained on such partially nonaqueous systems are not directly comparable to those obtained for dilute aqueous solutions and may be skewed high 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 4

5 Chemical/toxicological importance of ph Chemical importance of ph Use of ph to control product stability Flavorful aldehydes can form acetals with PG and VG at less than neutral ph Acetal formation would decrease flavor amplitude Potential reactions between e-liquids and materials in contact with e-liquids and/or aerosols at other than neutral ph Toxicological importance of ph Potential adverse health effects from mechanical transfer of e-liquid to user Spills during filling of devices Bubbling of e-liquids from cartomizers Potential adverse health effects from inhaled aerosols with high ph (Stepanov & Fujioka, 2014) 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 5

6 Differences MSS and e-cigarette aerosols Parameter Cigarette smoke E-cig aerosol Source Particle mean size nm [CMD] nm [CMD] Wright, 2016 Aerosol particle number /cm ,000, ,000,000 TPM/ACM mg/puff 3R4F CINT Tar Water Nicotine 4.6 (3R4F, CINT) 3 5 (cigalikes, 25 puffs, CRM 81) Do these differences have any effect on observed ph of aerosols? Ingebrethsen et al., 2012 Wright, 2016 Bodnar et al., 2012 This work Example E-Cig CRM 81 PG Glycern Water Nicotine Do we need to be concerned with lack of carbon dioxide in e-cigarette aerosols? 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 6

7 Carbon dioxide appeared to matter in 2013 Health Canada Method T-113, Paper 78, 67 th TSRC, TSRC 76 LAUTERBACH & ASSOCIATES, LLC 7

8 Current approaches to technique Constant-vacuum, square-wave puffing system Robinair VacuMaster, 2-stage, 8-CFM pump Harbor Freight 11-gallon air tank as surge tank Puff on-off control Arduino UNO R3 µ-processor with Lenovo Thinkcentre PC SainSmart 8-channel relay module Sizto Tech 2P025-1/8-1G Direct-acting solenoid valve Puff-volume measurement and control Sigma-Aldrich ml bubble meter Cerulean SC#59138 Restrictor 10CSM (calibrated)(1 kpa) Swagelok SS-4MG-SL 10-turn metering valve Smoke traps HC T-113 by Prism Research Glass Normal flow (bottom aerosol inlet for Hanna electrodes) Reverse flow (side aerosol inlet for Hach ISFET electrode) Instrumentation for ph-determinations Hach H260G meter with Hanna H1413B (flat bottom), H1053B (conical), and Hach PHW77-SS (ISFET) probes 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 8

9 Samples used to evaluate technique All commercial samples purchased from manufacturers Internet web stores V2 ( 0, 0.6, 1.2, 1.8, and 2.4% nicotine Green and Red Blank cartomizers, battery sections, chargers GreenSmoke ( Mountain Clove and Menthol Ice, 2.4% nicotine Battery sections and chargers MarkTen XL ( Classic, 2.4% nicotine Fusion, 2.5% nicotine Menthol and Winter Mint, 3.5% nicotine Battery sections and chargers Research samples (500 mg, V2 blank cartomizer) Nicotine at 1, 3, 5% in PG=VG, 9 water Example: 44 VG, 44 PG, 9 water, 3 nicotine Nicotine solutions in PG or VG came from NicVape 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 9

10 Experimental setup Smoke trap with good aerosol density Poor aerosol from cartomizer defect Reverse smoke trap with ISFET electrode 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 10

11 Technical issues associated with technique Observed ph-values appear to be related to both aerosol density and nicotine concentration Factors affecting these parameters may include Weight of e-liquid in cartomizer Nicotine concentration of e-liquid in cartomizer Flow of e-liquid to wick before and during puffing Electrical resistance of cartomizer coil Pressure drops of cartomizer, battery section and combination of cartomizer and battery section Weight-, pressure-drop-selection may be needed Observed ph at 25 th puff taken as aerosol ph-value Further puffing increases variability Starting ph appears to be important in some cases Setting starting ph Good choice is film of 1:5 ph 6 buffer/water on electrode A drop (known volume)of 1:1 VG/pH 6 buffer on sensing element may best choice for ISFET electrode 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 11

12 Typical results for new cartomizer on each run 8.00 GreenSmoke Menthol Ice 2.4 and GreenSmoke Mountain Clove 2.4 HI 1053B Electrode ph th puff Time (seconds) GS CLOVE GS CLOVE GS MENTH GS MENTH TSRC 76 LAUTERBACH & ASSOCIATES, LLC 12

13 8.0 Sometimes something bad happens V2 Menthol 1.8 and V2 Red Tobacco 1.8 HI 1053B Electrode ph th puff 6.0 Defective cartomizer? Time (seconds) V2 RED 1 V2 RED 2 V2 MENTHOL 1 V2 MENTHOL 2 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 13

14 8.5 Some replicate samples hand crafted 1%, 3% and 5% nicotine in V2 Blank Cartomizers (500 mg loading) HI 1413B Electrode 8.0 Defective cartomizer? th puff 25 th puff ph 6.5 Defective cartomizer? Time (seconds) F1R1 F1R2 F1R3 F2R1 F2R2 F3R1 F3R2 F3R3 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 14

15 8.5 No- and low-nicotine cartomizers V2 Red Tobacco 0.0%, 0.6% and 1.2% Nicotine HI 1413B Electrode ph th puff Time (seconds) 0.0% run 1 0.0% run 2 0.0% run 3 0.6% run 1 0.6% run 2 0.6% run 3 1.2% run 1 1.2% run 2 1.2% run 3 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 15

16 8.5 A different brand of cartomizers MarkTen Menthol 3.5 and MarkTen Fusion 2.5 HI 1413B Electrode ph th puff Repeat runs of same cartomizer of each flavor Maximum weight loss difference was 5 mg between amount consumed in each run (about 125 mg) Time (seconds) Menthol 1 Menthol 2 Menthol 3 Fusion 1 Fusion 2 Fusion 3 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 16

17 Getting close, but no cigar for ISFET electrode 8.5 V2 Menthol 0.0% and 2.4% Nicotine Hach ISFET Electrode ph th puff 25 th puff Time (seconds) menthol 0.0% 1 menthol 0.0% 2 menthol 0.0% 3 Menthol 2.4% 1 Menthol 2.4% 2 menthol 2.4% 3 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 17

18 Conclusions Puff-by-puff ph-values on e-cigarette aerosols appear to be driven by more than nicotine alone Cartomizer and battery-section design features that affect pressure drop across the e-cigarette device Wicking and heater performance under puffing conditions specified by CRM 81 Physical and chemical properties of the e-liquid including ph-modifiers Techniques and instrumentation just described provide a very cost-effective analytical system Additional work is planned to understand the factors that contribute to variability in results This is an empirical approach and results may not have relevance to human nicotine uptake from e-cigarette use with a given e-liquid 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 18

19 Acknowledgement Much of the laboratory work just presented including all of the instrument interfacing, µ-processor programming, and data reduction was done by Sebastian J. Lauterbach, a contractor to Lauterbach & Associates, LLC. 70 TSRC 76 LAUTERBACH & ASSOCIATES, LLC 19