2017_ST10_JinCathy.pdf. SSPT Document not peer-reviewed by CORESTA

Size: px

Start display at page:

Download "2017_ST10_JinCathy.pdf. SSPT Document not peer-reviewed by CORESTA"

Marybeth Hart
5 years ago
Views:

Investigation of TSNA Formation in Electronic Cigarette Liquids and Aerosols Xiaohong Cathy Jin, Karen C. Avery, Georgios D. Karles, William P. Gardner, Matt S.

1 Investigation of TSNA Formation in Electronic Cigarette Liquids and Aerosols Xiaohong Cathy Jin, Karen C. Avery, Georgios D. Karles, William P. Gardner, Matt S. Melvin, Donna C. Smith, Willie J. Mckinney, and Karl A. Wagner Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 1

2 Introduction Preliminary data indicated that TSNA formation was possibly occurring during the generation of aerosols 1 TSNAs in tobacco are formed through the reaction of nitrite with nicotine and minor alkaloids 2 E-liquids typically contain tobacco derived nicotine and may also contain other tobacco constituents 3,4 No studies on TSNA formation in e-liquids and aerosol in literature Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 2

3 Objective Investigate the formation of TSNAs in e-liquids and aerosols Role of nitrite and minor alkaloids temperature, time, and concentration effects Evaluate TSNA levels in e-liquids and aerosols of commercial cigalike e-cigarette products Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 3

4 TSNA Formation Pathway Hoffmann et al. (1994) Nicotine Nornicotine Anabasine Anatabine Nitrosation NO 2 NO 2 NO 2 NO 2 NO 2 NNK NNN NAB NAT Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 4

5 Investigation of the TSNA Formation in E- liquids and aerosols Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 5

6 Role of Nitrite in TSNA Formation: E-liquids Lab fortified e-liquid (82.5% PG/Gly (50:50),15% water, 2.5% nicotine) was fortified with nitrite (2 µg/g - 50 µg/g) Temperature Storage time (ambient) TSNAs were analyzed by UPLC/MS/MS 1 Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 6

7 TSNA (ng/g e-liquids) TSNA in e-liquids at Different Temperatures E-liquid (82.5% PG/Gly (50:50), 15% water, 2.5% nicotine) fortified with 2 µg/g nitrite, heated for 5 min Rm Temp 80 C C 200 C 250 C NNK NAB NAT NNN Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 7

8 NNK (ng/g) NNN (ng/g) TSNA in E-liquids Over Time E-liquid (82.5% PG/Gly (50:50), 15% water, 2.5% nicotine) fortified with 3 levels of nitrite, stored at room temp, n=3 2µg/g NO2 10µg/g NO2 50µg/g NO2 NNK S=0.58 S=0.16 S= Days after nitrite fortified µg/g NO2 10µg/g NO2 50µg/g NO2 NNN S=0.04 S= Days after nitrite fortified Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 8

9 Role of Nitrite in TSNA Formation: Aerosols Aerosol generation Cartridges filled with the same fortified e-liquids Aerosol generation regimen: 55mL puff volume, 5s duration, 30s intervals Comparison of TSNAs in e-liquids and aerosols Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 9

10 TSNA (ng/g e-liquid or aerosol) TSNAs in E-liquids and Aerosols E-liquid (82.5% PG/Gly (50:50), 15% water, 2.5% nicotine) fortified with 2 levels of nitrite (n=3); cartridges filled with the fortified e-liquids, 50 puffs aerosols collected (n=4) µg/g NO2 2 µg/g NO2 10 µg/g NO2 liquid aerosol liquid aerosol liquid aerosol liquid aerosol NNK NAB NAT NNN Elevated TSNA levels in aerosol compared to e-liquid when nitrite is present. Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 10

Contributions of Minor Alkaloids When Nitrite is Present Minor Alkaloids: nornicotine, anabasine, anatabine E-liquid (85% PG/Gly (50/50) +15% water, without nicotine) fortified with 2 µg/g

11 Contributions of Minor Alkaloids When Nitrite is Present Minor Alkaloids: nornicotine, anabasine, anatabine E-liquid (85% PG/Gly (50/50) +15% water, without nicotine) fortified with 2 µg/g nitrite and 10 µg/g minor alkaloids Evaluate effects of temperature and storage time NO 2 NO 2 NO 2 Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 11

12 TSNA in E-liquids at Elevated Temperature When Minor Alkaloids and Nitrite are Present E-liquids fortified with 2 µg/g nitrite and 10 µg/g minor alkaloids, heated at 200 o C for 5 minutes (n=3) Minor alkaloids fortified NNK (ng/g) NAB (ng/g) NAT (ng/g) NNN (ng/g) Nornicotine <0.2 ND ND 49.2 Anabasine ND 7.1 ND ND Anatabine ND ND 8.4 ND *ND: not detected Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 12

13 TSNA (ng/g) TSNA in E-liquids Over Time When Minor Alkaloids and Nitrite are Present E-liquids (85% PG/Gly (50/50) +15% water) fortified with 2 µg/g nitrite and 10 µg/g minor alkaloids, stored at room temperature (n=3) initial 2 weeks 4 weeks 8 weeks NNN NAB NAT Nornicotine fortified Anabasine fortified Anatabine fortified Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 13

14 TSNA (ng/g) TSNAs in Liquids and Aerosol When Minor Alkaloids and Nitrite are Present E-liquids (85% PG/Gly (50/50) +15% water) fortified with 2 µg/g nitrite and 10 µg/g minor alkaloids (n=3); Aerosols were collected 150 puffs (n=4) Liquid Aerosol NNN NAB NAT Nornicotine fortified Anabasine fortified Anatabine fortified Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 14

15 Evaluation of TSNA in Commercial Cigalike e-cigarette Products Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 15

16 Evaluation of TSNA in Commercial e-cigarette Products 8 commercial cigalike e-cigarette products were evaluated TSNA in e-liquids and aerosols Nitrite and minor alkaloids in e-liquids Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 16

17 TSNA (ng/g) TSNAs in e-liquids of Commercial Products E-liquids were removed from e-cig cartridges and analyzed on the same day NNK NAB NAT NNN A B C D E F G H Products Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 17

18 TSNA (ng/g) TSNAs in Aerosols of Commercial Products 150 puffs collected or until battery exhaustion (n=4) NNK NAB NAT NNN A B C D E F G H Products TSNAs in aerosol per puff ranged from ND to 0.16 ng/puff Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 18

19 Nitrite and Minor Alkaloids in E-liquids of Commercial Products Products Nitrite (µg/g) Nornicotine (µg/g) Anabasine (µg/g) Anatabine (µg/g) A < ND ND B < ND 2.6 C <0.5 <2.5 ND ND D < ND ND E < F <0.5 <2.5 ND ND G 0.8 <2.5 ND ND H Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 19

20 TSNA (ng/g) Product B: TSNAs in e-liquids and Aerosols Liquid Aerosol NNK NAB NAT NNN No significant differences between TSNA levels in aerosols and liquids most likely due to no quantifiable levels of nitrite (< 0.5 µg/g) Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 20

21 TSNA (ng/g) Product H: TSNAs in e-liquids and Aerosols Liquid Aerosol NNK NAB NAT NNN TSNA TSNA levels elevated in aerosol compared to liquid most likely due to high levels of nitrite and minor alkaloids. Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 21

22 Conclusions Low levels of TSNAs were observed in e-cigarette liquids and aerosols. Nitrite in e-liquids could react with nicotine or minor alkaloids to form TSNAs: TSNA increased with time under normal storage when nitrite is present. TSNA formation is accelerated by elevated temperature when nitrite is present TSNA could form during aerosol generation when nitrite is present. This study provides useful information that may be used to develop and evaluate electronic cigarette products. Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 22

23 References 1. Jin, X. C, et al, Determination of TSNAs in e-cigarette Liquids and Aerosols by UPLC-MS/MS, Hoffmann D. et al., Tobacco-Specific N-Nitrosamines and ARECA-Derived N-Nitrosamines: Chemistry, Biochemistry, Carcinogenicity, and Relevance to Humans; J. of Toxi. And Envir. Health, 1994, 41, Farsalinos, K.E; et al, Int. J Envir. Res. Public Health, 2015 Apr, 12 (4): CORESTA e-cigarette Task Force Reference Report, Electronic Cigarettes: Assessment of Analytical Literature, May 2014 Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 23

24 Acknowledgement Yezdi Pithawalla Tammy Blake Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 24

25 Acknowledgement Yezdi Pithawalla Tammy Blake Altria Client Services Regulatory Sciences Xiaohong Cathy Jin October 9, Coresta -ST10 25

Thermal Degradation Studies of Electronic Cigarette Liquids Part 2: Development of a Model Reaction System Used to Study α-dicarbonyl Formation

Thermal Degradation Studies of Electronic Cigarette Liquids Part 2: Development of a Model Reaction System Used to Study α-dicarbonyl Formation Melvin, M.S.; Avery, K.C.; Ballentine, R.M.; Gardner, W.P.;