Potential for release of pulmonary toxic ketene from vaping pyrolysis of vitamin E acetate

Abstract

A combined analytical, theoretical, and experimental study has shown that the vaping of vitamin E acetate has the potential to produce exceptionally toxic ketene gas, which may be a contributing factor to the upsurge in pulmonary injuries associated with using e-cigarette/vaping products. Additionally, the pyrolysis of vitamin E acetate also produces carcinogen alkenes and benzene for which the negative long-term medical effects are well recognized. As temperatures reached in vaping devices can be equivalent to a laboratory pyrolysis apparatus, the potential for unexpected chemistries to take place on individual components within a vape mixture is high. Educational programs to inform of the danger are now required, as public perception has grown that vaping is not harmful.

Keywords: ketene; lung injury; pyrolysis; vaping; vitamin E acetate.

Fig. 1.

Chemical structures of vitamin E acetate 1, vitamin E 2, phenyl acetate 3, and ketene 4.

Fig. 2.

Positive-mode APCI-MS of (A) phenyl acetate 3 with source voltage of 15 eV showing loss of ketene; (B) vitamin E acetate 1 with source voltage of 20 eV showing loss of ketene from both the parent ion and a fragmentation species of m/z 207.2; (C) vitamin E 2 with source voltage of 20 eV with sole fragmentation to [Ar³OH₂]⁺.

Fig. 3.

APCI-MS fragmentation patterns of A phenyl acetate 3 and B vitamin E acetate 1 each of which are observed as +H⁺ masses in the mass spectra.

Fig. 4.

Calculated energy profiles for the pyrolysis of the three aryl acetate substrates 1, 3, and 6 via concerted [1,3] hydrogen shift mechanism. Relative free energies (kcal mol⁻¹) for starting materials, TS, and products formed for the pyrolysis of phenyl acetate, vitamin E acetate, and 6 leading to the elimination of ketene 4. For details of calculation data see SI Appendix, Figs. S4–S6. Simplified structures used for calculation of 1 and 2 without C₁₅H₃₂ alkyl group.

Fig. 5.

Optimized geometries [M06-2X/6–311G(d,p) level] for the TS corresponding to the pyrolysis of phenyl acetate 3 (Left) and vitamin E acetate 1 (Middle) and 6 (Right), leading to the elimination of ketene. Simplified structures used for calculation of 1 and 2 without C₁₅H₃₂ alkyl group. For details of calculation data see SI Appendix, Figs. S4–S6.

Fig. 6.

(Top) ¹H NMR spectrum of pure 1. (Bottom) ¹H NMR spectrum of entire isolated vaped mixture from 1. For clarity the peak at 7.36 ppm is not shown in cropped view, see SI Appendix, Fig. S9 for full spectra. Inset box (i) indicates VC; box (ii) indicates mixture of VC and NVC; box (iii) primarily NVC.

Fig. 7.

Portion of the ¹H NMR spectrum of vitamin E acetate 1, vitamin E 2, and the isolated NVC of vaped mixture. A red asterisk marks the aryl methyl signal for duroquinone 8 (full spectra in SI Appendix, Fig. S10).

Fig. 8.

Portion of the ¹H NMR spectrum of the isolated VC following vaping vitamin E acetate 1. See SI Appendix, Fig. S14 for full spectrum including benzene peak at 7.36 ppm. Red asterisk, 1-methyl-1-alkyl alkenes; blue asterisk, propene; black asterisk, butadiene.

Fig. 9.

Rationale of experimental and theoretical results from vape pyrolysis reactions of vitamin E acetate 1.

Fig. 10.

Chemical trapping of vaped produced ketene with benzylamine 9 forming benzylamide 10. Portion of the ¹H NMR spectra showing vape mixture from 1 isolated in CDCl₃ containing 9 and an authentic sample of benzylamide 10. Black asterisk, methylene peak of 9; red asterisk, methylene peak of 10. See SI Appendix, Figs. S15 and S16 for full spectra.

Fig. 11.

Apparatus setup for trapping vaped products of vitamin E acetate 1. Setup A: Apparatus for low-temperature trapping of all vaped material. Setup B: Apparatus for low-temperature trapping of all vaped material followed by separation of VC from NVC. Setup C: Apparatus for trapping of vape-produced ketene by benzylamine in CDCl₃.