Evaluation of the formaldehyde hemiacetals and acetals relevant to electronic cigarettes
In 2016, the Food and Drug Administration (FDA) issued draft Guidance to Industry regarding the submission of Premarket Tobacco Applications for Electronic Nicotine Delivery Systems (ENDS). In this draft guidance, the FDA recommends reporting toxicants in aerosols, including formaldehyde. Recent publications suggested that 1) formaldehyde levels in ENDS products were underreported because formaldehyde may react with propylene glycol (PG) and glycerin (Gly) in the aerosol to form hemiacetals; 2) the equilibrium would shift from the hemiacetals to the acetals in the acidic DNPH trapping solution. In both cases, neither the hemiacetal nor the acetal would react to form the target formaldehyde hydrazone due to the lack of the carbonyl functional group; thus, underreporting formaldehyde. These reports were studied in our laboratory. Our results showed that the aerosol generated from formaldehyde spiked e-liquids gave near quantitative recovery of formaldehyde in the aerosol suggesting that if any hemiacetal was formed in the aerosol it would readily hydrolyze to free formaldehyde in the acidic DNPH trapping solution. We demonstrated that a custom synthesized Gly-hemiacetal added to DNPH trapping solution would readily hydrolyze to form the formaldehyde hydrazone. We also demonstrated that acetals of PG and Gly added to DNPH trapping solution would not hydrolyze to form the hydrazone. In order to further investigate the reported presence of acetals in e-liquids and aerosols, we developed a qualitative GC-MS method for the identification of the PG and Gly acetals of formaldehyde. No acetals of PG/Gly were detected in the e-liquids or the aerosols. These results demonstrate that formaldehyde levels in e-cigarette aerosols are not underreported due to hemiacetal and acetal formation.