Structure-activity relationships of propylene glycol, glycerin, and select analogs for carbonyl thermal degradation products
In 2016, the Food and Drug Administration (FDA) issued draft Guidance to Industry regarding the submission of Premarket Tobacco Applications for electronic nicotine delivery systems (ENDS). In this draft guidance, the FDA recommends reporting several carbonyl compounds, including formaldehyde, acetaldehyde, and acrolein, whose presence in electronic cigarette aerosols is typically attributed to thermal degradation of propylene glycol (PG) and/or glycerin (Gly). Studies were conducted using carbon-13 labeled PG and Gly to elucidate the mechanisms and sources of the specific carbonyl compounds. These studies utilized a model reaction system based on microwave heating. Gly was found to be the primary source of formaldehyde while PG was found to be the primary source of acetaldehyde and acrolein. Formaldehyde and acetaldehyde generation from Gly is typically attributed to the retro-aldol condensation of 3-hydroxyproponal. This reaction was studied in further detail utilizing the microwave model system. These results were used to design PG and Gly analogs containing functional group substitutions to block reactive sites on the PG and Gly analogs. Blocking the reactive sites was anticipated to reduce the thermal decomposition of PG and Gly and thus provide information on the critical reaction centers required for the formation of the observed products. The results of these studies will be reported as well as the carbonyl yields from these PG and Gly analogs.