The recent outbreak of vape-related deaths and diseases in the United States could be due to pyrolysis, or thermal decomposition, of a vitamin E additive found in some unregulated vaping blends, according to researchers in Ireland. The team found that the process can create an extremely reactive organic compound whose effects resemble those of a WWI chemical weapon.
Pyrolysis of phenyl acetate produces a highly toxic gas, so it occurred to me that vitamin E acetate would likely have had similar chemical reactivity
Donal O’Shea, Royal College of Surgeons in Ireland
Since September 2019, the Centers for Disease Control and Prevention (CDC) have recorded 57 deaths and over 2600 cases of lung injury related to vaping in the United States in connection with unregulated vaping mixtures that contain tetrahydrocannabinol (THC) and cannabidiol oils ( CBD). Recent research has found that vaping health impacts were reported up to seven years ago. Early preliminary reports on the resolution of the mysterious deaths and vape diseases suggest that an accumulation of lipids or oils in the lungs may be responsible.
Vitamin E acetate, which has a honey-like consistency, soon became suspect as a chemical culprit because it was known to be used as a thickening or diluting agent in many THC and CBD formulations. It is considered non-toxic and used in vitamin supplements and skin creams, but inhalation could cause health problems.
As the mystery unfolded, however, an additional study conducted in October by Brandon Larsen at the Mayo Clinic in Scottsville, Arizona, analyzed 17 lung biopsies from patients with vaping-related injuries. His team found no evidence to support the idea that oil buildup in the lungs was the underlying cause. But the team saw signs of chemical burns similar to those found after exposure to toxic chemical fumes.2
Intrigued by the reports, chemists Dan Wu and Donal O’Shea of the Royal College of Surgeons in Ireland demonstrated how vitamin E acetate could actually be responsible for vaping-related deaths and injuries in a pre-press currently under peer review. When the molecule undergoes pyrolysis in a vaping device it creates a toxic gas that would explain death, lung injury and chemical burns.
“I was aware that pyrolysis of phenyl acetate produces a highly toxic gas, so it occurred to me that vitamin E acetate would likely have had similar chemical reactivity,” explains O ‘Shea. ‘I ordered some Vitamin E acetate and the first mass spectra we performed indicated that we were on the right track. ‘
Using mass spectrometry, computational calculations and entrapment experiments with a vaping device – although in conditions that do not exactly replicate the user experience – the team found that vitamin E acetate was transformed during pyrolysis for produce ketene. Primate toxicity studies have shown that inhalation of ketene has a similar mode of action and is as harmful as inhalation of industrial chemical phosgene, known for its use as a chemical weapon in the First World War. Tests also revealed the presence of carcinogenic alkenes and benzene found in normal tobacco smoke.
Ketene is a colorless and toxic gas with a sharp and penetrating odor, and at high levels it is particularly ugly. Seriously irritates eyes and skin and if inhaled it can cause serious lung damage, which can be delayed up to 24 hours after exposure. Animal studies with primates have shown that the minimum lethal concentration in the air is 200 ppm, resulting in death after a single exposure of 10 minutes.
“These findings are intriguing and offer a tempting glimpse of the problem,” comments Larsen, senior author of the previous lung biopsy study at the Mayo Clinic. ‘Our study suggested a direct lung injury similar to a chemical burn. This new work offers a potential explanation that fills this gap. It is certainly possible that toxic by-products from the pyrolysis of vitamin E acetate, such as ketene, could cause this injury, at least in some cases. “
Last month, the CDC confirmed the presence of vitamin E acetate in biological samples obtained from patients with vape-related lung lesions. Although its mere presence does not confirm a causal link with lung injury, it adds further evidence to the role of vitamin E acetate in vaping-related disease. Further research conducted by another team concluded that in 51 cases of probable or confirmed lesions in vapers, vitamin E acetate was found in lung fluid samples in 94% of patients.3
However, O ‘Shea warns that the implications of his latest work are wider than just vitamin E acetate. “The temperatures obtainable inside the vaping devices place them in the category of a small-scale laboratory pyrolysis apparatus which, if not used with precision and care, could have unexpected results,” he says. “The pyrolysis products obtainable from other components of the vaporizer mixtures, including flavors and additives, also require investigation as they too can produce toxic and carcinogenic substances.”