Unregulated chemicals found in black market vapes

Experts are calling for an investigation into the toxicity of nicotine alternative 6-methylnicotine and the health consequences of inhaling it.

Vaping has been on the increase in Australia, prompting a nationwide ban on the sale and import of vapes in July 2024.

From October 2024, people aged 18 and over will be able to buy a vape over the counter in pharmacies without a script.

But even though the product has been banned, it’s still available on the black market. And worse, the chemicals contained in these vapes escape regulation by the Therapeutic Goods Administration (TGA).

New research in the Medical Journal of Australia has discovered a new nicotine alternative in some vapes labelled as ‘nicotine free’, which is more toxic than nicotine.  

The authors of the study, Caitlin Jenkins, Celine Kelso and Jody Morgan investigated new e-cigarette products in Australia whose manufacturers claim contain a nicotine alternative and could pass a nicotine detection test.

Before the laws banning all vapes for sale, it would have meant that these imports could have passed legally into Australia, as nicotine-free vapes were allowed until July 2024.

For the study, the authors bought e-cigarettes from three manufacturers in 2023: five ready to use and four that required dilution before use. They were analysed using gas chromatography-mass spectrometry methods. The nicotine alternative was purified and fully characterised by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.

All nine products contained an ingredient that wouldn’t be identified by standard testing as nicotine. It was identified as 6-methylnicotine.

The authors raised particular concerns about the difference in toxicity between 6-methylnicotine and nicotine in the products they assessed.

This chemical’s psychotropic potency is three times higher than nicotine and in vitro affinity of 6‐methylnicotine for nicotinic cholinergic receptors is higher than that of nicotine. Due to the cytotoxicity exceeding nicotine at similar levels, a lower dose has been recommended.

“The differences in labelling and actual concentrations in these products could confuse users, increasing the risk of accidental exposure to high concentrations of a compound with unknown health effects,” the authors said.

Benzoic acid was found in seven out of nine samples. This chemical is included to reduce throat irritation caused by high levels of nicotine concentrations.

The authors acknowledge that they analysed a small sample in the study and say that chemical compounds other than 6-methylnicotine may also be substituted for nicotine.

They conclude that all nine “nicotine alternative” vapes contained 6-methylnicotine.

“The concentration range determined and the limited information on the toxicity and potential health effects of 6-methylnicotine are both concerning,” they said.

The authors are calling for an investigation into the toxicity of the compound and the health consequences of inhaling it, especially as a long term alternative to nicotine in e-cigarettes.

The authors also warn that new novel e-cigarettes could be developed to circumvent the new regulations.

Hidden in plain sight

The MJA’s editorial states that the identification of 6-methylnicotine is worrying for several reasons. The chemical has been around for more than 50 years and not a lot is known about its pharmacokinetics or potential toxicity.

“Jenkins and colleagues refer to studies that indicate that 6-methylnicotine could be more potent and elicit greater cytotoxic effects in an immortalised cell line than nicotine.”

One study, sponsored by an e-liquid manufacturer, also found that exposure led to “more differential gene expression than to nicotine.”

“These findings are concerning, as immortalised cells are typically more robustmore robust than primary cells in their response to inhaled insults.”

In the US, 6-methylnicotine is trademarked and manufactured as “Metatine”. The company says on its website, that it is outside the regulatory scope of the Food and Drug Administration’s Center for Tobacco Products.

The new regulations introduced in Australia can “place some limits on what chemicals a therapeutic vaping substance can include,” the editorial said.

“The findings by Jenkins and colleagues have implications for TGA procedures when testing for nicotine and related substances in vaping products,” the editorial said.

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