Nicotine lethal dose in humans: a common argument by regulatory authorities, based on poor science

By Dr Farsalinos

I am sure everyone has heard the “magic number”: 60mg is the nicotine lethal dose in adults. Τhis is a very low level, which would categorize nicotine as one of the most toxic substances available. It is a very common and strong argument of the regulatory authorities and of several anti-smokers activists who support very strict regulation on e-cigarettes and criticize the high levels of nicotine present mostly in refillable liquid bottles. Special concerns are usually raised for children, because lethal dose is expected to be much lower at this age group.

I always wondered how the lethal dose level was defined, because everyone mentioned that the lethal dose was just theoretical and was never really tested. In animals the lethal dose may be from 3mg/kg in mice to 50mg/kg in rats, while a 60mg dose means a 0.8mg/kg in humans. A brief search of the literature revealed some reports that cigarette ingestion in children has a benign prognosis CDC 1997, Kubo 2008), making it hard to understand how a 60mg lethal dose is realistic and accurate.

Yesterday however, a very important review was published in Archives of Toxicology. Professor Bernd Mayer from the University of Gratz performed an extensive review of available literature in an effort to identify the existing proof for defining the nicotine lethal dose in humans. He has also found several references mentioning that the acute lethal dose in humans has been estimated to be 50-60mg. However, no proof was provided for such figures. He had to go back to the mid of the 19th century to find that the lethal dose came from self experiments of Austrian pharmacologists, who described really peculiar and unrealistic symptoms after ingesting just 1-4mg of nicotine. Therefore, reports based on dubious experiments and results 150 years ago are still reproduced today…

More interestingly, Prof Mayer reports that the lethal level of nicotine as measured in postmortem exams was 2mg/ml of blood, corresponding to 4mg/ml of plasma. Such levels would correspond to ingesting 500-1000mg of nicotine. This is 10-20 times higher levels that those “accepted” today.

There is no doubt that nicotine is toxic and can be lethal. However, the levels currently mentioned in the literature seem to be extremely low and unrealistic. Nicotine solutions should always be handled with care, but there is no reason to produce excessive fear or accept poor science in order to terrorize the public.

It is worth reading the full review by Prof Mayer. It is available online with free access to everyone.

 

 

Dr Farsalinos is a researcher at Onassis Cardiac Surgery Center in Athens-Greece and at Medical Imaging Research Center, University Hospital Gathuisberg in Leuven-Belgium. He is actively involved in research on e-cigarettes’ safety and risk profile.

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