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New research into nicotine absorption through the skin

30, Nov, 2015

By Tom Pruen

New research published in the journal Regulatory Toxicology and Pharmacology[i] looked at the absorption through skin of nicotine, contained within e-liquid.

This is good news, in that this is the first study using actual e-liquid, with previous studies using different solvents. There has always been good reason to think this would matter, and this research confirms that.

The research appears to have been well conducted, and provides some useful information, but in many ways raises more questions than it answers.

 

What was done:

The testing was conducted using Franz diffusion cells, holding a sample of human skin (these were tested to validate their integrity). Franz cells are the standard method for research of this type, and more information can be found on these here (note that this is a commercial site, as the usual ‘neutral’ sources such as Wikipedia don’t seem to describe the Franz cell, oddly). The bottom of the cell contains a ‘receptor’ well, which was filled with a fluid chemically similar to human blood, and the cell was heated to 32°C to mimic human skin temperature, and continuously stirred. Samples were extracted after 1, 2, 3, 4, 8, 16 and 24 hours. The top contains a ‘donor’ well, which was filled with 8 mg/g strength e-liquid. Blank cells were also used to confirm measurements.

What was found:

It took 2 hours for any nicotine to transfer through the skin, and at an average rate of 4.82 (±1.05) µg/cm2/h (micrograms per cubic centimetre of exposed skin, per hour), or in the milligrams we are more accustomed to, 0.00482mg/cm2/h. The area of half of the human palm is considered to be between 90 and 100 cm2 so contamination of this area would give (assuming 100cm2 area) 0.482mg/hour.

What this tells us:

Since a lethal dose to an adult is in the region of 500mg[ii] it is very unlikely that accidental exposure to 8mg/ml e-liquid could result in serious toxicity.

However, given the lower body weight and potential for higher sensitivity, it does confirm that e-liquid should be kept out of the reach of children, even though the risk does not appear extreme.

What this doesn’t tell us:

Since the study only used a single concentration of nicotine (probably due to time and budget constraints), it doesn’t show how the rate of absorption changes with increasing concentration. Previous research[iii] has shown that absorption of nicotine through the skin does not increase linearly with concentration, and high nicotine levels (over 50%) actually lowering absorption, although in the range of interest for e-liquid we would expect the rate to increase with concentration.  It would therefore be really useful to see this repeated with different nicotine levels. However, unless the rate change is very marked, it is still unlikely to pose much risk to adults.

Since all the cells were exposed for 24 hours, it doesn’t show the effect of spilling nicotine solutions on skin, and then wiping or washing it off, which would be much more relevant to real world exposures.

Other issues, comments and concerns

The study reported the average rate and lag time of absorption. However, lag time is usually considered to be the time taken for absorption to reach a steady state – and the authors noted that “The absorption of nicotine gradually increased starting from the fourth hour, and did not reach the steady state at the end of the experiment (24 hours).”

This also indicates that if, as is likely in the real world, the spill of nicotine onto the skin is removed, the rate of absorption/transfer to blood will be slower than the average rate found in this study. However since, as indicated in the previous study already referenced, the skin acts as a buffer for nicotine, more may be absorbed into the skin, and then released more slowly into the body.

The level of nicotine was reported as 8mg/g, rather than the more usual 8mg/ml, and it is not clear if the slight difference between these two values (e-liquid has a slightly higher density than water, so an 8mg/ml solution would actually be slightly lower in mg/g) was considered. More alarmingly, this level was inaccurately reported as 8%, whereas it is actually 0.8%. Fortunately, all the calculations were conducted in w/w units so this mistake doesn’t appear to have affected the results, but it is surprising that this was not picked up during peer review.

 

 

[i] http://www.sciencedirect.com/science/article/pii/S027323001530129X

[ii] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880486/

[iii] http://annhyg.oxfordjournals.org/content/43/6/405.full.pdf+html

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