The levels of methanol within the gel, are safe both for the safe reference dose of 0.5 mg and the more recently revised reference dose of 2.0 mg/kg body weight per day[[1]] supplementary to a normal dietary intake. This is even assuming 100% absorption, which is highly unlikely. Additionally, average methanol consumption is estimated at 1,000 mg per day, owing mostly to vegetables and fruit [[2]].

However, the alleged surgical spirit showed it also contained acetaldehyde, which is a byproduct of fermentation, and present in many foods, including fruit, fruit juices, vegetables, bread, and alcoholic beverages. It is also used as a flavour additive in soft drinks and sweets.

Furthermore, ethanol is broken down into acetaldehyde in the liver as an intermediate step of alcohol metabolism. The rate of alcohol metabolism in humans is roughly 170 to 240 g per day, 7-10 g per hour, and 116-167 mg per minute in 70kg individuals though there is wide variation in individual tolerance [[3]]. Given that some individuals can consume 200-300 g of alcohol in a day, this can cause serious metabolic stress, and also production of acetaldehyde [[3]]. The average exposure to acetaldehyde in alcoholic beverages is thought to be 0.112 mg/kg body weight per day [[4]], or 7.84 mg for an individual weighing 70kg (not including acetaldehyde that is an intermediate product of alcohol metabolism).

Acetaldehyde is classified as a Class 2B carcinogen [[5]] meaning that it is “Possibly carcinogenic to humans” [[6]], this is the classification for substances with limited or inadequate evidentiary basis of carcinogenicity in humans; however, when “associated with consumption of alcoholic beverages” acetaldehyde is classified as a Class 1 carcinogen [[5]] meaning that it is “Carcinogenic to humans” [[6]]. The 4 classifications from the IARC is as follows.

Other examples of Class 2B carcinogens include: Aloe Vera extract, Catechol (an molecule that naturally occurs in fruit and turns reddish brown when oxidised, resulting in the bruising of fruit), Phenytoin (an anti-epilepsy medication), Nickel, Pickled vegetables, Progestins, and Carpentry and joinery [[5]].

The Joint FAO/WHO expert committee estimated daily intake of acetaldehyde as a flavour additive at 9.7–11.0 mg per day [[7]]. The Japanese FSC estimated daily intake as a flavour additive at 9.618–19.211 mg[[8]] and cited the work of Stofberg J. & Grundschober F. [[9]]  to estimate intake of natural dietary intake to be fourfold that used for flavouring, for a total exposure of 48–96 mg/day [[8]]. FEMA places average dietary intake at 35.261 mg/day [[10]], Morris et al. reiterates FEMA’s estimate at 35 mg/day and presents an example diet that yields 75 mg/day, while also citing the worst case dietary levels of 200 mg/day put forward by Technical Assessment Systems (TAS)[[11]].

While understandably concerning, it is also worth noting that the equivalent amount of acetaldehyde in 0.8 ml, or 4 pumps, of gel (0.463 milligrams) is equivalent to that directly present in: a half kilo of apples; 81 grams of apple juice; 120 grams of orange juice; 26.5–167 grams of yoghurt (depending on the yoghurt); 103 grams of canned peas; 309 grams of wheat and rye bread; 12 grams of certain roasted coffee powders (about 1 cup of coffee) [[12]]; 31-463 ml of beer (1/20^th – 4/5^th of a pint) [[13]]; 5–9 ml of wine [[14]]; 1–5ml of sherry wine [[15]]; and under 6% of the average 70kg individual’s direct daily consumption of acetaldehyde contained in alcoholic drinks (before alcohol metabolism) [[12]].

All of the above are for oral use, unlike gel, and the majority of gel use will likely be under 0.8 ml. Nor would gel meet the criteria of a Class 1 Carcinogen since it’s not associated with alcohol consumption.

Any ethanol or acetaldehyde would therefore be absorbed through the skin or inhaled from evaporation.

Transdermal absorption of ethanol in ethanol based hand sanitizer is negligible or nil in cases of regular use [[16]]. Even in excessive application, transdermal absorption is minimal. The even application of 80 millilitres of ethanol hand sanitizer (55%) over a 30 minute period showed absorption at a rate of only 0.9% [[17]].

A study by Thredgold L. et al showed transdermal absorption (the measure of a chemical’s ability to pass through the upper layers of the skin and travel into the body) of acetaldehyde is low even in cases of full body exposure at 996 ppm. Over a 30 minute timespan, average absorption was 22 µg/cm² [[18]]. In this study, the atmosphere was filled with 996 ppm acetaldehyde for 30 minutes yielding 22 micrograms (or 0.022 milligrams) of dermal absorption over this time. Dermal absorption was 9 micrograms (or 0.009 milligrams) per cm² at 20 minutes constant exposure [[18] ^{[figure 2.]}]. Dermal absorption was approximately 1 microgram ( or 0.001 milligram) per cm² at 10 minutes constant exposure [[18] ^{[figure 2.]}]. We can see from this that acetaldehyde is absorbed roughly linearly with time.

Dermal penetration (the measure of a chemical’s ability to enter and remain in the upper surface of the skin, the stratum corneum – taken using tape/swabs to find the presence of a chemical in the upper dead layers of skin) in the same study also showed an average dermal penetration of 5.29 µg/cm² at 30 minutes continuous exposure, an average dermal penetration of approximately 3.40 µg/cm² at 20 minutes continuous exposure, and an average dermal penetration of approximately 0.80 µg/cm² at 10 minutes continuous exposure[[18] ^{[figure 1.]}]. Once again this seems to show that acetaldehyde penetrates the skin roughly linearly with time.

Morris et al. stresses the importance of route specific carcinogenicity, noting that inhaled acetaldehyde is 14–35 times less potent on nasal mucosa than equal doses of inhaled formaldehyde, and 5 times less potent in terms of gastric injury when ingested, furthermore noting that the stomach is 10–60 times less sensitive to acetaldehyde and formaldehyde than the nasal mucosa. He goes on to note that while causing injury, such as stomach lesions, orally ingested formaldehyde lacks the carcinogenicity in the stomach that it displays in the nasal mucosa, and uses the pattern of reduced sensitivity to extrapolate a similar lack of tumorigenicity for orally ingested acetaldehyde—though he does note the importance of long term studies over simple extrapolation, despite its utility [[11]], though such studies are often confounded by other environmental and behavioural factors. Acetaldehyde’s decreased sensitivity relative to formaldehyde would indeed fit with its profile shown in the transdermal absorption study by Thredgold L. et al, where acetaldehyde’s power to cross barriers such as the epidermis and enter non-superficial cutaneous tissues is severely limited compared to that of formaldehyde [[18] ^{[figure 2.]}].

Corollary to this, the ECHA noted that no convincing evidence of formaldehyde dermal carcinogenicity existed, expressing that only the route of inhalation demonstrated tumorigenic effects, and even then only at doses sufficient to produce chronic irritation [[19]]. Animal studies on dermal application of formaldehyde likewise showed no carcinogenic effect, though when combined with another strong carcinogen while it didn’t increase the overall number of tumors formed, it did accelerate the speed at which they first appeared and the mean latency of carcinogenesis [[20]]. Given the decreased sensitivity of tissues compared to formaldehyde, and the relationship between acetaldehyde and formaldehyde sensitisation, it seems reasonable to extrapolate an equally low or lower dermal carcinogenicity for acetaldehyde. Where, for formaldehyde, the ECHA noted “Overall, there is no convincing evidence of a carcinogenic effect at distant sites or via routes of exposure other than inhalation” [[19]].

Following on ECHA’s note of carcinogenicity only occurring at doses sufficient to produce chronic irritation, it is possible that outside of inhalation, acetaldehyde’s mechanism of carcinogenesis when associated with alcoholic beverage consumption stated by IARC [[5]] is due to irritant levels of acetaldehyde associated with the nutritional and metabolic acetaldehyde burden associated with alcoholism, whereas regular dietary intake fails to produce irritation.

With an upper bound dosage of 0.8 millilitres of gel, only 0.463 milligrams of acetaldehyde would ever typically be dispensed. If all of this evaporated into the air, and remained in a 1m³ area at all times, this would only be equivalent to 0.463 mg/m³. Furthermore, with a molecular weight of 44.05 g/mol, we can calculate the ppm concentration of the contained quantity of acetaldehyde with the following formula:

Concentration (ppm) = 24.45 x concentration (mg/m³) ÷ molecular weight

24.45 x 0.463 mg/m³ ÷ 44.05 g/mol = 0.2569

https://www.cdc.gov/niosh/docs/2004-101/calc.html

Here we can see that the given atmospheric concentration would be 0.257 ppm (or 257 ppb), meaning any evaporated acetaldehyde poses negligible inhalation risk at over 3,800 times smaller than the concentration in the above transdermal absorption study by Thredgold L. et al. (the concentration (mg/m³) of this study works out to 1794.429 mg/m³), assuming that 100% evaporates and remains within one cubic meter. In reality, acetaldehyde that evaporates will disperse to irrelevance exceedingly quickly.

Comparing the 22 µg/cm² average absorption of 1794.429 mg/m³ for 30 minutes to that of 1 µg/cm² for 10 minutes, any dermal absorption through evaporated acetaldehyde would be extremely surprising.

However, were it to circulate around an individual, constantly replenishing itself for the next two years, it would still be 194 times lower than what would be required to produce any irritation in the human eye, 583 times lower than what would produce nose or throat irritation in humans [[21]] which are some of the most sensitive tissues to irritants in the human body. Furthermore it would be far below almost, if not all, existing safety guidelines on acceptable atmospheric concentrations for long term workplace exposure.

The majority of applied gel should evaporate within 15-20 seconds. This is 90-120 times shorter in duration of exposure to the concentrated atmosphere of Thredgold L. et al. It is over 1400 times shorter than the long term workplace exposure guidelines, most of which are for given durations of 8 hours.

Compounding to this rapid evaporation time, the boiling point of acetaldehyde is 20.2°C, compared to ethanol at 78.4°C, which will result in its extremely rapid evaporation upon skin contact and further reducing the potential for exposure and absorption.

With 22 µg/cm² average absorption of 1794.429 mg/m³ for 30 minutes, it is readily apparent that 0.463 mg/m³ for a dozen seconds at most will be of negligible effect. Even more so when considering the 1 µg/cm² average absorption for a duration of 10 minutes. There is simply insufficient time for absorption compared to its boiling point and the atmospheric concentration the gel can produce is insufficient to generate the required high concentrations seen in the study by Thredgold L. et al.

Penultimately, reinforcing the superior absorption of the oral route, as expected using Morris et al.’s extrapolation: while the oral toxicity of acetaldehyde is assessed at 1,230 mg/kg of bodyweight [[22]], the dermal toxicity requires dosages almost fourfold higher, once again pointing toward the poor dermal absorption of acetaldehyde. The SCCS stated the following about the acute dermal toxicity of acetaldehyde:

“By the dermal route of exposure Acetaldehyde is practically non-toxic. A dermal LD50 value of greater than 5,000 mg/kg bw has been reported in rabbits on the basis of single death in 10 animals administered 5,000 mg/kg bw” [[23]]

Finally, IMAP concluded that acetaldehyde was not a skin irritant, though they did note that some studies with high concentrations of acetaldehyde did produce slight irritation, and that patch tests in human volunteers resulted in erythema at 10% formulations, adding that concurrent exposure to other chemicals in the preparation might have contributed to the resultant irritation [[24]].