Tenuous Toxicity Concerns

FDA guidelines for acetaldehyde content in sanitizers may be questionable given the compound’s relative ubiquity. Independent consultants present a compelling challenge to the federal government's 'vague, unproven suspicion' of dermal toxicity.
By Jim Buchacker and Jim Forshaw | October 01, 2020

Corn is undeniably a bounty from nature. It has not only fed us well, but can also help protect us from one of nature’s deadliest agents: viruses. Ethanol made from corn has become an important weapon against COVID-19 when used as a hand sanitizer. While demand for sanitizer-grade ethanol has soared, fuel-grade ethanol plants witnessed a steep reduction in demand that has now rebounded but is still well below last year’s levels. For much of the industry, the spring downturn resulted in dramatic output reductions, plant idlings and even complete shutdowns. And while relatively few ethanol plants laid off employees, should the situation have persisted longer, the potential for massive job loss was real.

The Food and Drug Administration is charged with drafting health and safety standards, which govern the use of ethanol in sanitizers. These standards specify allowable limits of certain impurities in ethanol such as methanol, acetone, acetaldehyde, total acetal compounds, etc.

In March of 2020, the FDA published guidance titled “Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) Guidance for Industry.” Unlike some foreign ethanol producers, U.S. producers typically do not experience problems with methanol exceeding specified limits. Rather, the most frequent impurity that plagues U.S. producers is acetaldehyde. But the FDA’s limits on acetaldehyde in ethanol for hand sanitizer present a confusing contradiction with other studies, and even other substances ingested and applied to skin.

Perplexing Footnote
Unfortunately, the FDA states in Attachment 1 of its guidance that it has “received data indicating that certain fuel ethanol products contain excessive levels of acetaldehyde, which appears to be a genotoxic carcinogen when in direct contact with tissues.” A corresponding footnote reads: “The toxicology for acetaldehyde differs when ingested as part of an alcoholic beverage (versus applied to skin as with hand sanitizer), in part due to the liver’s metabolism of acetaldehyde.”

The main problem with this statement is that FDA purports to be in possession of said data, but fails to cite that data in its footnote. Searches of U.S. EPA, International Agency for Research on Cancer, Health Canada, National Toxicology Program, National Institute for Occupational Health, and the European Commission on Public Health’s sites produced no data or references to the “special” carcinogenicity/mutagenicity risk that acetaldehyde poses to human skin. We are not saying that the data does not exist; however, we were not able to establish its existence.

And while this guidance document is classified as non-binding, it would certainly be nice to see the data that FDA is basing its suspicions on. It should also be noted that this non-binding guidance document could be taken to heart by American juries, who frequently have been found to take a dim view of defendants who do not follow “guidelines,” no matter how unproven they may be.  

Dermal Toxicity
To muddy the waters even further, a 1995 study entitled “Could Bacterial Acetaldehyde Production Explain the Deleterious Effect of Alcohol on Skin Diseases” found that certain bacteria commonly found on human skin were capable of producing high levels of acetaldehyde when exposed to ambient levels of ethanol. Although this study was done in-vitro, the data can be extrapolated to individuals who consume alcohol. These individuals, whose epithelium is bathed in sweat (which according to the authors would contain more than enough ethanol to fuel the production of acetaldehyde in these bacteria), would have a significant amount of acetaldehyde present on the surface of their skin for hours after imbibing alcoholic beverages. This information is not necessarily earth shattering news, but is certainly food for thought.

After an in-depth investigation of the facts surrounding the dermal toxicity and carcinogenicity of acetaldehyde, one glaring deficiency has been identified: Where are studies that quantify how much acetaldehyde actually binds to skin after application of ethanol or acetaldehyde? It has been reported that hand sanitizer only remains on the skin for a matter of seconds before it evaporates. The boiling point (BP) of ethanol is 173 degrees Fahrenheit at 760 millimeters of mercury (mm/hg), which is the major portion of hand sanitizer. The BP of acetaldehyde is 70 degrees at 760 mm/hg. With a human skin surface temperature that is 28.6 degrees higher than the BP of acetaldehyde, the question of how much of that volatile compound actually makes its way to epithelium seems to be the $100,000 question. Unfortunately, it does not appear that anyone has done that study yet.

But it is not a stretch of the imagination to say that if hand sanitizer only remains on the skin for a matter of seconds (not minutes), and acetaldehyde is at least 2.5 times more volatile than ethanol, the amount of acetaldehyde making its way to bare epithelium is going to be miniscule. This, coupled with the extremely low amounts of acetaldehyde present in ethanol, paints a sobering (excuse the pun) picture of how much of this compound actually contacts and remains on the skin. In the absence of real data concerning the migration of acetaldehyde to skin via hand sanitizer formulations, it would be wise to ponder the fact that every toxicologist knows: The dose makes the poison.

In Our Food
The FDA is very likely to rescind, in the near future, the temporary rules that allow for higher levels of acetaldehyde. The result will be a reduction in the availability of ethanol used to make sanitizers to protect the public from COVID-19.

This would certainly make sense if there was a greater reduction in risk to the public than the benefit received, but that is not the case. Acetaldehyde, it turns out, is not only found naturally in many foods such as fruit, but the FDA allows its presence in cosmetics. Acetaldehyde is also present in alcoholic beverages (regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives, not FDA) and yet, the dermal limits for acetaldehyde exposure are much lower than limits for internal exposure.
To make things even more confusing, the first metabolite created by the body when processing alcohol is, in fact, acetaldehyde.

It seems that EPA said it best in the following excerpt from Acetaldehyde Hazard Summary, January 2000, “Sources and Potential Exposure:”

“Acetaldehyde is ubiquitous in the ambient environment. It is an intermediate product of higher plant respiration and formed as a product of incomplete wood combustion in fireplaces and woodstoves, coffee roasting, burning of tobacco, vehicle exhaust fumes, and coal refining and waste processing. Hence, many individuals are exposed to acetaldehyde by breathing ambient air. It should be noted that residential fireplaces and woodstoves are the two highest sources of emissions, followed by various industrial emissions. (1) In Los Angeles, California, levels of acetaldehyde up to 32 parts per billion (ppb) have been measured in the ambient environment. (1) Exposure may also occur in individuals occupationally exposed to acetaldehyde during its manufacture and use. (1,2) In addition, acetaldehyde is formed in the body from the breakdown of ethanol; this would be a source of acetaldehyde among those who consume alcoholic beverages.”

How logical is it to allow the FDA to regulate a compound that is not only ubiquitous, but is also permitted by other federal agencies (ATF) to be consumed internally and in much greater quantities? Protecting ourselves from a virulent pandemic killer should always take precedence over protecting ourselves from a vague, unproven suspicion of dermal toxicity. The benefits clearly outweigh the risks at this moment in time.

Perhaps an exemption request for this acetaldehyde issue might be in order. Written exemptions provide a built-in legal insulation from torts and liabilities arising from ambiguities in vague regulatory rhetoric.  

Co-Authors: Jim Buchacker
Independent Consultant/Broker
Buchacker Consulting
704.492.3267
buchacker1@gmail.com

Jim Forshaw
Independent Consultant
843.461.0152
jimforshaw@gmail.com