The Effect of Hand Sanitizer on Blood Biomarker Analysis
Blood tests for Phosphatidylethanols (PEth)
Counterpoint Volume 5: Issue 1 - Article 4 (December 2020)
An article in the Mastery Skills II-1 Module
Jan Semenoff, BA, EMA
Forensic Criminalist
Article information:
1900 words (approximately 10-15 minutes)
Due to the increased use of hand sanitizers in recent months, supplies of product with sufficient alcohol concentration have been hard to come by. The key ingredient in most commercial or medical grade hand sanitizers is ethanol – plain old beverage alcohol, and it comes in with a very high ethanol concentration. Many local distillers have risen to the supply challenge and are producing hand sanitizers with the necessary ethanol concentration (at least 60-65% ABV). As with our discussion in the previous article about the effects of hand sanitizers on urinalysis, the biomarkers of blood analysis can lead to false-positive readings.
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The Effect of Hand Sanitizer on Urinalysis
We’ve discussed the effect of hand sanitizers on biomarker analysis in urine in a past article, specifically with false-positive readings associated with Ethyl Glucuronide (EtG) and Ethyl Sulfide (EtS): “The Effect of Hand Sanitizer on Urinalysis”, Counterpoint, Volume 4, Issue 4, Article 3 (August 2020) You may wish to read that article along with this one for a bigger picture of the issue. |
Biomarkers
First, we need to recognize that there are two main ways to measure a substance in the human body:
1. Directly measure the concentration of the substance itself, for example:
a) The level of ethanol found on the breath or in a blood sample
b) The level of glucose found in the blood
2. Indirectly measure the concentration of a metabolite of the substance (called a biomarker)
a) The level of Ethyl Glucuronide (EtG) or Ethyl Sulfide (EtS) found in urine to determine ethanol levels
b) The level of a metabolite of ethanol found in the blood, i.e. – PEth.
This brings us to the concept of the biomarker (or biological marker). A biomarker measures a sign of a normal biological process. Put another way, a biomarker is an indicator signalling that a biological event has occurred. We are concerned specifically with one group of biomarkers - biomarkers of exposure. Biomarkers of exposure are particularly useful for the objective assessment of current systemic exposure to chemicals that are readily absorbed through the skin, unfortunately, including ethanol.
Examples of Biomarkers:
- Mercury in hair samples or lead in urine samples could indicate a contaminated water supply (Flint, Michigan comes immediately to mind).
- COVID antibodies indicate past exposure to the COVID-19 virus
- Urinary ketones indicate the possibility of diabetic disorders
Phosphatidylethanol (PEth)
Your client can provide a blood sample that can be analyzed for the presence and concentration of a group of metabolites of ethanol consumption: Phosphatidylethanols or PEth.
Phosphatidylethanols are specific metabolites of ethanol, produced after the ethanol is exposed to cell membranes. So far, 48 different versions of PEth can be found in human blood samples. The most abundant of the PEth family, and therefore the one most often tested for, is called PEth homolog 16:0/18:1, and thank goodness, is simply referred to as PEth.
Figure 1 - A molecule of Phosphatidylethanol
As with EtG and EtS, PEth levels are used as biomarkers to test for the current or past presence of ethanol in situations where absolute abstinence from beverage alcohol is necessary, i.e. – military personnel, commercial pilots, health care professionals or following alcohol treatment programs, and of course, situations involving probation, and conditional or early release.
PEth can be detected in blood after as little as 30 minutes of exposure and peaked after 90-120 minutes. With alcohol consumption that occurs frequently, PEth starts to accumulate in whole blood. Even after a one-time consumption, PEth levels were measurable for 1 to 2 weeks following exposure, making PEth analysis an assessment tool for both recent and past consumption. As its level will build up after repeated exposure to ethanol, it can also be used to determine chronic excessive drinking behaviours, and relapse, in alcohol abstinence monitoring programs.
As with EtG testing, the disadvantage of PEth analysis is that false positives are possible, and have been well documented, after exposure either incidentally to mouthwashes containing ethanol, or from non-beverage exposure, such as hand sanitizers. It has been identified that exposure to mouthwash, fermenting foods, over-the-counter medications and dermal exposure to hand sanitizers have all resulted in false positive reported readings. Because the PEth levels can be detected in such small amounts, it is impossible to distinguish its presence between ethanol consumption and extraneous exposure to ethanol from other sources of contamination.
Cut off levels
In order to differentiate social drinking from excess consumption, the level of the PEth measured in the blood must be taken into account. This means establishing a PEth value that represents moderate but not excessive consumption patterns, and as you’d imagine, this value is open to interpretation and debate.
Currently, the value used to establish the threshold, or cut-off level is 20 ng of PEth per millilitre of blood, or 20 ng/mL. But there is debate as to whether this value is truly representative of non-abuse levels of consumption. Some advocate for a level as high as 50 ng/mL, or 2 ½ times higher than the currently used value. Italian researchers write:
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At the present time, the international scientific community has not yet established a cut-off value for PEth concentration in blood to be used for differentiating an acceptable social ethanol intake (<40 g for males and <20 g for females, according to the World Health Organization parameters), from an at-risk-alcohol-use (40–60 g/day) and chronic excessive drinking behavior (>60 g/day).
The present systematic review demonstrates that total Phosphatidylethanol (PEth), an abnormal phospholipid formed in the erythrocyte membrane exclusively in the presence of ethanol, exhibits high diagnostic sensitivity and specificity for detecting active chronic excessive drinking behaviors, with a regular daily alcohol intake of more than 60 g. [1] [1] Viel, Guido, Boscolo-Berto, Rafael, et al, “Phosphatidylethanol in Blood as a Marker of Chronic Alcohol Abuse Use: A Systematic Review and Meta-Analysis”, International Journal of Molecular Sciences, 2012, 13 14788-14812. |
Another problem these researchers identified was interpreting the correlation of consumption given the individual variability of the data obtained:
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The PEth concentration correlated well with past weeks alcohol intake, albeit with a large interindividual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking. [2]
[2] Helander, A., and OlofBeck, U., “Dose-Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth) – A Study of Outpatients in Treatment for Reduced Drinking”, Alcohol and Alcohoilism, Voume 54, Issue 6, November 2019, Pages 567-573. |
What are considered levels of social consumption versus abuse?
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While no formal internationally accepted cut-offs have been established, yet, PEth16:0/18:1 levels above 20 ng/mL indicate “social drinking,” while concentrations above 150 or 221 ng/mL (depending on the source) may be suggestive for chronic and excessive alcohol consumption. [3]
[3] Kummer, N., et al, (2016a), “Alternative Sampling Strategies for the Assessment of Alcohol intake of Living Persons”, Clinical Biochemistry, 49, Pages 1079-1091. |
PEth and hand sanitizer - A case study:
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I was recently contacted by a lawyer whose client’s blood PEth level was reported at just above the 20 ng/mL cut-off level (at 31 ng/mL – well below the proposed 50 ng/mL level). Some additional facts to consider:
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Regardless of the contradictory evidence, the medical board monitoring this physician has indicated a desire to proceed to sanction the client’s professional license on the basis of the PEth levels reported. In my opinion, the concentration of the PEth reading gives rise to the probability of contamination by ethanol other than beverage ethanol.
For the record, I turned this file over to another expert who is a physician, and who has considerable experience in both pharmacology and laboratory testing procedures. However, I still did some research in the matter (with both professional curiosity, and research for this article as my goal).
Sources of contamination
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My first area of inquiry was the hand sanitizer in question. Was it commercially prepared by a pharmaceutical company, as per pre-COVID times, or prepared locally? What was the disinfectant alcohol used? What was its concentration? It turns out that a few local distilleries in the area had begun production of hand sanitizers. A quick look at the labels of these sanitizers indicated “alcohol” at levels of about 65%+ in concentration.
First, we can assume “alcohol” means ethanol – it is being produced by a distillery, after all.
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Second, one of the sanitizers referred to the alcohol as “denatured”. This simply means that a bitterant compound (typically Bitrex™) is added to make the solution bitter, unpalatable, and not able to be consumed orally. We don’t need people squirting hand sanitizers into their mouths after finding out that it is 65% Vodka, after all…
So, the big questions are – Can the ethanol be absorbed through the skin (dermally)? Can it be absorbed in sufficient quantities to create a false-positive PEth result?
The answer to both questions is yes.
The answer to both questions is yes.
It has been established that both hand sanitizers containing isopropanol, and also those containing ethanol, can be absorbed through the skin (dermally). Again, I will refer you to the previous Counterpoint article regarding hand sanitizers and EtG levels that establish the notion of dermal absorption.
Swiss researchers at the University of Lausanne, Switzerland examined the effect of ethanol-based hand sanitizers and PEth readings. Their findings were rather significant, with albeit a small sample study of only three participants:
- The first test subject, a declared alcohol abstainer, washed her hands with a hand sanitizer containing 85% ethanol w/v and shortly thereafter provided a blood sample which was analyzed to possess a PEth concentration of 130 ng/mL.
- The second test subject washed her hands with regular soap and water and had a PEth concentration of 82 ng/mL. After using an ethanol-based hand sanitizer, her PEth concentration jumped to 430 ng/mL.
- The third subject also washed his hands with soap and water and had a PEth measurement of 140 ng/mL. After using an ethanol-based hand sanitizer, his PEth concentration increased to 240 ng/mL.
These results are all far higher than the 20 ng/mL cut-off being used to determine alcohol consumption, or 150+ ng/mL to determine chronic alcohol abuse. The researchers concluded:
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An abnormal elevation of PEth concentration in blood was observed after using ethanolic solution for hand cleaning. Thus, ethyl alcohol disinfection (has) to be avoid before blood sampling for DBS (Dried Blood Spots – Editor). If not, a rapid formation of PEth could happen during blood sampling, involving a risk of erroneous interpretation concerning alcohol consumption. [4]
[4] Augsburger, M., Lauer, E., et al, “Doctor, I do not understand the results of the test, because I swear I am not drinking alcohol.’ Truth or Lie?”, Toxicologie Analytique et Clinique, Volume 31, Issue 2, Supplement, 2019, Page S51. |
So again, interpret these forensic results based on the circumstances involved in how they were obtained. It is not unreasonable to think that the frequent application of ethanol-based hand sanitizers can produce measurable levels of PEth concentrations that can be misinterpreted as an indicator of recent alcohol consumption, or a pattern of chronic alcohol abuse.
Send me your questions or comments:
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For further study:
- Andresen-Streichert, H, Muller, A, et al, “Alcohol Biomarkers in Clinical and Forensic Contexts”, Deutsches Arzteblatt International 2018; 115: 309-315.
- Viel, Guido, Boscolo-Berto, Rafael, et al, “Phosphatidylethanol in Blood as a Marker of Chronic Alcohol Abuse Use: A Systematic Review and Meta-Analysis”, International Journal of Molecular Sciences, 2012, 13 14788-14812.
- Ghosh, S., Jain, R., et al, “Alcohol Biomarkers and their Relevance in Detection of Alcohol Consumption in Clinical Settings”, International Archives of Substance Abuse and Rehabilitation, 2019, 1:002, pages 1-8.
- Reisfiled, G., Teitelbaum, S., et al, “Blood Phosphatidylethanol Concentrations Following Regular Exposure to an Alcohol-Based Mouthwash”, Journal of Analytical Toxicology, bkaa147.
- Helander, A., and OlofBeck, U., “Dose-Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth) – A Study of Outpatients in Treatment for Reduced Drinking”, Alcohol and Alcohoilism, Voume 54, Issue 6, November 2019, Pages 567-573.
- Augsburger, M., Lauer, E., et al, “Doctor, I do not understand the results of the test, because I swear I am not drinking alcohol.’ Truth or Lie?”, Toxicologie Analytique et Clinique, Volume 31, Issue 2, Supplement, 2019, Page S51.
- Kechagias, S., Dernroth, D., et al, “Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study”, Alcohol and Alcoholism, 2015, Vol. 50, Iss. 4, Pages 399-406.
- Kummer, N., et al, (2016a), “Alternative Sampling Strategies for the Assessment of Alcohol intake of Living Persons”, Clinical Biochemistry, 49, Pages 1079-1091.
