Ethanol, the psychoactive ingredient in wine, beer and liquor, is one of the most intensely studied compounds in the history of toxicology. We know a great deal not only about alcohol consumption’s effects on human performance, but also on its disposition in the body. Once consumed, ethanol passes through the stomach into the small intestine, where it is absorbed into the blood. In the blood, it travels first through the portal vein to the liver (a process called “first-pass metabolism”), and then to the general circulation beyond. The liver breaks some of the ethanol down into acetaldehyde and then to CO2 by multiple enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, catalase and alcohol-inducible cytochrome P4502E1). Being hydrophilic (mixes or dissolves well with water), ethanol distributes throughout the body water and is found in highest concentrations in those tissues which have a high water content, such as blood. A small fraction of ethanol, less than 0.1%, is metabolized by a different route to ethyl glucuronide or ethyl sulfate. A small fraction (2 – 5%) is excreted unchanged in the urine.
Ethanol can be measured in any body fluid or tissue that contains water (which is to say, all of them). For OWI cases, most commonly blood is measured, but alcohol can also be found in urine, saliva, vitreous humor (tissue used in fatal cases only), sweat and milk. It can also be found in breath, because ethanol is volatile and is exhaled from the lungs along with CO2. Breath alcohol measurement occurs by a couple of different techniques, and has its own suite of complications, but that’s another article.
Blood or urine ethanol is commonly measured by immunoassay in most hospital or emergency room settings, and by headspace gas chromatography in forensic laboratories for purposes of OWI prosecution or death investigations. Both types of methods generally have a reporting limit of 0.01 d/gL. In all of these situations, however, the issue in question is how much ethanol the subject has in their system at the time – at the time or driving, or at the time of death. If the question instead is how much ethanol the subject has consumed over the last several days, these measurements are not likely to be of much help as ethanol is cleared from blood or generally within 24 hours. If we want to lengthen our window of detection, we must turn to other markers of alcohol consumption that can be detected for longer periods or at lower levels. Thus we come to EtG.
Ethyl glucuronide (EtG) is only a small fraction of the amount of ethanol consumed, but it takes longer to clear and can be detected down to lower levels – as low as 100 ng/ml. Depending on the amount of ethanol consumed, EtG can be detected in the urine up to 72 hours after drinking. This represents improved monitoring capabilities for subjects in court-ordered abstinence or treatment programs. There are published methods for EtG detection by both immunoassay and by LC/MS/MS, although for cases in which legal sanctions are possible, it is recommended that confirmation by LC/MS/MS be performed.
EtG has become a common and useful method for many court drug programs in the last five years. But as with all other forensic methods, there have been objections and claims of false positives. The most common claim is incidental exposure from household products containing ethanol. It is true that products such as mouthwashes, hand sanitizers and over-the-counter cough and cold elixirs contain ethanol. However, cutoffs used in court monitoring programs (500 – 1000 ng/ml) are much too high to detect ethanol from these products if they are used according to the manufacturers’ instructions. Published studies have shown that using hand sanitizer as directed will not produce an immunoassay positive EtG result. Washing one’s hands every five minutes for 10 hours a day for three days can¹ – but this extreme example is not likely to occur in real life. Similarly, using an ethanol-containing mouthwash as directed might give you an EtG level of 50 – 100 ng/ml – but this is well below the positive threshold². If you drink the whole bottle, however, you could be over the threshold – but you would also be abusing the product. There have been similar claims that eating “fermentable” foods such as bananas and sauerkraut can cause incidental positives³, but there is no actual evidence that consumption of these would get anyone close to the 500 ng/ml cutoffs. Thus we can confidently say that if EtG is confirmed by LC/MS/MS and is above 500 ng/ml, it is not likely to be from incidental use, unless it’s abuse of these products or some extreme or unusual circumstance.
Is there any kind of unusual circumstance where a confirmed, elevated EtG might be from something other than alcoholic beverage consumption? At the 2016 meeting of the Midwestern Association for Toxicology and Therapeutic Drug Monitoring, Alex Armfield presented a case where the subject had vaginal surgery, an open wound, and instructions to clean the area 30 times per day with medicated wipes containing 65.9% alcohol. The confirmed EtG level was 758 ng/ml. The rate of alcohol absorption across intact skin is known and could not account for this result, but direct application of ethanol to an open wound? Suffice to say there are no lab studies on this type of situation, so the best we could say was “inconclusive.” A poll of the audience showed that the US Drug Testing Labs in Des Plaines, IL, had had a similar case and they had rendered a similar verdict: can’t rule out that the low, confirmed EtG result was from direct absorption through an open wound, because there is no direct evidence against this being possible. Moral of the story: never say never. There’s always some weird situation out there that nobody has accounted for. But that is what makes this job so interesting!
References
1. Reisfield GM et al. J Anal Tox 35:85-91, 2011
2. Constantino A et al J Anal Tox 30:659-662, 2006
3. Musshoff F et al Int J Legal Med 124(6):623-630, 2010
4. Jatlow P et al Alcohol Clin Exp Res 38(7):2056-2065, 2014
