Ethyl glucuronide
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Ethylglucuronide, ethyl glucuronide, or EtG is the name for a chemical marker of recent alcohol (ethanol) exposure. EtG is a minor non-oxidative metabolite of ethanol.
In other words, when you drink alcohol some of it is converted into EtG which is eventually eliminated from the body. The benefit of testing for EtG is that it is present much longer in the body than alcohol itself and thus it can be a more durable and superior marker for recent alcohol exposure. EtG can be found in urine, blood, and all other body tissues (hair, liver, etc). It is only present after exposure to alcohol. EtG is fairly stable in urine (it is degraded by some bacteria, if present in the urine) and is detected by analyzing at a laboratory with either liquid chromatography and mass spectroscopy (LC-MS-MS) or by immunologic testing (ELISA). The ELISA test is relatively new (manufactured by Microgenics). EtG testing is particularly useful in monitoring individuals who have agreed to be abstinent (professionals who have been allowed to return to their jobs following problems with alcohol at work, who return on condition they will not drink alcohol, custody cases where alcohol use has been an issue, criminal jurisdictions where alcohol has been associated with crime, etc).
Ethyl glucuronide, EtG, as well as other non-oxidative metabolites of ethanol, including ethyl sulfate, EtS, and less commonly ethyl phosphate, EtP, are gaining popularity as they can detect ethanol use for up to 7 days post exposure (depending on the person and dose of ethanol). As such, EtG and these other markers should only be used in situations where total abstinence from ethanol is expected or required, such as for employees or licensees (pilots, doctors, etc) who have been allowed to return to work contingent on total abstinence, probationers who’ve agreed to abstinence, monitoring in child custody cases where total abstinence is imposed, or for underage children or young military recruits, etc. In all other situations drinking ethanol off duty is not prohibited and would cause a positive test but would be meaningless as far as the workplace is concerned. In other words these analytes detect any exposure and therefore having little to do with detection of impairment at work. EtG and/or EtS testing are proving to be very sensitive and specific in detecting exposure to ethanol; however, in the absence of a commitment or expectation of total abstinence (on and off work) they should not be used. It is always important when someone is being tested for these markers that they be advised that incidental exposure to ethanol can cause a positive and they should be advised in detail about products containing ethanol.
While <1% of ethanol is converted to EtG, it is known that this metabolic pathway has great inter-individual variability in activity. While there are no studies to provide information specific for EtG production, other metabolites formed by the same liver isoforms as EtG demonstrate up to a 7-fold difference for one metabolite and a 30-fold difference for another. This said, two people with identical exposures to environmental and dietary unknown/unintentional sources of alcohol may produce very different levels.
It’s also important to realize that EtG and EtS can be present in urine from non-beverage alcohol exposure. Following introduction of these tests numerous individuals came forward tenaciously claiming they were falsely accused of drinking because of positive EtG tests. Various products were tested on small numbers of individuals and it was found that ethanol containing mouthwash, sips of communion wine, alcohol free wine and beer, and OTC meds containing ethanol caused low positive EtG tests, up to 300-400ng/ml. A study using alcohol-based hand sanitizing gel (62% ethyl alcohol) indicated that inhalation, not skin absorption, is a major absorption route for ethyl alcohol, producing very significant EtG levels. Lab experiments utilizing these hand gels have yielded EtG results in the 500-800ng/ml range on multiple occasions.
The question of where to set the cutoff for EtG to increase specificity regarding alcoholic beverage use and to decrease sensitivity to avoid detection of what has come to be called “incidental exposure” is frequently asked. Laboratories are currently offering cutoffs of 100, 250, 500 and 1000 ng/mL. These cutoffs have no scientific foundation in terms of identifying beverage alcohol consumption. Early European studies used the cutoff of 100ng/ml because that was the lowest level at which their instrumentation was technically reliable. There are no published studies on the effects of non-beverage alcohol (termed "incidental alcohol") on EtG levels. There are no large-scale studies that establish that EtG levels in non-drinkers will consistently fall below 100, 250, or even 500ng/ml. That said, it is recommended that each agency select a cutoff that is appropriate based upon their flexibility (in dealing with investigations of false positive claims), sophistication in understanding the concepts, and severity of consequences from a positive test. Agencies must weigh the potential danger to the public against the possibility of a false accusation and the resulting consequences. As with any laboratory test, EtG is meant to be used as a tool in determining alcohol consumption. Other clinical factors should always be considered.
SAMHSA, the division of the U.S. Department of Health and Human Services that regulates workplace drug testing, issued an advisory on alcohol biomarkers, which includes the following 'black box warning' regarding EtG:
Currently, the use of an EtG test in determining abstinence lacks sufficient proven specificity for use as primary or sole evidence that an individual prohibited from drinking, in a criminal justice or a regulatory compliance context, has truly been drinking. Legal or disciplinary action based solely on a positive EtG, or other test discussed in this Advisory, is inappropriate and scientifically unsupportable at this time. These tests should currently be considered as potential valuable clinical tools, but their use in forensic settings is premature.
Many studies advise that EtG levels be “normalized” to a creatinine level of 100, which is expressed as “EtG100“. Particularly when levels are critically close to a cutoff level, such an adjustment may have crucial consequences. SAMHSA requires that a creatinine level be measured with all specimens tested for drugs. To normalize the level, use the following formula: “EtG100” = (EtG x 100) / Cr.
