Chart to help interpret EtG/EtS tests:
1. Urine alcohol positive with negative EtG and EtS = suggests fermentation (in-vitro) - doesn't suggest drinking
2. Urine alcohol positive with positive EtG and negative EtS = could be from fermentation and in-vitro synthesis of EtG, but could also be from drinking or incidental exposure
3. Urine alcohol positive with negative EtG and positive EtS = suggests in-vivo alcohol - either drinking or incidental exposure
4. Urine alcohol negative with positive EtG and/or positive EtS = suggests in-vivo alcohol - either drinking or incidental exposure
Question about cutoff levels from an MRO?
Wondering how you would respond to the comments on the discussion list that there can be incidental exposures with levels above 1000. I was reading the one on the individual who works with bread and currently dealing with a donor who claims that her only exposure after checking all bottles and ingredients in her house was using preparation H on a raw area. She indicated the label noted 7% alcohol. Her level was 700. I have no problem with EtG levels about 1000 in general but starting to be a bit concerned about those in the 500-1000. I know there have been a few studies on "tea-totalers" but... even with the Vicks, dilutes, and poppy seed issues, the problems were not picked up until large number of tests were done.
You are certainly correct about poppy seeds. It was known for over 30 years that poppy seeds could cause positive for morphine/codeine before it was explored enough to understand more than the basics about parameters. New data is continuing to come forward. It's going to be even more complex with EtG because there are so many more sources for incidental exposure. Everything done thusfar has been in small numbers and in contrived single exposure situations.
The problem with setting an upper limit for EtG that could be secondary to "incidental exposure" is that there is no clear definition of what could be considered the upper limit of "incidental exposure." I've recently testified in board hearings where individuals claimed "incidental exposure" to spiked punch, 100 times more tincture of ginko-biloba than recommended, a bottle of vanilla extract in a thermos of coffee per day, where in the end the board allowed these as possible incidental exposure. The EtG levels were between 800-5,000ng/ml. So if we can't define the limits of incidental exposure then we certainly won't be able to set an upper limit for EtG that could be caused by that exposure.
From a practical point of view any EtG over 100ng/ml means there has likely been exposure to ethanol. I would encourage anyone contacting an individual who has a positive EtG to approach the person in a non-confrontational way but affirmatively certain that the person has been drinking and encouraging them to accept help. When utilizing this approach most individuals have admitted beverage alcohol exposure. I think the initial approach to confronting the individual has much to do with the outcome. We don't currently know the limits of what could be produced from "incidental exposure" but if everything else in their monitoring looks good, they deny alcoholic beverage use, and some likely source of incidental exposure is identified then it is wise to consider the alternative explanation.
A couple of things I've recommended is 1. doing a creatinine on the urine so a U100 Creatinine can be deterimined to identify the influence of concentration, 2. if there is a suspected source of incidental exposure it can be tested to see if repeated exposure causes a positive (most of these have been negative) and 3. use of "lie-detector" testing can be helpful.
Supervising a testing program?
I joined this group to understand more about ETG as we have implemented this testing in the program I am account manager for. After scanning alot of the posts, it looks to me that it was stated that coming up positive in the 100 range could be incidental usage? If so there is there any other advice I can give my testers other than don't use cough medicine or mouthwash?
A couple thoughts for you:
1. It's a good idea if you are going to use EtG monitoring people for total abstinence to put a clause in the monitoring agreement in the section on not using any addictive drugs or alcohol, to include: "no alcohol of any kind including alcohol in foods, hygiene products, or OTC meds containing alcohol (eg vanilla extract, mouthwash containing alcohol, nyquil, cough syrups, etc), no communion wine, no topical gels or medications containing alcohol on skin or mucous membranes, etc.. I agree to avoid all alcohol containing products and understand that use of any of these products cannot be used as a defense to a positive urine drug test and will be considered a violation of this agreement."
2. We have studied use of products such as alcohol containing mouthwash on small numbers of subjects and have found positives up to about 300 or so peak levels of EtG when the products are used as directed or in excess of as directed in small numbers of subjects.
3. This means that, as with poppy seeds and morphine levels, there are really two cutoffs. A lower cutoff (100 - 500 or higher) that could represent the tail end of beverage alcohol use or "incidental exposure" and a higher cutoff (>500 - 2,000) that would represent very significant alcohol consumption (ie beverage alcohol or excessive use of mouthwash, vanilla, or other products far in excess of recommended doses). Exact cutoffs to represent these categories have not be worked out and will require more studies in larger numbers of patients with various types of exposures in various combinations.
4. Therefore, when you question someone with a positive EtG test (whether lower cutoff or upper cutoff) I would approach the person stating "We know from your urine test that you have consumed alcohol. Let us know the details regarding your alcohol use so that we can assist you" or something along these lines.
Hand sanitizers containing ethanol?
"We were wondering about the use of alcohol based hand sanitizer which we use countless times per day and the effect on EtG. We tried to research it on the Internet, and it says that it is absorbed by the body, however it stated that studies on those in recovery have not been performed. Could you please let me know your thoughts on this? Thank you for your time."
Yes. We were concerned to evaluate alcohol gels that have a high content of ethanol (>60%) and are commonly used in hospitals and elsewhere. Further evaluation is underway. It appears that inhalation of the vapor from ethanol hand gel does cause elevated EtG and EtS levels. These levels can be surprisingly high.
Differences between men and women?
Looking at superimposed graphs of blood alcohol levels from one drink in a men and one drink in a women, the women will have a higher blood alcohol level. Is this true also with the ETG levels? Theoretically, a women would have higher blood alcohol levels with incidental use also, and therefore higher ETG results. If this is true, shouldn't the cut-off levels be different for male and female?
This has not been specifically examined. There appears to be much variation in how much EtG one individual produces compared to another (due to polymorphism of the enzyme systems), which is probably a more significant factor. Also, because less than 0.1% of alcohol is metabolized into EtG, and because of urine concentration/dilution factors, time frame, etc, It is doubtful that it will be possible to have exacting precise cutoffs. In other words, the cutoff levels will need to be fairly high anyway and will probably not be greatly affected by slight changes in serum alcohol levels. However, time will tell, as more research is performed.
Positive urine alcohol and negative EtG?
We've had a few instances of positive urine alcohol (low levels) and negative ETG. We are suspecting perhaps our lab cut off for urine is lower and more specific, than the cut off for ETG. What do you think?
Urine EtG is actually more "specific" than urine alcohol since you can have alcohol in urine without drinking (if it ferments there) but the only way you can have EtG in the urine is if alcohol is in your body. So there are really only three reasons you can have a positive urine alcohol and negative urine EtG. 1. The alcohol fermented "in-vitro" in the urine, 2. The urine was obtained very soon after drinking, since it takes EtG longer to appear in urine than alcohol, or 3. The cutoff value for EtG is too high.
In the case of #1 there is evidence that not only can yeast ferment alcohol but also some bacteria and the amount of glucose neccessary can be small. So it's not just in diabetics with yeast in the urine that fermentation occurs. In the case of #2 it doesn't make much sense that someone would drink and then give a urine sample within 1 hour. In case #3 some labs are setting the cutoff for EtG high to avoid positive EtGs from "incidental alcohol use" and this is making EtG less sensitive.
In conclusion, we are using a 100 ng/ml cutoff and if the urine is positive for alcohol but negative for EtG we are assuming it was probably in-vitro fermentation (ie a false positive test). Nevertheless we still confront the participant and ask them if they've been drinking but we drop it there if they say no. We've not yet had one of this type who've admitted drinking.
EtG stability - warm weather?
Does warm weather during shipment cause a more rapid breakdown of EtG in urine?
Recent experiments show that heating urine to 100 C (boiling point of H2O) actually increased the stability of EtG. The data are showing that at room temperature, in some individuals with nitrites and/or blood in urine, that EtG can deteriorate over a week. We are surmising that esterases associated with infection may be causing breakdown of EtG. Heating seems to prevent breakdown, possibly due to neutralizing the bacteria. So, the fact is that heat doesn't cause breakdown of EtG, it actually increases stability.
Questions concerning the AWOL vaporizer:
This “new” method of alcohol abuse known as Alcohol Without Liquid (AWOL) vaporizer is discussed on the web sites www.awolmachine.com Following is the response from Dr. Ed Barbieri from National Medical Services, Willow Grove PA:, regarding an opinion about how this would affect EtG.
”We have looked into the AWOL machine from the website. Alcohol may enter the bloodstream in the manner that is described on the web site. For ethanol to get to the brain it MUST enter the bloodstream. If ethanol enters the bloodstream, it will be distributed to other tissues throughout the body including the liver and, therefore, will be metabolized. Once metabolized, ethylglucuronide can be formed and will be eliminated (along with some ethanol) into the urine. In summary, if someone is choosing to take in ethanol in this manner, it will still be metabolized through traditional pathways that may result in positive EtG findings. The EtG results would be dependent upon the time from exposure, amount etc., all of the same things that would need to be considered if alcohol was ingested in a liquid form through drinking.”
Incidental exposure to ethanol in the environment?
What about incidental alcohol use, such as in food, mouthwash, communion wine, etc?
This is an important question and an important issue to understand. Ethanol, unlike other drugs, is fairly ubiquitous in our environment. It's in food (ie vanilla extract). It's used as solvent in "over-the-counter" meds. It's used in ceremonies (ie communion, etc). It is recommended that anyone being tested (i.e. those in monitoring following alcohol problems) be advised that they should not consume food containing alcohol, avoid OTC meds containing alcohol, mouthwash with alcohol, and/or communion wine or anything else containing alcohol. It is possible in some circumstances that the urine EtG level could exceed the cutoff levels by this type of "non-beverage alcohol" exposure.
Reliability and legal status of EtG testing?
Is EtG dependable enough to rely on a positive determination to take legal action, such as revoking a license?
EtG appears to be highly specific, similar to testing for other drugs. It is a direct metabolite and is only present in urine following exposure to alcohol. However, no forensic toxicology test is 100% reliable. Therefore, we strongly recommend that for all urine tests found to be positive that the individual be referred for in-depth clinical evaluation. It is important with any laboratory test to obtain clinical correlation!
Confirming positive urine alcohol by EtG testing?
Should an EtG always be performed to confirm a positive urine alcohol test?
Urine alcohol as an indicator of alcohol consumption can be falsely positive secondary to in-vitro fermentation. Therefore, tranditionally, whenever there's a positive urine alcohol, labs have examined the specimen for glucose and yeast, which can suggest the possibility of fermentation. However, the presence of glucose and yeast doesn't prove the individual did not drink alcohol. In addition to false positives from fermentation, there's also been a question of positive urine alcohol tests due to "incidental" alcohol exposure (i.e. mouthwash, food, otc meds, etc). There is no data on this subject.
In-vitro fermentation can cause a positive EtG because bacteria and metabolize alcohol into EtG. This has not been shown with EtS proving the importance of performing EtS and EtS together whenever possible. Testing all positive urine alcohol samples for EtG and EtS makes sense.
Here is a suggested protocol: For a positive urine alcohol, confront the individual regarding the positive test. If they admit to drinking alcohol, of course you don't need to test further. If they deny use perform an EtG/EtS on the sample. If the EtG and EtS is negative consider the urine alcohol a false positive. (This doesn't actually prove it is a false positive, however, it substantially increases the likelihood.) If the EtS is positive, let them know you now have further proof they consumed alcohol (a positive urine alcohol and a positive EtG). The manner of approaching them in this situation matters. Using language such as, "we now know you did drink alcohol and it's not the end of the world, we just want to get you some help.". Click <here> to see decision flowchart.
EtG and CLIA?
Is EtG waived for CLIA?
CLIA, Clinical Laboratory Improvement Amendment, is an act that regulates "certification" for labs, and does not involve individual tests, therefore the answer is no.
Why are cutoff values different from different labs?
Re cutoffs values: The primary cutoff is a lab procedure to assure technical accuracy of the test. Depending on the technique and its accuracy the cutoff level reduces potential error from intrinsic variations from the test procedure. For these purposes labs believe they can substantiate the quality and validity of testing using a cutoff of 100 ng/ml. There is always a tension between sensitivity and speicificity, false positives and false negatives. The cutoff values should not be so low that the test picks up extraneous alcohol intake (food, mouthwash, etc) resulting in "false positives." On the other hand it is not desirable for the threshhold to be too high, which reduces sensitivity, and would create more false negatives.
Also, we know that very little alcohol (.02-.06%) is metabolized by non-oxidative glucuronidation. The "standard drink" in the USA is 14gm (about 1.5oz of vodka, 12oz beer, 5oz wine). Thus the small fraction of alcohol actually metabolized this route means that a significant amount of alcohol would have to be consumed to register positive even with a cutoff of 100 ug/L.
Click here to see a graph of EtG levels over time in an individual who drank 9gm of alcohol (~1 oz). (By the way, what substance abuser in their right mind would only drink one oz of alcohol.) Based on this single case EtG can be detected for about 30 hours with no "cutoff." If the cutoff were 250, EtG would be detected for about 14 hours after the drink. If the cutoff were 100, EtG would be detected for about 25 hours. Thus you can see how much better the 100 cutoff is, with almost twice the "time of detection," which is why EtG is valuable in the first place, to try and extend the detection time.
The 100 ng/ml cutoff is better for monitoring purposes, as long as clinical judgement is used in assessing the meaning of positives. More research and testing are underway and more data is needed and hopefully will be available soon.
EtG stability - cooking, etc?
Is EtG heat labile? (ie Does a positive EtG and a negative alcohol suggest cooking with alcohol as a source or just a lower level of exposure?)
EtG and EtS are not very heat labile (ie they withstand heat pretty well). Cooking with alcohol could cause positive EtG or EtS.
Medications causing false positives?
Are there any meds that would give a positive EtG?
So far only ethyl alcohol seems to produce EtG or EtS. The issue is really more where did the alcohol come from? Many medications include ethanol as a solvent (cough syrup, etc) and therefore could cause very low level of EtG or EtS..
Polyethylene glycol and EtG?
What about polyethylene glycol? Can it cause a positive EtG?
Probably not but no studies to our knowledge! Polyethylene glycol can be found as an ingredient in various tablets and OTC meds. There is no evidence that degradation of this compound produces ethanol, especially in enough quantity to cause a positive EtGEtS test.
Does the cutoff need to be increased?
If further research has shown some individuals producing higher quantities of ETG with incidental use, and the difficulty having a precise exact cut-off, will this change the current cut-off levels? How can it be assured the positive value of >100 or >250 (as currenty used)is from actual beverage alcohol intake? Is it possible the cut-off levels will change considering this new finding?
There is no known cutoff that distinguishes between drinking alcohol and other exposures to alcohol at this time.
Please clarify for me the units of measured urine EtG levels.
Please clarify for me the units of measured urine EtG levels. In the discussion of incidental exposure, you refer to 100-500 micrograms/liter as being possible incidental exposure but that it would unlikely be incidental at > 500 micrograms/liter. Then in a later discussion regarding laboratory cutoffs you refer to 100 mg/liter. Since the difference here is huge, I ask that you please clarify. In other points in your presented literature and discussions you also refer to nanograms/ml which would be equal to to micrograms/liter. The use of different unit values makes it very hard to draw conclusions. Thank you for the opportunity to read all the information presented in your web site.
Yes, the difference is 1,000. Sorry, there was an error. I've now corrected it. Some of the confusion stems from the fact that the european literature uses lower figures. For example in the European literature .4 mg/L or = .4 ug/ml and in the USA the same amount would be expressed as 4000 ng/ml or 4000 ug/L.