Random Tox Fact of the Week (RTFOW; thanks to Ken Spaith for this nugget of knowledge): Perfluoroalkyl and polyfluoroalkyl (PFAS) are compounds used extensively in non-stick surfaces, stain resistant textiles, as well as water proofing for outdoor gear, such as GoreTex™. One way to think of them is as fluorinated surfactants: Even though fluorine is the most electronegative element, their electron clouds are balanced so that they are super lipophilic and extremely hydrophobic. Exposure usually occurs through either contamination of drinking water near a manufacturing plant or through chronic consumer-level exposure; such as, scraping of a non-stick surface into food as it is being cooked or through leaching of the PFAS from clothing into the skin. PFAS exposure has been associated with asthma, hepatotoxicity, renal-toxicity, ulcerative colitis, pre-eclampsia, thyroid dysfunction, testicular CA, hyperlipidemia, and increased serum uric acid levels. The molecules are usually not formally charged, and due to this fact, they are not covalently bound to the surfaces on which they are sprayed; which means, they can relatively easily contaminate the users of products containing PFAS.

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The subject of this week’s Random Tox Fact of the Week (RTFOW) is Thienodiazepines, which are benzodiazepine analogs. Essentially, the benzene ring of the benzodiazepine class has been substituted for a triazolo moiety. Etizolam is the most readily available thienodiazepine. See structures below. A cursory review of the literature indicates that etizolam may have an equipotent pharmacodynamic effect to alprazolam

Many are unscheduled by the DEA and are readily available over the internet. For the curious: here is one place to get tablets. https://www.etizolab.com/product/etilaam/

AND here is one place to get powder: https://www.chemicalfrog.com/product/etizolam/ 

You can get 1 kg of powder for approximately 10,000 $USD. 1 kg has 1,000,000 single mg doses. If pressed and sold “xanny bars” on the street, only 1 kg would have a street value to 2 to 5 million $USD. Just food for thought: perhaps these need to be regulated and schedule in the US, and maybe we should be looking for these substances in seized counterfeit pharmaceuticals.

Etizolam

Diazepam

images are public domain

I have seen many people, including health care professionals, who are utilizing self-purchased PPE. When healthcare professionals use their own PPE, the PPE may not adhere to the standards set up by hospital infection control committees. One such glaring example I have seen in and out of the hospital is the use of N95 respirators with 1-way valves.

Effectively, the wearer breaths filtered air, but when exhaling, the 1-way valve opens allowing for un-filtered and, therefore, easier exhaust of the exhaled breath. This means N95’s with 1-way valves protect the wearer, but do not protect patients or the public. As such, if no other respirator is used, a surgical mask should be placed over the 1-way valve to prevent transmission should the wearer be in the active stages of a COVID-19 infection.

Below are some examples of N95 respirators with 1-way valves:

My Foray into YouTubing, what better time than now.

Background: Wells Brambl, MD is an emergency medicine physician and medical toxicology fellow in New York. In this 16 minute lecture, I summarize the virology of, diagnostic approach and limitations to, and emerging treatments for COVID-19. This lecture consists of my own interpretation of the data and opinions only. It does not reflect the institutions I work for, nor does it constitute medical advice. If you think you have symptoms and need a medical evaluation, see a doctor.

Based on the formula:

MeasuredOsm= 2*[Na] + [Glu]/18 +[BUN]/2.8+[EtOH]/4.6+[MeOH]/3.2+[Ethylene Glycol]/6.2

This calculator will estimate the max serum concentration of a single toxic alcohol if that is contributing to an osmolar gap. Please note it is possible for a patient to ingest both ethylene glycol and methanol. Serum estimations in the setting are impossible and a true serum concentration would be needed. Finally, not all elevated osmolar gaps are due to toxic alcohols.

Recently published work by Ernstgård, et al has shown that after 15 minutes, the false positive rate for a breathalyzer approaches zero. In a nut shell, the authors exposed healthy male and female volunteers to both inhaled ethanol (to mimic a workplace exposure) as well as commercially available ethanol containing mouthwash (21.6% EtOH w/w).

Their results show that neither scenario resulted in a significant elevation of blood alcohol concentration (BAC) at 15 minutes.

The study is available in Clinical Toxicology’s June 2019 release: https://www.tandfonline.com/doi/full/10.1080/15563650.2019.1626868

Interestingly, the elimination of mouth wash ethanol and inhaled ethanol appear to follow first order kinetics, which makes sense from a theoretical point of view. First and foremost, these study participants had no exogenous ethanol on board, so the elimination of ethanol from the oral cavity would be a combination of absorption and evaporation, both of which are concentration dependent in small quantities. Whereas, when ethanol is ingested in recreational doses, alcohol dehydrogenase becomes saturated, which results in linear, zero order kinetics.

In New York, it is standard practice for the arresting officer to wait 20 minutes from the time of a traffic stop, a smoked cigarette, observed imbibing of alcohol, chewing gum, or use of ethanol containing mouth wash prior to administration of a roadside breathalyzer test. When combined with the evidence presented in this limited study, this practice appears to nullify the possible legal defense that the client used ethanol containing mouthwash, resulting in a false positive BAC measurement.

This study is far from definitive in the sense that it is not a randomized control trial. The researchers were not blinded. Participants were not blinded. There was no control group (eg alcohol free mouth wash). Therefore, the scientific methodology of this study is too limited to make definitive conclusions. Furthermore, the study only exposed volunteers to 20 mL of Listerine mouthwash for 30s. This is not a very large exposure. Would someone who gargled an entire mouthful of mouthwash have had higher levels for longer amount of time? The study completely fails to address this fact, and as such could not necessarily be used successfully in a court of law to negate the mouthwash defense.

However, that is not how the law works. Criminal law is based upon a preponderance of evidence and proof beyond a reasonable doubt that the client is guilty. So, if we think that principles of the paper are most likely right, then it can stand up in court as the prosecutions counter argument to the mouth-wash argument in DUI defense.

However, there is a critical point that the authors of the paper fail to discuss. The kinetic model of this paper seems to suggest that at 20 minutes residual ethanol from the mouth wash could give a BAC reading of 0.01%. What if a client has a true BAC of 0.07%, but they used mouth wash and are breathalyzed at 20 minutes? At the time of measurement, they may be above the legal limit in terms of breathalyzer measured BAC, however their true serum BAC would be below the legal limit.

As a result, the kinetics used in this paper could be used to completely negate beyond a reasonable doubt the prosecution’s assertion that the serum BAC was truly above the legal limit. So, it would seem that law enforcement officers should check the breathalyzer BAC at 20 minutes and then again 20 minutes later to ensure an accurate estimation. A one time reading at 20 minutes could truly be below the legal limit if the client just used mouthwash and had exogenous ethanol in their blood stream. So, this kinetic data could be used as a valid defense for clients with a breathlyzer BAC above, but near the legal limit, and who had used any ethanol containing mouth freshening agent.

It is important to note, that the legal limit in Sweden of 0.02% BAC is much lower than in the United States. In their case, it is even more conceivable that a person could have had 1 drink, metabolized some of that drink and then use a mouth freshening agent upon being pulled over. So, a difference of 0.01% at 20 minutes, could even more easily be the difference between a DUI arrest or not.

Figures reproduced under Creative Commons 4.0 license:

Ernstgård L, Pexaras A, Johanson G. Washout kinetics of ethanol from the airways following inhalation of ethanol vapors and use of mouthwash. Clin Toxicol (Phila). 2020;58(3):171-177.

Poster presentation by Mark Huang, MD and Josh Nogar, MD