Hello again, and welcome to this brief overview of the Diamondback Rattlesnake! I’m Stacey, and I chose this animal to discuss based on a curiosity many years in the making. Once upon a time, I was visiting family in South-Eastern Arizona. We went for a hike, and around sunset on the way back we had to take an extensive detour through a more open area. When I asked why, I was told “Just listen…”. The silence of the desert was periodically broken a very distinct rattling sound, sometimes too close for comfort. We changed into the thick rubber boots we had packed, and carefully followed the path home. It wasn’t until years later that I really understood the risks in the area we were exploring; it was home to Diamondbacks (not just a baseball team!)

This blog attempts to explain some of the toxicity factors associated with this poisonous viper. Please be advised; the media in the content below are derived from both multimedia and published literature. Figures with numeric representation are those found in the corresponding literature, those with alphabetic representation are derived from multimedia. Enjoy!

• Introduction (1)

• • The Diamondback Rattlesnake a member of the Viper family, and is the longest and heaviest snake in North America
    • Average length can be 3-6 feet, with some as long at 8ft
    • This bulky species has large heads, and can weigh 10lbs on average
  • There are two sub-classifications of the Diamondback Rattlesnake in the US; the Western Diamondback (crotalus atrox) (a), and the Eastern Diamondback (crotalus adamanteus) (b)
    • 

      (a) The Western Diamondback Rattlesnake

      

      (b) The Eastern Diamondback Rattlesnake

      Both have a distinct diamond dorsal pattern, however due to habitat the pattern of the Western Diamondback tends to be much lighter in comparison. Colors can range from light tan to red depending on where they are found.

  • As you can see from the territory map in image (c), the range of Diamondbacks is mostly limited to the southern regions of the US, and is dwarfed in comparison to the Prairie and Timber rattlers. However, despite their limited territory, these snakes are ranked as the third most venomous in the US. Acute toxicity can occur in minutes to hours depending on the volume of venom introduced, and can be fatal if not treated appropriately.
    

    (c) Territory Map for Rattlesnakes in the US

• Source (2, 3)

• • The toxin itself comes from the snake venom
  • Venom is produced by organs that evolved from salivary glands
    • Non-toxic saliva contains enzymes that help to breakdown and digest food as it is chewed. Snake saliva includes enzymes that are highly toxic
  • Venom is introduced to the body via two fangs when the snake bites its victim

This video (d) gives a little bit of the background on Diamondbacks, as well as a short demonstration on how the venom is extracted through a process called “Milking”. Milking extracts the venom of a snake for the purpose of study and antivenom production.

(d)

• Biotransformation (2, 3)

• • Diamondback venom is hemotoxic; meaning it destroys red blood cells, disrupts clotting, and can cause organ degeneration with generalized tissue damage
  • The venom is a complex mixture of over 50 identified metals, macromolecules, and proteins. Each component had a different effect.
    • Two components of this mixture that have been well studied are phospholipase A2 toxins and metalloproteinases
      • Phospholipase A2 toxins demonstrate myotoxic, anti-coagulant, and neurotoxic effects
      • Metalloproteinases are thought to be key contributors to local tissue damage and hemorrhage

 

• Toxicokinetics (5, 6)

• • Absorption typically occurs from direct injection of the venom into the skin or muscle. Lymphatic vessels transport the venom into the blood stream and lymph system
  • Distribution is systemic and rapid once the venom reaches circulation
  • Metabolism of venom is still poorly understood, as envenomation is typically directly associated with lymphatic circulation and kidney damage
  • Elimination is also poorly understood. Current theories believe venom is excreted mostly through urine based on in-vivo evaluations examining the pharmacokinetics of antivenoms

 

• Carcinogenicity

• • It is currently unknown whether Diamondback Rattlesnake venom is a carcinogen

 

• Mechanism of Action (3)

• • The exact mechanism of action for Diamondback venom is unknown, however the generally accepted theory revolves around the mechanisms for phospholipase A2 toxins and metalloproteinases
    • As previously stated, phospholipase A2 toxins are multi-faceted. When considering the neurologic effects, these toxins are thought to inhibit neuromuscular transmission at the presynaptic level via blockage of presynaptic calcium-channels of the neuromuscular junction. This can lead to muscle group paralysis if concentrations are high enough. In terms of myotoxicity and anti-coagulant effects, phospholipases are also thought to damage platelet membranes. This can lead to platelet destruction and thrombocytopenia
    • Metalloproteinases are thought to be capable of cleaving peptide bonds of basement membrane components within capillary beds. This affects the interaction between basement membranes and endothelial cells, resulting in an altered morphology of endothelial cells and gap formation causing extravasation, or the leakage of blood, lymph, and other fluids from blood vessels. It is also thought that metalloproteinases from venom are capable of inducing myonecrosis in skeletal muscle and inducing the release of TNF-α, a local inflammatory response that characterizes snakebites.

 

• Target Organ(s) (2, 4)

• • Diamondback venom is toxic whether localized to the site of the bite or systemic as the venom breaches the lymphatic system
    • The venom is hemotoxic, and can cause significant damage to the heart, lungs, liver, spleen, and kidneys before causing damage to other organs/systems. Image (f) below provides a visual representation of the affected organs/systems

• Biomarkers (3, 7)

• • There is no diagnostic test to diagnose or identify the species causing envenomation. Key components for identification of venom are the presence of fang marks on the patient, and a history of their geographical location when bitten. The location will help clinicians identify the most likely species.
  • Frequent bloodwork is helpful for snakebite management. This includes;
    • Complete Blood Count (CBC)
      • Values for hemoglobin and platelets are indicative of red blood cell death or damage
    • Serum Chemistry
      • Altered blood gasses and electrolytes can indicate the degree of blood cell damage
    • Coagulation Panel
      • INR greater than 3.0 and PTT greater than 50 seconds are indications for clotting abnormalities
    • Fibrinogen
      • Low levels of this clotting factor can indicate hemolysis
    • Creatine Kinase (CPK)
      • CPK levels can indicate to severity of kidney damage from myotoxicity
    • Urinalysis
      • Evaluation for myoglobinuria, which can help assess for rhabdomyolysis, or the release of proteins and electrolytes into the blood from damaged muscle tissue

 

• Signs and Symptoms of Toxicity and Accompanying Treatments (3, 4, 9)

• • Signs and Symptoms of Acute Toxicity
    • Minimal envenomation requires no antivenom, but repeated labs and overnight monitoring
      • Swelling, pain, and bruising limited to site of bit
      • No systemic signs
      • Normal coagulation parameters or isolated mild alterations without clinically significant bleeding
    • Moderate envenomation typically requires antivenom in infrequent repeat dosing with repeated labs and several days of monitoring
      • Swelling, pain, and bruising greater than site of bite, but less than a full extremity or less than 50cm in adults
      • Systematic symptoms such as vomiting, mild hypotension, and mild tachycardia
      • Abnormal coagulation parameters without clinically significant bleeding
    • Severe envenomation requires immediate antivenom with frequent repeat dosing, frequent labs, and extended monitoring (days-weeks)
      • Swelling, pain, and bruising involving an entire extremity (or more) or threatening the airway
      • Systemic signs including altered mental status and hemodynamic instability
        • Additional systemic signs include hypotension, bleeding, oozing from IV sites, vomiting, diarrhea, angioedema, and neurotoxicity
        • Assessment for facial edema include tongue swelling and respiratory distress
      • Abnormal coagulation parameters with clinically relevant bleeding

• • Treatment for all degrees of Acute Toxicity
    • The greatest success for treatment relies on the immediate immobilization of the bite area to prevent the venom from spreading systemically through the lymph system
    • The bite area should be marked and monitored frequently for signs of spreading swelling and redness
    • There are two antivenoms currently approved for use in North America:
      • Crotalidae Polyvalent Immune Fab (CROFAB)  is an antivenom derived from the Western Diamondback, Eastern Diamondback, Mojave Rattlesnake, and Cottonmouth Rattlesnake. This compound is ovine derived, meaning it was initially immunized into sheep. The whole immunoglobulin is extracted and purified, then cleaved by papain into the terminal Fab fragment of the immunoglobulin. This agent is cleared through the kidneys and requires multiple doses via IV
        • This link (h) will take you to BTG Pharmaceuticals Information Page on CroFab; a video is included to demonstrate how this antivenom works
      • Crotalidae Immune F(ab)2 is an antivenom derived from the Bothris aspir and Crotalus duressis species. The compound is equine derived, meaning it was initially immunized in horses. The whole immunoglobulin is extracted, purified, and cleaved by pepsin digestion into fragments with two binding sites for venom; -F(ab)2. This molecule is larger than Crotalidae Polyvalent Immune Fab and remains in serum for longer periods of time, requiring less maintenance dosing

 

• • Signs of Chronic Toxicity and Associated Treatments
    • Complications have been noted following envenomation, despite the introduction of antivenom therapy. These issues tend to be chronic;
      • Hypersensitivity inducing anaphylaxis or anaphylactoid reactions to the antivenom. Delayed hypersensitivity reactions or serum sickness can also occur. Treatment for serum sickness is typically oral steroids
      • Necrosis is another well-known complication associated with rattlesnake bites. This is commonly managed with operative debridement or amputation in serious cases
      • Infection can correspond with tissue necrosis, and is rare to occur on its own. Treatment consists of anti-infective agents, surgical debridement, or amputation
      • Compartment Syndrome is a painful and dangerous condition in which pressure from internal bleeding and swelling of tissues builds within the muscles. This is characterized by pain, pale skin tone, numbness, faint pulse, and weakness with movement. Treatment typically includes repeated doses of antivenom, or surgery to relieve the swelling and pressure.
      • Rhabdomyolysis can be induced from the venoms myonecrotic capabilities. Kidney injury is also correlated. Monitoring for kidney injury is done through chemistry labs analyzing CPK. If CPK levels rise over hours to days following envenomation, the extremity should be evaluated for compartment syndrome and repeated doses of antivenom should be administered
      • Delayed venom effects occur in roughly half of Diamondback bite victims. This can include local swelling, delayed onset or recurrence of coagulopathy up to two weeks following the initial bite. Treatment is typically repeated doses with antivenom

 

• • The most effective method for the Diamondback Rattlesnake monitoring is avoidance!
    • People in the Diamondback Rattler territories should be aware of the distinct rattling sound from the snake’s tail and move away from the area slowly (see video (f) below!)
    • Seek medical treatment immediately following envenomation
      • Do not attempt to move or kill the snake
      • Tourniquets, ice, wound laceration, manual venom removal, and wound cauterization are methods made popular by the media – but should be completely avoided!

This video (f) shows the behavior expected by a Diamondback when it feels threatened. Be sure to turn your sound on to hear the rattle!

(f)

 

• Genetic Susceptibility or Heritable Traits

• • Diamondback Rattlesnake venom is chemically and biologically unbiased towards its’ victims. All who are bitten are at risk for toxicity.

 

• Historical or Unique Exposures (7,8)

• • Snakes tend to be more active at dawn and dusk during warm weather. Many recorded bites occur most prevalently during the late spring to early summer in early morning or early evening hours
  • According to ABC News, snake bites in Texas showed a 54% increase during 2020. Authorities attributed this phenomenon to an increase in people engaging in outdoor activities due to the Covid-19 Pandemic

 

• Essentiality and Deficiency

• • Diamondback Rattlesnake venom is not essential. Total deficiency in this case is the safest option!
    

    (g) Warning Sign for Reptiles

     

 

 

 

 

 

 

Content References:

Links to each can be found by utilizing the hyperlink included

1. OutdoorHub. 10 Most Venomous Snakes in North America. Land.com. Published July 1, 2017. https://www.land.com/lifestyle/most-venomous-snakes-in-north-america/. Accessed July 16, 2022

2. Hodgson E. Chapter Fourteen – Toxins and Venoms. ScienceDirect. Published January 1, 2012. Accessed July 16, 2022. https://www.sciencedirect.com/science/article/pii/B9780124158139000143

3. Patel V, Kong EL, Hamilton RJ. Rattle Snake Toxicity. PubMed. Published 2020. https://www.ncbi.nlm.nih.gov/books/NBK431065/

4. Dhar D. Compartment Syndrome Following Snake Bite. Oman Medical Journal. 2015;30(2):146-146. doi:10.5001/omj.2015.32

5. Sanhajariya S, Duffull S, Isbister G. Pharmacokinetics of Snake Venom. Toxins. 2018;10(2):73. doi:10.3390/toxins10020073

6. Rivière G, Choumet V, Saliou B, Debray M, Bon C. Absorption and Elimination of Viper Venom after Antivenom Administration. Journal of Pharmacology and Experimental Therapeutics. 1998;285(2):490-495. Accessed July 16, 2022. https://jpet.aspetjournals.org/content/285/2/490.long

7. Xu MH, Li J, Han L, Chen C. Persistent fibrinogen deficiency after snake bite: A case report. World Journal of Clinical Cases. 2021;9(33):10355-10361. doi:10.12998/wjcc.v9.i33.10355

‌8. Emma. Snake Bite Statistics In 2021 — Rates, Deaths & More. Published August 9, 2021. https://pawsomeadvice.com/wild/snake-bite-statistics/. Accessed July 16, 2022

9. Venomous Snakes: Employer & Worker Recommendations | NIOSH | CDC. www.cdc.gov. Published September 14, 2021. https://www.cdc.gov/niosh/topics/snakes/recommendations.html. Accessed July 16, 2022
‌

Multimedia References:

Links to each can be found in the hyperlinks listed below

a. Eastern Diamondback Rattlesnake Survey. NCASI. Published October 7, 2014. . https://www.ncasi.org/resource/eastern-diamondback-rattlesnake-survey/. Accessed July 16, 2022

b. Western Diamondback Rattlesnake Fact Sheet. Desertmuseum.org. Published 2019. https://www.desertmuseum.org/kids/oz/long-fact-sheets/Diamondback%20Rattlesnake.php.  Accessed July 16, 2022

Hello! And welcome to this brief overview of Sulfuric Acid! My name is Stacey Dillion, and I am here to present a few facts on this corrosive solvent.

I chose this topic based on what can only be described as a series of unfortunate events. Long ago in a kingdom far far away, I was working in a lab where this solvent was a frequent visitor. I would love to explain why, but my confidentiality agreement is outstanding until at least 2028. Long story short; a large bottle dropped, someone was burned through their Tyvek suit and rubber boots, and we watched the drain cover begin to sizzle as the acid went down into the pipes. Facility Hazard Response Teams were less than thrilled, and there was a lot of paperwork. The end!

Please be advised; the media in the content below are derived from both multimedia and published literature. Figures with numeric representation are those found in the corresponding literature, those with alphabetic representation are derived from multimedia.

With any luck, this post will help explain why that series of events was so dangerous, and maybe – just maybe – someone reading this will learn from our mistakes and stay safe!

SO! Without further ado – I present to you Sulfuric Acid!

 

Sulfuric Acid is a highly corrosive substance. It is colorless, odorless, and a viscous liquid that is miscible with water. “Miscible with water” roughly translates to a vigorous exothermic reaction that can boil, spit, and leave painful acid burns if the skin is exposed. 100%, non-diluted sulfuric acid is pictured in image (a)

• Source (1, 3)
  • As the name implies, sulfuric acid comes from Sulphur. Sulphur dioxide is created by molten sulfur in the presence of air.

 

• • Natural sources include the oceans, biological decay, and forest fires. Roughly 75% of released sulfur dioxide is from the burning of fossil fuels. 25-30% comes from burning oil, and the remainder comes from burning coal.
    • Combustion of sulfur dioxide creates sulfur trioxide, which is released into the air. When combined with water, sulfur trioxide becomes sulfuric acid.
    • Sulfuric acid can be suspended in the air for some time, but when it precipitates, it falls as rain. This phenomenon is known as “Acid Rain”
      • 

        (b) The Effects of Acid Rain on The Leshan Giant Buddha

        Image (b) is a photo taken of The Leshan Giant Buddha. This figure was carved out of the hill in the 1st century C.E (Common Era) and has suffered the effects of acid rain for decades.

• • Synthetic sources are lab-created utilizing chemical combinations of sulfur, oxygen and hydrogen. The chemical formula is H₂SO₄.

 

 

 

 

• Biotransformation (1, 3)
  • Sulfuric acid is highly reactive and dissolves most metals
    • It is a concentrated acid that oxidizes, dehydrates, or sulfonates most organic compounds. This often causes charring. For a fun visual, please see the “Added Bonus” section at the bottom of this post and enjoy the video!

 

• • Sulfuric acid reacts violently with alcohol and water, releasing heat
    • If briefly diluted with water, the acid can form a flammable hydrogen gas. This is typically considered an explosion hazard.

 

• • This acid is not combustible, but it is a strong oxidizer. Meaning; sulfuric acid does not burn, but it enhances the combustion of other substances.

 

• • Biotransformation in this case is not limited to whether the acid becomes structurally modified. Toxicities result as a catalyst for the reaction of sulfuric acid with water and/or oxygen
    • This is due to pH changes rather than the sulfate itself

 

 

• Toxicokinetics (3)
  • Absorption can be through direct contact (skin) or via inhalation
    • Clearance through the lungs can be very rapid depending on the dose exposed

 

• • Distribution can be difficult to determine as sulfate is a normal constituent of blood and toxicity is (typically) solely limited to local contact vs. systemic circulation

 

• • Metabolism can also be difficult to determine based on the normal presence of sulfur in blood. Sulfur trioxide in contact with water forms sulfuric acid with the evolution of heat. In the absence of extreme heat (roughly 450◦F) and continued exposure to water, sulfuric acid will dissociate into hydrogen ions and hydrogen sulfate ions, which are combined throughout the body. Sulfate does not need to be further metabolized to be excreted.

 

• • Excretion of sulfuric acid following dissociation is through urine

 

• Carcinogenicity (4)
  • Chronic exposure of sulfuric acid through mist or inhalation can often go unnoticed, however the International Agency for Research on Cancer (IARC) has classified this solvent as a Group 1 carcinogen.
    • Group 1 carcinogens claim sufficient evidence of cancer-causing capabilities in humans

 

• Mechanism of Action (3, 4)
  • The effects of sulfuric acid are due to the presence of the H+ ion and pH changes rather than the sulfate itself.
    • The number of hydrogen ions in a strong acid is reduced, thus causing the pH to lower.

 

• • Toxic effects of sulfuric acid are localized to the point of contact (skin, eyes, mouth) and are due to the protonation of protection molecules like keratin.
    • This weakens the surface of the tissue and makes it more susceptible to damage
      • The images for the effects of sulfuric acid on skin are quite graphic. I will let each reader search at their own discretion, however image (e) below is an example of a minor chemical burn that an occur in rapid time. Please understand that what you see is considered minor, thus any major injury can be deadly. The potential for catastrophic tissue damage is very high. Remember to use extreme precaution when handling.
        

        (e) Minor Effects of Sulfuric Acid on Skin

 

• Target organ(s) (3)
  • Target organs include any that are directly locally exposed to sulfuric acid
    • These typically include the eyes, mouth/teeth/gums and skin
      • The lungs and GI can be affected if the acid is in mist-form and swallowed or inhaled

 

• • Strong inorganic acids are extremely hazardous and can burns to the skin and eyes if direct contact is made.

 

• Signs and symptoms of toxicity (acute and chronic)(2, 4)
  • Signs and symptoms of toxicity are typically acute.
    • Sulfuric acid reacts with tissues and cells on contact.
      • Tissue injury appears within seconds of exposure and can continue for hours if not treated
    • Damage can range from irritation to chemical burns and necrosis at the site of contact
      • The extent of the damage is dependent on the dose received, length of exposure prior to treatment, and the molar concentration (strength) of the sulfuric acid solution
        • the higher the concentration, the greater the extent of the damage.

 

• • Chronic exposure can lead to tissue necrosis and severe chemical burns with scarring. Chronic exposure has also been linked to multiple cancers, including lung and skin, if the acid is in mist form.

 

• Treatments (3)
  • There are no medical tests to determine exposure to sulfuric acid
    • Breathing acid will alter the pH of saliva, but it cannot be determined which acid caused the exposure

 

• • Acute exposures can be treated with mild soapy solutions if the burns are not severe
    • The skin may feel hot, but the continued exposure to water will flush the acid off
    • Severe burns can be treated with continued flushing of the area exposed and standard-wound dressing for burns
      • Patients will likely be in pain, so pain management is also expected

 

• • Chronic exposures are likely unknown until patients present with malignancies. Treatment for sulfuric-acid related cancers would follow the care regimens in place for those specific malignancies

 

• Genetic susceptibility or heritable traits (3)
  • Sulfuric acid is highly acidic; it’s main uses are for the cleaning of metals, removal of impurities in oil, and the manufacturing of chemicals.

 

• • It can also be used in fertilizers, pigments and dyes, drugs, explosives, detergents, petroleum refining, and metallurgy.

 

• • Due to the wide variety of uses, there are no limits for who can be exposed
    • Susceptibility would be greater to those who are working with sulfuric acid directly

 

• • No heritable traits have been identified in those exposed to sulfuric acid

 

• Historical or unique exposures (5)
  • In 1984, scientists deliberately acidified Little Rock Lake, Wisconsin. The pH was intentionally decreased from 6.1 to 5.6, 5.1, and 4.7. The lake was allowed to recover from the fall of 1990. Image (c) demonstrates the pH scale of commonly found materials.

• • The experiment was conducted to evaluate the environmental effects of high acid and the natural acid neutralizing capacity (ANC) of the inhabiting fish populations. Image (f) is a photo of the aftermath.
    • While some recovery was observed, researchers believe the recovery has not closely followed the patterns predicted and several species are unable to fully reproduce as they would have without manipulation of their natural environment
      

      (f) Little Rock Lake, Wisconsin

 

• Biomarkers (6)
  • Acidity is the best indication for the presence of sulfuric acid in the environment
    • Measurement and monitoring for sulfuric acid is typically conducted by the Environmental Protection Agency (EPA). The greatest cause of concern is acid rain
      • Rain typically has a pH of around 5.6; it is slightly acidic due to carbon dioxide
      • Acid rain has a pH between 4.2 and 4.4
    • Monitoring is typically the task of the National Atmospheric Deposition Program’s (NADP) National Trends Network (NTN)
      • The NADP/NTN collects rain at more than 250 sites worldwide and measures for pH
    • Soil is also measured and monitored by the Clean Air Status and Trends Network (CASTNET)
      • The nitrogen and sulfur pollutants are provided from more than 90 world-wide locations

 

• Essentiality and deficiency 
  • Sulfuric acid has many uses and is an effective solvent when utilized under the proper conditions. However, due to its extreme corrosive potential, harmful environmental effects, and carcinogenic capabilities, I cannot in good conscience identify this solvent as essential. It seems that deficiency is more favorable.

 

• Added bonus
  • This video shows multiple items exposed to sulfuric acid. It doesn’t really “get good” until about 2 minutes in, so please have some patience. Please also don’t do what this guy did and handle these materials with bare hands! If you take nothing else away from this post, just remember that sulfuric acid is extremely corrosive and will cause injury. Wear gloves, wear eye protection, and always have a large source of clean water close by!(d)

 

Content References:

1. Saeid, A., and K. Chojnacka. “Sulfuric Acid.” ScienceDirect, Academic Press, 1 Jan. 2014, sciencedirect.com/science/article/pii/B9780123864543009908. Accessed 01 JULY 2022.

 

2. Robles, Heriberto. “Sulfuric Acid.” ScienceDirect, Elsevier, 1 Jan. 2005, sciencedirect.com/science/article/pii/B0123694000009121. Accessed 01 JULY 2022.

 

3. TOXICOLOGICAL PROFILE for SULFUR TRIOXIDE and SULFURIC ACID Agency for Toxic Substances and Disease Registry. 1998. https://www.atsdr.cdc.gov/ToxProfiles/tp117.pdf Accessed 01 JULY 2022.

 

4. Yang JH, Koedrith P, Kang DS, et al. A Putative Adverse Outcome Pathway Relevant to Carcinogenicity Induced by Sulfuric Acid in Strong Inorganic Acid Mists. J Cancer Prev. 2019;24(3):139-145. doi:10.15430/JCP.2019.24.3.139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786810/

 

5. Sampson, C.J., Brezonk, P.L., Frost, T.M. et al. Experimental acidification of Little Rock Lake, Wisconsin: The first four years of chemical and biological recovery. Water Air Soil Pollut 85, 1713–1719 (1995). https://doi.org/10.1007/BF00477227

 

6. United States Environmental Protection Agency. “What Is Acid Rain?” US EPA, United States Environmental Protection Agency, 12 May 2020, www.epa.gov/acidrain/what-acid-rain.

 

Multimedia References:

(a) “Tips for the Process Measurement of Sulfuric Acid from 0 to 110 Percent.” Www.process-Worldwide.com, process-worldwide.com/tips-for-the-process-measurement-of-sulfuric-acid-from-0-to-110-percent-a-827001/.

 

(b) Affected Landmarks. sahilacidrain706.weebly.com. Accessed July 1, 2022. https://sahilacidrain706.weebly.com/affected-landmarks.html

 

(c) United States Environmental Protection Agency. “What Is Acid Rain?” US EPA, United States Environmental Protection Agency, 12 May 2020, www.epa.gov/acidrain/what-acid-rain.

 

(d) “How Sulphuric Acid Reacts with Different Things.” Www.youtube.com, www.youtube.com/watch?v=DVAbwqlMh1E. Accessed 1 July 2022.

 

(e) “Hydrochloric Acid on Skin: Effects and Treatments.” Skin Care Geeks, 28 Feb. 2020, skincaregeeks.com/hydrochloric-acid-on-skin/.

 

(f) Native plants become a weapon in battle to save algae-choked Little Rock Lake. MPR News. Accessed July 1, 2022. https://www.mprnews.org/story/2019/08/06/photos-saving-little-rock-lake-by-drawing-down-the-water-central-mn

Arsenic is a metalloid occurring in several minerals. It can be found in both organic and inorganic forms, as well as in combination with sulfur and metals. Arsenic is also the topic of this blog post for metal toxicity.

My name is Stacey Dillion, and I chose this metal for – even I will admit – a slightly bizarre reason; I love the musical “Chicago”. When selecting metals for this post, I read the list and a got a very clear mental image of a specific scene after seeing “arsenic” as an option. For that reason, I elected to dive into further research. Please be advised; the media in the content below are derived from both multimedia and published literature. Figures with numeric representation are those found in the corresponding literature, those with alphabetic representation are derived from multimedia.

(there is a link here for the scene itself, but given the…nature…of the content, I’ll leave it at that    ) .

So, without further ado, I present to you an overview of arsenic!

(a)

 

 

• Source (1, 7)
  • Inorganic arsenic compounds are found in soil, sediments, and ground water
    • Occur naturally as a result of mining, ore smelting, and industrial use of arsenic
    • Ground water is the leading source of arsenic exposure
  • Organic arsenic compounds are found mainly in fish and shellfish
    • Organic arsenic compounds are typically considered less toxic than inorganic compounds

 

• Biotransformation (2)
  • Methylation occurs in the body by alternating reduction of pentavalent arsenic to trivalent with the addition of a methyl group from S-adenosylmethionine.
    • Glutathione may also serve as a reducing agent
    • The liver is the most important site of arsenic methylation
    • The end metabolites are methylarsonic acid (MMA) and dimethylarsinic acid (DMA)
      • MMA and DMA are less reactive and excreted in the urine
      • Intermediate reduced forms of MMA and DMA can be formed
        • MMA(III) and DMA(III) are methylated metabolites that are highly toxic and detectible in urine
      • Reactive intermediates may be formed, such as absorbed arsenate (As(V))
        • (As(V)) reduces rapidly in the blood to As(III) and is highly toxic

 

• Toxicokinetics (3)
  • Absorbed through the GI tract
  • Distributes to all tissues
  • Metabolized in the liver
  • Eliminated through bile and kidneys, primarily excreted through urine
    • Elimination can be direct through feces without absorption, or through feces and urine following plasma or tissue absorption

(3)

 

• Carcinogenicity (4)
  • Chronic exposure to arsenic through drinking water has been linked to an increased risk of bladder cancer and skin cancer
  • Medical exposure to arsenic has been linked to skin cancer
  • Cancers of the lung, digestive tract, liver, kidney, lymphatic, and hematopoietic systems have also been linked to arsenic

 

• Mechanism of action (6, 7)
  • The exact mechanism of action is unknown
  • Several theories exist
    • Inorganic arsenic in a pentavalent state may replace phosphate in several reactions
    • Inorganic and organic (methylated) arsenic in the trivalent state may react with critical thiols in proteins and inhibit their activity
    • Potential mechanisms of carcinogenicity include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion
    • Arsenic may inactivate up to 200 enzymes, particularly those associated with cellular energy pathways and DNA synthesis and repair

• Target organs (8)
  

  (c)

  • Kidney and liver
    • Highest concentrations are typically found in the liver (as demonstrated in figure (c) ). Concentrations above 0.01 parts per million (ppm) are considered toxic.

 

• Signs and Symptoms of Toxicity (1,5,7,9)
  • Acute
    • Nausea, vomiting, diarrhea, abdominal pain, dehydration, shock
    • Extreme cases can include numbness and tingling in the extremities, muscle cramping, and death
    • Treatment for acute poisoning includes:
      • • IV fluids and gastric lavage
        • Administration of activated charcoal with a cathartic such as sorbitol is frequently recommended
          • The efficacy of activated charcoal is still under consideration
          • If diarrhea is severe, cathartics should not be administered
        • Hemodialysis may be beneficial if the patient presents with concomitant renal failure
        • Dimercaperol (BAL), DMPS, and DMSA are the most common chelating agents recommended for acute arsenic poisoning
          • These should be used with caution due to their known adverse side effects
  • Chronic
    • Skin disorders, increased risk of diabetes, high blood pressure, several types of cancer
      • Skin disorders can include changes in pigmentation, lesions, and hard patches (hyperkeratosis) of the palms and soles of feet
        • These occur after at least 5 years of chronic exposure and may be a precursor to skin cancer
    • Treatment for chronic exposure includes the removal of high-level drinking water
      • • Substitution of high-arsenic sources with low-arsenic sources such as rain water treated with surface water
        • Identifying handpumps of high-arsenic sources with a different color paint than the handpumps attached to low-arsenic sources, or “do not drink” labels (as shown in figure (d) )
        • Blend high and low sources to achieve a lower concentration
        • Installation of arsenic removal systems
          • Technologies for this technique include oxidation, coagulation-precipitation, absorption, ion exchange, and membrane techniques.
        • There are no evidence-based treatments for chronic arsenic poisoning
          • Antioxidants have been proposed, but their benefit is not proven

(d)

• Genetic Susceptibility or Heritable Traits (5, 8, 10)
  • In utero and early childhood exposure has been linked to cognitive development deficit and deaths in young adults
  • Arsenic exposure has been associated with elevated Reactive Oxygen Species (ROS) and disruption of neuro-skeletal integrity
    • Increased ROS can lead to oxidative stress, DNA damage, dopaminergic neuron degeneration, decreased antioxidant enzymes, and increased lipid peroxidation
      • Associated conditions include impaired learning and memory and Parkinson’s Disease
    • Disruption of neuro-skeletal integrity can reduce nerve conduction velocity leading to peripheral neuropathy and neuropathic pain
    • A visual representation of this is shown in figure 8
  • Data collected from 2011-2012 nutrition examination surveys indicate Asian Americans tend to have significantly higher levels of arsenic detected in their urine as compared to several other races
    • This is thought to be due to dietary patterns
    • A graph representing this data is shown in figure 10

(8)                         (10)

• Historical or Unique Exposures (1, 5)
  • People are most likely exposed to arsenic through drinking water
  • Exposure can also be due to foods such as rice or seafood
  • WHO recognizes at least 140 million people in 50 countries consuming drinking water containing arsenic above the provisional guideline of 10ug/L. A visual representation of countries at risk, as well as those without data, is shown in figure (b). 
  • Arsenic recognition and contamination prevention gathered significant attention in 1990s when Bangladesh was identified to have highly toxic levels found in well-water. Since then, the number of people exposed has dropped by roughly 40%, however in 2012 it was estimated roughly 21% of all deaths in the country were arsenic related.
  • Arsenic poisoning has also been a theme in both fiction and non-fiction. Please see the video at the bottom this post!

(b)

• Monitoring (10, 11)
  • Biomonitoring is used for acute exposure risks rather than chronic
  • X-ray fluorescence is a promising technology used for detecting and measuring inorganic arsenic in soil without requiring aqueous soil extractions

 

• Testing (12)
  • Acute exposures can be tested through urine
  • Environmental testing can be completed through chromatography, optical methods, and mass spectrometry

 

• Biomarkers (10, 13)
  • Acute exposure can be determined by detection of arsenic in the hair, nails, blood, or urine
    • Presence of arsenic in these samples can indicate systemic absorption, but can also be complicated by potential external sources
      • I.E.; arsenic found in samples of nails can be due to systemic absorption or because the patient touched something contaminated with arsenic but never ingested it.
      • Evidence of arsenic in finger nails can be seen with Mees’ Lines, as show in figure (f)(f)

 

• Essentiality (14, 15)
  • Trace levels of arsenic are thought to be essential to grow and maintain a healthy nervous system
    • Levels above 0.00001% are considered greater-than-trace
  • Several animal studies have demonstrated that trace levels of arsenic are essential when methionine metabolism is stressed (pregnancy, lactation), however these results have not been translated to human nutritional guidelines
    • Recommendations based on this article are 12µg/day for humans, however these recommendations have not been substantiated in the 30 years since publication

 

• Deficiency
  • I have not been able to find a single source with substantial evidence of concerns related to arsenic deficiency

 

• Notes of Special Interest
  • Arsenic poisoning is a common theme in both fiction and history – I refer back to my original inspiration for choosing this metal, briefly mentioned in “Chicago”
  • This short video (complete with more rubber ducks than I’ve ever known a single person to own…) gives a brief summary of a few historical and fictional recounts of arsenic poisoning, antiquated methods of arsenic detection, and finishes with a minor rant about the salt content of soy sauce (not related, but the rest of the video is interesting, enjoy!)

(e)

Links to all sources can be found below in Content References:

1) Arsenic Factsheet | National Biomonitoring Program | CDC. www.cdc.gov. Published May 24, 2019. https://www.cdc.gov/biomonitoring/Arsenic_FactSheet.html#:~:text=Inorganic%20arsenic%20compounds%20are%20in. Accessed June 4, 2022

2) Vahter M. Mechanisms of arsenic biotransformation. Toxicology. 2002;181-182:211-217. doi:10.1016/s0300-483x(02)00285-8
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/12505313/

3) Chakraborti, Dipankar & Rahman, Mohammad Mahmudur & Das, B. & Nayak, Bishwajit & Pal, Arup & Sengupta, Mrinal & Hossain, Md & Ahamed, Sad & Sahu, Manabendranath & Saha, Kshitish & Mukherjee, Subhash & Pati, Shyamapada & Dutta, Rathindra & Quamruzzaman, Quazi. (2013). Groundwater arsenic contamination in Ganga–Meghna–Brahmaputra plain, its health effects and an approach for mitigation. Environmental Earth Sciences. 70. 10.1007/s12665-013-2699-y.
To read more, please follow this link: https://www.researchgate.net/figure/Illustration-of-the-absorption-distribution-metabolism-and-elimination-ADME-of_fig1_258168267

4) Arsenic – Cancer-Causing Substances. National Cancer Institute. Published December 31, 2018. https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/arsenic#:~:text=Which%20cancers%20are%20associated%20with
To read more, please follow this link: https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/arsenic#:~:text=Which%20cancers%20are%20associated%20with,skin%20cancer%20in%20epidemiological%20studies.

5) WHO. Arsenic. Who.int. Published February 15, 2018. https://www.who.int/news-room/fact-sheets/detail/arsenic. Accessed June 4, 2022
To read more, please follow this link: https://www.who.int/news-room/fact-sheets/detail/arsenic

6) Hughes MF. Arsenic toxicity and potential mechanisms of action. Toxicol Lett. 2002;133(1):1-16. doi:10.1016/s0378-4274(02)00084-x
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/12076506/

7) Ratnaike RN. Acute and chronic arsenic toxicity. Postgraduate Medical Journal. 2003;79(933):391-396. doi:10.1136/pmj.79.933.391
To read more, please follow this link: https://pmj.bmj.com/content/79/933/391

8) Kaur T, Singh A, Goel R. Mechanisms pertaining to arsenic toxicity. Toxicology International. 2011;18(2):87. doi:10.4103/0971-6580.84258
To read more, please follow this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183630/#:~:text=%5B62%2C63%5D%20The%20kidney,both%20hepatic%20and%20renal%20tissue

9) Arsenic Toxicity: How Should Patients Overexposed to Arsenic Be Treated and Managed? | Environmental Medicine | ATSDR. www.atsdr.cdc.gov. Published February 9, 2021. https://www.atsdr.cdc.gov/csem/arsenic/patient_exposed.html
To read more, please follow this link: https://www.atsdr.cdc.gov/csem/arsenic/patient_exposed.html

10) Biomonitoring Arsenic: Facts and Figures – MN Data. State.mn.us. Published 2009. https://data.web.health.state.mn.us/biomonitoring_arsenic
To read more, please follow this link: https://data.web.health.state.mn.us/biomonitoring_arsenic

11) Monitoring Arsenic in the Environment: A Review of Science and Technologies for Field Measurements and Sensors. Accessed June 4, 2022. https://clu-in.org/download/char/arsenic_paper.pdf
To read more, please follow this link: https://clu-in.org/download/char/arsenic_paper.pdf

12) Rajakovic L, Rajakovic-Ognjanovic V. Arsenic in Water: Determination and Removal. IntechOpen; 2018. https://www.intechopen.com/chapters/61143
To read more, please follow this link: https://www.intechopen.com/chapters/61143

13) Hughes MF. Biomarkers of exposure: a case study with inorganic arsenic. Environ Health Perspect. 2006;114(11):1790-1796. doi:10.1289/ehp.9058
To read more, please follow this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665401/#:~:text=Arsenic%20biomarkers%20of%20exposure%20include,can%20complicate%20the%20exposure%20analysis.

14) Pedersen T. Facts About Arsenic. Live Science. Published July 28, 2016. https://www.livescience.com/29522-arsenic.html
To read more, please follow this link: https://www.livescience.com/29522-arsenic.html

15) Uthus EO. Evidence for arsenic essentiality. Environ Geochem Health. 1992;14(2):55-58. doi:10.1007/BF01783629
To read more, please follow this link: https://pubmed.ncbi.nlm.nih.gov/24197927/

 

Multimedia References:

a) Team HJ. Arsenic sources, arsenic in food and water. Arsenic poisoning symptoms. Health Jade. Published October 21, 2018. https://healthjade.net/arsenic/. Accessed June 4, 2022

b) map_showing_estimated_risk.png. serc.carleton.edu. Accessed June 4, 2022. https://serc.carleton.edu/details/images/150833.html

c) New drug targets for a rare kidney and liver disease. Drug Target Review. Published 2017. https://www.drugtargetreview.com/news/25147/new-drug-targets-kidney-liver-disease/

d) Bangladesh failing to spare millions from arsenic poisoning. Tampa Bay Times. https://www.tampabay.com/news/world/bangladesh-failing-to-spare-millions-from-arsenic-poisoning/2272251/

e) Dr. Joe Schwarcz: All about arsenic. www.youtube.com. Accessed November 13, 2021. https://www.youtube.com/watch?v=7hUw6_t_Y4o

f) Team HJ. Mees lines fingernails causes, symptoms & treatment. Health Jade. Published March 25, 2020. https://healthjade.net/mees-lines/

 

Hello! Welcome to this blog posting on Formamidines. My name is Stacey, and I picked this pesticide based on a complete lack of knowledge over it. I chose this topic at random in the hopes of learning more and sharing what I was able to find. Please be advised; the media in the content below are derived from both multimedia and published literature. Figures with numeric representation are those found in the corresponding literature, those with alphabetic representation are derived from multimedia. Enjoy the read below!

Formamidines

• Source (link here for Reference #1)
  • Derived from formic acid
  • Synthetic compound
    • Includes amitraz and chlordimeform
      • Amitraz is used as an insecticide and pesticide
      • Chlordimeform was used as a pesticide, but has been removed from US markets after demonstrating carcinogenic potential (2)
        

        3D chemical model of Formamidine (1)

         

• Biotransformation (link here for Reference #2)
  • Toxicities associated with formamidines – specifically amitraz – are typically due to exposure by ingestion, inhalation, or dermal contact. Amitraz is classified as follows;
    • Class II – moderately toxic if absorbed through skin
    • Class III – slightly toxic if swallowed or inhaled
    • Class IV – slightly irritating to the eyes, but not a dermal irritant or sensitizer
  • Amitraz is metabolized rapidly to produce 2,4-dimethyl formanilide and active metabolite N’-(2,4-dimethylphenyl)-N-methyl-formamidine
    • This rapid metabolism results in a rapid onset of symptoms

(a)

• Toxicokinetics (2)
  • ADME:
    • Absorbed through skin/orally digested
    • Distributed in the blood stream
    • Metabolized by the kidneys
    • Excreted through urine

 

• Carcinogenicity (2)
  • Formamidines have demonstrated carcinogenic potential in animal species (such as mice)
    • shown an increase in risk for lymphoreticular malignancies and liver adenoma/carcinomas
  • Amitraz is classified as a possible carcinogen in humans
    • risks of genotoxicity, oxidative stress, cell death, immunotoxicity, endocrine disruption, and developmental toxicities are currently under investigation by the FDA
  • Chloridimeform has been classified as a carcinogen in humans and animals since 1977

 

• Mechanism of Action (2)
  • Agonist of a2-adrenergic receptors
    • Activation of these receptors has significant systemic fallout
      • Inhibition of histamine H1 receptors
      • Inhibition of prostaglandin snythase
      • Inhibition of monoamine oxidase
      • Inhibition of calcium ion channel activation
      • Inhibition of cAMP signaling via adenylyl cyclase

 

• Target Organ(s) (2)
  • Endocrine system (see GIF below)

(b; endocrine system)

• Signs and Symptoms of toxicity (acute and chronic) (2)
  • Amitraz can cross the blood brain barrier, affecting both central and peripheral nervous systems
  • Acute toxicity can cause irritation to the eyes, skin, nose, and throat
    • a2-adrenergic receptor activation is depicted by the Toxic Effects Image (below) and can cause:
      • Hypotension
      • Bradycardia
      • Miosis
      • Mydriasis
      • Altered mental status
      • Hypothermia
      • Convulsion
      • Polyuria
      • Gastrointestinal hypomotility
      • Hyperglycemia
  • Chronic toxicity can cause MAO inhibition
    • Motor activity alterations
    • Aggressiveness
    • Neurodevelopmental toxicity
  • Central nervous system depression has been associated with both acute and chronic exposure and is dose-dependent
    • Sleepiness, drowsiness, or complete loss of consciousness

• Treatments for acute and chronic (including monitoring or testing) (2)
  • Testing for formamidine poisoning is typically symptom directed
  • There are no supportive treatments specifically for formamidine poisoning
    • The supportive care includes monitoring respirations, cardiovascular function, and CNS function
    • Contaminated clothing should be removed
    • Skin should be washed with soap and water
  • Activated charcoal has been deemed safe for use with acute amitraz poisoning, but the clinical benefit is yet to be determined
  • Chronic toxicity is treated via symptom management unique to each patients’ presentation

• Biomarkers (3)(image (e))
  • Altered sensorium, miosis, and bradycardia are the three most common markers of formamidine poisoning
    • These are easily confused with organophosphate poisoning
  • Clinical indications such as hyperglycemia, hypothermia, and constipation (reduced GI motility) also support formamidine poisoning over organophosphate poisoning
    • The presence of salivation, lacrimation, perspiration, and diarrhea would indicate organophosphate toxicity

(e)

• Genetic susceptibility or heritable traits (2)
  • Mothers exposed to amitraz have reported toxicities in their offspring
    • Developmental neurotoxicity has been reported
      • Includes altered behavior, neurochemistry, neurophysiology, and gross dysmorphology of the central nervous system

 

• Historical or unique exposures (Link here for Reference #3)
  • Amitraz poisoning is complicated to identify, as the signs and symptoms are consistent with organophosphate poisoning unless specific key complaints are noted
  • A semi-recent systemic review identified only 310 cases out of a wide variety of case studies

 

• Essentiality and deficiency
  • The use of amitraz is not essential
  • Amitraz deficiency is actually a good thing

(c)

 

Additional information can be found in this summary video below. This video specifically highlights the effects Amitraz can have on pets (d)

Information References including images:

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 68047, Formamidine. https://pubchem.ncbi.nlm.nih.gov/compound/Formamidine. Accessed May 17, 2022.
2. Javier del Pino, Paula Viviana Moyano-Cires, Maria Jose Anadon, María Jesús Díaz, Margarita Lobo, Miguel Andrés Capo, and María Teresa Frejo
   Molecular Mechanisms of Amitraz Mammalian Toxicity: A Comprehensive Review of Existing Data Chemical Research in Toxicology 2015 28 (6), 1073-1094 DOI: 10.1021/tx500534x
3. Dhooria S, Agarwal R. Amitraz, an underrecognized poison: A systematic review. Indian J Med Res. 2016;144(3):348-358. doi:10.4103/0971-5916.198723

 

Multimedia References:

(a) https://giphy.com/gifs/reaction-help-leave-t7VHWISa7iN0s. Accessed 17MAY2022

(b) https://giphy.com/gifs/science-biology-labxchange-eCNcFbev3ydP2Vf9SI. Accessed 17MAY2022

(c) http://appleshinenyc.com/too-much-of-a-good-thing-is-bad/. Accessed 17MAY2022

(d) https://www.youtube.com/watch?v=YpS6jLKrFMs. Accessed 18JULY2022

(e) https://www.roshreview.com/blog/ep-11-cholinergic-toxidrome-svc-syndrome-metabolic-acidosis-rosc-acrocyanosis-mushroom-poisoning/. Accessed 17MAY2022

“It Smells Like Almonds…”

A brief history of the 1982 Chicago Tylenol Murders

Abstract

The evolution of pharmaceutical safety can be traced back to several significant events in history. Whether it be the illegal experimentation of people without their knowledge, or the secret tampering of products (just to name a few), the process of protecting human rights and safety is an ongoing battle.

One of the events leading to an evolution in safety was the 1982 Chicago Tylenol Murders. These tragic homicides prompted pharmaceutical giant Johnson & Johnson to rethink how consumers could be protected against malicious intent, and introduced a concept we now know very well; tamper-evident packaging. At the time of the Murders, pill bottles were easily accessible to manipulation throughout the manufacturing process. A fact an unknown individual took advantage of when they chose Tylenol to randomly spike with potassium cyanide.

This post, along with the media clip included at the very bottom, is intended to give a general overview of the few facts that are known about these poisonings, as well as the series of events leading to the discovery and evidence of potassium cyanide toxicity.

Searchable keywords: Johnson & Johnson, Chicago Tylenol Murders, Tylenol, Potassium Cyanide, Almonds, RetroReport

Introduction

The fall of 1982 forever changed the pharmaceutical industry when seven people in the greater Chicago area fell victim to lethal cyanide poisonings. Each of these individuals had ingested what seemed to be standard over-the-counter Extra Strength Tylenol, manufactured by Johnson & Johnson and purchased at local drug stores. Unbeknownst to all, an unidentified individual had laced these bottles, and potentially many more, with fatal concentrations of potassium cyanide. While the perpetrator for these random acts of homicide has yet to be identified, security measures resulting from his/her actions are still in place today. These include additional quality checks of products prior to distribution, increased security within manufacturing, and – perhaps the most beneficial – the presence of tamper-evident seals placed across the openings of pill bottles immediately after they are filled during manufacturing. Additionally, warning labels are featured on every product instructing the user to discard the bottle should that seal appear damaged in any way¹.

Potassium cyanide appears as a white granular or crystal solid, and in the case of the Chicago Tylenol Murders, camouflaged perfectly with the consistency of the tablets. Exposure can be rapidly fatal even with minimal concentrations and has systemic consequences. The hydrogen cyanide gas released by potassium cyanide acts as a toxic asphyxiant, limiting the use of oxygen within the body. Thus, organs that are highly oxygen dependent such as the brain, heart, and lungs, are most detrimentally affected². Symptoms reported by each victim able to communicate before passing included dizziness, confusion, shortness of breath, and headache. However, the cause of death attributed via autopsy was suffocation- despite blood oxygen levels being above normal. It was only after extensive interviews and post-mortem toxicology reports identifying the presence of potassium cyanide that health and police officials were able to establish a commonality¹.

 

Claim (Research Question)

How was cyanide poisoning identified as the cause of death during the Chicago Tylenol Murders of 1982?

Why this topic? (Reason)

I am unashamedly a ‘true-crime junkie’; I was listening to an Apple Podcast and happened to come across “Poisoned Pill – The Chicago Tylenol Murders” on “Unsolved Murders; True Crime Stories”³. As I was listening, I kept wondering “How did they know it was cyanide? How did they figure out it was the Tylenol? How was someone able to poison the pill, weren’t there tamper-evident seals? Could something like this happen again?” This assignment gave me an opportunity to answer those questions.

 

 

 

Poisoned Pill; The Chicago Tylenol Murders

 

 

Evidence

Mary Kellerman – Female, age 12 died Sept. 30, 1982
Adam Janus – Male, age 27 died Sept. 30, 1982
Stanley Janus – Male, age 25 died Sept. 30, 1982
Mary Reiner  – Female, age 27 died Sept. 30, 1982
Mary McFarland –  Female, age 35 died Sept. 30, 1982
Paula Prince – Female, age 35 died Oct. 1, 1982
Theresa Janus – Female, age 19 died Oct. 1, 1982

Series of events:

Firefighter Inspector Richard Keyworth noted Tylenol listed as medications for the first 4 victims. However, this fact is quickly dismissed as “everyone in the world took Tylenol. That didn’t seem out of order” – Keyworth⁶

 

 

 

 

Public Health Nurse Helen Jensen is first to identify a connection between the Janus Family deaths and Tylenol; “I found a bottle of Tylenol and there were six capsules missing – and three people dead. In my mind, it had to be something to do with the Tylenol.” – Jensen⁶

 

Potassium cyanide has an odor similar to that of raw almonds. However, that odor is often undetected and is not a sufficient warning. At best, only 60% of the population might be able to smell cyanide, yet of that 60% a large fraction may suffer olfactory fatigue, making immediate identification even less likely⁵. Fortunately, Cook County Medical Examiner’s Office Investigator Nick Pishos is one of the rare few able to detect the scent of almonds extruded by potassium cyanide. After recovering the bottles of Tylenol from several of the victims’ homes, Dr. Pishos noted a peculiar similarity; all the remaining pills smelled like almonds. He is credited for the second connection and first significant association between Tylenol and all the known poisoning victims.

 

Dr. Thomas Kim, Medical Director of Northwest Community Hospital’s ICU, also deduced cyanide poisoning was the most likely cause of death, however far-fetched the idea seemed. He sent blood for toxicology testing – an act that was thus far uncommon. The reports came back showing 100-1,000 times the minimum lethal dose of potassium cyanide (250mg⁸)

Discussion

Within 24 hours of the first reported deaths, officials identified tampered Tylenol bottles with control number MC2880 to be the source of cyanide exposure. Johnson & Johnson immediately recalled all containers from that lot and all Tylenol products nationwide within days. The mass recall was estimated at 31 million bottles valued at more than $100 million⁶.

 

 

This mass recall was the first of its kind. Many predicted it would permanently mar the company, however the act contributed to a very positive public response. In the months that followed, Johnson & Johnson was reported as a transparent company who “placed consumers first” and showed dedication to product safety by reissuing Tylenol with triple-ply tamper-proof packaging (three times the FDA minimum) and new safer tablet forms. Replacement products were also offered free of charge. Despite these new measures costing the company millions, revenue and market sharing quickly recovered to the standings observed prior to fall of 1982^7,9.

 

The Chicago Tylenol Murders of 1982 remain unsolved. However, one suspect was closely followed after Johnson & Johnson received a letter demanding ransom for the cessation of poisonings. James Lewis was adamantly questioned and requitted of his theoretical connection to the murders. However, as Mr. Lewis did in fact send this letter – and an additional one to the White House, along with several other crimes – he was charged with fraud and extortion and sentenced to 20 years in jail⁴.

 

 

Although undoubtedly tragic, the Tylenol Murders have been able to contribute several advances in the safety of pharmaceuticals, as well as motivation for toxicologists to better understand the effects of potassium cyanide. These understandings have led to many documents identifying potential routes of exposure, methods of action, and available antidotes². Also as a direct result, the U.S. Congress passed The Federal Anti-Tampering Act (aka the “Tylenol Bill”) in 1983, making tampering with packaged consumer products a federal offence. Potassium Cyanide continues to be studied, with specific emphasis on antidotes and sensory identification (I.E. – identification by means other than lab tests, colorimetric  analysis,  and gas chromatography–mass spectrometry  (GC-MS)). However, further research is needed to truly combat this poison.

Unfortunately, no new information on these homicides is available as the case was reopened in 2009. The Tylenol Murders are now considered under open investigation and media coverage is limited¹¹.

 

 

As to the “million-dollar question”; could this happen again? The short answer is ‘maybe’ – there are people all over the world who have demonstrated random destructive and malicious intent. However, thanks to the federal regulations surrounding all aspects of pharmaceuticals and known toxic substances, the odds of copy-cat performances are substantially minimized.

References:

1. The Associated Press. Chronology of Events in Tylenol Poisonings with AM-Tylenol. The Associated Press 1986 February 13, 1986.

 

2. National Institute for Occupational Safety and Health (NIOSH). Potassium Cyanide. 2011;UN 1680 (Guide 157).

 

3. Roy C, Mackenzie W. “Poisoned Pill” – The Chicago Tylenol Murders. 2017. Retrieved from https://podcasts.apple.com/au/podcast/e130-poisoned-pill-the-chicago-tylenol-murders/id1122804248?i=1000428209591 April 15, 2021

 

4. Criminal Minds F. The Tylenol Killer. 2021; Available at: https://criminalminds.fandom.com/wiki/The_Tylenol_Killer#Known_Victims. Accessed March/14, 2021.

 

5. Department of Health, New York State. The Facts About Cyanide. 2004; Available at: https://www.health.ny.gov/environmental/emergency/chemical_terrorism/cyanide_tech.htm#:~:text=Between%2020%20and%2040%20percent,detect%20the%20odor%20of%20cyanide. Accessed March/14, 2021.

 

6. Revisiting Chicago’s Tylenol Murders. Chicago Magazine 2012:March/14, 2021.

 

7. Rehak J. Tylenol Made a Hero of Johnson & Johnson : The Recall that Started them All. International Herald Tribune, The New York Times 2002:March/14, 2021.

 

8. Jethava D, Gupta P, Kothari S, Rijhwani P, Kumar A. Acute Cyanide Intoxication: A Rare Case of Survival. Indian Journal of Anesthesia 2014;58(3):312-314.

 

9. Funding Universe. Johnson & Johnson History. 2001; Available at: http://www.fundinguniverse.com/company-histories/johnson-johnson-history/. Accessed March/14, 2021.

 

10. Johnson & Johnson, Our Story. 2018; Available at: https://ourstory.jnj.com/timeline. Accessed March/14, 2021.

 

11. Coen J, Marx G, Ahmed A, Bzdak Z, Janega J, Lighty T, et al. FBI Reopens Tylenol Tampering Case. Chicago Tribune 2009:March/14, 2021.

 

12. Markel H. How the Tylenol Murders of 1982 Changed the Way We Consume Medication. 2014; Available at: https://www.pbs.org/newshour/health/tylenol-murders-1982. Accessed March/14, 2021.

 

13. Mystery of Seven Deaths. 2021. Available at: https://prezi.com/kvab9j9hjaxj/mystery-of-seven-deaths/?frame=2f255d34b1eae9853a20ff090a897983d5334d1d. Accessed March/14, 2021

 

14. Coen J, Marx G. FBI Reopens Tylenol Tampering Case. Chicago Tribune 2009:March/14, 2021.

 

15. Digital Staff M. How an Unsolved Murder Mystery Changed our Pill Bottles. 2018; Available at: https://www.wsmv.com/news/us_world_news/how-an-unsolved-murder-mystery-changed-our-pill-bottles/article_4b1e4b4f-2f24-5947-85d2-14f0b2f19ba9.html. Accessed March/14, 2021.

Additional Media Coverage via #RetroReport

Reference for above video:

A Trusted Pill Turned Deadly. How Tylenol Made a Comeback | Retro Report Sept. 16, 2019. Available at https://www.youtube.com/watch?v=l1R0EnzGB3I&t=26s. Accessed April 17, 2021.