Let me tell you the tale of the scorpion’s… tail

Striped Bark Scorpion

Here is one in action.

Video 1: Striped bark scorpion. (1)

There are more than 1,700 different species of scorpions, and striped bark scorpions are one of the more common ones in North America. Striped bark scorpions can grow up to around two and a half inches long. (2) They are arthropods that use their venom for feeding and defense. This venom is composed of neurotoxins, proteases, and cytotoxic peptides. (3)

Below is a real-time reaction to a scorpion sting. Most of the time, the pain would be gone in around 20 minutes.

Video 2: Getting stung by a striped bark scorpion. (2)

If anyone has any interest in keeping them as pets, here is a brief video on how to care for them.

Video 3: Caring for bark striped scorpion. (4)

Scientific name: Centruroides vittatus
Class: Arachnida
Size (Adult): 0.98 inches to 2.73 inches (5, 3)

This map shows the distribution of this type of scorpion in North America.

Figure 1: Striped bark scorpion territorial map. (5)

The venom that is produced by the striped bark scorpion has neurotoxins that are of low toxicity and non-lethality to humans, but they could cause sharp pain immediately as well as local swelling. Numbness and irritation may linger afterwards. Additionally, they could cause skeletal muscle spasms and paresthesias at the sting site, face, and tongue. (6, 5)

Striped bark scorpions are described as having long slender bodies with two-toned coloring, two long stripes on back, and black stinger tip:

  • Dark brown abdomen
  • Pale yellow-ivory pincers, legs, and tail (5, 7)


Striped bark scorpions in North America are found in warm, dry climates. (8)

They are found in Texas and in the following Mexican states:

  • Tamaulipas
  • Coahuila
  • Neuvo Leon
  • Chihuahua
  • Durango

Also found in the following states in the United States:

  • Arkansas
  • Colorado
  • Illinois
  • Kansas
  • Louisiana
  • Mississippi
  • Missouri
  • Nebraska
  • New Mexico
  • Oklahoma
  • Tennessee (7)

Striped bark scorpions are nocturnal and live in areas that are damp and cool (e.g., rocks, boards, fallen logs, dead vegetation, and indoors). The venom is located in the poison glands in the swollen tip of the tail. It is a mixture of a few peptides, and they bind to the following different families of ion channels in nerve and muscle excitable membranes:

  • Na+
  • K+
  • Cl-
  • Ca2+ (7)

The peripheral sensory neurons, or nociceptors, get activated and the pain is sensed while transmitting information to the central nervous system. Nociceptors cell bodies are located in dorsal root ganglia (DRG), just outside of the spinal cord. The following DRG-expressed voltage-gated sodium channels (VSGSc) are the primary means of the venom’s toxic effects:

  • Na(v)1.7
  • Na(v)1.8
  • Na(v)1.9 (9)

Biotransformation and toxicokinetics

Striped bark scorpions penetrate the skin of its target with the stinger containing venom glands to inject the venom. The venom peptides injected are the scorpion ⍺-toxins, which bind to voltage-gated sodium channels to inactivate them, causing prolonged depolarization with neuroexcitation and disturbances to the autonomic nervous system. (10) The toxins overcome the hosts’ defense systems, including proteases and/or pH variations. (11)

If antivenom is not administered, venom could remain in serum at detectable levels for many hours. The biological half-life in serum is 200 to 500 minutes. (8)

In the five minutes after envenomation, venom is found to be 28% in the blood, 30% in muscle, 13% in bone, 12% in kidney, 11% in liver, and the rest in the other organs. The venom undergoes rapid clearance from the circulatory compartment with the initial high blood level at 28% at 5 minutes in which it declined to 12% at 30 minutes. Kidney had higher level of venom than the liver. Venom is excreted via the kidney and liver. The renal uptake maximum was 32% at 30 minutes, and it dropped to 22% at 3 hours, indicating the slow clearance of the venom from the kidney. Based on the immunoreactivity study, the localization of the venom was in the kidney as opposed to the other organs. The study of the adrenal uptake at specified time points was comparable to a radiopharmaceutical for neural crest tumors, revealing the venom to have effects on the sympathetic nervous system. In summary, venom follows an open two-compartment pharmacokinetic model with rapid distribution half-lives and slow overall elimination half-lives. Absorption occurs before venom enters the general circulation in that it is rapid and appreciable with approximately 70% of the maximum blood concentration achieved within 15 minutes. To reach the maximum blood venom concentration, it takes 101 + 8 minutes, and, for it to reach nearly complete absorption, it takes 7 to 8 hours. (12)


There is lack of information on whether the scorpion venom is a carcinogen, but studies have shown one of the other species in the Centruroides genus, Centruroides tecomanus, to have potential toxic effects on cancer cells in vitro. The peptides in the venom are highly selective and bind to cancer cells to initiate their killing. (13)

Mechanism of Action

Let’s discuss the impact of venom on sodium and potassium ion channels. Remember the cytotoxic peptides contained in the venom from the beginning of this post; there are the disulfide-bridged peptides, and there are non-disulfide-bridged ones. The neurotoxins are the disulfide-bridged peptides, and they modulate sodium and potassium channels. They make up a large part of the total proteins in the venom. As for the non-disulfide bridge peptides, less is known about them, but they exhibit pro-inflammatory, antimicrobial, and hemolytic activity. Below are the steps explaining how the neurotoxins inflict their modulatory effects on the sodium and potassium channels: (3)

  • Na+ channels
    • Toxins bind to the channels
    • Channels get altered in their gating mechanism
    • This alteration causes the channel to be likely open near resting membrane potential
    • The fast inactivation gets inhibited
    • The flow of Na+ ions gets prolonged through the pore
  • K+ channels
    • Toxins bind to the channels, and block the K+ ion flow through the channel
    • The membrane gets prevented from returning to resting potential after depolarization (9)

Shown below is a graphical representation of the scorpion venom’s mechanism of action.Related image

Figure 2: The mechanism of action in scorpion envenoming. (17)

The below figure compares the mechanism of action for the scorpion venom to that of other species’ venoms.

Figure 3: The mechanism of action for scorpion venom is displayed along with those of mamba, cobra, and widow spider venoms. (18)

The modulatory effects of the toxin on sodium channels expressed in nociceptors cause the pain when stung, and this pain could last from several hours to days. The effects on Na(v)1.7 were reduced in mutants although the effects were not eradicated. 

Striped bark scorpions are considered to be New World scorpions, and their venom was compared to that of the Old World scorpions. It was found that they both exhibit their effects on Na(v)1.7 with similar activities, but their ⍺-toxins have diverged in sequence. In conclusion from the study that compared the New World scorpion venom with the Old World scorpion venom, the New World pain-inducing toxin is produced from convergent evolution in which it came from a common ancestor with the Old World non-neurotoxin producing scorpions. (9)

Target organ(s)

Central nervous system

Respiratory tract


Cardiovascular system

Autonomic nervous system, causing autonomic storm, releasing

    • Catecholamines
    • Angiotensin II
    • Glucagon
    • Cortisol
    • Insulin secretion changes (12)

Signs and symptoms of toxicity

Death from striped bark scorpion’s venom is rare in humans. (14, 7) The venom is neurotoxic and kills insects, but it would cause extreme discomfort in a human. In cases of deaths in humans, it would be caused by anaphylactic shock rather than the direct toxic effects of the sting. (7)

In adults, the following signs and symptoms may occur:

  • Tenseness
  • Anxiety
  • Tachycardia
  • Hypertension
  • Increased respirations
  • Difficulty in focusing and swallowing
  • General weakness
  • Pain

The following occurs in rare cases:

  • Convulsions
  • Ataxia
  • Muscle incoordination

In the first 12 hours following the sting, most adults exhibit no symptoms (asymptomatic), but they may experience generalized weakness for 24 hours or at least. (14)

Historical or unique exposures, and genetic susceptibility or heritable traits

The exposure to the venom could vary based on the differing proteomic and genomic profiles of the individual scorpion venom glands based on the geographical location, venom synthesis rates, and foraging behavior. When comparing an adult scorpion with another of the same species but from different geographical locations, their venom composition signatures were not identical. They differed in proteomic expression intensity. Diet changes could also play a role in the variation in the venom composition signatures due to their impact on gene expression by affecting post-translational modifications. (3)

Physiological resistance to the venom has been observed in grasshopper mice (Onychomys torridus and Onychomys arenicola) that feed on them. Grasshopper mice portrayed no scorpion envenomation effects following stings. To determine their resistance, five populations of grasshopper mice were injected with the venom. All five populations showed levels of venom resistance greater than that of non-resistant Mus musculus. Additionally, intra- and interspecies variability was observed, and this concludes that venom resistance in grasshopper mice is an adaptive response as a result of their feeding on neurotoxic scorpions. (15)

Below is a map showing the geographical locations of grasshopper mice (O. arenicola) and striped bark scorpions (C. vittatus).

Figure 4: Geographical distributions of mice and scorpions. (15)


Below are some preventative measures that could be taken to avoid exposure in areas with scorpions:

  • Wearing long sleeves, pants, and gloves
  • Shaking out clothing or shoes
  • Carrying an epinephrine auto injector (EpiPen) (for those who are allergic)

If envenomated:

  • Supportive care and pain management
    • Apply pressure compression and ice pack to sting site
  • Severity dictates whether to use antivenom
    • Antivenom for severe grade III and grade IV strings
  • Goat serum-derived antivenom
    • Concern is the serum sickness
  • FDA-approved Anascorp
    • First treatment specific for scorpion sting by Centruroides in the United States
    • Made from horses’ plasma immunized with scorpion venom
  • Capture scorpion for identification if able to (8)


A study evaluated venom gland gene expression and venom potency. Scorpions from size class I-II (immature) and size class IV (adults/penultimate instars) had their venom toxicity measured. It was found that size class IV is 2.7 fold more potent. To analyze venom gland gene expression, next generation sequencing was used, and it revealed that expression in transcripts are associated with the modulatory effects of sodium and potassium channels. Sodium channel modulator expression was more apparent in size class IV, and potassium channel modulation was more in size class I-II. In al, differences in venom potency is accounted for by the differences in venom-related genetic expression. (3)

Below is a picture showing the differences in the sizes of the scorpions from each class.

Figure 5: Size classes of Centuroides vittatus. (3)


Lastly, as we are on the subject of plant and animal toxins, see below.

Figure 6: A comical take on the subject matter. (16)


  1. Gisi K. [Internet] Striped Bark Scorpion. YouTube; 2017Apr1 [cited 2019Jul17]. Available from:
  2. Hansler B. [Internet]. Painful Encounters: The Bark Scorpion. YouTube; 2015Aug5 [cited 2019Jul17]. Available from:
  3. McElroy T, McReynolds CN, Gulledge A, Knight KR, Smith, WE, Albrecht EA. Differential toxicity and venom gland gene expression in Centruroides vittatus. PLoS One [Internet]. 2017Oct4 [cited 2019Jul21];12(10):e0184695. Available from:
  4. Rattlesnake Zack. [Internet]. Bark scorpion care sheet. YouTube; 2016Mar29 [cited 2019Jul17]. Available from:
  5. Striped Bark Scorpion [Internet]. Insect Identification. Updated 2019 Mar 14 [cited 2019Jul17]. Available from:
  6. Demain JG, Goetz DW. Immediate, late, and delayed skin test responses to Centruroides vittatus scorpion venom. Journal of Allergy and Clinical Immunology [Internet]. 1995 [cited 2019Jul17];95(1):135-7. Available from:
  7. Schaefer J. Centruroides vittatus [Internet]. Animal Diversity Web. [cited 2019Jul19]. Available from:
  8. North American Centruroides (Bark Scorpion Venom) [Internet]. TOXNET Toxicology Data Network. U.S. National Library of Medicine, National Institutes of Health; Updated 2013 Feb 13 [cited 2019Jul17]. Available from:
  9. Rowe AH, Xiao Y, Scales J, Linse KD, Rowe MP, Cummins TR, et al. Isolation and Characterization of CvIV4: A Pain Inducing alpha- Scorpion Toxin. PLoS One [Internet]. 2011Aug24 [cited 2019Jul21];6(8):e23520. Available from:
  10. Rodrigo C, Gnanathasan A. Management of scorpion envenoming: a systematic review and meta-analysis of controlled clinical trials. Syst Rev [Internet]. 2017Apr8 [cited 2019Jul21];6:74. Available from:
  11. Petricevich VL. Scorpion Venom and the Inflammatory Response. Mediators of Inflammation [Internet]. 2010Jan4 [cited 2019Jul21];2010, Article ID 903295, 16 pages. Available from:
  12. Murthy KR. The scorpion envenoming syndrome: a different perspective. The physiological basis of the role of insulin in scorpion envenoming. J. Venom. Anim. Toxins [Internet]. 2000 [cited 2019Jul21];6(1). Available from:
  13. Investigacion y Desarrollo. “Scorpion venom is toxic to cancer cells.” ScienceDaily. ScienceDaily, 27 May 2015. Available from:
  14. Watkins JB, III. Toxic Effects of Plants and Animals. In: Klaassen CD. eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition New York, NY: McGraw-Hill; 2013. Accessed July 21, 2019.
  15. Rowe AH, Rowe MP. Physiological resistance of grasshopper mice (Onychomys spp.) to Arizona bark scorpion (Centruroides exilicauda) venom. Toxicon [Internet]. 2008Oct [cited 2019Jul21];52(5):597-605. Available from:
  16. Imgur.jpg. Available from: 2019 Jun 16.
  17. Laraba-Djebara F. Scorpion Venoms: Pathogenesis and Biotherapies. Scorpion Venoms. 2014 Dec 24;4:63-85 [cited 2019Jul29]. Available from:
  18. Muller GJ. Scorpion sting in southern Africa: diagnosis and management. Continuing Medical Education. 2012 Sep;30(10):356-61 [cited 2019Jul29]. Available from:

The Mighty Methanol …but not so mighty when ingested!

A colorless, watery liquid whose odor is slightly sweeter than ethanol, methanol caused poisoning “endemics.” Poisonings come from preparing adulterated beverages in that distilling and fermenting errors occur. (1, 2, 3)

Figure 1: Word cloud concept of methanol. (4)

Methanol word cloud concept Stock Photo - 62027899

Other names for methanol:

  • Methyl alcohol
  • Wood alcohol (5)
    • “Methylene” from Greek roots for “wood wine” (6)

Chemical structure of CH3OH (5)

  • Four parts hydrogen
  • One part oxygen
  • One part carbon (7)

Video 1: 3D molecule animation of methanol. (8)

Methanol is one of the “toxic alcohols”

  • Other toxic alcohols include:
    • Ethylene glycol
    • Isopropyl alcohol (3)

Figure 2: 3D molecule model. (9)

Methanol toxicity:

  • Ingestion
    • Most common is drinking windshield washer fluid in suicide attempts
    • Accidental ingestion in children
    • Abused as a substitute for ethanol
      • Food-warming fuel
  • Dermal absorption
  • Inhalation
    • Abuse with carburetor cleaner

Individuals at risk:

  • Toddlers and young children
  • Alcoholics
  • Individuals with suicidal tendencies (3)


Isolated from boxwood (also known as “spirit of box”) (6)

Produced by natural gas, coal, and renewable sources (municipal waste, biomass, and recycled carbon dioxide), pure methanol is made from natural gas via reformation of the gas with steam and converting it and distilling it. (7)

Figure 3: Methanol product chain. (10)



  • Windshield washer fluid
  • Carburetor cleaners
  • Gas line antifreeze (3)
  • Copy machine toner (6)
  • Perfumes
  • Food-warming fuel (3)

Methanol is a starting material for the synthesis of the following:

  • Formaldehyde
  • Acetic acid
  • Methacrylates
  • Ethylene glycol
  • Methyl tertiary-butyl ether (5)

Figure 4: Applications of methanol by derivative and by region. (10)



This is a video on the oxidation of methanol using potassium permanganate that produces formate salt.

Video 2: Oxidation of methanol. (11)

Methanol gets oxidized to formaldehyde and then to formate. This takes place mainly in the liver, and it results in formation of free radicals. Free radicals damage cells’ components including proteins and lipids. (12)


Methanol gets absorbed and distributed quickly. It travels to the body water in which it is not bound to proteins. The metabolism occurs slowly via the alcohol dehydrogenase. For comparison, it occurs at a speed that is approximately one-tenth to that of ethanol. Half-life of methanol is 2-24 hours. (25)

Methanol is potentially lethal at 30 to 240 mL or 1 gram per kilogram. It may take a minimum of 30 mL for permanent damage to vision to occur. The primary toxic metabolite, formic acid, contributes to the anion gap metabolic acidosis and end-organ damage. The increase in the anion gap is accompanied by decreases in the osmolar gap as methanol is metabolized.

As formic acid and formate are not readily eliminated, they can accumulate and disrupt oxidative phosphorylation. Formate inhibits cytochrome oxidase. Lactatemia also occurs due to formate inhibiting mitochondrial respiration, causing formate to be able to cross the blood-brain barrier as formic acid.

The shunting of pyruvate to lactate leads to elevations in lactate due to increased NADH/NAD ratio as a result of alcohol metabolism. Retinal toxicity along with end-organ damage are caused by formic acid’s oxidative stress. Basal ganglia lesions in putamen and globus pallidus cause parkinsonian-like symptoms. (3)

Figure 5: Visualization of methanol metabolism. (13)


Methanol is not known to be a carcinogen. However, when there is chronic or repeated methanol exposure, there is potential for developmental toxicity risk in which birth defects of the central nervous system may occur. (2)

Mechanism of Action

Methanol acts as a CNS depressant. It can take just a mouthful for it to be toxic. It gets metabolized in the liver by alcohol and aldehyde dehydrogenase to form the toxic metabolites formaldehyde and formic acid.

Formic acid leads to anion gap metabolic acidosis and ocular toxicity. It inhibits cytochrome oxidase in the eye, and it causes the axons in the optic disc to swell. Visual impairment results from the edema. (14)

Figure 6: Photograph of right eye (top) and left eye (bottom) of patient with acute methanol toxicity showing prominent congestion of disc and edema of retina, giving way to optic disc pallor in that no useful vision was recovered. (15)

Target organs

Ocular/ophthalmologic targets (16, 2)

  • Visual disturbances
  • Blurred vision
  • Photophobia (light sensitivity)
  • Hallucinations (of visual nature: misty vision, skin over eyes, snowstorm, moving spots, and/or flashes)
  • Partial or total vision loss
  • Eye pain in rare cases
  • Dilated pupils (fixed) in severe exposures (14)
  • Retina (optic disc and optic nerve)
    • Optic disc edema and hyperemia
    • Changes to optic head, intraorbital areas of optic nerve, axons, glial cells, rods, cones, and Mueller cells (16)

Central nervous system (16, 2)

  • Dizziness
  • Agitation
  • Acute mania
  • Amnesia
  • Decrease in level of consciousness
  • Coma
  • Seizure (14)
  • Complications in survivors
    • Parkinsonism
      • Severe tremors and mild rigidity (16)

Gastrointestinal (14, 2)

  • Nausea
  • Vomiting
  • Anorexia
  • Abdominal pain
  • Gastrointestinal hemorrhage
  • Diarrhea
  • Abnormal liver function
  • Pancreatitis (2)

Signs and symptoms of toxicity

Ingestion of methanol causes serious toxicity with non-specific clinical manifestations which makes the diagnosis challenging.

  • If untreated, acute poisoning may result in the following:
    • A period of latency with no symptoms for 12 to 24 hours (if methanol ingestion is combined with ethanol ingestion, then the onset may be delayed by 24 hours)
    • The latency period is followed by the following early signs:
      • Abdominal discomfort
      • Nausea
      • Vomiting
      • Mild depression of the central nervous system (5, 1)
    • The following are the late onset signs:
      • Anion gap acidosis
      • Neurological dysfunction
      • Ophthalmological disturbances (1)
    • Others
      • Formic acidemia
      • Ocular toxicity in which the visual symptoms occur is the most specific clinical features (5, 1)
        • Disturbances to the vision usually develop 18 to 48 hours after ingestion and can include:
          • Mild photophobia
          • Misty or blurred vision
          • Reduced visual acuity
          • Complete blindness (5)
      • Confusion (17)
      • Coma
      • Death in some cases (5)
  • Lethal dose (orally) is 1 mL/kg
    • There have been cases of death and blindness at lower doses
  • Toxicity occurs once methanol is oxidized to formaldehyde and formic acid which are the active metabolites of methanol (1)

Genetic susceptibility or heritable traits

Aldehyde dehydrogenase 2 polymorphism affects susceptibility to methanol exposure. This polymorphism affects the enzymes in which genetic variants of them are produced, and they affect methanol metabolism and the individual’s susceptibility to acute methanol exposure. (18) Genetic factors contributing to methanol toxicity require further studies. (19)

Historical or unique exposures

Figure 7: Ancient Egyptians used methanol as one of the components of the embalming fluid. (6, 20)

A denaturant for some alcohols including ethyl and isopropyl alcohols, methanol results in them being “unfit for consumption” and poisoning from “adulterated bootleg whiskey.” (5)

Exposure to the general population via free methanol or methanol precursors via:

  • Fruits
  • Fruit juices
  • Vegetables
  • Alcoholic beverages

Indirect exposure via hydrolysis of the following:

  • Artificial sweetener
  • Aspartame
  • Absorption from the gut

Very low-level exposures:

  • Ambient air
  • Drinking water (5)


Airway protection with supportive measures is crucial in cases of methanol toxicity. (14)

It is important to diagnose and treat early. (1) Methanol exposures cause degrees of toxicity in which there is a range of treatments from laboratory monitoring to antidote administration and dialysis.

Primary treatments: Ethanol or fomepizole (with dialysis is often recommended) (3)

Dialysis works to eliminate methanol and its main toxic metabolite, formate. (14)

Definitive diagnosis involves measuring the serum concentration of methanol. (1). Urine and blood may be collected for not just methanol determination but also formic acid. (21)

  • The gold standard test is blood gas panel/gas chromatographic determination of methanol levels and confirmation of elevation in methanol level measured at >6mmol/L (20mg/dL) (1, 17)
  • Osomlar gap calculation may be performed as an alternative if unable to measure methanol levels (1)
  • Rapid qualitative spot test to determine methanol in blood, and simple quantitative method to quantitate by colorimetry at 570 nm. (21)

Appropriate management: Inhibit methanol’s enzymatic oxidation to formic acid by administering an antidote which can be fomepizole or ethanol, and this is crucial in the prognosis of patient’s visual ability. (1)

The antidote of choice is fomepizole although its superiority to ethanol has not been determined.

In addition, to enhance elimination and accelerate formic acid metabolism, hemodialysis and folic acid intravenous administration may be used. (1, 14)

  • Folic acid (leucovorin) intravenous administration at 50 mg every 4 hours for a few days
    • Works to potentiate folate-dependent metabolism of formic acid to carbon dioxide and water
    • Ethanol infusion may be considered if there is an idiopathic osomlar gap and/or elevated anion-gap metabolic acidosis (14)
  • Gastric lavage decontamination
    • Apply within the first hour of ingestion
    • Activated charcoal does not adsorb alcohols, so it is not recommended
  • Alcohol dehydrogenase inhibitor therapy
    • Ethanol (17)
      • Methanol gets metabolized by ADH and CYP2E1 in which ethanol also interacts with; ethanol’s affinity for ADH is relatively high, competitively inhibiting methanol’s metabolic activation. Ethanol induces CYP2E1 in that metabolic activation is enhanced and methanol’s toxicity is reduced
    • Fomepizole
  • Leucovorin calcium
    • Speeds up formate’s metabolism
  • Thiamine
    • Given to chronic alcoholic use
    • Prevent Wernicke-Korsakoff syndrome
  • Hemodialysis
    • Severely intoxicated (5)
  • Amantadine (16)

This video gives an overview of what’s been discussed for methanol. It goes into more details on why ethanol would be administered in cases of methanol toxicity.

Video 3: Methanol lecture. (22)


The detection of methanol in the blood serves as an alcohol biomarker. The downside is that methanol can be produced endogenously, and this could lead to misinterpretation. (23)

Methanol serves as one of the breath biomarkers associated with liver cirrhosis that is useful for diagnostic purposes. Alveolar breath samples were taken from 31 patients with cirrhosis and from 30 people as healthy controls. The samples were analyzed via the mass spectrometer. Twelve of the patients had their samples taken after liver transplant, and five of them were followed post-transplant. Seven volatiles were shown to be elevated in patients’ breath versus their healthy counterparts. Five of the volatiles were statistically significant in their decrease post-transplant, and methanol was one of them. The others were limonene, 2-pentanone, 2-butanone, and carbon disulfide. Limonene showed the best diagnostic functionality. In all, limonene, methanol, and 2-pentanone are considered breath markers for cirrhosis. There is potential for them to serve as markers for early-stage liver disease. (24)


  1. Anyfantakis D, Symvoulakis EK, Cristodoulakis EV, Frantzeskakis G. Ruling in the diagnosis of methanol intoxication in a young heavy drinker: a case report. J Med Life. 2012;5(3):332–334. Accessed June 25, 2019. 
  2. CDC – The Emergency Response Safety and Health Database: Systemic Agent: METHANOL – NIOSH [Internet]. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention; [cited 2019Jun30]. Available from:
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  4. Stock Photo [Internet]. 123RF Stock Photos. [cited 2019Jun30]. Available from:|&mediapopup=62027899
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  6. Wiener SW. Toxic Alcohols. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank’s Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; 2015. Accessed June 25, 2019.
  7. Methanex Corporation [Internet]. How Methanol is Made | Methanex Corporation. [cited 2019Jun30]. Available from:
  8. C IB. [Internet]. Methanol or Wood Alcohol: 3D Molecule Animation. YouTube; 2015 [cited 2019Jun30]. Available from:
  9. 3d illustration of molecule model. Science or medical background.. [Internet]. 123RF. [cited 2019Jun30]. Available from:
  10. Sahu A. Methanol opportunity as a fuel substitute augurs well for GNFC and Deepak Fertilisers [Internet]. Moneycontrol. MoneyControl; [cited 2019Jun30]. Available from:
  11. The Bohring Chemistry Channel. [Internet]. Oxidation of Methanol to Formic Acid using Potassium Permanganate. YouTube; 2016 [cited 2019Jun30]. Available from:
  12. Skrzydlewska E. Toxicological and metabolic consequences of methanol poisoning. Toxic Mech Methods. 2003;13(4):277-93. Accessed 2019 Jun 24.
  13. Toxic Alcohols [Internet]. Relias Media – Continuing Medical Education Publishing. [cited 2019Jun30]. Available from:
  14. Methanol Toxicology [Internet]. methanol_toxicology [TUSOM | Pharmwiki]. [cited 2019Jun30]. Available from:
  15. Lin RC, Mieler WF. Chapter 16 – Retinal toxicity of systemic and topical medications. In: Nguyen QD. eds. Retinal Pharmacotherapy: Elsevier Inc.; 2010. Accessed June 30, 2019. 
  16. Bitar, Z. , Ashebu, S. and Ahmed, S. (2004), Methanol poisoning: diagnosis and management. a case report. International Journal of Clinical Practice, 58: 1042-1044. doi:10.1111/j.1368-5031.2004.00034.x [cited 2019Jun25]. Available from:
  17. Keskin Arslan, Elif & Erol, Hilal & Karadaş, Barış & Kaplan, Yusuf. (2016). Management of Methanol Poisoning: A Review of Eight Cases [cited 2019Jun25]. Available from:
  18. Hubacek JA, Jirsa M, Bobak M, Pelclova D, Zakharov S. Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans. Clin Genet. 2018 Nov;94(5):445-449. Accessed June 30, 2019.
  19. Methanol (EHC 196, 1997). [cited 2019Jun30]. Available from:
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  21. METHANOL (PIM 335). [cited 2019Jun30]. Available from:
  22. Wadsworth R. [Internet]. Methanol from Alcohol lecture Pharmacology. YouTube; 2015 [cited 2019Jun30]. Available from:
  23. Cabezas J, Lucey, MR, Bataller R. (2016), Biomarkers for monitoring alcohol use. Clinical Liver Disease, 8: 59-63. doi:10.1002/cld.571 [cited2019Jun30]. Available from:
  24. Río RFD, Ohara M, Holt A, Pemberton P, Shah T, Whitehouse T, et al. Volatile Biomarkers in Breath Associated With Liver Cirrhosis — Comparisons of Pre- and Post-liver Transplant Breath Samples. EBioMedicine. 2015;2(9):1243–50 [cited2019Jun30]. Available from:
  25. TaharSuliman. Volatile Poisons [Internet]. SlideServe. 2015 [cited 2019Jul29]. Available from:

Magnesium the Magnificent …but not so when it’s deficient!

Known for its extraordinariness, magnesium is the fourth most abundant mineral in the body. (1, 2) In the earth’s crust, magnesium is the eighth most abundant. It is the most abundant when water bodies are accounted for. In salt water, magnesium averages 1290 parts per million (ppm). (3)

Figure 1: Magnesium food sources. (4)Image result for magnesium

Magnesium (Mg)

    • Lightest metal element (1.738 g/cm3) (20℃)
    • Atomic number: 12
    • Element category: Alkaline metal (3, 5)

Figure 2: Magnesium, an element of the periodic table, is displayed. (6)the history of magnesium supplements

History of Magnesium

Figure 3: Picture of magnesium. (3)Crystalized Magnesium

In 1755, magnesium became known as one of the elements. The name came from Magnesia, the Greek word for a Thessaly district where magnesium was first found. (5) In 1618, farmer Henry Wicker tried giving water to his cows but the cows refused because the water tasted bitter. Henry noticed the water appeared to heal scratches and rashes. This took place in Epsom, England, and this then became widely used and was later recognized as magnesium sulfate, MgSO4, commonly known as Epsom salts. (7)

Figure 4: Epsom salts, magnesium sulfate, are used in baths. (8)

Magnesium Sources

  • Nuts
  • Cereals
  • Seafood
  • Meats (5)

Figure 5: Sources of magnesium. (2)

Magnesium production:

  • Dolomite and magnesite ore
  • Magnesium chloride containing salt brines (3)


    • Antacids or cathartics
      • They contain magnesium citrate, oxide, sulfate, hydroxide, and carbonate
    • Antidote for poisoning
      • Magnesium hydroxide (milk of magnesia)
    • Inflammation relief
      • Magnesium sulfate applied topically
    • Seizure treatment for eclampsia in pregnancy and acute nephritis
      • Administration of magnesium sulfate parenterally (5)


In microbial cells, magnesium is needed for cell metabolism as one of the macronutrients. Magnesium is present in optimal quantities in soils. Magnesium together with calcium, sulfur, potassium, and iron is crucial to cell synthesis. (9)


  • Oral magnesium
    • Absorption occurs mostly in the small intestine
      • Magnesium is also absorbed by the colon
  • Competitive absorption
    • Magnesium competes with calcium
      • When there is excess calcium, magnesium absorption gets partially inhibited
  • Levels of magnesium in serum
    • Constant
  • Excretion
    • Occurs via the digestive tract in bile and juices of pancreas and intestine
    • 60% to 65% of magnesium in the body is in bone
      • 27% of magnesium is in muscle
      • 6% to 7% of magnesium is in other organs
      • 1% of magnesium is in the fluid (extracellular fluid)
    • Magnesium gets filtered by the glomeruli
      • Approximately 95% gets reabsorbed–this contributes to the homeostasis maintenance (5)


Magnesium supplementation is known to inhibit carcinogenesis, and magnesium deficiency contributes to increasing the incidence of cancer. When magnesium is administered parenterally with a carcinogen, local anticarcinogenic effects result (in comparison to zinc where zinc produces systemic effects). Magnesium supplementation reduces the binding of the carcinogen to cells and DNA, and such mechanisms may include metal-carcinogen interactions at target cells’ enzymatic and regulatory sites. Studies show magnesium to have stimulatory effects on the host immune system. (10)

Mechanism of Action

In the intracellular fluids, magnesium is the second most abundant, and it participates in many enzymatic activities, neurochemical transmission, and muscular excitability. As magnesium sulfate, it causes reductions in striated muscle contractions, and it reduces acetylcholine release at myoneural junction, causing blockage of peripheral neuromuscular transmission. Another action by magnesium is that it inhibits the influx of calcium through channels, resulting in magnesium’s relaxant action on vascular smooth muscle. (11)

Below is a brief video on the mechanism of action of magnesium as well as its uses in the clinical setting.

Video 1: Magnesium’s mechanism of action as well as its clinical uses. (18)

Target Organs

As magnesium oxide, the target organs are eyes and respiratory system. (12) As magnesium sulfate injection, the possible target organs are the gastrointestinal tract, nervous system, cardiovascular system, and heart. (13)

Signs and Symptoms of Toxicity

Industrial exposures

  • Metal fume fever through inhalation of magnesium oxide that’s recently generated
    • Similar to zinc oxide (5)

Nonoccupational exposures

  • Persons with severe renal failure can suffer from magnesium toxicity through ingestion of antacids and other magnesium-containing drugs (5)

Signs and symptoms

  • Nausea
  • Vomiting
  • Hypotension
  • Electrocardiograph abnormalities
  • Central nervous system effects
  • Coma
  • Systolic cardiac arrest (5)

Below talks about magnesium sulfate being used as a drug to help pregnant women, and it explains what to look for in possible magnesium sulfate toxicity.


Figure 6: Magnesium sulfate use in pregnancy and its toxicity. (19)

Genetic Susceptibility or Heritable Traits

Hypomagnesemia has been shown to be associated with several single nucleotide polymorphisms (SNPs) along with traits linked to serum magnesium levels which include:

  • Kidney function
  • Fasting glucose
  • Bone mineral density (14)

There are common variants at six genomic regions, listed below, that are associated with serum magnesium levels at genome-wide significant levels.

  • MUC1
  • ATP2B1
  • DCDC5
  • TRPM6
  • MDS1 (14)


How to counteract magnesium toxicity

  • Infusion with calcium (5)


Biomarkers indicating magnesium status exist, and there is a total of 20 of them. The majority are for magnesium supplementation, and the rest are for magnesium depletion. Serum/plasma magnesium concentration, red blood cell (RBC) concentration, and urinary magnesium excretion are in response to alterations in diet. Those biomarkers appear to be useful in magnesium status of the general population. (15)

Essentiality and Deficiency

Magnesium is an essential metal in nutrition in which it participates in many crucial cellular reactions. (5)

  • Enzyme cofactor (for many enzymes), meaning it is a “helper molecule” in biochemical reactions (5, 2)
    • For the seven important enzymes in the glycolytic cycle, the divalent magnesium is required
  • Enzymes containing magnesium
    • Used in citric acid cycle
    • Beta-oxidation of fatty acids (5)

Magnesium deficiency can result from the following:

  • Malabsorption syndromes
  • Renal dysfunction
  • Endocrine disorders (5)

Magnesium deficiency can cause the following:

  • Neuromuscular irritability
  • Frank tetany
  • Convulsions
  • Inflammatory syndrome induction
  • Be a risk factor for:
    • Diabetes mellitus
    • Hypertension
    • Hyperlipidemia
    • Ischemic heart disease (5)

To determine the presence of a magnesium deficiency, a blood test may be taken. (1) Magnesium levels may be measured in the serum where 0.79 millimoles per liter or lower is considered to be low in magnesium (and a high magnesium level measures at 0.90 millimoles per liter or above). (4)

Below are also associated with not enough magnesium in the body:

  • Cramps
  • Muscle pain
  • Muscle spasms
  • Brittle bone
  • Fatigue
  • Anxiety
  • Migraines
  • Mood swings
  • Digestive or malabsorption issues (1)

The below image covers the symptoms of severe magnesium deficiency.

Image result for magnesium deficient

Figure 7: What severe magnesium deficiency looks like. (17)

To ameliorate, magnesium supplementation can derive benefits. It may be administered intravenously or orally. (5)

How prevalent is this deficiency though? Approximately 50-70% of American adults are deficient because they do not ingest enough of what’s recommended for their daily dose of magnesium. (2, 1)

Below is a table of what is the recommended daily amount of magnesium based on age, gender, pregnant, and lactating.

Table 1: Recommended daily amounts of magnesium. (16)

Thank you for reading about magnesium!

Figure 6: Magnesium dietary sources (1)Related image


  1. Signs Your Body Needs More Magnesium [Internet]. Pharmacy Solutions 223. 2018 [cited 2019May28]. Available from:
  2. 10 Evidence-Based Health Benefits of Magnesium [Internet]. Healthline. Healthline Media; [cited 2019May28]. Available from:
  3. Bell T. Everything You Want to Know About Magnesium [Internet]. The Balance. The Balance; 2019 [cited 2019Jun9]. Available from:
  4. Sandoiu A. Too much or too little magnesium can raise dementia risk [Internet]. Medical News Today. MediLexicon International; 2017 [cited 2019May28]. Available from:
  5. Tokar EJ, Boyd WA, Freedman JH, Waalkes MP. Toxic Effects of Metals. In: Klaassen CD. eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition New York, NY: McGraw-Hill; 2013. Accessed May 25, 2019.
  6. Treefrog Inc. Magnesium: A History [Internet]. Mvua Magnesium. 2018 [cited 2019Jun9]. Available from:
  7. Administrator. History [Internet]. Magnesium… Morgo Magnesium Limited; [cited 2019Jun9]. Available from:
  8. Romero VR, Christ-follower VRRA. How To Take A Detox Bath | Vanessa Rae Romero [Internet]. Healthy Living How To. 2019 [cited 2019Jun9]. Available from:
  9. Session II-1: Biotransformation/Biodegradation overview. [cited 2019Jun9]. Available from:
  10. Kasprzak KS, Waalkes MP. The role of calcium, magnesium, and zinc in carcinogenesis [Internet]. Advances in experimental medicine and biology. U.S. National Library of Medicine; 1986 [cited 2019Jun9]. Available from:
  11. Magnesium sulfate [Internet]. DrugBank. [cited 2019Jun9]. Available from:
  12. CDC – NIOSH Pocket Guide to Chemical Hazards – Magnesium oxide fume [Internet]. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention; [cited 2019Jun9]. Available from:
  13. Hospira. Material Safety Data Sheet | Product Name: Magnesium Sulfate Injection, USP. Old Saybrook:; 2005. Available from:
  14. Meyer TE, Germaine C. Verwoert S-JH, Glazer NL, Smith AV, Rooij FJAvan, Ehret GB, et al. Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels [Internet]. PLOS Genetics. Public Library of Science; 2010 [cited 2019Jun9]. Available from:
  15. Witkowski M, Hubert J, Mazur A. Methods of assessment of magnesium status in humans: a systematic review [Internet]. Magnesium research. U.S. National Library of Medicine; 2011 [cited 2019Jun9]. Available from:
  16. Office of Dietary Supplements – Magnesium [Internet]. NIH Office of Dietary Supplements. U.S. Department of Health and Human Services; [cited 2019May28]. Available from:
  17. Magnesium – The Miracle Mineral [Internet]. Nu U Nutrition. [cited 2019Jul29]. Available from:
  18. Anaesthesiologist T. [Internet]. YouTube. YouTube; 2018 [cited 2019Jul29]. Available from:
  19. Tr-I-Life. [Internet]. Tr. 2012 [cited 2019Jul29]. Available from:

Beware of the methyl bromide, a pest’s worst nightmare

You may be wondering, why does “methyl bromide” invoke such scary thoughts, not just for humans, but also for animals and insects?

Let’s find out…

Figure 1: Chemical structure of methyl bromide. (1)

Methyl bromide is a pesticide with its “broad-spectrum” effects–it acts on:

  • Insects
  • Mites
  • Nematodes
  • Weed seeds
  • Fungi
  • Rodents (2, 3)

Why would hurting such things be beneficial to us humans? Well, methyl bromide serves to improve the quality and quantity of agriculture. It is true that it could hurt us if we use methyl bromide improperly, and doing so has resulted in about 300,000 deaths per year from its poisoning. Improper uses could mean using it illegally and/or not utilizing safety precautions, such as wearing full face shield or safety glasses. An incident reported in 2015 involved a family of four Americans who got exposed to methyl bromide while on a trip to the U.S. Virgin Islands. The mother underwent treatment, but the father and the two teenage sons remained hospitalized at the time of the reporting. (10) Not only that, but also methyl bromide is known to cause ozone-depleting effects, an environmental danger. (2, 10)

Figure 2: Strawberry farmers view methyl bromide as being the most effective in controlling pests and improving their crops but at the cost of damaging the earth’s ozone layer. (4)

Here is a summary of how methyl bromide is used:

  • Soil fumigation: methyl bromide gets injected into soil, then it gets covered with plastic sheeting (or other tarping materials) for several days to increase the crops’ quality and yield
  • Structural fumigation: may be a commercial or residential structure that is covered by a tent. The structure is fumigated and aerated
  • Postharvest commodities fumigation: occurs in warehouses, grain elevators, and ship holds where wheat, cereals, and fruit are stored to eliminate pest infestations and aerate until fumigant concentration levels are safe (3)

Let’s investigate further into the mechanisms of action, toxicity, and target organs:

Methyl bromide is a gas that may be inhaled as its most common route of exposure. It is also absorbed quickly via the oral and dermal routes. Once absorbed, methyl bromide or its metabolites are distributed immediately to the tissue, which includes the liver, brain, adrenals, lungs, kidneys, fat, and testis. What is currently known about the metabolism of methyl bromide is that methyl bromide undergoes partial conversion into inorganic bromide in that bromide concentrations increase in target organs and blood from exposure. Bromide gets metabolized to methyl glutathione via the enzyme glutathione S-transferase (GST), and then it gets converted into formaldehyde’s and methanethiol’s metabolites that are neurotoxic (2)

Elimination of methyl bromide: Metabolized methyl bromide makes up 16% to 40% of the total amount exposed, depending on the exposure route, that gets eliminated in the urine. The 4% to 20% of exposed methyl bromide gets eliminated via expired air. About 46% of the elimination is accounted for by biliary excretion that occurs around within 24 hours after oral exposure. Animal models show that upon metabolism of methyl bromide, it produces methanol and hydrobromic acid via hydrolyzation. (2)

Methyl bromide’s acute toxicity is related to its concentration and exposure duration. (3) Below are the signs and symptoms of methyl bromide toxicity:

  • Acute exposure
    • Respiratory
    • Gastrointestinal
    • Neurologic
      • Lethargy
      • Headache
      • Seizures
      • Paresthesias
      • Peripheral neuropathy
      • Ataxia (3)
  • Severe exposure
    • Tremor
    • Convulsion
    • Rapid loss of consciousness
    • Dysrhythmias
    • Death (2)

The following figures shows the mechanisms of toxicity.

Figure 3: Methyl bromide’s mechanisms of toxicity. (11)


Figure 4: Methyl bromide-induced neurotoxicity. (11)

Related image

Death from methyl bromide inhalation may result from it being over 10,000 parts per million (ppm) for at least a few minutes. (2)

If a patient has inhaled methyl bromide, below are the actions and treatments that should be taken:

The patient should be removed from where exposure occurred. Their outer clothing would need to be taken off carefully–methyl bromide could adhere to it. The skin that is affected should be cleansed with soap and water. Following those rescue methods, decontamination should be done in that it is performed by personnel with personal protective equipment on. The eyes should be irrigated with plenty of 0.9% sodium chloride solution or water. If patient has cardiac or respiratory arrest, personnel should immediately initiate cardiopulmonary resuscitation. Management involves general and supportive care, but it could include intensive care unit management of kidney failure, ARDS, coma, seizures, and hepatic failure. The supplemental oxygen should be given while the ARDS, bronchospasm, and seizures should be treated. Seizures may require pentobarbital, thiopental in high dose, and propofol when typical methods fail to control them (anticonvulsants: benzodiazepines and phenytoin). Monitoring should last from 24 to 48 hours at minimum to watch for symptoms that may be delayed, including ARDS. Less severe methyl bromide poisoning may use British anti-Lewisite (dimercaprol), but it is not effective in more severe cases. (2)

Methyl bromide should be banned!

This is where it gets confusing…

Actually, the United States is no longer using methyl bromide as of January 2005, and the developing countries had until 2015 to stop its use and production. (3) However, in the United States, there are many agricultural companies who received exemptions and use methyl bromide. (2) Exemptions could be obtained for “critical uses” and for “quarantine and preshipment uses”. (6)  As of 2002, methyl bromide is still one of the most extensively used pesticides in the United States. (3)

Table 1: Inventory of methyl bromide in the United States per Environmental Protection Agency (EPA). (6)

Year Amount of Inventory at the End of the Year (Metric Tons)
2003 16,422
2004 12,994
2005 9,974
2006 7,941
2007 6,458
2008 4,271
2009 3,064
2010 1,803
2011 1,249
2012 627
2013 357
2014 158

Let us travel back in time…

Methyl bromide’s use dates back to 50 years ago (3)–actually, it had already been in use since the early 1900s when it was used as an anesthetic. It turned out to not be a good idea when it was realized that it was causing deaths. It was then used as a pesticide, also known as a fumigant, and its several other uses include:

  • In manufacturing, it serves as a methylating chemical
  • In oil extraction from nuts, seeds, and flowers, it is used as a solvent
  • Used as a refrigerant and a fire retardant

As a fire retardant, it was used in fire extinguishers, from which some of the deaths have occurred (2)

Biomarkers are useful tools in that they indicate the relationship of biological effects to conditions. In this case, the circulating mitochondrial DNA (mtDNA) in the serum is linked to methyl bromide exposure. Such elevated levels are caused by early preclinical lesions, and could indicate the initiation or progression of diseases including those that are degenerative. The mitochondrial destabilization, which is what is detected via the presence of circulating mtDNA, is produced by methyl bromide target organ(s). (7)

Figure 5: Source of mitochondrial DNA. (8)
Related image

Not only have we learned about the dangers of methyl bromide to their intended target species but also what effects it has on humans, how does it perform such reactions, what to look for in signs and symptoms of methyl bromide poisoning, what should be done for treatment, and how could biomarkers be utilized in the detection of exposure to methyl bromide in the human body.

Video 1: A human being’s unfortunate exposure to methyl bromide. (9)


  1. What is methyl bromide? – The News Reporter [Internet]. The News Reporter. 2018 [cited 2019 May 19]. Available from:
  2. Shadnia S. Fumigants. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank’s Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; 2015 [cited 2019 May 18]. Available from: 
  3. Costa LG. Toxic Effects of Pesticides. In: Klaassen CD. eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition New York, NY: McGraw-Hill; 2013 [cited 2019 May 15]. Available from:
  4. Methyl bromide. [cited 2019 May 19]. Available from:, Environ/Methyl.html#note
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  8. Porter MJ. Study shows mitochondrial DNA can be passed through fathers – what does this mean for genetics? [Internet]. The Conversation. 2018 [cited 2019 May 19]. Available from:
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