UMEM Educational Pearls

Category: Toxicology

Title: Deadly in a drop!

Keywords: Botulinum, Dimethylmercury, VX, Tetrodotoxin (PubMed Search)

Posted: 8/17/2017 by Kathy Prybys, DO (Emailed: 8/31/2017) (Updated: 8/31/2017)
Click here to contact Kathy Prybys, DO

Botulinum
  • Most poisonous substance known to man
  • LD50 oral dose 1 mcg/kg
  • Heat labile single polypeptide chain undergoes proteolytic clevage irreverisibly binds  and blocks cholinergic transmission causing a deadly neuroparalytic syndrome
  • Rx: Botulin antitoxin (equine derived against Clostriduim botulinum A,B,E)
Dimethylmercury (CH3)2 Hg
  • Highly toxic, restricted availability is rapidly absorbed and metabolized to methylmercury crosses CNS
  • LD50 of 50 mcg/kg means a dose as little as 0.1ml can result in severe poisoning
  • Death of Darmouth inorganic chemist Karen Wetterhahn who spilled a few drops on back of her latex gloved hand, quickly permeated, and absorbed causing severe neurotoxocity and death 10 months later
  • Rx: Chelation

VX ("venomous agent X") 

  • Organophosphate nerve agent has been used as chemical weapon
  • Colorless, odorless, low volatility, and high lipophilicity
  • LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption
  • Blocks acetylcholinesterase enzyme causing excess accumulation of acetylcholine at the neurojunction and cholinergic poisoning
  • Rx: Decontamination, Atropine, 2-PAM
Tetrodotoxin
  • 100 fresh and salt water varieties (pufferlike fish/blue ringed octopus, frogs)
  • Heat stable, water soluble found in fish skin, liver, ovaries,intestine, and muscle
  • 25 mg (0.000881 oz) expected to be lethal to a 75 kg person
  • Neurotoxicity by inhibition of Na-K pump and blockade neuromuscular transmission
  • Rx: Supportive measures

LD50 expresses the dose at which 50% of exposed population will die as a result of exposure.

References

 
Challenges in searching for therapeutics against Botulinum Neurotoxxins. Pirazzini m, rossetto O. Expert Opin Drug Discov. 2017 May;12 (5):497-510.
 
Toxicology of organophosphorous compounds in view of an increasing terrorist threat. Worek F, Willie T, et al. Arch Toxicol. 2016. Sep;90(9):2131-45. doi: 10.1007/s00204-016-1772-1. Epub 2016 Jun 27.
 
The need for empriricaly derived permeation data for personal preotective equipment. Blayney MB. Appl Occup Environ Hyg. 2001 Feb:1692): 233-236.
 
Death by food. Byard RW. Forensic Sci Med Pathol. 2017. Jul 15 doi: 10.1007/s12024-017-9899-9 [Epub ahead of print].