Sweet and Spooky

Poisonings
 Fact or Fiction?

• Lots of crazy people out there poison children’s candy on Halloween.

Fiction: Only one case of intentional poisoning of a child’s candy on

Halloween. (1)
 Timothy Marc O’Bryan
• October 31st 1974 in Pasadena,
Texas
• Pixie Stix laced with cyanide and
given to 4 other children
• Found to be poisoned by father,
Ronald Clark O’Bryan for life
insurance
• Timothy only fatality
 Symptoms Mechanism of
Action
• Nausea/Vomiting • Inhibition of
• Dizziness mitochondrial
• Headache cytochrome oxidase
• Tachycardia -> • Prevents utilization of
bradycardia
• Tachypnea -> respiratory oxygen in oxidative
arrest phosphorylation,
• Weakness inhibiting ATP
• Convulsions production
• Loss of Consciousness • Lethal Dose: 1-5 mg/kg
• Death (2) (3)
 Trick or Treatment
• ABCs first a foremost

• Decontamination (one dose of AC, 50g in children) (4)

• Give antidote using one of the following

 Antidotes
• Cyanokit
• Hydroxocobalamin binds cyanide directly -> cyanocobalamin -> urinary excretion
• Dose IV at 70mg/kg
• If severe, can add sodium thiosulfate
• Dicobalt edetate (less popular, more side effects)
• 20ml of 1.5% solution infused over 1 minute
• Methemoglobinemia
• Amyl nitrite, sodium nitrite, or dimethylaminophenol (4-DMAP)
• Converts Fe2+ to Fe3+
• Cyanide binds to form cyanomethemoglobin
• Reverse with methylene blue
 1858 Bradford sweets poisoning
• Sweets sold by “Humbug Billy” in Bradford, England

• Sugar expensive and would “adulterate” with other ingredients

• Arsenic trioxide confused for powdered gypsum called “daft”

• Poisoned over 200 people/20 fatalaties including several children

• Led to the passage of the Pharmacy Act of 1868 (5)

Arsenic Trioxide PowderedGypsum
 Symptoms (6)

• Tasteless and odorless

• Starts with nausea, vomiting, abdominal pain, severe diarrhea
• Garlic odor on breath
• QTc prolongation -> Torsades de Pointes
• Encephalopathy, confusion, and headache over several days
• Hepatitis and pancytopenia if they survive the first days
• Painful sensorimotor peripheral neuropathy after 1-3 weeks
• Increased incidence of cancer, even long after exposure
 Mechanism of Action (8)
• Not well understood
• Causes numerous DNA changes
• Metabolism from trivalent to pentavalent arsenicals is involved in the toxicity
• May replace phosphate in biochemical reactions
• Oxidative stress and fragmentation of DNA

• Lethal Doses of 600mcg/kg (7)

• Estimated double the lethal dose per humbug

 Trick or Treatment (9)
• Chelation!
• Dimercaprol (British Anti-Lewisite/BAL) –United States
• 3-5mg/kg every 4-6 hours until 24-hour urinary arsenic <50mcg/L
• Formulated with peanut oil/avoid if allergic
• Avoid with G-6-PD deficiency

• Meso-2,3-dimercaptosuccinic acid (DMSA/succimer) –United States

• Sodium 2,3-dimeracapto-1-propane sulfonate (unithiol/DMPS) –Germany

 2016 Punjab sweet poisoning (10)
• Took place in Punjab, Pakistan on May 8, 2016
• Confection called laddu was laced with insecticide called chlorfenapyr
• Made for a family gathering celebrating the birth of a new child
• At least 50 people consumed the treat
• 10 dead on the first day
• 33 dead total including 5 children and the father, six uncles, and aunt
of the newborn baby
Laddu
 Chlorfenapyr
• Used as pesticide since 1995
• Member of the pyrrole family
• Metabolized into CL 3030268
• Highly toxic to humans
• Not well studied
• Thought to uncouple oxidative phosphorylation inhibiting ATP
production
 Symptoms
• Described only in a few case reports (11)
• Low back pain
• Lower limb weakness
• Drowsiness
• Progressive paralysis
• Coma
• High Grade Fever
• Brainstem and white matter changes on MRI
• Can involve a latent period of several days or weeks
 Trick or Treatment
• Supportive care
• Management of symptoms

• Piperanoyl butoxinide
• Inhibits cyp450 enzymes
• Interferes with conversion to toxic metabolite
• Needs much more study
 References
1.) https://www.snopes.com/horrors/poison/halloween.asp
2.) https://emergency.cdc.gov/agent/cyanide/basics/facts.asp
3.) http://www.cyanidecode.org/cyanide-facts/environmental-health-effects
4.) https://www-uptodate-com.proxy.medlib.uits.iu.edu/contents/cyanide-
poisoning?source=search_result&search=cyanide%20poisoning&selectedTitle=1~48
5.) http://www.pharmaceutical-journal.com/news-and-analysis/features/arsenic-and-the-bradford-poisonings-of-
1858/20003896.article
6.) Mundy SW. Arsenic. In: Goldfrank's Toxicologic Emergencies, 10th ed, Hoffman RS, Lewin NA, Howland MA, et al (Eds), Mcgraw-Hill
Education, New York 2015. p.1169
7.) US Environmental Protection Agency. Technology Transfer Network Air Toxics. Available at:
www.epa.gov/ttn/atw/hlthef/arsenic.html
8.) Michael F Hughes, Arsenic toxicity and potential mechanisms of action, In Toxicology Letters, Volume 133, Issue 1, 2002, Pages 1-
16, ISSN 0378-4274
9.) https://www-uptodate-com.proxy.medlib.uits.iu.edu/contents/arsenic-exposure-and-
poisoning?source=search_result&search=arsenic%20poisoning&selectedTitle=1~22
10.) https://www.ndtv.com/world-news/mass-food-poisoning-kills-33-including-5-children-in-pakistans-multan-1401483
11.) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724086/