The Case of Jagger the Irish Setter

At the beginning of March, it was reported that a European show dog, a 3-year old Irish Setter named Jagger, had died with possible suspicious circumstances while competing in the Crufts show in the United Kingdom. Toxicological analyses were completed on specimens drawn during autopsy of the animal. According to the latest reports, the dog’s blood was positive for aldicarb and carbofuran - two substances that should not be found. At all.

What are aldicarb and carbofuran?

 

They are pesticides.

 

Highly potent pesticides.

 

Highly potent and restricted pesticides.
 

 

Aldicarb is a carbamate pesticide primarily used historically as a nematicide in potato production, but also used for the control of pests such as aphids and spider mites. Its IUPAC name is 2-methyl-2-(methylthio)propanal O-(N-methylcarbamoyl)oxime. Molecular formula is C₇H₁₄N2O₂S and molecular weight is 190.2 g/mol. Aldicarb is excreted in the urine primarily as metabolites over approximately 1-10 days. Common urinary metabolites include aldicarb sulfoxide, aldicarb sulfone, aldicarb oxime, and aldicarb nitrile. The trade name for aldicarb is Temik. Its use was banned in 2003 in the European Union.

Carbofuran is a carbamate pesticide that is used on various field crops such as potatoes and corn. It is also effective against soybean aphids. Its IUPAC name is 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl-methylcarbamate. Molecular formula is C₁₂H₁₅NO₃ and molecular weight is 221.2 g/mol. Carbofuran is excreted in the urine primarily as 3-hydroxycarbofuran, carbofuranphenol, and 3-ketocarofuranphenol. Trade names for carbofuran include Furadan and Curater. It has been banned for use on all crops grown for human consumption in the European Union since 2008 and in the United States since 2009. Carbofuran is highly toxic to vertebrate organisms. It has an LD₅₀ of 19 mg/kg in dogs and 8-14 mg/kg in rats.

How do these substances act in the body?

From a pharmacological perspective, these substances act via the parasympathetic nervous system (PSNS) as reversible inhibitors of the enzyme acetylcholinesterase (AChE). Typically, acetylcholine (ACh) is released into the neural synaptic cleft and binds to ACh receptors post-synapse, which then relays a signal from the nerve. AChE halts the signal transmission via hydrolysis of ACh into acetate and choline. AChE functions rapidly and has a very high catalytic activity – it has been demonstrated that AChE can degrade about 25,000 molecules of ACh per second. Choline is then taken up by the presynaptic nerve and ACh is constructed from choline and Acetyl Coenzyme A (acetyl-CoA) via another enzyme, choline acetyltransferase.  As AChE inhbitors, aldicarb and carbofuran inhibit or slow down the normal function of this enzymatic pathway of ACh which results in an accumulation of ACh in the neural synaptic cleft. This accumulation can result in devastating consequences for the organism.

The mnemonic SLUDGEM has been used to describe the symptoms and effects of substances such as these:

Salivation stimulation, usually excessively

Lacrimal stimulation, leading to tearing or watery eyes

Urination via urethral internal sphincter muscle relaxation and contraction of the detrusor muscle

Defecation via internal anal sphincter relaxation

Gastrointestinal upset via changes in smooth muscle tone possibly leading to diarrhea

Emesis or vomiting

Miosis or pinpoint pupils

Other adverse effects include blurred vision, bronchial secretions, bronchoconstriction, constriction of the pharynx, bradycardia, diaphoresis, hypotension, hypothermia, vasodilation, tremors, and convulsions.

Many poisonings of humans and animals have occurred using these two substances – some of these have been accidental through occupational exposure or eating contaminated crops, while others have been intentional through attempted suicide or homicide. Many deaths have occurred.

Other substances that act similarly in the body via acetylcholine include nerve agents such as VX and Sarin, organophosphate pesticides such as diazinon and parathinon, the Alzheimer’s disease medications donepezil (Aricept) and galantamine (Nivalin).

In this case - who administered the substances? By all reports, it is unknown at this time, but I'm sure one day, we'll find out who poisoned Jagger the Irish Setter.

 

References

Baselt, R.C. (2014) Aldicarb. Disposition of Toxic Drugs and Chemicals in Man. Tenth Edition. Pages 58-59. Biomedical Publications, Seal Beach, CA 90740.

Baselt, R.C. (2014) Carbofuran. Disposition of Toxic Drugs and Chemicals in Man. Tenth Edition. Pages 351-352. Biomedical Publications, Seal Beach, CA 90740.

Bayer CropScience. Temik material safety and data sheets (MSDS)
https://www.bayercropscience.us/products/insecticides/temik/label-msds
Retrieved 2015-03-17

NIOSH Pocket Guide to Chemical Hazards. Carbofuran. National Institute for Occupational Safety and Health (NIOSH). http://www.cdc.gov/niosh/npg/npgd0101.html

Retrieved 2015-03-17