Toxication

Toxication or toxification is conversion of chemical compounds into more toxic forms in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. Both the parent drug and its metabolite can be chemically active and cause toxicity.^[1]

Parent non-toxic chemicals are generally referred to as protoxins. While toxication is generally undesirable, in certain cases it is required for the in vivo conversion of a prodrug to a metabolite with desired pharmacological or toxicological activity. Codeine is an example of a prodrug, which is metabolized in the body to the opiate known as morphine.

Examples

Methanol in itself is toxic due to its CNS depressant properties, but acquires more dangerous toxicity through its metabolites formic acid and formaldehyde, which can cause severe acidosis, damage to the optic nerve, and other life-threatening complications.

Paracetamol (acetaminophen) produces the hepatotoxic metabolite NAPQI via the cytochrome P450 oxidase system.

Ethylene glycol (common antifreeze) metabolizes into toxic glycolic acid and oxalic acid in mammalian organisms.^[2]

Other examples of toxication include:

• Nitrites into carcinogenic nitrosamines
• Nicotine into the carcinogenic NNK (4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone)
• Benzo[a]pyrene into the carcinogenic benzo[a]pyrene diol epoxide (BP-7,8-epoxide into BP-7,8-dihydrodiol into BP-7,8-dihydrodiol-9,10-epoxide)

See also

• Detoxification
• Toxicity
• Prodrug

References

1. ↑ Pirmohamed, Dr Munir; Kitteringham, Neil R.; Park, B. Kevin (2012-10-26). "The Role of Active Metabolites in Drug Toxicity". Drug Safety 11 (2): 114–144. doi:10.2165/00002018-199411020-00006. ISSN 0114-5916. 
2. ↑ Wayne Wingfield; Marc Raffe (29 September 2002). The Veterinary ICU Book. Teton NewMedia. pp. 1042–. ISBN 978-1-893441-13-2.