Toxication or toxification is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymaticmetabolism in the organisms, as well as by abioticchemical reactions. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis. Different classes of enzymes, such as P450-monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver. 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, metabolized in the body to the active compounds morphine and codeine-6-glucuronide.
Toxication by enzymatic metabolism
CYP450 enzymes
Phase I of drug metabolism are bioactivation pathways, which are catalyzed by CYP450 enzymes, produce toxic metabolites and thus have the potential to damage cells. The unusual level of activity CYP450 enzymes might lead to the changes in drug metabolism and convert drugs into their more toxic forms. Among Phase I CYP450 enzymes, the subfamilies CYP2D6 and CYP3A are responsible for hepatotoxicity during drug metabolism with a number of different drugs, including flucloxacilin, trioleandomycin, and troglitazone. Hepatotoxicity indicates the drug's toxicity to liver. Paracetamol is converted into the hepatotoxic metabolite NAPQI via the cytochrome P450 oxidase system, mainly by the subfamily CYP2E1. Hepatic reduced glutathione will detoxify this formed NAPQI quickly by if APAP is taken at a proper level. In the case of overdoses, the storage of GSH will not be enough for NAPQI detoxication, thereby resulting in acute liver injury.
Increases in toxicity can also be caused by abiotic chemical reactions. Non-living elements affect the abiotic chemical reactions. Anthropogenic trace compounds have potential toxicity to the organisms in aquatic system. Arsenic contamination in drinking water can be chemically toxic. The uptake and metabolism of arsenic may result the damage to body. When organic arsenic is converted into more toxic inorganic arsenic, it causes carcinogenesis, cytotoxicity and genotoxicity.