Thallium - poisoner’s poison: An overview and review of current knowledge on the toxicological effects and mechanisms

Abstract

Thallium (Tl) is one of the most toxic metals and its historic use in homicides has led it to be known as “the poisoner’s poison.” This review summarizes the methods for identifying Tl and determining its concentrations in biological samples in recently reported poisoning cases, as well as the toxicokinetics, toxicological effects, toxicity mechanisms, and detoxication methods of Tl. Recent findings regarding Tl neurotoxicological pathways and toxicological effects of Tl during pregnancy are also presented. Confirmation of elevated Tl concentrations in blood, urine, or hair is indispensable for diagnosing Tl poisoning. The kidneys show the highest Tl concentration within 24 h after ingestion, while the brain shows the highest concentration thereafter. Tl has a very slow excretion rate due to its large distribution volume. Following acute exposure, gastrointestinal symptoms are observed at an early stage, and neurological dysfunction is observed later: Tl causes the most severe damage in the central nervous system. Alopecia and Mees’ lines in the nails are observed within 1 month after Tl poisoning. The toxicological mechanism of Tl is considered to be interference of vital potassium-dependent processes with Tl⁺ because its ionic radius is similar to that of K⁺, as well as inhibition of enzyme reactions by the binding of Tl to -SH groups, which disturbs vital metabolic processes. Tl toxicity is also related to reactive oxygen species generation and mitochondrial dysfunction. Prussian blue is the most effective antidote, and metallothionein alone or in combination with Prussian blue was recently reported to have cytoprotective effects after Tl exposure. Because Tl poisoning cases are still reported, early determination of Tl in biological samples and treatment with an antidote are essential.