# Thallium Use, Toxicity, and Detoxification Therapy: An Overview
## 3 Thallium Toxicity
Thallium is accumulated in the liver, bones, brain, kidney, testes, stomach, lungs, spleen, and skin of the scalp; it has also been detected in hair, nails, tears, and breast milk. Concentrations of TI in human organs follow this order: brain (0.42-1.5 ng/g), liver (1.5 ng/g), kidney (6.1 ng/g), hair (150-650 ng/g), bone (600 ng/g), and nail (1200 ng/g) [38]. The major route of elimination of this metal is mainly in urine and feces. The urine test is the most reliable and accurate way to determine TI concentrations in the human body. Under normal conditions, thallium in urine does not have to exceed 1 mg/g creatinine and can be detected after 1 h for up to 2 months after exposure [1]. The measurement is usually carried out for spectrophotometric determination. The method is focused on the oxidation of 3-methyl-2-benzothiazolinone hydrazone hydrochloride by TI\({}^{3+}\) to diazonium cation, in the presence of impiramine hydrochloride in phosphoric acid medium to obtain a blue-colored solution with a maximum absorption length of 635 nm [39]. A possible mechanism of TI toxicity is its ability to affect glutathione (GSH) activity. Indeed, glutathione binds heavy metals, including thallium, through its -SH group, inhibiting their toxicity. In addition, glutathione blocks the formation of ROS while maintaining the oxidant homeostasis of the plasma. [PERSON] and collaborators studied the effects of TI on rat liver mitochondria [40]. TI\({}^{+}\) in different concentrations induced a significant increase in mitochondrial ROS formation, ATP depletion, glutathione oxidation, mitochondrial membrane potential (MMP) collapse and mitochondrial outer membrane rupture with cytochrome C release, and peroxidation of membrane phospholipids, especially binding to anionic head groups (Figure 1). This suggests that TI\({}^{+}\) may alter the fluidity of the mitochondrial membranes, acting on phospholipid packing and affecting the activities of membrane-associated transport systems and enzymes, and disrupting receptor functions. TI does not have biological functions; however, TI\({}^{+}\) can enter cells through potassium uptake channels due to its similarity in charge and ionic radius to potassium (K\({}^{+}\)). The estimated absorption of this metal through the respiratory apparatus in unpolluted environments is below 0.005 \(\upmu\)g/day [41]. TI follows potassium distribution pathways and, in this way, alters many of potassium-dependent processes. For example, TI may inhibit the enzymatic activity of Na\({}^{+}\)/K\({}^{+}\)-ATPase [42]. Thallium can substitute K\({}^{+}\) in Na\({}^{+}\)/K\({}^{+}\)-ATPase and shows a tenfold greater affinity for Na\({}^{+}\)/K\({}^{+}\)-ATPase by inhibiting the activity of this enzyme. This enzyme with an antiport mechanism across the cellular and mitochondrial membranes makes three sodium ions move against two potassium ions. This difference in charge provides the driving force to import with support mechanism glucose, amino acids, and nutrients (Figure 1). In addition, in mitochondria TI alters the balance of Bax/Bd/Bcl-2 proteins, activating caspase-9, caspase-8 and caspase-3, thus leading to apoptotic death [5]. TI compromises mitochondrial energy production by inhibiting pyruvate dehydrogenase, succinate dehydrogenase, complexes I, II and IV of the electron transport chain (ETC), and uncoupling oxidative phosphorylation with decreasing ATP synthesis (Figure 1). In addition, thallium takes the place of potassium in the stabilization of ribosomes, as well as in physiological muscle contraction. Other possible mechanisms of TI poisoning include cell mitosis, cell metabolic disorders, interference with DNA synthesis and the induction of chromosomal abnormalities. This metal interferes with the mechanisms of energy production especially in glycolysis, the Krebs cycle and oxidative phosphorylation [43]. Other mechanisms of TI toxicity include the interference of TI with the active sites of several enzymes as it interacts with amino-sulfhydryl groups.