# Thallium Poisoning: Case Report and Scoping Review on Diagnostic Delay and Therapeutic Outcome
## 5 Discussion
### Adverse Effects of Thallium
Mortality rates for acute thallium toxicity have been reported to range from six to fifteen percent. A lethal dose for human beings ranges from 10 to 15 mg/kg, but mortality can still occur at lower dosages [71; 72; 73]. The major hazard for the general population is exposure to polluted water. Water pollution is generally attributed to the interaction between groundwater and thallium-bearing pyrite ores. In China, a water source contaminated with thallium (with values up to 10 mg/L) caused significant public health problems [74]. In Italy, high levels of pollution (up to 9000 mg/L) have been observed in wastewater from abandoned mining plants [75; 76; 77; 78; 79] and resulting in the contamination of the water drunk by the surrounding population [80]. Exposure to low doses of thallium, far below the US EPA maximum allowable level in drinking water (2 mg/L) [81], is a threat to human health [82]. Over 10 years ago, the US EPA aimed to lower the maximum contaminant level of thallium in drinking water to 0.5 mg/L, but this measure has not yet been adopted in America or any European country. Studies conducted on general population subjects with moderate thallium absorption (urinary levels less than 0.2 mg/L) reported a number of health problems, including impaired thyroid function [83], metabolic changes (increased waist circumference and body mass index) [84], hypertension [85], impaired glomerular filtration [86], and autism spectrum disorders [87; 88], as well as osteoarthritis [89]. The placenta transports about 50% of the metal from mother to fetus [90] and maternal exposure is associated with a low birth weight [91] and preterm birth [92]. Thallium is also associated with genetic and epigenetic changes [93]. Although we cannot state that there is consolidated evidence of harm, the complex set of reports suggests that careful monitoring of the possible effects on populations drinking water with thallium levels between 0.5 and 2 mg/L is necessary. Thallium is similar in structure to potassium and is, consequently, processed in a comparable manner at the cellular level [94]. Thallium toxicity is associated with some primary toxicologic effects. Tissues exhibiting elevated potassium concentrations accumulate significant levels of thallium. This results in initial stimulation, subsequently leading to the inhibition of potassium-dependent processes. The inhibition of pyruvate kinase and succinate dehydrogenase disrupts the Krebs cycle and glucose metabolism, resulting in decreased ATP production, swelling, and vacuolization due to the impairment of the sodium-potassium ATPase. Thallium's strong capacity to form disulfide bonds interferes with the cross-linking of cysteine residues, leading to a decrease in keratin synthesis. Riboflavin sequestration caused by thallium and the inhibition of flavin adenine dinucleotide disrupts the electron transport chain, resulting in decreased ATP production [95]. Ribosomes are adversely affected by thallium, particularly impacting protein synthesis through damage to the 60S ribosome. The reduction in ribosome synthesis and its biogenesis results in the impairment of protein synthesis, blockage of the cell cycle progression, and apoptosis [96]. Thallium at high doses induces the degeneration of myelin in both the central and peripheral nervous systems [29]. Low-dose exposure is associated with mitochondrial dysfunction, neurite shortening, a loss of substrate adhesion, and an increase in cytoplasmic calcium [97; 98]. The toxicokinetic phases of thallium are divided into three distinct stages: (1) the Intravascular Distribution Phase, during which, in the first 4 h following exposure, thallium is distributed to organs through the bloodstream; (2) the CNS Distribution Phase, in which, over a period of 4 to 48 h, thallium is distributed within the central nervous system; and (3) the Elimination Phase that commences approximately 24 h after exposure and is primarily facilitated through renal excretion and fecal elimination.