Pulmonary Toxicity, Genotoxicity and Carcinogenicity Evaluation of Molybdenum, Lithium, and Tungsten

Recently, researchers from the Danish National Research Centre for the Working Environment clarified the doses of molybdenum (Mo), lithium, and tungsten (W) for inhalation toxicity and evaluated the genotoxicity and carcinogenic potential of these three elements.

The study titled “Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review” has been published in the journal Toxicology 467 (2022). The study was carried out by Niels Hadrup, Jorid B. Sørli, Anoop K. Sharma.

Mo, Li, and W are components of many products, and humans may be exposed to these elements in their productive lives and work. Mo, lithium, and tungsten are components of industrial products, such as lubricants in spray form. In addition to its use in industry, the transition metal molybdenum is an important trace element that binds to the molybdopterin cofactor and plays an important role in several enzymes.

The alkali metal lithium is used in the treatment of bipolar disorder and is also is a major component of automotive batteries. W binds to molybdopterin cofactors in bacteria and other organisms, but it is not an essential trace element in humans. Studies have also found that W occurs naturally in groundwater in some locations. In addition to being exposed through lubrication processes and welding fumes, workers are exposed to W in the metal industry during production. Soldiers are also exposed to W in combat, as some ammunition often contains W.

Hard metal lung disease has been observed in some individuals after workers or soldiers have been exposed to hard metals. Hard metals combine synthetic compounds of W carbide and cobalt, as well as some other metals. A unique feature of this hard metal lung disease has been reported as giant cell interstitial pneumonia.

During manufacture and use, workers are potentially exposed to these elements through inhalation. Therefore, it is important to determine at what inhalation levels they are toxic. Researchers from the Danish National Research Centre for the Working Environment have studied the pulmonary toxicity, including toxicokinetics, of Mo, lithium, and W. All exposure pathways and in vitro genotoxicity of hard metals were also reviewed.

They emphasize that the inclusion of all exposure routes and in vitro studies is due to the severity of cancer and because genotoxic effects are often the result of single-cell internal processes, independent of the exposure route.

Following lung exposure, Mo and W are increased in several tissues, while the distribution of lithium is less pronounced than that of Mo and W. In addition, all three elements are excreted in the feces and urine.

In a 2-year inhalation study in rats and mice, Mo trioxide exhibited pulmonary toxicity with the lowest observed adverse effect concentration (LOAEC) of 6.6 mg Mo/m³. Following subacute inhalation in rabbits, the LOAEC for lithium chloride was 1.9 mg Li/m³. W oxide nanoparticles had a NOAEC of 5 mg/m³ following inhalation in hamsters. in another study, W oxide blue had a LOAEC of 63 mg W/m³ in rats.

Regarding genotoxicity, for Mo, the in vivo genotoxicity after inhalation remains unknown; however, there is some evidence for the carcinogenicity of Mo trioxide. There are no clear data on lithium genotoxicity, and one carcinogenicity study suggests that it is not genotoxic. W appears to have genotoxic potential, but the data on carcinogenicity are also unclear. In addition, in the general population, increased levels of W in urine are associated with an increased risk of cardiovascular disease and stroke.

In conclusion, for three elements, molybdenum, lithium, and tungsten, this study determined doses for inhalation toxicity and assessed genotoxic and carcinogenic potential.

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