An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

Abstract

Tungsten is a relatively rare metal with numerous applications, most notably in machine tools, catalysts, and superalloys. In 2003, tungsten was nominated for study under the National Toxicology Program, and in 2011, it was nominated for human health assessment under the US Environmental Protection Agency's (EPA) Integrated Risk Information System. In 2005, the Agency for Toxic Substances and Disease Registry (ATSDR) issued a toxicological profile for tungsten, identifying several data gaps in the hazard assessment of tungsten. By filling the data gaps identified by the ATSDR, this review serves as an update to the toxicological profile for tungsten and tungsten substances. A PubMed literature search was conducted to identify reports published during the period 2004–2014, in order to gather relevant information related to tungsten toxicity. Additional information was also obtained directly from unpublished studies from within the tungsten industry. A systematic approach to evaluate the quality of data was conducted according to published criteria. This comprehensive review has gathered new toxicokinetic information and summarizes the details of acute and repeated-exposure studies that include reproductive, developmental, neurotoxicological, and immunotoxicological endpoints. Such new evidence involves several relevant studies that must be considered when regulators estimate and propose a tungsten reference or concentration dose.

Environmental Metals and Cardiovascular Disease in Adults: A Systematic Review Beyond Lead and Cadmium

“…The elimination time of tungsten in most tissues, except bone, is 5 days (70% of the dose) and 100 days (30% of the dose). Consequently, urinary tungsten reflects recent exposure [109, 112]. Occupational inhalation of hard metal dust containing tungsten and cobalt causes asthma and fibrosis called hard metal disease [113, 114].…”

“…Although toxicological evidence regarding cardiovascular disease is sparse, in vivo studies suggest tungsten causes histological lesions in the heart [115] and can inactivate molybdenum-enzymes by replacing molybdenum binding sites [116]. Tungsten likely causes oxidative stress [7, 11, 112, 117] and can modify cobalt toxicity [118]. There is little epidemiological evidence of tungsten exposure and cardiovascular disease in the general population, although tungsten exposure has been associated with elevated blood pressure [119], excretion of reactive oxygen species [117], and DNA methylation and hydroxymethylation [120].…”

Accumulation of persistent tungsten in bone as in situ generated polytungstate

“…Phosphotungstate is a known redox active catalyst, and thus, if formed during bone remodeling, may have numerous deleterious biochemistries affecting essential bone functions, including growth, structure and immune cell formation. As ongoing studies continue to implicate tungsten in a variety of medical conditions, including promoting tumorigenesis, it is a concern that the World Health Organization has no water regulations for tungsten 3,4 . The findings reported are essential for ongoing efforts to understand tungsten's effects on various biological processes and are crucial for the development of new, effective therapeutic methods for its mobilization and removal.…”

“…The prevalent belief that it is innocuous, coupled with its many unique properties, has led to the pervasive adoption of tungsten in a surprising range of technologies 2,3 . However, the recent association of a cluster of acute childhood lymphocytic leukemia cases in Fallon, Nevada, with elevated levels of tungsten in the community's ground water 4 has led to a reappraisal of its potential toxicity. As there remains a lack of toxicological data, tungsten was nominated as an emerging contaminant for further investigation by the US Environmental Protection Agency and National Toxicity Program.…”

“…As there remains a lack of toxicological data, tungsten was nominated as an emerging contaminant for further investigation by the US Environmental Protection Agency and National Toxicity Program. 4 When mice ingest solubilized tungsten in the form of orthotungstate (WO 4 2− ), it rapidly accumulates in their bones 5 . Other bone-accumulating metals, such as lead and strontium 6 , substitute for calcium in hydroxyapatite, the calcium-phosphate matrix of bone, and can be removed using standard chelation therapy 7 .…”