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 Additional information was also obtained directly from unpublished studies from within the tungsten industry.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.

Due to unknown effects of the potential exposure of the terrestrial environment to tungsten substances, a series of toxicity studies of sodium tungstate (Na(2) WO(4) ) was conducted. The effect on earthworm (Eisenia fetida) survival and reproduction was examined using Organisation for Economic Co-operation and Development (OECD) Guideline 222. No effect on either endpoint was seen at the highest concentration tested, resulting in a 56-d no-observed-effect concentration (NOEC) of ≥586 mg tungsten/kg dry soil (nominal concentrations). The effect of sodium tungstate on emergence and growth of plant species was examined according to OECD Guideline 208: oat (Avena sativa), radish (Raphanus sativus), and lettuce (Lactuca sativa). No effects on emergence, shoot height, and dry shoot weight were observed in oats exposed to the highest concentration, resulting in a 21-d NOEC of ≥586 mg tungsten/kg dry soil. The NOECs for radish and lettuce were 65 and 21.7 mg tungsten/kg dry soil (nominal concentrations), respectively. Respective 21-d median effective concentration values (EC50) for radish and lettuce were >586 and 313 mg tungsten/kg dry soil (based on shoot height) (confidence level [CL] -8.5-615); EC25 values were 152 (CL 0-331) and 55 (CL 0-114) mg tungsten/kg dry soil. Results are consistent with the few other tungsten substance terrestrial toxicity studies in the literature.

The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO.

Although aquatic toxicity data exists for tungstate substances, insufficient data of high quality and relevancy are available for conducting an adequate risk assessment. Therefore, a series of acute and chronic toxicity tests with sodium tungstate (Na(2)WO(4)) were conducted on an aquatic invertebrate (Daphnia magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio). Collectively, the data from these studies suggest that sodium tungstate exhibits a relatively low toxicity to these taxa under these test conditions. All studies were conducted in the same laboratory under good laboratory practice standards using Organisation for Economic Co-operation and Development guidelines with the same stock of test material and the same analytical methods. All results are reported as mg W/L. The following toxicity values were based on mean measured concentrations. For D. magna, the 21 day test no-observable effect concentration (NOEC) was 25.9 mg W/L, and the 48-h median effective concentration (EC(50)) from the acute test was >95.5 mg W/L (the highest concentration tested). The P. subcapitata test yielded an ErC(50) of 31 mg W/L. A 38-day test with zebrafish resulted in an NOEC ≥5.74 mg W/L with no effects at any concentration. The 96-h LC(50) from the acute test with zebrafish was >106 mg W/L. The results of the current acute study for daphnids and fish are consistent with published literature, whereas the algae results are different from previously reported values. Transformation/dissolution (T/D) studies, which were conducted according to United Nations Globally Harmonized System of Classification and Labelling of Chemicals protocol, confirmed that the WO (4) (-2) anion accounted for most of the tungsten in solution. For classification purposes, the algae ecotoxity reference value was then compared with T/D data and would not classify Na(2)WO(4) as an aquatic toxicant under the European Union Classification, Labelling and Packaging scheme.

The article contains sections titled: 1. Introduction 2. Properties 2.1. Physical Properties 2.2. Chemical Properties 3. Raw Materials 3.1. Natural Resources 3.2. Tungsten Scrap 4. Production 4.1. Mining and Ore Beneficiation 4.2. Pretreatment of Ore Concentrates and Scrap 4.3. Hydrometallurgy 4.3.1. Digestion 4.3.2. Purification 4.3.3. Conversion of Sodium Tungstate Solution to Ammonium Tungstate Solution 4.3.4. Crystallization of Ammonium Paratungstate (APT) 4.4. Production of Tungsten Oxides 4.5. Production of Tungsten Metal Powder 4.6. Production of High‐Purity Tungsten Metal (99.999 ‐ 99.9999%) 4.7. Powder Metallurgy (PM) 4.8. Metal Injection Molding 4.8.1 MIM Process Overview 4.8.2 General Guidelines 4.8.3 MIM of Tungsten, Tungsten Alloys, Tungsten–Copper Composites, Tungsten Heavy Alloy, and Cemented Carbide 4.9. Additive Manufacturing of Tungsten and Cemented Carbides (WC–Co) 4.10. Fabrication of Wrought PM Tungsten 4.10.1. Shaping–Mill Products 4.10.2 Mechanical Bonding of Tungsten to Tungsten and Other Metals 4.11. Surface Treatment 4.12. Melting 5. Tungsten Alloys 5.1. Single‐Phase Solid‐Solution Alloys 5.2. Multiphase Alloys 5.2.1 Tungsten Heavy Metals 5.2.2. Tungsten–Copper and Tungsten–Silver Composites 5.2.3. Non‐Sag Tungsten 5.2.4 Alloys with Oxide Dispersions 5.2.5 Porous, Infiltrated Tungsten 6. Uses of Tungsten 6.1. Tungsten and Tungsten Alloys 6.2. Cemented Carbides (WC–Co) 6.3. Tungsten Coatings 7. Tungsten in Melting Metallurgy of Steel and Superalloys 7.1. Tungsten in Steel 7.2. Tungsten in Superalloys 7.3. Master Alloys 7.3.1 Ferrotungsten 7.3.2. Tungsten Melting Base 7.3.3. Master Alloys for Superalloys 7.4. Production of Master Alloys 7.4.1. Production of Ferrotungsten 7.4.2. Production of Tungsten Melting Base 7.4.3. Production of Master Alloys for Superalloys 8. Tungsten Compounds and Their Application 8.1. Tungsten Chemistry 8.2. Aqueous Solutions of Tungsten 8.3. Intermetallic Compounds 8.4. Compounds with Nonmetals 8.4.1. Tungsten–Boron Compounds 8.4.2. Tungsten–Carbon Compounds 8.4.3. Tungsten–Silicon Compounds 8.4.4. Tungsten–Group 15 Compounds 8.4.5. Tungsten–Oxygen Compounds 8.4.6. Tungsten–Chalcogenide Compounds 8.4.7. Tungsten–Halogenide Compounds 9. Tungsten in Catalysis 10. Tungsten Recycling 10.1. Direct Recycling 10.2. Semi‐Direct Methods 10.3. Hydrometallurgy 10.4. Melting Metallurgy 11. Analysis 11.1. Raw Materials 11.2. High Purity Intermediate Products, Tungsten Powder and Sintered Tungsten Metal 11.3 Trace Elements in High‐Purity Tungsten Metal 12. Economic Aspects 12.1. Production 12.2. Consumption 12.3 Price 13. Toxicology and Occupational Health 13.1. Toxicokinetics 13.2. Acute Toxicity 13.3. Subchronic and Chronic Toxicity 13.4. Genotoxicity 13.5. Carcinogenicity 13.6. Reproductive Toxicity 13.7. Developmental Toxicity 13.8. Immunotoxicity 13.9. Human Biomonitoring Data 13.10. Occupational Health 14. Acknowledgements

Under the European Community (EC) Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), the risk to humans may be considered controlled if the estimated exposure levels to a substance do not exceed the appropriate derived no-effect level (DNEL). In order to address worker exposure, DNELs are derived for the worker population. The most significant route of exposure to workers to both soluble and sparingly soluble tungsten substances is through inhalation. In order to meet the REACH registration requirements, occupational long-term inhalation DNELs were developed according to the European Chemical Agency (ECHA) REACH guidance on characterization of dose-response for human health. The inhalation DNELlong-term for sodium tungstate, from which all other soluble tungsten substance DNELs were derived, is 3 mg sodium tungstate/m(3) (1.7 mg W/m(3)), and the inhalation DNELlong-term for tungsten blue oxide, from which all other sparingly soluble tungsten substance DNELs were derived, is 7.3 mg tungsten blue oxide/m(3) (5.8 mg tungsten/m(3)). Although derived using different methodologies and supported by different studies, the occupational inhalation DNELslong-term for soluble and sparingly soluble tungsten compounds are similar to the current National Institute for Occupational Safety and Health (NIOSH) recommended exposure level (REL) and the American Conference of Industrial Hygienists (ACGIH) threshold limit value (TLV) 8-h time weighted average (TWA) of 1 mg tungsten/m(3) for soluble tungsten compounds and 5 mg tungsten/m(3) as metal and insoluble tungsten compounds.

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