Overview of environmental and occupational vanadium exposure and associated health outcomes: An article based on a presentation at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology, Washington DC, August 15–18, 2012

Abstract

Vanadium (V) has a variety of applications that make it suitable for use in ceramic production and decoration, production of pigments for a variety of products, an accelerator for drying paint, production of aniline black dye, and as a mordant in coloring textiles. Taking advantage of its hardness, resilience, ability to form alloys, and its resistance to corrosion, V is also used in the production of tools, steel, machinery, and surgical implants. V is employed in producing photographic developers, batteries, and semi-conductors, and in catalyst-based recycling processes. As technologies have evolved, the use of V has increased in jet aircraft and space technology, as well as in manufacture of ultraviolet filter glass to prevent radiation injury. Due to these myriad uses, the potential for occupational exposure to V is ever-evident. Similarly, there is an increased risk for environmental contamination by V agents themselves or as components of by-products released into the environment. For example, the use of V in sulfuric acid production results in the release of soot and/or fly ash rich in vanadium pentoxide. Petroleum refinery, smelting, welding, and cutting of V-rich steel alloy, the cleaning and repair of oil-fired boilers, and catalysis of chemical productions are other sources of increased airborne V-bearing particles in local/distant environments. Exposure of non-workers to V is an increasing health concern. Studies have demonstrated associations between exposure to airborne V-bearing particles (as part of air pollution) and increased risks of a variety of pathologies like hypertension, dysrhythmia, systemic inflammation, hyper-coagulation, cancers, and bronchial hyper-reactivity. This paper will provide a review of the history of V usage in occupational settings, documented exposure levels, environmental levels of V associated with pollution, epidemiologic data relating V exposure(s) to adverse health outcomes, and governmental responses to protect both workers and non-workers from exposure to this metal.

• Environmental exposure
• occupational exposure
• vanadium

Opening comment

For the purposes of this paper, the authors first must stipulate for the reader that there are clearly many forms of vanadium that can be encountered in the occupational and environmental setting. While we may utilize the designation ‘V’ throughout the paper, this is not to be confused with the actual form elemental vanadium, nor a single oxidation state of vanadium (as it can exist in many forms from 0 to +5), let alone a single species of vanadium, as vanadium can be routinely encountered as various forms of vanadyls, vanadates, and oxides, including VO₂, VO₃, VO₄, as well as vanadium pentoxide (V₂O₅). Further, we wish to make clear to the reader that, while most of the epidemiologic and toxicologic data concerning health effects of exposure to vanadium arose from inhalation exposures, there are increasingly incidences of exposure (and changes in host health) arising via other routes. These include the use of ingested vanadium-bearing products or medications and the insertion of vanadium-containing implants. Some of these are also discussed herein.

There are a multitude of papers in the literature wherein the reader can find chemically-detailed information about the exposures presented in this review; several of these are cited in this paper to help in that process. This paper was meant to reflect a presentation that was the opening plenary of a forum on ‘Environmental Vanadium & Environmental/Occupational Exposure(s) to Vanadium’ at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology held in Washington DC in August 2012. This particular forum included presentations on the Relationship between occupational and environmental exposition to vanadium compounds and the reprotoxic and genotoxic effects by Dr Mario Altamirano Lozano (Genetics and Environmental Toxicology Research Unit, Universidad Nacional Autonoma de Mexico [UNAM], Mexico City, Mexico), Cellular and molecular mechanisms of vanadium pentoxide-induced airway disease by Dr James Bonner (North Carolina State University, Raleigh, NC), Carcinogenicity of vanadium pentoxide and possible modes of action by Dr Douglas McGregor (Toxicity Evaluation Consultants, Aberdour Fife, UK), and Relevant historical control data show no evidence for carcinogenicity of inhaled vanadium pentoxide in F344/N rats: Implications for risk assessment by Dr Thomas Starr (Toxicology Consulting Services, Arnold, MD). A paper reviewing one of these presentations, specifically that of Dr Altamirano Lozano, follows this paper. Other papers from this session, as well as the V8 meeting itself, will be available to readers interested in vanadium chemistry, biochemistry, and toxicology in Dalton Transactions at a later date.

Introduction

Vanadium was discovered twice and in both occasions was named in homage to its chemistry full of colors. Its first identification was in 1813 by a Spanish mineralogist Andres Manuel del Rio; at that time he named the element panchromium because of its colorful spectrum regarding its oxidation state, and because of its similarity with chromium. In this regard some chemists from that time did not recognize the discovery because they argued that it was chromium and not a new element (Aldersey-Williams, 2012). Nils Sefstrom in 1831 purified vanadium as an oxide which, this time, was recognized as a new element, and because of the beauty of the colors observed in its oxidant states Sefstrom named it Vanadis after the Norse goodness for love, beauty, and fertility (Aldersey-Williams, 2012; Barceloux, 1999; Mukherjee et al., 2004).

Vanadium is a transition metal, element 23 in Group 5 in the periodic table. In general, vanadium is ductile, malleable, and a good conductor of heat and electricity. Vanadium metal itself has a density of 6.11 g/cm³, atomic mass of 50.95, melting point of 1950 °C, boiling point of 3600 °C, and an [Ar] 4s²3d³ electronic configuration. As vanadium metal has outer orbitals that contain 11 and two electrons (in, respectively, shells 3 and 4), this allows for numerous electronic exchange reactions and the formation of a wide range of organic and inorganic complexes that ultimately contain vanadium in different oxidation states.

Uses of vanadium

Vanadium is widely used because its addition improves the hardness, malleability, and fatigue resistance of steel (Barceloux, 1999); it also confers metal resistance to fractures at extreme temperature modulations. Vanadium is also employed in the production of synthetic rubber for automobile engines because it helps increase temperature resistance. The utility of vanadium was clear even in the early 20th Century; vanadium was used in some mechanical parts of the ‘Model T’ and other Ford cars as it helped provide toughness and increased metal fatigue resistance (Moskalyk & Alfantazi, 2003). More recently, vanadium is also widely used in jet and space technology, the atomic energy industry, and in the ever-expanding field of nanotechnology. In the latter case, vanadium dioxide (VO₂) on sapphire or aluminum oxide (Al₂O₃) has been applied in the creation of optical-devices (Zhou et al., 2011). For the production of aerospace products, vanadium alloys (mostly in titanium-vanadium-aluminum) are widely used as they help confer low density and high strength at high-operating temperatures, properties of great value in outer space. To date, no other alloy has been found to serve as an adequate substitute for this purpose (Chemicool.com, 2012; Moskalyk & Alfantazi, 2003).

Other applications that utilize vanadium agents are in the production of glass. For example, vanadium-titanium alloys are used in the generation of telescopes and other types of lenses and vanadium pentoxide (V₂O₅) are employed to provide ultraviolet filtering properties in some glass that is used in buildings and car windshields. Vanadium is also included in the production of several commonly-used pigments, varnishes, reducing agents, and inks that are important to the ceramics, printing, and textile industries, as well as in photography (Moskalyk & Alfantazi, 2003). Pesticides, fungicides, and fertilizers production also incorporate vanadium compounds (Rodriguez-Mercado & Altamirano-Lozano, 2006). Lastly, vanadium compounds have also been utilized as color modifiers in mercury-vapor lamps, and as part of target materials used in X-rays (Moskalyk & Alfantazi, 2003).

The main concern about this element is the growth of occupational and environmental exposure sources that have been developing during the last decades. The well-known occupational activities at which exposure takes place are during processing and refining vanadium ores, manufacturing of vanadium-containing products, burning of fuels rich in vanadium content, and in a variety of processes in the chemical industry (Barceloux, 1999; Ehrlich et al., 2008). The other source of vanadium exposure is the environment through the inhalation of particulate matter produced by the combustion products generated by metallurgic plants and burning of gasoline obtained from petroleum rich in vanadium, such as Venezuelan, Mexican, Iraqi, Iranian, and Kuwaitian sources (Barceloux, 1999; Fortoul et al., 2011; Rodriguez-Mercado & Altamirano-Lozano, 2006).

With an increased understanding of the physicochemical properties of vanadium agents, new applications have been devised; unfortunately, this has concomitantly resulted in new sources of potential exposure. Thus, it is important to know what are the new areas of vanadium applications and to understand the possible toxicities that could arise among workers in these processes as well as among those (residents, non-workers) in the surrounding environments. This review reports on the well-known and the new possible sources of occupational and environmental exposures to vanadium and its agents. Articles were chosen from internationally recognized bibliographic data such as PubMed, Medline, and Scopus. Keywords selected for search were: vanadium, occupational exposure, and environmental exposure. In addition, a ‘snowball strategy’ was used to obtain older sources of information, since reports of occupational exposure date back to the beginning of the 20th Century.

Occupational exposure

Barceloux (1999) noted that Dutton, in 1911, was the first to report dry cough and eye irritation following an occupational inhalation exposure to vanadium-containing fumes and/or dusts. In fact, mining and vanadium processing are one of the first types of occupational exposures for which information of vanadium exposure/toxicities was published. Forty years later, Sjoberg (1951) undertook a study in 703 workers inhalationally exposed to vanadium on the job and reported an increased incidence in nasal irritations, throat dryness, and chest pain, as well as anemia. Kiviluoto et al. (1979) monitored 63 employees from a factory wherein vanadium was extracted from magnetite ore. Concentrations in eight separate measures of jobsite total airborne dusts ranged from 0.2–0.5 mg V/m³. In that report, because there were descriptions of respiratory problems in the workers, a variety of serum parameters (e.g. albumin, chloride ion, urea, bilirubin/bilirubin-conjugate) were evaluated—but no significant differences were found relative to values in non-exposed subjects. A subsequent study in the same population (Kiviluoto et al., 1980) reported a decrease in the exposure concentrations, but still some respiratory symptoms, with the most prevalent being wheezing. Irsigler et al. (1999) and Agramunt et al. (2003) monitored urine V concentrations in 26 workers in a hazardous waste incinerator and found that these levels were increased with length of exposure. Unfortunately, in those studies, health-related symptoms were not reported.

Workers involved in the cleaning and maintenance of oil-fired boilers are exposed via inhalation to V₂O₅; epidemiological studies of these populations have reported upper and lower respiratory symptoms similar to those seen in workers involved in the processes of obtaining the element (Kim et al., 2004; Sjoberg, 1951). In studies from Great Britain, Sweden, and Canada (Lees, 1980; Ross, 1983; Williams, 1952), there were reports of an increased incidence of respiratory symptoms including rhinorrhea, sneezing, sore throat, and chest pain, many of which appeared earlier during or after the exposure (i.e. within 1–12 h of initiation). Dry cough, wheezing, dyspnea, fatigue, and bronchial irritation were reported after ∼6–24 h of the start of the exposure. Many of these symptoms persisted for 1–3 weeks after the exposure ended. A very recent report about children who worked in the manufacture of surgical instruments also noted urine V concentrations higher than those in control children; these children also presented with changes in respiratory function (Sughis et al., 2012) (Table 1, Figure 1).

Figure 1. The variety of occupational and environmental sources of vanadium exposure. Other sources are also identified, i.e. body building supplements and prosthesis.

Table 1. Vanadium occupational exposure reports related to different work activities.

Authors	Year	Concentration	Activity	Subjects	Type study	Symptoms
Dutton	1911	unknown		unknown	Unknown	Dry cough and eye irritation—Vanadism
Sjöbern	1951	>0.5 mg/m^3	Mining/processing	703	Cohort	Nasal/throat irritation; anemia
Kiviluoto et al.	1979	0.028 mg/m^3	Processing	63	Unknown	Respiratory issues
Kiviluoto et al.	1980	0.01–0.04 mg/m^3	Processing	63	Unknown	Respiratory issues
Levy et al.	1984	0.05–5.3 mg/m^3	Conversion of an oil power plant to coal	55 Boiler workers	Major symptoms reported questionnaire	Cough with sputum, sore throat, dyspnea, chest pain or discomfort, headache, runny nose or sneezing, eye irritation, wheezing
Irsigler et al.	1999	>0.15 mg/m^3	Oil-burning maintenance	40	Clinical histories	Airway irritation, chest pain, pharyngitis, laryngitis, conjunctivitis
Agramunt et al.	2003	unknown	Hazardous waste incinerator	28	Survey
Riediker et al.	2003	unknown	Drivers	50 patrols	Unknown	Data not collected
Liu et al.	2005	10–500 µg/m^3	Boilermakers exposed to fuel-oil ash particles	18 workers 11 utility workers	Unknown
Irsigler	1999	>0.15mg/m^3	Oil-burning maintenance		Clinical histories	Airway irritation, chest pain, pharyngitis, laryngitis, conjunctivitis
Sughis et al.	2012	unknown	Children working in surgical instruments manufacturing units	75 children (male)	Analyses of urinary metals	Children were also exposed to Cr and Ni

As a consequence of the cumulative toxicologic and epidemiologic evidence that has accrued over the years, many governmental agencies have established clear exposure limits for workers in various vanadium-utilizing/-generating industries. The American Conference of Governmental Industrial Hygienists (ACGIH), the Occupational Safety and Health Administration (OSHA), the Agency for Toxic Substances and Disease Registry (ATSDR), and the National Institute for Occupational Safety and Health (NIOSH) each established occupational exposure limits to vanadium metal/its compounds. The ACGIH (2008) proposed a maximum permissible level of exposure is 0.05 mg V/m³ in dusts or fumes of V₂O₅ per 8 h shift during a 40-h week, while the recommended exposure limit according to NIOSH (2012) was 0.05 mg/m³ for a 10 h shift during a 40-h week, with concentrations ≥35 mg/m³ being considered dangerous to life. Other agencies such as OSHA (2012) established industrial limits that are generally higher: 0.5 and 0.1 mg/m³ in dusts and fumes of V₂O₅, respectively. In the specific case of ferrovanadium powders, the permissible exposure limit is 1 mg/m³ for 10 h/day during a 40-h week. ATSDR (2009) estimated the minimum risk level (estimated daily human exposure) to be 0.0008 and 0.0001 mg of V/m³ for acute and chronic inhalation, respectively, 0.01 mg of V/m³ orally, and 0.009 mg/Kg/day for prolonged exposure to V₂O₅.

Environmental exposures

Vanadium is widely distributed in the Earth’s crust, and usually appears at low concentrations. This metal ranks 22 among the most abundant elements, with a presence of 0.014–0.02%. Vanadium is found in natural deposits along with minerals of other metals, particularly iron, titanium, and uranium. There are ≈70 minerals that contain vanadium, of which 40 are composed of vanadates. Worldwide crude-oil deposits and all fossil materials are reservoirs of large amounts of vanadium (in the form of organometallic complexes) that, consequently, pose an environmental risk for human exposure when they are acted upon either by natural forces or a result of man-made processes and the metal (in one or more various chemical forms) is released (Rodríguez-Mercado & Altamirano-Lozano 2006; Tracey et al., 2007).

A significant amount of the vanadium that is released into the atmosphere is derived from soil erosion, volcanic emissions, forest fires, and other biogenic processes (IPCS, 2001; Rodríguez-Mercado & Altamirano-Lozano, 2006). However, of the ≈64,000 tons of vanadium released annually into the atmosphere, ≈91% stems from burning of crude oil, coal, and heavy oils, and other metallurgic/mining activities (Nadal & Schuhmac, 2004). Because vanadium is often present at high levels in most fossil fuels (especially in Mexican petroleum [Fortoul et al., 2002; IPCS, 2000; Rodriguez-Mercado & Altamirano-Lozano 2006]), the main risk for exposure to environmental vanadium is a consequence of fuel combustion, i.e. the inhalation of suspended particulate matter (PM), primarily those particles in the fine aerodynamic range (i.e. PM_2.5; ≤2.5-µm diameter). With respect to these particles, the majority of the vanadium is found mainly as insoluble oxides; however, soluble forms (i.e. vanadates) are also present. As a result, upon inhalation, vanadium agents enter the airways and are either processed by local cells (i.e. engulfed/solubilized if insoluble or penetrate cells via phosphate ion channels) or traverse the airway lining, thereby entering the systemic circulation and affecting distal organs/systems in the body (reviewed in Cohen, 2004; Ustarroz-Cano et al., 2012).

Some measurements have been performed using personal monitoring/sampling pumps that clearly demonstrated the presence of vanadium in the urban PM being analyzed (Riveros-Rosas et al., 1997). There are also clear differences in vanadium content depending on a given city or region of a country; these differences have their roots not only in levels of traffic, but also reflect regional differences in manufacturing industries, proximity to the oceans, etc. (Moreno et al., 2010; Pandolfi et al., 2011; Prophete et al., 2006). Of course, as indicated by the previous statement, there are non-anthropogenic sources that contribute to vanadium in the air. These natural sources include volcanic activity, sea salt spray, and forest fires (Fortoul & Rojas-Lemus 2007; Rodriguez-Mercado & Altamirano-Lozano 2006; Verma et al., 2009).

Other sources of vanadium exposures can include motor vehicle traffic. These types of exposures are well known to occur among drivers of trucks, buses, patrol cars, and taxis who spend the majority of their working time being exposed to combustion fumes (Riediker et al., 2003). Smoking is another source of personal ‘environmental’ exposure; the mean concentration of vanadium in cigarettes of 1.11 ± 0.35 μg V/g, and the mean concentration in cigarette smoke has been found to be 0.33 ± 0.06 μg/g (Adachi et al., 1998) (Table 2, Figure 1). Sadly, there are other means for exposure as well. Disasters brought up by humans, such as wars (including the starting of large-scale oil facility fires; Ustarroz-Cano et al., 2012) or terrorist attacks such as in the WTC disaster, have been shown to result in the liberation of significant quantities of particles that carried metals within or on their surface, including V. These particles were then inhaled by local residents (non-combatants) and, in the case of the World Trade Center (WTC) disaster, many emergency personnel who had responding to the tragedy (McGee et al., 2003).

Table 2. Environmental vanadium exposure sources.

Authors	Year published	Exposure	Mode of Sampling
Riveros-Rosas et al.	1997	Air	Battery operated personal pumps
Adachi et al.	1998	Tobacco smoke	Cigarettes Tobacco smoke
Fortoul et al.	2002	Air	Lung autopsy samples
Riediker et al.	2003	Air	Air samples inside patrols
McGee et al.	2003	Air	Particulate matter from WTC event
Nadal and Schuhmac	2004	Soil Chard	Areas near petrochemical industries
García et al.	2009	Air	Air samples
Verma et al.	2009	Wildfires	Air samples
Moretti et al.	2012	Hip prosthesis	Blood

While this review clearly indicates that there are a multitude of resulting toxicities that can occur following exposure to vanadium-bearing particles/agents, mechanisms of effect are moreover lacking. Recent studies have begun the process of trying to ascertain more precisely how vanadium, primarily in its role as a constituent of airborne pollution, might be imparting some of its toxicologic effects. Specifically, it has been repeatedly demonstrated that there is an increased incidence in pulmonary infections associated to PM_2.5 exposure as well as overall decreases in host resistance following toxification with vanadium agents (Cohen, 2004, 2007). In the lungs, one current theory for these changes in host resistance is that the interaction of vanadium in the particles causes changes in iron (Fe) homeostatic mechanisms (Ghio & Cohen, 2005), resulting in decreases in utilization of Fe in alveolar lining fluid and a subsequent decrease in its activity in local phagocytic cells, including diminished antibacterial phagocytic activity and immunocompetency (Doherty et al., 2007). Other recent studies have shown that the presence of vanadium in PM (or alone) can induce significant formation of reactive oxygen species (ROS) in vivo and in vitro, resulting in induction of oxidative stress (see review by Valko et al., 2005) and a subsequent cascade of changes in the lungs (Ghio et al., 2012) or lung-associated cells, including changes in DNA integrity (Di Pietro et al., 2011b), mitochondrial structure/function (Di Pietro et al., 2011a), and apoptosis (Montiel-Davalos et al., 2012).

Elective (unintended) exposures

Dietary and water intakes

It is estimated that the population in the US has a dietary intake of ≈6–18 μg V/day and that people in the UK ingest ≈13 μg V/day (Anke, 2004). Some publications have noted that values may be higher in some other regions, i.e. Germany and Mexico; values for women were found to range from 10–20 μg/day and in men >20 μg/day (Anke, 2004; EFSA, 2004). Significant quantities of vanadium enter the body via water and food, and concentrations ranging from 1–40 μg/kg fresh weight have been found in the latter. In spices such as black pepper or dill, the concentration of vanadium is ≈431 and 987 μg V/kg, respectively (Adachi et al., 1998; Barrio & Etcheverry, 2010; Rojas et al., 1999). Whether the sources of vanadium in these food products or water sources are due solely to natural toxication or a result of exogenous activities (i.e. deposition from vanadium-contaminated rain or aerosolized particles dropping onto water surface, crops, etc.) would clearly affect the potential daily intake values.

Anabolic and insulin mimetic effect

Some vanadium salts mimic insulin actions, and these have been proposed for use as an adjuvant in the treatment of Type 2 diabetics (Barrio & Etcheverry, 2010; Crans, 2000; Crans et al., 2011). However, in healthy adults, no benefits have been yet noted (Williams, 2005). Because of its insulin-mimetic effects, vanadium salts have been added to dietary supplements as body builders; however, again, there is not enough evidence to support its use to increase muscle growth (Kreider, 1999).

Prosthetics

A recent report indicates the possible toxicity by the use of prosthesis to replace different body parts (Moretti et al., 2012) (Table 2, Figure 1). In previous reports Ti-6A1-4V alloy has been reported as a possible cause of vanadium toxicity because of the release of this element from the alloy to the surrounding tissue (Manivasagam et al., 2010).

Conclusions

Vanadium is not only special because of its beautiful color palette but also because of its multiple physical and chemical properties that confer beneficial properties to all the products in which it is used. Because of this, its uses in industry are still increasing as well; conversely, of course, this also means that there are increasing possible sources of vanadium contamination on the job as well as in the environment. This is the curse of vanadium; with increasing usage in new applications, the concurrent new possible sources of exposure and subsequent health effects in exposed workers and in those living near and/or exposed to contaminated waste will only increase as well.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Acknowledgments

Data for this manuscript was supported in part from DGAPA-PAPITT-UNAM-IN209612 grant.